THE MISCLASSIFICATION OF MARIHUANA David Gunnells The first known record of the use of cannabis as a medicine was published

in China five thousand years ago in the reign of the Emperor Chen Nung. It was recommended for malaria, constipation, rheumatic pains, absentmindedness and "female disorders." Another herbalist of the same era recommended a mixture of hemp resin and wine as an analgesic during surgery. Cannabis may have been cultivated for as long as ten thousand years, certainly since at least 4000 B.C. in China and 3000 B.C. in Turkestan. It has long been used as a medicine in India, China, the Middle East, Southeast Asia, South Africa and South America. It was noted as a remedy by Galen and other physicians of the Classical and Hellenistic Eras and was highly valued in medieval Europe. In the West, cannabis reached its heyday as a medicine in the midnineteenth century, where from 1839 to 1900, more than one hundred papers were published recommending cannabis for various illnesses. [FN 1] During the latter half of the 19th century, cannabis was prescribed for a wide variety of diseases including: rabies, rheumatism, epilepsy, tetanus [FN 2], neuralgia, dysmenorrhea, asthma [FN 3], chronic bronchitis, gastric ulcers and migraines. [FN 4] It was found to be a very effective pain reliever [FN 5], particularly as a topical anesthetic, and preferable to opium in many respects [FN 6], especially as a sleep-inducing drug. [FN 7] Toward the end of the century, the use of opiates for fast pain relief greatly increased due to the invention of the hypodermic syringe in the 1850s. Because cannabis preparations were insoluble in water and therefore not easily administered by injection, its medical use fell into decline. With the development of synthetic drugs such as aspirin, chloral hydrate and barbiturates, cannabis fell further by the wayside. By the 1940s, it was clear, however, that these new drugs had deadly disadvantages (more than 1000 people die each year in the U.S. from aspirin-induced bleeding) and it might have been expected that physicians looking for safer alternatives would have revisited cannabis and studied the chemical relatives of THC, which had been made possible by then, but unfortunately, the Marihuana Tax Act of 1937, which was designed to prevent "recreational" use of the drug, had effectively undermined any such possibility. Under Harry Anslinger, a former Assistant Commissioner for Alcohol Prohibition, the Federal Bureau of Narcotics, formed about the same time that Prohibition ended, by Secretary of the Treasury Andrew Mellon, Anslinger's wife's uncle, urged onward by the paper industry of Hearst and DuPont, organized a misinformation campaign which persuaded the public and Congress that cannabis was addictive and that its use led to violent crimes, psychosis and mental deterioration. The film "Reefer Madness," made as a part of this campaign, although a joke to sophisticated modern society, was then regarded as serious and the atmosphere and misbegotten attitudes it promoted continue to influence our culture today. Thus began the present climate of psycho-pharmacological McCarthyism that prevents rational political discussion of the irrational prohibition of cannabis. The presently established system for certifying drugs is designed to regulate the commercial distribution of drug company products and to protect the public against false or misleading claims about their efficacy or safety. The term "drug" in this context generally refers to a single synthetic chemical that has been developed and patented, usually by a pharmaceutical company. 1

