The endocannabinoid system is involved in many pathways in the body, including regulation of appetite and fat burning. Anyone who has experienced “the munchies” can attest to the fact that many cannabis strains and edibles with THC can increase hunger. Hunger is increased by activating the endocannabinoid system, and thus scientists thought blocking the endocannabinoid system with drugs could decrease hunger and increase weight loss.
The Opposite of The Munchies
A second-generation of CB1 inhibitors have been developed, this time working only on peripheral cannabinoid receptors and not crossing the blood-brain barrier. These second-generation drugs, like AM6545, do not have the same psychiatric side effects rimonabant does but reduce elevated metabolic parameters including cholesterol and insulin.
Rimonabant also induced nausea and vomiting, while AM6545 has minimal nausea side effects. AM6545 only decreased weight in mice that are obese due to a high-fat diet, and not normal mice. This is important because it shows CB1 inhibitors will not be abused by normal weight or underweight patients looking to drop 10 pounds in a week
Tam, J., et al., Peripheral CB1 cannabinoid receptor blockade improves cardiometabolic risk in mouse models of obesity. J Clin Invest, 2010. 120(8): p. 2953-66.