Endocannabinoids and 3,4-methylenedioxymethamphetamine (MDMA) interaction

Cannabis and MDMA are two of the most widely used recreational drugs. This review considered their neuropsychological effects, when taken singly or in combination, in humans or animals. In humans, prolonged use of MDMA and cannabis together is associated with a variety of psychological problems, including elevated impulsiveness, anxiety, somatic complaints, obsessive–compulsive patterns,and psychotic behavior. It is not clear to what extent the combination of MDMA and cannabis contributes to fatal motor vehicles accidents though an additive adverse effect on visual perception in MDMA/D9-THC users has been reported. Neurocognitive deficits (memory, learning, word fluency, speed of processing, and manual dexterity) in several brain areas (hippocampus, frontal lobe) have been reported in those taking both drugs. Endocrine abnormalities in MDMA users have been closely related to their use of cannabis too. A recent study investigated whether coadministered cannabinoids and MDMA in rats affected the long-term neurotoxic properties of MDMA through a hypothermic action, an antioxidant action, or both. Very few studies have set out to clarify the consequences of chronic exposure to concomitant cannabinoids and MDMA for their abuse liability in animals. MDMA showed some cross-discriminative stimulus effects with cannabinoids (delta9-THC), and it has been demonstrated in rats that the endocannabinoid system is involved in MDMA selfadministration.However, these findings have not been confirmed by microdialysis studies in mesolimbic structures which might further clarify this interaction. These findings may help explain the use of marijuana and MDMA together by polydrug users in order to overcome the unpleasant effect which often arise as the initial euphoria dissipates. It has recently been confirmed,using a CPP task, that the endocannabinoid system is involved when the reinforcing properties of MDMA, given centrally, were blocked by pretreatment with SR 141716.