Psilocybin Shows Promise as Single-Dose Treatment for Cocaine Use Disorder

A double-blind study in *JAMA Network Open* gave 19 adults with cocaine use disorder a single oral dose of psilocybin and 17 a diphenhydramine placebo. All participants received identical psychotherapy. The psilocybin group showed a higher rate of cocaine abstinence during follow-up than the placebo group.

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Cocaine use disorder has no FDA-approved medication, and stimulant-related deaths are climbing in the United States. The United Nations’ latest global drug report notes a worldwide increase in cocaine-related mortality as production reaches a record high.

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The trial was led by Dr Peter Hendricks, behavioral health professor at the University of Alabama at Birmingham. Co-authors included Gabrielle Agin-Liebes of Yale School of Medicine and neuroscientist Robin Carhart-Harris, noted for psychedelic research.

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Nineteen participants received psilocybin and seventeen received placebo; most were low-income Black men, a group disproportionately affected by cocaine-related criminal-justice involvement in Birmingham. Both arms received the same therapeutic support.

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Researchers suggest psilocybin boosts neuroplasticity and psychological flexibility, allowing a single session to act as a catalyst for lasting cognitive change. Unlike opioid or nicotine replacement, it does not target cocaine’s neurochemical pathways but induces a profound altered state that may disrupt rigid, impulsive patterns.

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Hendricks stressed that cocaine use drives incarceration, especially for Black men, making a rapid-acting therapy urgent. Agin-Liebes emphasized that psilocybin’s single-session model differs from maintenance drugs. Carhart-Harris noted that increased neuroplasticity could help individuals escape the “ruts” of addiction and related mood disorders.

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A commentary warned that excluding participants with comorbid depression or anxiety limits generalizability. Critics also noted that the design may reduce expectation bias but cannot fully prevent participants from guessing their assignment based on the drug’s distinctive effects.

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The report does not include long-term follow-up beyond the immediate post-treatment period, and the sample is limited to Birmingham, leaving uncertainty about broader geographic or socioeconomic applicability.

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• “It’s more like a catalyst within a therapeutic process,” — Gabrielle Agin-Liebes, Clinical Psychologist, Yale School of Medicine

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• “psilocybin is different” — Gabrielle Agin-Liebes, Clinical Psychologist, Yale School of Medicine

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• “people get stuck in ruts” — Robin Carhart-Harris, Neuroscience Researcher

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• “we wanted to recruit people who were dependent on cocaine or had cocaine use disorder, and wanted to stop” — Peter Hendricks, Behavioral Health Professor, University of Alabama at Birmingham

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The team calls for larger, multisite trials to confirm efficacy, assess long-term abstinence, and include participants with co-occurring mental health conditions. Successful replication could provide the first evidence-based medication for cocaine use disorder, a condition linked to disproportionate criminal-justice involvement among low-income Black men.

The Guardian