The semisynthetic cannabinoid Hexahydrocannabinol (HHC)

Abstract

Abstract Cannabis is a double-faced plant with uncountable therapeutic properties, on one side, and controversial psychotropic activities, on the other side, modulated by CB1 endocannabinoid receptors. Δ9-Tetrahydrocannabinol (Δ9-THC) has been identified as the main component responsible for the psychotropic effects, while its isomer cannabidiol (CBD) has shown completely different pharmacological properties. Based on the remarkable beneficial effects, Cannabis has spread worldwide and it is openly sold in shops and online. In order to overcome restrictions due to legal issues, nowadays semi-synthetic derivatives of CBD are often added to cannabis products, obtaining “high” effects similar to those given by Δ9-THC. The first semi-synthetic cannabinoid appeared in the EU was obtained by cyclization and hydrogenation of CBD, and known as hexahydrocannabinol (HHC). At present, very little is known about HHC, its pharmacological properties, and diffusion, since it is not commonly investigated in routine toxicological assays. In the present work, the synthetic strategies aimed to obtain an excess of the active epimer of HHC were investigated and the two epimers were purified and individually tested for their cannabinomimetic activity. Lastly, a simple and fast chromatographic method with a UV detector and a high-resolution mass spectrometer was applied to identify and quantify up to ten major phytocannabinoids, as well as the HHC epimers in commercial cannabis samples.