Δ9-Tetrahydrocannabivarin (THCV)

Δ9-Tetrahydrocannabivarin (THCV) is a cannabis-derived compound with unique properties that set it apart from the more common cannabinoids, such as Δ9-tetrahydrocannabinol (THC). The main advantage of THCV over THC is the lack of psychoactive effects. In rodent studies, THCV decreases appetite, increases satiety, and up-regulates energy metabolism, making it a clinically useful remedy for weight loss and management of obesity and type 2 diabetic patients. The distinctions between THCV and THC in terms of glycemic control, glucose metabolism, and energy regulation have been demonstrated in previous studies. Also, the effect of THCV on dyslipidemia and glycemic control in type 2 diabetics showed reduced fasting plasma glucose concentration when compared to a placebo group. In contrast, THC is indicated in individuals with cachexia. However, the uniquely diverse properties of THCV provide neuroprotection, appetite suppression, glycemic control, and reduced side effects, etc.; therefore, making it a potential priority candidate for the development of clinically useful therapies in the future. Hopefully, THCV could provide an optional platform for the treatment of life-threatening diseases.

Background

The therapeutic benefits of the extracts from the plant Cannabis sativa L. and its subspecies (hemp, marijuana) have been extensively studied. Cannabidiol (CBD), Δ-9-tetrahydrocannabinol (THC) and Δ-9-tetrahydrocannabivarin (THCV) are the major components isolated from Cannabis sativa and have been reported extensively in modern literature. THC is the primary psychoactive component of Cannabis sativa and its medicinal properties are attributed to its specific interaction with the endocannabinoid system (ECS) (Borgelt et al. 2013; McPartland et al. 2015; Chakrabarti et al. 2015). ECS consists of two types of endogenous G protein-coupled cannabinoid receptors (CB1 and CB2) that are located in the mammalian brain and throughout the central and peripheral nervous systems (Pertwee 2008; Solinas et al. 2008). The EC system represents a major neuromodulatory system involved in the regulation of emotional responses, behavioral reactivity, and social interactions. Pathophysiologic manipulation of the ECS has been exploited as a key tool in the management of severe disease conditions of the central nervous system. For example, in recent years, elements of the ECS and its pathways have been explored as therapeutic measures for mitigating some central nervous system diseases such as Autism Spectrum Disorder (ASD) and epilepsy (Chakrabarti et al. 2015). The endocannabinoid system is also responsible for the maintenance of energy homeostasis and the regulation of lipid and glucose metabolism (McPartland et al. 2015). In the same vein, molecular markers have been identified in the ECS membrane transporters (AM404) that could trigger autistic behavior when the cannabinoid receptors are activated (Chakrabarti et al. 2015).

THC produces various psychoactive effects by activation of the CB1 cannabinoid receptors in the brain, especially the basal ganglia, substantia nigra, globus pallidus, hippocampus, cerebellum, etc. These locations indicate that THC is involved in the modulation of memory, emotions, and movement. Activation of the CB1 receptors leads to inhibition of adenylyl cyclase and blockade of voltage-operated calcium channels, which in turn suppresses neuronal excitability and inhibition of neurotransmission of serotonin (Pertwee 2008). Therefore, the therapeutic benefits of THC include the management of conditions associated with depression, Parkinson’s disease, Alzheimer’s disease, resistant childhood seizures, chronic pain, multiple sclerosis, convulsions, glaucoma, neuropathic pain and a variety of other conditions (Hill 2015; Grant et al. 2012). It is important to note that Cannabis sativa is not a miracle plant. Despite the medicinal benefits of marijuana, its chronic use has been linked with conditions such as psychotic disorders and cannabis use disorder, while acute consumption is linked to psychotic symptoms, hyperemesis syndrome and anxiety (Bridgeman and Abazia 2017).

Therefore research efforts have been intensified to develop several synthetic high-affinity analogs of CB1 cannabinoid receptor antagonists and inverse agonists as therapeutic drugs for the management of drug dependence, metabolic syndrome, and diabetes. Literature is replete with inverse agonists of the CB1 cannabinoid receptors that have been developed for the management of drug dependence, metabolic syndrome, type 2 diabetes and dyslipidemia (Brown 2007).

