“Herbal incense”: Designer drug blends as cannabimimetics and their assessment by drug discrimination and other in vivo bioassays

Abstract

Recently, synthetic cannabinoids originally designed for testing in the laboratory only have found use recreationally in designer herbal blends, originally called “Spice”. The myriad of compounds found are for the most part potent full agonists of the cannabinoid receptor 1, producing effects similar to tetrahydrocannabinol (THC) and marijuana. Drug discrimination of these compounds offers a specific behavioral test that can help determine whether these new synthetic compounds share a similar “subjective high”with the effects of marijuana/THC. By utilization of drug discrimination and other behavioral techniques, a better understanding of these new “designer” cannabinoids may be reached to assist in treating both the acute and chronic effects of these drugs. The paper provides a brief exposé of modern cannabinoid research as a backdrop to the recreational use of designer herbal blend cannabimimetics.

Discriminative Stimulus Properties of Phytocannabinoids, Endocannabinoids, and Synthetic Cannabinoids

“…In the early 2000s, they were diverted and started to appear on drug abuse monitoring sites in products labeled "Spice" or "herbal incense" [86]. As reviewed previously [87], these compounds produce Δ 9 -THC-like intoxication in humans [88,89] and engender Δ 9 -THC-like discriminative stimulus effects in rodents and nonhuman primates [27,90]. Binding and other pharmacological properties of these compounds have been reviewed elsewhere [91,92].…”

A validated, sensitive HPLC‐MS/MS method for quantification of cis‐para‐methyl‐4‐methylaminorex (cis‐4,4'‐DMAR) in rat and human plasma: application to pharmacokinetic studies in rats

“…Many of the NPS appearing in the recreational drug marketplace are synthetic derivatives of existing controlled drugs, analogues of pharmaceutical products, previously researched substances, or naturally occurring compounds . These NPS are sold under various names such as ‘research chemicals’, ‘incense’, ‘bath salts’, ‘plant food’, and ‘dietary supplements’ . The scant knowledge about these new emerging drugs can pose a challenge to healthcare providers when treating patients presenting acute toxicity due to their use …”

Structure elucidation of the designer drug N‐(1‐amino‐3,3‐dimethyl‐1‐oxobutan‐2‐yl)‐1‐(5‐fluoropentyl)‐3‐(4‐fluorophenyl)‐pyrazole‐5‐carboxamide and the relevance of predicted 13C NMR shifts – a case study

“…In the last ten years, the illicit market has been flooded with a continuing stream of new so‐called designer drugs, which can be defined as clandestinely synthesized drugs which produce pharmacological effects similar to those of controlled substances. Among these, synthetic cannabinoids – also named synthetic cannabimimetics – play an important role and show high structural diversity . They are found for example in so‐called legal highs which are distributed worldwide via the Internet.…”

“…Among these, synthetic cannabinoidsalso named synthetic cannabimimeticsplay an important role and show high structural diversity. [1][2][3][4][5] They are found for example in so-called legal highs which are distributed worldwide via the Internet. Cannabimimetics act, like Δ 9 -tetrahydrocannabinol (THC), as agonists at the CB1 and CB2 receptors, but selective agonists as well as antagonists like SR141716A are also gathered under this generic term [6] ; other targeted receptors for this compound class are discussed, too.…”