Deadly Short Cuts

"It's so good. Don't even try it once." intravenous heroin user Heroin is named after the German word for powerful, heroic, heroisch. According to popular legend, its substitute, methadone, was initially christened Dolophine in honour of Adolf Hitler. In reality, the name comes from the Latin dolor, meaning "pain", and fin, meaning "end": hence "end of pain". The consumption of heroin is marked by a euphoric rush, a warm feeling of relaxation, a sense of security and protection, and a dissipation of pain, fear, hunger, tension and anxiety. When heroin is snorted or smoked, the rush is intense and orgasmic. Subjectively, time may slow down. Any sense of anger, frustration or aggression disappears. Users enjoy the feeling of "being wrapped in God's warmest blanket". Heroin is the most fast-acting of all the opiates. When injected, it reaches the brain in 15-30 seconds; smoked heroin reaches the brain in around 7 seconds. The peak experience via this route lasts at most a few minutes. The surge of pleasure seems to start in the abdomen; a delicious warmth then spreads throughout the body, or at least the somatosensory cortex. After the intense euphoria, a period of tranquillity ("on the nod") follows, lasting up to an hour. Experienced users will inject between 2-4 times per day. After taking heroin, some people feel cocooned and emotionally self-contained. Others feel stimulated and sociable. Either way, there is a profound sense of control and well-being. The euphoria gradually subsides into a dreamy and relaxed state of contentment. Higher doses of heroin normally make a person feel sleepy. At higher doses still, the user will nod off into a semi-conscious state. The effects usually wear off in 3-5 hours, depending on the dose. Heroin is not inherently toxic to the organ systems of the body. Whereas a 200-400mg dose of heroin could kill a novice, a chronic user may take 1800mg without ill-effects. But in prohibitionist society the mortality of street users is high. Diacetylmorphine, or heroin, was first synthesized from morphine in 1874. It is formed simply by adding two acetyl groups. Heroin is around three times more potent than morphine. Its increased lipid solubility allows heroin to cross the blood-brain barrier more quickly. The drug is reconverted back to morphine before it binds to brain-tissue receptors. Pure heroin is a white, odourless powder with a bitter taste. Most illicit heroin, however, varies in color from white, pink/beige to dark brown. This is because of impurities left from the manufacturing process or the presence of additives. In the late nineteenth century, it was fondly believed that if only one could filter out the "addictive" properties of opium, then one would capture its therapeutic essence. Heinrich Dreser, in charge of drug development at Bayer, tested the new semi-synthetic drug on animals, humans, and most notably himself. Dreser was impressed. He pronounced heroin an effective treatment for a variety of respiratory ailments, especially bronchitis, asthma and tuberculosis. Commercial production of heroin began in 1898. Heroin was advertised under its well-known trademark by German manufacturers Bayer as "the sedative for coughs". The new wonderdrug enjoyed widespread acceptance in the medical profession. This was because heroin induces a

serene, un-manic euphoria with minimal interference with sensation, motor skills or intellect though chronic opioid use typically diminishes the inclination to abstract thought. Bayer was soon enthusiastically selling heroin to dozens of countries. Free samples were handed out to physicians. The medical profession remained largely unaware of the potential risk of addiction for years. Eventually news filtered out. Doctors noticed that some of their patients were consuming inordinate quantities of heroin-based cough remedies. It transpired that heroin was not the miracle-cure for morphinism that some of its early boosters had supposed. In 1913, Bayer halted production. They wrote the drug out of their official company history, and focused instead on marketing their second blockbuster drug, aspirin. Comprehensive control of opiates in the United States was first established in 1914 with the Harrison Narcotic Act. In 1924, federal law made any use of heroin illegal. Within a decade, the Bureau of Narcotics had arrested some 50,000 users and 25,000 physicians. Most of the problems suffered by contemporary users derive, directly or indirectly, from the criminalisation of heroin use and the draconian penalties inflicted on those who take it. Likewise, most of the needless pain suffered by the physically ill today derives, directly or indirectly, from the demonisation of opioid drugs and from the reluctance of physicians to prescribe stigmatised remedies for pain that really work. During World War One, newspaper editors, police forces, politicians and "patriots" whipped up a climate of hysteria against seditious "dope fiends" enslaved by "the German invention". Heroin use was associated with anarchy, violence, foreigners and Bolshevism. Prohibition led inexorably to control of the heroin business by organised crime. Jewish gangsters such as Meyer Lansky dominated distribution in the 1920s. In the 1930s, they were superseded by the Mafia: this was the era of "Lucky" Luciano, the celebrated Sicilian mobster. Drug law was widely flouted. In explaining the failure of decades of prohibitionist legislation, former chief of police of the USA, Joseph D McNamara, wrote in National Review... "It's the money, stupid. After 33 years as a police officer in three of the country's largest cities, that is my message to the righteous politicians who obstinately proclaim that a war on drugs will lead to a drug-free America. About $500 of heroin or cocaine in a source country will bring in as much as $100,000 on the streets of an American city. All the cops, armies, prisons and executions in the world cannot impede a market with that kind of tax-free profit-margin. It is the illegality that permits the obscene mark-up, enriching drug-traffickers, distributors, dealers, crooked cops, lawyers, judges, politicians, bankers, businessmen..." Choking off the supply of narcotics at source isn't a realistic prospect either. Myles Ambrose, one of President Nixon's closest advisers in the War on Drugs, was scathing in his judgement of some of his fellow drug-warriors... "...The basic fact that eluded these great geniuses was that it takes only ten square miles of poppy to feed the entire American heroin market, and they grow everywhere...." Traditionally, the purity of heroin in a bag has ranged from 1% to 10%; more recently, heroin purity has ranged from 1% to 98%, with a US national average of 35 percent. Pure heroin is rarely sold on the street. A bag may contain 100 mg of powder, only a portion of which is heroin; the remainder could be sugars, starch, powdered milk, or quinine. Until recently, heroin in the United States was almost exclusively injected, either intravenously, subcutaneously ("skin-popping"), or intramuscularly. Injection is the most practical and efficient way to administer low-purity heroin. The availability of higher-purity heroin, however, allows users to snort or smoke ("chasing the dragon"). Snorting is most widespread in those areas where high-purity heroin is easy to obtain.

When injected, heroin provides an extremely powerful rush. After 4 to 8 hours, the effects start to wear off. Tolerance develops to the respiratory depressant, sedative, analgesic, emetic and euphorigenic effect. So users tend to increase their daily dose - sometimes as much as a hundredfold or more - if financial resources permit. Financial resources frequently don't: the term "junkie" derives from addicts who stole junk metal to support their habit. Injecting drugs can be a risky business in prohibitionist society. This is because hygiene is difficult, education is minimal, and fluctuations in quality can lead to accidental overdose. US opposition to needle-exchange programs at home and abroad has massively promoted the spread of HIV and hepatitis in users - and non-users - alike. Noxious tobacco-smoking aside, the Supreme Court of the United States has never been sympathetic to a drug-based lifestyle.... "To be a confirmed drug addict is to be one of the walking dead....The teeth have rotted out, the appetite is lost, and the stomach and intestines don't function properly. The gall bladder becomes inflamed; eyes and skin turn a bilious yellow; in some cases membranes of the nose turn a flaming red; the partition separating the nostrils is eaten away-breathing is difficult. Oxygen in the blood decreases; bronchitis and tuberculosis develop. Good traits of character disappear and bad ones emerge. Sex organs become affected. Veins collapse and livid purplish scars remain. Boils and abscesses plague the skin; gnawing pain racks the body. Nerves snap; vicious twitching develops. Imaginary and fantastic fears blight the mind and sometimes complete insanity results. Often times, too, death comes-much too early in life....Such is the torment of being a drug addict; such is the plague of being one of the walking dead..." (1962) Heroin is sometimes smoked with crack cocaine. This combination delivers an even more intensely rewarding experience than taking either drug alone. "Speedballs" are hugely addictive and ruinously expensive. Yet in a clinical setting and among the terminally ill, the simultaneous use of cocaine, methylphenidate or amphetamines with heroin or morphine can augment the opioid's analgesic and anxiolytic effect while allowing its dosage to be lowered. The risks of respiratory depression are thus diminished. Why do we like opium and its derivatives so much? Heroin mimics the action of natural chemicals, endorphins, produced by the body in response to pain. Endorphins are small-chain peptides that activate our endogenous opioid receptors. Opioid receptors are proteins embedded in the cell membrane; opioid agonists bind to the receptors to initiate their effects. The highest density of opioid receptors is found in the limbic system. Their activation produces feelings of happiness, relaxation, fearlessness and tolerance to pain. Endorphins are hundreds or even thousands of times more potent than morphine on a molar basis. Their potency means their concentrations in vivo are low. Endorphins are also involved in respiration, nausea, vomiting, pain modulation, hormonal regulation and itching.

Opioid drugs also act in these limbic brain regions. Yet except at very high doses, the opioids don't block the pain messages themselves. Rather, they change the subjective experience of the pain. This is why people receiving morphine for pain-relief may say that they still feel the pain - but that it doesn't bother them any more. Many users self-medicate: opioids are powerful antidepressants and antianxiety agents. Response and remission rates are high; but so are tolerance, dependence and addiction.

Search Of The Big Bang
What is Crack Cocaine?

In

Cocaine is an alkaloid found in leaves of the South American shrub Erythroxylon coca. It is a powerfully reinforcing psychostimulant. The drug induces a sense of exhilaration in the user primarily by blocking the reuptake of the neurotransmitter dopamine in the midbrain. If the predictions of The Hedonistic Imperative are vindicated, then future millennia will witness what Robert Anton Wilson once called "hedonic engineering". Mature enhancements of currently druginduced states of euphoria will be transformed into a absolute presupposition of sentient existence. Gradients of life-long happiness will be genetically pre-programmed. "Peak experiences" will become a natural part of everyday mental health. Cocaine, alas, offers only a tragically delusive short-cut. In pre-Columbian times, the coca leaf was officially reserved for Inca royalty. The natives used coca for mystical, religious, social, nutritional and medicinal purposes. Coqueros exploited its stimulant properties to ward off fatigue and hunger, enhance endurance, and to promote a benign sense of well-being. Coca was initially banned by the Spanish. In 1551 the Bishop of Cuzco outlawed coca use on pain of death because it was "an evil agent of the Devil". The noted 16th century orthodox Catholic artist Don Diego De Robles declared that "coca is a plant that the devil invented for the total destruction of the natives." But the invaders discovered that without the Incan "gift of the gods", the natives could barely work the fields - or mine gold. So it came to be cultivated even by the Catholic Church. Coca leaves were distributed three or four times a day to the workers during brief rest-breaks. Returning Spanish conquistadores introduced coca to Europe. Even Shakespeare may have smoked it - and inhaled. The coca plant is perishable and travels poorly. Yet coca was touted as "an elixir of life". In 1814, an editorial in Gentleman's Magazine urged researchers to begin experimentation so that coca could be used as "a substitute for food so that people could live a month, now and then, without eating..." The active ingredient of the coca plant was first isolated in the West by the German chemist Friedrich Gaedcke in 1855; he named it "Erythroxyline". Albert Niemann described an improved purification process for his PhD; he named the product "cocaine". The name stuck. Sigmund Freud, an early enthusiast, described cocaine as a magical drug. Freud wrote a song of praise in its honour; and he practised extensive self-experimentation. To Sherlock Holmes, cocaine was "so transcendentally stimulating and clarifying to the mind that its secondary action is a matter of small moment". Robert Louis Stephenson wrote The Strange Case of Dr Jekyll and Mr Hyde during a sixday cocaine-binge. Intrepid polar adventurer Ernest Shackleton explored Antarctica propelled by tablets of Forced March. Doctors dispensed cocaine as an antidote to morphine addiction. Unfortunately, some of their patients made a habit of combining both.

Normally. self-confidence. Thus cocaine was a popular ingredient in wines. this technique is physically dangerous. Benzoylecgonine can be detected for up to five days in casual users. A coca leaf typically contains between 0. Hence a more convenient method of producing smokeable free-base became popular. Until 1916. To obtain crack-cocaine. What happens to the discarded cocaine is obscure. sexual interest. Coca-cola was introduced in 1886 as "a valuable brain-tonic and cure for all nervous afflictions". The new beverage was invigorating and popular. in the West. Ryno's HayFever and Catarrh Remedy ("for when the nose is stuffed up. In chronic users.1 and 0. Yet there are very strong cultural prejudices against injecting recreational drugs. the inactive benzoylecgonine. one could buy it at Harrods: a kit labelled "A Welcome Present for Friends at the Front" contained cocaine. This type of base-cocaine makes a cracking sound when heated. If chewed in such form. toothache cures and patent medicines. the cocaine alkaloid yields a further potently reinforcing compound. Since the hydrochloride salt decomposes at the temperature required to vaporise it. "free-base" cocaine was typically produced using volatile solvents. Architect Frédérick-Auguste Bartholdi remarked that if only he had used Vin Mariani earlier in his life. and in chocolate cocaine tablets. it rarely presents the user with any social or medical problems. royalty and even the Pope. and render the sufferer insensitive to pain". Its product is crack. Indeed coca-chewing may be therapeutic. only the intravenous route of administration could be expected to deliver the more potent and rapid hit they have been seeking. in coca cigarettes "guaranteed to lift depression". ordinary cocaine hydrochloride is concentrated by heating the drug in a solution of baking soda until the water evaporates. Sensation-hungry thrillseekers have long sought the ultimate high from the ultimate "rush". hence the name "crack". (S)he will access heightened states of being whose modes are . the drink still contains an extract of coca-leaves. Yet old-fashioned cocaine hydrochloride still wasn't good enough. The solvent tends to ignite. When the leaves are soaked and mashed. The CocaCola Company imports eight tons from South America each year. Sold today. notably Vin Mariani. usually ether. When combined with alcohol. now known to be cocaethylene. It was promoted as a temperance drink "offering the virtues of coca without the vices of alcohol". then he would have engineered the Statue of Liberty a few hundred meters higher. This is the powdered cocaine most common.9 per cent pure cocaine. So a smokeable form was developed. Initially. Nowadays the leaves are used only for flavouring since the drug has been removed .in the words of pharmaceutical firm Parke-Davis .Coca wine received endorsement from prime-ministers. Unfortunately. cocaine hydrochloride. a typical serving contained around 60mg of cocaine. Cocaine was widely used in tonics. Crack-cocaine delivers an intensity of pleasure completely outside the normal range of human experience. Prospective buyers were advised . and the most intense sense of being alive. the coca-paste is 60 to 80 per cent pure. urinary detection is possible for as long as three weeks. syringes and spare needles. After the organic solvent used has evaporated.though molecular traces of cocaine remain. cocaine is instead converted to the liberated base form. conversational prowess and intensified consciousness to be derived from just snorting cocaine. cocaine is then extracted as a coca-paste. the user will ever enjoy. so it can be easily inhaled via a heated pipe. Base-cocaine vaporises at a low temperature.that cocaine "could make the coward brave. however. Until 1903.9 percent cocaine. One fast-selling product. red and sore") consisted of 99. until recently. It offers the most wonderful state of consciousness. the silent eloquent. Drug testing for cocaine aims to detect the presence of its major metabolite. morphine. It is usually exported in the form of the salt.Cocaine was soon sold over-the-counter. They haven't been satisfied with the enhanced mood.

The brain has evolved a truly vicious set of negative feedback mechanisms. extreme fatigue and possibly paranoia. anhedonia. Drug-naive virgins . An intense craving for more cocaine develops. Physical health may deteriorate. Their functional effect is to stop us from being truly happy for long. For to do so. When Is It Best To Take Crack Cocaine? As a rule of thumb. Whole communities can be disrupted by crack-abuse. Certain estimable English doctors were once in the habit of administering to terminally-ill cancer patients an elixir known as the "Brompton cocktail". During a "mission". The compulsion may become utterly obsessive. This is at best very imprudent. So may tactile hallucinations of insects crawling underneath the skin ("formication"). Whereas "empathogens" such as MDMA / Ecstasy . and affective analogue of Absolute Zero. Nature is cruelly parsimonious with pleasure. Once-loved partners and children may be callously cast aside. Indeed.will typically promote empathy. Relatives of the stricken patient were pleased. trust. In heavy users. agitated delirium. "dopaminergic" drugs such as cocaine or amphetamines. the emotional baseline. Thus the brain's capacity to experience pleasure is diminished. users may consume up to 50 rocks a day. too. cocaine tends to be a "selfish" drug. This was a judiciouslyblended mixture of cocaine.unknown to chemically-naïve contemporaries. The social consequences of heavy cocaine use can be equally unpleasant. irritability. But simplistically. compassionate love and sociability.cannot be confident (unless in thrall to ill-conceived logical behaviourist theories of meaning) that they have grasped the significance of such an expression. if taken on their own and to excess. This story has complications . The illusion of free-will is likely to disappear. can easily have the reverse effect. harmless and both emotionally and intellectually satisfying. Groping for adequate words. The neural after-effects of chronic cocaine use include changes in monoamine metabolites and uptake transporters. steal and commit crimes of violence. stereotyped compulsive and repetitive patterns of behaviour may occur. Ultimately. essentially a 3-4 day crack-binge. it is profoundly unwise to take crack-cocaine. heroin and alcohol. at the new-found look of spiritual peace and happiness suffusing the features of a loved one as (s)he prepared to meet his or her Maker. There is down-regulation of dopamine D2 receptors to compensate for their drug-induced overstimulation. Most of their money and time is spent thinking about how to get more of the drug. cheat. a drug which induces a secular parody of Heaven commonly leads the user into a biological counterpart of Hell. Non-recreational users are likely eventually to alienate family and friends. and also a syndrome sometimes known as toxic paranoid psychosis.which trigger the release of more serotonin than dopamine . There is perhaps a single predictable time of life when taking crack-cocaine is sensible. The initial short-lived euphoria of a reinforcer as uniquely powerful as crack will be followed by a "crash". depression. crack-takers sometimes speak of the rush in terms of a "whole-body orgasm". . it would be necessary to take the drug via its distinctive delivery-mechanism oneself.slightly shop-soiled or otherwise .cocaine's affinity for the serotonin transporter is actually greater than for the dopamine transporter. This involves anxiety. They tend to become isolated and suspicious. It may be higher than the rapturous transports of the most euphoric coke-binge in paleo-human history. for such an occasion it may be commended. Severe depressive conditions may follow. The results were gratifying not just to the recipient. characteristic of post-humanity in its hedonically enriched modes of awareness may be greater than anything we can now grasp. To obtain more. In the meantime. crack addicts will often lie.

An age of society's children weaned on the ideals of high-speed communication and accelerated culture has prided itself in mastering many of the facets of human existence -. while seemingly benevolent as "Have a Coke and a smile" have sold the link to chemical substances like caffeine and nicotine to "the good life. one is conceived in pleasure and may reasonably hope to die in it. high speed music and 24-hour lifestyles brought the specter of drugs to the fold as a necessity for being able to attain more. A few generations hence.a whirl of minutes. capitalism fuels the idea. the pace of modern life seems fleeting -. founded equally in the post-conservative underground late-'80s and the chaotic early-'90s. Our society is based upon the mass consumption of these substances. BUILT FOR SPEED? Methamphetamine has reclaimed a place in the lexicon of "party" drugs. In a predominantly secular society. high-speed transportation and pharmacology of this modern age has evolved. However. more unreal and still somehow manageable. sleeping less. Roberts Here at the end of the millennium. Dreams were the frivolous luxuries of childhood. this appeal was heightened by raising the stakes in the '80s on what it meant to have fun. Sleep became a barrier for success. For it promises to spare friends and relations the miseries of vicarious suffering and distress they are liable to undergo at present as they witness one's decline. the limitations of human existence. high-speed modems. We have pushed the limits of the modern world further -. The hyperreality of today goes hand in hand with the drugs being administered. In the meanwhile. humans have equipped themselves with the tools to move faster. we have moved dangerously toward the fine line between extinction and evolution. intelligence and prestige. without chemical aid. in the '80s these stimulant drugs became tools -. the elimination of primitive evolutionary holdovers such as the ageing process and suffering will make the hedonistic death advocated here redundant.doing more. In dealing with the changes. Hailed by nocturnal adventurers. can turn dying into the culmination of one's existence rather than its present messy and protracted anti-climax. Our generation (see Gen X. 20-somethings) could be considered the sleepless generation.utilitarian devices to gain wealth. condemned by raver idealists. In many ways. the human capacity to handle the velocity becomes a fragile balance.ATMs. Leaps away from the psychedelics of the '60s. In a race to outdo ourselves. smart bombs and bullet trains. hours and days. Therefore. There is another good reason to finish life on a high note. For our generation. adopting a hedonistic death-style is much more responsible from an ethical utilitarian perspective. That is. more efficiently. and not a pathetic and godforsaken whimper." Today. . stimulants are the bedrock for consumer culture. Raves.Drawing life to a close with a transcendentally orgasmic bang. Late night clubs. is speed a sleepless dream or an addictive nightmare? by Todd C. Cultural ideals. may still provide the stumbling block for infinite realization. At the same time a dependence for the marketing. like sleep. are part of the pastiche that has consequently become more dream-like. The machines of this age have in a way enabled us to create a 24-hour lifestyle.

most often prescribed for weight loss. a single hit creates a high that lasts for hours and several hits can wire a user for days. However. making it a perfect candidate for injection. Speed rose to popularity in California.) A probable direct reaction to the Depression and Prohibition. many old-schoolers have been turned off by the newbie vibe that came with speed's rise in popularity. they are "tweakers. (popular for its availability and price) has somehow replaced MDMA and LSD as the perfect rave drug. Now. more potent and easy to make. whereas "crystal" usually refers to the free-base form of methamphetamine. the drug was used and abused by non-asthmatics looking for a buzz." the common name for sniffing lines of speed. Hitler was supposedly injected with methamphetamine. Another form "Ice." has taken the place of pharmaceutical amphetamine as an easy-to-get alternative. Absent from their faces are the smiles of midnight. for some reason it was shocking for some to see methamphetamine take hold. vacant stare of sleepless dreams. It's the drug of choice for long-distance truckers and college students pulling all-nighters. the price of taking 3-4 pills of ecstasy became too expensive an option. Around the speaker bins are small packs of animated dancers grinding their feet into the floor and shaking their hands in front of them. was discovered in Japan in 1919. purer form of crystal meth is smoked." "Tweaking. sold under the trade name Desoxyn. It is still legally produced in the U.. Amphetamine was first synthesized in 1887. in 1932. speed has been given a bad rap. subsequently bringing down a whole Summer of Love with violence and angst. its high price prevents it from taking hold. It has been called a trailer park drug for decades. allowing users the clear head and stamina to keep dancing long after their bodies have gone to sleep. What is often misunderstood is the relationship between speed and crystal meth. due to the fact that it can be cooked up so cheaply and easily. Where speed had been seen in every scene from metal to the punk scene. (Amphetamine is widely known as a bronchio dialator. Speed came to the rave scene in 1992. some equated it with the greed of drug dealers.000 on the street. They have a name in the rave community. Over the counter ephedrine.partiers needed to find latenight/early morning activities like after-hours. home of many of the largest meth labs in the country. A gram of "ice" commands about $5. Bikers have been historically blamed for introducing the drug into the psychedelic '60s. Since then. keeping it from dying.It's 6 a. The crystalline powder was soluble in water. Some were casualties themselves of the drug's addictive nature. allowing asthmatics to breathe more freely. Judging from today's roster of events throughout the nation. the drug methamphetamine. Some likened the rise to the quash of young newcomers. . amphetamines elevate mood.m. raves are still alive and well. As the name "speed" suggests. Others say that speed alone is what fuels the rave scene. Theory: when the parties in '92 started to get really good. Jazz great Charlie "Bird" Parker would remove the inhaler's Benzedrine strip and soak it in his coffee. Methamphetamine. First popularized by pharmaceutical company Smith Kline & French as the nasal inhaler. The common reference to speed in the rave scene is the methamphetamine salt (HCl powder). Benzedrine. replaced by the blank." a higher-grade. or "white crosses. even though MDMA (an amphetamine-like substance) had been circulating for years. Also smoking the drug creates a similar rush. Consequently. The lookie-loos and weekend warriors have long since gone home. speed took over as an easier to get and cheaper alternative. A prominent opinion during the aftermath of the Los Angeles Summer of Love was that speed killed the rave scene. riding on the back of biker gangs. heighten endurance and eliminate fatigue. However. the police were cracking down more on the prime-time parties -. explaining the drug's popularity with the military.S.

because it is definitely a part of my thought pattern now. feel energy and stay up all night.the center for self-satisfaction and emotional systems. it is very addictive." he says "Whenever I get tired or wish I had more energy.the standard street price in Los Angeles for a gram of speed is approximately $100. Ecstasy primarily effects serotonin in the brain -." "Speed does not belong in the underground scene. The problem is major parts of the scene moved away from enlightenment. What's unusual. hoping to defend the drug against his critical peers. I was first introduced to it about five years ago by a girl I was dating. (Oddly. If you want to get amped. Ecstasy does not necessarily contain speed. "I believe that speed/crystal is one of the most psychologically addictive drugs around. he is still connected to the drug. is much more profoundly addicting. something that could never be achieved by shoving a few rails of driveway cleaner up your nose. if there is anything evil it is the society we live in which dictates that they are illegal and thus makes them harder to get. One major misconception is the link between methamphetamine and ecstasy [MDMA]. While many admit openly to taking MDMA. "[MDMA] induces a sense of spiritual enlightenment. MDMA is "cut" with speed to lower the street price of the drug. "Once you take it a few times. And I haven't done speed for over 3 weeks now. In some places it is synonymous. speed and ecstasy supposedly give off "glows" that are far different." he goes on." "I will admit one thing. speed would . also finds some criticism for it. The two are similar in chemical makeup but one cannot be made from the other. and sometimes social understanding. alcohol also affects a dopamine center. Slightly changing the chemical makeup produces a wholly different effect in the human brain. speed.some say it was the death of the ideal. they will not condone or even accept speed as a "valid" recreational drug. each affects a far different region of the brain resulting in different psychological effects.) Often. because of its dopamine ties. Speed affects dopamine primarily. and I think to myself. his opinion is that ecstasy has opposite effects and could actually save the rave scene." says Velour. you will continue to think about it after you stop. In that respect. "Speed is evil. and everything she did revolved around speed. "Something that is so damn negative could never co-exist with the positive ideals that we try to promote. "I have seen more people's lives twisted up off that drug than anything else in the world. $150 or more. where ecstasy sells for approx. However. Speed too has been linked to the rave scene -. "They are simple chemicals. I basically watched her use of it turn from an occasional party thing to basically the sustenance of her life." says Dominic." Even though his experiences have not all been good.using speed just to stay up is a total cop out. a neurotransmitter linked to pleasure and reward. "Preferably organic chemistry. in my mind are not evil." says another critic. While both have addictive potential. even if by chemical means. I haven't done speed for a month now and still some days will go by where I have only had 3 or 4 hours sleep. Ecstasy has a definite link to the rave scene. are the differing opinions about speed. The stigma that goes with "tweaking" can be quite severe. thus changing the overall effect. I always think how nice it would be to have some speed. "Amphetamines. yet both contain the methamphetamine structure. 'You know. Michael. happiness. Qualitatively. given the qualitative similarities between the two. I am addicted. 19." he continues. transcendence and betterment of the self through involvement in community" A regular user of the drug is DJ Velour." However. try alternatives -. Her body withered way." "I'm all for consciousness expansion.

They not only stimulate latent emotions." CAT is notorious for its hardcore addictive potential. that is what makes me a more responsible user. mentions speed's many different appearances that make for different psychological outcomes. This group is a tribute to the idea that some things stay the same across time or space. high dosage methamphetamine club. irritability." says Mark. some hang in there after their lights have gone out. avoiding the felonies. a local low-grade speed that was in vogue about six years ago. and crippling motorcycle accidents. "I've been drinking the stuff since Jr. croak. but they can also enforce emotions much in the way ecstasy can. legal landscapes.' However. "Many of my friends are long time users of speed. there are worse things that can happen." He feels that his ability to control his habit is more powerful than his lust for it. no drug or state of mind is worth dying for. But despite all this. some leave quietly.really help out right now. In other words. As strange as this may sound.. there are a few of us who have managed to hang around the periphery for decades. He also." Speedlore and Methology: Part I "Of all the separate realities. watching the planes bomb the Iraqis. I not only realize my desire for speed and other amphetamines and I curb the habit.. However. It's the only drug I've done at work. High School as my get me up and go thing. But the relationship with amphetamines starts six or seven years ago with poppers (ephedrine. no subculture seems as pervasive or uniform as the nationwide-eyed. Epsom salts and battery acid. . "Speed and other stimulants can be a positive part of a raving community. I have had some very "happy" speed that made me feel as happy as when I was on X. or disappear. "I realized how bad my problem was when right around the time the land war in Iraq began." "Things got really serious when I started doing CAT. Other than luck. than having to lay down and go to sleep for a week. among others. some go snitch. I had stayed up for days on end. an addict that relates his experiences back to an early age. and sleeplessness. I started taking them to stay awake in college to finish papers and the like. on your own. and avoid the biggest bear-trap in the speed circus: taking yourself too seriously. the members come and go. big ripoffs. The CAT I knew dearly also tweaked me on methamphetamine when the CAT seemed to loose its luster. and metabolic metropolis that thrive beneath the surface of the Cleaver's USA. different speeds can evoke different emotions. and quite a few are dragged off at 6:00 a.. To this day what was a six month period still seems to me to be several weeks. or doing hard time for.m." DJ Velour believes that the rave community can co-exist with a drug like methamphetamine." CAT. However.. Getting in too deep is what we do." (Speed Phreak) "My experience with speed-like substances really begins with coffee.. gunshots. mini-thins). On the flip side I have had some lower grade speed that made me feel depressed. the key to staying alive is knowing when to take a step back. apparently strong enough to hook users after just one sample. Friday morning by blue windbreakers with yellow writing. by no means have they ruined their lives.. or methacathinone. It's also the only drug I've done where my peers at work noticed mood swings. increasing their strength. is a popular substance made from common household chemicals like drain-cleaner. it's who we are. killing for. Truly not giving a fuck is the only way to maintain perspective.. just like any other drug it depends upon the person taking it and the purity/mixture of the drug..

" says an anonymous post to one of the world wide web's drug archives. If you take ephedrine and reduce it you get methamphetamine. You think you've got it under control when you first do it because it's usually so nasty on the sinuses and your body that you don't ever think you could get used to the feeling. It's what you do with it that makes a difference. he describes the typical problem with drugs like speed." For "Pat. [However]. But the difference between jonesing for a sugar fix and a speed fix is only partially chemical and physiological. "My brain was so clear when I used this.lamont@hyperreal. even though I do think E is much safer). THC. is nothing more than an inert substance. But I think more people than not overestimate their ability to handle drugs. if you take ephedrine and oxidize it then you've got methcathinone. He was prescribed methamphetamine for a learning disability and consequently produced a problem through abuse. is the feeling of invulnerability. whether it's strychnine." "I do in fact know some people who skate through life without problems with drugs. it's the setting involved. It makes you feel (and probably actually does) like your IQ jumped quite a bit. I've had really intense thought about observations of myself. The reference to "drain-cleaner and battery acid" is to common sources of the chemicals sodium hydroxide and H2SO4 which are used in chemical synthesis. But a drug. you do. but that has fallen off to a much less frequent. "What a joke. but they also tend to get in the way of being a functional human being with multi-dimensional interests." says Benboy." "It can be a transcendental drug if you do enough. as opposed to being a full-time club kid.[Editorial Note: Methcathinone is related to ephedrine similarly to how speed is related to ephedrine. -." "What caught me about speed. I think I get from speed what most cocaine users get from coke.. At first I did it about once a month. This continued for about another year. which gets you nowhere fast.org ] "Even after I kicked the CAT habit.. "Speed is funny. Drugs can be fun. as dangerous as a head of lettuce in itself." Asked if the drug has improved his life. "But I have seen many speed freaks go out like that." the drug poses a serious paradox. Improve? Beyond the nominal gain of being able to dance until the wee hours of the morning." According to some medical journals. it doesn't. The feeling of being on top of the world." Still. that I came up with answers to problems that had been bugging me for months." The drug itself is not the problem. "I have Attention Deficit Disorder [and] speed seems to improve my attention span." he says of meth. As a raver. or new ideas about what I'd like to do with my music. methamphetamine does . And productivity? Any gains are ephemeral and short-lasted. speed is also a convenient way to keep dancing long after your body has gone to sleep." Other users bring up the fact that MDMA also has an addiction factor. he answers. and what catches me now. but still regular usage. Most of it is social. And I've seen a few 'E' freaks buy the farm too. "This stuff makes your brain work at 100% efficiency and doubles processor speed. "I'm able to work with concentration on something far longer than a few hours. caffeine or Prozac. Most recently (for about a year) I moved to MDMA as the speed kick. Methcathinone is not "made from" those substances but can be "made using" those substances. This occurs with other psychedelic drugs that I've done. or other creative thoughts. The availability and the motive to remain awake for long hours may compound the addiction of speed. that many only attribute to meth. Still others attribute a great deal of positive qualities to methamphetamine. "I like speed just fine. I would usually indulge my speed addiction by crushing up minithins and snorting them.

The punk. an unsettling velocity. Still many would attribute "wonder drug" status to meth.. Seemingly synthesized as an accessory to a fast car. enabling them to get more done without sleep. hackers and late-night workers rely on the drug to keep them awake. Students. a sort of collective unconsciousness. industrial and rave .. high speed lifestyle. "Sleep will never even occur to you." the post continues. A twisted wisdom creeps into those of us who manage to survive. into glassware 15 minutes after shooting a 1/4g at stoplights in mid-sentence in mid-shot in mid-fuck" (Speed Phreak) Speed was created for a future world where everything moves at a faster clip. though performance of only "simple mental tasks" is improved. although the amount of errors is not necessarily decreased. again You're nodding out. you will feel better than if you had skipped the drug and slept all night!" Speedlore and Methology: Part II "The American Speedfreak is not a lost soul. We know how to have fun between the first ether gasp and locking ourselves in the closet. As a matter of fact. and you will never miss the sleep from the night before. "Do two hits in the morning before work. it has made mutations over the years to evolve for a new race.produce slight improvements in mental acuity. an unspoken Crankster ideology: It's time to get some sleep when: You're out of crank Your face is bouncing off the table Your veins have completely disappeared beneath pasty goose flesh Your shoes don't fit anymore 24 simultaneous projects have stalled for lack of floor space suddenly everyone is a cop You've just set yourself on fire. cyber.

