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THCV vs THC: What Are the Differences?

Feb 09, 2021

THCV vs THC: What Are the Differences?

Tetrahydrocannabinol (THC) and tetrahydrocannabivarin (THCV) are both cannabinoids which, if present in high enough doses, can interact with the body’s endocannabinoid receptors to induce psychoactive effects.

But that is pretty much where the resemblance ends. Despite their similar names, the two are derived from different parent molecules, elicit difference effects at different doses, and are naturally present at dramatically different levels within the cannabis plant.


What is THCV?

At first glance, the chemical structure of both compounds also appears remarkably similar – the only real difference being a longer hydrocarbon chain present on the THC molecule.


But while both molecules may look similar on the surface, they are actually derived from completely different parent molecules and chemical pathways.

THC, along with other well-known cannabinoids including cannabidiol (CBD) and cannabichromene (CBC), are derived from cannabigerolic acid (CBGA). This precursor acid itself is synthesized in a reaction between olivetolic acid and geranyl pyrophosphate.

The parent molecule for THCV and its acidic form tetrahydrocannabivarinic acid (THCVA) is cannabigerovarinic acid (CBGVA), which is formed when geranyl pyrophosphate reacts with divarinolic acid instead of the olivetolic acid that produces CBGA. Both CBGVA and CBGA go through a similar reaction with a THC synthase enzyme and subsequent decarboxylation to form THCV and THC, respectively.


At high levels, THCV can act similarly to THC as an agonist of the body’s CB1 endocannabinoid receptor, although the effects of THCV are much weaker. But crucially, there is also evidence that THCV can behave as a CB1 receptor antagonist at lower doses, meaning that it has the potential to attenuate some of the less-desirable effects of THC that are thought to be CB1 receptor mediated, such as poorer motor control, lessened cognitive function, and even the food craving “munchies.”

Like with any cannabinoid, the amount of THCV present in cannabis flower will vary greatly depending on the genetics of the strain, as the reactions that form CBGVA are catalyzed by the plant species’ natural enzymes. THCV appears to be more prevalent in strains that originated in Africa, such as Durban Poison, but there are also a number of strains that have been specially cultivated to produce higher than average levels of THCV.

But genetics alone cannot guarantee that a specific strain will contain higher amounts of THCV; the best way to be sure is to check the label and/or lab results associated with a given product. While some high-throughput forms of cannabis analysis will not routinely screen for THCV, there are high-sensitivity and high-resolution methods that allow for the quick and easy analysis of THCV content, as well as other commonly requested cannabinoids.


The potential benefits of THCV

THCV is playfully nicknamed the “race car” or the “sports car” of cannabinoids, as high doses reportedly give users a short-lasting but very energetic high. The compound has also been linked to a variety of other physiological effects that make it an notable prospect for medical cannabis research.


Appetite suppression and obesity

Its ability to inhibit the action of CB1 receptors has made it a particular focus for research into appetite regulation. Research has found that low doses of THCV in the region of 5 to 7.5 milligrams can effectively reduce appetite, while other studies have suggested that the compound may even be able to improve connectivity in certain areas of the brain that are altered in some people with obesity.

While THCV’s documented action as an appetite suppressant is of interest in terms of tackling obesity, it is also important that cannabis users who already underweight, undergoing treatment for anorexia, or who are otherwise being treated for problems with low appetite be aware of this effect, so that they can avoid products containing non-negligible amounts of THCV.


Diabetes

Slightly higher doses of THCV between 10 to 20 milligrams have been found to assist in the regulation of blood sugar levels and can reduce the body’s resistance to insulin – a finding that makes the compound of interest as a novel treatment for diabetes.

There have been numerous studies conducted into the action of THCV on various hallmarks related to diabetes, including a number of randomized controlled clinical trials. One such trial, published in the American Diabetes Association journal Diabetes Care, concluded that THCV “could represent a new therapeutic agent in glycemic control in subjects with type 2 diabetes,” after finding that the compound significantly improved pancreatic cell function while still being well tolerated by the study participants involved.


