Nicotine and endogenous opioids: toward specific pharmacotherapy

To address the theoretical framework behind opioid receptor antagonism for the treatment of nicotine abuse. The current literature is reviewed with a focus on opioid-nicotine interactions in animals and humans. Furthermore, previous studies addressing the effect of opioid antagonism on smoking behaviour are reviewed critically with a focus on suggestions and implications for future trials.

Computerized data bases and reference lists of existing articles were searched for prior publications in 3 areas: 1) the association between nicotine and endogenous opioids, 2) nicotine and reward, and 3) opioid antagonism in the treatment of nicotine use.

Nicotine affects the mesolimbic reward pathway postsynaptically via nicotinic cholinergic receptors and presynaptically via the central nervous system's (CNS) neurohumoral pathways. Thus nicotine results in the release of endogenous opioids that bind to mu receptors, which increases the release of dopamine along this pathway. Studies to date have shown mixed results on the effect of opioid antagonism on smoking behaviour.

The role of opioid antagonism on smoking behaviour is unclear, despite the publication of 5 trials on the subject. Further trials of longer duration should be undertaken and use both longer-acting medications and those more specific to the mu receptor to further focus on the rewarding aspects of nicotine ingestion, thus addressing the craving for this drug. The development of adequate compounds has just begun, and psychiatrists can hope to have a more specific pharmacotherapy to address the cravings and short-term rewards of nicotine use.