Synthetic THCv vs. Natural THCv
https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-020-0016-7
Δ9-Tetrahydrocannabivarin (THCV): a commentary on potential therapeutic benefit for the management of obesity and diabetes
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).
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that rimonabant is effective in controlling blood glucose levels and reducing weight in obese patients; however, it was withdrawn from the global market in 2008 due to increased incidences of nausea, upper respiratory tract infections, and serious psychiatric side effects including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.