CNS Drugs

, Volume 19, Issue 8, pp 693–707 | Cite as

The Opioidergic-Alcohol Link

Implications for Treatment
Review Article


Preclinical and clinical data implicate the endogenous opioid system in alcohol dependence. In vitro studies show that rodent pituitary and hypothalamic tissue responds to acute exposure to alcohol by releasing β-endorphins. In vivo studies suggest differential activity of endogenous opioid receptors in rodents with high and low alcohol preference. Similarly, humans with a family history of alcohol dependence also show a heightened endorphin response to an acute challenge of alcohol compared with those with no family history of alcohol dependence.

The effects of opioid agonists and antagonists on rodent and human alcohol consumption further support the opioid-alcohol link. In rodents and humans, small doses of opioid agonists increase alcohol consumption, while pretreatment with large doses decreases consumption. The opioid antagonist naltrexone decreases rodent alcohol consumption, particularly in low doses under acute and intermittent schedules.

Most clinical trials in patients with alcohol dependence support modest therapeutic effects of naltrexone in decreasing alcohol consumption. Efforts to identify subgroups of alcohol-dependent patients responsive to naltrexone, as well as psychosocial and pharmacological augmentation strategies, may further improve the clinical usefulness of the drug.



We acknowledge Drs Nancy Petry, Lance Bauer and Victor Hesselbrock for their comments, Dr Kranzler for his help, and Judy Herkimer and Vera Dynder for typing the manuscript. No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.


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Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  1. 1.Addiction Services, Connecticut Valley Hospital, Merrit HallMiddletownUSA
  2. 2.Department of PsychiatryUniversity of Connecticut School of MedicineFarmingtonUSA

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