A Different Kind of Door: What a New Psilocybin Trial Means for Cocaine Use Disorder
- Joyce Knieff, ND, LAc
- Jun 4
- 7 min read
Cocaine addiction has been one of the most stubborn problems in addiction medicine. Despite decades of research and considerable money spent, no medication has ever been approved for cocaine use disorder. Use is rising in the United States and globally. Most people who want to stop are offered cognitive behavioral therapy and contingency-management approaches, both of which help, neither of which works as reliably as patients and clinicians wish. A trial published this month in JAMA Network Open tested a different kind of intervention, a single high-dose session of psilocybin paired with psychotherapy, and the results are getting attention because they exceed what any prior pharmacological approach has shown.
TL;DR: A single high-dose psilocybin session paired with therapy sharply cut cocaine use in one small trial, though it needs larger replication before becoming clinical practice.
Key takeaways:
A 40-person trial paired one psilocybin dose with therapy for cocaine use disorder.
The psilocybin group had far higher abstinence; no placebo participant fully quit.
The study deliberately enrolled mostly Black, lower-income adults often left out of research.
It's still investigational and illegal outside approved trials, not a self-treatment.
What the research found
The trial, led by Peter Hendricks at the University of Alabama at Birmingham and built over more than a decade, enrolled 40 adults with cocaine use disorder who were motivated to quit. Participants were randomly assigned to receive either a 25 mg/70 kg oral dose of psilocybin or an active placebo (diphenhydramine, an antihistamine that produces some sedation and cognitive slowing without psychedelic effects). The active placebo design matters because it makes blinding more honest. Everyone in the trial received four to five sessions of cognitive behavioral therapy beforehand and additional psychotherapy sessions afterward to help integrate any insights from the experience into actual life changes.
What makes the participant pool unusual is worth pausing on. Most psychedelic research has been done in predominantly white, college-educated, higher-income samples. Hendricks deliberately set out to recruit the population most affected by cocaine use disorder in his region. Of the 40 enrolled participants, 33 (82.5 percent) were Black, and 26 (65 percent) reported annual incomes of $20,000 or less. This isn't a small detail. It addresses one of the most legitimate critiques of psychedelic research: that the evidence base has been built in populations that don't reflect the people who most need addiction treatment.
The outcomes at 180 days were measured several ways. The psilocybin group had a substantially higher percentage of cocaine-abstinent days (a difference of about 29 percentage points). They were dramatically more likely to be completely abstinent from cocaine (odds ratio 18.4). The risk of returning to cocaine use over time was reduced by 72 percent. Six participants in the psilocybin group reported complete abstinence at 180 days, with urinalysis confirming no cocaine in their systems. None of the placebo participants achieved complete abstinence. The average cocaine use in the psilocybin group at follow-up was 1.5 times per month, compared with 12 times per month in the placebo group. No serious adverse events occurred.
The most honest reading is that this is a small study (40 people), conducted at a single site, with all the limitations that come with that. The effect size is large enough to be striking, but replication at larger scale and across multiple sites is the appropriate next step before this becomes clinical practice. The investigators are pursuing that work.
Where this fits in the broader literature
Psilocybin-assisted therapy has been showing promise across a range of conditions where conventional treatment has hit limits. A 2022 randomized trial published in JAMA Psychiatry by Michael Bogenschutz and colleagues at NYU tested psilocybin-assisted therapy in 95 adults with alcohol use disorder and found a substantial reduction in heavy drinking days compared with placebo, with the effect sustained through 32 weeks of follow-up. A 2024 review in the American Journal of Psychiatry by Imperio and colleagues synthesized the neuroscience of substance use disorders and the emerging evidence base for psychedelics and other neuroplasticity-targeted approaches, framing psilocybin within a broader shift in how the field is thinking about addiction recovery.
The proposed mechanism runs through a few pathways. Psilocybin activates serotonin 2A receptors in the brain, which triggers a temporary state of heightened neural plasticity. That window of plasticity, when paired with skilled psychotherapy and meaningful psychological work, appears to help some people loosen entrenched patterns of behavior, motivation, and self-narrative in ways that conventional therapy hasn't been able to match. The session itself is a single experience, but the change appears to come from what the person does with that experience in the weeks and months afterward.
This is not a story about a drug that fixes addiction. It is a story about a particular kind of pharmacologically-assisted therapeutic experience that, in carefully designed protocols, appears to help some people make changes they couldn't make on their own.
The naturopathic perspective
A few framing pieces are important here, because this is an area where the discussion can easily go off course in either direction.
First, psilocybin is currently a Schedule I controlled substance under U.S. federal law and most state laws. The Hendricks trial was conducted under FDA and DEA research authorization, in a tightly controlled clinical setting, with extensive medical and psychological screening, dedicated preparation and integration therapy, and monitoring during the dosing session. Recreational or unsupervised use is a different picture entirely, with real risks, including challenging psychological experiences, destabilization for people with certain psychiatric histories, and the absence of the therapeutic frame that appears to be doing much of the work in clinical trials. The trial result is not an endorsement of self-treatment.
