The Scientific And Legal Basis for the End of Marijuana Prohibition by Jon Gettman The Controlled Substances Act mandates that schedule I drugs have a "high potential for abuse." A judicious reading of both the statute and the legislative history finds that this abuse potential is the key criterion for its scheduling under the CSA.(NORML v. DEA, 559 F.2d 735 (1977))(21 USC § 812 (b)(1)) However, it has long been recognized that marijuana does not satisfy this essential criterion. Therefore the justification for marijuana's continued placement in schedule I is a presumption rather than a finding.(See U.S. Cong. and Admin. News 1970 p. 4578, p. 4579, p. 4629. See also 51 FR 22947 (1986)) As of April, 1995, the Drug Enforcement Administration was "unaware of any new scientific studies of marijuana that would lead [them] to re-evaluate its classification at this time." According to a letter from Thomas Constantine, Administrator of DEA, if this author "has access to scientific data concerning marijuana which he wishes to bring to our attention, we will be pleased to consider it, should he care to share the documentation with us." Extensive documentation was provided to Constantine on July 10, 1995 as part of an administrative petition subjecting DEA's consideration of these issues to judicial review. The CSA establishes an eight item list of scientific and medical factors that are to be considered in scheduling decisions. (21 USC 822 (c)) These factors are defined further in the legislative history.(see U.S. Cong. and Admin. News 1970 p 4601 - 4603) The first factor is the drug's relative or actual potential for abuse. The contemporary paradigm for evaluating the abuse potential of a drug has been developed by the Committee on the Problems of Drug Dependence.[7] They have concluded that self-administration in animal studies is the necessary characteristic of a drug with a significant, severe potential for abuse.[3, 7, 21, 32] However, animals will not self administer marijuana.[1, 17, 32] The second factor is evidence of the drug's pharmacological effects. In 1989 Leo Hollister remarked that: "Our studies of cannabinoids over the past 22 years have touched upon virtually every aspect of their actions. They constitute the largest series of studies of the human pharmacology of marijuana on record."[15] Since then further research by the likes of Donald Tashkin, Mario Perez-Reyes, Julian Azorlosa, for example, have supplemented the classic work on the chemistry and pharmacology of marijuana by Agurell, Dewey, Hollister, Martin, Mechoulam, and Razdan. The third factor considered in scheduling decisions is scientific knowledge about the substance. In 1988, it became obvious that scientists had been wrong in their theories about how marijuana acted on the brain.[17, 18, 27] Recent Evidence affirms that marijuana activates a unique receptor system in the brain.[16, 17, 18, 31] In another current finding, it has been discovered that tolerance to marijuana is the result of receptor down-regulation, rather than receptor desensitization as was previously believed.[25, 29] In addition, the theory that marijuana's lipophilic qualities produce a harmful effect has also been contradicted.[22, 30] The receptor has been cloned[23], an endogenous ligand for the cannabinoid receptor has been discovered[9], and an orally effective cannabinoid antagonist has been created.[28] The fourth factor is the history and current pattern of abuse, including "social, economic, and ecological characteristics of the segments of the population involved in such abuse." Critical evaluations of the National Household Survey, the Monitoring the Future Project, the Drug Abuse Warning Network and other federally sponsored reports provide more than adequate data to evaluate this factor. Key observations are that marijuana use and adolescent access persist despite increased enforcement. Moreover, the National Household Survey indicates that risk perception associated with marijuana use decreases as education and age increase.[34] The most interesting factor for advocates of harm reduction policies, though, is the fifth factor: scope duration and significance of abuse. According to the legislative history, "in reaching [her] decision, the Attorney General should consider the economics of regulation and enforcement attendant to [a scheduling decision]. In addition, [she] should be aware of the social significance and impact of such a decision upon those people, especially the young, that would be affected by it." This fifth factor allows the introduction of several critical issues, such as the impact of schedule I status and enforcement policies have on the private therapeutic use of marijuana[12] as well as their effects on the cultivation of marijuana for medicinal or personal use[11]. This factor also allows the introduction of cost/benefit analyses of decriminalization laws in various states[2], as well as the evaluations of various state legislatures on the significance of marijuana abuse as it is reflected in the scheduling of the substance under state law.