Damian Karl1, J Malte Bumb1,2, Patrick Bach1,2, Christina Dinter1, Anne Koopmann1,2, Derik Hermann1,2, Karl Mann1, Falk Kiefer1,2,3, Sabine Vollstädt-Klein4,5. 1. Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany. 2. Feuerlein Center on Translational Addiction Medicine (FCTS), University of Heidelberg, Heidelberg, Germany. 3. Mannheim Center for Translational Neurosciences (MCTN), University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany. 4. Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany. s.vollstaedt-klein@zi-mannheim.de. 5. Mannheim Center for Translational Neurosciences (MCTN), University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany. s.vollstaedt-klein@zi-mannheim.de.
Abstract
RATIONALE: Alcohol use disorder is a common and devastating mental illness for which satisfactory treatments are still lacking. Nalmefene, as an opioid receptor modulator, could pharmacologically support the reduction of drinking by reducing the (anticipated) rewarding effects of alcohol and expanding the range of treatment options. It has been hypothesized that nalmefene acts via an indirect modulation of the mesolimbic reward system. So far, only a few imaging findings on the neuronal response to nalmefene are available. OBJECTIVES: We tested the effect of a single dose of 18 mg nalmefene on neuronal cue-reactivity in the ventral and dorsal striatum and subjective craving. METHODS:Eighteen non-treatment-seeking participants with alcohol use disorder (67% male, M = 50.3 ± 13.9 years) with a current high-risk drinking level (M = 76.9 ± 52 g of pure alcohol per day) were investigated using a cue-reactivity task during functional magnetic resonance imaging (fMRI) in a double-blind, placebo-controlled, cross-over study/design. In addition, self-reported craving was assessed before and after exposure to alcohol cues. RESULTS: An a priori defined region of interest (ROI) analysis of fMRI data from 15 participants revealed that nalmefene reduced alcohol cue-reactivity in the ventral, but not the dorsal striatum. Additionally, the subjective craving was significantly reduced after the cue-reactivity task under nalmefene compared to placebo. CONCLUSION: In the present study, reduced craving and cue-reactivity to alcohol stimuli in the ventral striatum by nalmefene indicates a potential anti-craving effect of this drug via attenuation of neural alcohol cue-reactivity.
RCT Entities:
RATIONALE: Alcohol use disorder is a common and devastating mental illness for which satisfactory treatments are still lacking. Nalmefene, as an opioid receptor modulator, could pharmacologically support the reduction of drinking by reducing the (anticipated) rewarding effects of alcohol and expanding the range of treatment options. It has been hypothesized that nalmefene acts via an indirect modulation of the mesolimbic reward system. So far, only a few imaging findings on the neuronal response to nalmefene are available. OBJECTIVES: We tested the effect of a single dose of 18 mg nalmefene on neuronal cue-reactivity in the ventral and dorsal striatum and subjective craving. METHODS: Eighteen non-treatment-seeking participants with alcohol use disorder (67% male, M = 50.3 ± 13.9 years) with a current high-risk drinking level (M = 76.9 ± 52 g of pure alcohol per day) were investigated using a cue-reactivity task during functional magnetic resonance imaging (fMRI) in a double-blind, placebo-controlled, cross-over study/design. In addition, self-reported craving was assessed before and after exposure to alcohol cues. RESULTS: An a priori defined region of interest (ROI) analysis of fMRI data from 15 participants revealed that nalmefene reduced alcohol cue-reactivity in the ventral, but not the dorsal striatum. Additionally, the subjective craving was significantly reduced after the cue-reactivity task under nalmefene compared to placebo. CONCLUSION: In the present study, reduced craving and cue-reactivity to alcohol stimuli in the ventral striatum by nalmefene indicates a potential anti-craving effect of this drug via attenuation of neural alcohol cue-reactivity.
Authors: Patrick Bach; Georg Weil; Enrico Pompili; Sabine Hoffmann; Derik Hermann; Sabine Vollstädt-Klein; Karl Mann; Ursula Perez-Ramirez; David Moratal; Santiago Canals; Serdar M Dursun; Andrew J Greenshaw; Peter Kirsch; Falk Kiefer; Wolfgang H Sommer Journal: Addict Biol Date: 2019-02-12 Impact factor: 4.280
Authors: Gavin Bart; James H Schluger; Lisa Borg; Ann Ho; Jean M Bidlack; Mary Jeanne Kreek Journal: Neuropsychopharmacology Date: 2005-12 Impact factor: 7.853
Authors: Philippe Castera; Edmund Stewart; Josef Großkopf; Carlos Brotons; Maiken Brix Schou; Doris Zhang; Björn Steiniger Brach; Didier Meulien Journal: Eur Addict Res Date: 2018-11-28 Impact factor: 3.015