Talk of "addictive personalities" have recently been founded valid." full of energy. the effects of methamphetamine become much more severe. like in most drugs.high gloss veneers and space travel-. it doesn't generate the same kind of craving. how much can be attributed tot the drug and how much to sleep deprivation is unclear. "The increase in motor activity involves the noradrenaline system." With long-term abuse. The user feels "wired. the addictive potential inherent in the drug. Although abuse potential is there. continued use despite knowledge of harm to oneself or others. specific to methamphetamines usually sets in after a time which is said to include "suspicion. creating the "come-down blues. While the social definition for addiction is debatable. "Drugs that don't have a major effect on dopamine generally aren't 'addictive' in the same way -. 1990). heroine)." Prevalent discussion between users on either side of the methamphetamine argument involves addiction. and the more damaging the effects. an Organic Chemistry graduate student at U. sniffing) is associated with dopamine release from reservoirs in neurons in the brain. "Many drugs that are addictive." Simply put. but then is subsequently degraded in the synapse. heart attacks occur from over stimulation and energy depletion. these symptoms can last up to five years. psychology. amphetamine. because their cells are receiving massive stimulation. the more intense the rush is. Also apparent is some nerve damage in habitual users (primarily crystal smokers) -. cocaine. the destruction that comes from the come-down can be severe. Like a space capsule falling to earth. sweats and exhaustion are prevalent. the chemical and physical activity in the body is founded in one of several compounds in the brain. criteria for addiction includes: unsuccessful attempts to quit. psilocybin and LSD ranked at least 50 points lower than meth on a 100 point scale. persistent desire and craving.scenes has exemplified their fetish for speed. taken nasally ranks over cocaine. there's not as much as there normally should be. The come-down is what many users refer to as "the crash. involving individual physiology. marijuana. Hence your body acts as if there were more of it around. caffeine and PCP (angel dust) in addictive qualities. According to several studies.is not inhuman. psilocybin. anxiety and auditory hallucination. LSD. but cannot re-absorb them in the presence of cocaine or speed. In worst case scenarios. The "high" produced is a result of extra activation chemicals in the brain. making you high. have primary or major effects on the dopamine system (nicotine. nicotine being the highest above both crack and crystal meth. So once you come down. The cell secretes activation chemicals. Tolerance is an issue. social . but the problem comes with the human limitation to handle the extremes of rocket travel or the side-effects of re-entry." says Plunkett. stimulants cause their effects by blocking re-uptake of neurotransmitters at a presynaptic membrane. Dopamine is normally involved with pleasure and reward." says Matt Plunkett. [The drug] mimics the molecule noradrenaline (norepinephrine) at the receptors for this neurotransmitter.jaw clenching and facial ticks. The come down is a result of the chemical being released all at once. Apparently. methamphetamine.Marijuana.However." Though reportedly. According to one study that appeared in In Health magazine (Dec. much more acute are the changes in lifestyle and eventually in personality that manifest. Users exhibit an affective disorder and subtle change in psychological temperament. The more concentrated the drug is. alcohol. among many other biochemical roles." Usually symptoms like chills.C." Psychosis. where more of the drug is needed to get "high. MDMA. MDMA. Meth is one of the most addictive drugs of today's commonly used drugs. Many who have witnessed the changes in habitual users report the shift to aggressive or non-affectionate behavior which may also be attributed to methamphetamine. nervous twitching. taking the drug to avoid or relieve withdrawal. The desire for future frontiers -. etc. "The so-called stereotypic behavior in animals (compulsive gnawing. Berkeley.

drug theorist and author Terence McKenna calls the "dominator" drugs -synthetic drugs that have been refined and concentrated. rumors. Methamphetamine may have the ability to chemically fuel the ride. Western world -. Therefore. many theorists contend that stimulants -. while naturally resilient to much self-inflicted abuse. Many other drugs have been part of the rave community over the years -.the center for ego-dominator culture. pretending that our own addictions are more manageable. Some drugs like alcohol and nicotine have long been legal and subsidized by dominator culture. There is however a great deal of dangerous propaganda -. Special K (ketamine) and especially ecstasy (MDMA) but none have exhibited the burn-out or addiction rate associated with methamphetamine. He relates the emergence of drugs like methamphetamine back to the institutionalized abuse of these substances.the way in which one drug has been cynically encouraged and used to support the introduction of others -." While I am no proponent of speed or drug abuse. however tobacco addicts (smokers) might kill for their fix too if they had to. but instead they simply walk out to a 7-Eleven and buy cigarettes. Ethnobotanist. "The hypocrisy of dominator culture as it picks and chooses the truths and realities that it finds comfortable. however." he writes in his book Food of the Gods. physically it may just prove the limitations for human society.hear-say." he continues. nicotine. I have become glaringly aware of the hypocrisy prevalent in mainstream and underground culture regarding the legitimation of certain drugs.lumping in caffeine. And then. Misinformation sometimes is more dangerous than no information and real answers are only found through communication. it can also be abused and exploited to the point where the need for it besides soothing a craving is the only point. but the bigger problem is sweeping it into a closet. "The history of commercial drug synergies -." a culture interested in the mass consumerism of these legitimate substances -. therefore losing their natural link to the planet and to human-kind. He equates them with the religious fundamentalism and beige fascism of the post-industrial. to be more intuitive and based upon the natural human spirit.it only perpetuates the cycle for needing more.sugar.and economic pressures to suggest a person's vulnerability to drug dependency. While meth (or any drug) is an inert substance that we cannot attribute blame to. however their qualitative separation from drugs like cocaine or speed is still unclear. . Addiction is a problem. is virtually nill. concentrated addictive substance -. There is very little factual information about amphetamines and their dangers available to the lay person. "Dominator" drugs have been established and validated by "dominator culture.by their nature are addictive and must be reconsidered by society. there is no point. pretending it isn't real. Speed is a potentially dangerous substance. may not be a reliable container for the soul at high speeds. it is important to remember the glass houses we all live in. aside from medical journals.nitrous oxide.over the past five hundred years is not easy to contemplate. Some may argue that there is an aesthetic. Still. It can also be used as a recreational drug. Research on the subject. "[These drugs] are still at the depths of drug depravity especially considering the violent or illegal acts that the craving may induce [because of their illegal status]. McKenna considers the natural psychedelics. When finger-pointing. However. nicotine and amphetamines -. It can be used as a tool. a qualitative high. caffeine. lies. psilocybin and even LSD. it does rely greatly on the person when talking about their potential for abuse. like late-night coffee drinkers. by methamphetamine's nature -as a refined. by its nature it has raised the question "Are we really built for speed?" It seems that the human body.

not so pure) forms of methamphetamine. The term "ice" is generally considered to apply to 4-methyl-aminorex. 4-methylaminorex. caffeine. there does not appear to be a comprehensive source of information relating to methamphetamine. Overview Methamphetamine (also known as speed. The author does not endorse the abuse of any drugs. legal or otherwise. crystal. and other chemicals. Disclaimer Do not use this information. This is for informational purposes only. When precision is needed. expressed or implied.e.com April 15. this one attempts to answer technical questions related to the chemical methamphetamine. the term "speed" can mean methamphetamine or amphetamine. including amphetamine. since the street names do not have a one-to-one correspondence to actual chemicals. there tends to be a great deal of street lore that is blatantly wrong about methamphetamine and similar compounds. This is a preliminary document and should be considered fictitious until proven otherwise. of the suitability of this information for any particular purpose. Terminology In this document. Don't let them control you. and sometimes confusingly called ice) is a chemical widely known for its stimulant properties on the human body. Use of this information for illegal purposes is not condoned. ephedrine. both legal and illegal.Control drugs. meth. We shall use the term "methamphetamine" to refer to the substance in either its free base (i. simple. rather than by "street names". I am not a chemist. crank. This document also attempts to point out some of the more common myths. It is frequently confused with other drugs that share similar symptoms. we shall explicitly state one form or the other. 1996 Abstract Surprisingly. and provide rational explanations. The author makes no warranty. This information has been gathered from openly available sources. For example. October 1995 Methamphetamine Frequently Asked Questions deadlock@paranoia. . Unfortunately. While no list is ever complete. we shall refer to the drugs by their common chemical names. but is often used to refer to relatively pure (and in some cases. Article originally appeared in URB Magazine. unadorned) or salt (usually hydrochloride) form.

Effects These include euphoria. and other general symptoms of increased sympathetic nervous activity. due to oral ingestion) can prolong the effects relative to time of administration. but is probably on the order of 4 . Administration Methamphetamine can be taken orally. The physical effects are almost assuredly due to interactions between the amphetamine structure and human physiology. It can be detected in the urine one hour after use and up to 48 hours after use. Delayed absorption (for example. Plasma Life The length of time that methamphetamine will stay in the plasma (blood) is between 4 to 6 hours. 50 milligrams of pure drug for a non-tolerant user. in approximately increasing order of immediacy of onset. partially because there is very little "science" involved. snorted. In fact. Dosage A toxic reaction (or overdose) can occur at relatively low levels. incessant talking. dizziness. .8 hours. and probably also due to confusion over terminology. Mental capacity is not diminished directly by the drug. The pharmacological effects of methamphetamine are very similar to those of similarly structured molecules. Elevated blood pressure. hyperexcitability. Duration Duration is subjective. and drug strengths vary. Of course. insomnia. so there is no way of stating a "safe" or "unsafe" level of use. Different peoples' metabolisms work at different rates. The literature gives conflicting reports. larger doses last longer due to the fact that it is removed from the blood at a finite rate. or can take as long as 30-40 minutes if ingested orally. tooth grinding. and other effects. Vasoconstriction (tightening of blood vessels) and pupil dilation are also common. among other things. heart rate. Methamphetamine and other CNS stimulants have strong bronchodilation effects. Onset Onset can be immediate (in the case of injection). accelerated heartbeat. probably due to the similarity to adrenaline (epinephrine). smoked or injected.Pharmacology This is one of the most difficult sections to write. due to the fact that many criterion are subjective. restlessness. sweating. some studies have shown slight increases in mental capacity on simple tasks. It has been prescribed for attention deficit disorder. extreme nervousness.

The same reaction which attracts the free base to HCl could also attract it to other molecules. For More Information Add references for pharmacological data here Chemistry This is the easiest section to write. causing irritation and other symptoms.alpha-dimethylphenethylamine Alternate Names: • • • • • • d-N-methylamphetamine d-deoxyephedrine (e.alpha-Dimethylbenzeneethanamine Previous name: d-N. This is for physiological reasons.Confusing reports here tend to center around the effects of fatigue on mental capacity. Trademarks: • • Amphedroxyn Desfedrin . minus an oxygen) d-desoxyephedrine 1-phenyl-2-methylaminopropane d-phenylisopropylmethane methyl-beta-phenylisopropylamine Trademarks: Norodin Methamphetamine Hydrochloride: What we mean by hydrochloride is that it has formed a "salt". right-handed ephedrine. since I can be relatively sure of the facts. Preliminary doses tend to produce the former. but an HCl molecule has become attracted to the free base.g. for three or more days) tends to produce the latter. Emotional responses may range from euphoria to anger and paranoia. although I have not seen a good reference on this yet. while continued use (e. Naming Methamphetamine Free Base: Chem Abstract Service (9th+ CIP) uninverted name: N.g. Molecular Information All information is on free base unless otherwise noted. You will notice that the salt form is much more common. The basic structure is unchanged. It appears that these feelings may be linked to the neurotransmitters dopamine and/or serotonin. and the most fun. the hydrogen from the HCl has become attracted to the nitrogen in the free base. In this case.

13% N 9.is cool. energy. The human terms: The d.48% H 10. If you have time.39% Melting Point 170-175 degrees C Chirality Explain isomers in chemical terms. remember. the l.into d.by oxidizing it and reaminating it as described in the "critique" of the Phrack synthesis. you can separate the two and reprocess the l.is shit. etc. Discuss other opinions (some say chirality does not matter. and equipment.24 Percent Composition C 80.) For More Information The Merck Index Synthesis Industrial Methods (add references) • Reduction of ephedrine or pseudoephedrine .• • Methedrine (many others) Structure Formula Methamphetamine Free Base: C6H6CH2CH(NHCH3)CH3 Hill Convention: C10H15N Molecular Weight 149.

will give d-meth. Hydrogenating this product is easy: use lithium aluminum hydride. whether direct or via the halide. requires the use of not just ether.ca (Yogi Shan) Hydrogenation starting with (-) ephedrine. Apartment manufacture of meth is not possible.• • Reducing condensation product of BMK and methylamine Synthesis from D-phenylalanine Field Methods General Add a lot here on different methods. which does the reducing.edu (Lamont Granquist) From Fester. the alcohol grouping of ephedrine. From: lamontg@u.edu (Jason Kennerly) writes: Manufacturing methamphetamine. an easy synthesis with a very high yield is to reduce the condensation product of phenylacetone and methylamine. you get dl-meth. but none to practical to attempt. BAD STUFF! There are other recipes. on the other hand.) From Ephedrine or Pseudoephedrine From: ez026264@dale.bnr. The equilibrium is shifted in favor of dissociation by adding red phosphorus to the mixture. From: yshan@bcarh697.ucdavis. Reduction of ephedrine with HI is a little better than LAH reduction.gina. Condensation Product of Phenylacetone and Methylamine From: ez026264@dale. . The dissociation is reversible. but reducing agents such as LiAlH4. The benefit of this method is that different amines can be used to produce novel N-alkyl amphetamines (ethamphetamine.washington.edu (Speed Raver) Assuming you don't have amphetamine lying around. etc. The product of this step is N-methylamphetamine and HCl. or PPA is reduced by boiling one of these compounds in a mixture of hydroiodic acid and red phosphorus. Hydroiodic acid works as a reducing agent because its dissociates at higher temperatures to iodine and hydrogen.ucdavis.edu (Lamont Granquist) jkenner@cello. Reduction With Hydroiodic Acid and Red Phosphorus From: lamontg@u. Secrets of Meth Manufacturing: METHOD 4: REDUCTION WITH HYDROIODIC ACID AND RED PHOSPHORUS In this procedure. Reacting your ephedrine with thionyl chloride replaces the OH with Cl to produce N-methyl-alphachloroamphetamine as an intermediate. pseudoephedrine. sodium borohydride. If you start with dl-ephedrine.washington.calstate. The only difference between methamphetamine and (pseudo)ephedrine is that damn alpha-hydroxy group. or even hydrogen gas with nickel or platinum metal as a catalyst. The red phosphorus reacts with the iodine to produce PI3.edu (Speed Raver) Making it from ephedrine or pseudoephedrine is possible. tertbutylamphetamine. Evaporate off the water and you have methamphetamine hydrochloride.

iron oxide. Those who insist on finding out for themselves. This method has the advantage of being easy to do. and the mixture is boiled for one day. Also added to the flask are 40 grams of red phosphorus and 340 ml of 47% hydroiodic acid. Now red phosphorus is on the California list of less restricted chemicals. I can't say . Since the production of HI from iodine and red phosphorus gives off a good deal of heat. MnO2. To do the reaction. when making hydroiodic acid from iodine and red phosphorus. Naturally. A typical composition of the striking pad is about 40% red phosphorus. One might think that this is easily gotten around by making your own red phosphorus. I would think that so long as one is over 3 molar acid. Exactly how strong the acid needs to be. page 2305. In some reductions. The way around the roadblock here is to just boil off some more of the water from the ephedrine pill extract.which then further reacts with water to form phosphorus acid and more hydroiodic acid. With a small amount of due care. it is wise to chill the mixture in ice. As I recall. the red phosphorus acts as a recycler. This same acid and red phosphorus mixture can be prepared from adding 150 grams of iodine crystals to 150 grams of red phosphorus in 300 ml of water. it seems basic precautions are routinely ignored. I can tell you that experiments have shown that one molar HI is ineffective at reducing ephedrine to meth. The 47% acid mentioned above is a little over 3. The determined experimenter could obtain a pile of red phosphorus by scraping off the striking pads of matchbooks with a sharp knife. the acid is prepared first. will see Journal of the American Chemical Society. They can be avoided in the first place if. It was formerly the most popular method of making meth from ephedrine. The use of the sulfate salt is unacceptable because HI reduces the sulfate ion.5 molar. From checking out typical samples of street meth. Since the hydrogen atom of the HI is being absorbed by the ephedrine. along with about 30% antimony sulfide. This will be a hassle for some. and slowly add the iodine crystals to the red phosphorus-water mixture. so this interferes with the reaction. a 1000 ml round bottom flask is filled with 150 grams of ephedrine hydrochloride (or PPA-HCl). This length of time is needed for best yields and highest octane . the reaction will work. but this is a process I would not want to undertake. stealing. Another problem with this method is that it can produce a pretty crude product if some simple precautions are not followed. The striking pad on books of matches is about 50% red phosphorus. it is a tedious process to get large amounts of red phosphorus by scraping the striking pads off matchbooks. and allowed to come to complete reaction for 20 minutes before adding the ephedrine to it. The red phosphorus then goes on to make HI by the above mentioned process. the Poor Man's James Bond also has a formula for making red phosphorus. or making your own pure hydroiodic acid. I believe that the by-products in the garbage meth are iodoephedrine. If a careful fractional distillation is done. Those with a knack for scrounging from industrial sources will profit from knowing that red phosphorus is used in large quantities in the fireworks and matchmaking industries. the need for HI is dispensed with just by mixing red phosphorus and iodine crystals in a water solution. Ever hear of phosphorus shells? I would much rather face the danger of exploding champagne bottles. and glass powder. This should produce the strong hydroiodic acid solution needed. and make the acid mixture in fresh pure water. and the previously mentioned azirine. volume 68. these products can be removed. I don't think these contaminants will seriously interfere with the reaction. so an increased level of subterfuge is called for to obtain significant amounts. and lesser amounts of glue. this is an excellent alternative to either purchasing. With the ingredients mixed together in the flask. because the obvious procedure to follow is to use the water extract of the ephedrine pills to make the HI in. a condenser is attached to the flask.

When all of the l-ephedrine had been added. and the atmosphere above the condensed ammonia was not flushed with nitrogen gas. JFSCA. The next step in processing the batch is to neutralize the acid. With free base meth now obtained. If the chemist's cooking has been careful.. the next step. The strongly basic solution is shaken vigorously to ensure that all the meth has been converted to the free base. the red phosphorus is filtered out. If so.numbers on the product. A red color may indicate that all the phosphorus is not yet out. A. The THF layer was . The remaining solution was removed from the flask to a separatory funnel. D. as usual. Vol. To do this. with no special treatment of the tetrahydrofuran (THF).C. This brings the meth out as liquid free base floating on top of the water. the mixture is quite red and messy looking from the red phosphorus floating around in it. A three-neck flask was cooled in a dry ice/acetone bath. The filtered solution should look a golden color. It can be removed by adding a few dashes of sodium bisulfate or sodium thiosulfate. is to form the crystalline hydrochloride salt of meth. a distillation is called for to get pure meth free base. The flask was removed from the cooling bath. pp. The filtered-out phosphorus can be saved for use in the next batch. A series of doubled up coffee filters will work to get out all the red phosphorus. When one day of boiling under reflux is up. If this is the case. but real filter paper is better. and added to the condensed ammonia. the color of the toluene extract will be clear to pale yellow. where the aqueous layer was discarded. an additional funnel containing l-ephedrine base in THF was fitted into one side neck. 3. water was added to the remaining solution until it cleared and any remaining lithium metal was decomposed. A deep royal blue color was noted as the lithium metal dissolved in the condensed ammonia. the product is sufficiently pure to make nice white crystals just by bubbling dry HCl gas through the toluene extract as described in Chapter 5. 720-723 Procedure: All the chemicals were reagent grade. Small pieces of lithium metal were rinsed in petroleum ether. Anhydrous ammonia gas was condensed and collected in the flask. The l-ephedrine was added drop wise to the lithium ammonia solution over a period of approximately 10 minutes with stirring." Journal of Forensic Sciences. patted dry. If the toluene extract is darker colored. it is filtered again. While it is cooking. May 1990. 35. No. R. and the meth free base extracted out as usual. "Lithium-Ammonia Reduction of Ephedrine to Methamphetamine: An Unusual Clandestine Synthesis. A condenser was fitted in the center neck. and a rubber stopper fitted with a glass tube extending to the bottom of the flask was fitted in the third neck. and the condensed ammonia was allowed to warm to room temperature and evaporate from the flask through the side necks. The yield of pure methamphetamine hydrochloride should be from 100 to 110 grams. and McGrath. Next. then it is diluted with an equal volume of water. the flask is allowed to cool. If filtering does not remove the red color. ammonium chloride was added slowly to the solution. Lithium-Ammonia Reduction Reference: Ely. there may be iodine floating around the solution. The procedure for that is also described in Chapter 5. a few hundred mls of toluene is added to the batch. When most of the ammonia had evaporated. A strong lye solution is mixed up and added to the batch with shaking until the batch is strongly basic.

adding water to quench will *definitely* be exciting. using the same procedure except that the reaction was not quenched with ammonium chloride. quite an entertaining and educational article . after they replaced that wing of the lab. if one were using Na rather than Li (Na is the Birch. The time required for the reaction to proceed from the condensing of the ammonia gas in the reaction flask until the excess lithium was decomposed was approximately one hour. using Na. The same procedure was used. and then. From: dmurphy3@aol.>) From: eleusis@netcom. All in all. it was found that the reaction converted phenylpropanolamine to amphetamine and methylephedrine to dimethylamphetamine. It would have been even more interesting had they used the real Birch method. Also. a slightly modified Birch reduction known by some other name I can't recall). any extra Li (or Na if doing the straight Birch method) would convert to the Hydroxide.-). but typically a water quench leads to the alcohol.com (Eleusis) Yep . which might fuck the product up a bit. Apparently they were following the guys handwritten notes. It was also found that the ephedrine would reduce to methamphetamine without the addition of ammonium chloride as a quenching agent. From: eleusis@netcom.com (DMurphy3) This may be so (in fact I read the same article). and the hydrochloride salt of the methamphetamine was made by bubbling hydrogen chloride through the THF. A second synthesis was conducted with l-ephedrine.dried with magnesium sulfate. which is what we were trying to get rid of to start with.For. Results: The reaction was found to reduce l-ephedrine to d-methamphetamine quickly and easily .-). substituting phenylproponolamine and methylephedrine as the starting materials. From Phenylalanine From: ez026264@dale.apparently that would be the case.edu (Speed Raver) . Furthermore. I like this article especially because the rinky-dink DEA chemists that wrote it didn't seem to entirely grasp the concept of the procedure they were doing (in fact. they decided not to "publish" those results . particularly considering the flammability of THF or ether.Sci. The majority of this time was spent waiting for the condensed ammonia to evaporate from the reaction flask. I too forget the Li named reduction). As well.ucdavis. article describing a "novel method of amphetamine production". especially when they tried the water quench .com (Eleusis) According to the infamous J. the researchers concluded that with or without an ammonium chloride quench yields were good. I bet you they *did* do that the first time.

) Phenylacetone From: jkenner@cello.. a solvent) and some gaseous pyridine. The difference between amphetamine and methamphetamine is the addition of a single methyl group (CH3) to the amino group sticking off the middle carbon atom in the chain. If you use hydrogen and metal for that step. which is more or less amphetamine with a COOH where the CH3 should be at the end of the chain. the amino group takes the methyl from the chloromethane and lets a hydrogen go. but let's just pretend you have some and you want to spice it up a bit. The hydrogen joins the liberated chlorine. The pyridine is optional.calstate. I'm interested in this since I haven't seen it anywhere else (unlike some people. which falls off and is replaced by H when you give it lithium aluminum hydride. Adding it drives the reaction a bit by pulling the excess HCl out of the equation. Methylamine From: dnaugler@sfu. Synthesis from Amphetamine From: ez026264@dale. because 1 its more readily available and 2 it will prevent any diphenyl/triphenyl/xphenyl acetone from forming. Vaporize your amine (your amphetamine) with a bunch of vaporized chloromethane (CH3Cl.A surprisingly simple synthesis is possible from the amino acid phenylalanine. which is available at health food stores for about $14 for 100 tablets. When that carbonyl is reduced. you could even just go with acetone as the solvent too. An excess of methylamine will inhibit the secondary reactions. but it's not necessary. Hell. but still may serve as interesting lessons in applied chemistry. if your making straight amphetamine. so best save time + effort and use them and do both reductions at once. voila.edu (Speed Raver) One of the easiest ways to make methamphetamine is from amphetamine. you'll ha v e to reduce the carbonyl group with one of the hydrides. Typically. and the resulting HCl is soaked up by the pyridine.edu (Jason Kennerly) Let me know how bromobenzene + acetone + NaOH turns out. sodium borohydride. Phenylalanine is 2-amino-3-phenylpropanoic acid.gina.calstate. or hydrogen gas and nickel/platinum. Fortunately. substituting amines is really simple.ucdavis. if you could come up with a good way to separate the 2-aminopropane you'd make with the . a reductive amination done in a parr bomb or using sodium cyanoborohydride is done with a five times molar excess of methylamine (or methylamine hydrochloride. Go back up to that first one I mentioned for upgrading amphetamine into methamphetamine.ca (David Naugler) jkenner@cello. Thionyl chloride will replace the OH with a Cl. I don't have the Abstracts in my closet :) Make sure to use an EXCESS of acetone. producing a crazy looking monster with two "wings" This last question is solved be reference to a principle called the law of mass action. Incomplete Syntheses These are methods that are subjectively evaluated to be less useful. you now have amphetamine. Of course..gina. this assumes you have amphetamine in the first place.edu (Jason Kennerly) writes: Does the P2P method [reductive amination] ever end up attaching TWO chains to the same methylamine.

I'd suggest a two solvent system with methanol and methylethylketone. Note: There is no doubt a segment of the dealers who will add food coloring . don't get it on you or breathe the fumes. their solvency power will greatly increase. Read a lab handbook about two-solvent purification by crystallization. this can happen unexpectedly and when it does. Coloration From: jkenner@cello. it shouldn't be too hard. However. Related Chemistry amphetamine ephedrine pseudoephedrine phenylalanine Street Knowledge Very scientifically unsound.njin. the BASE form is miscible w/ H2O! Amphetamine BASE is only "slightly" soluble in water.net (Sean Casey) For a purification by crystallization of any of the HCL salts of ephedrine and related illegals. Smells like ammonia though. Given that this gunk has a bp of 33 or 34 degrees at standard pressure. products on the market today are often not colorless. Then precipitate the crystals with dry HCl or H2SO4? Question is. The following is a table of some common impurities and the colors associated with them. how much ammonia and reducing agent are you willing to waste on making 2aminopropane? Purification by Crystallization From: csc@pilot. Yes.. so if your really a purist you can dissolve your "mostly amphetamine some 2aminopropane" in ether and backwash with water maybe ONCE. As with any distillation there will be some left over. I wouldn't suggest ethanol or acetone as they tend to easily collect H2O. 2aminopropane (or "isopropylamine") is water MISCIBLE. maybe you should "catch" it in HCl water when you distill. but interesting nonetheless. redissolving your crystals. This tends to occlude a slight amount of solvent so keep your crystal size small and grind and dry the result. Never fear. Fascinating stuff. Be careful as methanol is toxic.edu (Jason Kennerly) Methamphetamine in its pure hydrochloride salt form is colorless. Both these solvents are easily available if you know where to look.gina..amphetamine. Street Doses An average wrap of speed contains less than 10% Amphetamines. (often as low as 2%) and over 90% of adulterants.calstate.

and run this test on it as well. Worth Noting: Cathinone and Methcathinone. If many "swirlies" appear. when reduced. Might be 100% cut [read: nothing] also. Rotate one filter. d-methamphetamine is. This is probably one of the more effective ways of smoking meth if you are careful. The DLPA-crank may in fact only be dlamphetamine. A handy thing to use as a "calibration" of sorts is to extract the l-desoxyephedrine from a Vicks Inhaler (which is l-methamphetamine). Same as Vicks: You've been ripped off ! -or. and when the resulting powder is heated (and the methamphetamine HCl melts) CO2 and methamphetamine base vapor is given off.. Dissolve the methamphetamine in distilled water. however the hydrochloride salt is often the form smoked as the base form is often an oil and is difficult to store. I am not sure what the cause of this is. but ethyl-ether would be better suited for this as it dries faster.there's so much unchanged ephedrine as to cancel the dextrorotary effects of the meth (l-ephedrine. This oil is often removed with acetone.. GREEN: Copper (or other metallic) salts somehow made their way in to the mixture. This is relatively uncommon however. or make sure the solution is well stirred.or some other such color to their drug to make it more appealing. BROWN: Oxidized red coloring (see above). probably due to the reaction vessel used in the manufacture.. and some of the sulfate was reduced to sulfur. optically active. but its most likely some form of oil. Dextrorotary product is almost certainly methamphetamine (or extracted dexedrines?) as its is not worth the trouble to get other dextrorotary precursors or resolve dl-amphetamine. . Pure methamphetamine HCl melts at around 170c (338f ). After you have done this. is dextrorotary (see explanation elsewhere) Opposite of vicks compared to water: DL-methamphetamine. or tablating agent was present in the reduction. • • • • • RED: The product was made from pseudoephedrine. You can test methamphetamine HCl for optical activity with the greyishclear plastic pieces from a pocket video game. The crystals can be carefully chopped and mixed with sodium carbonate. RESULT: • • • • Same as water: DL-methamphetamine (or other inactive) Most likely made from P2P (methamphetamine) or DLPA (phenylalanine).. with the philosophy that a brightly-colored product may sell better than an off color product. but in the "opposite" direction. and the red coloring of the tablet was not adequately washed away (it is difficult) ORANGE: Ephedrine sulfate was used. by nature. then place one of the optical filters (the grayish clear things from the games LCD display) in front. and one in behind of the solution. but do not dry out properly.. either formed in the reaction or left over from a very poor solvent. will become racemic due to the nature of the molecule (keytone). Smoking the HCl form is OK if you don't mind a small quantity of pyrolysed drug. It may or may not be harmless depending upon what it is. repeat the procedure with distilled water.. PURPLE: Iodine from a phosphorus-iodine reaction was not washed out. and work with. I'm not sure what other conditions cause this but I am aware that it happens easily. when dissolved in methanol. l-methamphetamine is also optically active. so methcathinone from the black market is almost definitely racemic. either use a different vessel to hold the solution in. and note the angle that is brightest and the angle that is darkest. Sometimes "speed" is present as waxy rocks that almost seem wet. transport.

I haven't forgotten my promise to post this paper. The smell of basic methcathinone has been reported to resemble that of "pistachio ice cream".. Suffice to say that if there is more than a very small amount left afterwards. Or a dealer uses Ephedrine as cut. It is more than likely the "didesoxyephedrine" referred to by Emde. You should become familiar with this as well. nirvana. Often this is a brown color as you stated for other by-products. The "BURN TEST" [residue test] Methamphetamine HCl is heated on a piece of foil over a flame. it will never dry out as completely one might suspect. giving it away in an instant. Often the fumes will ignite. including ammonia. Suffice to say that it is sweet. there is either cut or by-products present. in order to be able to know if suspected methamphetamine is in fact actually methcathinone. The problem with Ephedrine (far more so than pseudephedrine) is its beta-agonist properties . Thus you are smelling fatigue.com (DMurphy3) Sometimes 'speed' is present as waxy rocks that almost seem wet. there's no good way to tell which. The *oil* may be removed. either formed in the reaction or left over from a very poor solvent. As far as the rest of the post. especially considering it relies upon subjective senses too much IMHO. Methcathinone HCl has a higher melting point than methamphetamine HCl (like over 190c at least) and a characteristic smell. All amphetamines will pass this test that I am aware off. Even drying under heavy vacuum leads to only a temporary solution. From: dmurphy3@aol. followed by some degree of numbness. This isn't the most useful test in the world. Residue left behind may be by-product or "cut". I am currently trying gif type scans. from the body. as just such a procedure can be used on freshly produced methamphetamine to verify that the (pseudo)ephedrine was in fact reduced. pleasant. . either by resolution or by actually measuring it with optical filters). And no. but do not dry out properly. It may or may not be harmless depending upon what it is. by washing with ether.The EPHEDRINE/CAT TEST Its probably not too uncommon that some guy screws up a synthesis. It should first melt (at over 170c) then begin to fume. It appears to some extent in almost all syntheses relying on reduction and typically appears at the very end of the process of forming the HCl salt by bubbling HCl through the mixture. Myths and Rumors "Smelling meth on a person" Fatigue causes secretion of different chemicals.it raises blood pressure and pulse far more per "unit of high" than methamphetamine. but its most likely some form of oil. The scans just sucked when I tried to scan as text (5 pages magically became 10-15 of scrambled text). including the over-the-counter l-isomer present in vicks inhalers (the *only* way to check this is to check optical activity . and to a cat-head. Once it is exposed to air it quickly becomes an oil again. but it may help discern the product.. Methamphetamine is also more active on serotonin that amphetamine according to net resources. as you stated. Amphetamine has a bitter taste. It is advisable to become familiar with the many ways of synthesizing methcathinone from (pseudo)ephedrine. However. but by some chance gets a partial yield. I find it very useful and agree with it completely. The TASTE TEST [illegal without prescription snicker snicker] Methamphetamine has a very bitter taste. I am not sure what the cause of this is. not meth. a product of the coupling of two radicals of the reduced ephedrine or pseudoephedrine.

Usually something much cheaper (and less clean) is used. if possible. You can smoke it. The druggists at the drug store usually will know what's goin on if you buy quantity. What to do with it once you have made it. and swallow. and don't forget to cut it. "Used to cut other drugs" Overstated in this role. Issue Four. then you can just say yer from some nursing home. you probably already have.00 a gram. "Meth Oil" ?? "Speed Bumps" Incorrect Syntheses Phrack Magazine Volume One. mix it with vitamin B-12. Sodium Hydroxide--> This. and wrap it in tissue. "VICKS" nasal inhalers--> USE ONLY VICKS!! No other kind will work that I know of. unless its winter time. etc. Don't worry. You can also sell it. and snort it like cocaine. You need 12 of em. drinkable salt water can be made from lye and muriatic acid. They call it muriatic acid. It's used for cold weather starting of gasoline engines. For example.. LIST OF EQUIPMENT • • • • • • • Two large eyedroppers ten small glass bottles one large glass or porcelain bowl coffee filters one small jar with a top one Pyrex baking dish one glass test tube. it's drain cleaner. this does not mean it is itself poisonous. Take a ball about the size of a lead pellet. this is pure stuff!! List of chemicals and materials • • • • Dilute Hydrochloric acid--> This may be purchased at the hardware store. Remember."Made from poison" Made from several toxic chemicals. Phile / 8 of 11 THE TRIED AND TRUE HOME PRODUCTION METHOD FOR "METHAMPHETAMINE" Written and tested by: The Leftist. Otherwise buy em' 2 at a time. . and you're stockin up for the patients. it's a breez Just go to your local K-mart or Auto parts store. for about $65-70. but don't buy em' by the dozen. It's called "lye" at most places. Ethyl Ether--> You'll probably have to make this. These are at any drug store or grocery. and get a can of that "STARTING FLUID" it comes in a spray can. It sold as a brick and driveway cleaner. Get a friend to help you. or you can put it in capsules and use it.

