Clinical Report: Psilocybin for Cocaine Use: Signal or Noise?

Overview

A small randomized clinical trial suggests that psilocybin combined with intensive psychotherapy may increase cocaine-abstinent days and reduce the risk of cocaine lapse compared to an active placebo. However, the findings are preliminary and warrant further investigation due to significant methodological limitations, including compromised blinding and small sample size.

Background

Cocaine use disorder currently lacks approved pharmacotherapy, with contingency management being the only consistently effective intervention. The potential of psilocybin as a treatment option could represent a significant advancement in addressing this challenging addiction. Understanding the efficacy and safety of psilocybin in this context is crucial for developing future treatment strategies.

Data Highlights

Key Findings

• Psilocybin led to approximately 29 more percentage points of cocaine-abstinent days compared to placebo.
• Complete abstinence through day 180 was achieved by 6 patients in the psilocybin group, none in the placebo group.
• Patients receiving psilocybin were 18 times more likely to achieve complete abstinence.
• No serious adverse events were reported; however, adverse events were more common in the psilocybin group, including hypertension and emotional distress.
• Blinding was compromised, with many participants correctly guessing their treatment assignment, raising concerns about expectancy effects.

Clinical Implications

The findings suggest that psilocybin may be a promising adjunct to psychotherapy for cocaine use disorder, potentially increasing abstinence rates. However, clinicians should consider the preliminary nature of these results and the significant methodological limitations before integrating psilocybin into treatment protocols.

Conclusion

While psilocybin shows potential in enhancing treatment outcomes for cocaine use disorder, further research is necessary to confirm these findings and address the limitations of the current study, particularly regarding blinding and sample size.

Related Resources & Content

1. JAMA Network, JAMA Network Open, 2026 -- Psilocybin in the Treatment of Cocaine Use Disorder: A Randomized Clinical Trial
2. The ASAM/AAAP Clinical Practice Guideline on the Management of Stimulant Use Disorder, 2024
3. conexiant, 2025 -- Psilocybin Beats Nicotine Patch in Smoking Trial
4. the asco post, 2025 -- Psilocybin-Based Therapy May Address Mental Health Issues in Patients With Cancer, Addiction
5. conexiant, 2025 -- Psilocybin Trial in Treatment-Resistant Depression Shows Mixed Results
6. the asco post — Psilocybin May Benefit Patients With Cancer, Major Depressive Disorder
7. The ASAM/AAAP Clinical Practice Guideline on the Management of Stimulant Use Disorder
8. Psilocybin in the Treatment of Cocaine Use Disorder: A Randomized Clinical Trial | Psychiatry and Behavioral Health | JAMA Network Open | JAMA Network
9. Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial | Trials | JAMA Psychiatry | JAMA Network