Published June 30th, 2020 by Jeev Trika

THCV, A Novel Cannabinoid

Most of us are familiar with CBD and THC, the two most common phytocannabinoids from the marijuana plant. However, there are over 100 other cannabinoids of which we have just begun to study some of the more predominant ones, like tetrahydrocannabivarin or THCV. THCV is a minor cannabinoid that comes from the marijuana plant and is sold medicinally by some marijuana stores in legal states. THCV is only present in some strains of marijuana plants, so it is a unique cannabinoid.

THCV Structure

There is only one thing that differs THC from THCV and that is the presence of a 3-carbon group instead of a 5-carbon group in the molecular structure. That makes all the difference in the effects achieved, a minor molecular change.

      Figure1. Structure of THCV 

THCV Chemistry

THCV acts as a CB1 receptor antagonist and a partial agonist of CB2. CB1 and CB2 are the two major cannabinoid receptors. It also interacts with other cannabinoid receptors including the transient receptor TRPV2, which contributes to the analgesic, anti-inflammatory and anti-cancer properties THCV is claimed to have. It is known to activate serotonin receptors and is a partial agonist of the cannabinoid receptor GPR55. 

 A receptor agonist binds to the receptor in a lock and key manner. The key (agonist) binds to the lock like in a door and opens the receptor (door) so that biological reactions can occur. An antagonist blocks the action of the receptor. An antagonist is like a key that doesn’t fit into the lock and therefore the door won’t open.

THCV as Potential Medicine

Recent years have shown an interest in THCV as a therapeutic medicine due to its many beneficial effects. THCV is an analgesic, an anti-inflammatory, and a neuroprotective of the nervous system. It has anti-nausea properties, helps with bone health and formation, is sleep promoting, acts as an anti-epileptic, anti-anxiety, and anti-psychotic, helps to lower blood sugar and cholesterol and acts as an appetite suppressant. Given all these effects, it leaves a huge area for study on applications to diseases such as chronic pain, epilepsy, insomnia, osteoporosis, diabetes, obesity, Alzheimer’s Disease, and mental problems.

THCV and Weight Loss/Obesity-

We’ve all heard of the marijuana munchies and it is well known that THC can stimulate the appetite. It is used in anorexia as an appetite stimulant. However, chronic cannabis users show an inverse relationship to obesity. A recent 2019 study, building from previous studies with similar findings, found an inverse association with chronic cannabis use and body mass index (BMI) increase. Other studies support this finding. In a study done by Le Strat and Le Foll it was found that there was a lower prevalence of obesity in cannabis users compared with non-users. Other cross-sectional findings have found similar results. Speculation on why this occurs aside from THCV involvement is that the CB1 receptors decrease after continuous or frequent marijuana use and THC, a CB1 agonist, may not be as effective at stimulating the appetite as it is for new users of marijuana. Stimulation of the CB1 receptor increases appetite and weight, so if fewer receptors exist this biologic action does not occur.

In animal studies THCV decreases appetite, increases satiety, and up regulates energy metabolism causing the animals to burn more calories than normal for age, sex, weight, race and activity.  If this same mechanism of action could be applied to humans, it would benefit the treatment of obesity and diabetes. THCV is an antagonist to CB1 while THC acts via CB1, so the effects on the receptor are exactly opposite of each other, at least at low concentrations. This, however, is not the only mechanism for the appetite decrease.

The metabolic effect of THCV can best be explained by its actions at the TRPV1 receptor in addition to its effect on CB1. THCV has been shown to restore insulin sensitivity in diet-induced obese mice and reduce obesity by regulating the metabolic processes through its interaction with this receptor. Another anti-obesity effect might be achieved through the interaction of THCV through the GPR55 receptor. The TRPV1 and GPR55 are both cannabinoid receptors. Again, more research is needed, particularly human clinical trials which has been thwarted by federal regulations against the marijuana plant and its psychoactive extracts.