It is very important to expose ever molecule of the free-base to the ether for as long as possible. combine 1. don worry about it) You'll use this in the procedure below. Put the cap on it. and put it in the refrigerator if you can. Break open the inhalers. cap the bottle and shake for 5 minutes. Cap the bottle. of ether. Shred cottons in this solution. Repeat this step until the mixture remains cloudy. Squeeze all juice out of filters after you knead. Pour 1/4 teaspoon of the lye crystals into the bottle and agitate.-==*(> N O T I C E <)*==PLEASE! DON'T SMOKE IN THE SAME ROOM WHEN YOU DO THIS. THE TRIED AND TRUE HOME PRODUCTION METHOD 1. If there is anything left from step (3). 6. but I have found that if you leave it on top of a hot-water heater (like the one that supplies hot water to your house) for about 2-3 days. 11. Pour enough of the solution into a small bottle to fill it 1/3 full. Tap the side of the bottle to get this layer as thin as possible.1/3 oz. 4. Throw the filters away. and throw the rest away. repeat the procedure with it. 7. Place the cottons that were inside in a jar and close the lid. When it settles. Save any leftover juice for the second batch. The chemicals in the inhalers have been bonded to the HCl. Shake the bottle for 2 minutes. The free base has now been bonded to the HCl/water mixture.) 2. 10.) You can do it bare-handed if you' got tough skin. (Remember you use all 12 cottons. Save the top layer. and throw away the water layer. Some notes: Police are now calling this the "New Cocaine". Repeat this until you have about 3 oz. 8. and the oils have been filtered off. THIS RECIPE HAS BEEN TESTED AND THIS IS T BEST WAY TO DO IT. AND DON'T EVEN START TO DO THIS UNLESS YOU HAVE ABOUT 3 HOURS SPARE. 5. Remove the top layer with the eyedropper. water and 2/3 oz. (If you can't. In the bowl. remove the top layer and throw it away. Do this carefully. Then fill the rest of the way with water. Then. a pair of real sharp scissors does this good. There will be a middle layer that is very thick. FOLLOW THESE INSTRUCTIONS EXACTLY. as the mixture will become hot. OPEN A WINDOW IN THE ROOM IF POSSIBLE. and agitate for about 8 minutes. Pour the top layer from step (8) into the bottle. . the remaining crystals will be Methamphetamine. and knead for 5 minutes with hands. and about 10 drops of acid. and give off a gas. Let the mixture settle. You can do this o the stove. Fill a bottle half-way with water. draw off the top layer with the eyedropper. Fill the bottle from step (5) up the rest of the way with ether. DON'T TAKE SHORTCUTS. 3. It will be necessary to this several times to get that awful smelling oil out. and throw em away. Filter the remaining liquid into the quart jar. being careful not to get any of the middle layer in it. (ALWAYS BE SURE THERE'S CLEAN RUBBER GLOVES on your hands. Evaporate the solution in the Pyrex dish on low heat. PREPARING ETHER! (DO THIS FIRST) Take one of the small bottles and spray starter fluid in it till it looks half-full. and cap it. 9. muriatic acid.

or experiment bottles seem to work the best for smaller batches.can be obtained from hardware stores. is the "tried and true method" for prepping meth from Vick's nasal inhalers. such as Prestone. in the pool section. then reduce it. NaOH .. Also known as methamphetamine. usually from a large supermarket. Sorry. The measurements are not exact.it's really cheap. The d.isomer of methamphetamine is the relatively inactive one. These are found at any drug store or grocery. aspirin.also called lye . You'll get l-meth and that's that. reformulated: List of chemicals and materials • • • • • Dilute HCl . so you don't have to be either.aka Diethyl Ether . Look for one that says "high ethyl ether content". They contain 50mg of l-desoxyephedrin e per container.ucdavis. so you have no reason to use the nasty stuff from the tap. Do things right. Distilled water . be sure you don't use too much water. . from Phrack magazine. In step 9. but the Isomer Fairy can't wave her magick wand and reverse the chirality of the molecule. There are better recipes out there but if you cant get your hands on sodium borohydride and a reflux condenser then don't even mess with this recipe! But the ETHER extraction method is as true today as it was then! From: ez026264@dale. Desoxyephedrine .can be obtained from supermarkets in the "drain cleaner" section. etc. so be sure you are well ventilated. Ethyl Ether .It is very easy to become delirious off the ether fumes. "Red Devil Lye" recommended." The l.also called Muriatic acid . The procedure described would extract the l-meth from the inhalers and collect it and that's it. usable as a (mild) nasal decongestant.edu (Speed Raver) One. ==Phrack Inc.com (Admiral Hunter) (WARNING!) This recipe is bogus! YOU WILL NOT HAVE METHAMPHETAMINE! You have simple extracted pseudoephedrine! All this stuff will give you is engziety(sp?). I'm sorry. condense it with methylamine. but soaking inhalers in HCl then separating the "juice" with Et2OH just won't do it.. 6 containers will give 300mg of l-desoxyephedrine. I mean it!!! Small.== From: rkhunter@hale. this is the water you have to use to evaporate. Remember. The only way to change between the two isomers is to oxidize the l-meth into phenylacetone.isomer is the one that every one wants and that Uncle Sam has declared is just too cool for any one except doctors. Vick's nasal inhalers contain "l-desoxyephedrine. The same recipe (for extraction of l-isomer).Et-0-Et ." another name for "l-methamphetamine.can be obtained from "VICKS" nasal inhalers.cts.can be obtained from engine starting fluid.

Take the unmarked small bottle and spray starter fluid in it until it looks half-full. This step neutralizes the HCl in the salt. as the mixture will become hot. Rinse the other bottle and let it stand. Do this carefully. and tap the side to try and separate the clear upper layer. and put it in the freezer if you can. Place the cottons that were inside in a bottle (the unmarked one) and close the lid. draw off the top (ether) layer with the eyedropper. Place the ether in the marked container. avoid any flames as usual. of ether. Save any leftover juice for the second batch.5oz. and knead for 5 minutes with your gloves on. and give off hydrogen gas and/or steam. Do not use ethyl ether near flame or non-sparkless motors. 3 oz. Let it sit for a minute or two. and throw away the lower (water) and cloudy layer. Pour 1/8 teaspoon of the lye crystals into the bottle and agitate. The salt is soluble in water. cap the bottle and shake for 5 minutes. Put the cap on it. but not important) o one should be marked at 1. H2 gas is explosive and lighter than air. Even a small evaporated amount is quite noticeable. I use 6 cottons. 3. use tape on the outside to mark it (you might want to label it as ether) o one should be clear (and it can't be the marked one) a Pyrex dish (the meatloaf one is suggested) a glass quart jar sharp scissors clean rubber gloves coffee filters a measuring cup measuring spoons • • • • • • • Preparing your reagents Preparing Ethyl Ether WARNINGS: Ethyl Ether is very flammable and is heavier than air. This step bonds the HCl to the meth. 2. It is also an anaesthetic and can cause respiratory collapse if you inhale too much. Squeeze all juice out of filters after you knead.List of equipment • • a glass eyedropper three small glass bottles with lids (approx. Extracting l-desoxyephedrine 1. leaving the insoluble free base (l- . Shred cottons in this solution. 4. 5. a pair of real sharp scissors does this well. Repeat this until you have about 1. In the Pyrex dish.5 oz. It will be necessary to this several times to get the awful smelling oils (check the packaging if you are interested in which ones).. Then fill the rest of the way with water. Ethyl ether is very pungent. The chemicals in the inhalers have been bonded to the HCl. combine 2/3 oz. and thus dissolves. Remember to wet the filters with distilled water before you pour. forming the HCl salt (what you want). muriatic acid. and the oils have been filtered off. Pour enough of the solution into the clear bottle to fill it 1/3 full. Then. otherwise you'll lose some product. Discard the filters and clean the Pyrex dish. water and 1/3 oz. Break open the inhalers. and discard them. Filter the remaining liquid into the quart jar. Repeat this step until the mixture remains cloudy.

or a weak acid. and about 5 drops of muriatic acid. Cap the bottle. As with the Vick's Inhalers "recipe. I suggest no more than 5-10s at one time. If there is anything left from step 3. Microwaving can result in uneven heating. Place the removed ether layer into a third bottle. First Batch: 120mg Meth HCl Estimated: 300mg (100% of theoretical. I'm sorry to say that no method attempting to directly reduce (pseudo)ephedrine's hydroxyl group is going to work. or even lithium aluminum hydride and expect it to reduce at all.09 $ 3. 8. repeat the procedure with it. 11. that means you have too little liquid left to microwave. There will be a middle layer that is very thick. but reduction with sodium borohydride.desoxyephedrin e) again. 6.73 $ 1. If you microwave it. Make sure to get rid of all the ether before going to step 11! 10.92 Pyrex measuring cup: $ 2. This is why this bottle should be clear. This time. Add to the third bottle enough water to fill it half-way. we're getting rid of ether-soluble impurities. For 3 oz. If it starts "popping". You can put it under a bright (100W) lamp instead. You can't expose it to a strong acid. Cap it. The free base has now been bonded to the HCl again. 9. You can do this on the stove or nuke it in the microwave (be careful of splashing). disregarding HCl) Estimated Cost of Material (in US dollars): Ethyl Ether: Inhalers: Eyedroppers: Pyrex dish: $ 1. Let the mixture settle.79 Catalytic Reduction From: ez026264@dale. this should take only 3 repetitions or so. Tap the side of the bottle to get this layer as thin as possible. Evaporate the solution in the Pyrex dish on low heat. Shake the bottle for 2 minutes." you get a lot of . but I have found that if you leave it on top of a hot-water heater (like the one that supplies hot water to your house) for about 2-3 days. This will cause the free base to dissolve into the ether (it -issoluble in ether).edu (Speed Raver) A more credible sounding one mentions that "methamphetamine is prepared by the calalytic reduction of pseudoephedrine in acetic acid" blahblahblah and then goes on to describe. forming a water soluble salt.59 $19. remove the top layer and throw it away. It is very important to expose every molecule of the free-base to the ether for as long as possible. Why do we do this? So that we can get rid of any water-soluble impurities. not catalytic reduction via acetic acid. Remove the top (ether) layer with the eyedropper. or sodium borohydride. Fill the bottle from step 5 up the rest of the way with ethyl ether.ucdavis. anyway.55 Lye: $ 2. bottles. When it settles. the remaining crystals will be Methamphetamine HCl. 7. being careful not to get any of the middle layer in it. and agitate for about 8 minutes.

and acids. but it's not and there's not. Your post was interesting. All you'll be left with is your (pseudo)ephedrine and a bunch of acid. This is because the hydroxyl group (the OH in ephedrine) is on a very acidic carbon (the first carbon away from the ring) and a hydroxyl group is very basic. From: yshan@bcarh697. You're not getting a basic group off an acidic carbon without a fight. and LiAlhydride aren't gonna fight that hard. but this is not quite true. but it ain't d-meth. there might be some chance. You add a little perchloric. If the hydroxyl were on the second carbon from the ring (the carbon with the amine group. UTOPIAN PHARMACOLOGY Mental Health in the Third Millennium MDMA and Beyond . borohydride.bnr. lithium. like you mentioned. Direct hydrogenation over Pd or Pd on a carrier is well known and facile. Thus making the intermediate halide via SOCl2.ca (Yogi Shan) I'm sorry to say that no method attempting to directly reduce (pseudo)ephedrine's hydroxyl group is going to work.SOMETHING. the NH2 or NHCH3). phosphoric or sulphuric acid. which esterifies the-OH group that you're complaining about. and/or sodium and lotsa hydrogen gas. is unnecessary.

Merck were searching for a good vasoconstrictor. Jacobsohn. SmithKline were interested in MDA's potential as an antidepressant and a slimming-drug. MDMA's military potential was not realised. openness and sense of closeness to others induced by MDMA can promote an honesty of self-disclosure that might be manipulated for malign ends. MDA was patented by drug company SmithKline French for use as a tranquilliser (1960) and appetite-inhibitor (1961). MDMA is listed on Merck's patent-application merely as a chemical intermediate "for products of potential pharmaceutical value". was tested at the US Army's Edgewood Arsenal in Maryland. 2. MDMA differs structurally from MDA only in its additional methyl group attached to the nitrogen atom. a styptic to reduce bleeding.350. Merck's researchers had no idea of the significance of what they had done. However. 8. . 5. 6. code-named EA-1475. sustainable analogues of MDMA be developed? There is an urgent need for non-neurotoxic empathogens and entactogens suitable for lifelong use. pigs. 4. The CIA's Project MK-Ultra was investigating new techniques of brainwashing. In 1912 two of their chemists. rats.4-methylenedioxyamphetamine [MDA] was first synthesized in 1910 by the same two unsung Merck researchers who went on to create MDMA. A brief history of MDMA MDMA [3. MDA's own empathy-enhancing effect at low doses was explored by Chilean anthropologistpsychiatrist Dr Claudio Naranjo in his private practice. Mannish and W. monkeys and dogs. MDMA was used only on non-human animals: mice. MDMA's parent and longer-acting metabolite. Thankfully. Alas no single "magic bullet" yet exists that replicates the subjective effects of MDMA on a long-term basis. created MDMA as a by-product while attempting to synthesise hydrastinin. and promptly forgotten. 9. MDMA.1. Dr Naranjo discusses MDA-assisted therapy in his classic The Healing Journey (1973). Hence most of us are doomed to display the quasi-psychopathic indifference to each other characteristic of the MDMA-naïve state. The heightened emotional responsiveness. unlike LSD or the ill-named "truth drug" scopolamine. Germany on May 16th 1914. For although MDMA is no infallible truthserum. 3. 3. espionage and mind-control. issue number 274. 7. MDMA/Ecstasy A brief history of MDMA The MDMA Experience MDMA : neurotoxicity MDMA : neuroprotection Ecstasy for life? The molecular machinery of magic Post-Darwinian Medicine Beyond MDMA : mental superhealth MDMA/Ecstasy Can safe. MDMA was patented in Darmstadt.4-methylenedioxy-methamphetamine: 'Ecstasy'] was first1 synthesized in 1912 by the German pharmaceutical company Merck. lowering of defensive barriers. Fortunately. this hasn't yet happened on an organised scale. G. MDMA surfaced again briefly as one of a number of agents used in clandestine US military research during the 1950s. its effects on the human user might indeed be abused for sinister purposes by skilled interrogators. In 1958 human trials were conducted.

R. Leo Zeff. Later. I have never felt so great or believed this to be possible. Rapturous delight. no one wanted a re-run of the 60s. but how many people know what it means?" Condemned by purists as a cynical marketing ploy. was coined in 1981 by a member of a Los Angeles distribution network. Dr Shulgin himself reportedly felt MDMA came closest to fulfilling his ambition of finding the perfect psychotherapeutic drug.E." In the first published scholarly paper [Shulgin. MDMA's now universal brand-name. J Adler ["High on 'Ecstasy". a state of sudden intense feeling. the brand-name "Ecstasy" isn't wholly misleading [ecstasy: "an overpowering emotion or exaltation. MDMA was commonly known as "Adam". PiHKAL describes the synthesis and systematic testing on human subjects of a range of novel or neglected phenethylamine research drugs.: Characterization of three new psychotomimetics.A. Dr Shulgin had himself synthesized MDMA in 1965. quoted in Bruce Eisner's Ecstasy:The MDMA Story (1989). Unsurprisingly..R. an error of omission he later did much to repair. and there is nothing but pure euphoria. 1978] on MDMA use in humans. They in turn introduced MDMA to colleagues as a valuable adjunct to psychotherapy. The unnamed distributor. April 15 1985] likened his MDMA experience to "a year of therapy in two hours". MDMA was profiled by the San Francisco Chronicle as "The Yuppie Psychedelic" (10 June 1984). an allusion to "being returned to the natural state of innocence before guilt." The well-connected stepfather of MDMA soon introduced the drug to the wider scientific community. & Willette. PiHKAL also offers a uniquely sophisticated methodology for human psychopharmacology and the scientific study of mind as an experimental discipline. and marvelous feeling of solid inner strength continued throughout the rest of the day and evening. Dr Shulgin and his wife Ann published PiHKAL [Phenethylamines I Have Known And Loved]: A Chemical Love Story.C. In: Stillman. Inevitably word leaked out. a graduate student in the medicinal chemistry group he advised at San Francisco State University. notably the "Johnny Appleseed of MDMA".T. Dr Shulgin and Dr David Nichols describe the effects of MDMA on the human psyche as "an easily controlled altered state of consciousness with emotional and sensual overtones. Tipped off by Merrie Kleinman. "Ecstasy". The identity of the first human being to take MDMA/Ecstasy isn't known. Mental transport or rapture from the contemplation of divine things"].unfortunately the compound was to prove too psychedelic for licensed clinical use. The frenzy of poetic inspiration. Some of Dr Shulgin's friends. the legendary Californian psychedelic chemist Alexander ("Sasha") Shulgin synthesized and taste-tested MDMA at incrementally ascending doses.) The Pharmacology of hallucinogens. over a thousand private psychotherapists in the USA were using MDMA in their clinical practice.D. shame and unworthiness arose".. The drug gained prominence only in the late 1970s. But MDA was popular as "the love drug" in the counterculture of the 1960s. 'Empathy' would be more appropriate. but hadn't tried it. The cleanliness. (Eds. . By the early 1980s. Some people report feeling truly well for the first time in their lives. MDMA was used discreetly. were professional therapists. Many first-time MDMA users do indeed become ecstatic. Harpers Bazaar described MDMA as "the hottest thing in the continuing search for happiness through chemistry".E. & Nichols. clarity. I am overcome by the profundity of the experience. In Newsweek. MDMA use soon spread beyond the couch and clinic to the wider world. in 1991. Ironically. The effects of a 120mg dose of MDMA are recorded in Dr Shulgin's lab-notes (Sept 1976): "I feel absolutely clean inside. apparently chose the name "Ecstasy" because "it would sell better than calling it 'Empathy'. New York: Pergamon.

perhaps 10%-15% of tablets consumed contain MDMA as the sole active . disciples of the Bhagwan Shree Rajneesh. Purity varies. to "Ecstasy". Yet the Criminal Justice and Public Order Act 1994 sought to criminalize an entire youth-culture by suppressing music played publicly with "sounds wholly or predominantly characterised by the emission of a succession of repetitive beats". MDMA was especially popular in Texas. Ibiza was popularly known as "XTC Island". a tongue-in-cheek allusion to the botanical origins of its precursor. Germany.e. Mass-production of MDMA by the so-called "Texas Group" began in 1983. MDMA and assorted psychedelic amphetamines had been outlawed in the UK since 1977. Cult members slipped MDMA into the drinks of rich sympathisers to open up their hearts and their wallets. The drug was even marketed via pyramid-style selling-schemes. Otherwise. These primary precursor chemicals of MDMA are produced in India. In 1985 the drug-warriors succeeded in having MDMA made Schedule One. dill. the psychotherapeutic tool. Safrole is also present in nutmeg (Myristica fragrans). isosafrole. Schedule One is the most restricted of all drug categories i. The Conservative Government and its allies in the British press were aghast. and increasingly elsewhere. Hundreds of thousands of tablets were consumed each weekend in the famous "Summer of Love" (1988). The DEA reacted by petitioning to have MDMA banned altogether. Ecstasy could be bought in little bottles at convenience stores under the label "Sassyfras". where the Southwest distributor for the Boston Group launched his own commercial operation. Over twenty recipes have been described in the literature. Soon production and distribution of the world's leading empathogen-entactogen fell into the hands of organised crime. perhaps 80-90% of the world's MDMA was manufactured in Belgium and the Netherlands. Russian-Israeli syndicates and Eastern European chemists are now increasingly active too.In the early 1980s. MDA. then today it might be marketed as "natural" or "naturally-inspired". Poland. parsley seed. vanilla beans. Ecstasy became associated with the birth of Acid House music in the Spanish tourist resort of Ibiza. Only seven are common. supply (and demand) soon mushroomed. in high schools and on dance-floors. A moral panic set in at the threat to the nation's youth. If MDMA were on-patent. MDMA was first introduced to Europe via the sannyasins. By the turn of the millennium. and calamus. but Nature has not been so kind. it lacked safety for use even under medical supervision. saffron. American production of MDMA beyond the research laboratory was effectively controlled by chemists known as the "Boston Group". or safrole. Oil of sassafras is found in the root-bark of US East Coast tree Sassafras albidum and from the above-ground woody parts of the South American tree Ocotea pretiosa. an estimated several million people worldwide were taking Ecstasy and allied research chemicals each month on college campuses. China. It could be purchased via toll-free 800-numbers by credit card. MDMA had metamorphosed from "Adam". MDP2P (3. "Sannyasa" is a Sanskrit word meaning complete or perfect renunciation. Somewhat incongruously. MDMA had allegedly "no legitimate medical use or manufacturer" in the USA. The essential oil safrole occurs naturally as the primary constituent of oil of sassafras. By the summer of '86. Early in the twenty-first century. Groups with access to MDP2P can make MDMA via a simple conversion process. The UK's rave scene was born. the party drug. Typically. and it carried a "high potential for abuse". Ecstasy was distributed openly in bars and nightclubs in Dallas and Fort Worth. Returning tourists and disc-jockeys took the message back home. MDMA must be synthesized from piperonal. safrole or isosafrole are first converted to MDP2P. crocus.4methylenedioxyphenyl-2-propanone) is a commercial product used by the flavouring and fragrance industry. Clandestine production is easiest starting with MDP2P. The expertise needed in MDMA production varies according to the route of synthesis. But by then MDMA's fame had spread across the Atlantic. MDEA.

ingredient. its increased synaptic release. Pills sold in clubs often contain less. The consequent additional flood of serotonin in the user's synapses is soon followed by an increased release of dopamine especially in the reward centres of the striatum and nucleus accumbens. Higher levels substantially increase oxidative stress and magnify the risk of toxicity. Taking MDMA causes both an increased neuronal reuptake inhibition of the neurotransmitter serotonin (5-hydroxytryptamine. the drug is snorted. MDMA is more fat-soluble than its structural parent. surges too via stimulation of the serotonin 5-HT(1A) receptors. "coming up" is naturally faster on an empty stomach. MDMA is usually taken orally as a tablet. First-time MDMA users occasionally feel confused or anxious before the dose-dependent dopamine-release kicks in. though a modest drink later to ease any comedown may be useful. so their optimal dosage may be lower. Inside the nerve cell. A transient hint of nausea is common when coming up. more stimulating. MDMA is readily absorbed from the gastrointestinal tract into the bloodstream. more subjectively rewarding. MDMA alters the configuration of the transporter protein so it binds to cytoplasmic serotonin. about 125mg] but optimal dose ranges from perhaps 75mg to as much as 250mg.e. Onset of action is normally within twenty to sixty minutes or so after administration. There are gender differences in response. a capsule. MDA can itself induce a state of sensual euphoria. The MDMA Experience Pure MDMA salt is a white crystalline solid. more dopaminergic. after which the transporter dumps serotonin outside the cell. Most of the body's serotonin is found outside the brain. The preferentially metabolised (+)-enantiomer ("mirror image") of MDMA is more active. MDMA increases the rate of transporter-mediated serotonin outflow. critically. so its speed of onset is slightly faster and its duration of action shorter. More rarely. smoked or injected.e. Illicit knowledge of the "penicillin of the soul" is spreading rapidly around the world. Taking higher and/or more frequent doses of the drug disproportionately increases levels of plasma MDMA. MDMA has a complex nonlinear pharmacokinetics. 5-HT) and also. notably in neurons of the enteric nervous system. Thus MDMA is best taken while completely sober. MDMA does not readily decompose in heat. or a powder. but in corrupt and contaminated form. The optimal adult dose of racemic MDMA is probably around 120-130mg [around 2mg/kg of body weight i. The user's peak experience or plateau phase after the exhilarating dopaminergic "rush" doesn't last much more than ninety minutes to two hours. our "little brain" inside the smooth muscles of the gut. The clarity and unique psychological effects of MDMA can be impaired by ethyl alcohol. the "cuddle hormone". MDMA's primary effects wear off after some 3-4 hours. Release of oxytocin. and more neurotoxic than the (-)-enantiomer. Here MDMA acts to reverse the normal direction of the socalled serotonin reuptake pump. The MDMA molecule is small enough to be taken up via the membrane-bound serotonin transporter into the presynaptic serotonin axon terminals. When MDMA is administered by the oral route. With oral MDMA dosing. The compound is chemically stable. Therapists then sometimes add(ed) a final 50mg booster-dose. reversing the normal inward-bound direction of the transporter channel i. though in humans the . proportionately to body-weight. peak concentration in the plasma follows after around two hours. It looks white and tastes bitter. air or light. Heavy recreational users are not always so restrained either in dosage ["stacking"] or top-up schedule ["piggybacking"]. women are normally more sensitive than men to the sub-acute and longer-term effects of MDMA. MDMA is metabolised via N-demethylation to the active metabolite MDA.

but the opportunities for MDMA recycling by the cost-conscious are normally wasted. MDMA is indeed structurally related to mescaline. Even so. the natural world seems vibrant and awe-inspiring.and brain MDMAconcentrations may occur if the user then takes more of the drug. some of them. The bodyimage looks and feels wonderful. MDMA "provides a centering experience. The term "empathogen" to describe MDMA and other closely related phenethylamine "empathy drugs" [MDA. The euphoria is usually gentle and subtle. users feel they can introspectively "touch inside" to their ideal authentic self with total emotional self-honesty. Taking MDMA induces an amazing feeling of closeness and connectedness to one's fellow human beings. though neither will win any marketing awards. The experience of colour is gorgeously intensified. primarily by the polymorphic cytochrome P450 enzyme CYP2D6. to refer to substances that generate a sense of "touching within" or "produce a feeling in one's innermost being". But hallucinations on MDMA taken at therapeutic dosages are extremely rare. MDEA. a lifetime of Judaeo-Christian guilt. MDMA metabolism seems to run up against such a metabolic saturation-point somewhere between 120 and 150mg. A large but variable quantity of the parent compound is excreted unchanged. together with a deep love of self and a no less emotionally intense empathetic love of others. set and setting inevitably shape the MDMA experience. On MDMA. The drug's influence feels highly controllable. other enzymes are involved in its degradation beside CYP2D6. Other people look and feel wonderful too. Dr Shulgin reported . Idiosyncratic responses to MDMA aren't rare.most exquisitely perhaps the sense of touch. The term "entactogen" was coined in 1986 by Dr David Nichols. shame or disgust at the flesh melt away to oblivion. MDMA may feel mystical. or DMT. MDMA triggers intense emotional release beyond the bounds of everyday experience. At least four other metabolites have been identified. don't typically induce a profound sense of inner peace. but sometimes profound. not diminish it. Minutes after dropping a pill. though it may also cause a "softening of the egoboundaries".5-dimethoxy-4methylamphetime (DOM). at a 1983 conference at the University of California at Santa Barbara. MDMA can promote an extraordinary clarity of introspective self-insight. MDMA's primary effects on the user are surprisingly consistent. MDMA's methylenedioxy (O-CH2-O-) group is attached to positions 3 and 4 of the aromatic ring of the amphetamine molecule. MDMA is sometimes described as a cross between a psychostimulant and a mild hallucinogen. On the contrary. and psychostimulants. but it doesn't feel weird. Professor of Medicinal Chemistry and Pharmacology at Purdue University and co-founder of the Heffter Research Institute. MDMA is perhaps best characterised as belonging to a functionally unique class of "empathogen-entactogen". When the high-affinity enzymes are saturated. Since it's a methoxylated amphetamine. are saturated at relatively low MDMA concentrations. Philip Wolfson). MDMA has even been described as a drug that "could be all things to all people" (Dr Shulgin). perhaps even enchanted. The drug also enhances the felt intensity of the senses . Thus MDMA exhibits a different profile both from the prototypical "serotonergic" 2. psilocybin. unlike MDMA. with its psychedelic 5-HT2A-mediated mechanism of action. and also from the prototypical "dopaminergic" stimulant (+)-amphetamine. When MDMA is taken outdoors. especially when the drug is taken at higher doses. MDMA also acts as a euphoriant. rather than an ego diffusing experience" (Dr. Culture.conversion rate from MDMA in the body is low. MDMA "opens up the heart". MDMA tends to enrich the user's sense of self-identity. Sometimes a degree of derealisation on MDMA may occur. unlike the wilder psychedelics such as LSD. As well as acting as a "gateway to the soul". a disproportionately large increase in blood. However. MDMA is broken down mainly in the liver. MBDB] was proposed by Ralph Metzner. These words don't mean a great deal in the MDMA-naïve state. like CYP2D6 itself. but rarely depersonalisation in the ordinary sense of the term. Both terms are quite apt. Dean of the California Institute of Integral Studies. magical or sublime.

the hostile amygdala is subdued. Ecstasy users tell each other affectionately what beautiful people they are." a "religious experience. highly-charged and even hitherto unmentionable problems may be discussed with (rose-tinted) candour. shorn of any speculative metaphysics. possibly for ever. Heightened feeling allows long-forgotten and repressed emotional memories from childhood can be retrieved with unusual ease. our sexually uninhibited primate cousins. pages 964-965)" Plus Fours are rare. +2 and +3 of the measuring of a drug's intensity. (PiHKAL. a participation mystique. To ease MDMAinduced performance difficulties. Although once dubbed "lover's speed". but if it had been present in the Eucharist. it is conceivable that it would signal the ultimate evolution. orgasm is more intense than normal but delayed: MDMA retains a residual sympathomimetic activity. boyfriends or culturally inappropriate love-objects.. Superfluous clothes tend to get shed. On pure MDMA. recalls one American clubber. and perhaps the end of. self-forgiveness and complete self-acceptance. this is not a recipe for safe sex." a "state of Samadhi" and many other names in other cultures. Carl A. MDMA may sometimes cause "inappropriate bonding". author of the book E for Ecstasy (1993). Some MDMA users undergo life-changing spiritual experiences. A minority of first-time MDMA users undergo what the inventor of the Shulgin scale christened a Plus Four. (++++) A rare and precious transcendental state. They discover an enhanced sense of self-worth. if only for a few hours. a connectedness with both the interior and exterior universes. . "Entheogen" is a term proposed in 1979 by the scholars R. irritability and ingrained fear dissolve." "divine transformation. And eternity in an hour.P. "PLUS FOUR. Before the Orwellian-sounding Drug Enforcement Administration [DEA] placed MDMA on Schedule 1 of controlled substances. MDMA is not normally classed as an entheogen. The effects of MDMA on bonobos ("pygmy chimpanzees"). In men.how mountains he'd observed many times before appeared to be so beautiful that he could barely stand looking at them. a lifetime of accumulated psychological barriers and defence-mechanisms go down. even the most jaded and world-weary soul with a tin-ear for poetry may "see a world in a grain of sand. Gordon Wasson. Jonathan Ott. Hold infinity in the palm of your hand. which has come about after the ingestion of a psychedelic drug. subjects feel at peace with themselves and the world. but which is not necessarily repeatable with a subsequent ingestion of the same drug. Unless carefully premeditated. If a drug (or technique or process) were ever to be discovered which would consistently produce a plus four experience in all human beings. Nicholas Saunders. are unknown. But on MDMA. somehow magicked out of existence with a pill. Yet MDMA is used by a variety of spiritual practitioners of widely diverse beliefs as a gateway to the divine. the human experiment. triggering a detumescence of the male organ. MDMA is proverbially more of a hugdrug than a lovedrug: "I kissed someone I was in love with and almost felt as if I was going to pass out from the intensity"." MDMA is sensuous and sensual in its effects without being distinctively pro-sexual. today. n. In some settings. Jeremy Bigwood and Danny Staples for agents "generating the god or the divine within". It is not connected to the +1. prudery and sexual hang-ups means that lovemaking while under its spell is not uncommon. And a heaven in a wild flower. and they do so from the depths of their hearts. However. Anger. which has been called a "peak experience. MDMA may not be "Christ in (al)chemical form". professional therapists in the USA found MDMA a valuable tool for counselling and marriage-guidance sessions. MDMA's capacity to induce empathetic bliss. MDMA's capacity to dissolve a lifetime's social inhibitions. It is a state of bliss. On MDMA.. cites a Benedictine monk who finds MDMA "opens up a direct channel to God". Aspects of life normally too sensitive to talk about can be explored freely. painful. Ruck. then we would all still be devout Christians. Prudence should be exercised before taking it with ex-girlfriends. flagging Romeos increasingly combine Ecstasy with Viagra ('Sexstasy'). Cynical thoughts and negative feelings disappear.

the FDA granted permission for Dr John Halpern's proposed study of MDMA-assisted psychotherapy for patients diagnosed with severe anxiety related to advanced cancer. Investigational drugs are labtested by Big Pharma to discover whether or not non-human animals will self-administer them. Such a problem doesn't always bedevil today's lame "antidepressants". If the magic of MDMA could be replicated safely and sustainably. MDMA-assisted therapy-sessions are rare. Yet as an empathogen. As of 2010. "Butylone") is a more enjoyable and stimulating empathogen than MBDB. the results of whose trials often struggle to reach statistical significance. the Multidisciplinary Association for Psychedelic Studies (MAPS) has been seeking funding and FDA-approval for controlled trials of MDMA-assisted therapy for PTSD. Functional analogues of MDMA may one day be employed in other kinds of insight-oriented therapy as well. MDMA can be therapeutic for victims of Post-Traumatic Stress Disorder (PTSD). In December 2004. MDMA is unsurpassed and possibly unmatched. MDMA is a warm. it's hard scientifically to validate claims of long-lasting therapeutic success. A minority of subjects find they enjoy the experience too much to focus on the emotional baggage of the past. MDMA doesn't cloud consciousness even at relatively high doses. then the fear of death and dying could in principle be banished in . On the other hand. non-sedating mood-enricher that banishes social anxiety and physical pain alike. not awakened for exorcism. affirmed one beneficiary of MDMA-assisted therapy. MBDB's chemical cousin beta-keto-MBDB (bk-MBDB. placebo-controlled trials effectively impossible. while paradoxically diminishing egotism. then MAPS hopes that MDMA could eventually become a prescriptionmedicine. Dr David Nichols suspects that the related phenethylamine entactogen MBDB ("Eden": 2Methylamino-1-(3. There is no compulsion to talk . On a more sceptical note. Sessions are most likely to be productive with an experienced MDMA therapist. In the Prohibitionist era. formed by extending the 3-carbon chain of MDMA to a 4-carbon chain. Explored in a controlled setting. Either way. eating disorders and obsessive-compulsive disorder (OCD). The likelihood of DEA approval of the protocol is unknown. might prove superior to MDMA as an adjunct to psychotherapy. many traumatized or seemingly emotionally frigid people who can never otherwise speak about their innermost fears and feelings find they can spontaneously open up.heightened introspection and an increased ability and desire to communicate feelings can create a rapport with the therapist and accelerate a successful outcome. By contrast. "I love the world and the world loves me". long-acting MDMA analogues may prove therapeutic in the treatment of social phobia. This is because Dr Nichols' creation lacks significant dopaminergic activity. Safe.just a dissipation of the social anxieties that make us normally tight-lipped. It's thus less likely to induce a distracting euphoria. For on MDMA.4-Methylenedioxyphenyl)Butane). if and when the substrates of blissful self-insight can be sustained indefinitely. its human use is still extremely limited. Unlike opioids or the anxiolytic benzodiazepines. If these trials are successful. arguably a perverse route to uncovering antidepressants with good clinical efficacy and high patient compliance. The user's sense of social isolation vanishes. Candidate compounds are normally discarded if the animals do so. For MDMA's stunning short-term results make double-blind. then who'll need therapy? Perhaps some inner demons are better left to die of neglect. MDMA acts to boosts self-esteem and self-confidence. This doesn't stop less cerebrally-inclined ravers from getting "cabbaged" by swallowing pills all weekend. Against formidable odds. MDMA's residual dopaminergic amphetamine-like action contributes a euphoric warmth to the user's intensified feelings and also the desire and ability to express them freely. fast-acting. a case can be made that MBDB is indeed a "purer" entactogen than MDMA.

