Saturated Cannabinoids: Update on Synthesis Strategies and Biological Studies of These Emerging Cannabinoid Analogs

Natural and non-natural hexahydrocannabinols (HHC) were first described in 1940 by Adam and in late 2021 arose on the drug market in the United States and in some European countries. A background on the discovery, synthesis, and pharmacology studies of hydrogenated and saturated cannabinoids is described. This is harmonized with a summary and comparison of the cannabinoid receptor affinities of various classical, hybrid, and non-classical saturated cannabinoids. A discussion of structure-activity relationships with the four different pharmacophores found in the cannabinoid scaffold is added to this review. According to laboratory studies in vitro, and in several animal species in vivo, HHC is reported to have broadly similar effects to & UDelta;9-tetrahydrocannabinol (& UDelta;9-THC), the main psychoactive substance in cannabis, as demonstrated both in vitro and in several animal species in vivo. However, the effects of HHC treatment have not been studied in humans, and thus a biological profile has not been established.

Automated summary

This article describes the discovery of natural and non-natural hexahydrocannabinols (HHC) by Adam in 1940 and its emergence in the drug market in the United States and some European countries in late 2021. The article provides background information on the synthesis and pharmacology studies of hydrogenated and saturated cannabinoids and discusses the cannabinoid receptor affinities of different types of saturated cannabinoids. The effects of HHC treatment have been studied in vitro and in several animal species in vivo, showing similarities to Δ9-tetrahydrocannabinol (Δ9-THC), but no studies have been conducted in humans to establish its biological profile.