The Emergence and Promise of Synthetic Cannabinoid Analog Drugs

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The U.S. Department of Health and Human Services is required by law to publish a report on “Drug Abuse and Drug Abuse Research” every three years. The Second Triennial Report to Congress was written in 1986 and published in 1987. The title of the chapter on marijuana research is “Marijuana and the Cannabinoids.”(23) In discussing research on “Marijuana and Reproduction” the report describes current theories and data on “the effects of cannabinoids on the hormones that modulate the reproductive process,”(24) “regular marijuana use”(25), and “effects caused by the chronic treatment of animals with THC.”(26) The review of research on “Effects Upon Fetal Development” refers to “marijuana’s effects”, “marijuana use”, “exposure to THC, cannabinol, and cannabidiol,” “cannabinoid administration”, and plasma “cannabinoid levels.”(27) A review of research on “Immune Status” reviews research on “THC”, and “marijuana smokers.”(28) Discussion of “Psychomotor Functioning” makes reference to correlations between “marijuana intoxication” and “THC or its acid metabolite”, and “blood levels of THC”(29) “High Priority Research Questions” include research on “heavy use of current higher potency marijuana”, “significance of the cumulation of cannabinoids”, and “the retention of THC.”(30)

The same pattern of use is present in the Third triennial report.(31) The relationship between the individual effects of cannabinoids and their sum total effect in marijuana is not the objective of modern research, but its fundamental foundation. Certainly scientists will learn more about marijuana by learning more about the interrelationships of cannabinoid effects, but lack of knowledge about these relationships neither inhibits the production of valid theories about marijuana nor does it dominate discussion of the effects of marijuana on the human body. The family relationship among cannabinoids is viewed by scientists as an asset, not a liability, in their work to better understand the effects of human, non-therapeutic use of marijuana.

“The rapid increase in the use of marijuana that occurred in the late 1960s and early 1970s resulted in an intensive research effort to identify the effects of cannabinoids on normal physiological function. There has been particular interest in the effects of cannabinoids on the brain in an effort to better understand their behavioral effects. Although much information has been gathered on the biochemistry of cannabinoids in the brain, it is unclear whether biochemical effects are responsible for the behavioral alterations caused by marijuana use. It is reasonable to ask why answers to this question have not been forthcoming. Part of the answer may be found by comparing cannabinoid research with that which has led to the much better understanding of opiod actions in the brain. Certainly opiods have been researched much more intensely for a much longer period of time. Two major factors that led to the elucidation of the opiod receptors and the subsequent identification of the endogenous opiods were the availability of structural analogs with widely varying agonist potencies and specific antagonist. Although progress in cannabinoid research lags behind that of opiods, recent evidence suggests that these same tools are becoming available to cannabinoid researchers.

“Considerable effort has been expended in synthesizing cannabinoid analogs largely because of the need to develop new therapeutic agents.(32) These synthetic analogs have also been extensively used to characterize cannabinoid actions . . .

“For the past several years, other synthetic analogs have been emerging that are both highly potent and highly stereoselective.(33) It is these properties of the analogs which suggest very specific mechanisms in the central nervous system that are involved in the behavioral effects of the cannabinoids.”(34)