or some combination thereof. Mozart sounds great on Ecstasy. the mood and ethos is well captured by the ravers' motto P. GHB (gamma-hydroxybutyrate: "liquid ecstasy"). Dr Holland also provides supporting evidence to back up anecdotal reports that MDMA can induce temporary remission of symptoms in victims of otherwise intractable schizophrenia. Individual pills bought by the end-user typically cost between US$7 and US$25. The music may be techno. a subneurotoxic dose of MDMA can be made toxic by adding (+)-amphetamine. hardcore. ephedrine. Dr Julie Holland. jungle. even pharmaceutical-grade MDMA taken at moderate doses in optimal conditions is not a wholly . or simply anyone with a negative body self-image. lasers. Raves are held in clubs. trance or form an improvised. will serve as that manual". 2-CB (4-Bromo-2. though the fear of personal mortality is probably the prime mover of scientific progress in anti-aging research.. In darkened clubs.L. PMA (paramethoxyamphetamine). its devotees have likened it to group-therapy or meditation. I hope. it should be used by people who are properly trained. Professionally-made tablets of MDMA are stamped with distinctive logos. 2C-I. editor of the invaluable Ecstasy:The Complete Guide (2001). Understanding and Respect"]. Often raves last a whole weekend. The transformation can be magical.. chronic heavy use of the methoxylated amphetamines or any other "club-drug" poses risks to the user's health. "Bromo"). The atmosphere is astonishingly friendly. And like any powerful tool. Tablets can be massmanufactured for as little as 50 cents. loving glow" to their acid trips. though it would be imprudent to repeat the experiment two days later. It may be testimony to the comparative safety of MDMA that millions of young people use MDMA in the absence of a manual or any training. Alas counterfeit goods are still rife. or "kittyflip" with ketamine. DXM (dextromethorphan). This book. Dr Holland notes that "Like any powerful tool.5 Dimethoxyphenethylamine: ''Nexus". Most commonly today. A minority of psychologically robust or reckless clubbers purposely mix MDMA with LSD ("candyflipping") to impart a "warm. MDMA can also be used just to have fun. Love. to view themselves in the mirror while euphorically loved-up on MDMA. This list is far from exhaustive.125mg dose of MDMA a few times or so a year is likely to cause any long-term harm to the user's mental or physical health. Cannabis is widely smoked as well. warehouses or more exotic outdoor settings and open fields. educated and supervised. education and supervision at all. the product now passed off as "Ecstasy" is adulterated with other agents. and squanders the therapeutic opportunities. strobe lights. To outsiders.4methylenedioxyethylamphetamine: "Eve"). the intoxicating atmosphere of the rave is enhanced with artificial fog. aromas are fragrantly enriched]. "Venus". glow sticks.U. Alas Prohibitionism puts the young and vulnerable at unnecessary risk. it should come with an instruction manual. pseudoephedrine. Sometimes "Ecstasy" doesn't contain MDMA at all. but high-energy all-night dance parties celebrated with techno-pop house music are more standard. This would be a substantial payoff. teenagers and young adults take Ecstasy to rave. supervised and single oral doses of MDMA as a psychiatric medicine. ["Peace. Nevertheless. The worldwide street price is falling.R. In many cases. caffeine." In her introduction to the guide. But either way. the dissociative anaesthetic ketamine ("Special K"). MDEA (3. whistles and Vicks inhalers [on MDMA. tentatively endorses "the judicious. MDMA: neurotoxicity No compelling evidence exists that taking a single c. In defiance of scepticism from medical orthodoxy. This is because MDMA manufacturers and merchants seek to promote brandawareness and customer loyalty. but MDA.the population at large. eclectic mix of styles harder to categorise. Ecstasyfuelled raving might seem mindless hedonism. Or they "hippieflip" with psilocybin mushrooms. Less controversially. Ravers who want to dance all night may prefer Ecstasy laced with speed. it's possible for victims of body dysmorphic disorder (BDD). amphetamine ("speed").

apparently fall 3-6 hours after taking the drug. specific transporters are presumably needed to take up the neurotoxic metabolite into the brain. A biphasic post-E serotonin profile in the user has been reported: users' serotonin levels . hypothermia-inducing agents are (partially) neuroprotective against Ecstasy damage.8-9 hour elimination half-life from the blood. less stimulating (-)-MDA enantiomer has 5-HT2A activating effects resembling low-grade LSD. Beyond warm memories. and the identity and precise mechanism of the chemical(s) causing the oxidative stress is unclear. and then decline again. The functional deficit the dip reflects may last ten days or more . increased Ca2(+). most users experience the serotonin dip. Elevation of body temperature can seriously worsen possible MDMA-induced toxicity. Currently the three leading candidates for guilty agent are: 1] toxic metabolites of MDMA 2] toxic metabolites of dopamine 3] impaired cellular energetics An excellent review of the published scientific evidence on neurotoxicity is offered by Matthew Baggott and John Mendelson on the indispensable Erowid. However. but their identity or even existence isn't known either. The problem isn't (just) the toxic adulterants used by dance-floor pharmacologists or the botched syntheses of bathtub chemists.benign drug. If they do exist. and the thermogenic effect of MDMA is magnified in a hot environment like an indoor rave. but there's still no sign of neurotoxicity. Nor does experimental central MDMA perfusion trigger the toxicity-enhancing higher body temperatures likely from the peripheral route. The issue is also controversial. and a toxic intraneuronal metabolite of serotonin. A role has also been proposed for nitric oxide. otherwise selegiline wouldn't be protective against MDMA-induced neurotoxicity.in some cases possibly weeks or months. albeit tired and slightly spaced-out. Certainly. Since drug metabolites are normally more hydrophilic than their parent drug. the nature of any such possible toxic metabolite(s) is unknown: thioether conjugates of alpha-methyl dopamine have been mooted. Deceptively. Excessive MDMA intake triggers oxidative damage to the user's serotonergic nerve cell fine axon terminal lipids and proteins via the production of toxic free radicals. But two days or so after taking MDMA. Experimental microinjection of MDMA. then presumably they are monoamines. MDMA can be centrally injected to induce the release of just as much serotonin as the toxic peripherally-administered dose. then recover to nearly normal levels after around 24 hours. this afterglow may in part be explained by MDMA's residual amphetamine metabolic by-products: MDMA itself has a long. If systemic metabolism of MDMA is indeed necessary for neurotoxicity. MDA or other amphetamine analogues directly into the cerebrum doesn't produce the toxicity to the serotonergic axons ascending from the dorsal raphé nucleus that follows high and/or frequent doses of the peripherally administered drug. and in 2009 neurotoxic thioether adducts of MDMA were detected in humans. c. . and in contrast to most other recreationally used drugs. and the primary role of dopamine in MDMA-induced toxicity may actually be to elevate body temperature via its increased action on the dopamine D1 receptors rather than its uptake into the depleted serotonergic axon terminals.though hard to measure and interpret . When MDMA is centrally administered in animal experiments. the threshold dose for any lasting MDMA-induced toxicity is unknown. MDMA itself (probably) isn't the culprit. ingesting pure MDMA can sometimes leave the user feeling better than normal the next day. The dip ranges from the almost imperceptible to the markedly unpleasant. not even artificially inducing hyperthermia in the victim is enough to produce serotonergic damage. But consensus on the molecular mechanisms behind MDMA megadose-induced damage remains elusive. and its main metabolite's longer-acting.

For many but not all users. may actually be hyperinnervated. most users eventually stop taking MDMA. They do so after either they find the E-magic wears off. The prospect of love. Such cases are exceptional. but reinnervation of the dorsal cortex is sparser. Even listening to glowing. MDMA users themselves may find the magic of the initial drug-induced epiphany tends to fade with frequent use. Adverse side-effects tend to become more troublesome. the incidence of depression seems to be more common than healed minds or any enduring therapeutic benefit. not darken it. The prospect of serotonergic axon terminal degeneration doesn't sound much fun. even if the axons re-sprout . Even so. Depending on one's ideological agenda. only become apparent after 70-80% of dopamine cells have been lost. Not even heroic doses of MDMA are likely to kill off serotonergic brain cells. this is not inherently a sign of "brain damage". MDMA users may be less anxious or panic-stricken in response to the normally anxiogenic challenge of a 5-HT2C agonist such as mchlorophenylpiperazine (m-CPP). a magical drug becomes just a feelgood drug. Calling it dystopian pharmacology might seem more apposite. Taking weed-killer. first-person accounts of the MDMA experience is curiously uninspiring when refracted through the lens of our normal Darwinian consciousness. In any case. glue sniffing or swallowing rat poison sounds marginally less dangerous. peace and empathy seems less exciting than a round of Quake 3. and that the tablets . We are all prone to mood-congruent thoughts. a brain structure critical for episodic memory formation. Likewise. the MDMA-induced pruning of the serotonergic axon tree seen at high-dosage regimens leads to altered patterns of reinnervation by ascending axons projecting especially to forebrain sites. actually demonstrated methamphetamine-induced dopaminergic neurotoxicity instead. self-medicating or otherwise. In the process of recovery from a prolonged MDMA-binge. Among heavy "recreational" MDMA users. Ricaurte's September 2002 paper Severe Dopaminergic Neurotoxicity in Primates After a Common Recreational Dose Regimen of MDMA ("Ecstasy") in Science. It is fiendishly hard to demonstrate MDMA-induced dopaminergic cell damage without virtually killing the victim. this diminished response to m-CPP can be described as evidence either of serotonergic "toxicity". The disturbing parallel drawn here is with neurodegenerative disorders: clinical signs of Parkinson's disease. was retracted in September 2003. This unfortunate study. its publication timed to coincide with debate in US Congress over the "Anti-Rave Act". MDMA use increases sensitisation to the rewarding effects of euphoriant dopaminergics such as cocaine. Worryingly. However. reports of real and serious health problems from excess E-use are not all prohibitionist propaganda or part of a government-inspired conspiracy to stop young people having a good time. may still be subtly damaging his or her serotonergic "functional reserve". or the unwanted side-effects of heavy E-use begin to outweigh its joys.Whatever the mechanism at work. Doctors report that one Englishman consumed an estimated 40. but the spectre it raised of a post-E generation of Parkinsonian zombies may prove harder to dispel. in contrived circumstances it can be done. though there have been unconfirmed reports of MDMA-induced apoptosis in mega-dosed rats. Higher doses are needed to gain the same effect. Only the most alarmist commentators anticipate a delayed epidemic of demented depressives as a result of serotonergic carnage caused by MDMA abuse. It has been suggested that the heavy MDMA user who discerns no long-lasting ill effects. the hippocampus. The persistent elevation of dopamine function reported in the nucleus accumbens of some MDMA veterans might otherwise be expected to enhance mood. Users lament that "the E isn't as pure as it used to be". or alternatively as a pointer to the substrate of a long-lasting "therapeutic" effect. and who displays minimal functional impairment.one way or another.000 tablets of MDMA over a nine year period. possibly indicating its disinhibition from normal serotonergic control. some heavy MDMA users claim they don't experience any long-term adverse effects. Prolonged MDMA administration can even cause a long-lasting increase in the dopamine content of the nucleus accumbens. no alien anthropologist in his right mind who merely read the gruesome scientific literature on MDMA would want to self-experiment with such a deadly neurotoxin. a progressive disorder caused by outright dopaminergic cell death and frequently prefigured by depression. Yet the most notorious attempt to show MDMA-induced dopaminergic neurotoxicity. and once more. But equally. Again.

depression. Researchers are still unsure if this fade-off is a symptom of long-term neuroadaptation or serotonergic damage. MDMA: neuroprotection No safe. if any. a neurotoxicologist at John Hopkins University School of Medicine. Yet we won't be trapped in brutish states of consciousness for ever. Currently around 500. add perpetual magic to our lives. Psychostimulants like cocaine and amphetamine notoriously promote egotism and aggression. Currently the balance of neurochemical and neuroanatomical evidence. Ever more alarming animal studies conducted over a decade by George Ricaurte. at best. elevated cortisol. serotonin's major metabolite which serves as a marker of central serotonin (5-hydroxytryptamine. but it is unclear whether recovery is complete.are weaker.MDMA is unclear. 5-HT) neural function. Enzyme-induction plays a role. and functional measures of serotonin . Perhaps we shouldn't be so surprised at the "loss of magic". Some such drugs are billion-dollar moneyspinners for Big Pharma. Other psychoactive drugs are used mainly for "unrecognised" and non-medical purposes. sleep problems. So is MDMA itself best reserved as a sacrament for special occasions? Or can it be safely taken "recreationally" and socially? What dosage. suggest that taking high and/or frequent doses of MDMA causes damage to the terminals of serotonin axons in the brain. functional analogues of MDMA promise to enhance mental health. structural protein elements on the presynaptic outer axonal membrane that recycle the released neurotransmitter. In the near future. though the phenomenon isn't fully understood. Empathetic bliss isn't inherently toxic. Pharmacodynamic tolerance to a drug is normally reversible.000 "drug-offenders" languish in American jails alone. but a physiological explanation for so-called "cumulative tolerance" must be sought as well. Lowered serotonin levels. MDMA has the attributes of both. is prudent? Is the MDMA experience so tantalising that it's best avoided altogether lest the rest of one's life pall in contrast? Would one want one's sixteen year-old daughter to take it. Our vital organs can't know the difference between the elixir of life and a poison. They are clinically licensed and widely prescribed in the guise of psychiatric medicines. and in the African bush. In principle. severe anxiety. the psychopathologies of everyday life can all be cured. The liver (and the brain) is adapted to life on the African savannah. yet some users of MDMA report they never quite recapture the initial ecstatic glory even if they abstain for a year or more. Drugs that consistently induce the opposite syndrome are legion. MDMA offers a foretaste of life in post-Darwinian paradise. Yet repealing ill-conceived drug laws is only part of the answer in protecting mental health. the latter is a more realistic outcome. The number of serotonin transporter sites. only a fleeting hint of the magic to come. Cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA). and beautify our troubled minds. Often indeed this is true. though its reactive metabolites may be. Long-term MDMA-induced changes in the availability of the serotonin transporter may be reversible. and millions more young people throughout the world are at risk. confusion. and with whom? Currently the risk-benefit analysis of taking . indefinitely sustainable entactogens-empathogens yet exist. may be reduced too. In some cases. and paranoia are common. disinhibited and stupid.or missing out on . Victims of the law-enforcement agencies frequently suffer long-term neuropathological changes. may be lower in human MDMA users than in putatively matched controls. the neurological damage may be permanent. Probably the gravest threat to the long-term emotional and physical health of the user is getting caught up in the criminal justice system. but it delivers. Drinking ethyl alcohol tends to make the user relaxed.

Dr Shulgin fell victim to a DEA raid on his research lab.except for MDMA taken at unrealistically high doses. "All substances are poisons: there is none which is not a poison. the so-called stereotype threat. and marred by a failure adequately to exclude confounding variables . But in 1994. Yet this license has lately been revoked in the name of the War Against Drugs. The UN's World Health Organization and foreign governments have been leaned on. Studies of MDMA can be lawfully conducted only under government license by ideologically-vetted researchers.Dr Shulgin once suggested a maximum of four times a year.neurons. It's rather that just as the strongest predictive factor in the outcome of a published clinical trial of any psychiatric drug is the identity of the funding body. Intuitively.g. Some published toxicity studies include a large percentage of self-reported "Ecstasy" users who've never even taken MDMA. The right dose differentiates a poison and a remedy. The chemical keys to the locks themselves have been outlawed. likewise the investigation of MDMA isn't a disinterested search for scientific truth. But systemic bias and the habit of internalised selfcensorship extends throughout the apparatus of peer-reviewed journals. "I can see having maybe two or three people in the higher echelons of the government who may not like what I do. Most natural scientists are scornful of social constructivists who think that power structures underwrite the way we see the world.a "Faustian bargain" according to MAPS's Rick Doblin. not that they can be potentially therapeutic. Dr Shulgin's license to work with scheduled drugs was withdrawn. Suppression of "illicit" knowledge in academia and the overground research community isn't normally so melodramatic or heavy-handed. Arguably. So I published it. retrospective rather than prospective. Every law-abiding citizen is now locked into traditional modes of consciousness on pain of criminal prosecution and imprisonment. . Thompson than Sasha Shulgin. Authors and licensed researchers are implicitly paid to show how prohibited drugs are harmful. As Paracelsus (1493-1541) noted centuries ago. and I did not want particularly to have all of this be seizable and burnable. But in a daring extension of the Papacy's Index Librorum Prohibitorum.e. MDMA's apologists aren't convinced that the neurotoxicity evidence is persuasive . but MDMA is now a Schedule One drug. at least. it might seem axiomatic that in a democratic free society every person should have "the license to explore the nature of his own soul" (Dr Shulgin). it is best to take MDMA infrequently and reverently or not at all . Nor do their paymasters expect them to investigate the design of safer. more sustainable analogues to improve the user experience. Yet the biggest problem in evaluating the published evidence isn't so much sloppy science or value-judgements masquerading as statements of fact. Independent funding is critical to the integrity of biomedical research. Now you cannot get rid of it. Dr Shulgin acted to thwart the obscurantists before it was too late. In the USA itself. sponsored conferences." Most early studies of the possible long-term adverse effects of MDMA use in humans have been methodologically flawed . knowledge of entire state-spaces of potential experience has been outlawed following passage of the USA's Controlled Substance Analogue Enforcement Act of 1986. Other studies rely on a small minority of users whose drug-taking methodology owes more to Hunter S. suggests that it is imprudent to take MDMA or other ring-substituted methamphetamine derivatives without also taking neuroprotective precautions. the world's most celebrated psychedelic chemist and leading authority on MDMA has been stymied from conducting human research on Schedule One compounds after publishing his trailblazing autobiography-cum-cookery book. Worried that his life's work might be quite literally destroyed by the drug-warriors. Researchers certainly aren't paid to report that some illegal drugs are potentially life-enhancing agents. bribed or dragooned into the War On Drugs too." Dr Shulgin had a DEA analytical license . Published papers that examine possible confounding variables in MDMA "toxicity studies" omit to mention the greatest biasing factor of all.inadequately controlled. Under the transparent pretext of "health-and-safety" infractions.

SSRIs inhibit the binding of MDMA to the serotonin transporter. and this in turn reduces dopamine-release in the striatum. subtle cognitive deficits. apparently prevents the uptake of dopamine (and any toxic metabolite(s)?) into the serotonergic nerve terminals by binding to the serotonin reuptake transporter with higher affinity than MDMA or serotonin. On the one hand. or at least not if they intend to continue using their hugdrug of choice. immune system dysfunction. MDMA's defenders would say that the same is true of lithium.' Parrott himself has had two papers of this sort turned down.and mainstream clinical medicine. rejection-sensitivity. the persistence of metabolite-induced MDA-like states of consciousness the next day is not unexpected. Monoamine neurotransmitters. Two days and more after taking MDMA. They consume abnormally high quantities of pills to gain the desired E-like effect. Such publication bias is insidious and endemic. MDMA can indeed be life-transforming. In practice. Post-E Prozac in particular mitigates the oxidative stress and consequent risk of serotonergic axon damage caused by reactive products of dopamine deamination..get published. Unfortunately. two or three days after communing on Ecstasy and declaring their undying love. MDMA enthusiasts find it hard to write even-handedly too. couples are more likely to have rows and split up.' says [Andrew] Parrott. adopting a prophylactic SSRI regimen isn't a realistic long-term option for frequent MDMA users either. and a sense of derealisation or depersonalisation for several weeks or months afterwards. As noted by New Scientist in Ecstasy on the Brain (April 2002): "'It's an open secret that some teams have failed to find deficits in ecstasy users and had trouble publishing the findings. unsociable and subtly less empathetic than before their weekend binge: the "Terrible Tuesday's" syndrome of midweek blues.and can't . Conversely. body temperature dysregulation. Among MDMA's "unlicensed" and independent researchers. The longacting SSRI Prozac/fluoxetine. This is because most potential psychedelic research projects can't get official permission or funding in the first place. but unless it's used sparingly and at conservative doses. This is because a sustained regimen of SSRIs largely blunts MDMA's empathogenic and entactogenic effects. serotonin synthesis is choked off following oxidative inactivation of tryptophan hydroxylase. are depleted from the axon terminals. aching limbs. So with cruel irony. Thus pre-treatment with SSRIs prevents MDMA-triggered serotonin-release. Alas. Some studies suggest that possible MDMA-induced neurotoxicity to the serotonin system can be largely prevented by taking a double dose of fluoxetine (Prozac) or another SSRI shortly after starting to "come down". even those who aren't self-medicating for a pre-existing malaise. 'It's a source of bias. amphetamine-like and eventually dysphoric effects start to predominate. none of which are banned. penicillin or paracetamol. insomnia. If MDMA is taken several days in a row. there is a natural tendency to believe any agent that triggers such sublime states must essentially be good for you. the after-effects are often modulated by cannabis and alcohol. emotional burnout. subdued." Of course bias cuts both ways. Even this biasing factor massively understates the problem. At this dosage range. may experience depression. fatigue.The journals are very conservative. "positive" toxicity results from studies run by primate vivisectionists using chronic or near-fatal MDMA doses are newsworthy and fundable. most chill-out rooms don't offer Prozac. and its even longer-acting metabolite norfluoxetine. Other heavy regular MDMA users. Tolerance to MDMA itself develops quite rapidly with steady use.. Some SSRI users who like to rave nonetheless continue to take MDMA. and so they don't bother to submit what they know can't be accepted. although liquid refreshment is now freely available at most MDMApropelled raves. heavy recreational users are typically more irritable. most drastically serotonin. it's underestimated because prospective authors are broadly aware of what can . and the nerve-cell . negative results and non-results from toxicity studies are difficult to publish or publicise. it is still a potentially toxic drug. This litany of woe sounds a high price to pay even for the peak experience of a lifetime. anxiety.

These toxic free radicals are liable to exhaust or overwhelm the free radical scavenging systems of the cell. Agilect) for E-users. 2 x 5mg daily or less. and selegiline itself. Prozac too has MAO-B inhibiting properties. is a weak inhibitor of MAO-A. Yet MDMA's non-addictive profile is no guarantee that (as was once fondly hoped). Taken at dosages of above 2 x 5mg per day. But with MDMA. Even so. adopting a long-term selegiline regimen doesn't impair MDMA's subjective effects. Both enantiomers of MDMA itself have MAO-inhibiting effects. but they aren't widely available on the street or average dance-floor. Why exactly the serotonin reuptake transporters lose their normal selectivity for serotonin and take up dopamine isn't known for certain. Individual variation in MAO status makes it imprudent for the MDMA user to take selegiline even at 10mg daily. after a subject has taken a high dose of MDMA. After the directionality of the reuptake pump is reversed by MDMA. Selegiline also protects against MDMA-induced inhibition of tryptophan hydroxylase." The mind/brain isn't built like that. Prohibitionism and a consequent absence of quality-control means that the "Ecstasy" sold in clubs often contains liberal quantities of amphetamine. Selegiline has lifespan-extending properties in "animal models". it soon ceases to be rewarding. autonomic instability and altered muscle tone. In any event. Wiser heads save the drug for "special occasions". Possibly it's because by this time there's far less serotonin around for the reuptake pump to use. the serotonin fine axonal terminals are broken down by lipid peroxidation. and its primal magic gets sullied or forgotten. and the serotonin syndrome. is potentially lethal. excess dopamine is taken up by the so-called serotonin transporters into the depleted serotonin terminals. . Thus MDMA is not addictive in the conventional sense. but mainly MAO-B is present in the serotonergic axonal terminals. Taken chronically. Selegiline itself has additional free radical scavenging properties that may exert a neuroprotective action. the monoamine oxidase inhibitor selegiline [ldeprenyl/Eldepryl] appears to be neuroprotective at monoamine oxidase type-B-selective dosages i.e. One reason for such caution beyond a reflex Just-Say-No dogmatism is that it's potentially dangerous to tamper with the MAO enzyme. no controlled clinical trials of their co-administration are currently planned. It will be instructive to compare the neuroprotective efficacy of selegiline with rasagiline (Azilect. There are other options for neuroprotection besides taking post-Ecstasy Prozac. but if used recklessly. and possibly in humans too. selegiline is potentially valuable too because. you want to hear it again and again. unlike taking a SSRI. Here its oxidation produces a glut of toxic free radicals .highly reactive chemicals with one or more unpaired electrons . the extra dopamine released into the synapses is transported into the depleted serotonin axonal terminals where it is deaminated by the enzyme monoamine oxidase type-B present in the terminal. These differ in their substrate affinities and inhibitor sensitivities: the MAO-A isoenzyme has a greater affinity than the MAO-B isoenzyme for serotonin. rasagiline lacks selegiline's trace amphetamine metabolic by-products. Interestingly. "once you get the message you hang up the phone. where it breaks down "foreign" neurotransmitters. MAO-A and MAO-B. If you really like a drug-delivered message. MAO has two isoforms. serotonin released into the synapse can't be recycled back into the cell. like MDMA. and so it diffuses away. Rasagiline is a selective MAO-B inhibitor licensed from mid-2005 in the EC for the treatment of Parkinson's disease. and these may contribute to its neuroprotective effect. preferentially for isoenzyme type-A. selegiline loses its selectivity for MAO-B. However. characterised inter alia by hyperthermia.receptors re-regulate. MAO-A deaminates serotonin. Whatever the older compound's neuroprotective efficacy compared to rasagiline.such as hydrogen peroxide (H2O2). Serotonin 5-HT2A antagonists like ketanserin (Sulfrexal) can inhibit the syndrome. In consequence. Amphetamine and MAO inhibitors should not be combined. then it could abruptly shorten life instead: selegiline is an irreversible MAO-B inhibitor. Even dedicated ravers typically don't binge more than once a week. the message can subtly change with time. On one hypothesis of MDMA-induced serotonergic neurotoxicity.

More encouragingly. L-tryptophan and 5-HTP can be taken chronically without blunting MDMA's effects. The serotonin precursors L-tryptophan and 5-hydroxytryptophan (5-HTP) are also neuroprotective against MDMA-induced toxicity. Indeed some clubbers pre-load with Ltryptophan or 5-HTP to intensify and enrich the MDMA experience and prevent serotonin depletion. what's tested in these rituals of abuse isn't our children's emotional well-being.Milder cases of the serotonin syndrome are not uncommon among the hard-rolling stackers and piggybackers dancing all night at crowded ill-ventilated raves. 5-HTP is the metabolite of L-tryptophan. This can cause hyponatraemia (literally "low salt": "water intoxication"). MDMA also increases the body's secretion of antidiuretic hormone. 5-HTP is sometimes used as an antidepressant and antianxiety agent. Organisations like the Berkeley-based Dancesafe. hasn't yet been established. levels of reflective self-insight. any responsibly designed drug cocktail. the synthesis of serotonin isn't subject to strong end-product inhibition. Heat exhaustion and severe hyperthermia are probably the gravest risk to the raver's health. So more realistically for now. arginine-vasopressin. tips found on the Net are no substitute for systematic. Merck never planned to develop MDMA as an appetite-suppressant. excess preloading with 5-HTP may potentially precipitate or exacerbate the serotonin syndrome. hopefully without the usual animal holocaust that accompanies drug testing today. antioxidants also reduce tolerance between exposures. Nor do schools and colleges offer courses in effective technologies to promote them. during. Even at high dosage. Critics of exam-culture claim an "education" based around competitive testing screws kids up far more than empathetic drugs. and after dropping an E to maximise their respective neuroprotective action. MDMA tends to raise body temperature by a degree or so. An examination system akin to ritualised child-abuse wreaks terrible damage on the young minds incarcerated in our educational institutions. In contrast to the catecholamine neurotransmitters dopamine and noradrenaline. Unfortunately. well-planned healtheducation programs. Though such a tactic is sensible enough in theory. Yet the company might well have done . Unfortunately. A healthcare revolution of this magnitude isn't going to happen tomorrow. Indeed it would be safer if sports drinks were distributed with each E-tablet sold as a matter of course. sometimes by quite a bit more if the user dances all night without rest ["Saturday night fever"]. Serotonin depletion increases the vulnerability of the axon terminals to damage. and minimise any post-ecstatic hangover. Such a revolution in mental healthcare for young people is sorely needed. So care is in order. the neuroprotection such antioxidants offer may be inadequate for heavy MDMA users. an idealised stone-age diet can be especially valuable for heavy MDMA users. Unlike SSRIs. not just risk-averse research scientists. The optimal mix and dosage before. With or without 5-HTP supplementation. possibly in part because of their antioxidant effect but mainly because of their precursor role. Until psychopharmacology becomes part of the educational core curriculum. alpha-lipoic acid. alpha-tocopheryl-acetate (Vitamin E). perhaps accompanied with a neuroprotectant mix and a health-tips sheet thrown in for good measure. capacity for loving empathy or social intelligence. Like L-tryptophan. Clearly a lot more research is needed. funded by Microsoft millionaire the late Bob Wallace and founded to promote safe raving. are rare. clubbers seeking neuroprotection against MDMA-induced toxicity may do well to use humble antioxidants such as ascorbic acid (Vitamin C). Sipping a couple of sportsdrinks every hour or so instead is a prudent way to maintain electrolyte balance. it seems to have a relatively narrow therapeutic window. and L-cysteine. It's the direct metabolic precursor to serotonin (5-HT). their activities are also controversial. and any harm-reduction program. Contrary to a once widely-propagated but now discredited myth. Ravers sometimes overcompensate for the risk of dehydration by gulping down too much pure water. Dehydration and overcrowding tend to worsen drug-induced toxicity. must be formulated with the recklessness of a minority of sensation-seekers in mind. zinc.

