Evaluation of glycine treatment for reducing alcohol craving and self‐administration in individuals with alcohol use disorder: A human laboratory trial

Abstract Background Alcohol use disorder (AUD) has limited treatment options and glycine receptors (GlyRs) in brain reward regions have emerged as tentative targets for pharmacotherapy. The rationale derives from studies showing that glycine, an endogenous GlyR agonist, alters dopamine (DA) transmission and reduces alcohol intake in rats. This study sought to translate these findings to individuals with AUD by examining whether glycine treatment reduces craving for alcohol and laboratory alcohol intake. Methods Individuals with AUD were randomized to oral glycine (0.12 g/kg) or placebo treatment for 5 days. Thereafter, 48 participants completed an alcohol challenge including priming for alcohol followed by self‐administration of up to four drinks of 12 g alcohol. Alcohol craving and subjective effects of alcohol were measured throughout the study. Results Glycine treatment raised serum glycine levels by 125%. Neither alcohol intake nor craving or subjective effects of alcohol differed between treatment groups, except for peak stimulatory effects, which were slightly higher in the glycine‐treated group. The relationships between craving for alcohol or “wanting more” on the Drugs Effects Questionnaire and laboratory alcohol intake were dissociated in the glycine‐treated group. In the full sample, serum glycine levels at baseline were inversely associated with recent drinking history. Conclusion Glycine treatment does not reduce craving or laboratory alcohol consumption in individuals with AUD per se, but results are equivocal as the association between alcohol‐induced craving or “wanting more” and the ensuing self‐administration of alcohol was abolished in the glycine‐treated group. The inverse association observed between glycine levels at baseline and self‐reported recent drinking could be a consequence of alcohol intake or support a protective role for glycine activity in limiting alcohol intake. Further studies are warranted to delineate how GlyR activity is linked to alcohol consumption in humans and to establish whether targeting this system may constitute a new treatment concept for AUD.