Psychedelics

CHAPTER 12

Psychedelic/Hallucinogens

Called by many different names Psychotogens Psychotomimetics Psychedelics

Primary effect is to produce perceptual changes

& hallucinations Can influence several sensory systems, perception of time, space & events

Different Types of Psychedelics

Serotonergic

Cholinergic

LSD Psilocybin/Psilocin DMT - Ayahuaca Bufotenine Ololiuqui

Catecholamine-like

Mescaline MDMA (ecstasy)

MDA MDE

Muscarine Scopolamine Glutamatergic PCP Ketamine Dextromethorphan Opioid Salvinorin A

DOM
Myristin and Elemicin

Serotonergic Psychdelics

LYSERGIC ACID DIETHYLAMIDE (LSD)

Lysergic acid Derived from ergot alkaloids

Ergot is a poisonous fungus that infects rye &

other grains & grasses Albert Hoffman: 1938 - synthesized #25 in series of new molecules doing ergot alkaloid chemistry 1943 - returned to #25 making new batch & absorbed some through skin

LSD in the USA

Came to U.S. in 1950s in two ways: Clinical usage: Supplied to psychologists and psychiatrists

encouraged their taking drug

Military Usage: U.S. military and CIA as incapacitating agent and truth drug U.S. government gave LSD to unsuspecting individuals to study effects

LSD in the USA

1960s - popular use advocates East Coast: Timothy Leary (clinical psychologist at Harvard) West Coast: Ken Kesey (noted author)
graduate student in California got dose in psychology study shortly after this goes to work in psychiatry year later, writes One Flew Over The Cuckoo's Nest

LSD in the USA

Spread through country with huge publicity until

peak 1968 to 1972 Schedule I in 1968 Stuffy politicians didnt know what to do because LSD was used by white, middle to upper class, college students Early 1990s - LSD came back

LSD & Neurotransmission

Binds to 5-HT2A receptors agonist effect Increases amount of

sensory information getting to cortex through overriding filter mechanisms

This is how the drug influences perception, especially for vision

Pharmacology of LSD
Pharmacological Effects Effects heavily dependent on dose taken

not just intensity of effects, but type of effects

Low doses = mild

perceptual alterations

comparable to effects of marijuana use, but greater clarity

Effects of LSD
High Doses progression through mental and emotional experiences 6-12 hrs duration Each trip unique, highly dependent upon setting and personal expectations Can alter subjects emotional feelings during trip by experimenters previous behavior warm and supportive or suspicious and nonsupportive

Effects of LSD
Effects of drug come on in about 30 min first signs are autonomic activation followed by overt behavioral signs - loosening of emotional inhibitions
giddiness, laughter for no reason mood euphoric and expansive, but labile mood swings notable

abnormal color sensations, luminescence

colors reported as more brilliant

Effects of LSD

space and time disorders

added depth with loss of perspective - up/down

altered close in space influenced more than distant general slowing of time reported

LSD Hallucinations
gratings, latticework,

honeycomb, chessboard, tunnels, funnels, alleys, cones, vessels, and spirals

can be present with eyes open or closed

involve bright light in center

with figures moving in from periphery forms appear to move in depth and take on color shades, red common Sounds can take on visual forms

music may take on enhanced meaning or intensity

LSD & Bad Trips

Psychological impact - traumatizing, imagery

dark, insights appalling Usually occur in novice users, feel out of control Generally negative set and setting are key contributing factors Can lead to suicide or prolonged psychotic reaction Can usually be talked down from a bad trip

LSD & Flashbacks

Spontaneous recurrence of trip after period of normalcy can occur after long periods of abstinence more common after multiple high dose use prolonged afterimages for days and weeks after

tripping mechanism unknown

can be brought on by other drugs or setting most commonly reported in low light situations not intrinsically dangerous and usually go away

Psilocybin/Psilocin
Magic Mushrooms, Liberty

Caps

Central America and northwestern U.S. Last about 6-10 hours Need a lot to get same effect as LSD 5-HT2A agonist Same basic effects as LSD Mushrooms occasionally toxic

DMT
Dimethyltriptamine 5-HT2A agonist Alkaloid Often smoked Main ingredient in Ayahuasca Same effects as LSD

Bufotenine
Dimethyl-serotonin

A product of abnormal serotonin breakdown Like LSD and others Can occur in urine of people with psychiatric disorders
Psychosis Paranoia Depression

Ololiuqui
Substance found in morning glory seeds Similar to LSD Significant nausea, vomiting and cramping

Tolerance/Dependence
Not significant producers of tolerance or

dependence No withdrawal either People and animals do not self-administer Problems related to the things people do while under the influence
Accidents Suicide Aggression/violence Toxic reactions

Catecholamine-like Psychedelics

Mescaline
Active drug in peyote Structurally similar to NE However, most of the

effect is mediated by our friend, the 5-HT2A agonist action Legal for members of the Native American Church