Δ9-Tetrahydrocannabivarin (THCV)

Rimonabant, a first-generation synthetic inverse agonist / selective antagonist of the CB1 receptor, was approved in Europe in 2006 for the treatment of anorectic obesity (Bridgeman and Abazia 2017). This drug exerts its effect on the ECS by selectively blocking the CB1 receptors; thus, reducing appetite and inducing hypophagia. In a randomized double-blind, rimonabant-placebo controlled trial; rimonabant produced a significant reduction in body weights of subjects from 2.6 to 6.3 kg relative to placebo among the groups taking 20 mg of rimonabant daily. HbA1C in obese patients decreased by 0.5–0.6% compared to metformin or sulphonylurea, and 0.8% reduction compared to 0.3% reduction in placebo group. High-density lipoproptein cholesterol (HDL-C) also increased significantly by 22.3% compared with 13.4% in the placebo group while the level of triglycerides decreased in all trials by 6.8% compared with an increase of 8.3% in the placebo group (p < 0.0001). The levels of adiponectin, a protein hormone regulating glucose level and fatty acid breakdown in humans, increased significantly by 23% from the baseline in the 20 mg rimonabant group. It was concluded that rimonabant is effective in controlling blood glucose levels and reducing weight in obese patients; however, it was withdrawn from the global market in 2008 due to increased incidences of nausea, upper respiratory tract infections, and serious psychiatric side effects including depression and suicide ideation (Buggy et al. 2011; Christopoulou and Kiortsis 2011; Le Foll et al. 2009). This left a huge research gap as many pharmaceutical companies abandoned the development of inverse CB1 receptor agonists. It was opined that the development of novel compounds that are neutral antagonists of the CB1 receptor with selectivity for peripheral receptors may be of great value in obtaining similar metabolic results with little or no psychiatric adverse effects. Therefore, research in this area is continuous.

THCV is an inverse agonist / selective antagonist of the CB1 receptor, similar to rimonabant but it does not have the identified adverse effects of rimonabant. This short review discusses the potential therapeutic benefits of THCV, a naturally occurring analog of THC, in the management of obesity and type 2 diabetes, its potential side effects, and the mechanism of action within the ECS.

What are THCV’s effects and benefits?

As its name suggests, THCV is similar to THC in molecular structure and psychoactive properties, but it provides a variety of pronounced and altogether different effects. A note for vaporizer enthusiasts: THCV has a boiling point of 428 °F (220 °C), so you’ll need to turn it up higher than you would THC.

  • THCV is an appetite suppressant. In contrast to THC, THCV may dull the appetite. This may be good for consumers focused on weight loss, but THCV should be avoided by patients treating appetite loss or anorexia.
  • THCV may help with diabetes. Research shows promise in THCV’s ability to regulate blood sugar levels and reduce insulin resistance.
  • THCV may reduce panic attacks. It appears to curb anxiety attacks in PTSD patients without suppressing emotion.
  • THCV may help with Alzheimer’s. Tremors, motor control, and brain lesions associated with Alzheimer’s disease appear to be improved by THCV, but research is in progress.
  • THCV stimulates bone growth. Because it promotes the growth of new bone cells, THCV is being looked at for osteoporosis and other bone-related conditions.

Where can I find THCV?

So you’re looking for the effects mentioned above, but you aren’t sure where to start your search for high-THCV strains and products. Most strains only contain trace, undetectable amounts of THCV, making it difficult to achieve the desired therapeutic effect. We can assume that more THCV-rich products will be introduced alongside its growing popularity, but in the meantime, here are some useful hints for locating this rare therapeutic gem.

  • Look for African sativas. Lab results show that THCV is most abundant in sativas, particularly landrace strains from Africa. Durban Poison is one of the more common high-THCV strains, but other options can be found in the strain list below.
  • Ask about parent genetics. Having trouble finding an African sativa? Plenty of strains have hybridized African genetics that predispose it to a higher THCV potential. Cherry Pie, for example, may express a high THCV content by way of its Durban Poison parent. Look for lineage information in Leafly’s strain pages or ask your budtenders to point out their African hybrids.
  • Request test results. Genetics alone can’t promise a high-THCV content, and cannabinoid contents can vary from harvest to harvest. If possible, ask your budtender for lab-tested strains to ensure that you’re indeed getting a THCV-rich product.

How THCV works

Like all other phytocannabinoids, THCV is synthesized in the cannabis trichomes, the glandular hairs found on the surface of the plant. THCV binds to both CB1 and CB2 receptors, the most studied cannabinoid receptors in the body. 

Δ9-Tetrahydrocannabivarin (THCV)

Can THCV get you high?

In many ways, THCV lives in the shadows compared to other cannabinoids. Research is only just beginning to examine the molecule’s effects and potential. THCV’s psychoactive potential is complex and largely dependent upon dosing. Given its low concentrations in cannabis cultivars, THCV is not yet available as an isolated concentrate on its own so the question is a bit of a moot point right now. Many strains high in THCV are also high in THC so the high is built in. 

Is THCV legal?

There isn’t yet much legislation specifically dictating the legal status of THCV. On the one hand, THCV is not explicitly included on the list of federally banned substances. On the other hand, substances, including flower, high in THCV may by definition be illegal at the federal level since they are, in effect, marijuana.

If you live in a weed-legal state, you’ll be able to find products containing THCV quite easily, including strains with THCV. However, if you live in a place where marijuana is illegal, THCV products will probably be much harder to find and of questionable legality. The one exception may be hemp-derived CBD oils that happen to also contain THCV.

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