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Intranasal Oxytocin Selectively Modulates Social Perception, Craving, and Approach Behavior in Subjects With Alcohol Use Disorder

Mitchell, Jennifer M. PhD; Arcuni, Peter A. BA; Weinstein, Dawn NP; Woolley, Josh D. MD/PhD

doi: 10.1097/ADM.0000000000000213
Original Research

Objectives: A pharmacotherapy that both improves social abilities and promotes abstinence may be particularly helpful for the treatment of alcohol use disorder. Recent clinical and preclinical evidence suggests that oxytocin has prosocial and antiaddiction effects. We performed a pilot, laboratory-based, preclinical trial of oxytocin in subjects with alcohol abuse (as per Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria) to evaluate therapeutic potential and assess tolerability.

Methods: Social perceptual ability, cue-induced craving, and approach bias for alcohol and appetitive imagery were quantified after intranasal oxytocin and placebo administration to 32 nontreatment-seeking individuals with alcohol abuse in a double-blind, crossover study. Because attachment style can moderate the effects of oxytocin, we also explored whether attachment style moderated oxytocin's effects on our behavioral measures.

Results: Oxytocin significantly improved recognition of easier items on a social perception task, but had no significant group-level effect on cue-induced craving. However, oxytocin effects on craving were moderated by attachment anxiety, with oxytocin reducing craving in more anxiously attached individuals and increasing craving in less anxiously attached individuals. Subjects did not display an approach bias to alcohol images on the placebo day, preventing meaningful analysis of this measure. Subjects did display an approach bias to appetitive images on the placebo day, which was significantly reduced by oxytocin administration. No adverse reactions were observed.

Conclusions: Intranasal oxytocin has potential to improve social perception, reduce cue-induced alcohol cravings, and reduce appetitive approach bias in subjects with alcohol abuse, and can be safely tolerated in this population. The effects of oxytocin are complex, however, and require further investigation.

Department of Neurology (JMM, DW), University of California San Francisco, San Francisco, CA; and Department of Psychiatry (JMM, PAA, JDW), University of California San Francisco, San Francisco, CA.

Send correspondence and reprint requests to Jennifer M. Mitchell, PhD, Department of Neurology, University of California San Francisco, San Francisco, CA 94143. E-mail:

Received 23 October, 2015

Accepted 1 March, 2016

Clinical Trial Registration: The effects of intranasal oxytocin on social cognition, implicit preferences and craving in moderate to heavy social alcohol drinkers. identifier: NCT01829516.

Funding: This work was supported by a grant from the UCSF Wheeler Center for the Neurobiology of Addiction and by California State Funds for research on drug and alcohol abuse. In addition, Dr. Woolley's work is supported by the United States Department of Veterans Affairs, Office of Research and Development, Clinical Science Research and Development program under Career Development Award (award #CX000758) and the use of facilities at the San Francisco Veterans Affairs Medical Center.

The authors have no conflicts of interest to declare and do not have a “financial relationship” with the organization that sponsored this research.

© 2016 American Society of Addiction Medicine