 Administration of plant derived THCV to rodents resulted in weight loss, reduced food intake, reduced body fat content, increased energy expenditure and reduced liver triglycerides. It has been observed that lower doses of THCV have opposing effects compared to high doses of the cannabinoid. This needs further research to be able to determine the sweet spot or target dosage by which to achieve these appetite suppressing, calorie burning effects in humans. 

Blood Sugar Regulation

This is probably the most important role found yet for THCV. According to the results of animal studies, this cannabinoid can be useful in stabilization of the blood sugar levels due to its ability to improve glucose tolerance and help in insulin level regulation. THCV has been shown to restore insulin sensitivity and to increase glucose tolerance in animal models treated with this unique cannabinoid. THCV produced positive glycemic (blood sugar) changes in two different mouse models of obesity normalizing oral glucose tolerance tests and liver triglycerides.

In a randomized, double-blind, placebo-controlled pilot study the safety and efficacy of THCV and CBD were evaluated in patients with type 2 diabetes using glycemic and lipid parameters. Sixty-two patient volunteers with non-insulin treated type 2 diabetes were randomized to receive THCV 5 mg twice daily with a 1:1 ratio of CBD and THCV, 20:1 ratio of CBD and THCV (100 mg/5 mg. twice daily) and matched placebo for 13 weeks. THCV significantly decreased fasting plasma glucose compared to the placebo group which increased. It also improved pancreatic beta cell function. Adiponectin, the protein hormone involved in regulating plasma glucose levels and fatty acid concentrations, was increased significantly. Adiponectin has important anti-atherogenic activity.  It was concluded that CBD alone and in combination with THCV were well tolerated in type 2 diabetic patients, but CBD alone did not have any effect on glycemic parameters. It is evident that THCV may provide a therapeutic template for future drug treatments of this disease. Lipid parameters were not affected in this study. Also, interestingly, there was no change in body weight for this study group as in the animal models. Part of this effect could be due to dosage problems since the dose used was lower than in other studies where such effects were observed.

It is generally accepted that an overactive endocannabinoid system leads to abdominal obesity and other risk factors for heart disease and diabetes. THCV may be a valuable treatment, therefore, for metabolic syndrome and diabetes with beneficial effects on the heart through changing the balance of the endocannabinoid system. Furthermore, studies show that THCV might be a therapeutic target for the metabolic syndrome related disorder of fatty liver disease. Heart disease that leads to heart attack or stroke is the leading cause of death in those with diabetes.

Control of Panic Attacks

THCV has been shown to subdue anxiety similar to CBD. It has, like CBD, shown promise in controlling panic attacks without dulling emotions. It may also help in other mental disorders where panic attacks are frequent. Studies have also shown that THCV does not suppress emotions, only the ability to panic. Studies have shown a potential benefit in mental illness and cognitive impairment.

Muscle Control and Neuroprotection

THCV can reduce muscular tremors. This means that it may be highly beneficial in treating such diseases as Parkinson’s disease and amyotrophic lateral sclerosis or ALS. There is also some evidence that THCV can reduce the frequency and severity of epileptic seizures. Researchers claim that THCV can be taken preventively or during an actual seizure to obtain relief.

Given its antioxidant properties and abilities to inhibit CB1 while being a selective CB2 agonist, THCV has shown a promising pharmacological profile to delay the progression of Parkinsonian symptoms and to decrease or eliminate symptoms associated with this disorder. This was the conclusion at the termination of a study on animals. Another study on mice showed a delay in the progression of neuromuscular changes, a decrease in intensity of symptoms already present, and neuroprotection in the mice with induced Parkinson’s Disease. Current treatments for Parkinson’s Disease only treat the symptoms and do not delay the progression of the disease, thus the hunt for a novel treatment for this neuromuscular disorder.

