The synthetic CB₁ cannabinoid receptor selective agonists: Putative medical uses and their legalization

More than 500 molecules have been identified as components of Cannabis sativa (C. sativa), of which the most studied is Δ⁹-tetrahydrocannabinol (Δ⁹-THC). Several studies have suggested that Δ⁹-THC exerts diverse biological effects, ranging from fragmentation of DNA to behavioral disruptions. Currently, it is accepted that most of the pharmacological properties of Δ⁹-THC engage the activation of the cannabinoid receptors, named CB₁ and CB₂. Interestingly, multiple pieces of evidence have suggested that the cannabinoid receptors play an active role in the modulation of several diseases leading to the design of synthetic cannabinoid-like compounds. Advances in the development of synthetic CB₁ cannabinoid receptor selective agonists as therapeutical approaches are, however, limited. This review focuses on available evidence searched in PubMed regarding the synthetic CB₁ cannabinoid receptor selective agonists such as AM-1235, arachidonyl-2′ chloroethylamide (ACEA), CP 50,556–1 (Levonantradol), CP-55,940, HU-210, JWH-007, JWH-018, JWH-200 (WIN 55,225), methanandamide, nabilone, O-1812, UR-144, WIN 55,212-2, nabiximols, and dronabinol. Indeed, it would be ambitious to describe all available evidence related to the synthetic CB₁ cannabinoid receptor selective agonists. However, and despite the positive evidence on the positive results of using these compounds in experimental models of health disturbances and preclinical trials, we discuss evidence in regards some concerns due to side effects.