Researchers at Michigan state university have discovered the many ways in which cannabinoid receptors can cause obesity to the human body. It’s has been found that when these receptors are not present in the body it confers protection from weight gain which confirms that both cannabinoid 1 (CB1R) and cannabinoid 2 (CB2R) receptors play an important role in obesity
The findings of the research are found in the journal Obesity. The recent findings help to reach a common point between the pre-existing conflicting studies. It sheds light on the receptors involved in the digestion of glucose and body weight.
Role of CB1R in cannabis
Many people report of experiencing increased hunger due to an active ingredient in cannabis, delta-9-tetrahydrocannabinol (THC). The appetite-stimulating effect of cannabis is because of the activation of an associated gene in cannabis in CB1R.
Recent studies have shown that CB1R is responsible for weight gain in people using cannabis. However, when rodents were administered CB1R agonists it was that they cut down on food intake and weight gain. In human beings, the agonists like rimonabant show similar results like weight loss and bettering the metabolic syndrome in general.
Role of CB2R in cannabis
Increased calorie intake with the use of cannabis could trigger obesity and type 2 diabetes because of the activation of cannabinoid receptors. However, some of the studies state otherwise. According to them, the use of cannabis could reduce the risk of diabetes, insulin resistance, and obesity.
Studies regarding CB2R have not been as effective as those related to CB1R. But some studies like the one which was published in 2015 in PLoS One show that when rodents were administered a CB2R agonist it resulted in lesser weight gain and less food intake in obese rats. But a similar study which got published in 2016 in the British Journal of Pharmacology said: using a specific CB2R agonist the following year did not give the same results.
The agonist, when administered to diet-induced obese rata, did not prevent weight gain or give rise to lower food intake.
Study regarding mice lacking both CB1R and CB2R
A high-fat diet was fed to mice lacking CB1R and CB2R for 12 weeks. The same diet was administered to wild type mice. After calculating body weight and food intake each week for twelve weeks it was observed that there was no significant change in weight gain in the wild type mice and those lacking CB2R (average gain was of 19 g versus 21 g). But the ones lacking CB1R showed 5 g lesser weight gain as compared to the other two groups of mice.
The automated measurements of the food intake showed that the decreased body weight and lean phenotype among the CB-DKO mice were not linked with a low amount of food intake and increased movement.
However, the increased rate of heat production and respiratory rate was observed in CB-DKO mice. The CB-DKO mice also showed low adiposity, increased thermogenesis, and a low amount of cholesterol. Further, insulin sensitivity in CB-DKO mice as compared to the CB2-/- mice confirmed the findings.
The team explained, indirect calorimetry showed that inactivating both CBR1 and CBR2 receptors have the potential to hinder the development of obesity by increasing the use of energy.
It was suggested that this leanness in mice lacking CB1R maybe because of role CB1R in energy balance. But this conclusion isn’t reliable because this study did not involve a CBR1 model. The team suggests that downregulation of these receptors is responsible for declined obesity and insulin resistance.
CB1R shows predominance in leanness
Considering the role of CB1R in energy balance, it can be drawn that CB1R may be driving the leanness and thermogenesis in CB-DKO mice. However, the researchers say that this conclusion has some limitation because the CBR1 knock put model was not mentioned in the study.
On the other hand, researchers also focus on the fact that this phenotype may not be only the result of the predominance of CBR1 but this may be due to the combined effect of both the receptors.
The team says that as cannabis contains many other ingredients other than THC, which may pass through the cannabinoid receptors and other mechanisms, the future studies are attested.
Despite the controversy, Olson and his team concluded that the low rate of obesity and insulin resistance among cannabis users is due to the downregulation of cannabinoid receptors.