An FMRI study of nalmefene on alcohol effects in reward anticipation in alcohol dependence

A. Lingford-Hughes, J. McGonigle, I. Mick, D. Quelch, R. Flechais, D. Erritzoe, M. Bolstridge, A. Ramos, D. Meulien, D. Østergaard Nilausen, L. Breuning Sluth, C. Von Der Goltz, B. Steiniger-Brach, D. Nutt

Research output: Contribution to journalConference articlepeer-review


Nalmefene is an opiate receptor modulator recently licensed for the reduction of alcohol intake in alcohol dependence. This study investigated the effects of nalmefene on anticipation of reward with alcohol dependence and high drinking risk level (>60g /day) under an alcohol clamp.

18 mg nalmefene or placebo was randomized in this cross-over, double blind study. Pulsed arterial spin labelling pre and during alcohol infusion (0.8‰) was undertaken to evaluate the impact of alcohol on blood flow. During the alcohol infusion, participants completed our fMRI protocol to assess reward, impulsivity and stress responsivity in addiction using monetary incentive delay, go-nogo and evocative tasks.

Complete data were available for 18 men. As expected, alcohol infusion resulted in an increase in blood perfusion, while treatment did not differentially impact blood perfusion. Analysis revealed a significant decrease in the contrast “reward anticipation > neutral anticipation” on nalmefene compared with placebo in the striatal ROI: t = 2.78, p = 0.013, d.f. = 17. Analysis confirmed that this was due to a decrease in BOLD response during reward, not an increase during neutral anticipation. Further, whole brain analyses observed three clusters (Z > 2.3, p < 0.05 corrected for multiple comparisons), encompassing the dorsal striatum bilaterally and parts of brain stem.

In the presence of alcohol, nalmefene pretreatment resulted in reduced BOLD response in the striatum during anticipation of reward in non-treatment seeking alcohol dependent individuals. This provides strong evidence to support the hypothesis that nalmefene's mechanism of action involves modulating the reward system.

Original languageEnglish
Article numberP-79
Pages (from-to)65
Number of pages1
JournalAlcohol and Alcoholism
Issue numberIssue_suppl_1
Publication statusPublished - 30 Aug 2015
Externally publishedYes


  • alcohol
  • nalmefene
  • placebo
  • adult
  • alcoholism
  • arterial spin labeling
  • blood flow
  • BOLD signal
  • brain analysis
  • brain stem
  • clamp
  • clinical article
  • conference abstract
  • controlled study
  • dorsal striatum
  • drinking
  • drug therapy
  • human
  • impulsiveness
  • infusion
  • male
  • perfusion
  • randomized controlled trial
  • reward
  • physiological stress


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