By @RQueim
We, the “general public”, tend to associate cannabis with its main and most famous compounds with pharmacologic effect, THC and CBD, and with their most characteristic effects like hunger, drowsiness, and some other brain-level effects more complex to define. In other spheres, forensic for instance, they have been discussing THCV (tetrahydrocannabivarin) since the year 2000, as a marker to determine if the presence of THC in biological samples came from the consumption of drugs like Sativex or, otherwise, from the consumption of cannabis.
That was the first utility of this cannabinoid, for obvious reasons if we look at it from the perspective of chemical structure. Don’t worry, I’ll use some drawings to make it easy to understand for those lacking expertise in organic chemistry.
The relation between the THC and CBD is very easy to explain if we focus on their graphic representations (FIG 1). If you look at them you can clearly see how the content of THC and CBD can be modified by the way the plant is conserved or dried, depending on the maturity stage of the plant, or even the way it is consumed, for instance because of the heat in the combustion.
(PIE:) Structure of THC (1) and CBD (2). The difference can be seen here, and it is the opening in one of its rings.
The opening can occur in a relatively easy way, in the presence of a bit of humidity or a catalyst like sunlight or the heat from combustion. For this reason, the established differentiation between the different cannabis according to their content in CBD/THC, (like the sativa / indica classification) is to a certain extent something used only for guidance. It’s just a matter of letting the plants mature longer or to dry them under the sun to turn a big part of the THC into CBD. It means as well that the synthetic origin of both compounds is the same, and that is why there is a close relation. In other words, if there is no THC there will not be any CBD, or, for it to have CBD it must have had THC before.
Well, in the case of this cannabinoid, the THCV and its open-ring analogous compound CBDV, things are a bit tricky. Here the difference lies in the aliphatic chain, a chain of five carbon parts in the case of THC and only three in the THCV. (Fig. 2) This means the transformation of one of them into the other is not possible, and that means their origin is different. We won’t go into what causes this difference, whether it’s the consequence of a different chemical precursor or a separate synthesis route. In this case, moreover, the amount of THCV does not have to be necessarily proportional to the THC one, so, if you would allow me to digress: Is this being considered when performing a drug test for drivers? I should look into that.
(PIE:) Fig. 2: 1) Structure of THC; 2) Structure of THCV
If we look at fig. 2, the structural difference seems minimum at first glance, that is why the possibility of false positive results in some cannabinoid detection test is plausible. Moreover, that minimum difference has pharmacological consequences. For starters, on a chemical level, a shorter aliphatic chain would mean a lower lipophilicity. We can verify this by visiting a database like pubchem, where we will indeed find two different values for XLogP3: 7 for THC and 5,9 for THCV. This value gives us an idea of its affinity for fatty or watery substances. The higher the value, the higher its lipophilicity, meaning it penetrates better the fatty layers, like cell membranes. This means THC will have an easier access to our brain, and it will also take longer to be eliminated from the body. In pharmacological terms, that tiny difference has important consequences. For starters, CBDV and CBD administered orally to rats appeared in higher concentration in the rats’ brains than THCV. On the other hand, one of the characteristics of this cannabinoid is its antioxidizing power. It also causes certain effects in the glutamate circuitry, which has led some authors to describe it as a promising tool for treating Parkinson.
That last bit has proved interesting enough to draw attention on this cannabinoid, although not really in the Parkinson investigation field. See, this cannabinoid activates CB2 receptors but at the same time antagonizes the CB1 receptors. That means some of its effects will be the opposite of those of the THC. Which ones, for example? Well, the influence on appetite is one of them. And considering the obesity epidemic that we might be facing in the near future could turn it into a key molecule for studying. It can suppress appetite, as it does the rimonabant drug, another well-known antagonist of the CB1 receptors.
Regarding the effects of THC vs those of THCV, let’s talk about a pilot study performed in 2015. The investigation had clear limitations (mainly the limited sample studied) but it did make very interesting points. Ten cannabis consumers were orally administered either 10 grams of pure THCV or a placebo for five days, and 1mg of THC intravenous on the fifth day. It was a double-blind crossover study: neither the participants nor the investigators knew who was taking the drug and who was taking the placebo.
In the study, the THCV could not be differentiated from the placebo. What that means is the patients never got high. But they did when the THC was administered to them, although it didn’t cause psychotic problems and it didn’t affect their short-term memory either. In contrast, the group that received the placebo had their memory affected after getting high on the THC, which could mean THCV could work as protection against those undesired effects from THC.
But that’s not all. The group that took the THCV doses prior to the THC did not have their heart rate affected by the latter dose. Of course, there is a downside, as 9 of 10 patients found their “high” to be less intense. The conclusion is THCV inhibits some of the THC effects and boosts others.
So there you have some facts about this cannabinoid.
On the other hand, thanks to its capacity to suppress appetite, the cannabis varieties high on THCV are being advertised by some irresponsible individuals as good for “fighting” obesity, a condition serious enough for those who suffer from it to seek professional help and stop the nonsense. The varieties that synthesize more THCV (and CBDV too) come from areas of high temperature in Asia, like Afghanistan and Thailand.
References
1) ElSohly MA, Feng S, Murphy TP, Ross SA, Nimrod A, Mehmedic Z y Fortner N. (1999). Delta 9-tetrahydrocannabivarin (delta 9-THCV) as a marker for the ingestion of cannabis versus Marinol. Journal of Analytical Toxicology. 1999 May-Jun;23(3):222-4.
2) https://pubchem.ncbi.nlm.nih.gov/compound/93147
Consulte on February 2018
3) Deiana, S., Watanabe, A., Yamasaki, Y. et al. Psychopharmacology (2012) 219: 859. https://doi.org/10.1007/s00213-011-2415-0
4) García, C., Palomo-Garo, C., García-Arencibia, M., Ramos, J., Pertwee, R. and Fernández-Ruiz, J. (2011), Symptom-relieving and neuroprotective effects of the phytocannabinoid Δ9-THCV in animal models of Parkinson’s disease. British Journal of Pharmacology, 163: 1495–1506. doi:10.1111/j.1476-5381.2011.01278.x
5) Raffa, R. B. and Ward, S. J. (2012), CB1-independent mechanisms of Δ9-THCV, AM251 and SR141716 (rimonabant). Journal of Clinical Pharmacy and Therapeutics, 37: 260–265. doi:10.1111/j.1365-2710.2011.01284.x
6) Englund, A., Atakan, Z.,Kralj, A., Tunstall, N., Murray, R., Morrison, P., (2015), The effect of five day dosing with THCV on THC-induced cognitive, psychological and physiological effects in healthy male human volunteers: A placebo-controlled, double-blind, crossover pilot trial. Journal of Psychopharmacology. 30 (2), 140-151.