Synthesis and pharmacological activity of the epimers of hexahydrocannabinol (HHC)

Cannabis is a multifaceted plant with numerous therapeutic properties on one hand, and controversial psychotropic activities on the other hand, which are modulated by CB1 endocannabinoid receptors. & UDelta;9-Tetrahydrocannabinol (& UDelta;9-THC) has been identified as the main component responsible for the psychotropic effects, while its constitutional isomer cannabidiol (CBD) has shown completely different pharmacological properties. Due to its reported beneficial effects, Cannabis has gained global popularity and is openly sold in shops and online. To circumvent legal restrictions, semi-synthetic derivatives of CBD are now frequently added to cannabis products, producing high effects similar to those induced by & UDelta;9-THC. The first semi-synthetic cannabinoid to appear in the EU was obtained through cyclization and hydrogenation of CBD, and is known as hexahydrocannabinol (HHC). Currently, there is limited knowledge regarding HHC, its pharmacological properties, and its prevalence, as it is not commonly investigated in routine toxicological assays. In this study, synthetic strategies were explored to obtain an excess of the active epimer of HHC. Furthermore, the two epimers were purified and individually tested for their cannabinomimetic activity. Lastly, a simple and rapid chromatographic method employing 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.

Automated summary

Cannabis has both therapeutic properties and controversial psychotropic activities, with CB1 endocannabinoid receptors playing a role. The main psychotropic component is & UDelta;9-THC, while its isomer CBD has different pharmacological properties. Semi-synthetic derivatives of CBD are added to cannabis products to produce similar effects to & UDelta;9-THC. Synthetic strategies were explored to obtain the active epimer of HHC, and a chromatographic method was used to identify and quantify phytocannabinoids and HHC epimers in commercial cannabis samples.