The Impact of Disulfiram Treatment on the Reinforcing Effects of Cocaine: A Randomized Clinical Trial
Open accessAbstract
BACKGROUND: Clinical trials indicate that disulfiram (250 mg/d) reduces cocaine use, though one study found that treatment with lower doses of disulfiram (62.5 and 125 mg/d) increased cocaine use. We conducted the present study to better understand how disulfiram alters the reinforcing effects of cocaine in cocaine users. METHODS: Seventeen non-treatment seeking, cocaine-dependent volunteers participated in this double-blind, placebo-controlled, laboratory-based study. A cross-over design was utilized in which participants received placebo in one phase and disulfiram (250 mg/d) in the other. Following three days of study medication participants completed two choice sessions. In one they made 10 choices between receiving an intravenous infusion of saline or money that increased in value (US$ 0.05-16) and in the other cocaine (20 mg) or money. RESULTS: Participants chose cocaine more than saline under both disulfiram and placebo conditions (p<0.05). Unexpectedly, disulfiram increased both the number of cocaine and saline infusion choices (p<0.05). We next examined the relationship between disulfiram dose and cocaine choices. Disulfiram dose (mg/kg bodyweight) was negatively correlated with number of choices for cocaine (p<0.05). Disulfiram also enhanced cocaine-induced increases in cardiovascular measures (p's<0.05-0.01). CONCLUSIONS: Disulfiram's impact on the reinforcing effects of cocaine depends on dose relative to body weight. Our results suggest that the use of weight-based medication doses would produce more reliable effects, consistent with weight-based dosing used in pediatrics and in preclinical research. TRIAL REGISTRATION: Clinicaltrials.gov NCT00729300.
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The findings of clinical trials (NCT00729300, NCT00149630, NCT00913484) provide limited support for the efficacy of disulfiram for reducing cocaine dependence.
“the findings of clinical trials (NCT00729300, NCT00149630, NCT00913484) provide limited support for the efficacy of DIS for reducing cocaine dependence.35,36,37”
From Off-label and repurposed use of disulfiram beyond alcohol dependence: A systematic review of clinical and preclinical evidence (2026) · cites this paper as [35]
The Trial Registration identifies this paper as NCT00729300. Its Discussion reports that higher weight-adjusted doses were associated with fewer choices for IV cocaine, offering limited support for a potential benefit. But the Results report increased cocaine-infusion choices with disulfiram overall, and this short-term laboratory study did not establish reduced cocaine dependence. (LLM, conf=0.85)
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- Authors
- Haile, C. N., De La Garza, R., Mahoney, J. J., Nielsen, D. A., Kosten, T. R., & Newton, T. F.
- Affiliations
- Michael E. DeBakey VA Medical Center (US)
- Corresponding author
- Newton, Thomas F.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-11-08
- Volume
- 7
- Issue
- 11
- Pages
- e47702
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3493584
- OpenAlex
- W2073736163
- Cited by
- 26
- References
- 48
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2021: 1 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 4 · 2013: 4 · 2012: 1
- FWCI
- 2.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- RTI International
- Deutsches Krebsforschungszentrum
- National Institutes of Health (RR-00188)
- National Institute on Drug Abuse (R01DA017705, R25DA028976, K24DA017754)
- National Center for Research Resources (M01RR000188, M01 RR-00188)
- Topics
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Keywords
- disulfiram, cocaine, cocaine dependence, cocaine reinforcement, drug selection, dose-response relationship, weight-based dosing
- MeSH terms
- Adult, Choice Behavior, Cocaine, Disulfiram, Dose-Response Relationship, Drug, Double-Blind Method, Female, Heart Rate, Humans, Male, Treatment Outcome, Cross-Over Studies, Cocaine-Related Disorders
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