Gabapentin increases the abuse liability of alcohol alone and in combination with oxycodone in participants with co-occurring opioid and alcohol use disorder
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Updated: Aug 25, 2025

Investigating Drivers of Antireward in Addiction Behavior with Anatomically Specific Single-Cell Gene Expression Methods
Published on: August 4, 2022
F Castillo1, J D Jones1, R R Luba1
1Division on Substance Use Disorders, New York State Psychiatric Institute, Department of Psychiatry, Vagelos College of Physicians and Surgeons of Columbia University, 1051 Riverside Drive, Unit 66, New York, NY 10032, United States of America.
Background:
People who have co-occurring Alcohol Use Disorder (AUD) and Opioid Use Disorder (OUD) carry a higher risk of adverse outcomes, including drug overdose. Early clinical and preclinical studies suggested that gabapentin may be effective in treating both disorders. The present study was designed to assess the effects of gabapentin on the subjective and physiological effects of oxycodone (OXY) and alcohol (ALC), alone and in combination.
Methods:
During an 8-week, inpatient, within-subject, randomized, double-blind, placebo-controlled crossover study, non-treatment seeking participants (N = 13; 12 M/1F; 44.1 ± 3 years of age) with OUD and AUD were maintained on oral morphine (120 mg daily). Under gabapentin (1800 mg/day) and placebo (0 mg/day) maintenance, participants completed nine separate test sessions (three sessions per week) during which they received an oral solution containing 0, 15, or 30 mg/70 kg OXY in combination with 0, 0.5, or 0.75 g/kg ALC. During test sessions, subjective effects and physiological responses were assessed repeatedly on 100-mm visual analog scales (VAS). The primary outcome variable was the VAS rating of drug liking after receiving the drug challenge.
Results:
Alcohol alone (but not oxycodone alone) produced dose-related increases in several positive subjective responses, including drug liking. Gabapentin significantly increased drug liking when given in combination with ALC and OXY + ALC (p < 0.05). Gabapentin did not clinically compromise respiration or other vital functions.
Conclusions:
Gabapentin may increase the abuse liability of ALC and OXY + ALC in those with co-occurring OUD and AUD.
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