HHC metabolites: 10-OH-HHC, 8-OH-HHC… A world yet to be discovered

When we expanded our catalog to include 10-OH-HHC, we told you about the two active metabolites of HHC, 10-OH-HHC and 8-OH-HHC, but as you may suspect, these are not the only by-products created by the consumption of HHC.

 

In fact, there are about ten of them. Some are active, others inactive, and some are hypothetical. Today, we're giving you a complete overview of the other HHC metabolites : their names, their effects and/or uses, as well as the studies on them!

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But before we begin, if you need a quick recap on HHC, we refer you to the article we dedicated to it: “HHC: what is it and why was it banned?”

Summary table of HHC metabolites

Metabolite	Kind	Origin	State of research
10-OH-HHC	Active, psychoactive	HHC Metabolism	Preliminary studies
8-OH-HHC	Active, psychoactive	HHC Metabolism	Preliminary studies
9-OH-HHC	Synthetic	Synthetic impurity	Very little studied
11-OH-HHC	Active, conventional	HHC and THC Metabolism	Limited data
COOH-HHC	Terminal (pbatchter)	Oxidation of metabolites	Recent studies (screening)
Carboxy-hydroxy-HHC	Hypothetical	Advanced Oxidation	Theoretical hypothesis
HHC-sulfates	Hypothetical	Elimination conjugation	Theoretical hypothesis

Metabolites: what are they?

 

Metabolites are byproducts of an active molecule (cannabinoids, medications, alcohol, etc.). Most are created by the body when it processes them for elimination. Others, as we will see, are purely chemical creations.

Among the byproducts created by the body, some, like primary metabolites, are direct byproducts of the active molecule. Others, like terminal metabolites, are byproducts of the first metabolites.

For more precise information on the definition of metabolites, we refer you to the items where we already address this subject: the items on 10-OH-HHC, 8-OH-HHC, as well as the one on THC metabolites: 11-OH-THC, 10-OH-THC and COOH-THC.

 

The active metabolites of HHC

 

This class of "active" metabolites refers to metabolites that produce effects on the body. These effects can be purely biological, without necessarily inducing psychoactive effects, or the opposite, as is the case with 10-OH-HHC and 8-OH-HHC, which obviously fall into this category. But these are not the only ones:

 

9-Hydroxy-hexahydrocannabinol (9-OH-HHC)

Formation and status of 9-OH-HHC

Relatively unknown, 9-OH-HHC is not produced by the body. It is a synthetic metabolite. It is considered a byproduct of chemical synthesis and an impurity formed during these processes, particularly during the synthesis of Δ⁸-THC.

The data available at present indicate that 9-OH-HHC has not yet been found as a natural product, either in hemp or in the body. Nevertheless, some structurally similar analogues, such as 9α-hydroxyhexahydrocannabinol, have been identified as minor components in Cannabis sativa.[1]

Limited potential applications

Currently, 9-OH-HHC is very little studied. Some preliminary studies carried out on animal models have shown that it possesses pharmacological activity, but with a potency about ten times lower than that of Δ⁹-THC, and roughly similar effects.

Its low potency and its status as an impurity resulting from a chemical creation limit scientific and medical interest in it.

 

11-Hydroxy-hexahydrocannabinol (11-OH-HHC)

11-Hydroxyhexahydrocannabinol (11-OH-HHC) is a more conventional metabolite, in that it is produced by the body. But where it differs from 10-OH-HHC is that it has been observed not only in users of HHC, but also in those who have consumed Δ⁹-THC. This makes it a common metabolite of both THC and HHC.[2]

 

Potentially powerful effects

Specific information on 11-hydroxyhexahydrocannabinol (11-OH-HHC) is limited. However, the hydroxylation at the 11-position of HHC makes it similar to 11-OH-THC, a molecule known to produce effects potentially four times stronger than those of THC, from which it is derived.

If 11-OH-HHC worked similarly, it could therefore be more potent than HHC, with a faster and stronger action, but also potentially more pronounced side effects.

 

 

Tracer metabolites: COOH-HHC

As with THC, HHC also produces terminal metabolites. These are the end product of THC or HHC ingestion, resulting from the oxidation of major metabolites such as 10-OH-HHC or 11-OH-HHC.

Recent studies have shown that, like 11-OH-HHC,HHC-COOH can be metabolized in humans after the consumption of delta-9 THC. Indeed, in an analysis of 308 blood samples taken during roadside checks, 84% of THC-positive users, in whom traces of THC-COOH were found in the blood, had also metabolized HHC-COOH, albeit to a lesser extent.[2]

These results show that certain HHC-derived metabolites could be detected when THC was consumed, and vice versa. This offers interesting perspectives for understanding cannabinoid metabolism and improving detection methods.

 

HHC metabolites: a world yet to be discovered

 

HHC metabolites are still largely unknown. Although some, such as 8-OH-HHC and 10-OH-HHC, are gaining renewed attention due to their availability on the market, the world of metabolites, their creation process, their effects, and the mechanisms that allow their degradation and elimination remains quite unclear.

Furthermore, it would appear that the known metabolites, such as those mentioned, represent only a portion of all HHC metabolites. Indeed, these discoveries are often made while research focuses on the effects and byproducts of THC, potentially leaving some HHC byproducts undetected.

This is especially true since some of them could be different enough that the techniques developed so far do not allow them to be detected.

Among these potential metabolites, some have been suggested as hypotheses. They could exist based on our understanding of how the body and cannabinoids function. This is particularly true of γbox-hydroxy-HHC, which could be an advanced form of oxidation of hydroxylated metabolites, and HHC sulfates, resulting from a conjugation process that facilitates their elimination by the body.[2]

This suggests a number of in-depth research and potential discoveries to be made to better understand the functioning of cannabinoids as a whole, as well as the impact of metabolites on the body and their use in toxicological analyses.

 

Studies are underway and expected outcomes

Currently, some studies on by-products are underway.

Recently, one of them proposed examining how HHC and its derivatives are transformed and eliminated by the human body, by studying biological samples such as blood, urine, and saliva3]

Furthermore, a technical report from theEuropean Monitoring Centre for Drugs and Drug Addiction (EMCDDA) highlights the lack of studies on the human pharmacology of HHC and the absence of analytical methods allowing for rapid and accurate detection of HHC or its metabolites in urine.[4]

These studies are indeed of great importance, because knowledge of the metabolites of HHC as well as THC is crucial, both for understanding these molecules and cannabinoids, for their classification and regulation, or for the potential properties that could prove interesting from a medical and pharmacological point of view.