Cannabinoid receptor antagonist

A cannabinoid receptor antagonist, also known simply as a cannabinoid antagonist or as an anticannabinoid, is a type of cannabinoidergic drug that binds to cannabinoid receptors (CBR) and prevents their activation by endocannabinoids. They include antagonists, inverse agonists, and antibodies of CBRs. The discovery of the endocannabinoid system led to the development of CB₁ receptor antagonists. The first CBR inverse agonist, rimonabant, was described in 1994. Rimonabant blocks the CB₁ receptor selectively and has been shown to decrease food intake and regulate body-weight gain. The prevalence of obesity worldwide is increasing dramatically and has a great impact on public health. The lack of efficient and well-tolerated drugs to cure obesity has led to an increased interest in research and development of CBR antagonists.^[1][2] Cannabidiol (CBD), a naturally occurring cannabinoid and a non-competitive CB₁/CB₂ receptor antagonist, as well as Δ⁹-tetrahydrocannabivarin (THCV), a naturally occurring cannabinoid, modulate the effects of THC via direct blockade of cannabinoid CB₁ receptors, thus behaving like first-generation CB₁ receptor inverse agonists, such as rimonabant. CBD is a very low-affinity CB₁ ligand, that can nevertheless affect CB₁ receptor activity in vivo in an indirect manner, while THCV is a high-affinity CB₁ receptor ligand and potent antagonist in vitro and yet only occasionally produces effects in vivo resulting from CB₁ receptor antagonism. THCV has also high affinity for CB₂ receptors and signals as a partial agonist, differing from both CBD and rimonabant.^[3]