@article{ref1,
title="Studies pertaining to the emerging cannabinoid hexahydrocannabinol (HHC)",
journal="ACS chemical biology",
year="2023",
author="Nasrallah, Daniel J. and Garg, Neil K.",
volume="ePub",
number="ePub",
pages="ePub-ePub",
abstract="We report studies pertaining to two isomeric hexahydrocannabinols (HHCs), (9R)-HHC and (9S)-HHC, which are derivatives of the psychoactive cannabinoids Δ9- and Δ8-THC. HHCs have been known since the 1940s, but have become increasingly available to the public in the United States and are typically sold as a mixture of isomers. We show that (9R)-HHC and (9S)-HHC can be prepared using hydrogen-atom transfer reduction, with (9R)-HHC being accessed as the major diastereomer. In addition, we report the results of cannabinoid receptor studies for (9R)-HHC and (9S)-HHC. The binding affinity and activity of isomer (9R)-HHC are similar to that of Δ9-THC, whereas (9S)-HHC binds strongly in cannabinoid receptor studies but displays diminished activity in functional assays. This is notable, as our examination of the certificates of analysis for >60 commercially available HHC products show wide variability in HHC isomer ratios (from 0.2:1 to 2.4:1 of (9R)-HHC to (9S)-HHC). These studies suggest the need for greater research and systematic testing of new cannabinoids. Such efforts would help inform cannabis-based policies, ensure the safety of cannabinoids, and potentially lead to the discovery of new medicines.<p />",
language="en",
issn="1554-8929",
doi="10.1021/acschembio.3c00254",
url="http://dx.doi.org/10.1021/acschembio.3c00254"
}