[24] The sixth factor concerns the risk, if any, to public health. "If a drug creates no danger to the public health, it would be inappropriate to control the drug under this bill." A recent editorial in favor of harm reduction policies in the American Journal of Public Health calls for development of "a new system that is consistent with present scientific knowledge and able to incorporate new scientific findings."[8] The Controlled Substances Act provides such a system, and reformers should try and make the CSA work the way it was intended to before contemplating a new system. This factor alone allows for the introduction of harm reduction policies into scheduling and national drug policy. The reputed threat to public health presented by marijuana is a result of the drug's perceive relation to the use of other dangerous drugs. The contemporary gateway theory, though, acknowledges that alcohol and cigarette use precede marijuana use, and that marijuana use does not predict in any way use of more serious drugs.[6, 20, 33, 35, 36] Consequently, the policy ramification of the gateway theory is that the public health would benefit from successful policies that delay the age of first use of any drugs.[20] Why is marijuana singled out? Norman Zinberg clarified the relationship of drug, set, and setting to the understanding and treatment of drug use and abuse in 1984.[37] An emerging public health model that advocates harm reduction, the study of use and abuse, and performance evaluation is evidence of gaining recognition for the utility of Zinberg's ideas.[13, 34] A meta-analysis of correlations between school-aged use of alcohol, marijuana and tobacco conducted by the Bowman Gray School of Medicine concluded that the primary correlates of school aged drug use were prior use and access.[13] There is considerable social science data and theory to support the rescheduling of marijuana under these last two factors representing the epidemiology and the significance of a drug's actual use in the population. The animal models used to determine the abuse potential of a drug represent synergy between pharmacology and root behavioralism.[4] Despite their excellent predictive validity, they do not present a biological marker. This lack of a biological clarification of marijuana's abuse potential has been the excuse to keep marijuana in schedule I. The discovery of the cannabinoid receptor system annihilates that excuse. The seventh factor is the substances physic or physical dependence liability. It has been long recognized that marijuana is not physically addictive.[1, 14, 17] Advances in neurobiology have provided a biological model for explaining substance abuse.[19, 21, 33] Drugs of abuse affect the production of dopamine, a neurotransmitter associated with response and reward and now held to explain the compulsive self-administration of drugs.[10, 19, 21, 33] However, cannabinoid receptors are not located on dopamine producing neurons.[17] In vivo microdialysis has shown that unlike other drugs[10] THC, the active chemical in marijuana, does not affect striatal dopamine levels.[55] (Earlier research that had indicated a cannabinoid effect on dopamine was found to be strain-specific, and has not been replicated in other animal studies.[1, 17, 33]) Heroin (schedule I), cocaine (schedule II) and amphetamines (schedule III) all affect dopamine production. Marijuana, cannabinoids, and THC do not. Where shall we schedule marijuana under existing provisions of controlled substances act? The eighth factor concerns the relation of the substance to other scheduled chemicals. The discovery of the receptor system provides the scientific basis for considering cannabinoids as a family with a similar mechanism of action. This is especially accurate with regards to the drug's dependence potential. Scientists have long accepted the validity of assertions about marijuana based on research on its constituent parts, such as THC, cannabinol, marijuana smoke, and experimental cannabinoids. There is no basis for distinguishing between the marijuana and THC in a consideration of dependence potential. As a result of this and other information, I believe that marijuana, cannabinoids, and THC should be removed from schedules I and II, and I have begun the administrative proceedings to consider this issue. By law, petitions for rulemaking changes are sent to the DEA.