Saturated Cannabinoids: Update on synthesis strategies and biological studies of these emerging cannabinoid analogs.

03 August 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


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 Δ9-tetrahydrocannabinol (Δ9-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.


CB1 receptor
CB2 receptor


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Comment number 1, István Ujváry: Aug 04, 2023, 04:57

NOTE THE 1st DESCRIPTION OF HHC by Adams in 1940 (not in 1944 as cited on p. 4): "Upon reduction the tetrahydrocannabinol, regardless of the rota￾tion it possesses, gives a hexahydrocannabinol (IV) of constant rotation (colorless, viscous oil, b. p. 153-155’ (0.10 mm.), [@]D -70’, found: C, 79.35; H, 10.43); this reduction product is also physiologically active." Adams et al: J Am Chem Soc. 1940;62(9):2402-2405. doi:10.1021/ja01866a0407