INTRODUCTION: Studies have shown that opioid antagonists like naltrexone are 
efficient in reducing heavy drinking. The neurobiological mechanism by which 
opioid modulators affect drinking behavior is based on the strong connection 
between the endogenous opioid system, the dopamine system and the influence of 
the CNS stress response.
AREAS COVERED: This review provides an overview of the pathophysiological role 
of the opioid system in alcohol dependence and the neurobiological mechanisms of 
possible pharmacological interventions. An extensive Medline and Internet 
research was performed to retrieve information on existing and currently 
investigated opioid modulators. The findings were assessed critically and 
interpreted with regard to an individualized therapy for alcohol dependence.
EXPERT OPINION: The opioid system is of crucial importance in the genesis and 
maintenance of alcohol dependence. Naltrexone- and to a lesser extent nalmefene- 
is an agent that modulates opioidergic transmission in the CNS and it shows a 
limited but well-studied efficacy in treating alcohol dependence. Several agents 
(LY2196044, ALKS-29, ALKS-33) that are currently undergoing Phase II and Phase 
III studies are of interest but first their efficacy must be proved in clinical 
practice.