Critics of the drug-warrior mentality claim that MDMA's possible neurotoxicity served only as a pretext for banning it. Therefore taking aspirin before MDMA use may also indirectly block the conversion of amphetamines into reactive oxygen species responsible for long-term neurotoxicity. the authorities opted simply to outlaw MDMA altogether. There are interspecies differences e. and MDMA causes opposing sensorimotor gating effects in rats and humans. nor would any rush to judgement on the safety. then investigation of the particular ways MDMA is metabolised in humans will be critical in determining safe dosages. Users and independent researchers alike were criminalised. Instead of aiming to prevent possible MDMA-induced neurotoxicity by tweaking or enhancing the agent in question. are responsible for neurotoxicity. The size of the cumulative death toll in the tobacco epidemic almost defies comprehension: yet we continue energetically to market a lethal drug to hundreds of millions of youngsters in the Third World. vivisect and then "sacrifice" our fellow creatures in drug discrimination studies and medical research.to human beings.so: MDMA's appetite-suppressing effect is quite strong. MDMA is anxiogenic rather than anxiolytic in some mouse strains at low doses. Yet ethically. selegiline. The case for making.genetically. MDMA administered to rats in cold ambient temperatures induces hypothermia. it's hard enough for articulate humans who take insight-and-empathy drugs to verbalise their processes of introspection. say. and more vulnerable to MDMA-induced serotonergic damage. Rats and monkeys are in some ways uncannily similar . but the risk/benefit ratio of its use is both favourable and well-known. the biggest long-term obstacles to preventing neurotoxicity and drug-related mental health problems are ideological. then this is potentially a godsend . If oxidative metabolites. One novel and unlikely-sounding proposal to minimise MDMA-induced neurotoxicity is pretreatment with aspirin. But if aspirin pretreatment does prove an effective harm-reduction strategy. Fortunately. Using principles of interspecies scaling. where it could mix with innumerable contaminants and organised crime. how can we . As of 2010. Aspirin inhibits the enzyme prostaglandin H synthase (PHS). Aspirin itself cannot strictly be described as risk-free. The discovery that MDMA is not always the harmless fun-drug that a number of its recreational users (understandably) first supposed has caused the medical establishment to demonise MDMA or dismiss its psychotherapeutic potential completely. etc) carry hazards of their own in conjunction with Euse. Both the electrical-signalling properties and molecular machinery of neurons are widely conserved across the animal kingdom. not pharmacological. tobacco a schedule-one drug isn't notably less compelling. Scientific investigation was crippled. or seeking ways to antagonise possible toxic metabolites. Yet the fundamental similarity of "animal models" to human beings is precisely why we use. although species differences in MDMA's pharmacokinetics and active metabolites make the details of such scaling controversial. no controlled trials of aspirin have yet been conducted with MDMA-using humans. or running health campaigns promoting the co-administration of free radical scavengers or other neuroprotectants. behaviourally and biochemically . it is possible to estimate the crude physical effects of comparable MDMA doses on people after conducting animal experiments.not least because other candidate neuroprotectants (SSRIs. But beyond the narrow physical effects of MDMA on the brain. scientific research on MDMA has lately revived. than matched controls. MDMA was driven underground.g. not MDMA itself. The contrast between the treatment of dealers in tobacco products and MDMA distributors couldn't be much starker. albeit under license and mainly on non-humans. However.and even more data from experiments on live humans. PHS catalyses the transformation of amphetamines into toxic free radical products. What can we learn about entactogenesis by mega-dosing a rhesus monkey? All sorts of intellectually fascinating physiological data can be gleaned from experimenting on live animals . medical use or addictive potential of tobacco-products seem so premature. Lazy and reluctant eaters who regularly take Ecstasy are at greater risk of vitamin and mineral deficiencies. Drugs that directly or indirectly activate the serotonin 5-HT1B and 5-HT2 receptors tend to be anorexiants. or designing better functional analogues.

not investigational agents designed to enhance our quality of life or enrich "normal" human mental (ill-)health. what if any drug or drug-cocktail can safely replicate the acute subjective effects of MDMA? Second. refractory depression. Ecstasy for life? What are the presently available options for enhancing and extending the MDMA experience? Two separate questions need to be distinguished. but so. "You need pain to appreciate pleasure". As intracranial self-stimulation studies attest. Short of labelling the agent as a "food supplement" . the psychiatrists' bible. A long-term regimen doesn't seem . Even if animal research throws up a true wonderdrug ideal for human use . it may soon seem quaint. we can be nicer. what if any drug or drug-cocktail or genetherapy can best induce E-like consciousness over the long-term? The holy grail of safe. A condition that isn't medically acknowledged can't be treated by state-licensed pharmacotherapy.] But such superstition is pre-scientific. In law. are the biochemical substrates of happiness. depression. the potential wonderdrug couldn't get a product-license. but it needn't be illegal. life-enriching subjective profile. pure pleasure induced by electrical stimulation of the ancient mesolimbic pleasure centres of the brain shows no tolerance. Even if this perverse restriction on legal drug availability were lifted. ["You can't have the sweet without the sour". sustainable miracle-pill with a well-defined therapeutic window. only medicines to treat well-defined clinical disorders can be licensed. Asperger syndrome and autism. Eventually. In principle. The hedonic treadmill can be dismantled. Empathy-And-Insight Deficiency-Disorder isn't covered in DSM-IV.and remission-rates are 100%. etc. Response.humanely experiment on members of other species when we can't "predict whether a particular molecule will open the gates of heaven or stoke up the fires of hell" (Dr David Nichols). In the present era. So profit-driven pharmaceutical companies aren't interested in funding pilot studies.the so-called "animal model" of subjective drug effects. lucid self-insight and even saintly empathetic bliss. in theory. PTSD. These super-cocktails and sustainable MDMA analogues should prove life-enhancing for "normal" self-regarding people who would like to improve themselves too.or the horrors we inflict on their minds and bodies.a safe. safe long-lasting E-like supercocktails and enhanced functional analogues of MDMA may indeed be both patentable and judged therapeutic for "officially" sanctioned medical conditions such as anti-social personality disorder. sustainable entactogen-empathogens almost certainly won't be found in the guise of structurally-tweaked chemical homologues of MDMA. Unfortunately this utopian outcome won't result from a chronic regimen of MDMA. happier and smarter indefinitely.which might be stretching it a bit for MDMA and its analogues . So members of other species can't describe the illegal knowledge drug-naïve humans are missing out on . and its neurogenetics rewritten. Such usage may or may not stay "off-label". bitter experience of the hedonic treadmill of Darwinian life instils a reluctance to believe anything so magical as the MDMA experience could be sustained and enriched indefinitely.true pharmacological life-enrichers will be condemned to legal limbo. and no significant adverse side-effects . MDMA itself has long been off-patent. and perhaps one day in practice. The gloom-and-doom shouldn't be overdone. its inhibitory feedback mechanisms redesigned. Human clinical trials cost tens of millions of dollars to run. Clearly nonhumans can't describe the effects on their consciousness of psychoactives.then under today's regulatory regime. even though they can be taught to "discriminate" them . self-ignorance and sociopathy are demonstrably sustainable over a lifetime. First. In the meantime. then any prospective blockbuster most likely still wouldn't get regulatory approval in practice.

so has our library of serotonergic molecular probes. our options may soon extend beyond the crudely hedonistic. though most of us might prefer the services of a molecular psychiatrist to a neurosurgeon. Fortunately. non-neurotoxic amphetamine derivatives that acutely induce transporter-mediated serotonin release. or continually re-created as desired. but the delight of E-like consciousness needs to be divorced from its intimate association with pill-popping. say. Thus the substrates of a lifelong capacity for E-like consciousness can't be engineered via. This may be feasible.and post-synaptic receptors activated by an acute flood of extra serotonin/dopamine in the synapses . The idea here would be to reproduce E-like euphoric and empathogenic-entactogenic effects. Hence there is a need for novel agonists. The inhibitory feedback mechanisms that keep our Darwinian brains so meanspirited need to be sabotaged. This multiple targeting strategy is technically challenging.feasible even if the exact structural requirements needed to reproduce MDMA's acute stimulus effects were understood. but because a tobacco abuser need wait only seven seconds or so between taking a puff and the miniscule hit.or at least not in the same way. MDMA itself rapidly depletes serotonin from the axon terminals and inactivates the enzyme tryptophan hydroxylase needed for its renewed biosynthesis. Prolonged receptor activation typically leads to receptor desensitisation and/or down-regulation. Although there are indeed other. deliver sustained ecstasy without emotional burnout. even worse. The practice of tobacco-smoking. yet so too has a realisation that agents previously reckoned to be selective for a particular class of serotonin receptor are less selective than originally claimed. but because postponing the onset of drug-induced reward minimises a medicine's "abuse-potential" without compromising its efficacy. This is not just because the magic should be sustainable without limit. Such receptor re-regulation might involve a time-lag of one-to-three weeks. taking a controlled-release maintenance dose of functional analogues of MDMA may seem as natural as swallowing a multivitamin pill. and just what the doctor ordered. inhibiting the molecular machinery needed for its renewed synthesis. Depleting the brain's serotonin or. for instance. but via delayed receptor subtype-specific reregulation. Wireheading is uniquely effective. via a cocktail of agents rather than monotherapy. ideally. Indeed within a few decades. could. is a recipe for clinical depression. Alternatively. each individually designed ligand would be targeted selectively at the potentially magicsignalling receptor subtypes [or at second-messenger pathways coupled to the G-protein-linked signal-transduction system. The reward from oral MDMA takes somewhat longer. antagonists and inverse agonists with far greater selectivity for each receptor subpopulation. Inducing lifelong egoistic bliss is less of a technical challenge. Delayed-onset magic. if achievable. a mechanism akin to the MDMA-induced reversal of the serotonin reuptake pump. By contrast. To make the magic last for ever. as is normal with conventional "antidepressants". only a long-lasting homeostatic re-regulation of the central nervous system will work. or at least to induce it at will over several decades. but its orchestration will be much harder than it sounds. not acutely. would offer an immense social and therapeutic advantage. or in theory direct mechanisms of gene regulation and expression]. achieving the all-important goal of sustainability may entail . but it's probably more promising than relying on a single "dirty" non-specific indirect serotonin agonist like MDMA. 5HT2A(?). Such a profound homeostatic shift in normal waking consciousness might conceivably be delivered by functional analogues of MDMA. dopamine D2(?)]. not Heaven-on-Earth. On this approach. altering the density and signal-transduction efficiencies of the mission-critical receptor subtypes [5-HT1B(?). not kicked into gear. is so addictive not because of the surpassing joys of inhaling a cigarette. Alas the brain's post-synaptic signal-transduction mechanisms aren't yet sufficiently understood to bring about a magical E-like re-regulation of waking consciousness indefinitely. the neurochemical substrates of MDMA-like magic may be preserved. Nor can the substrates of perpetual empathetic bliss be delivered by tonic stimulation of the same pre. As the catalogue of serotonin receptor subtypes has grown.

but the two drugs are chemically unrelated. and deep sleep without inducing a hangover. GHB is an endogenous neuromodulator derived from GABA. and on slightly firmer grounds. Unlike MDMA. the main inhibitory neurotransmitter of the brain. This is a term popularised by the late Claude Rifat (Claude de Contrecoeur). GHB has anxiolytic properties. and perhaps more plausibly. paranoia and aggression. despite their pharmacological differences. the neurotransmitter GABA acts to reduce the firing of the dopaminergic neurons in the tegmentum and substantia nigra. serotonin reuptake accelerators analogous to the memory-enhancing antidepressant tianeptine (Stablon). A naturally-occurring fatty acid derivative. both GHB and MDMA deliver a rare emotional intensity of experience. or perhaps using better designed analogues of the emotion-deepening agent Gamma-HydroxyButyrate (GHB). GHB is a metabolite of normal human metabolism. GHB has been touted as an . it suppresses suicidal ideation. Sold as a medicine. GHB increases both the transport of tryptophan to the brain and its uptake by serotonergic cells. and it promotes enhanced feelings of love. and GHB-specific mechanisms by which GHB works. it enhances the recall of long-forgotten memories and dreams.g. and then once again co-administering receptor subtype-selective ligands and/or serotonin releasers. Taking GHB stimulates growth hormone secretion. though interestingly. GHB and MDMA are indeed sometimes mixed at raves. though GHB also modulates the GABA(A) receptor complex too. Whatever the exact GABA(A). Alternatively. GHB is known by clubbers if not structural chemists as "liquid ecstasy". profound emotional depth over many decades rather than a few hours may entail. GHB stimulates tissue serotonin turnover. In contrast to mainstream psychiatric drug therapies. ideally. GHB also stimulates tyrosine hydroxylase. One option here would be inserting "good" variants of the tryptophan hydroxylase gene. locking in the neural substrates of empathetic bliss as a default-state of consciousness may be achievable only via gene therapy. 1] new synthetic allosteric modulators of the serotonin 5-HT1B autoreceptors that regulate the evoked release and synthesis of serotonin.the use of drug cocktails. GHB offers cellular protection against cerebral hypoxia. 4] the right dopaminergic(s) or. when taken at optimal dosage GHB typically acts as a "sociabiliser". for example. In general. This is all still very speculative and unfunded. agents targeting the medium spiny GABAergic projection neurons in the rostromedial shell of the nucleus accumbens directly. GHB is licensed as an oral solution under the brand name Xyrem for the treatment of cataplexy associated with narcolepsy. ethyl alcohol). Rifat was GHB's most celebrated advocate and an outspoken critic of Anglo-American psychiatry. GABA(B). it's useful against panic attacks. A brief comparison of GHB and MDMA may be instructive because one therapeutic challenge ahead will be to design agents that reverse SSRI-like flattening of affect without inducing mawkish sentimentalism (cf. GHB has its own G protein-coupled presynaptic receptor in the brain. not flooding the synapses with extra serotonin followed by extra dopamine release as in acute dosing with MDMA. The sedative/hypnotic effect of GHB is mediated by its stimulation of GABA(B) receptors. subsequently metabolised to dopamine. GHB swiftly banishes depression and replaces low mood with an exhilarating feeling of joy. 3] the right 5-HT2C receptor antagonist or inverse agonist to make the E-like state more ecstatic. Like MDMA. GHB induces mild euphoria in many users. Similar therapeutic claims have been made for GHB as for MDMA. or perhaps enhancing the love-and-nurturance-promoting oxytocin system. or perhaps a hybrid gene-and-drug combination treatment. Thus one might explore combining e. Tyrosine hydroxylase converts Ltyrosine to L-dopa. but instead using e. pretreatment with the GABA(B) agonist baclofen also prevents an MDMA-induced rise in core body temperature. The main effect of GABA(B) agonism is normally muscle relaxation. Unlike MDMA.g. albeit an intensity different both in texture and molecular mechanism. which codes for the rate-limiting enzyme of serotonin biosynthesis. Our immediate options are limited. hence its popularity with bodybuilders. Pharmaceutical interventions aimed at extending. followed the next day by a refreshing dopamine rebound. the acute effects of GHB involve first inhibiting the dopamine system. author of GHB: The First Authentic Antidepressant (1999). it inhibits hostility. 2] agents acting selectively on the 5-HT1B-autoreceptors and heteroreceptors.

it's still flawed.e. that promises to deliver SuperEcstasy Mark 2. Thus MDMA's immediate homologue and closest relative. PMMA [N-methyl-1-(4-methoxyphenyl)-2-aminopropane] and TDIQ [5. Other such derivatives have been devised by entrepreneurs whose synthesis of designer drugs aims more at circumventing legal restrictions than pushing back the frontiers of knowledge. and more introverted in its typical subjective effects. This is because a significant percentage of the population will combine any drug whatsoever with alcohol regardless of the consequences to health. methylone is also available in . the phenethylamines as a whole exert a spectrum of action from the purely stimulant activity shown by "noradrenergic/dopaminergic" amphetamine to the almost entirely psychedelic activity of the "serotonergic" DOM .4-methylenedioxymethcathinone. the effects of the N-methylation of its primary amine. MDMA's subjective effects only partially cross-generalise to DOM and amphetamine. GHB may intensify emotion and affection.distributed at ultra-high doses in HaightAshbury San Francisco 1967 under the name of 'STP': Serenity. or to structurally related agents. Indeed MDMA only partially cross-generalises to the other two hypothetical family prototypes currently identified. then GHB could be a valuable addition to the bathroom pharmacopoeia. intenser. different monoamine-releasing amphetamine analogues become less subjectively rewarding as their serotonin-releasing potency is increased relative to dopamine-releasing potency. Branded rather unsubtly as "Explosion". There's no obvious new tweak of its molecular structure. Yet pure preparations of individual enantiomers are not always readily to hand. overdoing GHB makes the user fall profoundly asleep. exclusive 3-4 di-substitution on the aromatic ring. In drug discrimination studies. nor a route to lifelong wisdom if they were. GHB is probably unsafe to commend to clubbers. Only a handful of papers appear in the published scientific literature. but not introspective depth or intellectual acuity. users forget what they did under the influence of the drug.. one option is administering only (+)-MDEA. It's dangerous to combine GHB with other depressants. Tranquillity. and deeply relaxes his or her body. the beta-ketone analogue of MDMA. Higher doses will cause anterograde amnesia i. So what are the prospects for richer."]. and Peace. Research chemists have designed a host of ring-substituted amphetamine derivatives with one or more substituents attached at different positions to the phenyl ring of the amphetamine or methamphetamine structure. Unlike taking too much MDMA.3-dioxolo[4. GHB has a steep dose-response curve.5-g]isoquinoline] from the "fourth dimension". GHB disinhibits the user. even though systematic overground exploration of their effects on the human psyche has been strangled at birth. the optical isomer responsible for racemic MDEA's entactogenic quality. and this guy gave me a drink. Next thing I know. methylone (3. Whatever their parentage. than its sister molecule. MDA.8-tetrahydro-1. sustainable insight-and-empathy drugs from MDMA's phenethylamine sisters and cousins? Post-Shulgin. Inevitably. is poorly researched.6. MDMCAT). MBDB. or even if there were. Indeed MDEA is actually less warm and empathetic. So despite GHB's therapeutic and pro-social potential. the quantified structure-activity relationships of MDMA and related compounds (MDEA. but it's not going to deliver lifelong empathetic bliss. Curiously. MDEA (3. is an interesting agent in its own right. The drug is sold (expensively) as a "research chemical" over the Net. In general. If our consciousness is to be durably enhanced. If used wisely. to suppose the supermagic would be truly sustainable. I've no idea what happened in between.. etc) have been investigated.aphrodisiac: GHB heightens and prolongs the experience of orgasm. formed by swapping the 1 carbon methyl group for a 2 carbon ethyl group. GHB has been demonised as a date-rape drug ["I was at this party.7. and in a different cultural milieu. MDMA itself is truly "one of kind" (Dr Shulgin). sparingly.. both structurally (i. MMDA.4-methylenedioxyethylamphetamine: "Eve"). then sedative-hypnotics have only a limited role to play in the transition ahead. it's morning and I'm in someone's bed. But even then.e. its anomalously potent (+)-enantiomer) and subjectively. Methylone is another creation of Dr Shulgin. Instead of taking MDEA as the racemate.

taking MAO-inhibiting agents with anything serotonergic is normally contraindicated because of the risk of the serotonin syndrome. It is not as potent as MDMA. Its empathogenic qualities diminish. PMMA." Alas application of means-ends rationality is rarely the norm in drug-policy debate or in psychiatric medicine. . will serve but to demonstrate and confirm it. and it has a higher dosage range. However. it's completely unsustainable in regular use. benignly addictive lead compounds that maximise the user's well-being in lastingly empathetic.. In general. This is the distinctively E-like happiness that inspires love. Thus we continue with Rube-Goldbergish efforts to improve our well-being via environmental scene-shifting with mixed success. in all we think: every effort we can make to throw off our subjection. but it is a short-acting stimulant whose pharmacokinetics and toxicology are unknown. it may nonetheless fall within the scope of analogue drug laws. its stimulant effects become more pronounced. Methylone is mood-elevating. nurturance and understanding rather than egotism and dominance behaviour. Tolerance soon sets in: a sad and familiar story. 2-Methylamino-1-ptolylpropan-1-one) can be acutely rewarding. though its ortho-isomer. It's hard to imagine that any such futuristic love-drugs won't be "abusable" too. If methylone is taken chronically. even at relatively low dosage levels of 120150mg. pain and pleasure. It should be stressed that the comparative safety of methylone has not yet been well established. entactogenic and socially responsible ways. In the immortal words of Jeremy Bentham.. Recently it has become very popular in the scientific counterculture. but there can still be a very noticeable comedown. was once UK-licensed in tablet form as the bronchodilator Othoxine. the warm self-acceptance and empathetic love of others experienced on MDMA feels so clean and pure precisely because its mechanism is so messy. Thus methylone has activating and empathetic effects while inducing less emotional outpouring. Reputedly there is less serotonergic toxicity than MDMA. but its potency in promoting the synaptic accumulation of the catecholamine neurotranmitters noradrenaline and dopamine is similar. the empathetic euphoriant mephedrone (4-Methylmethcathinone. Nor is the pursuit of happiness undertaken much more rationally elsewhere. Yet rather than scorning the pleasure principle by seeking to minimise drug-induced reward. PMMA's reduced dopamine-releasing action makes it less "abusable" than other family members with overlapping psychostimulant effects. In any case..they govern us in all we do. PMMA [N-methyl-1-(4-methoxyphenyl)-2-aminopropane] a structural hybrid of paramethoxyamphetamine and methamphetamine. Methylone is not specifically scheduled (as of 2010). like most methoxylated amphetamines. PMMA arguably better represents a pure entactogenic [inward-looking. peaceful] family prototype than MDMA.several Dutch smartshops. From a theoretical perspective. DOM or amphetamine. self-accepting. higher doses induce a clear-minded and serene euphoria. "Nature has placed mankind under the government of two sovereign masters. is interesting. it might instead be more rational to design safer. Alas our knowledge (2010) of its properties comes wholly from user reports rather than peer-reviewed scientific journals. lacks MDMA's residual psychedelic or speedy effects: PMMA is thus clearly distinct from the other hypothetical family prototypes. and also from TDIQ. But if a drug isn't remotely rewarding or habit-forming. is potentially neurotoxic. Methylone causes less inhibition of serotonin reuptake and triggers less serotonin release than MDMA. on the other hand. Many subjects experience an E-like "magic". PMMA itself is a potent drug with a very low therapeutic index: the combination of serotonin-release and MAO-A inhibition integral to its entactogenic profile makes it hazardous in overdose. methoxyphenamine. though the two drugs can readily be distinguished by experienced users. Unfortunately PMMA. in all we say. then it probably isn't any good.. Likewise. This is still a new drug. about whose psychotropic effects rats currently know more than Homo sapiens. Well-designed (or serendipitously rediscovered) empathetic euphoriants can trigger socially responsible happiness.

Of course the biological route to nirvana has its share of pitfalls too. As it is. within any adequate scheme of classification. Yet even the most astonishing centrally active compounds are only research tools or therapies. They might conceivably do so if the PiHKAL-inspired compounds they ought to contain evoked the magical experiences their structures should ignite. Within a few decades. Who knows what else is accessible from Nature's psychoactive library by means of even "trivial" molecular genetic tweaks to our nerve cells? Disparate new categories of experience. we're trapped. can do more than select from a pre-existing menu of brain-states composing the subject's mind/virtual world. Needless to say. At least until we can genetically enrich the human mind/brain. and "psychedelic" are provisional and theoretically illmotivated terms. and MDMA is merely one of its most alluring seductions. and hopefully revolutionary conceptual schemes to navigate them. Rutherford provocatively once proclaimed. Inevitably this is all a bit lame. no drug or research chemical. and if some organic compounds didn't have the potential to unlock the doors to the kingdom of heaven.however magnificent their acute action on the user. "entactogen". The lack of an overall map. Thus by using. "entheogen". or even the ghost of a theory of consciousness to guide us. Fortunately there is an escape-route. Whereas merely E-like states are normally inaccessible because their owners would get eaten or outbred. Such modes of consciousness have been barred to us by natural selection. The creation of genetically enriched neurons should allow the exploration of multidimensional search-spaces of consciousness which we presently lack the molecular wetware to imagine or even name. not sacraments. "Empathogen". school chemistry-lessons and standard textbooks rarely set young imaginations ablaze. or volition from cognition or emotion. or disgust. nor indeed any irritation of the body's surface sensory transducers by the environment. The differences in gene-expression profile between neurons mediating the experience of. or the spectrum of altered experience disclosed by psychedelic amphetamines. For what matters. Seekers of sustainable ecstasy would be rash to fetishise any particular drug or family of pharmacological tools . makes it impossible to place MDMA. They either diminished their user's Darwinian fitness or would have entailed crossing gaps in the evolutionary fitness landscape to get there. are presumably waiting to be unlocked just by inserting new sets of neurological instructions. it's necessary first to find the specific neurochemical signature of the family of enchanted states we're targeting. In this sense. Novel neurally-expressed polypeptide sequences should disclose modes of experience hitherto unknown. Unfortunately we lack any God's-eye taxonomy of consciousness that might let us act like physicists and "carve Nature at the joints". transgenic . then Rutherford might have been right. the insertion of entirely new genes and variant alleles into our genome promises to revolutionise our stunted Darwinian minds. We've barely begun to ring the changes within the state-space of consciousness we've got. the genetic choices. say. for example. In practice. today's psychonauts are reduced to describing the subjective effects of psychoactive drugs by contrasting them with their "normal" states of being. In order to replicate and sustain the family of MDMA-like magical states safely and reliably. Each new state-space may be as different from the others as is sound from vision. varieties of drug habit and modes of consciousness of our post-human descendants are a matter for conjecture. In retrospect. is the otherwise inaccessible modes of experience such agents can unlock in the mind/brain . presumably. Yet the subjective differences in texture ("what it feels like") that their respective postsynaptic intracellular cascades generate are clearly spectacular. not the structure and pharmacology of the molecular probe alone. "All science is either physics or stamp-collecting". today's entire dreaming and waking consciousness may prove to be only minor variants on a theme whose motif can't be grasped from within.not the chemical structure of the agent that happens first to disclose their existence. A mature psychoactive taxonomy will need to be formulated relative to the architecture of particular phenotypes of mind. Alas the results of animal "drug discrimination studies" are no substitute for explanatory depth.and ways to sustain them . these unDarwinian modes of consciousness are quite possibly orthogonal to anything accessible today within our existing mental architecture. colour. No psychoactive drug currently gives access to these hypothetical state-spaces. or humour (or being loved-up) may strike us as subtle. the false prison can be transcended.

The prospect that we might personally choose to enrich our genetic repertoire from an ever-expanding library of newlycreated DNA sequences. sounds far-fetched.and mastering the types of mind/virtual-world these genes . then one option may be to protect ourselves by inserting new genes or new alleles into our legacy genome. MDMA's acute adverse side-effects i. and intervene to regulate their complex post-transcriptional editing. loss of coordination ["ataxia"]. as it were. Or we may choose to design. SPECT (Single-Photon Computed Tomography). so can we. Even pure. transgenic mice carrying the sequence of the human CuZn superoxide dismutase enzyme are resistant to MDMA-induced serotonergic damage. and an ever vaster neuroactive proteome. Radical enhancements of. If one's soul has been purified. Could we really cope with such an enlarged freedom of choice? In practical terms. say. Once the E-like signature is established. tachycardia. First. the use of personalized somatic gene-therapy may enable future scientists of the mind.to MDMA's psychological and physiological effects. However. sounds still more remote. teeth-grinding ["bruxism"]. Sustainable E-like consciousness is just one option among myriad flavours of sentient existence.and what's unwanted or inessential . Or we may simply induce the overexpression of endogenous antioxidant enzymes already coded for. PET (Positron Emission Tomography) and MRI (Magnetic Resonance Imaging) scans. humans can benefit from genetically enhanced neuroprotection no less than intoxicated rodents. even as the biotech revolution gathers pace. MDMA-induced incidence of these syndromes was apparently unknown in clinical practice prior to the drug's legal proscription. and pre-treatment with other pharmacological ligands that activate or antagonise or act as inverse agonists at particular subtypes of receptor in the brain. End-user ignorance of the low-level molecular machinery is fully compatible with everyday expertise acquired in managing the kinds of consciousness one's genes code for . with adequate medical research the mildest bad experience on MDMA should be preventable. Or by contrast. yes. antisense regulation of protein expression. or unabashed hedonists. however. refine and extend its magic. and rationally. it's possible some or all genetically enriched post-humans may shun adulterants of their beautiful forms of consciousness altogether. low-dose MDMA does not suit everybody. it should be possible for ideologically committed bioscientists to discover what is crucial . eye-wiggling ["nystagmus"]. atypical reactions to any drug at all should be expected. For instance. We're already on the brink of tailoring our drugs to our genes. why defile it? To suppose that we might opt deliberately to micromanage even a subset of the thousands of neurally active genes of one's genome. hyperthermia or idiosyncratic reactions to MDMA need to be eliminated and not just minimised. Nature uses lateral gene transfer. The modes of experience they generate may thereby become available. on tap. hyponatremia-induced cerebral and pulmonary edema (caused by drinking too much water).e. cardiac arrhythmias. Much more speculatively. even if sustainable ecstasy is only a staging-post on the route to a richer biochemistry ahead. jaw-tension ["trismus"]. If ever we wish to adopt a potentially life-enhancing but otherwise hazardous drug-regimen indefinitely. but in principle we can tailor our genes to our drugs.receptor-knockout "animal models". appetite-suppression. to sustain an otherwise neurotoxic drug regimen in safety. The really nasty stuff . the sorts of user-friendly visual interface we rely upon to interact with our PCs today can potentially be exploited to manage the neuroactive expression and regulation of one's individual genotype. insert. neuroscientists can then work how to mimic. rhabdomyolysis (the breakdown of skeletal muscle). and disseminated intravascular coagulation (inappropriate blood-coagulation leading to severe bleeding) are statistically very rare. and switch on and off as desired a suite of structural and regulatory genes for whatever life-enriching chemical exotica (or old favourites) we seek to enjoy. nausea. profuse sweating ["diaphoresis"]. dry mouth. Conversely. quantitative EEG with densemapping electrode arrays. not all the problems of MDMA use can be blamed on Prohibition and the lethal mix of ignorance and criminality it spawns. In the era of pre-genomic medicine. and perhaps surprisingly. Ideology aside.hepatotoxicity.

Intriguingly. in mice at least. tomorrow's domestic quantum computers may be harnessed anywhere and everywhere to more humanly empowering pursuits than the factoring of thousand-digit numbers that so excites contemporary cryptographic theorists. be shielded from the complex chemical minutiae of what is happening many virtual layers of complexity below. promoting safety. and far more ubiquitous. For now. So which ingredients of MDMA's primal magic are most worth mimicking pharmacologically in the near-term future? Preventing tolerance. in principle. the time-lag effectively collapses. Pessimists might argue that the opportunity for such life-transforming manipulations will be solely the privilege of a rich elite.2 dimethoxyaporphine). In practice. for instance. just as most PC users today wouldn't recognise machine code if it bit them on the nose. The friendliest. Thus the non-specialist user of genetic management software could. Sustainable E-like empathogen-entactogens may become as familiar as aspirin. around 10 years in the case of the PC. The molecular machinery of magic Lifelong ecstatic wonderpills and genetic self-mastery are at best some way off. and a greater or lesser hint of trippiness? Pre-treatment studies with receptor antagonists indicate that dopamine D2 antagonists such as haloperidol (Haldol) attenuate MDMA's positive hedonic effects. With information-based products. some 20 years for the TV. This doesn't mean we won't need all the help we can get in mastering the awesome software tools soon available to personalise our own genome and drug-regimen of choice.and drug-combos in search of promising leads for one's personal development program. more or less calmness or behavioural activation. voice-activated. But choosing who and what we want to be should feel exhilarating rather than intimidating. and SSRIs like citalopram (Celexa / Cipramil. The design of E-like hugdrugs. a product-pipeline of better. the behavioural and physiological effects of MDMA are selectively antagonised by the plant alkaloid nantenine (9. "scarcity" is a far more elusive concept than in the era of material commodities. purer empathogenic or entactogenic action. the most selective of the SSRIs) diminish if not abolish the full spectrum of MDMA's psychoactivity. Irritating bottlenecks notwithstanding. . much safer in overdose. and indefinitely extending duration are vital. Yet how desirable is inducing more or less euphoria. It took perhaps 50 years to democratise the radio. the "counterfeit" generic version is in no way inferior to the brand-name product.express. 5-HT2A antagonists like ketanserin suppress MDMA's residual psychedelic activity. the resources of. lovedrugs and euphoriants. Technically. such predictions may prove too tame to be realistic. For the time-lag between the introduction of a new technology and its diffusion to the population at large has been progressively shrinking. This anxiety is (probably) misplaced. certainly. and perhaps later the genetic programming of E-like waking consciousness. cheaper and safer designerdrugs and drug-and-gene-combos should in principle be accessible to everyone within 15-20 years. On this analysis. the prospect of a loved-up world reads like overheated science-fantasy. Thus the gap between an expensive software release in Redmond and its availability to the population of Thailand is perhaps a few hours. In this optimistic scenario. Drug discrimination studies performed on captive rodents may overlook certain subtleties of the MDMA experience. information is cheap.10-methylenedioxy1. faster. Nantenine is "antiserotonergic" and an alpha1-adrenoceptor antagonist. could be just the beginning of a whole new genetic and chemical cornucopia for mature post-Darwinian life. In a mature information-based society. most visually compelling user-interfaces that creative designers can build may make seizing control of one's destiny from a legacy genome a less daunting challenge than it seems today. A good place to start will be simultaneously screening an unimaginable multitude of alternate histories of gene. and even less for the mobile phone.

even though they don't explain it. glutamate antagonists or mu opioid agonists . serotonin is found in both the plant and animal kingdoms. To thicken the plot further. Serotonin entering the axonal vesicles is released over time in response to action potentials by exocytosis into the synaptic cleft. The serotonergic cell . Several of these serotonin receptor subtypes have functionally opposing roles. In the vertebrate CNS. As well as inducing a synaptic flood of serotonin. 14 sub-populations of G-protein-coupled receptors and one family of ligand-gated ion channels (the 5-HT3 receptor) have been cloned. Seven distinct families of serotonin neuronal receptors have been isolated. it's primarily a combination of enhanced oxytocin release and the interplay between the serotonergic and dopaminergic systems that underlies MDMA's discriminative stimulus effects/sublime magic. Increased synaptic availability of dopamine in turn inhibits glutamate-evoked firing in the nucleus accumbens. But the current consensus is that enhanced serotonin and dopamine release are crucial to the magic. serotonin-producing neurons regulate aggression. there's much more going on as well. 5-HT2A and 5HT2C). In addition. emotional resilience and romantic love. The hierarchy of their relative contributions to the subjective and behavioural effects of MDMA use may shift with increasing dosage and the course of the trip. Additionally. 5-HT2. prolactin. The serotonin system is uniquely complex. sleep. notably the effects of 5-HT1A and 5-HT2C receptor agonism on anxiety. serotonin released into the synaptic cleft activates multiple serotonin receptor subtypes (5-HT1. The full story is complex and still poorly understood. MDMA triggers the release of hypothalamic argininevasopressin and oxytocin (the "cuddle hormone"). sexual activity. sensorimotor integration. taking MDMA indirectly induces the release of extra dopamine in the mesolimbic reward centres. impulse-control. 5-HT4. Taking MDMA activates the poorly understood sigma(1) receptors. appetite.is the neurological signature of euphoric bliss. 5HT3. Dopamine levels are also increased by reuptake inhibition. and 5-HT7). Activation of the serotonin 5-HT1B and 5-HT2A receptors leads to an increase in the vesicular release of dopamine. On MDMA. These hormonal changes may influence some of MDMA's psychological effects. and inhibits its reuptake.and post-synaptic neurons. Our serotonin-producing neurons belong to a phylogenetically ancient neurotransmitter system. anxiety. The role of MDMA in activation the cannabinoid CB1 receptors to modulate its rewarding action is poorly understood.the effects of nantenine on ecstatic human subjects are unknown. mood. However. Dopamine released in the shell of the nucleus accumbens inhibits the firing of GABAergic medium spiny projection neurons. MDMA induces the release of noradrenaline (norepinephrine). temperature. contributing to its locomotor stimulant action. Inhibited excitability of the spiny projection neurons in the rostral shell of the nucleus accumbens . So does both the affinity of serotonin for its different receptor subtypes and the effects of serotonin agonists on second-messenger systems. As the user "comes up". MDMA exerts (weak) binding to the alpha-2 adrenergic and histamine H1 receptors. taking MDMA increases plasma cortisol. A whistlestop tour can't do it justice. MDMA also triggers the enhanced release of acetylcholine in the striatum and prefrontal cortex via serotonin 5-HT4 and dopamine D(1) receptor mechanisms. this binding contributes in unknown degree to behavioural stimulation. 5-HT5. Distribution. 5-HT6. But on present evidence. 5-HT1B. MDMA use alters the expression of several proteins involved in GABA transmission. Only a few hundred thousand of the 100 billion or so neurons in the brain manufacture serotonin.whether it's mediated by dopamine. The existence of the serotonin molecule in Nature long predates the brain. circadian rhythms. whatever its guise. dopamine synthesis is increased and turnover reduced. density and regulation of the serotonin receptors vary in different areas of the brain. and subpopulations (most notably. cognition. and dehydroepiandrosterone (DHEA) and aldosterone secretion. sensitivity to pain. Activation of the noradrenaline system causes an acute elevation of blood pressure. but rather by the structure of the post-synaptic receptor subtypes to which it binds. the narrow gap 10-20 nm across between pre. the effects exerted by a neurotransmitter on the post-synaptic membrane aren't determined by the chemical itself.

i. But it probably at least offers clues to the full story. Firing of the serotonin neurons causes exocytosis. Consequently. The receptor-based account below will soon be superseded by something deeper. Serotonin is metabolised. The subtypes play different excitatory and inhibitory roles. Depolarisation of the axon induces opening of voltage-sensitive calcium channels. the resultant calcium influx causes synaptic vesicles to fuse with the plasma membrane. The presynaptic 5-HT1B terminal autoreceptors form a vital part of a feedback mechanism regulating serotonin synthesis and release. The serotonin/5-hydroxytryptamine molecule itself is an indole amine synthesized from the essential amino acid L-tryptophan through the intermediate 5-hydroxytryptophan. serotonin exerts an action on both pre.e. Such knockout mice are also unusually partial to alcohol and supersensitive to . The neurotransmitter binds to multiple serotonin receptor subtypes.and post-synaptic receptor sites. Although some serotonin is present in the cytoplasm of serotonergic cell bodies and nerve terminals. but their projections extend to almost all areas of the brain and spinal cord. Whatever the precise details. taking MDMA causes a remarkable role-reversal of normal transporter function. sometimes termed serenics. aggression. the serotonin system helps to regulate a lifetime spent in complex social hierarchies where more ancient fight-or-flight reactions have been offset by the need for an increasingly complex cognitive. triggering a reconfiguration of the transporter so it binds to serotonin inside the cytoplasm of the nerve terminal. Most notably for E-users. not by calcium-dependent exocytosis of the serotonin-containing secretory vesicles. Amongst many other roles. Numerous studies have shown self-destructive violence. The reconfigured transporter then reverse-pumps the newly-bound intracellular serotonin out of the cell. Serotonin 5-HT1 agonists. repeating the process of depletion rather than recycling the neurotransmitter. changes configuration again. Current theory suggests that MDMA causes serotonin release via a diffusion exchange mechanism involving the serotonin transporter. The MDMA molecule binds with high affinity to the serotonin transporter and enters the presynaptic axon terminal. serotonergic projections innervate the dopaminergic nigrostriatal and mesocorticolimbic circuits. Extracellular serotonin is then normally taken back up into the serotonergic neuron via the highly efficient presynaptic transport pump. This prevents the neurotransmitter from being metabolised by the enzyme MAO. Receptor knock-out mice lacking the 5-HT1B receptor are superficially normal in appearance. dumps the serotonin into the extracellular space. This unique signalling complexity of the serotonin pathways and their multiple receptors ensures we can now be (un)happy in more ways than ever before. suicide. and highly reactive. these conditions are often conceived as disorders of "low serotonin function". a rapid calciumdependent process of neurotransmitter release. most serotonin in the axonal terminals is sequestered in small membrane-bound sacs. feeding patterns and breeding behaviour. investigators focus first on wherever they can probe most easily. reduced social status. and then takes up MDMA once more. The structure of the transporter protein determines how it couples ion gradients to substrate transport in ways that still need to be clarified.bodies are confined to the raphé area in the brainstem. show pronounced anti-aggressive properties. MDMA taken up into the presynaptic terminal unbinds from the uptake transporter. mainly by MAO-type A. poor impulse-control. emotional and behavioural response. So which receptor subtypes are of most long-term therapeutic and social-recreational interest to a notional paradise-engineer? Like the proverbial drunkard who searches for his lost keys only under a lamp-post "because that's where the light is". In the synapse. The ensuing flood of serotonin in the user's synapses sets the MDMA magic rolling. the synaptic vesicles. and some types of depression are associated with low concentrations of cerebrospinal fluid 5-HIAA. Aggressive behaviour is modulated in by the 5-HT1B receptors in particular. The serotonin system has co-evolved with dopaminergic projections in the course of primate evolution. where they empty their load of serotonin into the synaptic cleft. but they are ferocious. into the inactive metabolite 5-hydroxyindoleacetic acid (5HIAA).

