Alcohol consumption induces endogenous opioid release in the human orbitofrontal cortex and nucleus accumbens

Sci Transl Med. 2012 Jan 11;4(116):116ra6. doi: 10.1126/scitranslmed.3002902.


Excessive consumption of alcohol is among the leading causes of preventable death worldwide. Although ethanol modulates a variety of molecular targets, including several neurotransmitter receptors, the neural mechanisms that underlie its rewarding actions and lead to excessive consumption are unknown. Studies in animals suggest that release of endogenous opioids by ethanol promotes further consumption. To examine this issue in humans and to determine where in the brain endogenous opioids act to promote alcohol consumption, we measured displacement of a radiolabeled μ opioid receptor agonist, [¹¹C]carfentanil, before and immediately after alcohol consumption in both heavy drinkers and control subjects. Drinking alcohol induced opioid release in the nucleus accumbens and orbitofrontal cortex, areas of the brain implicated in reward valuation. Opioid release in the orbitofrontal cortex and nucleus accumbens was significantly positively correlated. Furthermore, changes in orbitofrontal cortex binding correlated significantly with problem alcohol use and subjective high in heavy drinkers, suggesting that differences in endogenous opioid function in these regions contribute to excessive alcohol consumption. These results also suggest a possible mechanism by which opioid antagonists such as naltrexone act to treat alcohol abuse.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Alcohol Drinking / blood
  • Alcohol Drinking / metabolism*
  • Case-Control Studies
  • Cerebral Cortex / metabolism*
  • Demography
  • Ethanol / blood
  • Female
  • Humans
  • Male
  • Nucleus Accumbens / metabolism*
  • Opioid Peptides / metabolism*
  • Positron-Emission Tomography
  • Protein Binding
  • Receptors, Opioid, mu / metabolism
  • Regression Analysis
  • Reward
  • Young Adult


  • Opioid Peptides
  • Receptors, Opioid, mu
  • Ethanol