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Cannabis is known to produce more than 120 unique cannabinoids, which interact with the endocannabinoid system (ECS) – a major neurotransmitter system in the human body.

The wide-ranging ECS is believed to regulate homeostasis in many physiological processes, including those related to pain, inflammation, metabolism, and mood.1

The ECS produces two natural endocannabinoids –  anandamide and 2-arachidonyl glycerol. These bind with, and influence, the activity of cannabinoid receptors (CB1 and CB2) in the brain, central nervous system, and immune cells.2

Plant-derived cannabinoids in cannabis also interact with the ECS, including delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). 

While THC and CBD are among the most studied cannabinoids for their therapeutic value, including pain-relieving and anti-inflammatory properties,3 a number of so-called minor cannabinoids are garnering attention from researchers. 

Below is information about two minor cannabinoids that are being researched for their potential therapeutic properties.

THCV is a non-intoxicating derivative of THC – the psychoactive ingredient in cannabis associated with its “high.” While THCV and THC share a similar chemical structure, THCV is an antagonist of CB1 whereas THC activates the cannabinoid receptor.

Preliminary studies suggest that THCV holds promise in the treatment of obesity, certain disordered eating, and diabetes. More research, however, must be done to fully understand the effects of THCV in humans.

Weight Control

Commonly referred to as the “munchies,” increased appetite can often be a side-effect of THC consumption. Early research, however, suggests that THCV may have the opposite effect.

Since first being isolated in 1971, low doses of THCV have been shown to reduce food intake and prompt weight reduction in mice.4

As a result, researchers believe THCV may have appetite-suppressing properties that can encourage weight loss, treat binge-eating disorders, and regulate the intake of food for other health reasons.

Diabetes

In insulin-resistant obese mice, THCV has also been shown to improve glucose tolerance, insulin sensitivity, and insulin signaling in liver and muscle cells.5 As such, THCV may be a potential treatment for obesity-related glucose intolerance.

Moreover, in a double-blind, placebo-controlled clinical trial on 62 people with type 2 diabetes, THCV was shown to decrease fasting blood sugar levels, increase adiponectin (a protein that regulates blood sugar), and improve beta cell functions that support sufficient insulin secretion.6

Like CBD, CBDV is a psychoactive but non-intoxicating cannabinoid. First isolated in 1969, CBDV may be effective in treating a range of ailments and conditions, including epilepsy, neurological disorders, and muscular dystrophy. Typically, cannabis cultivars with higher levels of CBD will also have higher concentrations of CBDV.

Epilepsy

While the clinical use of CBD to treat certain types of epilepsy is well-documented,7 research has shown that CBDV – a homologue of CBD (the two are structurally similar) – may also have anti-epileptic properties.

When tested on rodents, CBDV reduced both the amplitude (intensity of a brain wave signal) of epileptic bursts, as well as the duration (time between waves) of these bursts. 8

Because CBDV has shown anticonvulsant activity, clinical trials on the efficacy of the cannabinoid to treat epilepsy, in addition to other types of seizures, are underway. 

Rett Syndrome

CBDV has also been studied as a possible treatment for Rett syndrome (RTT) – a rare neurological and developmental disorder that affects girls almost exclusively. 9

In a study on mice with the same genetic defect as humans with RTT, CBDV appeared to help cognitive deficits related to recognition memory, and to delay neurological defects. 10

Duchenne Muscular Dystrophy

CBDV has also been investigated for potential benefits to patients with Duchenne muscular dystrophy, a genetic disorder that causes chronic inflammation and irreversible skeletal muscle degeneration. The study, which was conducted on dystrophic mice, found CBDV acted as an anti-inflammatory while restoring and enhancing muscle function. 11 

Much like THCV, additional research into the pharmacological properties of CBDV is required. With the legalization of cannabis for recreational and medical purposes in Canada, a number of regulatory barriers to cannabinoid research have been lifted. This will allow for further investigation into the potential benefits of minor cannabinoids such as THCV and CBDV.