These FDA rules, however, should not be applied to cannabis, which has been used for thousands of years by millions of people with little evidence of significant toxicity; there is absolutely no question about its safety. Any astute clinician with experience knows that it is efficacious to some degree for many people with various symptoms and syndromes. Large controlled studies would only be useful to determine what proportion of patients with a given symptom would get relief from cannabis rather than from the best presently available commercial medication. The marihuana plant traditionally has three basic preparations of varying potency. The least potent, referred to in India as "bhang" (whence comes the name Bangladesh - land of the bhang people), is the dried and crushed leaves, seeds and stems. Next is "ganja," the flowering tops of female plants, the standard recreational choice in the United States, and last is "charas" or "hashish", which is pure resin, the most potent. In its natural form, marihuana will never be able to be approved by the current system because: (1) as a natural product, it is not patentable, ergo no pharmaceutical company will invest the millions of dollars necessary for the required testing procedures; (2) as a plant, it contains many chemicals which interact with each other synergistically rather than a single ingredient; and (3) it is chiefly administered by smoking, unlike any other drug in the present pharmacopoeia. In theory, all the therapeutic properties of cannabis could be utilized if, in addition to THC, individual cannabinoids were isolated and made available separately as medicines. However, this would be an enormously complicated procedure; sponsors would have to determine the therapeutic potential and evaluate the safety of sixty or more substances, synthesize each one found to be useful and package it as a pill or aerosol. Due to the synergism of their action, it would be also necessary to look at various combinations of cannabinoids. No drug company would ever provide the resources for such a massive undertaking and, even if they would, as long as marihuana is available in its natural form, they would have great difficulty earning a profit. Ironically, in spite of its centuries of use by millions of people, the FDA is legally required to classify cannabis as a "new drug" and to demand the same testing regimen as for a completely unknown substance, although in reality, it's one of mankind's oldest medicines with an unparalleled record of safety and efficacy. Viewed in a medical context, marihuana is far more benign and far less damaging than the synthetic toxins routinely prescribed by physicians. The toxic effects of a drug can be classified as either acute (from a single dose) or chronic (from long-term use). A distinction can also be made between physical and psychological effects. The most common acute effects of smoking or ingesting cannabis are slight conjunctival hyperemia (reddening of the eyes) and a slightly increased heart rate, neither of which are uncomfortable or dangerous. As far as chronic effects, after five thousand years of cannabis use by hundreds of millions of people throughout the world, there is absolutely no credible evidence that this drug has ever caused a single overdose death and evidence from numerous studies over many years that long-term use of the more potent forms of cannabis might have debilitating effects is weak or nonexistent. [FN 8] The lethality of drugs in the present pharmacopoeia is measured by a value called the LD50, which is defined as the dose that will cause death in 50% of the animals or humans taking it. There is no LD50 for cannabis. The toxicity of a drug can be estimated by a number known as the "therapeutic ratio" or "safety factor," defined as the lethal dose divided by the effective dose. The following table compares the toxicity of barbiturates, which are Schedule IV drugs, alcohol, 2

which is unscheduled, and THC, which is in Schedule I if natural and Schedule II if synthetic: Drug Secobarbital Alcohol THC Effective Dose 100-300 mg. 0.05-0.1% 50 mcg./kg. Lethal Dose 1,000-5,000 mg. 0.4-0.5% 2,160,000 mcg./kg. Safety Factor 3-50 4-10 40,000

Because no human fatalities have ever been recorded for THC, the values given are for the effective human dose and the lethal dose for mice. [FN 9] Addiction is another problem often caused by chronic drug use, however, nerve receptors for the THC-like body substance anandamide (named after a Sanskrit word meaning "bliss") appear to be sparse in the human brain's reward center (the nucleus accumbens), where drugs like heroin and cocaine exert such powerful effects, which explains the lack of addictiveness in cannabis. The two most widely recognized signs of addiction - tolerance and withdrawal symptoms - are rarely serious problems for marihuana users. After continued heavy use, tolerance develops, to both physiological and psychological effects, but it varies considerably among individuals; almost no one reports an urgent need to increase the dosage to recapture the original sensation. Behavioral tolerance substantially reduces the effects of cannabis intoxication on attention and motor coordination in long-term users. In the Jamaican study referred to in FN 8, even heavy ganja users did not report abstinence symptoms when they were deliberately withdrawn abruptly from the drug during an experiment. To fully discount the final underpinnings of the Anslinger-Hearst-DuPont-inspired prohibition on cannabis, one need only read J. Gilfigan in Violence: Our Deadly Epidemic and Its Causes (1996), to learn that the only drug truly linked to violence is alcohol: marihuana and even heroin actually decrease aggression. Even if marihuana, currently classified in Schedule I, were available as a Schedule II drug, unlike other Schedule II drugs, such as cocaine and morphine, cannabis has many medical uses rather than just a few. In these days of rapidly rising medical costs, cannabis is a bright spot. Medical cannabis would be extremely inexpensive - at approximately $0.30 per cigarette, it is one hundred times cheaper than the best legally available treatment for nausea and vomiting caused by cancer chemotherapy (an 8 mg. ondansetron pill costs $30-$40 wholesale) and not a single case of lung cancer, emphysema or other significant pulmonary pathology attributable to cannabis use has been reported in the U.S. The British medical journal Lancet has stated unequivocally that, "the smoking of marijuana, even long-term, is not harmful to health." Even in the unlikely event that only a few people obtain relief from cannabis, it should be available because the cost is so little and the risks are so small. The question must be posed as to why regulators are so willing to accept anecdotal evidence of the adverse effects of cannabis, but not the therapeutic. For instance, there were no controlled experiments to determine the efficacy of chloral hydrate, aspirin, barbiturates, curare, insulin or penicillin [FN 10] and, under the Daubert precedent, negative anecdotal evidence is 3

