The effects of the monoamine stabilizer (-)-OSU6162 on craving in alcohol dependent individuals: A human laboratory study.
Alcohol dependence is associated with a dysregulated dopamine system modulating reward, craving and cognition. The monoamine stabilizer (-)-OSU6162 (OSU6162) can counteract both hyper- and hypo-dopaminergic states and we recently demonstrated that it attenuates alcohol-mediated behaviors in long-term drinking rats. The present Phase II exploratory human laboratory study investigated to our knowledge for the first time the effects of OSU6162 on cue- and priming-induced craving in alcohol dependent individuals. Fifty-six alcohol dependent individuals were randomized to a 14-day-treatment period of OSU6162 or placebo after their baseline impulsivity levels had been determined using the Stop Signal Task. On Day 15, participants were subjected to a laboratory alcohol craving test comprised of craving sessions induced by: i) active - alcohol specific cues, ii) neutral stimuli and iii) priming - intake of an alcoholic beverage (0.20g ethanol/kg bodyweight). Subjective ratings of alcohol craving were assessed using the shortened version of the Desire for Alcohol Questionnaire and visual analog scales (VAS). OSU6162 treatment had no significant effect on cue-induced alcohol craving, but significantly attenuated priming-induced craving. Exploratory analysis revealed that this effect was driven by the individuals with high baseline impulsivity. In addition, OSU6162 significantly blunted the subjective liking of the consumed alcohol (VAS). Although the present 14-day-treatment period, showed that OSU6162 was safe and well tolerated, this exploratory human laboratory study was not designed to evaluate the efficacy of OSU6162 to affect alcohol consumption. Thus a larger placebo-controlled efficacyclinical trial is needed to further investigate the potential of OSU6162 as a novel medication for alcohol dependence.
Department of Clinical Neuroscience, Division of Psychiatry, Karolinska Institutet, Stockholm, Sweden.
Lotfi
L
Khemiri
Department of Clinical Neuroscience, Division of Psychiatry, Karolinska Institutet, Stockholm, Sweden.
Pia
P
Steensland
Department of Clinical Neuroscience, Division of Psychiatry, Karolinska Institutet, Stockholm, Sweden.
Joar
J
Guterstam
Department of Medicine, Division of Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden.
Olof
O
Beck
Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Arvid
A
Carlsson
Department of Clinical Neuroscience, Division of Psychiatry, Karolinska Institutet, Stockholm, Sweden. Electronic address: johan.franck@ki.se.
Johan
J
Franck
Department of Clinical Neuroscience, Division of Psychiatry, Karolinska Institutet, Stockholm, Sweden.
Nitya
N
Jayaram-Lindström
D000328:Adult; D000437:Alcoholism / Q000188:drug therapy* / Q000523:psychology*; D066249:Craving / Q000187:drug effects*; D003463:Cues; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007175:Impulsive Behavior / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D013997:Time Factors
D010880:Piperidines; C109513:OSU 6162
Addiction; Alcohol; Craving; Dopamine stabilizer; Impulsivity; OSU6162