NICOTINE AND ENDOGENOUS OPIOIDS - TOWARD SPECIFIC PHARMACOTHERAPY

Objective: To address the theoretical! framework behind opioid recepto r antagonism for the treatment of nicotine abuse. The current literatu re is reviewed with a focus on opioid-nicotine interactions in animals and humans. Furthermore, previous studies addressing the effect of op ioid antagonism on smoking behaviour are reviewed critically with a fo cus on suggestions and implications for future trials. Method: Compute rized data bases and reference lists of existing articles were searche d for prior publications in 3 areas: I) the association between nicoti ne and endogenous opioids, 2) nicotine and reward, and 3) opioid antag onism in the treatment of nicotine use. Results: Nicotine affects the mesolimbic reward pathway postsynaptically via nicotinic cholinergic r eceptors and presynaptically via the central nervous system : (CNS) ne urohumoral pathways. Thus nicotine results in the release of endogenou s opioids that bind to mu receptors, which increases the release of do pamine along this pathway. Studies to date have shown mixed results on the effect of opioid antagonism on smoking behaviour. Conclusions: Th e role of opioid antagonism on smoking behaviour is unclear, despite t he publication of 5 trials on the subject. Further trials of longer du ration should be undertaken and use both longer-acting medications and those more specific to the mu receptor to further focus or? the rewar ding aspects of nicotine ingestion, thus addressing the craving for th is drug. The development of adequate compounds has just begun, and psy chiatrists can hope to have a more specific pharmacotherapy to address the cravings and short-term rewards of nicotine use.