Structure-Activity Relationships of Tricyclic and Nonclassical Bicyclic Cannabinoids

Abstract

The Research Analysis and Utilization System (RAUS) is designed to serve four functions: Collect and systematically classify the findings of all intramural and extramural research supported by the National Institute on Drug Abuse (NIDA); Evaluate the findings in selected areas of particular interest and formulate a state-of-the-art review by a panel of scientific peers; Disseminate findings to researchers in the field and to administrators, planners, instructors, and other interested persons; Provide a feedback mechanism to NIDA staff and planners so that the administration and monitoring of the NIDA research program reflect the very latest knowledge gleaned from research in the field. Since the number of research topics that can be intensively reviewed annually is limited, four subject areas are chosen each year to undergo a thorough examination. Distinguished scientists are invited to participate. Each scientist is provided reports from NIDA-funded research and asked to add information derived from the literature and his or her own research and to prepare a comprehensive, state-of-the-art review paper on an assigned topic. These papers, together with a summary of the discussions which take place at the review meeting, make up a RAUS Review Report in the NIDA Research Monograph series. In recent years a large number of reviews and books have appeared summarizing research advances in the chemistry, pharmacology, toxicology, metabolism, and distribution of cannabinoids and their synthetic analogs. Yet the volume of research on structure-activity relationships of cannabinoids appears to have decreased. In order to evaluate NIDA's current research program on cannabinoids, to rekindle interest in this critical area, and to focus attention on profitable avenues for future research, NIDA found it timely to bring together experts on the structure-activity relationships of cannabinoids for a comprehensive review. v

The molecular logic of endocannabinoid signalling

“…To complicate matters further, the hydrophobic nature of THC delayed experimentation and indicated that the compound might act by influencing membrane fluidity, rather than by combining with a specific receptor. This impasse was resolved by the development of new classes of potent and selective THC analogue 7 (FIG. 1), which led eventually to the pharmacological identification of cannabinoid-sensitive sites in the brain 8 .…”

Pharmacological characterization of repeated administration of the first generation abused synthetic cannabinoid CP47,497

“…As CP47,497 and CP55,940 belong to the bicyclic family of synthetic cannabinoids [44], it is not surprising that both of these compounds stimulated [ 35 S]GTPγS binding, though CP47,497 (i.e. 62.1% above basal activity) produced a significantly lower maximal stimulation of G-protein activity than CP55,940 (i.e.…”

Doors of deception—The diaspora of designer drugs

“…[11] Receptors for cannabinoids were difficult to identify due to the highly lipophilic nature of THC. [16] Identification of these receptors renewed efforts to synthesize THC analogues, to date numbering over 3000, [17] with the goals of enhancing activity and/or specifically targeting either CB1 or CB2. CB1 is primarily localized in the central nervous system, [12] and CB2 in cells associated with the immune system; [13] however, J. Kerwin there are exceptions, [14,15] and tentative evidence for additional receptors.…”

“…Since over 3000 compounds that bind to CB1 and/or CB2 have been synthesized, [17] it is not surprising that some of these have been exploited for recreational drug use. Since over 3000 compounds that bind to CB1 and/or CB2 have been synthesized, [17] it is not surprising that some of these have been exploited for recreational drug use.…”