There Has Never Been an FDA-Approved Medication for Cocaine Addiction. A Small Alabama Trial Just Showed Why That Might Be About to Change.

If you have tried to get help for cocaine use and been told there’s no pill for it, you were told the truth. Buprenorphine exists for opioids. Naltrexone and acamprosate exist for alcohol. Nothing FDA-approved exists for cocaine, and the FDA itself has only recently started publishing guidance on how a company would even design a trial to fix that. A small trial out of the University of Alabama at Birmingham, published in JAMA Network Open, just gave that gap its first real challenger — and it did it in a population psychedelic research has historically ignored.

A drug with no approved medication just got its first randomized evidence that one might actually work — for the patients most trials never enroll.

The trial, led by psychologist Peter Hendricks, randomized 40 adults with cocaine use disorder to a single dose of psilocybin (25mg per 70kg of body weight, the standard dose in modern psilocybin trials) plus cognitive behavioral therapy, or an active placebo plus the same therapy. Thirty-six participants completed the full 180-day follow-up. Thirty-three of the 40 were men; 33 identified as Black — a detail that matters more than a footnote, because psychedelic-assisted therapy trials have run overwhelmingly white and overwhelmingly recruited from people who could already afford therapy on their own. Cocaine use disorder, meanwhile, carries some of the steepest racial disparities in the entire substance use treatment system: Black Americans are diagnosed with cocaine use disorder at higher rates and are far less likely to be offered evidence-based treatment for it, in part because there hasn’t been one.

The topline result: participants in the psilocybin arm reduced their cocaine use to roughly 1.5 days per month by the end of the trial, compared to roughly 12 days per month in the placebo arm. Six of the psilocybin-arm participants were fully abstinent, with clean urine tests, at the 180-day mark — six months after a single guided dosing session. The most common side effect was a transient rise in blood pressure during the dosing day itself, not a lingering one. Hendricks framed the result the way a researcher should — as a promising signal, not a cure — telling UAB’s newsroom: “Cocaine use disorder has long lacked effective treatment options, and vulnerable populations have historically been underrepresented in psychedelic research trials.”

Here’s the layman version of why a mushroom-derived compound would do anything at all for a stimulant use disorder, since the mechanisms don’t obviously overlap the way, say, a nicotine patch obviously overlaps with a cigarette. Psilocybin acts on serotonin receptors in the brain in a way that appears to temporarily loosen rigid, well-worn thought patterns — the same rigidity researchers believe underlies compulsive craving loops, regardless of which drug built the loop. The therapy sessions around the dosing day are where that loosened window gets used: instead of medicating away the craving, the treatment tries to give someone a few hours where the craving’s usual grip on their attention weakens enough to actually look at it, with a therapist in the room. That is different in kind from how buprenorphine works on an opioid receptor, and it’s part of why researchers are testing psilocybin across several use disorders at once rather than treating it as a cocaine-specific drug.

The caveats are real and worth naming with the same weight as the result. Forty people is a small trial, not a population, and a treatment effect this size needs to replicate in a larger, more diverse cohort before anyone should treat it as settled science. It was not compared against an existing standard of care, because there isn’t one — the “control” is an active placebo, not a competing medication, which is a lower bar to clear than trials for opioid or alcohol treatments get to clear. And a single dosing session under therapist supervision is a resource-intensive intervention to scale into a health system that already can’t get enough people into contingency management, the one behavioral treatment for stimulant use disorder that does have solid trial evidence behind it — the NIDA Clinical Trials Network’s own 2024 stimulant use disorder task force is still running parallel trials of transcranial magnetic stimulation and repurposed medications precisely because no single approach has cleared the bar on its own.

The caveats are real and worth naming with the same weight as the result.

None of that erases what the trial actually shows: a population that treatment research routinely leaves out just produced the kind of signal that gets a Phase 2 program funded. Cocaine deaths remain entangled with the fentanyl supply in national overdose data — most cocaine deaths now involve fentanyl contamination, not cocaine alone — which means a real treatment option for the underlying use disorder isn’t a niche clinical curiosity. It’s a missing piece of the same crisis the newsroom covers every day under a different drug’s name. If you’ve been told to just wait for something to exist for cocaine the way it exists for opioids: this is what “something” starting to exist actually looks like, in its earliest, most honest form — small, promising, and not yet proof of anything beyond the fact that the question is finally being asked of the people it should have been asked of years ago.