ABSTRACT
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.
Subject(s)
Cannabinoid Receptor Agonists/chemical synthesis , Cannabinoid Receptor Agonists/therapeutic use , Controlled Substances/chemical synthesis , Receptor, Cannabinoid, CB1/agonists , Analgesics/chemical synthesis , Analgesics/therapeutic use , Animals , Anti-Anxiety Agents/chemical synthesis , Anti-Anxiety Agents/therapeutic use , Cannabinoids/chemical synthesis , Cannabinoids/therapeutic use , Controlled Substances/administration & dosage , Cyclohexanols/chemical synthesis , Cyclohexanols/therapeutic use , Dronabinol/analogs & derivatives , Dronabinol/chemical synthesis , Dronabinol/therapeutic use , Humans , Mental Disorders/drug therapy , Mental Disorders/metabolism , Pain/drug therapy , Pain/metabolism , Phenanthridines/chemical synthesis , Phenanthridines/therapeutic use , Receptor, Cannabinoid, CB1/metabolismABSTRACT
Cannabis and, to a lesser extent, synthetic cannabinoids are used during adolescence, a period in which multiple brain areas are still undergoing development. Among such areas is the hypothalamus, which is implicated in the control of sleep-wake cycle. In the present report, we show that exposing adolescent rats to the cannabinoid receptor agonist WIN 55, 212-2 (0.1, 0.3 or 1.0 mg/kg, i.p) for 14 days during adolescence (i.e., from post-natal day 30-44) resulted in significant sleep disturbances when the animals became adult (post-natal day 80). These included decreased wakefulness and enhanced rapid eye movement sleep. Furthermore, we found that labeling for NeuN, a marker of postmitotic neurons, was significantly increased the dorsomedial hypothalamic nucleus of rats treated with WIN 55, 212-2. The results suggest that excessive cannabinoid receptor activation during adolescence can persistently influence sleep patterns and neuronal activity later in life.
