[Pharmacological exploitation of the endocannabinoid system: new perspectives for the treatment of depression and anxiety disorders?].

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 Delta(9)-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 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.