John is a 28 year-old man who is coming to you to establish primary care. You’re running about 20 minutes late and thank John for his patience. He says he doesn’t have much time today because he has a work meeting shortly. He says that he is pretty healthy! He filled out a questionnaire as part of your clinic’s annual intake forms, noting that he drinks four or more drinks roughly five times a week. He also checked yes for “other substance use,” recreationally.
You confirm that John has no significant past medical history to review. You start off by talking about his alcohol use. Based on his report, this use is above healthy limits for men. This is the brief intervention (of SBIRT). With your nonjudgmental and welcoming attitude in reviewing his substance use history, you learn that at times, when John drinks, he also uses cocaine. He has noticed that on most days he looks forward to both alcohol and cocaine. He feels like he needs the cocaine to “enjoy the night” and at times to do his job during the day. John is embarrassed to talk with his partner about his substance use. He wonders if she knows because she encouraged him to get a PCP to “check up” on his health. He says he ultimately does want to reduce his alcohol and cocaine use for his health and before he has children.
John says that he uses cocaine sometimes because it’s just there when he’s drinking but occasionally because he needs energy to do something or just likes the feeling. He doesn’t like the anxious thoughts he has as the cocaine wears off and that’s often when he drinks more. John doesn’t want to do anything that would be bad for his health, especially his heart, as his grandfather died of a heart attack in his 60’s.
You discuss that from everything he has shared, it seems like he has developed alcohol and cocaine addiction.
You also review with John that when alcohol and cocaine are used together, people will often feel prolonged cocaine effects. This is because cocaine and alcohol together form a new psychoactive substance called cocaethylene, which has a longer half-life than cocaine. People experience a longer-lasting and more intense effect than with cocaine alone, potentially with increased cardiotoxicity compared to its parent drug cocaine (Pergolizzi 2022).
What medications can help patients reduce cocaine (and alcohol) use?
There is no FDA-approved medication to treat cocaine use disorder. The best evidence to reduce stimulant use is for behavioral treatment, specifically in the form of contingency management. Contingency management reinforces positive behavior change with variable rewards, as reviewed in a previous PsychSnap on treating methamphetamine use disorder.
There is some literature on pharmacotherapy for treating cocaine use disorder, but it is generally of low quality. A 2019 systematic review and meta-analysis reported that some studies have found positive signals for topiramate, bupropion, and the combination of topiramate plus mixed amphetamine salts, in particular around increased abstinence (Chan 2019).
We reviewed the robust data for topiramate in treating alcohol use disorder (off-label) in a previous PsychSnap. There are also a few studies of topiramate for treating cocaine use disorder.
In a double blind, randomized, placebo-controlled 12 week trial of 142 adults using cocaine in Virginia, 71 participants were randomized to receive placebo vs topiramate (300mg/day in weeks 6 to 12 after a 6 week titration) combined with weekly CBT. Those on topiramate were found to have increased mean weekly proportion of cocaine nonuse days (Johnson 2013).
Another 2013 trial looked at the impact of topiramate on cocaine and alcohol use in patients with addiction to both substances (like John!). This was a double-blind, placebo-controlled, 13-week trial with 170 patients in Philadelphia who used both substances. They were randomized to topiramate 300mg daily or placebo, in addition to weekly therapy. The primary outcome was self-reported alcohol and cocaine use (confirmed with urine drug screens). Topiramate combined with therapy was not better than placebo in reducing either cocaine or alcohol use. However, on secondary outcomes, people taking topiramate were more likely to be abstinent from cocaine during the last three weeks of the trial, and those with more severe cocaine withdrawal symptoms responded better (more cocaine-negative urine tests) to topiramate (Kampman 2013).
In the 2023 ASAM/AAAP Clinical Practice Guideline for stimulant use disorder treatment, there was committee consensus on low certainty evidence to support topiramate for reducing cocaine use based on at least 6 RCTs. That same guideline highlighted that bupropion (in doses of bupropion SR 150mg BID or bupropion XL 300mg daily) and the combination of topiramate and mixed amphetamine salts could be considered for patients with cocaine use disorder with moderate evidence. Look out for a future PsychSnap on this topic as more data emerges on their use.
Returning to John, you discuss the option of starting topiramate slowly over the course of weeks to see if that can help him reduce the number of days that he drinks and uses cocaine. He is ready to start the topiramate 25mg at bedtime this week and follow the slow titration schedule (topiramate 25mg bedtime x1wk, 25mg BID x1 wk, 25mg in AM/50mg at bedtime x1wk, then 50mg BID x1wk. Aim to get as close to 300mg total daily dose as per the trials above as tolerated with further weekly increases by 25-50mg based on how the patient tolerates the medication). John makes a follow up appointment in 3 weeks to check in.
Key Points
- Cocaethylene is a new psychoactive compound formed when alcohol and cocaine are mixed that lasts longer than cocaine and may be more cardiotoxic.
- Topiramate can be considered as off-label treatment for alcohol use disorder and cocaine use disorder to help patients reduce use.
Related PsychSnaps
“What treatments help patients stop using methamphetamine?” Era Kryzhanovskaya. March, 2024.
“What medications can help patients with alcohol use disorder reduce their drinking other than naltrexone?” Era Kryzhanovskaya. March, 2025.
“How do you help patients cut back on drinking?” Era Kryzhanovskaya. December, 2023
References:
Chan B, Kondo K, Freeman M, Ayers C, Montgomery J, Kansagara D. Pharmacotherapy for Cocaine Use Disorder-a Systematic Review and Meta-analysis. J Gen Intern Med. 2019 Dec;34(12):2858-2873. doi: 10.1007/s11606-019-05074-8. Epub 2019 Jun 10. PMID: 31183685; PMCID: PMC6854210.
Johnson BA, Ait-Daoud N, Wang X, et al. Topiramate for the Treatment of Cocaine Addiction: A Randomized Clinical Trial. JAMA Psychiatry. 2013;70(12):1338–1346. doi:10.1001/jamapsychiatry.2013.2295
Kampman KM, Pettinati HM, Lynch KG, Spratt K, Wierzbicki MR, O’Brien CP. A double-blind, placebo-controlled trial of topiramate for the treatment of comorbid cocaine and alcohol dependence. Drug Alcohol Depend. 2013 Nov 1;133(1):94-9. doi: 10.1016/j.drugalcdep.2013.05.026. Epub 2013 Jun 28. PMID: 23810644; PMCID: PMC3786029.
Pergolizzi J, Breve F, Magnusson P, LeQuang JAK, Varrassi G. Cocaethylene: When Cocaine and Alcohol Are Taken Together. Cureus. 2022 Feb 22;14(2):e22498. doi: 10.7759/cureus.22498. PMID: 35345678; PMCID: PMC8956485.https://pmc.ncbi.nlm.nih.gov/articles/PMC8956485/
ASAM/AAAP Clinical Practice Guideline: https://downloads.asam.org/sitefinity-production-blobs/docs/default-source/quality-science/stud_guideline_document_final.pdf?sfvrsn=71094b38_1
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