The science of THCV
Cannabis research has historically concentrated on THC and CBD, and for good reason. These two ‘major cannabinoids’ dominate the cannabinoid profiles of almost all cultivars available to medical cannabis. . .
Cannabis research has historically concentrated on THC and CBD, and for good reason. These two ‘major cannabinoids’ dominate the cannabinoid profiles of almost all cultivars available to medical cannabis patients around the globe. But recently, there has been a shift towards interest in the distinct pharmacological properties of comparatively rare cannabinoids, THCV in particular. James Duckenfield,CEO ofGlass Pharms®, explains why the emerging evidence is compelling, while cautioning that scientific promise should not be taken as outright clinical evidence. Since its inception, the wider cannabis industry has measured a cultivar (often referred to as a strain) on its potency, usually its THC content, as the most prized measure of value and prestige. But as the sector evolves, and the idea of cannabis as an effective therapeutic option becomes more accepted, the questions being posed around the plant and its medicinal compounds are becoming more specific. THC and CBD potency are still very much a relevant consideration, particularly around consistency and accurate dosing, but as we learn more about the true myriad compounds, not only cannabinoids, but also terpenes, flavonoids and other phytochemicals, our understanding of what shapes a cultivar’s effects has inevitably become more nuanced. And this is where THCV has entered the conversation, especially here atGlass Pharms. What is THCV, and what makes it scientifically and potentially therapeutically distinctive?Tetrahydrocannabivarin, or THCV, is a naturally occurring cannabinoid found in cannabis. Most cultivars contain only tiny amounts, which is one reason it has received far less attention than THC or CBD. THCV is closely related to THC, though its route of production is quite different. The “V” refers to thevarin branch of cannabinoids. THCV begins with divarinolic acid, while THC begins with olivetolic acid. The two compounds also have slightly different chemical structures: THCV has a three-carbon side chain, compared with THC’s five-carbon chain. This matters because THCV is not created when THC degrades, nor can it be produced by processing a THC-dominant cultivar, as is the case with certain other cannabinoids. The plant needs to start with the right genetics to make THCV. During growth, those genetics allow the plant to produce THCV through compounds known as CBGVA and THCVA. Heat then converts THCVA into THCV. For patients, the important point is that THCV-rich cultivars are chemically distinct from conventional THC-dominant cultivars. They are not simply high-THC plants with a different label. THC activates CB1 receptors, which not only explains the intoxicating effects it can offer at certain doses, but alsomuch of its therapeutic properties. Through its interactions with the endocannabinoid system receptors, THC can influence pain signalling, nausea and vomiting, muscle spasticity, appetite and sleep. THCV can interact with the same system, though it appears to do so in quite a different way. READ MORE…The pharmacology of THCV and emerging research are just as interestingTHCV can act differently at the CB1 receptor depending on the dose taken. At lower doses,it is generally described as a neutral antagonist. In simple terms, it can sit at the receptor without switching it on, while limiting the ability of cannabinoids such as THC to activate it. At higher doses,THCV may start to act as apartial CB1 agonist, producing some receptor activation of its own. This changing activity is one reason researchers are still working to understand its full effects. CB1 receptors are also involved in the brain’s regulation of hunger, reward, and the pleasure associated with food. THC’s strong interaction with CB1 receptors helps explain its well-known tendency to stimulate appetite. And as THCV can alter signalling at the same receptor, researchers have begun to look at whether it may affect appetite and food reward differently. Its activity at CB2 has also widened interest in its potential role in inflammation and metabolic health. Two human studies give an early sense of where that research is heading:Asmall trial involving people with type 2 diabetesexamined glycaemic and lipid markers. A90-day studyinvolving 44 participants compared two doses of a combined THCV and CBD formulation with placebo, looking at weight loss and metabolic markers. Both produced encouraging findings, but neither can give a definitive answer about THCV’s full clinical potential. The studies were small, and the later trial used THCV alongside CBD, so it doesn’t prove that the results come from THCV alone. Any conversation about using CB1 signalling to influence appetite also has to consider the case of rimonabant, another weight-management compound developed to interact with CB1 receptors. Why is THCV not simply another rimonabant?Rimonabant was a synthetic drug developed for weight management in the mid-2000s. It targeted CB1 receptors and initially appeared very promising, but concerns quite quickly emerged around depression, anxiety and suicidal thoughts, leading to thesuspension of its European marketing authorisation in 2008. The difference between rimonabant and THCV lies in how they affect CB1. Rimonabant was a CB1‘inverse agonist’, meaning it effectively blocked the receptor while also reducing its normal background activity. At lower doses, THCV is generally described as a‘neutral antagonist’. It may limit CB1 activation without suppressing that usual background signalling. And at higher doses, research suggests THCV may begin to act as a partial CB1 agonist, which is the total opposite effect of rimonabant. This difference is scientifically important, but it does not prove that THCV will avoid the same risks or definitely work as a therapeutic option for weight loss or management. Those questions need larger and longer human studies before any concrete claims can be made. From cannabinoid potency to cannabinoid precisionThe next stage of cannabinoid medicine will need more than cultivars with higher levels of THC or CBD. Researchers and clinicians need cannabis with clear, repeatable chemical profiles, so they can understand what they are studying and prescribing. At Glass Pharms®, that starts with genetics. Our next-generation glasshouse cultivation facilityis designed to help deliver consistency. We work from carefully selected tissue-culture clones rather than seed. This means each crop begins with the same genetic blueprint. Controlled growing conditions and analytical testing then help us produce cultivars with dependable cannabinoid profiles from one harvest to the next. THCV-rich genetics are just one part of that work. Glass Pharms is currently developing a THCV-dominant cultivar as part of its wider cultivation programme, including a novel plant called THCV HarmonyⓇThe science is still in its early stages, but consistent cultivars with distinctive cannabinoid profiles give researchers a better basis for understanding their potential. This is the kind of careful work cannabinoid-based medicine needs, from the genetics of the plant through to clinical research.