Please note: The information presented in this blog post is for educational purposes only. As such, Green Relief does not claim the efficacy of cannabinoid therapy in the treatment of the above conditions, diseases, and disorders.

Sources:

1. Pacher, P. The Endocannabinoid System as an Emerging Target of Pharmacotherapy. Pharmacological Reviews 58, 389–462 (2006).

2. Galiegue, S. et al. Expression of Central and Peripheral Cannabinoid Receptors in Human Immune Tissues and Leukocyte Subpopulations. Eur. J. Biochem. 232, 54–61 (1995).

3. Di Marzo, V. & Piscitelli, F. The Endocannabinoid System and its Modulation by Phytocannabinoids. Neurotherapeutics 12, 692–698 (2015).

4. Riedel G, Fadda P, McKillop-Smith S, Pertwee RG, Platt B, Robinson L. Synthetic and plant-derived cannabinoid receptor antagonists show hypophagic properties in fasted and non-fasted mice. Br J Pharmacol. 2009;156:1154–66.

5. Wargent ET, Zaibi MS, Silvestri C, Hislop DC, Stocker CJ, Stott CG, et al. The cannabinoid Delta(9)-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity. Nutr Diabetes. 2013;3:e68.

6. Jadoon KA, Ratcliffe SH, Barrett DA, Thomas EL, Stott C, Bell JD, et al. Efficacy and safety of cannabidiol and tetrahydrocannabivarin on glycemic and lipid parameters in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel group pilot study. Diabetes Care. 2016;39:1777–86.

7. O’Connell, Brooke & Gloss, David & Devinsky, Orrin. (2017). Cannabinoids in treatment-resistant epilepsy: A review. Epilepsy & Behavior. 70. 10.1016/j.yebeh.2016.11.012.

8. Fabio Arturo Iannotti, Charlotte L. Hill, Antonio Leo, Ahlam Alhusaini, Camille Soubrane, Enrico Mazzarella, Emilio Russo, Benjamin J. Whalley, Vincenzo Di Marzo, and Gary J. Stephens. Nonpsychotropic Plant Cannabinoids, Cannabidivarin (CBDV) and Cannabidiol (CBD), Activate and Desensitize Transient Receptor Potential Vanilloid 1 (TRPV1) Channels in Vitro: Potential for the Treatment of Neuronal Hyperexcitability. ACS Chemical Neuroscience. 2014 5 (11), 1131-1141. DOI: 10.1021/cn5000524.

9. Vigli, D., Cosentino, L., Raggi, C., Laviola, G., Woolley-Roberts, M., & De Filippis, B. (2018). Chronic treatment with the phytocannabinoid Cannabidivarin (CBDV) rescues behavioural alterations and brain atrophy in a mouse model of Rett syndrome. Neuropharmacology140, 121-129. https://doi.org/10.1016/j.neuropharm.2018.07.02.

10. Zamberletti, Erica & Gabaglio, Marina & Piscitelli, Fabiana & Brodie, James & Woolley-Roberts, Marie & Barbiero, Isabella & Tramarin, Marco & Binelli, Giorgio & Landsberger, Nicoletta & Kilstrup-Nielsen, Charlotte & Rubino, Tiziana & Di Marzo, Vincenzo & Parolaro, Daniela. (2019). Cannabidivarin completely rescues cognitive deficits and delays neurological and motor defects in male Mecp2 mutant mice. Journal of Psychopharmacology. 33. 026988111984418. 10.1177/0269881119844184.

11. Iannotti, Fabio Arturo & Pagano, Ester & Moriello, Aniello & Alvino, Filomena & Sorrentino, Nicolina & D’Orsi, Luca & Gazzerro, Elisabetta & Capasso, Raffaele & Leonibus, Elvira & De petrocellis, Luciano & Di Marzo, Vincenzo. (2018). Effects of non-euphoric plant cannabinoids on muscle quality and performance of dystrophic mdx mice. British journal of pharmacology. 10.1111/bph.14460.

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