Amphetamine. but results are mixed. Unlike. However. and the subjective effects of high-dose BZP cross-generalise to amphetamines in drug discrimination studies. Even combined with a dopaminergic. BZP is relatively safe if used in moderation. Taking BZP doesn't give rise to the inner serenity. Taken in the absence of a dopaminergic psychostimulant. So-called Party Pills. methamphetamine and BZP alike do indeed release dopamine from non-vesicular pools. Perhaps with this crude behavioural measure in mind. sensory enhancement and a low-key euphoria are typical. BZP use is now spreading world-wide. Acute activation of 5-HT1B receptors is known to play a role in MDMA-induced locomotor activity: 5-HT1B agonists and MDMA show cross-tolerance. Yet subjects who hope to replicate the full richness of the MDMA experience will be disappointed. a critical advantage for a recreational drug. Dry mouth. BZP was originally (1944) synthesised. there is substantial evidence to indicate that some endogenous serotonergic pathways normally activate rather than suppress motor output. currently the world leader in BZP consumption and export. The Social Tonics Association of New Zealand (STANZ) has developed a Code of Practice to encourage responsible use. No fatality has yet been recorded from BZP use alone. emotional release or extraordinarily empathetic compassion of MDMA. perhaps. "A2". some "unlicensed" psychonauts try combining a supposedly 5HT1B-selective agonist such as the piperazine derivative TFMPP [1(3trifluoromethylphenyl)piperazine monohydrochloride] with psychostimulants like 1-benzylpiperazine (BZP. so psychedelic effects are comparatively minor at sensible doses. In 2002 the drug was made Schedule 1 and its US users criminalised. The MDMA effect is hard to emulate: MDMA is "a multifaceted jewel". Over 20 million such tablets and capsules have reportedly been sold in New Zealand. Inevitably. 5-HT1B antagonists restrain the hyperlocomotion that rodents and clubbers typically undergo on serotonin-releasers like MDMA. suggestive of a common mechanism of action. It is now known that TFMPP binds at multiple serotonin receptors with only limited selectivity. "Flying Angel". . Legal Party Drugs. commonly mixed with various amino acids. The affinity of BZP for the serotonin 5-HT2A receptor is quite low. By contrast. BZP also acts as a relatively non-selective serotonin agonist. vitamins. BZP use tends to be self-limiting.the effects of cocaine. "Nemesis". though no clinical trials have been conducted into its long-term efficacy. herbs and other agents designed to modulate the core BZP experience and minimise side-effects. though these traits may reflect a compensatory enhancement of the dopamine system rather than offer a direct pharmacological model of 5-HT1B receptor function. appetite suppression and insomnia are common adverse side-effects. Many piperazine drugs tend to paralyse intestinal parasites. but to discourage thrill-seekers who might otherwise snort rather than swallow it. Moderate behavioural activation. developed and manufactured by Wellcome as a potential antiparasitic. the subjective effects of BZP are more subtle than crude speed. "Frenzy". say. Legal Herbal Highs and the like are marketed under numerous brand names. Social Tonics. BZP promotes the release and (to a lesser degree) inhibits the reuptake of the monoamine neurotransmitters dopamine. Some 1-benzylpiperazine users report that low-dose BZP is itself mildly E-like. allowing unwanted fauna to be flushed from the body. "Altitude". Many BZP-based preparations contain black pepper. TFMPP's activation of the 5-HT2C receptors makes some users feel anxious. In the 1970s. the FDA has now banned BZP on grounds of abuse potential. The BZP analogue N-ben-zyl-piperazine-picolinyl fumarate was even briefly marketed in Hungary under the brand name Trelibet as an antidepressant. Consumption is mostly by clubbers seeking a safer legal alternative to MDMA or amphetamines. The effect can indeed be E-like. noradrenaline and serotonin with different relative potencies. etc) to try and replicate the acute effects of taking MDMA. a tribute not to BZP's wholesome natural origins (it's synthetic). In "animal models". not a cheap-and-cheerful euphoriant. BZP proved effective in reversing melancholic/retarded/hypersomnolent depression. but nor is BZP a classic dopaminergic power-drug like amphetamine. 5-HT1B receptor agonists diminish alcohol-heightened aggression. BZP was investigated as an antidepressant. Used experimentally. Surprisingly. TFMPP does not feel akin to MDMA. Development was halted after BZP was discovered to have amphetamine-like properties. Sale in the UK was banned in 2007. cocaine. 5-HT1B receptor agonists such as the drug anpirtoline exert "serenic" effects.

Regulation of 5-HT1B receptor function itself is under the control of 5-HT-moduline.as distinct from "mere" raw bliss . an endogenous tetrapeptide that controls 5-HT1B receptor efficacy. The demeanour that an animal exhibits after "serenic" administration may indeed be submissive.is going to pose a formidable technical challenge. they can also curb aggression. potentially. and act on the 5-HT1B receptors as allosteric modulators themselves. But 5-HT1B antagonists and inverse agonists such as SB-236057-A are under investigation for possible clinical use as long-term and relatively fast-acting antidepressants. This isn't to deny that 5-HT1B agonists may have therapeutic potential. the possible existence of multiple subpopulations of 5-HT1B autoreceptors and heteroreceptors makes inadequate selectivity of ligands even more of a problem. function as heteroreceptors to inhibit GABA release. alcoholism or disorders of impulse-control and aggression. Cognitive function is affected by their use too. even if such agents induce a syndrome outwardly suggestive of inner tranquillity.There are further subtleties in the way of replicating MDMA's acute effects. In fact some so-called "serenics" may enhance fear/anxiety reactions: it's only their use in combination with dopamine-releasing euphoriants that makes such agents especially interesting to the psychonaut. Yet "serenity" tends to connote an inner E-like peace that may be lacking . Since the GABA terminals in the VTA and substantia nigra exert a tonic inhibitory influence on dopamine function. inhibition of GABA by inhibitory 5-HT1B heteroreceptors leads to the disinhibition of dopamine activity. Thus agents acting directly or indirectly as 5-HT1B agonists can cause the release of dopamine in the striatum and nucleus accumbens. assertive and aggressive behaviour of 5-HT1B knockouts. The syndrome of learned helplessness is associated with excess production of 5-HT1B receptors that are churned out in greater profusion by the depressive brain. Rationally designed synthetic drugs that recognize the 5-HT-moduline binding-site on the 5-HT1B receptors. 5HT1B receptors acting as autoreceptors regulate serotonin release via inhibitory feedback at the presynaptic terminals of serotonergic neurons. are clinically effective for treating migraines. Thus 5-HT1B heteroreceptors regulate the release of other neurotransmitters. for instance. coordinating their effects on a variety of different cerebral functions. serotonin 5-HT1B/1D receptor agonists. . circumvent the development of tolerance. "learned helplessness" and "behavioural despair"]. they play different functional roles. anxiolytic and mood-brightening effects by increasing serotonin release. 5-HT-moduline plays a pivotal role in synchronising the serotonergic signalling activity of the different terminals of individual neurons. A single serotonin neuron can modulate different brain functions and multiple cellular targets in virtue of the thousands of non-synaptic varicosities on its axonal branches that project to multiple areas and neurotransmitter systems. whether in bipolar disorder.e. The serotonergic system has both 5-HT1B autoreceptors and post-synaptic 5-HT1B heteroreceptors. and even more obstacles to sustaining the magic indefinitely. researchers can breed passive and depressive rats that show signs of abject misery [i. Allosteric modulators bind to a different binding site from the natural agonist and can. Indeed supersensitive 5-HT1B autoreceptors are implicated in depression and obsessive compulsive disorder. In general. 5-HT-moduline is a so-called allosteric modulator. antagonists and inverse agonists of the 5-HT1B receptor can improve the consolidation of learning.and not just in the unfortunate laboratory rodent. Thus the triptans. Acute 5-HT1B autoreceptor blockade can increase serotonin release. 5-HT1B receptors within the ventral tegmental areas (VTA). turnover and release of serotonin are typically increased under conditions of acute stress. care must be taken in describing serotonin 5-HT1 agonists as "serenics". This simplified outline of the neurobehavioural role of a single family of serotonin receptor subtype illustrates how inducing lifelong E-like states . Whereas 5-HT1B agonists may adversely affect memory via inhibition of acetylcholine release in the hippocampus. dopamine release is also regulated by 5-HT1B heteroreceptors within the glutamatergic hippocampo-accumbens pathways. autism. passive and timid in contrast to the fierce. especially for seekers of precision-tools rather than chemical coshes. By introducing extra copies of the gene for 5-HT1B receptors into serotonin neurons. In this case. 5-HT-moduline is released from adrenal medulla in response to acute stress. Indirectly again. 5-HT1B heteroreceptors are located on the terminals of nonserotonergic neurons. may potentially exert long-term serenic. however.

If prompted. tandospirone and ipsapirone are under investigation. MDMA activates post-synaptic 5-HT1A receptors of the paraventricular nucleus and supraoptic nucleus of the hypothalamus. Taken over a prolonged period. In future. 5-HT1A agonists facilitate male sexual behaviour. Hopefully. is licensed for generalised anxiety disorder. formulated to enhance people's trust in you!"[sic]. Intriguingly. MDMA typically causes its users to trust each other to an exceptional degree. 5-HT1A agonists are well tolerated. The MDMA molecule. Such drug-induced intimacy may partly be mediated by an increased release of oxytocin via MDMA-activated 5-HT1A receptors. In rats at least. the role of 5-HT1A receptor activation in MDMA's effects needs elucidation via more first-person experimental studies. But they may also on occasion induce dizziness. Clinically. in rats at least. especially the dextrorotatory "+" isomer. This may explain why it's never been wildly popular with patients. Recent research from Sydney University neuropharmacologist Iain McGregor suggests that post-synaptic serotonin 5-HT1A receptors contribute to MDMA's acute pro-social action via the enhanced release of oxytocin. many Ecstasy users report altered time perception. leading serotonergic neuronal activity to rebound. chronic activation causes the receptors to desensitise. Commercially. opening up the possibility of genetically amplifying our capacity for spirituality beyond anything humanly accessible today: it may be premature to assume that our descendants will be secular rationalists. Density of the 5-HT1A autoreceptors is also inversely correlated with the reactivity of the amygdala to threatening stimuli. There are methodological problems with the use of rats as test subjects in this context. 5-HT1A receptors are located solely on serotonergic nerve cell bodies within the dorsal raphé nucleus. Co-administration of MDMA and an oxytocin antagonist would test this hypothesis in humans. Oxytocin in turn reduces activity and weakens connections in the fear-processing circuitry of the amygdala. increased food intake and produce hypothermia. the role of the 5-HT1A receptors in MDMA's acute subjective effects still isn't clear. However. Oxytocin is a nine amino-acid peptide hormone and neurotransmitter that promotes pair-bonding. The paraventricular nucleus and supraoptic nucleus contain oxytocin neurons.the first Oxytocin product. Experiments with human as well as non-human animals show a . but any visual distortions are usually mild: the N-methyl group of the MDMA molecule prevents it from fitting as comfortably into the 5-HT2A receptor as does the trippier (-)-MDA enantiomer of its structural parent. MDMA analogues may conceivably be marketed with similar restraint. Alas taking them doesn't remotely engender the extraordinary sense of inner peace induced by MDMA. Similar agents like gepirone (Ariza). but the evidence is suggestive. though 5HT1A antagonists reduce discrimination of MDMA in animal models. a 5-HT1A partial agonist. Gepirone. confiding intimate personal feelings and secrets they would never otherwise share. hypotension. albeit a weak one. buspirone (Buspar). trust and social recognition. 5-HT1A receptor density is reported to be inversely correlated with susceptibility to spiritual experience. nausea. Buspirone itself is also a dopamine D2 antagonist. This is why taking the drug within the normal dose-range typically induces only minor perceptual changes. allegedly lacks significant activity at the dopamine D2 receptors. However. Whereas serotonin 5-HT1B receptors are found mainly on terminal processes. and headaches. has only a low affinity for the serotonin 5-HT2 receptor. 5-HT1A knockouts are timid. Pretreatment with a serotonin (5-HT1A) receptor antagonist apparently reduces MDMA's pro-social effect. flesinoxan. anxiety-ridden creatures. Acute activation of the presynaptic 5HT1A receptor on the raphé nuclei tends to reduce both the rate of firing of serotonin neurons and the corresponding release of serotonin from the nerve terminals. In general. It's also very slow to work. gepirone will prove a clinically useful anxiolytic and antidepressant. selective 5-HT1A receptor agonists typically exert a delayed-onset anxiolytic as well as (sometimes) a mood-brightening activity. Their (modest) therapeutic efficacy relies on an adaptive neuronal response. probably linked to their postsynaptic receptor action rather than presynaptic anxiolytic effect. oxytocin is marketed by Verolabs as a spray: so-called trust-in-a-bottle: "Liquid Trust Spray . none of which are prominent sequelae of MDMA use. Gepirone acts as an agonist at the presynaptic 5-HT1A receptors and a partial agonist at the post-synaptic 5-HT1A receptors.Whereas serotonin 5-HT1B receptor knockout animals are aggressive by nature. on the other hand.

Alas the unique effects of such doses [and likewise higher doses of other stellar phenethylamines] cannot safely be investigated in depth until the neurotoxicity of MDMA's metabolites and/or toxic free radicals can be prevented. The lucidity of the entactogenic effect of MDMA may be especially pronounced at low-to-moderate dosages. by taking only the (+)-MDMA enantiomer rather than the standard racemate. By contrast. MDA (which lacks it) is an all-in-one cocktail that can be hallucinogenic as well as empathetic and slightly speedy. feel the neurobabblers have lost the plot. Some psychonauts. Conversely. This is because their obnoxious molecular substrates will have been edited out. in safety. Thus one unintended consequence of scheduling MDMA has been to widen youthful exposure to psychedelia. But either way. entheogenic rapture. Despite the low affinity of MDMA for the 5-HT2 receptor. "Optimal" dosage of psychotropic agents taken for "nonapproved" purposes is most often empirically determined by the user investigating what level induces maximal enjoyment. We don't need a deep understanding of how and why consciousness is generated (or alternatively. . and map out even the most outlandish reaches of psychedelia. Most of today's storytelling about altered states and the chemistry of mind will doubtless seem no less archaic to our descendants than the Greek humoral psychology of classical antiquity strikes the contemporary molecular biologist. 5-HT2A receptor inverse agonists act as antipsychotics. Unlike us. Nonetheless at higher. None of this neurobabble should disguise the fact that psychedelia is still scientifically uncharted. MDMA can itself sometimes deliver psychedelic euphoria. as with so many psychoactive drugs. Activation of the 5-HT2A receptors is a prerequisite of the "classic" hallucinogenic effects exerted by tryptamine psychedelics such as LSD and phenethylamine psychedelics like DOM. it's also hard to prepare at home. Materialistic neuroscience has failed to close the ontological gulf between neural porridge and consciousness . We can guess even less about the possible altered states of consciousness of our redesigned successors. (-)-MDMA at normal doses is only minimally active at the "psychedelic" 5-HT2A receptor owing to its (comparatively) bulky methyl group. Alas our own less robust minds are psychologically vulnerable to even "physically" harmless psychedelics that aren't also euphoriants. especially when taking fast-onset euphoriants. Dual-action dopamine. "sub-optimal" dosages that more subtly modulate consciousness may be of greater value for facilitating personal growth. our genetically enriched descendants may revel in the assurance that bad trips are inconceivable. Low-to-moderate dosage E-experience may be easier to integrate into the rest of one's E-less life. understandably enough.whether "ordinary" or "altered" states. if the user desires a completely clear sensorium. some philosophers allege. very often "less is more". Sadly.and serotonin-releasers like MDMA are the latter. its fundamental immanence in the world). This piety is easy to intone but hard to practise. It's often too weirdly exotic for words. and psychological damage is impossible. we need manufacture only the sufficient neural conditions for beautiful states of consciousness. then perceptual alterations might seem eliminable altogether. albeit psychedelia in its warmest and most gentle introductory guise. With MDMA. though they aren't always harmless. Yet fortunately for the engineering purposes of inducing sustainable E-like bliss. our emotionally invincible descendants should be able to explore entheogens.correlation between a drug's psychedelic potency and 5-HT2A receptor binding affinity. pharmacological blockade or genetic knock-out of the 5-HT2B receptor abolishes MDMA-induced hyperlocomotion and serotonin release in the nucleus accumbens and ventral tegmental area of the brain. We don't know whether the "explanatory gap" between the physical facts and phenomenal mind can ever be closed. In the meantime. and some very interesting exotica indeed. quite possibly neurotoxic doses of 200mg or so. in principle. pure (+)-MDMA is scarce. Yet the effects of lower.

Yet the multiple serotonin pathways play functionally different roles. Dopaminergic activity in the brain and motor behaviour may be crudely interpreted as under the inhibitory control of the serotonin system. According to one hypothesis. At lower doses.Alternatively. entering the activated receptor state in the absence of an agonist. at least at ordinary dosages. VTA dopaminergic neurons in the brain's reward centres are under continuous inhibition by GABA. MDMA may itself bind. activation of 5-HT2C receptors is anxiogenic. the halogenated amphetamine appetite-suppressant fenfluramine (Pondimin)]. Convergent strands of evidence indicate that dopamine release is critical to the MDMA magic. So trying to eliminate perceptual alterations completely while retaining the full-blooded E-magic may be difficult. Post-E levels of dopamine in the mesolimbic reward circuitry are far higher than would be explained by MDMA's relatively weak additional release of dopamine via the uptake carrier. and the human behavioural evidence. sometimes evidently more effectively than others. However. Although some MDMA users prefer reflective tranquillity and intimate group hug-ins. But serotonin-releasing agents [e. there are complications. and its ratio of serotonin to dopamine release is higher. 5-HT2A antagonists have the additional advantage of preventing MDMA-induced hyperthermia that exacerbates toxicity. Such receptor stimulation can trigger marked hyperactivity. many loved-up clubbers opt to dance for hours at raves .g. hypothermia-inducing agents enhance neuroprotection.a form of hyperlocomotion one would expect from Peruvian marching-powder rather than a serotonergic agent. than amphetamine. MDMA-induced locomotor activity is caused mainly by the released serotonin's preferential activation of the 5-HT1B receptor. Compared to amphetamine this is true: MDMA's affinity for the serotonin transporter is greater. The release of serotonin following an MDMA-induced reversal of the reuptake pump results in a stimulation of the 5-HT1B receptors and. the extra serotonin released by MDMA stimulates 5HT2A receptors located on inhibitory gamma-aminobutyric acid (GABA) striatonigral neurons. A further complicating factor is that MDMA-induced release of serotonin stimulates the 5-HT2C receptors. Animal drug discrimination studies. to the 5-HT2A receptor. Thus 5-HT2C receptors tonically inhibit dopamine release in the nucleus accumbens. demotivating and generally unpleasant. this account is still simplistic. tend to support this dopaminergic account. mostly it seems in virtue of their constitutive activity i. Stimulation of the serotonin 5-HT2A receptors contributes to the rewarding effects of MDMA. Even MDMA's extra release of dopamine partly depends on its activation of the 5-HT2A receptors. MDMA is often reckoned a "serotonergic" drug. Other things being equal. at higher doses. Stimulation of the 5-HT2A receptors inhibits these GABA neurons. conversely. Certainly the stimulant effects of MDMA are greatly enhanced following treatment with a 5-HT2C . Activation of the 5-HT2C receptors serves to mask expression of MDMA-induced hyperactivity. if uncomplicated perceptual clarity is sought then a 5-HT2 antagonist such as ketanserin or the 5-HT2A selective MDL-11939 might help preserve total lucidity. especially in young MDMA users who rave. taken on their own. or at least plays a permissive role in dopamine release. To complicate matters. The various subpopulations of 5-HT2C receptor located on GABAergic neurons in the ventral tegmental area and the substantia nigra tend to exert a tonic inhibitory influence over the mesolimbic dopamine system. The enhanced release and reuptake inhibition of dopamine is essential to MDMA's tendency to promote blissful well-being and to colour its entactogenic-empathetic effect. thereby allowing the disinhibition of dopamine biosynthesis. aren't notably rewarding or entactogenic/empathetic. The greater flood of serotonin in the synapses triggered by higher doses of MDMA promotes locomotor activity via 5-HT2A receptor-mediated dopamine stimulation as well. This is because serotonin has a somewhat higher affinity for the 5-HT1 receptors than the 5-HT2 receptors.e. Neurotoxic hydroxyl radical formation is temperature-mediated. increasingly of the 5-HT2A receptors as well. albeit weakly. However.

Thus the MDMA-induced disinhibition from social anxiety. 3) The mesocorticolimbic pathway extends from the ventral tegmental area to the nucleus accumbens and the medial prefrontal cortex. we're probably all anhedonic. there are complications: all 5-HT2C receptors are not the same. the receptor story illustrates at the molecular level that being blissful isn't the same as being blissed out. First. 1) The nigrostriatal pathways extend from the substantia nigra pars compacta to the striatum. This pathway is critical to the control of involuntary motor movement. an unavoidably fast-and-furious tour of the dopamine system is in order. and emotion. If acute serotonin-mediated enhanced dopamine-release is indeed essential to the magic of MDMA. and the lowering of psychological defensive barriers. appetitive behaviour of all kinds. simply banishing all capacity for social anxiety isn't going to work. With none of these drugs or drug categories is a reduction in the user's social anxiety matched by an E-like upwelling of empathy or sensitivity to the feelings of others . there are many pitfalls in choosing the right dopaminergic for the job.or indeed by alcohol or opiates. So some form of dopaminergic augmentation is a therapeutic step in the right direction. They regulate movement. 2) The tuberoinfundibular system extends from the hypothalamus to the pituitary gland. Empathy entails caring about others. Specific and selective 5-HT2C receptor antagonism may well prove a worthwhile goal. but it's too early to say what the MDMA experience may gain or lose in consequence. and several other neuropsychiatric disorders such as Tourette's Syndrome. its dysfunction is implicated in the tremor.in fact quite the reverse. dopamine is critical to sensorimotor integration. As usual. rigidity and akinesia of the "dopamine deficiency disorder" Parkinson's disease. and their individual roles in modulating the MDMA effect aren't properly understood. The mesocorticolimbic system is central to emotion. not lacking a care in the world. However. and the regulation of lactation and fertility. But beyond these superficial generalities. and the orchestration and activation of the motor output system. the modulation of thought-processes. and this process is mediated by both dopamine and serotonin receptors. It's involved in prolactin. There are subtleties of the MDMA experience that haven't yet been explored. inhibition of glutamate-evoked firing in the nucleus accumbens is an ingredient of the E-magic: it is known that firing-inhibition depends on both dopamine and serotonin release. a direct chemical assault on the hedonic treadmill rarely works. Less speculatively. using a cocktail of subtype selective serotonin agonists and gentle dopaminergic psychostimulants still looks like the easiest way to mimic and enhance the entactogenic-empathogenic effect induced by MDMA-like compounds. and they naturally invite dual-action remedies. and what can be done about it. The CNS has three main dopaminergic pathways. whether socially or subjectively. Numerous 5-HT2C receptor isoforms are produced as a result of RNA editing. This failure is witnessed by the unsatisfying and usually counterproductive effects of using catecholamine-depleting psychostimulants. 5-HT2C antagonists such as agomelatine (Valdoxan) are under investigation as potential clinical antidepressants. Compared to our descendants. In contrast with intracranial electrical stimulation. Until the dawning of the era of wholesale genomic rewrites and true designer babies. more subtly. In crude terms again. hormonal secretion.and growth hormone-secretion. is radically distinct from the sort of anxiolysis induced by SSRIs or the benzodiazepines . motivation.antagonist. So it's worth reviewing how and why the substrates of human well-being are held in check. To sustain empathetic love. Darwinian-era mood and motivation is regulated via a multitude of indirect mechanisms of feedback-inhibition. Sustained antagonism of the 5-HT2C receptors might well we harnessed to intensify the hedonic properties of long-lasting E-like consciousness. working out how to replicate sustainably at the molecular level the precise neurochemical signature of peak experiences will be hard. Dopamine has also traditionally been described as the brain's "pleasure . In general. Each projects from dopaminergic cell groups in the midbrain. willed action and. "Dual-deficit" models of everyday E-less malaise are plausible. then a wide range of safe long-acting dopaminergics are already on offer to augment any hypothetical subtype-selective "serotonergic" therapies. Clearly. the capacity to switch from one course of behaviour to another.

who are neither clinically depressed nor loved-up on MDMA . excitability. Like the other catecholamine neurotransmitters. MDMA inhibits the neuronal reuptake of dopamine. exploration. L-tyrosine is transported across the blood-brain barrier into the dopaminergic nerve cell. increased post-E administration activity of the serotonin 5-HT1B and 5-HT2A receptors causes the dopaminergic neurons themselves to fire more rapidly.comparatively anhedonic and hypodopaminergic? The dopamine neurotransmitter is under powerful homeostatic control. In common with amphetamine. each type of dopamine receptor belongs to the superfamily of G-protein-coupled receptors that activates or inhibits different forms of adenylyl cyclase inside the cell. For better or worse. Further. the dopamine system doesn't quite rival the molecular. This higher impulse-frequency causes increased dopamine-release via exocytosis of the dopamine-containing vesicles in the normal manner. significance and a feeling of things-to-be-done. But this formulation can be misleading.chemical". Couched in the language of psychology rather than neuroscience. within a few decades prospective parents will be able to select such alleles and their rationally redesigned enhancements when choosing the parameters of their future offspring. For example. However. consistent with the dopamine theory of reward. Intriguingly. after a user has taken a classic amphetamine. Such naturally loved-up kids may prove more easily adorable than today's Darwinian default-models. At the cellular level. electrically or pharmacologically stimulating microcircuits in the rostromedial shell of the nucleus accumbens produces intense pleasure in the absence of any goal-seeking behaviour. pharmacological and functional diversity of the serotonin system. The molecular substrates of pure pleasure are still elusive. or alternatively. Dopamine levels tend to rise if one is anticipating a rewarding event. E-like temperament. Further. The mesolimbic dopamine system mediates "wanting" more than "liking". though alas not a loving. but the two "classic" types of dopamine receptor (D1-like and D2-like receptors) have several subtypes and alternate splice-forms. recycling it as normal. Depending on concentration gradient. and its druginduced or electrical stimulation may increase incentive-salience rather than the raw intensity of pleasure itself. Dopaminergic neurotransmission is critical to incentive-motivation and all forms of purposeful behaviour. and an optimistic mood. the number of different messenger RNA and dopamine binding sites substantially exceeds the five dopamine receptor genes of the human genome. They rapidly terminate the action of the neurotransmitter on the receptors if it isn't metabolised by the MAO or COMT enzymes. This trait is characterised by a tendency to impulsiveness. So what leaves so many "normal" Darwinian people . cueing potentially (Darwinian) fitness-enhancing stimuli so they can acquire control over an organism's behaviour. the carrier can transport dopamine from the cell terminals into the synaptic cleft. individuals with genotypes containing the seven-repeat allele of the dopamine D4 16-amino acid repeat polymorphism tend to exhibit the personality trait of "novelty-seeking". dopamine release and spontaneous action-potential generation in dopamine-producing cells is modulated by a . So is the density and signal-transduction efficiency of the receptors to which it binds. Certainly. the presence or absence of variant alleles of dopamine receptor subtypes and their signal-transduction mechanisms is correlated with variants of human behaviour and personality. dopamine itself is synthesised from the nonessential amino acid L-tyrosine. and levels then tend to fall if the anticipated reward fails to materialise. At the synapse. risk-taking. Ldopa is then rapidly converted to dopamine by L-amino acid decarboxylase. Next dopamine is sequestered in synaptic vesicles by a dopamine transporter. the dopamine carrier can transport dopamine back into the nerve cell. albeit more weakly than MDA. a diversity that reflects the genetic polymorphism and alternative splicing events in normal dopamine gene-expression. enhanced dopamine release in the pleasure centres imparts a sense of urgency. L-tyrosine is converted to L-dopa by the enzyme tyrosine hydroxylase. the dopamine nerve terminal displays high-affinity uptake sites. Feedback-inhibition of dopamine synthesis.

g. the lithium used to treat . In addition. It is activated by "reward stimulation" of the ventral tegmental area. simply increasing raw dopamine levels per se is not enough. Augmentation should in any case be tried only cautiously and in controlled-release preparations (e. These neurons come in two types. Indeed Ldopa-maintained dopamine knock-out mice become hyperactive and sexually vigorous. libido-enhancer and mood-brightener. clubbers and alternative therapists alike have explored taking freeform amino acid supplements of L-tyrosine and L-phenylalanine in a bid to boost native dopamine levels or reanimate a drug-frazzled brain. some psychonauts. Yet when such dopamine knock-out mice are abundantly maintained on L-dopa. For instance. an agent such as alpha-methylparatyrosine that inhibits tyrosine hydroxylase.variety of functionally distinct dopamine autoreceptors that regulate membrane excitability. In a more controlled setting. presynaptic dopamine receptors modulate the rate of tyrosine hydroxylation. Whatever the mechanism. The dopamine neurotransmitter itself functions as an end-product inhibitor of tyrosine hydroxylase. So unlike tryptophan-loading and/or 5-HTP-loading to increase neural levels of serotonin production. Precisely what dopamine actually does in the all-important dopaminesensitive shell of the nucleus accumbens is unclear. But well-controlled. taking L-dopa does increase synaptic dopamine levels. this "dopaminergic" precursor strategy typically doesn't work. For instance. the rate-limiting enzyme in catecholamine synthesis. notably serotonin. It regulates motivation and pleasure. This subtype projects directly back to the ventral tegmental area. and ruins the MDMA magic. drink or do very much in this world at all. such magic-prevention experiments are an important pointer to what's needed to sustain the MDMA spectrum of consciousness. Indeed activity of the mesocorticolimbic dopamine system is regulated by multiple neuronal pathways containing different neurotransmitters. By contrast. The main effect of its release seems to be the inhibition of the GABAergic medium spiny projection neurons (MSNs). On the other hand. So how can this cruel and complex web of inhibitory feedback mechanisms best be modified? If our aim were pure-and-simple cloud nine euphoria. rodents engineered so they can't synthesize dopamine initially develop quite normally. or our deficit thereof. only to die miserably a few weeks after birth following a failure to eat. Sinemet SR) since high levels of L-dopa may increase oxidative stress. they can flourish. Administering dopamine D2-blockers tends to induce apathy and anhedonia. But tyrosine hydroxylase is normally saturated. GABA and glutamate. dynorphin and dopamine D1 receptors. and the regulation of old ones improved. This sort of GABAergic medium spiny cell projects from the nucleus accumbens to the ventral pallidum. This is especially so when L-dopa is combined (as in Sinemet for Parkinsonians) with a peripheral decarboxylase inhibitor such as carbidopa to prevent its metabolism outside the brain. This complicates any simplistic catecholamine-depletion theory of retarded depression. Crude "natural" interventions to enrich dopamine function aren't effective. and most mesolimbic dopamine neurons possess cholecystokinin-autoreceptors and neurotensin-autoreceptors that regulate dopamine function as well. Nasty but instructive. All the classical dopamine D2-blocking neuroleptics blunt will-power and flatten emotion. opioids. then better drugs to decrease glutamate and GABA currents in the critical medium spiny neurons of the nucleus accumbens might be adequate at least until new genes and gene networks can be more readily inserted in the genome. dopamine-releasing agents demonstrably tend to induce euphoria. the rate-limiting step in dopamine production. high-functioning euphoria is more elusive than mind-blowing rapture. One subtype expresses dopamine D2 receptors and enkephalin. but in non-depressives it doesn't reliably do so. Nevertheless. dopamine receptor antagonists like haloperidol are dulling and dysphoric. Dopamine synthesis is also modulated by the rate of impulse-flow from the nigrostriatal pathway. taking L-dopa can be an effective motivator. Conversely. might be expected to produce a state of melancholic depression. This manipulation has not yet been attempted in dopamine knock-out humans. Enhanced phosphatidylinositol hydrolysis is implicated in euphoric mania. At least for a minority of "normal" subjects. The other subtype of GABAergic medium spiny projection neuron co-expresses substance P. It's known that stimulation of the dopamine D2-like receptor causes an increase in phosphatidylinositol hydrolysis by activating enzyme phospholipase C. Dopamine plays this role by competing with a tetrahydrobiopterin co-factor for a binding site on the enzyme.

