New study sheds light on effects of HHC in the body

A new study by researchers in the US is the first to shed light on how HHC binds to receptors in the body – and proposes a safer, more consistent way to produce it. 

The new paper takes a closer look at hexahydrocannabinol, or HHC, an emerging cannabinoid which is gaining popularity in the recreational cannabis market in the US and Europe.

HHC is part of a group of substances known as intoxicating hemp-derived cannabinoids (IHDCs), along with the better-known Delta-8 THC. IHDCs are psychoactive compounds derived from the cannabis sativa plant that occur naturally, but can also be synthesised from other cannabinoids.

Despite the fact that we know relatively little about HHC and its effects on the body, online searches and sales are increasing rapidly and it has now been identified in over 20 European countries, with many moving bring in tighter controls around the substance. 

READ MORE: What is HHC? Its effects, safety and legal status in Europe

In the new study, for the first time, researchers at UCLA systematically evaluated how well HHC binds to receptors in the human body.

HHC products on the market today typically contain a mixture of two different versions, or isomers, of the HHC molecule. The scientists found that although both isomers bind to the same cannabinoid receptors in the body as THC does, only one of the isomers binds as well as THC does — which suggests that it is the only HHC isomer with effects comparable to THC.

Senior author of the paper, Neil Garg, UCLA’s Kenneth N Trueblood Professor of Chemistry and Biochemistry, explained in a press release: “The compounds have been tested in animals before, but the basic binding assays of each isomer were somehow not done or not reported.

“That is unusual for a product that’s widely available to consumers, and it reflects the need for more fundamental research in this rapidly evolving field.”                            

A safer way, more consistent way to produce HHC?

The paper, published in ACS Chemical Biology, also highlights the variability in HHC products currently being sold to consumers.

Most HHCs found in commercially available products are synthesised from THC by manufacturers using a process called catalytic hydrogenation. The technique produces both isomers of HHC in variable ratios. As a result, there is little consistency in the amount of each HHC isomer in HHC products — not only from one brand to the next but even among batches produced by the same manufacturer. 

As the ratios are variable, some HHC products being sold to consumers contain relatively little of the more biologically active isomer.

Professor Garg and Daniel Nasrallah, a UCLA assistant adjunct professor of chemistry, developed a new method for synthesising the more biologically active of the two HHC isomers, using a chemical process called hydrogen atom transfer. 

According to the researchers, this method is able to produce HHC yielding roughly 10 times more of the biologically active isomer than the less active one.

READ MORE: Experts call for HHC to be regulated rather than banned

The new method also is said to be safer than catalytic hydrogenation, a process that uses hydrogen gas, which when not handled carefully can lead to laboratory fires. Labs that use catalytic hydrogenation also often use potentially toxic heavy metals like platinum or palladium as part of the process. 

Professor Garg said: “If a medical drug was being synthesised using these metals, careful analysis would be required to ensure these metals are not present in the final commercial products in order to avoid any toxicity concerns.

It is understood that generally this is not happening with HHC products not analysed for the presence of platinum or palladium, according to Nasrallah.

Further research on cannabinoids and their effects is essential, say the researchers.

Professor Garg added: “These studies are crucial if we are to have laws and policies that are fair and allow for consumer safety, while allowing scientists and society alike to explore the potential therapeutic effects of new cannabinoids.”

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