THCV’s targets for control of epilepsy are the CB1 and CB2 receptors and the TRPV1, TRPV3 and TRPV4 receptors. THCV has shown a potential use in convulsions. Current studies are focused on the creation of marijuana strains that have a minimal amount of THC and medium THCV content. Such a balance of cannabinoids would be helpful in developing a non-intoxicating product that can be used for epilepsy treatment for patients of all ages.

In a cell study, THCV stimulated muscular cell differentiation, a factor important in treating certain degenerative muscle conditions. 

Pain and Inflammation

In a mouse study, THCV showed therapeutic potential as both an anti-inflammatory agent and as a reliever of neuropathic pain. This is just one more potential benefit in THCV’s plethora of potential healing abilities.

Anti-psychotic Effects

Activation of the serotonin receptor 5-HT1A has been shown to have anti-psychotic effects as evidenced by previous studies.  It has been reported that THCV can interact with 5-HT1A receptors in rat models who have had schizophrenia-like symptoms induced by drugs. The interaction observed in the THCV treated mice resulted in a reversal of the schizophrenia-like symptoms and improved cognitive impairment. These effects seemed to be in part mediated by the 5- HT1A receptor. Behavioral changes induced in the schizophrenic mice were reversed by the administration of THCV and social behaviors improved. The study concluded that THCV can reverse schizophrenic typical behavior, reduce the amount of time spent immobile and normalize hyper locomotor activity, social behavior, and cognitive performance.

What about the Psychoactive Properties of THCV?

Whenever anyone sees the words THC, they immediately think of getting high. THCV is no different. It has been called “the sports car of all cannabinoids.” What this means is that some sources state that this cannabinoid can provide users with a powerful high without the munchies. 

Considering THCV’s cannabinoid siblings, THC and CBD, the psychoactive properties are completely different. While the psychoactive high of THC is well known and CBD is known for its psycho-purity, what does science say about THCV? The behavior of this molecule changes with the dose. While at lower doses, THCV acts as an antagonist of CB1 receptors without providing any high feeling, the situation changes at higher doses when THCV changes and starts acting as a CB1 agonist much in the same manner as THC resulting in a euphoric high feeling.

The high caused by THCV is said to be clear-headed and stimulating unlike the effects typically associated with THC. Although, it has also been claimed to accentuate THC’s high but for a shorter length of time and without the munchies. 

Where to Find THCV, Top Ten Strains

THCV can potentially boast of many health benefits, but it is hard to find, especially in any quantity. There are some specific strains and products available if you know where to look. For example, the following ten strains have appreciable levels of THCV in them:

  • Doug’s Varin: The THCV amount ranges from 3-6%
  • Durban Poison: The concentration of THCV is about 1% but the strain suppresses the appetite and has energizing and focusing effects. More info on Durban Poison can be found on this website here
  • Pineapple Purps: The percentage THCV is about 4% and is said to be very psychoactive, creative, and energetic.
  • Power Plant: Has a high THC content and may be too intoxicating for some.
  • Jack the Ripper: Boasts a THCV content of about 5% while THC can range from 15-25%.
  • Willie Nelson: This strain provides users with a happy, creative, uplifting, euphoric effect. It can help with depression, anxiety, and stress.
  • Durban Cheese: Its effects have been described as uplifting and euphoric. It is also good for stress and pain relief.
  • Red Congolese: Effects are said to be euphoric with focus and mental clarity. It is good for nausea, tension, or stress.
  • Skunk #1: This strain offers elevated creativity with a high energy buzz.
  • Pink Boost Goddess: Contains 4.24% THCV and 18.7% THC that creates an appetite suppressant, anxiety reducing buzz.

Other Products

Level Stimulate Tablinguals contains THCV extracts with 15 mg of cannabinoid per tablingual. They are available here.

Conclusion

THCV may be a minor cannabinoid but with major potential medical benefits that warrant further study. Granted most of our research is animal based with anecdotal evidence from observations and small clinical trials, but the future is ripe with possibilities for this cannabinoid.

 
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