Δ9-Tetrahydrocannabivarin (Δ9-THCV)

Cannabinoid industry has been proliferating in the past decade with removal of some regulatory barriers and more favorable political landscape following recent nation-wide legalization in Canada. Major focus of cannabinoid research has been heavily emphasized on the major cannabinoids, THC (Δ9-tetrahydrocannabinol) and CBD (cannabidiol). However, cannabis contains over 100 other phytocannabinoids, and with the acceleration of research, less abundant but important minor cannabinoids and their therapeutic potentials have been identified including CBG (cannabigerol), CBN (cannabinol), CBC (cannabichromene), and Δ9-THCV (Δ9-tetrahydrocannabivarin).

A naturally occurring analog of THC, Δ9-THCV, is a phytocannabinoid that acts as an inverse agonist / neutral antagonist of the CB1 receptors and partial agonist of CB2 receptors. Unlike THC, Δ9-THCV is non-psychoactive and has been getting a lot of attention along with other minor phytocannabinoids [1]. More surprising difference between THC and Δ9-THCV is their effects in appetite. While THC generally induces feeding behavior and enhanced appetite, Δ9-THCV can suppress appetite and has hypophagic effects suggesting its potential for weight management [2]. Endocannabinoid system is responsible for various functions including feeding behavior, maintenance of energy homeostasis and glucose metabolism [3]. Δ9-THCV also showed metabolically beneficial effects through its action with CB1 receptors in rodent studies on obesity and insulin sensitivity [1, 4]. Moreover, Δ9-THCV has demonstrated many promising results in animal models of seizure, Parkinson’s disease, and inflammation [5-7].

Another brain function endocannabinoid system plays crucial role is related to addictive drug-induced reward and relapse. In animal models against a broad range of addictive drugs, CB1 antagonists and CB2 agonists have shown anti-addiction efficacy [8]. Since Δ9-THCV’s mechanism of action involves CB1 antagonism and CB2 agonism, its more stable synthetic analog, Δ8-THCV was tested in rodent models of nicotine dependence. Δ8-THCV significantly decreased nicotine craving, self-administration, and nicotine withdrawal in rodents [9]. Minor phytocannabinoids including Δ9-THCV have been receiving increasing attention for their therapeutic potentials recently, and it is a matter of time before they become as widespread as major cannabinoids.

While potential therapeutic benefits of various cannabinoids are undisputable, these compounds are known for their highly lipophilic nature. This leads to an issue of absorption as human bodies are not capable of absorbing lipophilic compounds efficiently. For instance, oral bioavailability of CBD can be as low as 6%. This means we need to consume significantly more in quantity and waste the unabsorbed portion of the drug. This applies to Δ9-THCV and other minor phytocannabinoids. Increasing the bioavailability and absorption rate can decrease the consumed amount while achieving the therapeutic benefit. By doing so, side-effects associated to active ingredients are also reduced since less amount is consumed. Learn more about our SSRM technology to enhance bioavailability and absorption with much faster onset of action.

  1. Abioye, A., Ayodele, O., Marinkovic, A., Patidar, R., Akinwekomi, A., & Sanyaolu, A. (2020). Δ9-Tetrahydrocannabivarin (THCV): a commentary on potential therapeutic benefit for the management of obesity and diabetes. Journal of cannabis research, 2(1), 6. https://doi.org/10.1186/s42238-020-0016-7
  2. Riedel, G., Fadda, P., McKillop-Smith, S., Pertwee, R. G., Platt, B., & Robinson, L. (2009). Synthetic and plant-derived cannabinoid receptor antagonists show hypophagic properties in fasted and non-fasted mice. British journal of pharmacology156(7), 1154–1166. https://doi.org/10.1111/j.1476-5381.2008.00107.x
  3. McPartland, J. M., Duncan, M., Di Marzo, V., & Pertwee, R. G. (2015). Are cannabidiol and Δ(9) -tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review. British journal of pharmacology, 172(3), 737–753. https://doi.org/10.1111/bph.12944
  4. Wargent, E. T., Zaibi, M. S., Silvestri, C., Hislop, D. C., Stocker, C. J., Stott, C. G., Guy, G. W., Duncan, M., Di Marzo, V., & Cawthorne, M. A. (2013). The cannabinoid Δ(9)-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity. Nutrition & diabetes, 3(5), e68. https://doi.org/10.1038/nutd.2013.9
  5. Hill, A. J., Weston, S. E., Jones, N. A., Smith, I., Bevan, S. A., Williamson, E. M., Stephens, G. J., Williams, C. M., & Whalley, B. J. (2010). Δ⁹-Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats. Epilepsia, 51(8), 1522–1532. https://doi.org/10.1111/j.1528-1167.2010.02523.x
  6. García, C., Palomo-Garo, C., García-Arencibia, M., Ramos, J., Pertwee, R., & Fernández-Ruiz, J. (2011). Symptom-relieving and neuroprotective effects of the phytocannabinoid Δ⁹-THCV in animal models of Parkinson’s disease. British journal of pharmacology, 163(7), 1495–1506. https://doi.org/10.1111/j.1476-5381.2011.01278.x
  7. Bolognini, D., Costa, B., Maione, S., Comelli, F., Marini, P., Di Marzo, V., Parolaro, D., Ross, R. A., Gauson, L. A., Cascio, M. G., & Pertwee, R. G. (2010). The plant cannabinoid Delta9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice. British journal of pharmacology, 160(3), 677–687. https://doi.org/10.1111/j.1476-5381.2010.00756.x
  8. Galaj, E., & Xi, Z. X. (2019). Potential of Cannabinoid Receptor Ligands as Treatment for Substance Use Disorders. CNS drugs, 33(10), 1001–1030. https://doi.org/10.1007/s40263-019-00664-w
  9. Xi, Z. X., Muldoon, P., Wang, X. F., Bi, G. H., Damaj, M. I., Lichtman, A. H., Pertwee, R. G., & Gardner, E. L. (2019). Δ8 -Tetrahydrocannabivarin has potent anti-nicotine effects in several rodent models of nicotine dependence. British journal of pharmacology, 176(24), 4773–4784. https://doi.org/10.1111/bph.14844

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