Anti-inflammatory

Another well-documented research area for THCV is its potential to act as a powerful anti-inflammatory agent.

A 2010 study published in the British Journal of Pharmacology exploring THCV’s ability to activate the body’s CB receptors found that the compound was able to decrease signs of inflammation and related inflammatory pain in mice subjects, at least partly through its effects on the CB1 and/or CB2 receptors.

More recently, THCV has appeared in a study detailing the anti-inflammatory effect of a cannabinoid formulation in tackling Covid-19-related inflammation in the lungs. The study, published last month in the Nature journal Scientific Reports, found a CBD-rich fraction of cannabinoids including cannabigerol (CBG) and a low dose of THCV “may have clinical value” in reducing Covid-19-related inflammation in lung epithelial cells.

However, the researchers also noticed the fraction was associated with pro-inflammatory activity in macrophages, which could potentially lead to a worsening of the “cytokine storm” seen in severe Covid-19 patients. As a result, the study authors urge extreme caution in proposing that cannabis treatments could be useful for Covid-19 patients, when further research and study is clearly needed. Again, it should be stressed that no healthcare personnel or patients should be using cannabis for the purpose of Covid-19 prevention or treatment.


Seizure and motor control

Seizure prevention is a hot spot for research associated with many of the most prominent cannabinoids, such as THC and CBD. Naturally then, THCV has also been investigated as a potentially useful anticonvulsant medication.

One 2010 study, which encompassed an in vitro study of THCV on a brain slice model of epileptic activity, a CB1 receptor binding assay, and a general study of laboratory rats, found THCV to exhibit good antiepileptic and anticonvulsant effects when administered either during a seizure, or as a regular preventative medication. While there are cannabinoid formulations currently already approved in several countries as a treatment for select drug-resistant epilepsies, THCV appears to hold potential as a valid alternative if it can demonstrate similar promise in future clinical trials.

Epilepsy is not the only neurological disorder that has been tied to possible treatment with THCV. An experimental study using a rat model of Parkinson’s disease found that acute treatment with THCV was able to attenuate motor inhibition linked to Parkinson’s disease. Chronic administration of THCV was also seen to delay the progression of the disease by slowing the loss of neurons in the mid-brain.


Is THCV legal?

The legality of THCV is a complicated question.

Although THCV is structurally very similar to THC, it is not explicitly a prohibited substance at the federal level in the United States – but it is a gray area.

THCV does not fall under the definition of any of the “cannabimimetic agents” prohibited under the Controlled Substances Act, nor would it technically be included under the category of “tetrahydrocannabinols,” which are also prohibited under the act. While the act does prohibit cannabis and cannabis extracts, THCV could still possibly be legally derived from hemp under the provisions of the 2018 Farm Bill.

The potential gray area comes with the Federal Analogue Act, which may consider THCV to be structurally similar enough to THC to treat as scheduled substances. However, current feelings among legal and scientific minds familiar with the cannabis industry would indicate that THCV is substantially different enough to avoid being treated as an analogue and falling under the prohibited “tetrahydrocannabinols” label.

Conversely, in the United Kingdom, THCV is still considered a cannabinol derivative and is listed as a Class B drug under the Misuse of Drugs Act 1971 and a Schedule 1 drug under the Misuse of Drugs Regulations 2001. The issue of THCV being included under these rules was brought to ministers at least twice by the Advisory Council on the Misuse of Drugs, but presently THCV has remained in Class B and Schedule 1 with “no recognised medicinal benefit in the UK” and can only be researched under a special license awarded by the Home Office.


For earlier installments of this article series, see:


Alexander Beadle

Science Writer

@alexbeadlesci

Alexander Beadle has been working as a freelance science writer since 2017 and has covered the cannabis industry for Analytical Cannabis since 2018. He has also written for our sister publication, Technology Networks, and the cannabis industry consultant firm Prohibition Partners, among others. Alexander holds an MChem in materials chemistry from the University of St Andrews, where he won a Chemistry Purdie Scholarship and conducted research into zeolite crystal growth mechanisms and the action of single-molecule transistors.

 

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