Everyone knows that marijuana’s psychoactive effects are primarily caused by tetrahydrocannabinol (THC). Well, it turns out that everyone might be wrong, as scientists recently discovered that cannabis actually contains a cannabinoid that is 33 times more powerful than THC. Known as tetrahydrocannabiphorol (THCP), the compound has probably helped millions of people to get stoned over the years while THC took all the credit, and its discovery could drastically change the future of cannabis research.
What Makes THCP So Powerful?
The existence of THCP was announced to the world in a study that appeared in the journal Nature earlier this year[i]. According to the study authors, the potency of this newly-discovered molecule is derived from its alkyl side chain, which is longer than that of THC and therefore enables more efficient binding with the body’s cannabinoid receptors.
Previous research has shown that a cannabinoid must have a minimum of three carbon links in its alkyl side chain in order to bind to the CB1 receptor, and that binding affinity increases with every additional link until maximum activity is reached at eight links, after which affinity begins to decrease. Both THC and CBD have five links in their side chains, and until now, no natural cannabinoids with more than five links had ever been identified in marijuana.
To their surprise, however, the researchers found that THCP contains seven links in its alkyl side chain, leading them to suspect that it must be considerably more potent than THC. To test this, they checked the binding affinity of THCP to purified human CB1 receptors in a petri dish, which turned out to be 33 times higher than that of THC. Now that’s a spicy meatball.
Against the CB2 receptor, the binding affinity of THCP was five to ten times higher than that of THC.
The study authors then tested the effects of THCP on mice, and found that the rodents got severely stoned at a dose of just 5mg per kilogram of body weight. To put that into perspective, scientists never even bother using less than 10mg per kilogram of body weight when carrying out experiments with regular THC, as doses that low never have any effect.
Why Is This Significant?
The team responsible for identifying THCP say that its discovery significantly advances our understanding of the pharmacological effects of marijuana, and sheds light on why some cultivars generate experiences that can’t be explained by THC alone. In therapeutic contexts, the fact that different patients tend to react differently to cannabis-based medications containing equal doses of THC has created a great deal of confusion, yet the study authors say this can now be accounted for by presence of highly potent cannabinoids like THCP.
By studying THCP further, it may be possible to deepen our understanding of why certain cannabis extracts produce certain effects. Becoming familiar with the pharmacological properties of THCP will also open the door to the creation of new cultivars containing high levels of this particular cannabinoid, which can be specifically targeted for people seeking certain psychotropic or medicinal effects.
And For An Added Bonus…
Aside from THCP, the researchers also discovered a corresponding CBD homolog with seven links in its alkyl side chain, which they have called cannabidiphorol (CBDP). However, because CBD has a low affinity for both the CB1 and CB2 receptors, the team decided not to investigate how CBDP interacts with the body’s cannabinoid system.
Instead, they recommend further research be carried out in order to determine the anti-inflammatory, anti-oxidant and anti-epileptic potential of CBDB.
[i] Citti C, Linciano P, Russo F, Luongo L, Iannotta M, Maione S, Laganà A, Capriotti AL, Forni F, Vandelli MA, Gigli G. A novel phytocannabinoid isolated from Cannabis sativa L. with an in vivo cannabimimetic activity higher than Δ 9-tetrahydrocannabinol: Δ 9-Tetrahydrocannabiphorol. Scientific reports. 2019 Dec 30;9(1):1-3. – https://www.nature.com/articles/s41598-019-56785-1