Synthetic Pot : Not Your Grandfather’s Marijuana

Benjamin M. Ford, Sherrica Tai, William E. Fantegrossi, and Paul L. Prather

Trends in Pharmacological Sciences, 2017, 38, (3), 257–276.

doi : 10.1016/j.tips.2016.12.003

Abstract

In the early 2000’s in Europe and shortly thereafter in the USA, it was reported that “legal” forms of marijuana were being sold under the name K2 and/or Spice. Active ingredients in K2/Spice products were determined to be synthetic cannabinoids (SCBs), producing psychotropic actions via CB1 cannabinoid receptors, similar to those of Δ9-THC, the primary active constituent in marijuana. Often abused by adolescents and military personnel to elude detection in drug tests due to their lack of structural similarity to Δ9-THC, SCBs are falsely marketed as safe marijuana substitutes. Instead, SCBs are a highly structural diverse group of compounds, easily synthesized, which produce very dangerous adverse effects occurring by, as of yet, unknown mechanisms. Therefore, available evidence indicates that K2/Spice products are clearly not safe marijuana alternatives.

Keywords : Synthetic Cannabinoids, K2, Spice, CB1 Cannabinoid Receptor, Marijuana Substitute

 

Synthetic cannabinoids (SCBs) : Not simply fake marijuana

Synthetic cannabinoids (SCBs) are a growing class of highly potent, highly efficacious cannabinoid agonists that, until recently, have been falsely marketed as “safe” and “legal” alternatives to marijuana [1]. As early as 2004, SCBs were promoted by Internet retailers and European “head shops” as meditation potpourris and tropical incense products under names such as K2 and Spice [2]. It was not until late 2008 that K2/Spice products were investigated by the European Monitoring Center for Drugs and Drug Addiction for their psychoactive properties [3, 4]. Upon analysis of these herbal mixtures, the synthetic cannabimimetics JWH-018 and CP 47,497-C8 were identified as the primary psychoactive components [1]. Since then, several structural classes of SCBs have quickly evolved and diversified to avoid forensic detection and legislative scheduling [1, 5]. Individual users have sought after SCBs to avoid detection in standardized drug testing as well as to achieve a more intense high than that associated with marijuana [3]. The purpose of this review is to summarize reported literature demonstrating that SCBs are neither similar nor suitable substitutes for marijuana and that use of these compounds can result in tolerance and dependence, as well as numerous other documented adverse, toxic and potentially fatal effects.

Evolution of Cannabinoid Nomenclature

The term “cannabinoid” originally referred to a number of structurally related C21 aromatic hydrocarbon compounds isolated from the Cannabis Sativa plant [6]. However, following characterization of Δ9-THC, the principal psychoactive constituent in cannabis [7], and cloning of cannabinoid receptors [8, 9], the term “cannabinoid” instead came to be associated with drugs sharing pharmacological profiles similar to Δ9-THC and exhibiting affinity for cannabinoid receptors, apart from any structurally similarity to compounds originally isolated from the cannabis plant [10]. Therefore, currently accepted nomenclature for “cannabinoids” are ligands that bind to and modulate the activity of cannabinoids receptors [11]. Cannabinoids are structurally diverse and range from compounds that are endogenously produced (endocannabinoids) [12], to plant-derived (phytocannabinoids) [13] and synthesized compounds (synthetic cannabinoids) [14]. This review will focus on the growing epidemic of synthetic cannabinoid abuse, sought primarily for agonist actions of these compounds at CB1 cannabinoid receptors [15].

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