Reported on the much-discussed scientific discovery of a THC analog thirty times more efficacious than the infamous D9-THC. An earlier study found THCP, as well as CBDP, which are larger forms of THC and CBD, respectively. Now, the same team of researchers from Italy bridged a gap between regular CBD and CBDP. They found a unique form of THC as well as CBDH, a new cannabinoid for pain.
The size of the cannabinoid depends, mostly, on the number of carbon atoms. Regular THC and CBD have side chains that consist of five carbon atoms, and the ‘phorol‘ cannabinoids contain seven. Whereas, CBDH (cannabidihexol) is a hexyl cannabinoid with a six-carbon sidechain. (1)
NEW THC FOUND WITHOUT LUCK
Adding to the discovery, the team also found THCH (Δ9– tetrahydrocannabihexol). However, the quantity they collected was insufficient for further tests. It is still unknown if THCH is an intoxicant; potent like THC or even THCP. In any case, the new variants came as no surprise considering a cannabinoid that resembles THCH was synthesized in 1949. This artificial substance, known as parahexyl, is psychoactive and similar in structure to THCH. So, the researchers decided to check. They had to make sure they were looking at new natural analogs of THC and CBD, not some previously known methylated groups.
The Regional European Development Fund financed the research project in Florence, Italy. The team studied a strain known as CIN-RO, which was bred by the Council for Agricultural Research and Economics (CREA) in Rovigo, Italy. And like all cannabis approved for research in the boot-shaped nation, the Italian Military cultivated and provided the cannabis.
CBDH OR BUST
When the team isolated CBDH, on the other hand, they collected enough to study its effects on mice. Interest that the researchers took in CBDH in this study contrasted the team’s research on phorol cannabinoids (THCP) one year prior. The earlier scientific discovery disregarded CBDP for its lack of cannabinoid receptor activity. But, regular CBD, with a five-carbon chain, lacks true activity at the cannabinoid receptor and instead has an allosteric relationship that took decades for man to truly appreciate. Now, the market is flooded and stocks have gone to mushrooms.
ORIGINS OF AN ANALGESIC CANNABINOID
Thankfully, without enough THCH on hand, the researchers took interest in CBDH and the new cannabinoid’s effect on pain. CBDH produced strong antinociceptive (painkilling) properties in mice at an (intraperitoneal) dose of one and two milligrams per kilogram. Interestingly, that effect was void at a higher dose of five milligrams per kilogram. The low dose is on par with regular CBD, but CBDH has atypical effects at larger doses which suggests a biphasic effect.
The team hypothesized the presence of CBGH as a logical origin of other hexyl-cannabinoids. This is because CBG is the origin of both, THC and CBD, much like CBGV which becomes CDBV or THCV. After much analysis, however, they did not find CBGH or any related cannabinoid. In the end, they could not determine how the hexyl cannabinoids, THCH and CBDH, formed in the plant. Clearly, science requires more research to truly understand new variants of THC and CBD found in analytical success stories.
CBDH exhibits pain-relieving qualities (much like its CBD counterpart)
This is the most interesting part of the study. When the Italian researchers identified CBDP a year ago, they found it had very little affinity with cannabinoid receptors and didn’t activate them the same way THCP did.
The same cannot be said for CBDH — not even in the slightest.
Researchers were able to obtain a sufficient sample of CBDH and analyze its pharmacological effects in mice test subjects. They found lower doses were more effective for pain relief and pain management. 1.2 mg/kg of CBDH reduced pain response and 2 mg/kg of CBDH significantly blocked the physiological detection of pain.
Interestingly, higher doses (3 and 5 mg/kg) had no pain-relieving effects, which isn’t wholly uncommon. High doses of certain cannabinoids don’t necessarily equate to more effective. Low and medium doses of, say, THC can be more effective than higher doses for certain ailments.
What the researchers say about CBDH’s pain-relieving properties
The researchers believe CBDH’s pain-relief and pain-management qualities could be the result of vanilloid receptor activation (TRPV1), which helps mediate pain, pain-perception, and body temperature. In higher doses, however, they believe CBDH may block CB1 and CB2 receptors involved in the body’s response to pain, causing no pain-relief at all.