inadmissible if contraindicated by epidemiological studies. [FN 11] There are many recent examples of the value of positive anecdotal evidence in the discovery of new uses for various drugs which were originally approved for other purposes, among which are: propranolol for angina and hypertension; diazepam for status epilepticus (a state of constant seizure activity); imipramine for childhood enuresis (bed wetting); minoxidil, originally developed to lower blood pressure, now marketed mainly as a treatment for baldness; tretinoin (Retin-A) for acne, but proven effective for removing wrinkles and liver spots; and aspirin, which could have saved an estimated 20,000 deaths a year from the mid- 1970s to the late 1980s had the medical establishment been quicker to accept its ability to prevent heart attacks. [FN 12] Current common medical uses for cannabis include treatment for: nausea or vomiting associated with cancer chemotherapy; glaucoma; epilepsy; multiple sclerosis; paraplegia and quadriplegia pain and tremors; AIDS wasting; migraine; rheumatic disease pain and inflammation; pruritis (severe itching as a symptom of atopicdermatitis); chronic pain; premenstrual syndrome, menstrual cramps and labor pains; and depression and other mood disorders. Less common medical uses include treatment for: asthma; insomnia; bacterial infections; dystonia (a neurological syndrome consisting of involuntary sustained or spasmodic muscle contractions); Adult Attention Deficit Disorder; schizophrenia; scleroderma (an incurable disease in which various organs of the body are damaged by fibrosis - replacement of normal tissue with scar tissue); Crohn's Disease (recurrent inflammation of the digestive tract); diabetic gastroparesis (paralysis of the stomach); pseudotumor cerebri (abnormally high pressure of the cerebrospinal fluid due to excess production); Post Traumatic Stress Disorder; phantom limb pain; tinnitus; and alcoholism and other addictions. Cannabis has been shown to be effective in controlling the violence associated with Aggressive Personality disorders and, in animal studies, has been found to reduce the size of cancer tumors. [FN 13] Recent evidence indicates that cannabis can counteract the effects of chemical free radicals on the nervous and immune systems, which cause a condition known as Excito-toxic Neuroendocrine Stress Response (ENSR) [FN 14], behavioral adaptations of which may manifest as hyperactivity (ADHD) in males and eating disorders in females. [FN 15] Over a lifetime of exposure, it is entirely possible that Alzheimer's, Parkinson's, senility and other degenerative afflictions of short-term consciousness and motor function are actually the result of the ENSR syndrome. [FN 16] A major source of free radicals is ultraviolet (UV) radiation caused by excessive depletion of the Earth's ozone layer. Although the middle ranges of UV radiation (UV-B) are necessary at low intensity for Vitamin D synthesis, it has increased in recent years to a biologically harmful extreme, as confirmed by the increased diagnoses of skin cancer in North America. One study shows that UV-B damages immunity in a dose dependent, cumulative fashion. Since the discovery of cannabinoid receptors in the human body, which are also found in mussels, indicating an evolutionary time span of approximately five hundred million years, research has shown that THC and cannabidiol can also prevent the toxic effects of excess glutamate in laboratory rats, which can kill brain cells after a stroke. [FN 17] There is a large area of overlap between disease and the problems of living, particularly in our stress-filled modern society. A doctor's prescription for a tranquilizer is often no different than a layperson's self-prescription of a beer or a marihuana cigarette, just as an alcohol-laced tonic often fulfilled the same function as whiskey in the 19th century. It's very difficult to draw a 4

