Exploração farmacológica do sistema endocanablnolde: Novas perspectivas para o tratamento de transtornos de ansiedade e depressão?

Abstract

Objective: The present review provides a brief introduction into the endocannabinoid system and discusses main strategies of pharmacological interventions. Method: We have reviewed the literature relating to the endocannabinoid system and its pharmacology; both original and review articles written in English were considered. Discussion: Cannabinoids are a group of compounds present in Cannabis sativa (hemp), such as D9-tetrahydrocannabinol, and their synthetic analogues. Research on their pharmacological profile led to the discovery of the endocannabinoid system in the mammalian brain. This system comprises at least two G-protein coupled receptors, CB1 and CB2, their endogenous ligands (endocannabinoids; e.g. the fatty acid derivatives anandamide and 2-arachydonoyl glycerol), and the enzymes responsible for endocannabinoid synthesis and catabolism. Endocannabinoids represent a class of neuromessengers, which are synthesized on demand and released from post-synaptic neurons to restrain the release of classical neurotransmitters from pre-synaptic terminals. This retrograde signalling modulates a variety of brain functions, including anxiety, fear and mood, whereby activation of CB1 receptors was shown to exert anxiolytic-and antidepressant-like effects in preclinical studies. Conclusion: Animal experiments suggest that drugs promoting endocannabinoid action may represent a novel strategy for the treatment of depression and anxiety disorders.