Nalmefene Reduces Reward Anticipation in Alcohol Dependence: An Experimental Functional Magnetic Resonance Imaging Study

Darren R. Quelch, Inge Mick, John McGonigle, Anna C. Ramos, Remy S.A. Flechais, Mark Bolstridge, Eugenii Rabiner, Matthew B. Wall, Rexford D. Newbould, Björn Steiniger-Brach, Franz van den Berg, Malcolm Boyce, Dorrit Østergaard Nilausen, Lasse Breuning Sluth, Didier Meulien, Christoph von der Goltz, David Nutt, Anne Lingford-Hughes

Research output: Contribution to journalArticlepeer-review


Nalmefene is a µ and δ opioid receptor antagonist, κ opioid receptor partial agonist that has recently been approved in Europe for treating alcohol dependence. It offers a treatment approach for alcohol-dependent individuals with “high-risk drinking levels” to reduce their alcohol consumption. However, the neurobiological mechanism underpinning its effects on alcohol consumption remains to be determined. Using a randomized, double-blind, placebo-controlled, within-subject crossover design we aimed to determine the effect of a single dose of nalmefene on striatal blood oxygen level–dependent (BOLD) signal change during anticipation of monetary reward using the monetary incentive delay task following alcohol challenge.

Twenty-two currently heavy-drinking, non–treatment-seeking alcohol-dependent males were recruited. The effect of single dose nalmefene (18 mg) on changes in a priori defined striatal region of interest BOLD signal change during reward anticipation compared with placebo was investigated using functional magnetic resonance imaging. Both conditions were performed under intravenous alcohol administration (6% vol/vol infusion to achieve a target level of 80 mg/dL).

Datasets from 18 participants were available and showed that in the presence of the alcohol infusion, nalmefene significantly reduced the BOLD response in the striatal region of interest compared with placebo. Nalmefene did not alter brain perfusion.

Nalmefene blunts BOLD response in the mesolimbic system during anticipation of monetary reward and an alcohol infusion. This is consistent with nalmefene's actions on opioid receptors, which modulate the mesolimbic dopaminergic system, and provides a neurobiological basis for its efficacy.
Original languageEnglish
Pages (from-to)941-948
Number of pages8
JournalBiological Psychiatry
Issue number11
Publication statusPublished - 1 Jun 2017
Externally publishedYes


  • Addiction
  • Alcohol dependence
  • Functional imaging
  • Nalmefene
  • Opioid
  • Reward anticipation
  • NCT01969617
  • nalmefene
  • placebo
  • adult
  • alcohol consumption
  • alcoholism
  • anticipation
  • article
  • BOLD signal
  • brain perfusion
  • brain stem
  • cerebellum
  • controlled study
  • crossover procedure
  • double blind procedure
  • drinking behavior
  • drug blood level
  • functional magnetic resonance imaging
  • functional neuroimaging
  • globus pallidus
  • human
  • major clinical study
  • male
  • nausea and vomiting
  • MRI scanner
  • priority journal
  • putamen
  • randomized controlled trial
  • reaction time
  • reward
  • single drug dose
  • thalamus
  • time to maximum plasma concentration


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