Ecstasy

MDMA (methylene-dioxy-methamphetamine)
Synthesized in 1912 Structurally related to amphetamines Sympathomimetic Weak in altering perceptual functions But strong effects on emotions - empathogen Used in combo with psychotherapy
O CH 3 O CH 2 CH NH CH 3

MDMA

Pharmacodynamics

Monoamine neurotransmission

increase synaptic DA and 5-HT blocks 5-HT transporter enters neuron and causes release of 5-HT

Ecstasy Effects
Stimulant effects typically noted shortly after

ingestion
increased heart rate increased blood pressure dry mouth decreased appetite increased alertness elevated mood jaw clenching

Subjective Effects

euphoria increased physical and emotional energy heightened sensual awareness subjective feeling of increased closeness or enhanced communication memory loss

Cognitive Effects

Ecstasy Effects

X Tox
Malignant hyperthermia and dehydration Idiopathic toxic response (not common but nasty) Renal failure Rhabdomyolysis disintegration of muscle tissue Street X is even more of a problem because its not

always X or may have other drugs

X Tox
Potent neurotoxin 1-2 times street dose depletes forebrain 5-HT (not DA) Kills the transporter receptor (SSRI) Degeneration of 5-HT terminals
Fine axons from dorsal raphe Can get 30% loss with single injection Up to 80% with repeated injections

Can induce psychiatric disturbance in

vulnerable individuals. Treatment refractory depression

MDMA & MDA neurotoxicity

5-HT immunoreactive fibers in rat parietal cortex PCA Normal MDA

9.9

Squirrel monkeys 18 mo post-trtmt

Control

5-HT immunoreactivity

Neocortex

Hippocampus

Caudate

MDMA
McCann et al. (1997)

What is PMA?
Paramethoxy-amphetamine "Death" "Mitsubishi Double Stack"

"Killer" "Red Mitsubishi" Substitute for MDMA Cheaper to make Slower, longer effects More hallucinogenic Incidence of toxic side effects much higher than MDMA (narrow safety margin)

Designer Psychedelics
DOM, MDA, DMA, MDE, TMA, AMT, 5MeO-DIPT All structurally related to mescaline and

methamphetamine; therefore MDMA. MDA is a metabolite of MDMA. May be responsible for much of the MDMA effect.

Myristin and Elemicin

Found in nutmeg and mace Structurally similar to mescaline Significant nausea and vomiting

The sick usually limit use

Glutamatergic Psychedelics
DISSOCIATIVE ANESTHETICS

Phencyclidine
PCP NMDA receptor antagonist Blocks the function of glutamate Used as an analgesic and anesthetic Can be administered by any route Oddly enough, animals self-administer

(euphoria) Induces amnesia and true psychosis

Hallucinations, paranoia, agitation, dissociation

Higher doses lead to stupor, coma

seizures, death A perfect example of a Schedule I drug

Ketamine
Special K Very similar to PCP, not

as powerful Liquid, but can be powdered for snorting or smoking But just as dumb, stupid, useless and unsafe Another perfect example of a Schedule I drug

Subjective Effects of PCP/Ketamine

Sensations of light coming through the body

and/or colorful visions Complete loss of time sense Bizarre distortions of body shape or size Altered perception of body consistency Sensations of floating or hovering in space Feelings of leaving ones body Visions of spiritual or supernatural beings Emotions ranging from euphoria to hositlity
Dalgarno & Shewan (1996)

Dextromethorphan
Active ingredient in most OTC cough medicine NMDA receptor blockade at high doses Mostly teenage males abuse it

Like PCP and K at 20-30 X OTC dose

Coricidin Bad news

Cholinergic Hallucinogens

Muscarine/Muscimol
Found in mushrooms

(Amanita Muscaria) Muscimol is a GABAA agonist

Trance-like, dreamy state with dreamlike illusions Like Ambien

Muscarine is an

Acetylcholine agonist (muscarinic receptors)

Not psychotropic Peripheral effects: sweating, limb twitching, seizure activity

Found in Atropa

belladonna, Datura Stramonium, Henbane

Acetylcholine

receptor (muscarinic) antagonists

Dissociatives that induces delirium , hallucinations, and amnesia Classic anticholinergic symptoms

Hot as hell Dry as a bone Mad as a hatter Blind as a bat Red as a beet

Used in the treatment

of motion sickness & to dilate pupils during eye-exams.

Atropine & Scopolamine

Comes from a plant in the mint family Salvia Divinorum Affinity for kappa opioid receptors Agonist action Like LSD and psilocybin Fresh leaves are chewed and left in mouth Dried leaves smoked Not effective if taken orally Most potent, but not most powerful, of all naturally occurring hallucinogens Its still legal, but not likely for long

Opioid Hallucinogen - Salvinorin A