Quite aside from their different molecular mechanisms of action. selective MAO-B inhibitors such as selegiline (Eldepryl) or rasagiline (Azilect). there are striking differences in subjective effect between MDMA and "serotonergic" centrally active psychiatric medicines. which it releases into the synapse before taking back more MDMA into the terminal. catechol-o-methyltransferase (COMT) inhibitors such as tolcapone (Tasmar). vanoxerine. MDMA occupies the serotonin transporter and prevents serotonin from binding. even though their action on reuptake inhibition increases the neurotransmitter's synaptic availability. is a veritable love-potion. whereas many dopamine reuptake inhibitors [e. however. nomifensine] "adaptively" diminish the neuronal release of dopamine over time. and zombies have no real insight into what they're lacking. emotions are heightened as well as enriched. the rest of us have the emotional intensity of zombies. Unfortunately. albeit not for long. by contrast. fluvoxamine/Luvox. SSRIs are mood-blunters and even. Other crude strategies to augment dopamine function involve taking dopaminergic agents such as the dopamine agonists pergolide (Permax) and bromocriptine (Parlodel). if fast-acting and taken in the absence of anything subtype selectively "serotonergic". SSRIs can also diminish the intensity of love. adenosine 2A receptor antagonists. Compared to loved-up ecstatics on MDMA. MDMA is small enough to be taken up by the serotonin reuptake transporter into the serotonergic cell. the SSRIs and other "serotonergic" antidepressants. For instance. But they don't promote depth of feeling. MDMA itself rapidly banishes all kinds of depression.and impulse-modulating presynaptic dopamine D2/D3 autoreceptors. though not to the same degree as SSRIs blunt MDMA-induced release of serotonin. centrally-active dopaminergic "pro-drugs" with higher bioavailability and fewer adverse side-effects are also under investigation. In reality there are profound differences between MDMA. may not induce serenely motivated well-being as distinct from compulsive pleasure-seeking. release. MDMA. dopamine-release promoting agents. increasing its availability in the synapse. However. SSRIs commonly make those who take them more resilient and less anxious. sertraline/Zoloft. even if some of us can talk as though we do. Ironically."uncontrolled" euphoria inhibits the phosphatidylinositol second messenger system and darkens mood in nondepressed "euthymic" people. This is one reason why so many remain depressed or "partial responders". for some people. psychic anaesthetisers. selective D2/D3 agonists such as pramipexole (Mirapex) or ropinirole (Requip). Understanding the principles behind the pharmacological induction of controllable non-stop euphoria will be a first step on the route to designing lifelong variations of the subtler forms of magic. another is opiophobia. Oral. On MDMA. Clinicallylicensed SSRIs [fluoxetine/Prozac. the potent. paroxetine/Paxil. Any tendency to cause uncontrolled dose-escalation is likely to cause toxicity. pro-sexual. Even victims of melancholic or retarded depression are widely denied access to clinically effective catecholaminergic antidepressants. In the meantime. dopamine antagonists like amisulpride (Solian) can be used at low doses preferentially to antagonise the synthesis-. fluoxetine (Prozac) was the first and most famous SSRI. long-acting D2 agonist cabergoline (Dostinex). More typically. thought disturbances or manic excitement. where its release from the transporter allows the transporter to bind to intracellular cytoplasmic serotonin. pre-treatment with high doses of dopamine reuptake inhibitors blunts MDMA-induced release of dopamine. florid psychoses and abuse. But there are obvious problems. intellectual dynamism or clarity of thought. bupropion. Like an SSRI. at a time when the loss of personal liberty entailed by prohibitionist drug laws is justified by the societal . Regrettably. MDMA is sometimes likened in the media to the much more commonly prescribed selective serotonin reuptake inhibitors. Thus a regimen of low-dose amisulpride may potentially enhance dopamine release and boost mood and motivation. In spite of its relatively powerful indirect dopaminergic activity. these worries about the "abuse-potential" of psychostimulants frequently generalise in mainstream wisdom to an unwarranted fear of all "dopaminergic" antidepressants/mood-brighteners. The serotonin transporter pulls the MDMA molecule up into the axon. and citalopram/Celexa] may make a small minority of people feel durably "better than well". and centrally active nicotinic receptor agonists. This taboo against "excessive" well-being can have serious medical consequences. what Claudio Naranjo aptly christened a "feeling intensifier".g.

In general. Some depressives. However. no firm conclusions have yet been reached on the advisability of taking DHEA supplements. One unwanted effect of MDMA. levels of DHEA decline with age after early adulthood. One technical (and ideological) challenge of the pharmacogenomic revolution in prospect at the interface between genetics and drug-design will be to investigate how the emotional honesty and extraordinary depth of feeling induced by MDMA can be sustained over a period of months. SSRIs. DHEA may brighten mood. On MDMA. SSRIs are prone to impair romantic ardour as well as libido. A wide range of cholinergics is now under development for the palliative treatment of Alzheimer's disease. possibly owing to dysregulation of the cholinergic-adrenergic axis. both philosophising and emotional self-honesty can be illuminating and fun. For the cholinergic system is vital to memory. Acetylcholine-release and muscarinic receptor activation probably play no direct role in the rewarding hedonic effects of MDMA. Taken on its own. but it's scarcely an E-like effect. rivastigmine (Exelon). There are further complications to overcome if any bid to replicate and sustain full-spectrum E-like consciousness is to succeed. higher thought-processes and verbal fluency. Nor is it known what role enhanced DHEA might play in sustaining enriched quality of life over the longer term. By reducing "neediness". or an optimal dosage if taken. While a great many depressed people report intellectual sluggishness and poverty of thought. MDMA is also a weak agonist of the acetylcholine muscarinic M1 receptors. can either save marital relationships or wreck them. "Dumb-drug" antimuscarinic agents commonly induce mild euphoria via their indirect enhancement of dopamine function. may actually benefit from the antimuscarinic anticholinergic effects that more intellectually fastidious clinicians would call an adverse side-effect of the older tricyclics. DHEA is the precursor to testosterone. tryptophan hydroxylase function must be enhanced. other melancholic and introspective depressives endure "hypercholinergic frenzy". though DHEA's precise contribution to the mood-elevation is unclear. SSRIs also diminish what today passes for love. . however. immune function and some forms of cognition. Long-term supplementation with DHEA seems to have beneficial effect on libido. Cholinergics such as piracetam (Nootropil) are used as nootropics or "smart drugs". MDMA's modest cholinergic activity may contribute to the exquisite lucidity of consciousness characteristic of pure MDMA taken in a therapeutic setting.costs of illicit drug-taking. MDMA triggers the release of the neurotransmitter acetylcholine via a histaminergic H1 mechanism. MDMA allows introspection to become insightful and enjoyable even to the naturally angstridden. estradiol and other steroids. the axon's vulnerability to oxidative stress is increased. muscarinic M4 receptor) agonists and cholinesterase inhibitors which have a tendency to subdue mood.g. In order sustainably to enhance our capacity for empathetic bliss. by enhancing the user's emotional self-sufficiency. MDMA causes a rise in the adrenal corticosteroid dehydroepiandrosterone (DHEA). Even though the acute functional loss of tryptophan hydroxylase in the cell terminal is reversible. years and decades rather than for two-hour bursts. and certainly to prevent any functional serotonergic deficit. Yet their subtle contribution to the texture of the magic can't be discounted. in spite of a wealth of research. By contrast. Sadly. "psychiatric" drugs are clinically prescribed by physicians regardless of the likely effect of a medication on the personal relationships of the patient. progesterone. and acetylcholinesterase inhibitors like galantamine (Reminyl). is its tendency inhibit to tryptophan hydroxylase by triggering a rapid oxidation of the enzyme's sulphydryl sites. Their moodbrightening effect stands in contrast to many cholinergic (e. tacrine (Cognex) and donepezil (Aricept) are used as palliative treatments of Alzheimer's disease. Another enigma is the role of DHEA. a progressive neurodegenerative disorder characterised by profound cholinergic deficits. The rise and peak physiological values of DHEA between around 1 to 2½ hours postMDMA administration is correlated with user-reported euphoria. Tryptophan hydroxylase is the rate-limiting enzyme in serotonin synthesis. innumerable depressives among life's walking wounded today find the examined life scarcely worth living: they cope with life only by "just getting on with it". It's a shame that such self-insight can't more readily be prolonged. especially when taken at higher doses.

only when the intracellular signal-transduction mechanisms.1%.e. increased serotonin synthesis also aggravates post-E neurotoxicity. the study of how an individual's distinctive genetic inheritance affects the body's response to drugs. Owing to genetic polymorphisms in drug-metabolising enzymes. This therapeutic opportunity is wasted because. restraint is prudent. Doubtless a regulatory minefield lies ahead. we may be able to generate sublime MDMA-like states . So as well as developing gene-therapy to prevent suicidality . the use of interventions to increase the biosynthesis of serotonin prior to MDMA use tends to trigger an increased synaptic release of dopamine. they are perennially active. and perhaps the selective silencing of gene expression via RNA-mediated interference of anything really nasty. for instance. In some cases. the redesigned "underexpression" of others. The advent of genetically personalised medicine should mean that these atypical cases can be excluded. thereby enhancing the user's euphoria. Ultimately.alleles .01% of people who take such agents suffer severe adverse reactions. research or "recreational" purposes. to date no stimulator (or inhibitor) of the biosynthesis of serotonin has been commercially marketed. of ourselves and each other by genetically enhancing our own minds. they show a greater activity in the genetic machinery churning out the 5-HT2A receptor itself. One momentous development is perhaps only a decade or so away. the set of particular forms of genes . and given other medication instead. Useful older drugs can be dusted off the shelves and re-licensed. Such access offers scope for fine-grained manipulations of the chemistry of our souls inconceivable in the Dark Ages of pre-genomic medicine. Unfortunately. can amplify desirable facets of our consciousness and suppress its darker and more poisonous variants. say. suicide victims.and forestall the whole spectrum of deeply unpleasant parasuicidal and self-destructive states .not inhibited. to order. In the imminent era of genomic healthcare. The two mechanisms are separable in principle. we may each enjoy access to a read-out of our own individual genotype i. valuable licensed medicines are pulled after post-marketing surveillance. other enzymes are expressed essentially only when . whether for medical. New agents can be developed and given faster regulatory approval. Interestingly. Psychoactive drug users in particular should benefit from the prospect of genetic selfknowledge.99% of the population can't get regulatory approval. 1%. such intimate genetic self-knowledge should allow the design and prescription of a drug-regimen tailored to each unique person. conversely. social. The orchestrated "overexpression" of some genes and the receptor proteins they code. tend to show heightened levels of serotonin 5-HT2A receptors. Cytochrome P450 forms a superfamily of hepatic enzymes with hundreds of different isoforms that catalyse the oxidative metabolism of a huge diversity of substrates.it should be possible. and regulation of genetic switching beyond the post-synaptic cascade. including MDMA. Genetically personalised medicine offers another bonus. However.at will.peculiar to each individual who isn't a monozygotic twin [triplet etc]. are better understood. Before death. a range of drugs beneficial to c. 0. Yet eventually we should all have optional access to the gene-expression profile of each neurotransmitter-specific neuronal subtype in the mind-brain. The duration of action and/or intensity of the effect of numerous drugs are determined by their rate of metabolism by cytochrome P450.for example rare polymorphisms of the cytochrome P450-2D6 system critical to drug metabolism. Whereas some "housekeeping" enzymes are expressed constitutively i.e. receptors and transporters. At first. This is because commercial drug companies prefer large markets. Freedom to optimise (or at least improve) one's genome should prove at least as personally liberating as the freedom to optimise one's drug-regimen. to engineer an unimaginably richer love of life. In the meantime. It should eliminate the possibility of idiosyncratic drug reactions caused by genetic abnormalities . or even 0. Thus at one terrible extreme. Harnessed to pharmacogenetics. and indefinitely . only the crudest stratification of patient populations by genotype may be the medical norm.

either instead or as well. Clearly genetic engineering and designer-drugs. all too often. Those of us who aren't morbidly interested in pain and suffering probably underestimate how dreadful primordial Darwinian life can be at its worst. then the roots of disenchantment can be investigated and prevented. or agents from categories currently too exotic to imagine. Such well-being may be modulated at will via entactogens-empathogens akin to MDMA. The biotechnology revolution throws up darker scenarios too. then longitudinal neuroimaging studies comparing the brainscans of. The spectre of biowarfare. More broadly. If enzyme induction accounts wholly or in part for the loss. no less importantly. it also binds to the enzyme. In the long run. like the printing press. however. by entheogens. but to our descendants. MDMA rapidly banishes the horrors of both. bioterrorism. forming an inhibitory complex. the sense in which its victims could be deluded in evaluating its dreadfulness is unclear. MDMA is not merely a substrate for CYP2D6. genomic medicine will deliver the freedom to choose who or what we want be. Indeed the magic itself can presumably be amplified. the enemy within. can be put to unethical use. better futurology than wide-eyed technophilia.triggered by the presence of the exogenous chemical. whether for MDMA or perhaps its still imperfect successors. and perhaps totalitarian state control over our reproductive decisions tends to loom larger in the contemporary imagination than utopian visions of boundless love and joy. If. conversely. Disturbingly. maybe more plausibly. Alas they soon return. The precise role of CYP2D6 in MDMA pharmacology is still unclear. nootropics. Thus better designed gene-and-drug combinations can perpetuate truly sublime modes of consciousness whereas. Some mental and physical torment is so bad its victims would snuff out the whole world to end it. Post-Darwinian Medicine Decoding the human genome offers the promise of lifelong emotional health via somatic or germline therapy. Prediction is always a hazardous business. a spectrum of mental superhealth that is orders of magnitude richer than anything accessible today can be genetically preprogrammed. our descendants may opt to abandon psychotropic drugs as pollutants of their genetically-enriched minds.the enemy from without and. probably more delightfully than an unenchanted Darwinian mind can grasp. psychedelics. It is possible these other metabolic pathways play an important role in everything from idiosyncratic responses to MDMA to the notorious "loss of magic". "Phenotypic plasticity" (the nearest analogue to free will a molecular geneticist will recognise) can be both vastly extended to enhance personal autonomy and. The near future may indeed be bleak. a predisposition to such ancient Darwinian horrors as sociopathy or suicidality can be genetically cured. the acute effects of MDMA are mostly all too reversible. central processes of neuroadaptation are at work. both as individuals and collectively as a species. The CYP2D6 enzyme is soon saturated even in efficient metabolisers. say. Or alternatively. When taken today. constrained where it's cruel and unwanted. Nightmarish dystopias make spine-chilling science-fiction and. A rewritten genome can potentially liberate us from all trace of psychopathy and depression . Inducible enzyme isoforms increase both in amount and activity in response to drugs. drug-virgins ninety minutes or so after dropping their first magical E (or perhaps its safer successor(s)) with brain-scans taken during their hundredth-odd trip should allow the neurochemical basis of any loss of magic to be pinpointed and reversed. breeding kids with anything like our own corrupt code may seem like wanton child abuse. . CYP-3A4 and CYP-2bB are critically involved in the oxidative metabolism of MDMA. Other human cytochromes P450 such as CYP-1A2.

isn't going anywhere. like chronic pain and despair. If mental superhealth does become the societal norm. Providentially.Yet human nature as encoded in our DNA isn't immutable. albeit in varying degree. If Homo sapiens' nastier alleles and their more sinister combinations can be silenced or edited out of the genome. precisely what modes might their genetically enhanced and perhaps . Some bioethicists would argue a world without suffering is the precondition for any civilised society. but in bug-ridden open source amenable to improvement. the lack of any inevitable tradeoff between happiness and critical insight undercuts one ideological obstacle to global moodenrichment. then the pessimists will be confounded. than the still radically incomplete conquest of "physical" pain dictates specifying the particular kinds of pain-free lives we should all lead. Given our current design-limitations. gradients of well-being can play a role informationally analogous to their nastier Darwinian counterparts while shorn of their unpleasant (and sometimes harrowing) subjective textures. then critical discernment can be functionally retained. The prospect of lifelong happiness strikes us as far more utopian in conception than the prospect of lifelong bodily health. Assuming here without argument a functionalist model of computational mind. by today's lights. and self-motivation enhanced. Predicting the dial-settings on the emotional thermostats of our descendants is unavoidably speculative. what's indispensable to intelligence in the broadest sense of the term are the triple processes of information. to a breathtakingly bold strategic move for our species. Most philosophers assume that suffering will endure as long as life itself. As contemplated today. then gradients of genetically predestined bodily and emotional well-being can constitute the presupposed backdrop to the diversity of everyday life. Plausible or not. But if (very controversially) post-Darwinian humans will innately feel superwell. if a predisposition to gradients of ecstatic well-being is ever genetically encoded as our default mood-spectrum. A major discontinuity in the development of intelligent life lies ahead. The existence of lives animated by gradients of well-being should be distinguished from lives spent in a state of uniform well-being. Only the horrific. not its focus. such uniformity would be a recipe for stasis. Mankind's barbaric track-record to date is an unreliable guide to our post-human future. and it seems they're getting smarter a lot faster than we are. By contrast. and new improved codesequences inserted instead. without sacrificing the humane ethic of a cruelty-free world. any mental health plan aimed at underwriting lifelong emotional wellbeing for the world's population no more entails developing a millenarian blueprint for a post-human Utopia. Yet in both cases. Ecstasy needn't be orgasmic. That said. purposeless cruelty of a living world evolved by natural selection makes an abolitionist agenda of "unnatural" selection so morally urgent. Even granted that paradise-engineering is technically feasible. or prophesying the imminent End Of History à la Francis Fukuyama. The intra-cranially self-stimulating rat or monkey . computation and feedback. For good or ill. Thus any fleshed-out examples of possible post-Darwinian forms of life are purely illustrative. scenarios of a post-Darwinian era of lifelong bliss demand a greater effort of imagination than the possibility of lives spent "merely" without "physical" suffering. is a condition that's technically possible to implement in the vertebrate CNS. The "raw feels" of unpleasantness are neither necessary nor sufficient for intellectual progress. Thus our silicon robots don't suffer anguish. This conjecture isn't idle. even when we recode their "affect programs". The futuristic scenarios feel "unreal". though it can be. we've learned that the DNA-driven world isn't written in God-given proprietary code it would be hubris to tamper with. not supplant them. It may never happen. Gradients of lifelong happiness can enrich our autobiographical narratives. Chronic heavenly bliss. The lifestyle options following success in either case are effectively limitless. the abolitionist project still amounts. any planning for a post-human population endowed with invincible mental health sounds ambitious in scope if not messianic in spirit.or human wirehead .

selection pressure has created suffering beyond belief. Sooner still. The non-specific prediction of genetically preprogrammed well-being for our descendants is contentious enough as it stands. So if we ever aspire to enjoy. or perhaps long-acting brands of entactogen-empathogen cleaner and safer than MDMA. or perhaps ultimately take forms that can't be grasped by the contemporary Darwinian mind. E-like rather than egoistic are therefore hugely more speculative. the loved-up edition of scientific utopianism is perhaps the most implausible (and unreadable) premise for a sci-fi novel one can imagine. Homo sapiens will soon have the collective scientific expertise to redesign our own nature. orgasmic or intellectual. At a minimum. then we can have it. Throughout the living world.either actively or by default . then apes can become angels. Our genetic programming will no longer be "blind". then in the impending reproductive era of preplanned designer babies we will also have to choose . "Genetic choice" in the early 21st century usually means nothing more ambitious than choosing the gender of one's child. genotypes will be purposely (re)designed . Instead. a regime change is imminent. Within a few centuries at most. emotionally self-reliant ubermenschen? Or could being loved-up on Ecstasy. an increasing range of genotypes will soon be chosen in deliberate anticipation of their phenotypical effects. in the aftermath of the post-Cambrian explosion of multicellular animal life and the evolution of central nervous systems. often in less than ideal circumstances. any prediction is hopelessly entangled with the wishes of the predictor. In this instance. As Dr Shulgin reminds us elsewhere. loving or self-centred. even if its early (re-)programmers will be only partially sighted. mutual loving empathy and intensified E-like consciousness is not impossible. Most recently. the vision of a whole civilisation. Mercifully. Thankfully. As wiring up the neural reward centres with microelectrodes shows. If we're so minded. For we're presently on the brink of the era of "unnatural" selection. Any more detailed explorations of the possibility that such enriched well-being might be. a regime of blind natural selection acting on effectively random mutations has governed the evolution of information-bearing self-replicators since the origin of life itself. Varieties of (post-)human genotype won't just be quasi-randomly generated via sex. say. Understanding and Respect" sounds sociologically naïve and (socio-)biologically impossible. and eventually the "transcriptome" and proteome beyond. The Darwinian Era has lasted for over four billion years. Whatever criteria are used. Yet as the human genome is deciphered. Stated so bluntly. But for the following reasons. Fortunately (or otherwise). however. not scientific ignorance of how to redesign the molecular machinery of emotion.and then sustaining . a staggering extension of freedom of choice will be thrust upon us. the practicalities of inducing . just far-fetched. and quite probably mistaken. This assumption is that societies based on the behavioural genetics of primate-style dominance-and-submission hierarchies will endure indefinitely. if we want our genetically enriched (grand-)children to be happy. genetic crossing-over and mutation. some scientific prophecies can become self-fulfilling if ever their makers acquire the power to implement them. hypomanic or serene. a civilization based on relationships of. and not just an all-weekend rave. both the reproductive biology and mode of selection pressure at work in the new era of genomic medicine will be different from the evolutionary past. founded on the neural substrates of an E-like "Peace. intelligent life will be able to rewrite the vertebrate genome and redesign the planetary ecosystem. no one needs to .whether the kinds of heritable well-being our offspring enjoy will tend to be solipsistic or social.even if the early designers barely know the ramifications of what they'll be doing. Needless to say. if there is one. Such bias might seem to defeat the enterprise from the start. lifelong ecstasy for our minds and bodies. it's worth sketching out an extended family of E-like scenarios as a corrective to a routine but unargued assumption that underlies rival predictions. offer a better model of social life in centuries to come? This sort of crystal-ball gazing clearly demands scepticism as well as a lively imagination. Viewed as an engineering problem. The ultimate stumbling-block. no such calculated sets of genetic decisions can be taken by prospective breeding couples at present. say.pharmacologically modulated well-being most plausibly take? Will such well-being be the egoistic happiness of amoral. Love. say.the neural substrates of bliss are technically quite easy. technically at least. For sure. will be traditional Darwinian-era ideologies.

and the lion can lie down with the lamb. craving.whether by gene-therapies or soul-medicines or varieties of both. and adverse reactions are common. is rightly viewed as a cruel and unusual punishment. this chronic dependence on human company gives short-term highs and even warm afterglows. mental superhealth can become the new benchmark of consensus-reality against which any departures are defined. our state-space of life-enriching options is poised rapidly to expand. Thus any currently foreseeable civilisation will be social in character. via the reward pathways and the neural projections they code. In extreme cases. at least until the abolition of senescence brings the throwaway era of traditional DNA mortals to a close. supply is erratic. Without friends. But dependency. then one urgent challenge will be to make our social interactions less emotionally costly. the MDMA experience demolishes the conventional wisdom that "artificially"-induced happiness must be amoral and selfish . Cue-elicited craving readily triggers relapse. constraints won't be absent. MDMA promotes a more altruistic mode of consciousness than has maybe ever existed on the planet. Yet it's hard to imagine parents wanting such modes of existence for their kids. Today. If nothing else. whether real or figurative. certainly among testosterone-driven young males. not drug-induced psychotic episodes. microelectrodes or gene-therapy. This compulsion to socialise is generally seen as healthy rather than dangerously addictive. and they share similar neural substrates. most people tend to become lonely. paroxysmal super-orgasms. suffering is an unnecessary evil. They are technically feasible to implement. Competitiveness is replaced by love. one-dimensional and shallow. Modulating bliss in controllable ways is trickier . This is true even with today's embarrassingly clumsy interventions. Gibbon's "register of the crimes. we tend to pay a terrible price for the benefits of group living. for a few hours. Yet as a taster of what's feasible in post-prohibitionist culture and a possible genetically-enriched future beyond. lovers or family. In theory. For instance. In any post-Darwinian reproductive era ahead.hedonistic. and misfortunes of mankind". love and self-insight induced by entactogen-empathogens will no longer seem an escapist holiday from Real Life when entactogenic-empathogenic states can be sustained indefinitely .whether by drugs. The menu of practical choices on offer to our enriched descendants isn't entirely limitless. and withdrawal-reactions are common when significant others are taken away from us or adulterated. or to devise evolutionary game-theoretic models where the prevalence of genotypes that permit such lifestyles could be globally stable. At its best. Feelings of hostility. tolerance and respect. the MDMA experience shows social life at its best. Our genes. family and colleagues may trigger within us. Short-term technical snags aside. On MDMA. Our very identities are bound up with our social roles. It's safe to say MDMA itself isn't going to change the world. loneliness and lovesickness can induce suicidal despair. We are physiologically dependent on the opioidergic. In abnormal conditions of social isolation. If so. Our sociability can spin out of control into a financially ruinous habit. the personality starts to deteriorate: solitary isolation. "unnatural" selection pressure will still be at work. It's not as though we have much choice about living together. More generally. MDMA offers perhaps the richest chemical tool for social intimacy in existence. at least.suffer. may well be viable lifestyle options one day for individuals. make us chronically hooked on the company of others. . sometimes agonisingly so. possibly romanticised under more poetic descriptions. Of course even with utopian biotechnology and mature nanotechnology. Bereavement and abandonment can be as traumatic as heroin-withdrawal. We spend lots of time and effort thinking about how to get more of whoever stimulates our mesolimbic reward circuitry most vigorously. Even in the absence of MDMA. oxytocinergic. not quasi-solipsistic. The costs of social existence are attested by the grisly chronicles of human history. Such social harmony seems "unnatural" if not miraculous when viewed from the poisonous miasma of mainstream society. the sense of heightened authenticity. human beings are still compulsively sociable. follies. decades spent in unceasing. Purity varies. despite the traumas it brings. For outside the embraces of loved-up ecstatics. or perhaps immersion in fantasy wish-fulfilment in virtual reality software. dopaminergic and serotonergic mechanisms that friends. one can love thy neighbour as thyself. bigotry and intolerance evaporate.

and not-so-subtle guises is a cross-cultural universal. By way of illustration. Less colourfully. a syndrome of sustained melancholy. Conflict to the point of warfare is genetically predisposed in our make-up. even though we compulsively need each other's company too. Human relationships can bring psychological rewards too. men and women. Embracing tribal life forms a valuable defence for a puny "naked ape" against big predators. and a preoccupation with personal failure and inadequacy is the internalised correlate of the yielding or "losing" behavioural sub-routine. But the "ultimate" evolutionary explanation seems to be. even the noblest of human sentiments are fragile. admiration into contempt. Love all too easily turns into hatred. often leading to trauma (e. when (s)he's goaded under conditions of stress. there are many subtypes of depression. Later on. We are forced to endure the savage competition of lookism . a multitude of pettier but still wounding frustrations.all have different and often conflicting genetic interests. say. loneliness. Counter-intuitively. and the wider spectrum of depressive and dysthymic disorders. It's endemic to human society. humiliations and misunderstandings can mar daily social life and sour personal relationships. Yet if anything the nastiness alluded to here is understated. and not all depressive moods and behaviours are genetically adaptive. Evolutionary psychiatry suggests that the cross-culturally ubiquitous phenomenon of depression. brothers and sisters.g. Arguing can be traumatic. The (involuntary) capacity for depression is one of a number of ancient. and rejection. we are predisposed by our genes to conflict with each other: mothers and children. .and sometimes desperately sad .) for mother and unborn child alike. jealousy. we replay the age-old sagas of sexual betrayal. Thus testosterone-driven males find themselves enacting decades-long competitive rituals to attract and retain genetically superior mates.Alas given a Darwinian genome the compulsion to socialise is all too often a dangerous. TV soap-operas and teledramas serve to sanitise just how emotionally unpleasant Darwinian life can be. preeclampsia etc. For sure. The genetic rot goes deeper. genetically-driven conflict plays itself out. frivolous term for a cruel and omnipresent phenomenon in human society. behavioural suppression. By contrast. heartache and emotional squalor all a bit overblown. On this "rank theory" hypothesis.personal dramas of our ancestral past. from a gene's eye view. Camouflaged genetic conflict underlies our disposition to squabble and fight amongst ourselves. Evolutionary psychology suggests that. that tempestuous rowing and its consequences serve as a brutal but effective way for prospective breeding couples to test each other out. Competitive status-seeking in its subtle . friends and relatives . depression has many proximate causes. Yet viewed in evolutionary perspective. is not a genetically dysfunctional anomaly. Living without Ecstasy. selfdestructive addiction.an inadequate. the (hypo-)manic spectrum of mood and behaviour is a manifestation of the "winning subroutine". consider. the worst pains in life are inexpressible. Thus states of depression or low mood ensure the weak "keep their heads down" and don't overreach themselves. Right from conception and the implantation of the conceptus in the womb. but the capacity to do so is [genetically] adaptive. deeply rooted in our biology. rather than later after you've sunk a substantial investment of time and resources in the partnership. For as human generation succeeds human generation. it's better to discover if a prospective partner will let you down sooner. genetically adaptive mechanisms and strategies for dealing with "social defeat" in a tribal environment. But thanks to the pressure of sexual selection. Under the genetic status quo. human tribal society imposes a cruel pecking-order of subordination relationships among members of the tribe. proverbial "lover's quarrels". at least in part. Only monozygotic ("identical") twins may hope to be spared this insidious rivalry. a conditionally activated tendency to depression may represent a fitness-enhancing adaptation to group living. There are innumerable "proximate" explanations of why star-crossed lovers often argue so painfully and vehemently. the involuntary activation of submissive and depressive states is an unpleasant but effective defence-mechanism for weaker individuals where any tendency to initiate or escalate conflict with a powerful dominant rival might easily be disastrous. Group living conferred advantages on otherwise vulnerable individual primates on the African savannah. Anyone having fun right now would find this drumbeat of misery. most of us are condemned at different stages of a lifetime to re-enact the messy .

inferior social status is associated with low serotonin function and low mood. On MDMA. metaphorically or otherwise. The contrast between raves packed with loved-up clubbers on hugdrugs and parties fuelled by alcohol or cocaine is striking. snobberies. Depression in human societies is far more prevalent than (hypo-)mania. not all submissive people are unhappy. Women are also more likely to suffer from the post-E serotonin dip. A lifetime's inferiority-feelings. Admittedly. and not all dominant and/or aggressive people are (hypo-)manic. Socially dominant Alpha males tend to be temperamentally expansive and optimistic. A capacity to switch mode can sometimes be adaptive too. the euphoria experienced by MDMA users doesn't take the form of uncontrolled manic excitement. Experimentally boosting or depleting the serotonin levels of social animals enhances or sabotages an individual's place in the pecking-order. At MDMA-animated raves. no one who's lovedup is trying to "diss" anyone else. But whatever the ultimate evolutionary roots of mood variation and affective disorders as interpreted by rank theorists.Clearly. serotonin-depleting E-regimen can disrupt the user's social status in the competitive urban jungle . even life's "winners". then nobody is anybody". E-less world. reflect a disguised expression of competitive power relationships. Indeed the tradition of rival displays of gift-giving finds echoes today in the competition between billionaire American plutocrats to endow the biggest charitable trust foundations. there are proportionately far more crushed and wounded spirits than there are at the top. Yet such comparisons are invidious. The neurological basis of social rank order can be investigated by various manipulations. even where the drug induces "behavioural activation". "It's not enough to succeed. there are also gender differences in serotonin activity. and slink away to die. Others must fail"] Yet short-term symptomatic relief for this syndrome already exists. more prone to depression. may become depressed themselves. Even apparent counter-examples don't challenge the generalisation. and status-anxieties dissipate in a flood of augmented serotonin and dopamine release. Back in the harsh. Unfortunately. there are too many confounding variables to test this hypothesis in methodologically rigorous studies on . and more likely to benefit from Prozac. class and money alike. as measured by CSF 5-HIAA levels. The mean rate of serotonin synthesis in men is over 50% higher than the mean rate of serotonin synthesis in women. mania and bipolarity first arose. emotional and perceptual effects that feel very different from crude dopamine-releasing amphetamine. Men and women alike of any social status at all can flourish far better in E-like states . MDMA abolishes the desire to put anyone down. primate dominance hierarchies dissolve in an egalitarian love-in. contemporary humans in all known societies are obsessively status-conscious. if deposed and defeated.while they last. MDMA's indirect. a heavy. The poison of competitive status-seeking might seem incurable. This greater prevalence probably reflects conditions in the evolutionary environment of adaptation where the spectrum of depression. and its long-acting analogues may one day offer complete remission. communal E-like consciousness simply isn't sustainable via chronic MDMA use. Thus dominant males tend to have far higher serotonin function. hence the probable evolutionary origins of bipolarity. Thus societies based around the potlatch. MDMA induces an almost miraculous transformation in the structure and relationships of any social group. Conversely.and probably elsewhere. For better or worse. So there are complications to the hypothesis and a legion of exceptions. Revealingly. a "peace that passeth all understanding". the Pacific Coast Native American custom of conspicuous gift-giving rather than wealth-accumulation. "winners" probably don't do [serotonin-depleting] drugs. albeit far less visible. than subordinate males. though idealistic E-users might suggest that zero-sum status-games are best not played at all. Even the most animated ravers taking pure MDMA tend to experience a profound sense of inner calm. serotoninmediated enhanced dopamine-release produces psychostimulant. Intriguingly. In wider E-less society. Women are more sensitive than men to both the MDMA magic and MDMA's adverse side-effects. Status-competition corrupts personal relationships in societies stratified by caste. Taken communally. Yet down at the bottom of the social heap. Identifying the neurochemical signature of states combining inward serenity and outer dynamism presents a wonderful therapeutic opportunity. ["If everybody is somebody.

