Naltrexone Plus Buprenorphine for Cocaine Use In People with Opioid Dependence

Preclinical and small clinical studies suggest that the concurrent administration of buprenorphine (BUP) with naltrexone may reduce cocaine use. Using a complicated and perhaps counterintuitive combination of an antagonist (naltrexone) and a partial agonist (buprenorphine), both of which were delivered in a manner in which they were physiologically active, investigators provided extended-release injectable naltrexone (XR-NTX) and weekly cognitive behavioral therapy to 302 treatment-seeking adults with current DSM-IV cocaine dependence and current or past opioid dependence, then randomized them to placebo, 4 mg/day of BUP, or 16 mg/day of BUP for 8 weeks. Follow-up occurred 4 and 12 weeks after the treatment period.

  • No between-group differences were detected for the primary outcome: urine drug screen (UDS)-corrected self-reported cocaine use days during the last 4 weeks of treatment.
  • Longitudinal analyses during the evaluation period showed that the 16 mg BUP group had a greater proportion of negative UDS for cocaine compared with placebo (51% versus 46%, odds ratio 1.71; 95% CI 1.19 to ∞).
  • No other secondary analyses showed benefits in terms of adherence or retention.


The study concludes that BUP plus XR-NTX deserves further “confirmatory” study as pharmacotherapy for cocaine use disorder. However, the null finding for the primary outcome, use of a single-sided test of significance, lack of adjustment for multiple analyses, and poor precision of the longitudinal effect estimate raise the likelihood that the one positive finding was by chance. The search for effective pharmacotherapy for cocaine use disorder continues.

Peter D. Friedmann, MD, MPH


Ling W, Hillhouse MP, Saxon AJ, et al. Buprenorphine + naloxone plus naltrexone for the treatment of cocaine dependence: the Cocaine Use Reduction with Buprenorphine (CURB) study. Addiction. 2016;111(8):1416–1427.

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