Cue reactivity and opioid blockade in amphetamine dependence: A randomized, controlled fMRI study

Drug Alcohol Depend. 2018 Oct 1:191:91-97. doi: 10.1016/j.drugalcdep.2018.06.023. Epub 2018 Jul 26.


Background: The opioid antagonist, naltrexone, has been shown to reduce the risk of relapse in amphetamine dependence, but the mechanisms behind this effect are not well understood. We aimed to investigate if naltrexone attenuates cue reactivity and craving in amphetamine dependence.

Methods: Forty men with severe, intravenous amphetamine dependence were randomized to one dose of naltrexone (50 mg) or placebo. In a BOLD fMRI cue reactivity paradigm, they were exposed to drug-related and neutral films and gave subjective ratings of craving after each film. Twenty-nine patients left data of sufficient quality to be included in the final analysis.

Results: The drug-related films elicited strong subjective craving and BOLD activations of the striatum, cingulate cortex, and occipito-temporal visual attention networks. Longer history of amphetamine use was associated with greater activations of the prefrontal cortex. Naltrexone as compared to placebo had no significant effects on brain activations or subjective ratings.

Conclusion: Patients with severe stimulant use disorder exhibit strong neural cue reactivity, the patterns of which are modulated by duration of drug use. In this sample, we found no evidence for any effects of naltrexone on cue reactivity.

Keywords: Amphetamine dependence; Functional magnetic resonance imaging; Naltrexone; Stimulant use disorder.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amphetamine-Related Disorders / diagnostic imaging
  • Amphetamine-Related Disorders / drug therapy*
  • Amphetamine-Related Disorders / psychology
  • Attention / drug effects
  • Conditioning, Psychological / drug effects
  • Corpus Striatum / drug effects
  • Craving / drug effects
  • Cues*
  • Female
  • Gyrus Cinguli / drug effects
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Naltrexone / pharmacology*
  • Narcotic Antagonists / pharmacology*
  • Occipital Lobe / drug effects
  • Prefrontal Cortex / drug effects
  • Time Factors


  • Narcotic Antagonists
  • Naltrexone