(21 CFR 1308.44) The DEA then forwards the petition to the Department of Health and Human Services for a scientific and medical evaluation that is binding on DEA in regards to scheduling decisions.(21 USC § 811 (b)) The Court of Appeals has ruled that petitions must be judged on merit.(NORML v. DEA, 559 F.2d 735 (1977)) The United States has an international obligation under various treaties to verify this information and take steps to change the international scheduling of marijuana. Meanwhile, the subject of where marijuana should be scheduled pending treaty amendment is open for debate. Twenty five years ago the government acknowledged marijuana did not deserve schedule I status. Unfortunately, however, it decided to wait for more evidence before ending marijuana prohibition. The scientific evidence has been mounting ever since, and none of it legitimately supports marijuana's schedule I status. Justice delayed is justice denied. The time has come for an end to marijuana prohibition, and to acknowledge that for the last 25 years marijuana users have been denied equal protection under the laws of the United States and its Constitution. (Jon Gettman is a former National Director of NORML, and is currently enrolled in a doctoral program in the Institute of Public Policy at George Mason University. His present research agenda concerns regional development and the agricultural and industrial technologies required for hemp-related development. The petition for repeal was the result of a research agenda concerning the policy implications of recent findings about the cannabinoid receptor system.) Author's note: The complete text of the petition for repeal will soon be available at the web site of the National Organization for the Reform of Marijuana Laws, http://norml.myhouse.com/. References [1] Abood, M., Martin, B. (1992), "Neurobiology of Marijuana Abuse," Trends in Pharmacological Sciences 13:201-206,. [2] Aldrich, M., Mikuriya, T. (1988), Savings in California Marijuana Law Enforcement Costs Attributable to the Moscone Act of 1976 -- A Summary. Journal of Psychoactive Drugs. Jan-Mar 1988 20(1):75-81. [3] Brady, J. (1988) "The Reinforcing Functions of Drugs and Assessment of Abuse Liability." In: Problems of Drug Dependence, 1987. Proceedings of the 49th Annual Scientific Meeting, The Committee on Problems of Drug Dependence, Inc. Harris, L. (ed), National Institute on Drug Abuse Research Monograph 81. Washington, D.C.: U.S. Govt. Print. Off., 1988. pp. 440 - 456. [4] Brady, J. What's a Radical Behaviorist Like You Doing in a nice Pharmacology Club like CPDD? In: Problems of Drug Dependence, 1992. Proceedings of the 54th Annual Scientific Meeting, The Committee on Problems of Drug Dependence, Inc. Harris, L. (ed), National Institute on Drug Abuse Research Monograph 132. Washington, D.C.: U.S. Govt. Print. Off., 1993. pg. 19 -28. [5] Castaneda, E., Moss, D.E., et al. (1991) "THC Does Not Affect Striatal Dopamine Release: Microdialysis in Freely Moving Rats" Pharmacology, Biochemistry & Behavior, Vol. 40, pp. 587-591. [6] Chen, K., Kandel, D. (1995) "The Natural History of Drug Use from Adolescence to the Mid Thirties in a General Population Sample. American Journal of Public Health, January 1995. 85:41-47. [7] Cicero, T. (1992) Assessment of Dependence Liability of Psychotropic Substances: Nature of the Problem and the Role of the College on Problems on Drug Dependence. Contractor Document for the Office of Technology Assessment. (Springfield, VA: National Technical Information Service. 1992.) (NTIS Doc. #PB94-175643) [8] Des Jarlais, D. (1995) "Editorial: Harm Reduction--A Framework for Incorporating Science into Drug Policy." American Journal of Public Health. January 1995, 85:1 pg. 10-12. [9] Devane, W., Dysarz, F., et al (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258: 1946-1949. [10] Di Chiara, G. and Imperato, A. (1988), "Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats." Proc. Natl. Acad. Sci., 85:5274. [11] Gettman, J. (1993) Cannabis Suppression and Marijuana Crop Value. Washington, D.C.:NORML. [12] Grinspoon, L. (1993) Marihuana, The Forbidden Medicine. New Haven: Yale University Press. [13] Hansen, W. (1994), Drug abuse in Schools: Contributing Factors and Preventive Interventions. Springfield, VA: National Technical Information Service. (PB#94-175635) 1994. [14] Hollister, L.E. (1986), "Health Aspects of Cannabis", Pharmacological Reviews, 38:1, 1-20. [15] Hollister, L. (1989) "Peregrinations Among Drugs of Dependence: Nathan B. Eddy Memorial Award Lecture." In: Problems of Drug Dependence, 1989. Proceedings of the 49th Annual Scientific Meeting, The Committee on Problems of Drug Dependence, Inc. Harris, L. (ed), National Institute on Drug Abuse Research Monograph 95. Washington, D.C.: U.S. Govt. Print. Off., 1990. pgs. 36-43. [16] Herkenham, M., Lynn, A.B. et al.