line between therapeutic and recreational uses of drugs, between normalizing and enhancing. If we are to use drugs in ways that best promote the full human potential, we shall have to live with this ambiguity, rejecting a sharp distinction between medical and other purposes. Marihuana does not conform to certain conceptual boundaries; it has many medical uses, but also the ability to enhance many pleasures and to relieve many everyday discomforts. It can be an intellectual stimulant, helping users to penetrate conceptual constrictions and increasing insight and creativity. It can heighten the appreciation of food, sexual activity, natural beauty and other sensual experiences. It can introduce new dimensions to the understanding of music and visual arts. It can promote emotional intimacy in some settings and can emphasize the comical aspects of life, healing with laughter. When we speak of the dangers of non-medical drug use, we use the broadest possible definition of health in order to justify the strongest restrictions, preferring to place more weight on the indeterminate notion of "social well-being" rather than on concrete or specific health problems. Concerns about individual freedoms become irrelevant. However, when we establish medical reasons for using drugs, we define health narrowly so that, again, severe restrictions may be applied. Protecting, preserving or enhancing general well-being is regarded as a legitimate reason for banning drugs, but not for using them. We pretend that eliminating drug traffic is like eliminating slavery or piracy, or like eradicating smallpox or malaria. The official view is that everything possible that can be done must be done to prevent anyone from ever using any controlled substances, but the moral consensus about the evil of cannabis is shallow and uncertain. There are many millions of cannabis users in the United States who not only disobey the law, but also do not acknowledge its moral authority on this matter. These citizens doubt that the "authorities" understand either the deleterious or the useful properties of marihuana. When the government resorts to and insists on using the rhetoric of war in reference to the "drug threat", it is a sure sign that the issue is far from settled in the minds of the people. In fact, as regards cannabis, in a 1995 poll of one thousand registered voters conducted by the ACLU, 84% thought that the legalization of marihuana for medical use was a good idea. Other polls have recorded similar findings. Thirty-four states and the District of Columbia have enacted laws supporting the medical use of marihuana and, in spite of intense pressure from the Federal government, such laws remain on the books of twenty-six states. [FN 18] Thirteen states have legalized medical use and, under a Federal program discontinued due to an overwhelming number of applications, eight patients continue to receive official U.S. Government-issued marihuana. The financial and social costs of cannabis prohibition are extremely high and rising. In 1997, some 700,000 people were arrested on marihuana charges, the highest number in U.S. history to that date. Since 1965, there have been more than 11 million such arrests. Billions of dollars are spent each year in enforcement and imprisonment costs. One third of all Federal prisoners are confined on drug charges and about 13% of all Federal prisoners on marihuana offenses alone. [FN 19] A great deal of crime and violence are produced by the black market in drugs, just as they were by the boot-legging of alcohol in the 1920s. Civil liberties are badly eroded and young people, after discovering the extent of the misinformation given them about cannabis, become cynical about the information given them on other drugs and more disdainful of their commitment to the law in general. In 1975, the Drug Enforcement Administration acknowledged that, contrary to previous 5

statements, international treaty obligations do not prevent rescheduling of marihuana and subsequently, in a ruling issued in 1988, the DEA's Chief Administrative Law Judge Francis Young said that approval by "a significant minority" of physicians was sufficient to meet the standard of "currently accepted medical use in the United States." He further ruled that “marihuana, in its natural form, is one of the safest therapeutically active substances known to man" and that "[o]ne must reasonably conclude that there is accepted safety for use of marihuana under medical supervision. To conclude otherwise, on the record, would be unreasonable, arbitrary and capricious." Judge Young concluded that marihuana "may lawfully be transferred from Schedule I to Schedule II." [FN 20] In April 1991, the District of Columbia Court of Appeals unanimously ordered the DEA to re-examine its standards, but in March 1992, the DEA rejected all pleas for the reclassification of cannabis and in 1994, the appeals court finally upheld the DEA's decision. Why is the U.S. Government so adamantly opposed to legalization of such a useful and benign drug? First and foremost is an oft-encountered bureaucratic and political inability to admit error when, for more than sixty years, the government has exaggerated the dangers of recreational marihuana use. Millions of lives, careers and families have been destroyed. It is impossible for the perpetrators of this holocaust to voluntarily acknowledge that a mistake has been made. A second reason is the huge number of vested interests desirous of maintaining a marihuana prohibition, ranging from the vast enforcement and "educational" bureaucracies that have been created, to the industries that feed them. A drug abuse-industrial complex to rival the military-industrial complex of the Cold War has evolved and is tenaciously guarding its flanks from any attempts to inject a note of reason into any debate. There are also industries that feel their products will be supplanted by the countless commercial possibilities of legalized hemp weighing in on the side of the prohibitionists. Finally, cannabis is thought by many to be a potent cultural symbol. The war on marihuana really has very little to do with health and everything to do with culture. Since the first campaign against it in 1937, cannabis has been deliberately associated with the "wrong elements:" Mexicans; blacks; jazz musicians; and non-conformists of all stripes. It was seen as a catalyst of anti-establishment agitation in the 1960s and 1970s. Many people perceived the free speech, civil rights and anti-war movements not as the healthy expressions of a vibrant democracy, but as symptoms of a society run amok. Obviously, something more than mere consumer protection is involved when the laws criminalize even the consumer and require such a massive police bureaucracy for their enforcement. We certainly do not fine or jail the patients of someone who practices medicine without a license. It is completely evident that the intent of these laws is ultimately aimed at containing what is perceived to be a threat to the social fabric and moral order. Marihuana is caught in a dual web of regulations - those that control prescription drugs in general and criminal laws controlling psychoactive substances - which strangle its medical potential. Ultimately, it will have to be given the same status as alcohol, removing it from the medical and criminal control system. It may be that, for all the reasons stated above, the government will find it all but impossible to gracefully extricate itself from the self-created morass of cannabis prohibition, and that commercial interests and industry, once they break their hidebound reliance on outmoded products and technologies, will have to come to the rescue. Certainly, the energy and paper 6

