Cue reactivity and opioid blockade in amphetamine dependence

Joar Guterstam, Nitya Jayaram-Lindström, Jonathan Berrebi, Predrag Petrovic, Martin Ingvar, Peter Fransson & Johan Franck Karolinska Institutet, Department of clinical neuroscience

Amphetamine dependent individuals exhibit strong drug cue reactivity. In this sample, naltrexone did not affect cue reactivity as measured with BOLD fMRI.

40 men with severe amphetamine dependence were randomized to one oral dose of the opioid antagonist naltrexone (50 mg) or placebo. They were then examined with functional magnetic resonance imaging (fMRI) while viewing drug related and neutral movie clips.

The patients reacted with strong subjective craving and activations of limbic areas and attentional networks when viewing the drug related, as compared to the neutral, films. Naltrexone was not found to affect the cue reactivity. fMRI image of activations when viewing drug related vs. neutral films (whole-brain results, p<0.05, Family-Wise Error corrected).

Introduction Between each video segment, the participants were The opioid antagonist naltrexone is used for treating alcohol asked to rate their level of drug craving on a single item and opioid use disorder, but is also a promising treatment for visual analog scale. amphetamine dependence. However, its specific mechanism of action in this condition is not well understood. In this study, fMRI was performed with a 3 T scanner (GE MR750 we aimed to investigate whether it would affect drug cue Discovery) at the MR research center of Karolinska reactivity in a sample with severe amphetamine dependence. University Hospital. Results were analyzed using SPM 12 (Wellcome Center for Neuroimaging, London). Hypothesis That naltrexone, as compared to placebo, would attenuate Results fMRI BOLD activations of brain motivational systems in The drug-related videos, but not the neutral ones, elicited amphetamine dependent patients when viewing drug related strong subjective craving responses in almost all the film clips. patients (mean scores of 68 vs. 16, p<0.001). Significant fMRI BOLD activations were found in the occipital, parietal and temporal cortices, the striatum, and cingular cortex. In Methods patients with particularly long histories of amphetamine 40 men, diagnosed with amphetamine dependence according use, we also found evidence of prefrontal activations. to DSM-IV, were included in the study. Inclusion criteria included: There were no significant differences between the naltrexone and placebo groups on any of these measures. - Amphetamine use during the last 30 days. - History of intravenous drug use. Conclusions - No current symptoms of psychosis or suicidal ideation. Amphetamine dependent patients exhibit strong cue - No contraindications for magnetic resonance imaging. reactivity, not only in limbic regions but also in cortical attention networks. In this sample, naltrexone did not affect All subjects were right-handed. Age was 44 ± 10 years, with cue reactivity, and there is a need for further studies to an average of 19 years of amphetamine use and having used understand its possible therapeutic mechanism of action the drug 22 days during the last month. for this condition. In the scanner, the participants were exposed to nine drug related and nine neutral films, each film lasting 16 s. The drug videos depicted intranasal and intravenous drug taking, while This work was done in the Karolinska Institutet group for the neutral videos contained social scenes unrelated to drugs. translational addiction research (PI Johan Franck). The order of the videos was randomized in order to minimize Further studies on the role of the opioid system in expectation effects. amphetamine dependence are currently ongoing.

Karolinska Institutet Joar Guterstam Supported by the Swedish Research Council, the MD, Psychiatrist Swedish Research Council for Health, Working life Centre for Psychiatry Research and Welfare, and the Swedish Brain Foundation. Norra Stationsgatan 69, 7th floor No potential conflicts of interest. 113 64 Stockholm E-mail: [email protected]