Preparation of Hexahydrocannabinol (HHC) (Case No. 2023-172)

Summary:

UCLA researchers in the Department of Chemistry & Biochemistry have developed a novel method to produce hexahydrocannabinols, which are derivatives of THC, 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 the less active 9S isomer. These methods usually involve catalytic hydrogenation, a method with significant safety concerns. Different isomers often have different effects on the body, so the ability to synthesize the preferred 9R isomer is important.  With the growing market for HHCs, there is a clear need for a safer, more precise approach to HHCs.

Innovation:

Researchers led by Professor Neil Garg developed a novel method for the reduction of THC, leading to controllable stereochemistry for HHC production. This method can be applied to both ∆⁹- and ∆⁸-THC, providing a superior alternative to previous hydrogenation reactions with ratios of 9R:9S up to 10:1. Significantly, 9R is the desirable bioactive diastereomer produced by this technology, but is not favored when using classical hydrogenation conditions. This new synthetic approach 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:

• Safer (less flammable production method)
• High stereoselectivity 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