industries, as well as the environment affected by them, would greatly benefit from utilizing the huge market potential of this ancient plant, especially in areas such as transportation and electric power generation. What is also clear is that political and moral pressure is building rapidly and that the status quo will not be maintained; far too much information is currently available to contradict the anti-marihuana propaganda put forth by the present regime.

7

FOOTNOTES FN 1. T. Mikuriya, ed., Marijuana: Medical Papers, 1839-1972, Oakland: Medi-Comp (1973) FN 2. W. O'Shaughnessy, "On the Preparations of the Indian Hemp, or Gunjah (Cannabis Indica): The Effects on the Animal System in Health, and Their Utility in the Treatment of Tetanus and Other Convulsive Diseases," Transactions of the Medical and Physical Society of Bengal (1838-1840) pp.421-461 FN 3. J. Reynolds, "Therapeutic Uses and Toxic Effects of Cannabis Indica," Lancet 1 (1890) p. 637 FN 4. J. Mattison, "Cannabis Indica as an Anodyne and Hypnotic," St. Louis Medical Surgical Journal (1891) 61:266-267 W. Osler, The Principles and Practice of Medicine, 8th Ed., New York: Appleton (1913) p. 1089 FN 5. H. Hare, "Clinical and Physiological Notes on the Action of Cannabis Indica," Therapeutic Gazette (1887) 11:271 F N 6. Mattison, Op. cit., p.271 FN 7. R. M’Meens, "Report of the Committee on Cannabis Indica," Transactions of the Fifteenth Annual Meeting of the Ohio Medical Society, Columbus (1860) FN 8. Report of the Indian Hemp Drugs Commission, 7 Vols. (1893-1894) Simla: Government Printing Office (1894) Mayor's Committee on Marihuana, The Marihuana Problem in the City of New York, Lancaster, Pa: Jacques Cattell (1944) D. Solomon, ed., The Marihuana Papers, Indianapolis: Bobbs-Merrill (1966) J. Hochman and N. Brill, "Chronic Marijuana Use and Psychosocial Adaptation,” American Journal of Psychiatry (1973) 130:132 M. Beaubrun and F. Knight, "Psychiatric Assessment of Thirty Chronic Users and Thirty Matched Controls," American Journal of Psychiatry (1973) 130:309 C. Culver and F. King, "Neurophysiological Assessment of Undergraduate Marihuana and LSD Users," Archives of General Psychiatry (1974) 31: 707-711 V. Rubin and L. Comitas, Ganja in Jamaica: A Medical Anthropological Study Chronic Marijuana Use, The Hague, Paris: Mouton & Co.; New York: Anchor 8

