Cocaine addiction remains one of the hardest problems in addiction treatment.
Despite rising cocaine-related overdose deaths in the US since 2019, there are still no approved medications for cocaine use disorder. Treatment options exist, but they’re limited. Contingency management (essentially rewarding people for staying abstinent) has shown some success, though it can be difficult to sustain outside controlled settings.
That’s why a new study published in JAMA Network Open is drawing serious attention.
Led by Peter Hendricks at the University of Alabama at Birmingham, this is the first clinical trial of any psychedelic for cocaine use disorder. The research took nine years to complete, running from 2015 to 2024, and the results suggest psilocybin may have an important role to play in a space where treatment innovation has been painfully slow.
A First-of-Its-Kind Study
The trial enrolled 40 adults with cocaine use disorder from the Deep South of the United States.
Importantly, this was not the kind of participant pool who often take part in psychedelic research.
The sample was deliberately representative. Around 82.5% of participants were Black, 65% had annual incomes of $20,000 or less, and cocaine use histories averaged more than two decades. Most participants had tried to quit before.
This matters.
Psychedelic research has long been dominated by what researchers call WEIRD populations — Western, Educated, Industrialised, Rich and Democratic. Hendricks and his team wanted something different. Participants first completed four to five two-hour preparation sessions using therapy that combined client-centred and cognitive behavioural approaches.
Then came the dosing session. One group received a single oral dose of psilocybin at 25mg per 70kg of body weight. The comparison group received 100mg diphenhydramine—an antihistamine used as an active placebo.
Five weekly integration sessions followed. Researchers then assessed outcomes at both 90 and 180 days after treatment.
The study design was rigorous from top to bottom. It was quadruple-blind, meaning participants, therapists, outcome assessors and statisticians were all unaware of who received which treatment.
For psychedelic research, that level of methodological care matters.
What Happened After Treatment?
The headline result is simple.
Psilocybin worked best.
And not just by a little.
Across the post-treatment period, participants who received psilocybin reported roughly 29 percentage points more cocaine-abstinent days compared with placebo.
Even more striking, six out of twenty people in the psilocybin group achieved complete abstinence from the end of treatment through day 180. In the placebo group, that number was zero.
The study also measured time to first lapse, and here again, psilocybin showed a strong effect.
The hazard ratio was 0.28 compared with placebo, meaning relapse risk was substantially lower in the psilocybin group.
At 90 days, 55% of people who received psilocybin had not lapsed, while in the placebo group, only 21% remained lapse-free.
No serious adverse events occurred. For a condition with no approved medications and notoriously difficult treatment outcomes, that’s a meaningful signal.
A Study That Looks More Like the Real World
One of the most important aspects of the trial isn’t just what happened — it’s who it happened to.
Hendricks has spoken openly about the demographic imbalance in psychedelic science.
“Psychedelics have long been popular among the college-educated elite, the intelligentsia, and, as you know full well, especially in recent times, the ultra-wealthy. When a psychedelic study is recruiting, these are the people on the lookout.”
That imbalance creates a problem, because if research only reflects highly educated or financially privileged participants, it becomes harder to understand how treatments work across the broader population.
Hendricks frames the issue directly.
“This is fundamentally a matter of collaboration rather than extraction. Science has for too long been extractive. We must be collaborative.”
The study’s participant makeup may also explain something unusual: the placebo performed relatively well.
Because only three participants had prior hallucinogen experience, diphenhydramine functioned as a reasonably effective active placebo. Around half the placebo group correctly guessed their allocation, roughly consistent with chance.
That’s a notable contrast with trials recruiting psychedelic enthusiasts, where blinding often collapses quickly.
How Might Psilocybin Help With Addiction?
The numbers matter. But addiction treatment is rarely just about numbers.
Hendricks served as the primary therapist throughout the trial, giving him an unusually close view of what participants were actually experiencing.
“I saw what appeared to be the resolution of ambivalence secondary to insights around the incompatibility of cocaine use with deeply held personal values and beliefs, and enhanced thought-action repertoire — engagement with a wider range of more adaptive behaviour to cope with negative affect, life stressors, and the urge to use.”
That description lines up with a growing body of psychedelic research pointing toward psychological flexibility.
Addiction is often characterised by rigid behavioural loops, self-reinforcing patterns that become increasingly difficult to interrupt.
Psilocybin appears to loosen those patterns.
Neuroimaging studies have shown that psilocybin reduces cohesion within the Default Mode Network while increasing communication between different brain regions. In simpler terms, the brain becomes temporarily less locked into habitual ways of operating.
At the same time, psilocybin promotes neuroplasticity, creating a window where learning, emotional processing and psychotherapy may carry amplified effects. And then there’s the subjective experience itself.
Hendricks describes something harder to measure but difficult to ignore.
“Anecdotally, I think for many people the reaction to the psilocybin experience was: ‘Enough is enough. I’m never doing this again. Once and for all, I’m done with cocaine.’”
That kind of shift echoes what psychologist William Miller called quantum change: sudden, durable transformations in behaviour and values that don’t follow the slow trajectory conventional therapy often assumes.
Psilocybin may be particularly effective at catalysing these moments.
Why The Results Held So Long
Perhaps the most surprising outcome was durability, as cocaine addiction is usually chronic and relapsing. Yet across 180 days, researchers found no significant group-by-time interaction. In other words, the treatment effect wasn’t fading during follow-up.
Hendricks admitted this surprised him.
“I guess I was, only because addiction is, by nature, a chronic, relapsing condition.”
Still, he reframes the issue differently. Cocaine use is ultimately a behaviour, one people can and do stop permanently.
“There are countless success stories from outside the world of psychedelics to support this idea.”
The next question is clear: could repeated psilocybin sessions improve outcomes further? After all, fourteen of the twenty psilocybin participants did not reach complete abstinence.
Hendricks is already thinking ahead.
“If a second (or third, or fourth, etc.) dose increases the likelihood of this outcome, then I think we should explore this.”
Important Limitations: And Why They Matter
This remains a small study. Forty participants is not enough to settle the science.
Confidence intervals were wide, psychotherapy fidelity monitoring wasn’t feasible, and Hendricks serving as lead therapist introduces possible allegiance effects, even within a manualised protocol, so, the researchers are appropriately cautious.
“Given the small sample size and resulting wide CIs around the effect size estimates, findings should be interpreted with caution and conceptualized as hypothesis-generating rather than confirmatory.”
That said, early-stage research is supposed to identify signals worth pursuing.
And this trial delivered one.
Kas toliau?
Hendricks already sees the roadmap.
“A large multisite trial or trials that can inform a new drug application — a priority in light of the executive order — pragmatic trials, and those that allow us to optimise dosing regimens and psychotherapy protocols.”
The executive order he references is the Trump administration’s 2025 directive designed to accelerate psychedelic research. Whether that momentum translates into better-funded studies and broader clinical access remains to be seen.
But something important has already happened. A rigorous first-in-condition psychedelic trial for cocaine addiction produced a clear positive signal in a representative population after nearly a decade of work.
For a condition long underserved by medicine, this feels like a genuine opening.
