The cannabinoid Δ9-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity

Summary & key facts

Researchers tested THCV, a cannabinoid compound, in two types of obese mice and in insulin-resistant liver and muscle cells. THCV was given by mouth in doses ranging roughly from 0.1 to 12.5 mg/kg for 30–45 days. It did not lower food intake or body weight in these obese mice. However, THCV raised energy use briefly, improved glucose tolerance and insulin sensitivity in diet-induced obese mice, and dose-dependently reduced glucose intolerance in genetically obese (ob/ob) mice. In cell experiments, THCV restored insulin signalling in insulin-resistant hepatocytes and myotubes. The experiments were done in mice and cells, so effects in people were not tested in this paper.

Key facts:

• THCV was given orally in mouse studies at doses from about 0.1 to 12.5 mg/kg, with treatment periods of about 30–45 days across different experiments.
• THCV did not produce a significant change in food intake or body weight gain in any of the mouse studies reported.
• THCV produced an early, transient increase in energy expenditure in the mice.
• In diet-induced obese (DIO) mice, THCV improved glucose tolerance and increased insulin sensitivity compared with vehicle-treated mice.
• In genetically obese ob/ob mice, THCV reduced glucose intolerance in a dose-dependent way.
• THCV did not consistently change plasma lipids (total cholesterol or HDL) across the studies.
• In cell experiments, insulin-resistant hepatocytes and C2C12 myotubes treated with 1, 3 and 10 μM THCV showed restoration of insulin signalling.
• The study used the CB1 inverse agonist AM251 as a positive control; THCV is described as a neutral CB1 antagonist with different pharmacology from inverse agonists.

Abstract

THCV is a new potential treatment against obesity-associated glucose intolerance with pharmacology different from that of CB1 inverse agonists/antagonists.

Topics

Cannabis and Cannabinoid Research Neurotransmitter Receptor Influence on Behavior Pancreatic function and diabetes

Categories

Health Sciences Medicine Pharmacology

Tags

Agonist AM251 Body weight Cannabinoid receptor Diabetes mellitus Endocrinology Insulin Insulin resistance Internal medicine Medicine Receptor Type 2 diabetes Weight gain

Substances

Cannabis