Obesity No Match For Cannabis
The endocannabinoid system appears to be overactive in the case of obesity, leading to increased food consumption and fat accumulation.
Obesity is a growing health concern, world-wide, but particularly in North America. Approximately one third of Americans are report a Body Mass Index (BMI) greater than 30. The number of Americans classified as obese is increasing every year, and this includes children.
Along with the rise of obesity comes a variety of related diseases, included type 2 diabetes. We can control type 2 diabetes, but we haven’t found an effective treatment for obesity. Interestingly, the endocannabinoid system plays a role in the development of obesity and could be a target for treating the disease.
The Endocannabinoid System’s Involvement
The endocannabinoid system appears to be overactive in people with obesity. This means there are too many endocannabinoids or cannabinoid receptors being produced, or endocannabinoids are not breaking down quickly enough. The increased activation of the endocannabinoid system, particularly in the liver, associates with increased food consumption and fat production. This also creates insulin resistance. The cannabinoid receptor CB1 is the main player here. Mice that lack CB1 receptors, for example, failed to become obese even with an increase in caloric intake.
The drug rimonabant is an “inverse agonist” of the CB1 receptor, inhibiting the signalling of this receptor. Clinical studies found this effectively treats obesity, but large-scale trials and use brought to light its unwanted psychiatric side effects, so they removed the drug from the market. Also, because the CB1 receptor plays an important role in the brain, reducing its activity throughout the entire body is a bad idea.
The cannabinoid delta-9-tetrahydrocannabivarin (THCV) is known as a “neutral antagonist” of the CB1 receptor. This means that it blocks the binding site of the receptor, so its activity cannot increase or decrease. Because it is not decreasing the activity, it should not have the same negative effects on the brain as rimonabant. It may, however, successfully dampen overactivity of the endocannabinoid system that leads to obesity.
There have been numerous studies of THCV in two types of animal models of obesity: first on dietary induced by the diet (DIO), and second on genetically created obesity (called ob/ob). In DIO mice, THCV improves glucose tolerance and insulin sensitivity. For the genetically altered mice, THCV reduces liver triglyceride levels (high levels are indicative of insulin resistance).
In humans, there is one study that showed THCV was successful at improving insulin responses and glucose levels in people with type 2 diabetes. This study is reliable because of placebo-control and double blind. Even still, though the study was fairly small with 62 patients. THCV helps patients maintain healthy blood glucose levels. Also, it has no severely adverse effects.
Because the endocannabinoid system links to obesity, dampening this effect with THCV is a promising treatment. In both humans and animal models, treatment with THCV has been shown to improve conditions associated with obesity and type 2 diabetes, such as glucose levels in the blood and decreased insulin resistance.