How does this differ from CBD?
CBD isn’t known for having the greatest relationship with your endocannabinoid system. Doesn’t bind to either cannabinoid 1 or cannabinoid 2 receptors. In fact, it barely even touches them (not directly at least). CBD has more of an affinity with other receptor sites e.g. serotonin (5-HT) receptors and the aforementioned vanilloid (TRPV1) receptors.
CBD’s targeting of serotonin and vanilloid receptors produces different effects and benefits from each other. Serotonin activation produces anti-depressant and anti-anxiety effects in rodent test subjects, whereas vanilloid activation results in the mediation of pain-perception, inflammation, and body temperature.
Because CBDH’s molecular structure is almost similar to CBD’s (CBDH has a six-alkyl side chain, while CBD has a five-alkyl side chain), it’s not unreasonable to assume they act in a similar way.
How CBDH could be used
To be perfectly honest, we can only surmise CBDH’s real-world uses based on one study.
If CBDH is a powerful pain-reliever in mice test subjects, there’s scope to suggest low-to-moderate isolated doses, alongside other analgesic cannabinoids such as CBD, CBG, and THC could be used in clinical treatment in the future.
This isn’t for certain, though. So much more needs to be looked at before we can accurately evaluate its uses beyond limited preclinical animal studies. We look forward to seeing how this exciting cannabinoid develops in the future.
Key Points:
- In low doses (1.2–2 mg/kg), CBDH reduced pain in mice test subjects. In higher doses (2–5 mg/kg), there was no pain-relieving effect.
- CBDH’s pain-relief qualities might be the results of vanilloid receptor activation — vanilloid receptors mediate pain and pain management.
- Real-world use of CBDH is still unknown but could be used as a potent pain-relief cannabinoid.
Researchers were unable to sufficiently test THCH’s effects
It’s always super exciting to read about a new THC variant. THC itself is a phenomenal cannabinoid responsible for a whole heap of amazing benefits such as pain relief, neuroprotection, sleep problems, antibacterial, and antiinflammation. Its variants (delta-8-THC, THCV, etc) are also incredibly useful to you.
Unfortunately, researchers were unable to extract enough THCH to sufficiently evaluate how it interacts with rodents. It’s unknown whether THCH is intoxicating or has unique benefits similar (or separate) from THC and its other variants.
However, a near-identical synthetic homolog of THC was inadvertently created in 1949 after scientists attempted to understand THC’s effects. This homolog, known as parahexyl (n-hexyl-Δ3-THC), is intoxicating, presumably binding tightly to CB1 receptors. Used as an anti-anxiety treatment in the 20th century but later banned and placed as a Schedule I controlled substance.
Does THCH cause these effects and benefits? Maybe. But we’ll only know when more research is carried out.
There are currently no CBDH or THCH-centered products on the market
Over the past couple of years, cannabis brands and manufacturers have sight their sights on other cannabinoids away from CBD and THC. High percentages of isolated minor cannabinoids such as CBG, CBN, and CBC can now be found in several products across the US.
Right now, CBDH and THCH are naturally found in regular cannabis products but not in high percentages.
It might be a while before we see CBDH or THCH isolated into a product but we’re more than excited to see it!
Or will CBDH become tomorrow’s wash of marketing gimmicks?
SOURCES
- Linciano, P., Citti, C., Russo, F. et al. Identification of a new cannabidiol n-hexyl homolog in a medicinal cannabis variety with an antinociceptive activity in mice: cannabidihexol. Sci Rep10, 22019 (2020). doi/10.1038/s41598-020-79042-2
- Morano, A., Fanella, M., Albini, M., Cifelli, P., Palma, E., Giallonardo, A. T., & Di Bonaventura, C. (2020). Cannabinoids in the Treatment of Epilepsy: Current Status and Future Prospects. Neuropsychiatric disease and treatment, 16, 381–396. https://doi.org/10.2147/NDT.S203782
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