Books (1975) R. Dornbush, A. Freedman and M. Fink, eds., "Chronic Cannabis Use," Annals of New York Academy of Sciences 282 (1976) W. Carter and P. Doughty, "Social and Cultural Aspects of Cannabis Use in Costa Rica," Annals of New York Academy of Sciences 282 (1976) p. 1- 16 R. Satz, J. Fletcher, L. Sutker, "Neurophysiologic, Intellectual and Personality Correlates of Chronic Marihuana Use in Native Costa Ricans," Annals of the New York Academy of Sciences 282 (1976) p. 266-306 M. Braude and S. Szara, eds., The Pharmacology of Marihuana, 2 Vols., New York: Raven (1976) C. Stefanis, J. Boulougouris and A. Liakos, "Clinical and Psycho-physiological Effects of Cannabis in Long-term Users," Pharmacology of Marihuana, 2: 659666 P. Lessin and S. Thomas, "Assessment of the Chronic Effects of Marihuana on Motivation and Achievement: A Preliminary Report," Pharmacology of Marihuana, 2: 681-684 C. Stefanis, R. Dornbush and M. Fink, Hashish: Studies of Long-term Use, New York: Raven (1977) W. Carter, ed., Cannabis in Costa Rica: A Study in Chronic Marihuana Use, Institute for Study of Human Issues, Philadelphia: ISHI 3401 Science Center (1980) Institute of Medicine, Marijuana and Health, Washington, D. C.: National Academy of Sciences (1982) R. Musty and L. Kaback, "Relationships Between Motivation and Depression in Chronic Marihuana Users," Life Sciences 56: 23-24 (May 5, 1995) pp. 2151-2158 FN 9. T. Mikuriya, "Historical Aspects of Cannabis Sativa in Western Medicine," New Physician (1969) p. 905 FN 10. L. Lasagna, "Clinical Trials in the Natural Environment," Drugs Between Research and Regulations, C. Stiechele, W. Abshagen and J. Koch-Weser, eds., New York: Springer-Verlag (1985) FN 11. Daubert, E. et ex. v. Merrell Dow Pharmaceuticals, Inc., 509 U. S. __, 125 L. Ed. 2d 469, 113 S. Ct. 2786 (1993) In reference to FN 8 9

FN 12. L. Grinspoon, M. D. and J. Bakalar, Marihuana: The Forbidden Medicine, New Haven, London: Yale University Press (1997) FN 13. Ibid. FN 14. J. Heicklen, Professor Emeritus of Chemistry, Pennsylvania State University, World Authority on UV-B Photochemistry, Ozone Depletion, Free Radicals, Antioxidants and Combustion J. Kabelik, Z. Krejci and F. Santavy, "Cannabis as a Medicament," Bulletin on Narcotics (July-September 1960) p. 5-23 E. Astwood, "Anterior Pituitary Hormones and Related Substances," The Pharmacological Basis of Therapeutics, L. Goodman and A. Gilman, eds., NY: MacMillan (1965) 68: 1512-1537 J. Jaffe, "Drug Addiction and Drug Abuse," The Pharmacological Basis of Therapeutics 16: 276-314 R. Carchmann, L. Harris and A. Munson, "The Inhibition of DNA Synthesis by Cannabinoids," Cancer Research (Jan. 1976) 36(l): 95-100 M. Sato, "Electrophysical Studies on Radiation-Induced Changes in the Adult Nervous System," Advances in Radiation Biology, J. Lett and A. Adler, eds., NY: Academic Press (l978) 7: 181-205 N. Vaziri, R. Thomas, M. Sterling, K. Seiff, M. Pahl, J. Davilla and A. Wilson, "Toxicity with Intravenous Injection of Crude Marijuana Extract," Clinical Toxicology (March 1981) l8(3): 353-366 T. Mills, III, W. Price, P. Price and J. Roberson, Instrumental Data for Drug Analysis, NY: Elsevier Science (1982) J. Leite, E. Carlini, N. Lander, R. Mechoulam, Delta-9-THC for Prevention of Vomiting and Nausea Caused by Chemical and Radiation Treatment, Harefuah (1983) 55:306 D. Pate, "Possible Role of Ultraviolet Radiation in Evolution of Cannabis Chemotypes," Economic Botany (1983) 37(4): 396-404 M. Kripke, "Immunological Unresponsiveness Induced by Ultraviolet Radiation," Immunological Review (1984) 80: 87-102 R. Mechoulam, ed., Cannabinoids as Therapeutic Agents, Boca Raton, FL: CRC (1986) 10

