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 have guessed, these are not the only by-products of HHC consumption.

 

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

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But before we get started, if you need a quick recap on HHC, we refer you to the article we've 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 (plotter)	Oxidation of metabolites	Recent studies (screening)
Carboxy-hydroxy-HHC	Hypothetical	Advanced Oxidation	Theoretical hypothesis
HHC-sulfates	Hypothetical	Elimination conjugation	Theoretical hypothesis

What are metabolites?

 

Metabolites are by-products of an active molecule (cannabinoids, drugs, alcohol...). Most are created by the body when it processes them to eliminate them. Others, as we shall see, are purely chemical creations.

Among the by-products created by the body, some, like primary metabolites, are direct by-products of the active molecule. Others, such as terminal metabolites, are by-products of the primary metabolites.

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

 

Active HHC metabolites

 

This class of "active" metabolites refers to metabolites that will produce effects on the body. These effects may be purely biological, without necessarily inducing psychoactive effects, or vice versa, as in the case of 10-OH-HHC and 8-OH-HHC, which obviously fall into this category. But they're not the only ones:

 

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

Formation and status of 9-OH-HHC

Little-known 9-OH-HHC is not produced by the body. It is a synthetic metabolite. It is considered a by-product of chemical synthesis and an impurity formed during these processes, notably 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

At present, 9-OH-HHC is very little studied. Some preliminary studies in animal models have shown it to possess pharmacological activity, but with about ten times less potency than Δ⁹-THC, and roughly similar effects.

This low potency and its status as a chemically created impurity limit scientific and medical interest in the subject.

 

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

11-Hydroxy-hexahydrocannabinol (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 was observed in HHC users, but also in those who had consumed Δ⁹-THC. This makes it a metabolite common to both THC and HHC[2].

 

Potentially powerful effects

Specific information on 11-hydroxy-hexahydrocannabinol (11-OH-HHC) is limited. Nevertheless, the 11-hydroxylation of HHC brings it closer to 11-OH-THC, a molecule known to produce effects potentially 4 times greater than those of the THC from which it is derived.

If 11-OH-HHC worked in a similar way, it could therefore be more potent than HHC, with a faster and stronger action, but also potentially more marked 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 enjoying a new lease of life as a result of their availability on the market, the world of metabolites, the process by which they are created, their effects, and the mechanisms by which they are broken down and disposed of, is still rather hazy.

What's more, it would appear that known metabolites, such as the ones we've been telling you about, represent only a fraction of the total HHC metabolites. Indeed, these discoveries are often made while research is focused on the effects and by-products of THC, potentially leaving some HHC by-products unnoticed.

All the more so as some of them may be sufficiently different that techniques developed to date are unable to detect them.

Some of these potential metabolites have been mentioned hypothetically. They could exist based on our knowledge of how the body and cannabinoids work. These include carboxy-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 points to 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 in progress and expected spin-offs

A number of by-product studies are currently underway.

Recently, one of them proposed to examine how HHC and its derivatives are transformed and eliminated by the human body, by studying biological samples such as blood, urine and saliva[3].

In addition, a technical report by 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 enabling rapid and accurate detection of HHC or its metabolites in urine[4].

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