Crushed. This good-will just needs genetic and pharmacological amplification. can indirectly detract from our own Darwinian fitness. is of limited comfort to its victims. then any nostrums for social reform. the (behavioural effects of the) happiness of others. even though we're not naturally loved-up. applying here Richard Dawkins' "extended phenotype" theory. however. anhedonic and submissive. are potential sexual rivals who directly or indirectly threaten one's reproductive success. What was selected for [as distinct from adventitiously selected] in the ancestral environment of adaptation wasn't the capacity to make others feel miserable as distinct from behave miserably. Of course. If we are looking for an evolutionary perspective on why we often behave so vilely to each other . they are less of a challenge to the inclusive fitness of one's genes. a proposed "E-users are losers" research proposal is more likely to gain official funding than a well-controlled trial of. extroverted males. life-enriching lovedrugs or improving the vertebrate genome would be futile. The distinction. If human malice were really genetically hardwired.humans. whose only solace in life is looking after the kids. Perennially chastened. Consequently their perceived happiness doesn't tend to give us as much joy as moralists might wish. too much happiness for one's nearest and dearest doesn't always suit one's genetic interests. Depending on a lot of other factors too. for instance. is liable to trigger involuntary feelings of jealousy and resentment. Sad to say. male or female alike. Even within the bounds of holy wedlock. A society based on "winners" and "losers" intuitively strikes us as natural. Even so. the health benefits of MDMA-assisted psychotherapy.then this kind of sexual selection pressure offers one possible explanatory framework. adversarial social relationships are probably inevitable. Happy. socially anxious and chronically depressive potential competitors are less likely to be sexually active and promiscuous. Of course the aspiration for a civilisation founded on relationships of shared love and respect sounds impossibly idealistic. even in those who are both. not merely has it been genetically adaptive for weaker social primates to have an inbuilt conditionally-activated capacity for depression. the evolutionary roots of everyday sociopathy run deep. Fortunately we're not systematically spiteful. alleles and allelic combinations may flourish if they conditionally promote the capacity to induce such anxiety and depression whether in strangers or tribe members who aren't allies or close kin .and if occasion demands. What reasons are . it can also be genetically adaptive for Alpha males (and aspiring Alpha males) to subdue potential rivals by making them depressed too. A cowed and depressive wife. say. Selection pressure works on the spectrum of behaviour such mood traits engender. it's worth stressing that natural/sexual selection doesn't care about the subjective textures of misery or happiness per se. With today's genes and the kinds of culture they promote. reports of good fortune befalling our fellows do not always inspire a warm glow of vicarious satisfaction.sometimes seemingly gratuitously so . On the contrary. To selfish DNA. or at best an envious ambivalence. Thus we witness their downfall with equanimity. Thankfully. Like depression. If it is adaptive to have others exhibit a spectrum of behaviour characteristic of low mood or high social anxiety. our suffering itself is incidental. So granting human beings no more than a minimal and diffuse benevolence. news of another person's lottery-win. by contrast. what can be done to make us temperamentally nicer to each other as well as happier and smarter? Would we individually and collectively be better off if perpetually loved-up on more advanced and sustainable analogues of E? Or are loved-up ecstatics just too vulnerable to genetic invasion by "defectors" and wolves in sheep's clothing for such genes or allelic combinations to flourish? Vulnerability to predatory and Machiavellian genetic rivals is presumably the reason why sweetheart suckers living in blissfully E-like states are thin on the ground in the drug-free Darwinian world. or its traditional counterpart on the African savannah. a malignant streak of human nastiness is matched by a common if ineffectual desire to improve ourselves and help others. sociable and possibly sexually adventurous bundle of joy. dominant. then other things being equal. can be less threatening to one's genetic prospects than an exuberant. For speculatively.

and some day it may be conspiring to help us. we don't want to turn into enfeebled and weak-minded Eloi. just as it's responsible for spontaneous nocturnal erections in males. and tackle the genetic origins of male violence and all-round nastiness. This particular intervention strikes us as a disconcerting prospect. The phenomenon of sexual reproduction itself has only persisted and evolved as a defence against parasitism. might seem (comparatively) more straightforward. Some genetic manipulations may involve computing the interactions between dozens or ultimately hundreds of alleles. the longterm role of the Y chromosome in the evolution of intelligent life is uncertain. just be edited out of the genome. Thus testosterone promotes what might be described as "strong-mindedness". Yet first there are many problems to be resolved here too. enlightened biomedicine should be able to edit out a predisposition to the more sociopathic forms of masculinity from the genome. an unlikely prospect right now. Testosterone can't. . However. however. Today the trait of strong-mindedness fosters what's often little more than callousness in pursuit of unworthy ends. Darwinian sexual and gender identities are central to social existence today. Other interventions. however. endurance and muscle-mass. even if we live in a world without Moorlocks. and a sense of competitive "edge". Even in a mature postDarwinian civilisation. increased dominance behaviour and even a propensity to sexual violence. The popularity of performance-enhancing anabolic steroids with athletes and bodybuilders stems only in part from the way such drugs enhance strength. The eradication of testosterone would indeed spell a world without war. or anything at all like it. For anabolic steroids are popular because they can also act as mood-elevating. Testosterone is the stereotypical "male hormone". even if we eventually discover that the rest of the world is on our side. then we must somehow curb the biological roots of masculine aggression. sexual aggression. Testosterone plays a role in female bone-strength. genetic diversity can be intelligently pre-planned. and the ethical value of testosterone-driven masculinity is unproven at best. Often their contributions to mental and behavioural traits won't be additive but dependent on a plethora of environmental contingencies. Taking anabolic steroids induces a sense of well-being sometimes amounting to euphoria. For instance. most of us may well prefer to cultivate "strong personalities". It's good to wake up each morning feeling ready to take on the world and win.there. It presents a daunting task of prediction and control. So at the very least. power. expository convenience aside. reduced male life-expectancy. Truly far-sighted genetic re-programming is a formidable challenge. mind-toughening personalitypills. But not always. This Problem of Conditional Activation threatens a combinatorial explosion of possibilities to calculate. and going bald. an increased tolerance of stress. if any. Normal endogenous male production of their native anabolic counterparts is risky enough already. On the other hand. the action of testosterone. even if the option of rearing functionally emasculated or chemically castrated offspring were an idea palatable to prospective parents. Yet testosterone is present in women too. More far-reaching strategies can be contemplated too. social violence and competitive dominance behaviour. But androgenic hormones can't be deleted altogether. recalling H. In the new reproductive era ahead. albeit in smaller amounts: it's important to female sexual response.G. and usually integral to who we think we are. as distinct from edited and re-regulated. is in large part responsible for war. speed. territoriality. and its hormonally active dihydrotestosterone metabolite. The genetic and/or pharmacological manipulation of testosterone may play a vital role in undercutting the darker horror scenarios for the future so popular in the science-fictional literature. for predicting that the nature of adaptive traits in the era of genetic engineering will change in ways that make beautiful minds more widespread? If genetic engineering or rational drug design are to deliver us from the Darwinian rat-race into everyday states of ecstatic grace. realistically. The price of using such drugs can be hypermasculine aggressiveness ["roid rage"]. Wells' The Time Machine (1898). muscle-mass and a general sense of well-being. an additional mechanism that promotes genetic variability is a powerful weapon in the evolutionary arms race against pathogens. Moreover. androgenic hormones are no more intrinsically evil than the MDMA molecule is intrinsically good. then there are short-term and wider evolutionary constraints to be overcome. If our species is to survive its newfound capacity to build weapons of mass-destruction.

This grim diagnosis isn't a counsel of despair. Weak-mindedness takes many forms. dopaminergic. especially among males. On the contrary: well-designed genetic and pharmacological interventions should in principle allow weaker spirits to be invigorated and frailer personalities empowered. and there's no natural remedy for weakness of will. people of either sex can and frequently do spontaneously embrace and caress each other complete strangers as well as intimate friends. In the meantime. or something different altogether.Today the world generally isn't on our side. Like MDMA. and pervasive feature of Darwinian human social relationships. act ineffectually and give up too easily. The other. so to speak. normally so eager to hymn the character-building virtues of suffering stoically borne. On MDMA. opioidergic. PEA and endocannabinoid dysfunction via gene-therapy and rationally designed pharmaceuticals. But SSRIs also tend to diminish the intensity of being in love. it also determines strength of will. thereby painting a falsely rosy picture of (male) mental health. biologically based strategy for saving the world will involve treating our. SSRIs tend to diminish jealousy. depressives can't pursue their projects with fanaticism. We'll soon have the option of making ourselves stronger. One way to put the world to rights invokes the tired nostrums of socio-economic and political reform. Low testosterone levels are also implicated in depressed mood. Such social engineering hasn't proven effective at curbing the frightfulness of life to date. Low testosterone function is associated with social defeat. Conversely. we can be superheroes. For the mesocorticolimbic dopamine system mediates not just the salience and intensity of anticipated reward. and far harder to cure. Yet the lessons to be drawn from the use of today's crude hugdrugs and lovedrugs extend far wider than the recipe for a good weekend out clubbing. fear and pain is bound to fail. almost as if we were clones rather than genetic rivals.the sort of personality often faked if you aren't. Critically. any kind of environmental approach to building a world without cruelty. even if the need for heroism may shortly pass. Depressive illness is reported to be twice as common among women as men. Depressives characteristically tire quickly. Therapists and sensitive physicians may take determined steps to reassure their clients that depression isn't a sign of weakness. passivity and subordination. by contrast. Yet with the right gene-and-drug combos.the nihilistic polar opposite to a hyperdopaminergic sense of urgency and significance. serotonergic. though for evolutionary reasons depressives find it harder to bluff. With better drugs and better genes. nor can they work indomitably to pursue what they believe to be morally right. vicious. It's also about as voluntary as sneezing. it's sexy for men to be cool. Life for depressed people too easily seems meaningless. It's an open question whether such strength of character will be egoistic or empathetic. one's idealised persona can be made flesh. innovative pharmacotherapy and/or genetic medicine will be vital if the weak-mindedness and weak willpower blighting so many lives today is to be overcome. say. One effect of administering MDMA is the way it eliminates jealousy. rarely find many positive words to say about the ennobling attributes of the green-eyed monster. it . confident and 'sussed' . congenital androgenic. Whereas exuberant hypomania is a signal of strength and resolve. SSRIs also act more sustainably than short-acting clubdrugs. Such behavioural effects present a bizarre and perhaps disturbing spectacle to the E-less Darwinian outsider. the spirit of depressives is easily broken. everyone naturally tends to love each other. and folk-wisdom is right. Pursued in a biological vacuum. For their capacity to anticipate reward is blunted. Even anti-abolitionists. Jealousy is a persistently nasty. Depression is popularly viewed as a sign of weakness. albeit a risky signal. Such a perception leads to its systematic underreporting. Potential new antidepressants are correspondingly tested for their capacity to reverse the learned helplessness and behavioural despair induced by chronically "stressing" [torturing] non-humans in "animal models". cocaine-like or E-like. By contrast. absurd and pointless . Alas this assurance typically isn't true. The syndrome of depression has both proximate and evolutionary roots. On MDMA. better-motivated and more steelyminded in character than even the bravest palaeo-Darwinian primitive or Nietzschean ubermensch.

but this isn't true in the eyes of the law or of our peers. MDMA promotes intimacy. to the sound of the Voice's richly affectionate. As it is.though it's worth recalling that Nazi "racehygienists" didn't use happiness as their touchstone of genetic excellence. truly loving oneself. Warnings from history aside. then jealousy. This option doesn't amount to a very soulstirring prospect. by contrast. Taboos on touching and the whole gamut of tactile experience are relaxed. and feeling (and being) wonderful all seem faintly embarrassing. the "ideal pleasure drug" featured in Aldous Huxley's uncannily prescient Brave New World (1932). Alas Ecstasy itself is something of a false prophet. the drug-catalysed outpouring of affection has subsided. baritone valedictions. the Deltas were kissing and hugging one another . "Natural" love sometimes lasts longer. and the rioters end up hugging each other: "Two minutes later the Voice and the soma vapour had produced their effect. In a largely anonymous mass-society. They are promptly pacified by the riot police with soma-gas. women can feel safe in public. "He who is rational about love is incapable of it". its expression is tightly regulated. being nice to everyone. Did one really let slip those gushing effusions to strangers one barely knew? Did one really hug that hateful brute of a rival for the affections of one's heart's desire? Viewed from [state-dependent] "reality" again a few days later. Even Helmholtz and the Savage were almost crying. gay people feel truly at ease. the angry low-caste Deltas riot. perhaps even a chemically-fuelled madness. possessive and exclusive. It's an adaptation that remains a shabby substitute for genetically-underwritten true love. At MDMA-driven raves. Where love does sporadically flicker or flare up among us. "It was the just the E talking". The classic dopaminergic psychostimulants like cocaine promote a hard-edged.entails choosing kinder genotypes for our offspring. and an empathetic sense of other humans beings as fellow subjects rather than objects. Of course. most Darwinian social life is soulless and loveless. The word itself. eventually killed off by receptor desensitisation and downregulation no less effectively than E-induced love is ended by serotonin depletion. and the prophets of doom will be right. For the fickleness of Darwinian affection has hitherto been genetically adaptive. the concept of "eugenics" is horribly tainted. But our genes do allow their vehicles to fall in and out of love with a small percentage of prospective mates in ways that tend to serve our reproductive success. Only by subverting some exceedingly cruel feedback-inhibition mechanisms can the depth and range of our affection for each other be enriched and sustained. E-less love is rarely allembracing: such Darwinian love tends to be jealous. originally a coinage of Sir Francis Galton (1822-1911). conflict and warfare will go on for ever (or kill us off). blubbering as though their hearts would . after a weekend of being "loved-up". the twins dispersed. Two days after taking the magic lovepill(s). mood-congruent post-E "reality" soon sets in. In tears. warmth. unless the Darwinian masculine identities of our evolutionary past are superseded. The law and social sanction impose penalties for loving too much or too little.half a dozen twins at a time in a comprehensive embrace. but Darwinian love is still ephemeral. After John the Savage threatens to disrupt their soma supply. A fresh supply of pill-boxes was brought in from the Bursary. The body no longer feels like a prison for the soul but an extension of it. Yet the lethal dangers posed by the genetic status quo coupled with advanced military technology are far greater than the risks of a genetic reform program predicated on the goal of world-wide personal happiness. MDMA-induced love is no more everlasting than its older and fitness-enhancing counterpart. Like our notions of psychoactive drugs. loving the wrong person at the wrong age or the wrong gender. don't-touch-me egoism. love and affection are in even shorter supply than among tribal hominids in African prehistory. is indelibly tarred with the pseudoscientific quackery of the Third Reich . a new distribution was hastily made and. One may recall from English literature the effect of taking soma. and sexually straight or bisexual clubbers can express love and affection for each other free from overt or internalised homophobia.

In the long run. then a shared celebration of life. Intervention can go further.a more elusive concept than that of an empathogen. The depressive realism of the serotonin-depleted and jaded cynicism of the chronically world-weary are often justified. dearest friends. said he disapproved. not sympathy for the misfortunes of others. Right now. perhaps. For that's the nature of social reality. Yet the biological roots to sustain "saintly" self-sacrifice just aren't there in most of us. The design of richer functional analogues of MDMA entails more than finding medicines to make us sweeter-natured. our genetic make-up ensures we simply feel indifference to the plight of all but a handful of significant others in our lives. but MDMA itself is not the recipe for perpetual sainthood. If we decode and opt to amplify the molecular machinery of volition too. In contrast. Love and Understanding and Respect. such compassion is usually ineffectual.contribute to the perception that E-like states of blissful empathy are inauthentic. Regrettably. hate. Good-bye my dearest. my dearest. More commonly. "Ecstasy enhances interpersonal relationships. my dearest. shallow or false. a larger proportion of one's money to Third World charities dedicated to those who need the resources more urgently than we do. Improving human nature is perhaps ethically all-important. however." The scary notion of kissing one's enemies. at the secret Delta G facility. in today's world. not a sign of drug-induced psychiatric disorder. How can the MDMA experience have true emotional depth if the cosmic hug-bunny of the dance-floor reverts back at the office next week to his old Darwinian mindset .. a former South African government scientist told a hearing of the Truth Commission that the minority Apartheid government had planned to use MDMA on rioters. contempt. MDMA offers "insight . anger. John Koekemoer. then such heightened compassion can be translated into effective action. disgust. Desperate to retain their faltering grip on power. Idealists might vaguely entertain the second-order desire to care more deeply and give. not the magical interlude of Peace. dearest friends. which is investigating human rights abuses during the apartheid era. it's too short-lived to do much good. may come to seem as natural as breathing. Yet most of us feel no overpowering moral urgency to do anything about it. resentment. "I did not believe Ecstasy was a good incapacitant and I told my superiors that". one knows dimly at some level that there is frightful and preventable suffering in the world. taking MDMA can give rise to a prodigious sense of compassion in even the otherwise morally inert. Fortunately. Yet right now too many people walk the Earth who have no cause to celebrate anything.. for instance. he told the commission. this may be so. former head of chemical and biological weapons research. The functional prototype of what's needed exists today in the form of a fast-acting hugdrug. Jealousy. perhaps half-recalled cameos from Huxley's satirical fiction . ridicule." Too far-fetched? In 1998. If and when we understand the neurochemical basis of empathy. "Good-bye. Ford keep you. then sustaining the molecular substrates of empathetic love can turn boundless compassion into an automatic reaction to distress. if biotechnology can be used to eradicate suffering from the living world. Yet our descendants may recognize that we are the sociopathic emotional primitives in the grip of an affective psychosis. say. compassion if not empathy for others may ultimately be redundant. Ford keep you! Good-bye. spite. schadenfreude and a whole gamut of nameless but mean-spirited states we undergo each day are a toxic legacy of our Darwinian past.and the reality of strangers of either sex at raves hugging each other on E and telling each other how wonderful they are . but MDMA is also an entactogen . an emotionally frazzled post-Ecstatic may reflect.break. envy. Sadly.and the (anti-)social vices it spawns? A corrosive cynicism easily sets in. Therapeutic agents designed to deepen empathy and sustainably awaken our compassion are a priority. the embattled regime apparently ordered its chemists to make one tonne of Ecstasy for riot-control. dearest. I told them I did not want to kiss my enemy. Thus the Calgary Herald (10 June 1998) reports: "Dr.

The nature of entactogenesis is far harder to fathom. They may be distributed as freely as aspirin if not smarties.should allow introspective depth and a capacity for higher-order self-reflection to be fabulously enriched as well. our (limited) vision of future civilisations tends to focus on their technological marvels . Yet the design of long-acting entactogens . But the deeply-felt sense of authenticity and emotional self-honesty of the MDMA experience is an unexpected delight. its sense semantically inaccessible to the MDMA-naïve. graded and quantified? What's their market value? Anyone in Western society with a tendency to quiet contemplation is likely to be stigmatised as lazy.whether designer genes or utopian pharmacology. Whether this idealised self-identity is created or discovered may be philosophically debatable. than the nature of empathy.yet we balk at the sorts of public health policy decision needed to accelerate the transition. or perhaps until quantum computers allow calculations orders of magnitude more powerful than today's toys. Ecstasy itself is too short-acting. if feasible. One just won't ever get to read about its nature in the peer-reviewed Journal of Introspective Studies. we are poised to acquire a literally life-transforming technology . let alone communicate. The clarity of MDMAmediated self-insight is perhaps a form of what Dr Charles Tart calls "state-specific knowledge". But a permanent distillation of the MDMA magic. How can they be tested. and prove safer in excess than either. Eless cynics may be sceptical. Even so. This prospect is some way off. It states that processing power in computers doubles every eighteen months or so. Ecstasy and rave-culture are an aberration. Drugs to enrich self-insight and heighten self-reflection may eventually become commonplace. offers an extraordinary if unorthodox vision of one post-Darwinian paradise to come. Understanding and Respect" sounds like a hollow slogan. . In similar manner.and their neurological analogues . at least until chip designers run up against the physical constraints of the nanoscale later next decade.and the supposed Darwinian dominance-battles of their sciencefictional inhabitants . Just what's the propositional content of this so-called "insight"? Couldn't it be delusive? ["It's not hard to hear voices. In Western culture."] But on pure MDMA. The word for such states comes close to being a primitive term. It's a rule-of-thumb about how many transistors we can cram onto successive generations of chip rather than a fundamental truth about Nature. and his larger-than-life ego on whose life-energies lesser mortals may feed. Tomorrow's counterparts of today's bunch of furtive adolescent introspectionists won't have to shuffle around faint little tickles of thought.rather than on odysseys into the inner depths of their souls. It's knowing whether they tell you the truth.a toolkit for enlightenment powerful enough to implement Heaven-On-Earth and beyond . a capacity for reflective self-insight is not highly prized.unlike the sound and fury of the lionised Man Of Action. Nothing in our education system is geared toward making young people feel that introspective self-analysis. In the jaundiced eyes of (most of) the older generation. Moore's Law has roughly held good since 1965 when it was first propounded. unsustainable and neurotoxic at high doses to form part of anyone's global health plan. Love. the subject can inwardly access the kind of person s/he wants to be. Full-blooded pharmacological and genetic emancipation is still decades away. "Peace. Today.without fear" (Dr Shulgin). An enriched conception of mental health is blocked by entrenched elites who've never sampled what they outlaw . the words can't be anything else. Yet the trend it captures seems set to continue. enhanced self-awareness or personal growth matters in the slightest. Beyond MDMA : mental superhealth? Moore's Law in computing is named after semiconductor engineer and Intel co-founder Gordon Moore. in the wider world. feckless and unenterprising . "the ideal me". not a portent. Introspective genius and a talent for meditation aren't respected in either academia or business.

Unfortunately, the dizzying rate of technical progress that Moore's law quantifies hasn't been matched by an analogous law of progress for generations of human mental health. On average, we are probably no happier than our malaise-ridden hominid ancestors. We aren't noticeably fonder of each other. By way of consolation, we can take refuge in the pre-scientific notion that happiness is unquantifiable. Yet if such quasi-objective indices of mental health as suicide rates are anything to go by, then we would probably be psychologically better off as hunter-gatherers. Over 800,000 people in the world took their own lives last year. The World Health Organisation (WHO) estimates that this figure will rise to around 1.5 million by the year 2020. Here in the UK, suicide is the most common cause of death for men under 35 years old. Globally, several hundred million people are clinically or "sub-clinically" depressed; and a spectrum of chronic anxiety disorders afflicts further hundreds of millions more. Even as we progressively conquer physical disease as conventionally defined, the toll of psychological distress is still rising. Admittedly, "mental illness" and "mental health" are value-laden, ideologically contested terms. Even the new scientific discipline of biological psychiatry is inescapably culture-bound. Yet "Progress" that doesn't leave us emotionally better off would seem something of a misnomer. Not merely has there been no discernible growth in average mental health to match the tempo of scientific advance, technophobes claim there never will be such a mental health revolution. As long as we rely on the same legacy wetware to animate our lives, the neo-Luddites and religious fundamentalists may even be right. Our levels of well-being - and ill-being - compute fitness functions that served the inclusive fitness of our DNA in our ancestral environment in Africa. Our genes didn't design us with the emotional welfare of their throwaway vehicles in mind. So the genetically adaptive hedonic treadmill - for many of us better named the dolorous treadmill ensures that average levels of well-being/ill-being of Darwinian life remain stagnant. Six months after winning the national lottery or becoming quadriplegic in a catastrophic accident, the winner/victim statistically reverts to his or her average level of ill-being/well-being before the win/trauma. Hence such affirmations as Rajinder Johar's "The Joy of Quadriplegia". Illustrating the hedonic treadmill at its most extreme, "locked-in syndrome" leaves its victims paralysed. The subject is fully conscious but unable to move any extremities, talk, or make horizontal eye movements. Yet in the words of James Hall, longest surviving (2002) American victim of a midbrain pontine stroke: "In some ways, my stroke was a blessing....Since my stroke, I've published books, articles, poems. I'm busier and happier than I've ever been." Completely paralysed, Mr Hall communicates by focusing on particular letters that his computer picks up from his limited eyemotions. Such triumph-of-the-human-spirit stories are comforting, up to a point. The downside of the emotional homeostasis they reflect is that millions of temperamentally depressive and dysthymic people would feel gloomy in the Garden of Eden. Again, this hypothesis isn't easy to test rigorously. The more dramatic manifestations of emotional homeostasis at work are hard to investigate ethically in well-controlled prospective studies. Anecdotes and impressions aren't science. Yet the cumulative evidence for a genetically constrained "set-point" in our pleasure-pain axis is compelling. The dismally low dial-setting doesn't bode well for any utopian project based around mere social reform. Fortunately there is no reason, in principle, why an analogue of Moore's law can't be implemented in successive generations of the reward circuitry of organic life-forms. The affective, aesthetic, intellectual, interpersonal (and spiritual?) well-being of neurochemical robots like us can be genetically pre-coded. If rationally redesigned, our enlightened successors may view today's "natural" rewards as poor surrogates for genetically underwritten happiness. When the mechanisms underlying bliss and its gradients are understood, the molecular machinery of the sublime can be modulated - and amplified indefinitely. Within a few decades at most, we will be scientifically enlightened enough to redesign the neurochemical pathways of emotion. Meanwhile our pleasure

centres are too small for us to flourish; and their functional architecture is inefficient. They needn't be either: our normal homeostatic "set-point" of well-being can be genetically ratcheted up to a far higher plane; and archaic Darwinian notions of mental "illness" and "wellness" consigned to oblivion. Gradients of indescribable happiness can potentially animate our lives no less powerfully than gradients of ill-being. Until this fabulous era dawns, then - to borrow the words of Oscar Wilde - "we are all in the gutter, but some of us are looking at the stars". Critically, such gradients of celestial bliss can also be lucid, serene, entactogenic and empathetic - i.e. MDMA-like and better, not manic or vulgarly hedonistic. The godlike powers of tomorrow's biotechnologists will allow the neurological substrates of empathy and self-insight to be permanently up-regulated. Aesthetically, the mundane ugliness of life in the present epoch can be replaced by gradations of hitherto unimaginable beauty. Potentially again, an E-like magic can imbue the texture of normal waking consciousness. If we so wish, our emotional palette can be genetically enriched, mixed and then pharmacologically refined in ways that transcend the crude primary colours of our Darwinian past. Counter-intuitively, yet indispensably for the long-term evolutionary stability of a ecstatic society of redesigned post-humans, allelic combinations that promote blissful empathy can also potentially be fitness-enhancing - in the technical Darwinian as well as in the popular sense of "fitness". The dawning reproductive era of "designer-babies" promises to be empowering because the capacity for parental love and nurture can be genetically and pharmacologically enhanced, not just levels of personal happiness, health and superintelligence. The age-old scourge of child-neglect (and worse) can be relegated to evolutionary history. Very speculatively, our future offspring may not merely be more loved by their caregivers, but much more "loveable" too. For if given the [genetic] freedom to choose, then parents-to-be may understandably want their offspring to be loving as well as smart and happy. The prospect of unleashing such parental freedom is disturbing to most of us. Why not leave babymaking, as before, either to the mysterious workings of Providence or the blind shufflings of selfish DNA? Yet now we're imminently free to choose, there is nothing self-evidently morally admirable about playing genetic Russian-roulette with the lifeforms we create. Many of the nastier behaviours and modes of consciousness that so often proved fitness-enhancing in the ancestral environment will cease to be adaptive if the alleles that promote them tend to be shunned by prospective parents intent on creating the children of their dreams. The "nastier" alleles may well get out-competed. Selection pressure will tend to favour a very different range of heritable adaptive traits once evolution is no longer "blind" i.e. when genotypes are parentally chosen or designed in anticipation of their likely effects on a child's behavioural phenotype. If we want to, we can systematically redesign ourselves and choose the traits of our offspring. The details, for sure, are sketchy. Reproductive science and genetic engineering are in their infancy. But Homo sapiens is poised to bootstrap its way out of the cruel Darwinian abyss. Inevitably, talk of treating humans like organic robots, and then mooting a baseline of mental health orders of magnitude richer than the Darwinian mind can contemplate, sounds fantastical today. In the context of our traditional conceptual framework, the idea of an analogue of Moore's law for successive generations of human mental health evokes thoughts of cloud-cuckoo-land, not a global health-plan. Set against the daily messiness of our ecstasy-impoverished lives, the prospect of using biotechnology to abolish suffering, and a post-Darwinian transition to paradise-engineering, strikes most of us as fanciful, its liberatory potential just a mirage. At best, such heady words fall lifelessly off the page or screen. Yet a major discontinuity - a momentous evolutionary transition in the development of life on earth - is imminent as the biotechnology revolution unfolds. The advent of genomic medicine is set to challenge the old Darwinian regime of natural selection and the emotionally crippled minds it spawned.

In the long run, genomic medicine can underwrite mental and physical superhealth for everyone. For in principle, lifelong well-being can be genetically hardwired from conception. In the short run, better-designed research tools and therapeutic agents can probe, and then repair, our damaged minds. As chemical stopgaps go, MDMA is a magical revelation. It's perhaps the best aid to insight-oriented psychotherapy ever synthesized. Tragically, when MDMA is used to excess the outcome can be harmful, not healing. So as a weekend club drug, MDMA is seriously flawed. Today, of course, empathogens and entactogens are outlawed for any purpose. The altered states of consciousness they induce are criminalised. People who take such agents are stigmatised as "drug abusers". Yet some MDMA users feel, rightly or wrongly, they've been granted a tantalising glimpse of what true mental health may be like in centuries to come; and an insight into what the rest of us are missing.

David Pearce (last updated 2010)

"Faster, faster, until the thrill of speed overcomes the fear of death." Hunter S. Thompson The amphetamines are potent psychomotor stimulants. Their use causes a release of the excitatory neurotransmitters dopamine and noradrenaline (norepinephrine) from storage vesicles in the CNS. Amphetamines may be sniffed, swallowed, snorted or injected. They induce exhilarating feelings of power, strength, energy, self-assertion, focus and enhanced motivation. The need to sleep or eat is diminished. The release of dopamine typically induces a sense of aroused euphoria which may last several hours: unlike cocaine, amphetamine is not readily broken down by the body. Feelings are intensified. The user may feel he can take on the world. The euphoria doesn't last. There follows an intense mental depression and fatigue. Amphetamine depletes the neuronal stores of dopamine in the mesolimbic pleasure centres of the brain. More than any other illegal drug, speed is associated with violence and anti-social behavior. Occasional light and infrequent use is probably relatively harmless; but heavy chronic use can lead to stereotypies of behavior, depressive disorders, "meth bugs" akin to cocaine-induced formication, strain on the cardiovascular system, increasing behavioral disintegration, and outright "amphetamine psychosis". Amphetamine is structurally related to ephedrine, a natural stimulant found in plants of the genus Ephedra. It is also structurally related to adrenaline, the body's "fight or flight" hormone. Amphetamine was first synthesised by Edeleano in Germany in 1887, but it only entered clinical medicine in the late 1920s when its psychostimulant effect was recognised. The US medical and pharmaceutical establishment was worried that supplies of ephedra in faraway China would be exhausted. Amphetamine promised a cheap and synthetic substitute. Like ephedrine, amphetamine dilates the bronchial small sacs of the lungs, a great blessing for sufferers from breathing disorders. So in 1932, Smith, Kline and French introduced the famous Benzedrine Inhaler.

Amphetamine sulphate was aggressively marketed for asthmatics, hay-fever sufferers and anyone with a cold. Amphetamine was soon available in pill form too. "Pep pills" were sold over the counter for all manner of ailments. Doctors prescribed amphetamine for depression, Parkinson's disease, epilepsy, travel-sickness, nightblindness, hyperactive disorders of children, obesity, narcolepsy, impotence, and apathy in old age. Soldiers on both sides in World War Two consumed millions of amphetamine tablets. This practice sometimes caused states of quasi-psychotic aggression in the combatants. From 1942, Hitler received daily methamphetamine injections from his quack doctor Morell. This corrupted his judgement, undermined his health and probably changed the course of the War.

'Ice' is recrystalised methamphetamine hydrochloride, a potent stimulant. Ice will dissolve in water and break down to smaller particles. It generally takes the form of clear crystallised chunks. Ice induces a profound sense of euphoria in the user by blocking the reuptake, and stimulating the release, of dopamine and noradrenaline in the central nervous system. Ice is a "power drug". Methamphetamine use is typically followed by prolonged depression and fatigue. In contrast to base cocaine, smoking meth will extend its effects for up to 24 hrs per ingestion. Smoked in a base form, meth is unappetisingly known on the street as SNOT. It can only be smoked. SNOT gets its name on account of its resemblance to the natural product of the same name. It is very addictive. The effects of using methamphetamine may include: • • • • • • • • • extreme elation wakefulness alertness enhanced self-confidence aggression talkativeness loss of appetite increased intiative increased physical activity

Withdrawal symptoms may include: • • • • • • severe craving deep depression fatigue inertia paranoia psychosis

Smokable methamphetamine is similar to smokable cocaine, crack. They may both briefly be delightful. But they offer only a toxic and delusive short-cut to the biological nirvana awaiting our descendants.

Add aluminum at a rate that maintains a steady effervescence and keeps temperature roughly in the 50°C range. 1-aryl-1-iodo-2(perfluoroalkyl)ethylenes are prepared by radical addition of perfluoroalkyl iodides to arylacetylenes. By using N. Initially. and tertiary amines. Graphical abstract A general method for the synthesis of fluoroalkylated amphetamine derivatives is presented starting from commercially available arylacetylenes.0in strips in 1g portions with manual stirring. Precipitated Nickel powder was added to 100ml 20% NaOH soln and manually stirred at 60°C for 30 min.N-dibenzylamine or N-benzylamines the corresponding primary and secondary perfluoroalkylated amines are easily available.0g Nickel Chloride hydrate (light green crystals) in 75 ml 95% ethanol w/ mag stirring and warming to 50°C. This reduction turned out to be easier than any so far encountered. Key step of the reaction sequence is the following dehydroiodination in the presence of n-BuLi to give 1perfluoroalkyl-2-arylacetylenes in situ. [1] While solution at 50°C slowly add 5g regular Reynolds wrap torn up into 0. The aluminum will SLOWLY react with the nickel salt forming the metal Ni(s) through metathesis as a dark grey chunky powder which settles to the bottom. This is not based on any of the excellent references pertaining to Urushibara that have been mentioned on the hive.25 x 1. which are reacted with secondary amines to produce perfluoroalkylated enamines in a new one pot procedure.http://amphetamines. Introduction First of all many thanks go to CHEM_GUY for his continuous urging of the Hive community to try Urushibara Nickel reduction on phenylnitropene. After salt is dissolved remove stir bar and add 1ml water and 1ml conc. A gentle effervescence of hydrogen occurs during reaction.html Abstract A general synthesis of perfluoroalkylated amphetamines is presented. Excess NaOH is decanted and nickel is washed with 5 x100ml aliquots of . If any color remains add another gram of aluminum and wait for soln to clear. Final hydrogenation yields the desired products in good yields. Note this may take up to two hours! At the end of Al addition all green color from nickel salt should be discharged. secondary. The method allows the preparation of primary. only chem_guys postings! Procedure Dissolve 4.com/refs/index. HCl.

Attempted magnetic stirring will result in frustration because nickel is ferromagnetic and will stick to stirbar preventing surface area exposure necessary for reduction. Aluminum will slowly dissolve with a more vigorous effervescence of hydrogen than the first step. it’s not poisonous like mercury or anything! Now decant off the top orange organic layer and distill off alcohol down to a orange stinky syrup completely different smelling than the P2NP. Maintaining good stirring with a glass stirring rod is essential in beginning. Dissolve 5g pure phenylnitropropene in 50ml Ethanol and add to Ni solution [2].distilled water to remove excess base. . Aluminum reacts slowly. Wear goggles and be careful! Base neutralization is highly exothermic! In 30 minutes all aluminum sludge will solvate into bottom aqueous layer and a nice orange alcohol layer reeking of amine will settle out on top. Use larger amount of nickel catalyst and more aluminum for H2 generation. Repeat adding acid and Al until 10 grams Al and about 30ml HCl has been added. After aluminum is dissolved add three more milliliters HCl and one more gram Al. At this point Urishubara nickel catalyst is prepared and ready for reduction. HCl [3] and 1 gram shredded aluminum w/ manual stirring. Dissolve these goodies in acetone and slowly add sulfuric acid to precipitate the amine sulfate. Re-extract aqueous NaOH/Al layer w/ toluene and work up in standard manner. It seems essential to add P2NP to rxn after Ni is fully precipitated. After all. Notes [1] Addition of water and acid found to be necessary to initiate rxn between NiCl2 and Al. Nickel is not dissolved by the NaOH so it will remain floating around between the two layers but this does not present a major problem. Increasing Yield: Use overhead mechanical stirring to keep nickel catalyst better suspended during reduction. longer if temp falls below 50°C. Voila!!!!!! about 3 grams light yellow amphetamine sulfate. [2] When nitropropene was added to NiCl2 soln before conversion to Ni powder was complete some polymerization occurred greatly reducing yield. Now slowly add 3ml conc. Expect addition to take about six hours. After all aluminum is added and mostly decomposed slowly pour in a soln of 30g NaOH in 100ml H20 with careful stirring. Constant stirring towards end is not necessary. [3] Use of Sulfuric acid produced inferior results causing polymerization of P2NP to red tar. just give mix a good stir occasionally.