TY  - JOUR
PY  - 2023//
TI  - Studies pertaining to the emerging cannabinoid hexahydrocannabinol (HHC)
JO  - ACS chemical biology
A1  - Nasrallah, Daniel J.
A1  - Garg, Neil K.
SP  - ePub
EP  - ePub
VL  - ePub
IS  - ePub
N2  - 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 />
LA  - en
SN  - 1554-8929
UR  - http://dx.doi.org/10.1021/acschembio.3c00254
ID  - ref1
ER  -