The article was updated on September 9, 2021, to remark on the inventions of Roger Adams.
A novel cannabinoid entered the public cannabis market for the first time anywhere recently, landing in Colorado. Hydrogenated THC, known as HHC, was previously, and is possibly still, restricted from any market due to patents and laws. Variations of HHC are even 1000 percent stronger than THC. Plus, production often uses heavy metals. Despite these considerations, HHC vape carts hit the market without an accredited Certificate of Analysis (COA) or toxicity data.
Where does HHC come from?
HHC is an acronym for hexahydrocannabinol. Adding hydrogen atoms to THC molecules — a process known as hydrogenation — creates it. Converting liquid vegetable oils into margarine, for example, uses a similar process.
A misconception grows in that there is more than one kind of HHC. For a start, hexahydrocannabinol was initially noted in patents by Roger Adams (US2419937A), the first chemist to identify CBD. Moving forward, there are more basic — hydroxylated — forms of HHC (alpha and beta-HHC). These compounds were initially discovered in the 1970s by scientists attempting to modify THC and conduct early studies on the endocannabinoid system (ECS) Whereas, Pfizer developed another derivative of HHC in the 1980s.
Additionally, Mark Scialdone, Ph.D. owns a patent that covers the more novel parent molecules, HTHC and 2-HM-HHC. Overall, there are well over a dozen different forms of this unusual cannabinoid.
Compared to THC, each variation of HHC has two more hydrogen atoms in the left-most ring of the molecule. Beyond this, HHC is shy by one pair of electrons because the additional hydrogens displace a crucial double electron bond in its eastern ring. These general characteristics only define the chemical structure, not the effects that each molecule has on the human body.
Is HHC the opposite of CBN?
I asked Markus Roggen Ph.D., President and CSO of Delic Labs, about side reactions in extracts, such as the formation of CBN. Oxygen can be incorporated into an extraction which can cause some THC to degrade into CBN and other unique cannabinoids (quinones.) Degradation occurs when hydrogens are stripped off of the THC molecule by oxygen atoms in a process called oxidation.
Rather than strip hydrogens away from THC, a processor must add hydrogens to make HHC — a reaction called hydrogenation.
Hydrogenation is the opposite of oxidation. So, hydrogenation is actually a reduction of the molecule.Dr. Roggen
Labs use metals to make HHC
Dr. Roggen noted that you do not have reducing environments in normal extraction techniques. In fact, metal catalysts are used to ensure THC is reduced to HHC.
So, no HHC is not a molecule you stumble upon in cannabis production normally. The reactions required to get it are so far away from what one would do in a cannabis production site, that there is no overlap.Dr. Roggen
Our guts are capable of reducing HHC into hydroxyl-HHC. A super potent edible theory?
After an edible is eaten, it will pass through the gut and into the liver, generally. Some of it is destroyed but any THC that arrives in the liver is faced with enzymes that can change its molecular structure. Commonly, the hydroxyl form of THC, known as 11-OH-THC, is discussed as part of an edible’s psychoactive outcome. This is because enzymes in the digestive system hydroxylate THC into 11-OH-THC.
Comparatively, the digestive system can naturally reduce HHC into alpha and beta-HHC molecules via biological hydrogenation. It should be noted that different species of animals metabolize HHC into different levels of alpha and beta-HHC.
Hydrogenation which is the addition of a hydrogen atom (H+). Whereas, hydroxylation of cannabinoids occurs when a hydroxyl group (OH-) replaces a methyl group (CH3). The two processes are far different, although the same cannabinoid can be modified both ways.
Spice, morphine, and super agonists – where cannabinoid reductions hide
Edible cannabis has been reported to be more potent in some individuals because of the levels 11-OH-THC they produce, a hydroxylated cannabinoid. But what about alpha and beta-HHC; does the gut reduce more basic HHC into super potent hydrogenated molecules?
Hydrogenated cannabinoids produced by Pfizer took up a notorious and widely discussed role decades after their development. The synthetic cannabinoid blend — Spice — is comprised of beta-HHC derivatives the pharmaceutical giant developed in the 80s.
To no ones surprise today, a study conducted on mice in 1977 suggested that D9-THC is not as potent as morphine in regards to pain relief. Beta-HHC, on the other hand, was equipotent as morphine but with significant differences in their effect. Old data suggests that beta-HHC is 1000% more potent than D9-THC. So, should untested hydrogenated cannabinoids sell on the open market in vape pens, gummies, and creams?
Selling HHC before accredited tests
Let’s pretend studies exist to ensure the synthetic cannabinoid is safe and each form of HHC in the product carries an ISO accredited COA. In this hypothetical case, the discussion on HHC boils down to ethics. Yet, we need to back up to safety studies and ISO accredited COAs since neither quality assurance exists for HHC in humans beyond analytical data. This is critical because ISO accredited lab tests ensure a product can be safe.
The position of each double bond defines a molecule’s effect and the idenity of the compound. For example, CBN is approximately 25% as potent as THC, and remember that difference between THC and CBN is a loss of hydrogens. So, if we take THC and add hydrogens then we have a drastically different molecule that needs further testing to understand it’s safety profile.
Hydrogenated cannabinoids have been studied on mice and this research suggests that HHC is a promising cancer treatment.
Spice is technically a super-agonist that over-saturates the endocannabinoid system, a problem for addiction and dependency. If a proper lab test does not exist, how can you ensure the HHC in that vape pen is not a completely unknown and synthetic super-agonist rather than a more simple reduction of THC?
Conclusively, unmodified plant compounds produced purely by natural creations of this Earth might not be safe, but they are different than novel drug substances. A new cannabinoid created by synthesis or heavy modification, whether it is HHC or any new drug, should have multiple years of data behind it before any public sale.
Show your work
- The reduction of THC adds two hydrogen atoms to the molecule, which reduces the cyclohexene ring into a cyclohexane ring.
- Basas-Jaumandreu, J., & de Las Heras, F. (2020). GC-MS Metabolite Profile and Identification of Unusual Homologous Cannabinoids in High Potency Cannabis sativa. Planta medica, 86(5), 338–347. doi/10.1055/a-1110-1045
- Bloom, A. S., Dewey, W. L., Harris, L. S., & Brosius, K. K. (1977). 9-nor-9beta-hydroxyhexahydrocannabinol, a cannabinoid with potent antinociceptive activity: comparisons with morphine. The Journal of pharmacology and experimental therapeutics, 200(2), 263–270.
- Huffman, J. W., Hepburn, S. A., Reggio, P. H., Hurst, D. P., Wiley, J. L., & Martin, B. R. (2010). Synthesis and pharmacology of 1-methoxy analogs of CP-47,497. Bioorganic & medicinal chemistry, 18(15), 5475–5482. doi/10.1016/j.bmc.2010.06.054
- Harvey, D. J., & Brown, N. K. (1991). Comparative in vitro metabolism of the cannabinoids. Pharmacology, biochemistry, and behavior, 40(3), 533–540. doi/10.1016/0091-3057(91)90359-a