Synthetic cannabinoids: how do they compare to delta-9-tetrahydrocannabinol: neurological effects and beyond

Delta9-tetrahydrocannabinol (THC) was discovered as the primary psychotropic constituent of Cannabis sativa in 1964. The cannabinoid CB1 and CB2 receptors were discovered as the primary molecular targets of THC and the endocannabinoids in the early 1990s, though some actions of these compounds have been identified as CB1 or CB2-independent.

Beginning in the 1970s, additional compounds that mimic the actions of THC by activating cannabinoid receptors, now termed synthetic cannabinoid receptor agonists (SCRAs), were developed as potential therapeutics and/or to facilitate characterization of the endocannabinoid system. Since then, thousands of SCRAs have been developed using a variety of chemical backbones. In recent years, the designer drug market has driven the development of an expanding variety of SCRAs as compounds that maintain the “high” sought by recreational drug users yet avoid detection by law enforcement as previously-recognized SCRAs or cannabinoids. While THC and cannabis have relatively mild short-term effects, it has been reported that at least some SCRAs are toxic and have even caused death in otherwise healthy people, usually follow seizures, heart attacks and/or strokes. This chapter will succinctly review the effects of THC compared to SCRAs in the most studied organ systems.