Animal models had shown that using cannabinoid receptor type 1 (CB1R) blockades can produce a “lean phenotype”, or a slimmer animal. The animals were also more resistant to weight gain from diet and a condition called dyslipidemia, which means there are unhealthy levels of fats in the blood.
However,animal models are not very representative of human obesity because there are many more complex psychological, environmental, and sociological factors involved in why humans gain weight and keep weight. Furthermore, it is difficult to observe personality and psychological changes in animals.
Here is the full scientific article if you wish to download it.
With this in mind, the authors tried using a cannabinoid receptor blocker to replicate the weight loss effects seen in animals in humans. The results were promising, showing a “decrease of body weight and waist circumference, and improvement in cardiovascular risk factors.”
The drug rimonabant was administered to over 1500 people over the period of 1 year in order to establish whether it could help people lose weight and improve health. Rimonabant is a synthetic cannabinoid antagonist, selectively blocking CB1 receptors in the body. Different doses were administered and the results were promising.
On the 20mg daily dose, 67% of patients lost 5% or more in body weight. Fully 39% lost 10% or more, and furthermore these effects were sustained for significant times, a rarity with metabolic drugs.
Not only did most patients lose significant amounts of weight with CB1R blockade, they improved their metabolic health and reduced their appetite. This is possibly through both the central nervous system CB1R and peripheral CB1R interactions, though this is unclear.
In this study, the drug rimonabant was generally tolerable, with 82% to 87% of patients not reporting side effects. When side effects were reported, they were not life threatening and were generally mild.
Although the results look positive for rimonabant in this study, it is a stage 1 clinical trial and the results are therefore not representative. The relatively small sample size (n=1507) and short duration (1 year) do not have the statistical strength to establish a safety profile. Side effects were relatively mild and rare but they did occur.
Metabolism and weight are very complex and not well understood processes in the body. Nearly every single weight loss drug ever developed has failed to be approved. Unbeknownst to the authors, rimonabant would never be approved in the USA and would be withdrawn from the market in the EU due to the side effects.
The relative tolerability of cannabinoids and the role of the ECS in metabolism make it a promising target for drugs. Further exploration of this system should produce effective drugs for weight loss and appetite reduction. The results of this study are hopeful, there are clear weight loss results from rimonabant and the drug was generally tolerable. However, later studies proved it was not safe.