Pharmacological exploitation of the endocannabinoid system: new perspectives for the treatment of depression and anxiety disorders? Exploração farmacológica do sistema endocanabinoide: novas perspectivas para o tratamento de transtornos de ansiedade e depressão? Correspondence

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 D-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, CB 1 and CB 2 , 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 CB 1 receptors was shown to exert anxiolyticand 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. Descriptors: Cannabis sativa; Cannabinoids; Endocannabinoids; Anxiety; Depression original article 1 Graduate Program in Neurosciences, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil 2 Max Planck Institute of Psychiatry, Research Group Neuronal Plasticity, Munich, Germany 3 Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil