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Finding Order in Chemical Chaos - Continuing Characterization of Synthetic Cannabinoid Receptor Agonists

NCJ Number
253877
Journal
Neuropharmacology Volume: 134 Dated: May 2018 Pages: 73-81
Author(s)
Julie A. Marusich; Jenny L. Wiley; Timothy W. Lefever; Purvi R. Patel; Brian F. Thomas
Date Published
May 2018
Length
9 pages
Annotation
This study examined eight new synthetic cannabinoids: AM-1220, AM-2232, AM-2233, AM-679, EAM-2201, JWH-210, JHW-251, and MAM-2201.
Abstract
The diversion of synthetic cannabinoids from the lab to drugs of abuse has become increasingly prevalent in recent years; moreover, as earlier synthetic cannabinoids were banned, manufacturers introduced a new supply of novel compounds to serve as replacements. Hence, the chemical diversity of synthetic cannabinoid analogs has also rapidly increased. In the current study, each of the eight compounds was assessed for binding affinity and functional activation of CB1 and CB2 receptors, and pharmacological equivalence with Ä9-tetrahydrocannabinol (THC) in THC drug discrimination. All compounds bound to and activated CB1 and CB2 receptors, although efficacy at the CB2 receptor was reduced compared to that for the CB1 receptor. Similarly, all compounds stimulated GTPãS binding through the CB1 receptor, and all compounds except AM-1220 and AM-2233 stimulated GTPãS binding through the CB2 receptor. Furthermore, these compounds, along with CP55, 940, substituted for THC in THC drug discrimination. Rank order of potency in drug discrimination was correlated with CB1 receptor binding affinity. Together, these results suggest that all test compounds share the THC-like subjective effects of marijuana. Interestingly, the most potent compounds in CB1 binding in the present study were also the compounds that have been found recently in the United States, MAM-2201, EAM-2201, JWH-210, AM-2233, and AM-1220. These results indicate that the evolution of the synthetic cannabinoid drug market may be focused toward compounds with increased potency. (Publisher abstract modified)