Spice drugs are more than harmless herbal blends: a review of the pharmacology and toxicology of synthetic cannabinoids

Abstract

"K2" and "Spice" drugs (collectively hereafter referred to as Spice) represent a relatively new class of designer drugs that have recently emerged as popular alternatives to marijuana, otherwise characterized as "legal highs". These drugs are readily available on the Internet and sold in many head shops and convenience stores under the disguise of innocuous products like herbal blends, incense, or air fresheners. Although package labels indicate "not for human consumption", the number of intoxicated people presenting to emergency departments is dramatically increasing. The lack of validated and standardized human testing procedures and an endless supply of potential drugs of abuse are primary reasons why researchers find it difficult to fully characterize clinical consequences associated with Spice. While the exact chemical composition and toxicology of Spice remains to be determined, there is mounting evidence identifying several synthetic cannabinoids as causative agents responsible for psychoactive and adverse physical effects. This review provides updates of the legal status of common synthetic cannabinoids detected in Spice and analytical procedures used to test Spice products and human specimens collected under a variety of clinical circumstances. The pharmacological and toxicological consequences of synthetic cannabinoid abuse are also reviewed to provide a future perspective on potential short- and long-term implications.

Figure 1

Representative packaging and herbal material typically found within (A) Spice and (B) K2 products. (C) An example of deceptive language typically used on Spice labels to indicate ‘not for human consumption’ and the absence of controlled synthetic cannabinoids.

Figure 2

A schematic representation that summarizes what is known about JWH-018 metabolism, excretion and potential downstream interactions with CB1 receptors and other physiological targets, like CB2 receptors. “+” indicates agonism, “−” indicates antagonism, “X” indicates no binding affinity, “?” indicates not known.