Summary:
UCLA researchers in the Department of Chemistry & Biochemistry have developed a novel method to produce hexahydrocannabinols, which are derivatives of the psychoactive component of cannabis.
Background:
As the cannabis industry evolves with changing legal and societal opinions, derivatives of the psychoactive components of marijuana, tetrahydrocannabinol (THC), are garnering interest for both recreational and medicinal purposes. Several pharmaceutical derivatives of THC have been approved by the FDA to treat chronic pain, chemotherapy-induced nausea, and more conditions. While hexahydrocannabinols (HHCs), a specific class of THC derivatives, have been known for over 80 years, synthetic methods to produce them generate a mixture of isomers with a preference for 9S. These methods usually involve catalytic hydrogenation, a method with significant safety concerns that favors one isomer over another without precise control over the products. Different enantiomers often have different effects on the body, so the ability to synthesize a mixture with a preferred enantiomer product is important. With the growing market for HHCs, there is a clear need for a safer, more precise approach to both diastereomers of HHC.
Innovation:
Researchers led by Professor Neil Garg developed a novel method for the hydrogenation of THC, leading to controllable stereochemistry of HHCs. This method can be applied to both ∆9- and ∆8-THC, providing a superior alternative to previous hydrogenation reactions with ratios of R:S up to 10:1. Significantly, 9R is the desirable bioactive diastereomer produced as a minor product in classical hydrogenation conditions. This new synthetic route minimizes risk while producing purer diastereomeric mixtures of medicinally and recreationally relevant cannabinoids for pharmaceuticals, research, and consumption. These endeavors may contribute to shaping cannabis-related regulations, improving the responsible and equitable utilization of cannabinoids, and eventually facilitating the exploration of novel medications.
Potential Applications:
- Pharmaceuticals
- Research of synthetic THC and HHC products
- Recreational cannabis products
Advantages:
- Improved safety (less flammable production method)
- High enantioselectivity for preferred isomer
- Ability to produce R and S diastereomers
Development-To-Date:
Method has been described in a peer-reviewed publication
Related Papers:
Studies Pertaining to the Emerging Cannabinoid Hexahydrocannabinol (HHC), Nasrallah & Garg, ACS Chemical Biology 2023 18 (9), 2023-2029.
DOI: 10.1021/acschembio.3c00254
Reference:
UCLA Case No. 2023-172
Lead Inventor:
Neil Garg