Second, this is one of those areas where naturopathic medicine has often been a quieter voice in the room, paying attention to the long history of how plant medicines and altered states have been used in healing contexts across cultures, while also taking seriously the safety considerations that any powerful intervention requires. The newer clinical research is converging with some of that older clinical instinct, with rigorous frameworks for screening, preparation, dosing, and integration. The frame that appears to matter most is the integration: the work done in the weeks and months after a session, with a skilled clinician, to translate any insights into actual changes in how a person lives.
Third, addiction is a whole-body condition with biological, psychological, social, and spiritual dimensions, and effective recovery work has always engaged all of those layers. Nutrition, sleep, movement, nervous-system regulation, social connection, meaningful work, treatment of any underlying mental health conditions, and (when relevant) medication-assisted treatment all matter. Psilocybin-assisted therapy, if and when it becomes available as a clinical treatment, would sit alongside that broader work as one component of a larger care plan.
The Hendricks trial is a meaningful result, particularly for a population that conventional treatment has often failed. It is also one piece of a larger picture in which substance use disorders are increasingly being met with multidimensional care rather than a single magic bullet.
How to apply this now
For most readers, the practical takeaway is not "find some psilocybin." Outside of approved clinical trials, that path carries real legal and clinical risk. The takeaway is closer to: the science on addiction is evolving in ways that should make us cautiously hopeful, including for the cocaine use disorder population that has been least well-served by existing pharmacology.
If you or someone you love is struggling with cocaine use, what is available today is real and worth using. Cognitive behavioral therapy, contingency management, mutual-support groups (Cocaine Anonymous, SMART Recovery, others), and integrated care that addresses underlying mental health conditions all have evidence behind them. Effective primary care that supports sleep, nutrition, movement, and the broader picture of recovery matters. So does treatment for any co-occurring conditions like depression, PTSD, or anxiety, which are common companions to substance use.
If you are interested in following the psilocybin research, the path forward will be larger multi-site clinical trials over the next several years, regulatory review, and eventually, if the data hold up, supervised access through trained clinicians within a defined protocol. That is the path that has the safety and efficacy evidence behind it. Bookmark it and watch the space.
Frequently asked questions
Should I try psilocybin for addiction?
Not outside an approved clinical trial. Psilocybin is a Schedule I substance, and this result came from a tightly controlled setting with medical screening, preparation, and integration therapy. Using it on your own carries real legal and psychological risk. The takeaway is hope about where the science is heading, not a green light for self-treatment.
What treatments for cocaine use disorder actually work right now?
There's no approved medication yet, but cognitive behavioral therapy, contingency management, and mutual-support groups like Cocaine Anonymous and SMART Recovery all have evidence behind them. Treating co-occurring depression, anxiety, or PTSD matters too, as does care for sleep, nutrition, and movement.
How strong is this study?
It's promising but small, with 40 people at a single site. The effect size was large, yet a result like this needs to hold up in bigger, multi-site trials before it changes clinical practice. The researchers are pursuing that work now.
Why does it matter who was in the study?
Most psychedelic research has been done in mostly white, higher-income groups. This trial deliberately enrolled the people most affected by cocaine use disorder in the region, and 82.5 percent were Black while most reported low incomes. That makes the findings far more relevant to the people who actually need treatment.
What does Yggdrasil recommend for someone struggling with substance use?
Recovery works best when it addresses the whole person, since the biological, psychological, social, and spiritual layers all feed into each other. That means evidence-based therapy and support groups, treatment for any underlying mental health conditions, and care for sleep, nutrition, movement, and nervous-system regulation. If you're struggling, reaching out to a qualified clinician is a strong first step.
References
Hendricks PS, Lappan SN, Shelton RC, et al. Psilocybin in the Treatment of Cocaine Use Disorder: A Randomized Clinical Trial. JAMA Netw Open. 2026;9(5):e2611029. PMID: 42096204. DOI. Original AANP digest link: https://www.science.org/content/article/magic-mushroom-compound-shows-promise-against-cocaine-addiction
Bogenschutz MP, Ross S, Bhatt S, et al. 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. JAMA Psychiatry. 2022;79(10):953-962. PMID: 36001306. DOI.
Imperio CG, Levin FR, Martinez D. The Neurocircuitry of Substance Use Disorder, Treatment, and Change: A Resource for Clinical Psychiatrists. Am J Psychiatry. 2024;181(11):958-972. PMID: 39380375. DOI.
A note before you go
This is for educational purposes and is not a substitute for individualized medical care. Psilocybin is currently a Schedule I controlled substance under U.S. federal law and is not available as a clinical treatment outside of approved research trials and a few specific jurisdictional exceptions. If you or someone you care about is struggling with substance use, please connect with a qualified addiction medicine clinician or mental health professional. Effective treatment is available, and asking for help is a strength.
Related reading
Reviewed by Joyce Knieff, ND, LAc on 2026-06-04.
If this resonates with what you're experiencing and you'd like to explore a naturopathic approach, book a consultation with our clinic.
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