S. Spector, T. Klein, C. Newton, M. Mondragon, R. Widen and H. Friedman, “Marijuana Effects on Immunity: Suppression of Natural Killer Cell Activity of Delta-9-Tetrahydrocannabinol," International Journal of Immunopharmacology (1986) 8(7):741-745 J. Lydon, A. Teramura and C. Coffman, "UV-B Radiation Effects on Photosynthesis, Growth and Cannabinoid Production of Two Cannabis Sativa Chemotypes," Photochemistry and Photobiology (1987) 46(2): 201-206 L. Hollister, "Marijuana and Immunity, Journal of Psychoactive Drugs (Jan. 1, 1988) 20(l): 3-8 S. Heishman, M. Huestis, J. Henningfield and E. Cone, "Acute and Residual Effects of Marijuana: Profiles of Plasma THC Levels, Physiological, Subjective and Performance Measure," Pharmacological Biochemical Behavior (Nov. 1990) 37(3): 561-565 M. Kripke, "Global Change Research: Ozone Depletion and Its Impacts," U.S. Senate Hearing: Committee on Commerce, Science and Transportation (1991), S. Hrg. 102-582: 25-31 The Merck Manual, "Reactions Due to Sunlight," Disorders Due to Physical Agents (16th Ed. 1992) 20:256; "Radiation Reactions and Injuries, Symptoms and Signs” 20: 260 J. Taijra, K. Mimura, T. Yoneya, A. Hagi, A. Murakami and K. Makimo, "Hydroxyl Radical Formiation by UV-lrradiated Epidermal Cells," Journal of Biochemistry, Tokyo (June 1992) 111(6): 693-695 The Merck Manual, "CNS Neoplasms," Neurologic Disorders 16th Ed. (1992) 11:126 D. Scurti, N. L'Abbate, D. Capozzi, R. Lofrumento, S. Crivellini and L. Ambrosi, "Ocular Hypertension in Radiologists and Radiology Technicians," Medical Laboratory (July 1992) 83 (4): 330-337 D. Compton, K. Rice, B. DeCosta, et al., "Cannabinoid Structure Activity Relationships: Correlation of Receptor Binding and In Vivo Activities," Journal of Pharmacological Experimental Therapeutics (1993) 265: 218-226 I. Valdez, J. Atkinson, J. Ship and P.Foz, "Major Saliva Gland Function in Patients With Radiation-Induced Xerostomia: Flow Rates and Sialochemistry," International Journal of Oncological Biophysics (Jan. 1993) 25(l): 41-47 11

S. Bondy and C. LeBel, "The Relationship Between Excito-toxicity and Oxidative Stress in the Central Nervous System," Free Radical Biology (June 1993) 14(6): 633-642 S. Madronich, R. McKenzie, M. Caldwell and L. Bjorn, "Changes in Ultraviolet Radiation Reaching the Earth's Surface," Environmental Effects of Ozone Depletion: 1994 Assessment Pursuant to Article 6 of the Montreal Protocol on Substances That Deplete the Ozone Layer, Under the Auspices of the United Nations Environment Programme (UNEP), Nairobi, Kenya (1994) Chapter 1 J. Longstreth, F. de Gruijl, M. Kripke, Y. Takizawa and J. van der Leun, "Effects of Increased Solar Ultraviolet Radiation on Human Health," Montreal Protocol, Ibid., Chapter 2 H. Schwarz, F. Blanco and M. Lotz, "Anandamide, An Endogenous Cannabinoid Receptor Agonist Inhibits Lymphocyte Proliferation and Induces Apoptosis." Journal of Neuroimmunology (1994) 55: 107-115 J. Derocq, M. Segui, J. Marchand, G. LeFur and P. Casellas, "Cannabinoids Enhance Human B-cell Growth at Low Non-molecular Concentrations" FEBS Letters (1995) 369: 177-182 F. de Gruij I, "Impacts of a Projected Depletion of the Ozone Layer," Consequences (1995; 1, #2) www.gcrio.org. K. Varga, K. Lake, B. Martin and G. Kunos, "Novel Antagonist Implicates the CB1 Cannabinoid Receptor in the Hypotensive Action of Anandamide," European Journal of Pharmacology (1995) 278(3): 279-283 L. Zimmer and J. Morgan, M.D., Exposing Marijuana Myths: A Review of the Scientific Evidence, NY: The Lindesmith Center (1995) R. Dawson, M. Beal, S. Bondy and D. DiMonte, "Excitotoxins, Aging and Environmental Neurotoxins: Implications for Understanding Human Neurodegenerative Disease," Toxicology Applied Pharmacology (Sept. 1995) 134(l): 1-17 U. Andley, B. Becker, J. Herbert, J. Reddan, A. Morrison and A. Pentland, "Enhanced Prostaglandin Synthesis After UV-B Exposure Modulates DNA Synthesis of Lens Epithelial Cells and Lowers Intraocular Pressure in Vivo," Investigative Ophthalmology & Visual Science (1996) 37: 142-153 M. Bayewitch, M. Rhee, T. Avidor-Reese, A. Breuer, R. Mechoulam and Z. Vogel, "(-)-Delta-9-TetrahydrocannabinoI Antagonizes the Peripheral Cannabinoid Receptor - Mediated Inhibition of Adenylyl Cyclase," Journal of 12

