An endocannabinoid hypothesis of drug reward

The dopamine hypothesis of drug reward remains a difficult area of research and perhaps a major problem and hindrance to progress in unraveling the biology of addiction. Pharmacological treatment of drug dependency has been disappointing and new therapeutic targets and hypotheses are needed. Since there is accumulating evidence indicating a central role of endocannabinoid physiological control system (EPCS) in the regulation of the rewarding effects of abused substances, an endocannabinoid hypothesis of drug reward is postulated. Endocannabinoids mediate retrograde signaling in neuronal tissues and suppress classical neurotransmitter release. This powerful modulatory action on synaptic transmission has significant functional implications and interactions with the effects of abused substances. Cannabinoids and endocannabinoids appear to be involved in adding to the rewarding effects of addictive substances including, nicotine, opiates, alcohol, cocaine and BDZs. Thus, the EPCS may be important natural regulatory mechanism for reward and a target for the treatment of addictive disorders.