The First Drug That Works for Cocaine Use Disorder Is a Psychedelic

Research Roundup — May 30, 2026

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There is no FDA-approved medication for cocaine use disorder. Not one. There is no equivalent of buprenorphine for stimulant use, no methadone, no naltrexone with a robust cocaine-specific evidence base. Contingency management — the behavioral intervention that rewards abstinence — works, and five states have now made it available through Medicaid. But medication? Nothing approved. Nothing close to approved.

On May 8, JAMA Network Open published a randomized controlled trial from the University of Alabama at Birmingham that may be the beginning of a path toward something. The trial tested a single high dose of psilocybin combined with psychotherapy against a placebo (diphenhydramine, an antihistamine used to blind participants without producing psychedelic effects) combined with the same psychotherapy. Forty participants, a relatively small but adequately powered Phase 2 study, recruited specifically to include underrepresented and vulnerable populations — people who are not typically enrolled in early psychedelic research.

At 180 days, roughly 30 percent of participants who received psilocybin had achieved complete cocaine abstinence, confirmed by urine toxicology. Zero percent in the placebo group. The difference was statistically significant and the effect size was large.

The study published in JAMA Network Open, Vol. 9, No. 5, was conducted by a team at UAB that had been quietly building a case for psilocybin in stimulant use disorders since 2022. The trial registered as the Red Light study in ClinicalTrials.gov was one of the first to specifically target cocaine use disorder rather than generalizing from depression or addiction-adjacent conditions.

What the trial actually measured — and what 30 percent means

The primary outcome was verified cocaine abstinence at 180 days. That is a hard endpoint. Urine toxicology, not self-report. Every participant in the psilocybin arm who had a positive screen at any point in the follow-up period was counted as a non-responder. The 30 percent figure is the fraction who reached the six-month mark without any confirmed cocaine use.

To understand why 30 percent is significant, consider the base rate for cocaine use disorder treatment. With current behavioral approaches — cognitive behavioral therapy, motivational interviewing, community reinforcement — 12-month abstinence rates in clinical trials typically run 8 to 15 percent. Contingency management, the most effective current intervention, achieves 20 to 30 percent negative urine screens during the active treatment period; abstinence rates at 6 months post-intervention are substantially lower. A single-dose intervention that achieves 30 percent verified abstinence at 180 days, with no ongoing active treatment in that window, is a result the stimulant treatment field has never seen from a pharmacological approach.

It is also a small trial. Forty participants is not a Phase 3 study. The confidence intervals are wide. The population was limited to Birmingham, Alabama, which has specific demographic characteristics. The researchers controlled for psychotherapy, which complicates isolating the psilocybin effect from the therapeutic context. No one should read this trial as “psilocybin cures cocaine use disorder.” That is not what it shows.

What it shows is a signal strong enough to justify a Phase 3 trial, and a mechanism plausible enough to explain why psilocybin might work where other approaches haven’t. The probable mechanism involves serotonin 5-HT2A receptor agonism and its downstream effects on neuroplasticity — specifically, the reorganization of maladaptive reward circuitry and the reduction of craving-associated neural activation patterns that maintain compulsive stimulant use. A single psilocybin session appears to induce a period of heightened neuroplasticity during which psychotherapy can make changes that would otherwise require months of sustained engagement.

Why cocaine use disorder is the hardest problem in addiction medicine

Cocaine and methamphetamine are the substances for which the existing treatment system is most clearly inadequate. There are no medications. The behavioral interventions work but require sustained engagement. The relapse rates are high. And in Arizona, methamphetamine was involved in 67 percent of fatal overdoses in 2024 — not as the primary substance, but as a co-occurring substance, often combined with fentanyl in the polysubstance pattern that now characterizes most fatal overdoses in the state.

Cocaine and methamphetamine are the substances for which the existing treatment system is most clearly inadequate.

A treatment field without pharmacological options for stimulant use disorder is a treatment field that relies entirely on the person’s engagement with behavioral change. That works for some people. For others — people in deep-phase stimulant use disorder, people with co-occurring mental health conditions, people for whom outpatient behavioral treatment has failed multiple times — it is an incomplete toolkit and they know it.

The Trump administration’s April 18 executive order directed at least $50 million in federal research funding toward psychedelic therapies for veterans, with specific mention of ibogaine for opioid addiction and PTSD. The order accelerated the regulatory pathway and directed agencies to reduce barriers to clinical trials. That policy context means the window between a positive Phase 2 result and a Phase 3 trial has never been shorter.

The limitations that require honesty

Forty people is a small trial. The placebo control for a psychedelic is methodologically imperfect — diphenhydramine blunts but doesn’t eliminate the expectation effect of receiving a substance in a therapeutic setting. The psychotherapy component was standardized but intensive; most people receiving psilocybin outside a clinical trial would not receive the same quality and quantity of therapeutic support. The follow-up period was six months; longer-term data doesn’t exist yet.

The trial specifically enrolled underrepresented populations, which is a genuine strength, but the Birmingham context may not translate directly to the demographics and polysubstance patterns of Arizona’s stimulant population.

These limitations are not arguments against the finding. They are the arguments for a Phase 3 trial — larger, multi-site, with longer follow-up and more diverse populations. If a Phase 3 replicates the Phase 2 result at half the effect size, it would still be the most effective pharmacological intervention for cocaine use disorder in history.

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The full trial is published as: “Single-Dose Psilocybin With Psychotherapy for Cocaine Use Disorder: A Randomized Clinical Trial.” JAMA Network Open, Vol. 9, No. 5, 2026. For continuing updates on psychedelic therapies in addiction medicine, see the Rize Newsroom’s psychedelics-empathogens coverage.