(1990), "Cannabinoid Receptor Localization in Brain," Proceedings of the National Academy of Sciences, 87:1932-1936. [17] Herkenham, M. (1992), "Cannabinoid Receptor Localization in Brain: Relationship to Motor and Reward Systems," P.W. Kalivas and H.H.Samson (eds), The Neurobiology of Drug and Alcohol Addiction, Annals of the American Academy of Sciences. 654:19-32. [18] Howlett, A.C., Bidaut-Russell, et al (1990), "The Cannabinoid Receptor: Biochemical, anatomical, and behavioral characterization." Trends in Neuroscience 13:10, 420-423. [19] Izenwasser, S., Kornetsky, C. (1992) "Brain-Stimulation Reward: A Method For Assessing the Neurochemical Bases Of Drug-Induced Euphoria." In Watson, R.A. (1992) Drugs of Abuse and Neurobiology. Boca Raton: CRC Press. [20] Kandel, D.B., Yamaguchi, K., Chen, K. (1992), "Stages of Progression in Drug Involvement from Adolescence to Adulthood: Further Evidence for the Gateway Theory." J. Stud. Alcohol 53: 447-457, 1992. [21] Koob, G. (1995) Animal Models of Drug Addiction. In Bloom, F., Kupler, D. (eds.) Psychopharmacology: The Fourth Generation of Progress. New York: Raven Press. pgs. 759 - 772. [22] Lynn, A.B., and Herkenham, M. (1993), "Localization of Cannabinoid Receptors and Nonsaturable High-Density Cannabinoid Binding Sites in Peripheral Tissues of the Rat: Implications for Receptor-Mediated Immune Modulation by Cannabinoids" Journal of Pharmacology and Experimental Therapeutics, 268:3 1612-1623. [23] Matsuda, L., Lolait, S., et al (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561-564. [24] National Criminal Justice Association (1991) A Guide to State Controlled Substances Acts. Washington, D.C.: National Institute of Justice. NIJ Ref No. 132321. [25] Oviedo, A., Glowa, J, and Herkenham, M.(1993), "Chronic cannabinoid administration alters cannabinoid receptor binding in rat brain: a quantitative autoradiographic study." Brain Research, 616:293-302. [26] Pertwee, R. (1993) The Evidence for the Existence of Cannabinoid Receptors. General Pharmacology. 29:4 pg 811-824. [27] Richardson, S., Mirasedeghi, S., et al (1990). "Synthetic and Biological Studies of Potential Affinity Ligands for the Cannabinoid Receptor Based on CP-55,244." In: Problems of Drug Dependence, 1990. Proceedings of the 52th Annual Scientific Meeting, The Committee on Problems of Drug Dependence, Inc. Harris, L. (ed), National Institute on Drug Abuse Research Monograph 105. Washington, D.C.: U.S. Govt. Print. Off., 1990. pgs. 140 - 146. [28] Rinaldi-Carmona, M., Barth, F., et al (1994). "SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Letters 350 (1994) pg 240 - 244. [29] Rodriguez De Foncesa, F., Gorriti, M., et al (1994) Downregulation of Rat Brain Cannabinoid Binding Sites After Chronic D9-Tetrahydrocannabinol Treatment. Pharmacology, Biochemistry, and Behavior. 47:33-40. [30] Thomas, B., Compton, D., Martin, N. (1990) Characterization of the Lipophilicity of Natural and Synthetic Analogs of D9-Tetrahydrocannabinol and Its Relationships to Pharmacological Potency. Journal of Pharmacology and Experimental Therapeutics . 255:2 pgs. 624 - 630. [31] Thomas, B., Wie, X., Martin, B. (1992) Characterization and Autoradiographic Localization of the Cannabinoid Binding Site in Rat Brain Using [3H]11-OH-D9-THC-DMH. Journal of Pharmacology and Experimental Therapeutics . 263:3 pgs. 1383 - 1390. [32] U.S. Congress, Office of Technology Assessment (1993), Biological Components of Substance Abuse and Addiction, OTA-BP-BBS-117 (Washington, DC: US Government Printing Office, September 1993). [33] U.S. Congress, Office of Technology Assessment (1994) Technologies for Understanding and Preventing Substance Abuse and Addiction, OTA-EHR-597 (Washington, DC: U.S. Government Printing Office, September 1994). [34] U.S. Department of Health and Human Services, Public Health Service, Substance Abuse and Mental Health Services Administration, Office of Applied Studies. (1994) Advance Report Number 5. Preliminary Estimates From the Drug Abuse Warning Network. Rockville, MD: SAMSHA. March, 1994. [35] Yamaguchi, K., Kandel, D. (1984) "Patterns of Drug Use From Adolesence to Young Adulthood: II. Sequences of Progression." American Journal of Public Health 74:7, July, 1984. [36] Yamaguchi, K., Kandel, D. (1984) "Patterns of Drug Use From Adolescence to Young Adulthood: III. Predictors of Progression." American Journal of Public Health 74:7, July, 1984. [37] Zinberg, N. (1984) Drug, Set, and Setting. New Haven: Yale University Press.