Biological Chemistry (1996) 271: 9902-9905 Y. Daaka, H. Friedman and T. Klein, "Cannabinoid Receptor Proteins Are Increased in Jurkat, Human T-Cell Line After Mitogen Activation," Journal of Pharmacological Experimental Therapeutics (1996) 276:776-783 NASA, "Surface Ultraviolet Radiation Levels Have Increased From 1979-1992," Associated Press Release (8/l/96) citing J. Herman, B. Bhartia, J. Ziemke, Z. Ahmad and D. Larko, "UV-B Increases (1979-1992) From Decreases in Total Ozone," Geophysical Resource Letters (1996) 23 (16): 2117 S. Skaper, A. Buriani, R. Dal Toso, L. Petrelli, S. Romanello and L. Facci, "The ALI-Amide Palmitoylethanolamide and Cannabinoids, But Not Anandamide, Are Protective in a Delayed Postglutamate Paradigm of Excitotoxic Death in Cerebellar Granule Neurons," Protocol of the National Academy of Sciences USA, (1996) 93: 3984-3989 L. Kolakowski, Jr. and K. Rice, "Accepted Mutation Parsimony Functionally Classifies G. Protein-Coupled Receptors," The Evolution and Classification of GPCRs FN 15. E. Hallowell and J. Radley, Driven to Distraction, NY: Touchstone (1994) A. Verri, M. Verticale, E. Vallero, S. Bellone and L. Nespoli, "Television and Eating Disorders. Study of Adolescent Eating Behavior," Minerva Pediatrics (June 1997) 49(6): 234-243 P. McNulty, "Prevalence and Contributing Factors of Eating Disorder Behaviors in Active Duty Navy Men," Military Medicine (Nov. 1997) 162(11): 753-758 D. Comings, "Genetic Factors in Substance Abuse Based on Tourette Syndrome and ADHD Probands and Relatives," Institute of Drug Abuse, Drug and Alcohol Dependence (1994) 235: 1-16 FN 16. M. Beal, "Role of Excitotoxicity in Human Neurological Disease," Current Opinion Neurobiology (Oct. 1992), 2(5): 657-662 D. Ben-Shachar and B. Youdin, "Iron, Melanin and Dopamine Interaction: Relevance to Parkinson's Disease", Progressive Neuropsychopharmacological Biological Psychiatry (Jan. 1993) 17(l): 139-150

A. Gordon, "Dangers of UV-B and Other Free Radical Sources: ENSR;" "Attention Deficit/Hyperactivity Disorder, Eating Disorders and ENSR," American Drug History Institute (1997) 13

FN 17. NIH Report in Proceedings of the National Academy of Sciences (July 1998) as cited in Scientific American, "Science and the Citizen: Herb Remedy" (Sept. 1998) FN 18. Medicinal Marihuana, The Lindesmith Center On-Line Library FN 19. C. Thomas, "Marijuana Arrests and Incarceration in the United States: Preliminary Report," Marijuana Policy Project (Nov. 1998) FN 20. Judge Francis Young's Opinion: DEA In the Matter of Marihuana Rescheduling Petition, Docket No. 86-22 (9/6/88)

WPT III (2000)

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