One Dose of Psilocybin Beat Cocaine Craving for Six Months. The Placebo Group Knew Within an Hour Which Pill They'd Gotten.

There is currently no FDA-approved medication for cocaine use disorder. Not one. Methadone exists for opioids, naltrexone and acamprosate exist for alcohol, and cocaine — despite decades of pharmaceutical trials for stimulant addiction — has nothing. That’s the backdrop against which a small randomized trial out of the University of Alabama at Birmingham landed in May, and why it’s worth writing about again now, in a substance category Rize’s own coverage has left almost entirely unaddressed this year: not one post on cocaine’s biology, its policy landscape, or the psychology of stimulant craving, in thirty days of daily publishing.

The trial, led by psychologist Peter S. Hendricks, randomized 40 adults with cocaine use disorder — 20 to a single high dose of psilocybin (25mg per 70kg body weight, paired with structured cognitive-behavioral therapy before and after), 20 to an active placebo of 100mg diphenhydramine plus the identical therapy schedule. Published in JAMA Network Open on May 7, it is the first controlled trial of psilocybin specifically for cocaine use disorder, and it was conducted almost entirely with a population psychedelic research has historically underrepresented: 82.5% of participants were Black, the median age was 50, most smoked crack rather than powder cocaine, and 65% earned $20,000 a year or less.

A drug you can only take once produced a measurable effect that lasted six months — in a population every other cocaine trial in the last two decades has mostly ignored.

The topline numbers are hard to dismiss. Over the 180-day follow-up, the psilocybin group’s percentage of cocaine-abstinent days ran nearly 29 percentage points higher than the placebo group’s — a gap with a 95% confidence interval of 18.22 to 39.67, well clear of chance. Thirty percent of the psilocybin group reached and sustained complete abstinence through six months; zero percent of the placebo group did. Framed as a number needed to treat — the standard way clinicians judge whether an intervention is worth deploying — that works out to roughly one additional person achieving full abstinence for every 3.3 people treated with psilocybin instead of placebo, a threshold most addiction pharmacotherapies never approach. Time to first lapse back into cocaine use was also meaningfully delayed, with a hazard ratio of 0.28 — meaning at any given point during follow-up, someone in the psilocybin group was roughly a third as likely to have relapsed as someone in the placebo group.

UAB’s own summary of the trial is notably more cautious in tone than the wave of press coverage that followed it, and outside commentary in Psychology Today flagged the same blinding problem independently. Safety-wise, nothing alarming turned up. No serious treatment-related adverse events were reported. Sixty-five percent of the psilocybin group experienced some adverse event, against 10% in the placebo group, but the list reads like a description of what a psilocybin session is supposed to feel like rather than a warning sign: elevated blood pressure in 30%, emotional distress in 25%, crying in 25%, most of it during the dosing session itself, not lingering afterward.

Here’s where the study’s own authors want you to slow down, and where a lot of the coverage racing to call this a breakthrough hasn’t. Ninety percent of people who got psilocybin correctly guessed they’d gotten psilocybin — which, if you have ever taken 25 milligrams of anything that makes the room breathe, is not surprising. You cannot blind a drug that alters your consciousness for six hours against a placebo that mostly makes you drowsy. That blinding failure means some portion of the effect could be expectation: people who know they just had a profound experience may report their subsequent cocaine use differently than people who know they got a sedating antihistamine, independent of any biological mechanism. The trial’s lead therapist also designed the psychotherapy protocol both groups received, a structural conflict researchers call allegiance bias — the person most invested in psilocybin working also shaped the therapy meant to help it work. And cocaine use itself relied heavily on participants’ own reports, backed up by urine testing but not eliminating the possibility of under-reporting. With only 40 people total, the confidence intervals on every outcome are wide enough that the authors — to their credit — describe their own findings as “hypothesis-generating rather than confirmatory,” not as proof psilocybin treats cocaine addiction.

You cannot blind a drug that alters your consciousness for six hours against a placebo that mostly makes you drowsy.

None of that erases what the study did establish. A single dose producing an effect that measurably persisted six months later, in a disorder with zero approved medications, in a population that gets left out of psychedelic research almost by default, is a real signal worth a larger, blinded, allegiance-neutral follow-up trial — the kind that could actually answer whether the effect is pharmacological, therapeutic, or some combination the field doesn’t yet have language for. What it is not, yet, is a finished answer. If you’re someone using cocaine and hoping this means a treatment is close, the honest version is: promising, unproven, years from your pharmacy — and in the meantime, the fentanyl contamination risk in today’s cocaine supply hasn’t gone anywhere, so test strips and naloxone remain the thing that’s actually available to you tonight, whatever a six-month trial eventually confirms.