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Marijuana: What the Experts Say

by Jon Gettman

Cannabinoids are the active ingredients in marijuana, and delta-9-tetrahydrocannabinol (THC) is the only psychoactive cannabinoid. Excerpts from frequently cited journal articles follow the brief statements below. Because these excerpts are taken out of context, the reader is encouraged to read the original journal articles.

The primary marker of a drug with a severe dependence liability is compulsive self-administration by animals in a clinical setting. Animals will not self-administer marijuana.

Cannabinoids are non-toxic; lethal effects are non existent.

The pharmacology of cannabinoids was well-characterized by the mid 1980's, and indicates that marijuana does not pose greater health risks than alcohol, tobacco, and caffeine.

The discovery of the neural mechanism, the cannabinoid receptor system, which accounts for the characteristic effects of marijuana began in 1989.

Drugs with the highest potential for abuse have a direct effect on the neurotransmitter dopamine; marijuana does not.

Tolerance to marijuana has also been explained. It results from a natural process and not cell toxification. Research has proven that tolerance to marijuana is not a characteristic of a dependence liability.

Marijuana does not harm the immune system.

The discovery of the neural cannabinoid receptor system provides evidence of the physiological basis for the medical use of marijuana and cannabinoids.

Before 1989, because no one knew how marijuana's effects were produced, scientists were allowed great breadth to speculate about the substance.

Much of the harmful speculation about marijuana prior to the receptor discovery has based in studies with severe methodological problems.

Prior to 1989, many of these speculative hypotheses were presented to the public as likely facts which supported various public policies; but no one really knew what they were talking about.

Primary Marker of Drug Dependence: "[S]elf-administration of a drug to the point where the behavior becomes obsessive and detrimental to the individual is the primary criterion which must be met to classify a drug as one with significant potential for dependence." 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) pg. 6.

Primary Clinical Test of Dependence Liability: "If the abuse liability of a substance as defined by the likelihood of it supporting drug-seeking and drug-taking, is to be evaluated, an assessment of its reinforcing functions by self-administration is clearly the method of choice." Brady, J.V. "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. pg. 452.

Marijuana Does Not Meet the Primary Test for Dependence: "While self-administration of drugs has been taken as an indication of psychological dependence and/or abuse potential, few reports claim to have established experimental models for self administration of Delta-9-THC . . . This observation suggests limited potential for development of . . . limited psychological dependence due to the weak reinforcing properties of Delta-9-THC." Abood, M.E., and Martin, B.R. (1992), "Neurobiology of Marijuana Abuse," Trends in Pharmacological Sciences 13:201-206. pg. 203.

The Toxicity of Marijuana: "lethal effects of overdose by humans are nonexistent or rare" Dewey, W. Cannabinoid Pharmacology. Pharmacological Reviews. 1986 Vol. 38, No. 2. pp. 151 - 178. pg. 172.

The Extent of Parmacological Research: "Our studies of cannabinoids over the past 22 years have touched upon virtually every aspect of their actions." Hollister, L. "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. pg. 36-43. pg. 42.

The Relative Abuse Potential of Marijuana: "Compared with other licit social drugs, such as alcohol, tobacco, and caffeine, marijuana does not pose greater risks." Hollister, L.E.(1986), "Health Aspects of Cannabis", Pharmacological Reviews, 38:1, 1-20. pg. 17.

The Mechanism of Action for Cannabinoid Effects: " [Quantatative radiography has established that a cannabinoid receptor system in the brain] "is the same receptor [system] that mediates all of the behavioral and pharmacological effects of cannabinoids . . ." Herkenham, M., Lynn, A.B., et al., (1990) "Cannabinoid Receptor Localization in Brain," Proceedings of the National Academy of Sciences, 87:1932-1936, 1990. pg. 1935.

Marijuana And Known Drugs of Abuse: "The effects of cannabinoids on dopamine circuits thought to be common mediators of reward are indirect and different from those drugs such as cocaine and morphine which directly affect extracellular dopamine levels and produce craving and powerful drug-seeking behavior." 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, 1992. pg. 29

Note: Dopamine-based craving is believed to be neural mechanism responsible for the phenomenon of denial, in which someone with a drug dependency has strong urges to deny their dependency, and engage in all sorts of fictions and escapades to maintain their supply and intake of a drug. The accounts of patients who have used marijuana medically are often dismissed on suspicion that these anecdotal accounts are motivated more by drug dependency than therapeutic benefits. The distinction noted above is evidence that this sort of denial is not an element in patient accounts of the therapeutic benefits of marijuana.

Tolerance to Marijuana : "The magnitude of the present effect, like the striking behavioral tolerance, may stem in part that, unlike other psychoactive agonist drugs, cannabinoids can be administered in very high doses. It is ironic that the magnitude of both tolerance (complete disappearance of the inhibitory motor effect) and receptor down-regulation (78% loss . . .) is so large, whereas cannabinoid dependence and withdrawal phenomena are minimal. This supports the claim that tolerance and dependence are independently mediated in the brain." 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. pg. 300.

Marijuana and Immunosuppression: "In humans, immune suppression is subtle and in many cases insignificant. There is little evidence for cannabinoid immunosuppression as a causative agent in disease." 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. pg. 1620.

The Cannabinoid Receptor System Discovery Explains Why Cannabinoids Have Medical Value: "Dense binding in the basal ganglia and cerebellum suggests cannabinoid involvement in movement control . . . Anticonvulsant and antiemetic effects of cannabinoids have therapeutic value. The localization of cannabinoid receptors in motor areas suggests additional therapeutic applications. Cannabinoids exacerbate hypokinesia in Parkinson disease but are beneficial for some forms of dystonia, tremor, and spasticity." Herkenham, M., Lynn, A.B., et al., (1990) "Cannabinoid Receptor Localization in Brain," Proceedings of the National Academy of Sciences, 87:1932-1936, 1990. pg. 1936.

Before 1989, Theories Substituted for Facts About Marijuana's Mechanism of Action : "Because the cellular and biochemical mechanisms of action of psychoactive cannabinoids were not understood, neuroscientists were allowed great breadth to speculate upon the influence that these compounds might have on the neurons of the brain." Howlett, A.C., Bidaut-Russell, M, Devane, W., Melvin, L., Johnsons, M., & Herkenham, M., "The Cannabinoid Receptor: Biochemical, anatomical, and behavioral characterization." Trends in Neuroscience 13:10, 420-423. 1990. pg. 420.

Before 1989, Studies which Caused Some Scientists Alarm Were Based on Faulty Research: "Most of the biochemical studies employed concentrations of Delta-9-THC that were in excess of physiologically meaningful concentrations that might be found in brain. In addition, the criterion of structure-activity relationship was not met -- that is, the potencies of the various cannabinoids in the in vitro assays did not correlate with their relative potencies in eliciting characteristic behavioral effects. Particularly damaging to the relevance of these in vitro studies was the absence of enantioselectivity." 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, 1992. pg. 19.

Before 1989, All Sorts of Research on Cannabinoids Was Conducted Because No One Knew How they Worked on the Brain: "Until recently, very little was known about the cellular mechanisms through which cannabinoids act . . .Without evidence that cannabinoids act through a specific receptor coupled to a functional effector system, researchers were prone to study the effects of cannabinoids on membrane properties, membrane-bound enzymes, eicosanoid production, metabolism, and other neurotransmitter systems in vitro." 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, 1992. pg. 19.