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Psychedelic research: the key studies and their limits

BySafe Ceremonies

Ceremony websites, podcasts and news stories cite the same handful of studies again and again. Usually you get one line: “Johns Hopkins found,” “a study in the New England Journal of Medicine showed.” This guide goes through those studies one at a time, with what each one tested, how many people took part, what it found and what it couldn’t show.

Two things are worth holding on to as you read. Most of this research used psilocybin or MDMA made in a lab, at a known strength, given to carefully screened volunteers in a hospital or clinic with trained staff and hours of therapy. And most of the studies are small. A promising result in 30 people is a reason to run a bigger study. It isn’t proof.

Why the research is so recent

Scientists studied psychedelics in the 1950s and 1960s. After most of these substances were banned in the early 1970s, research on them was limited for decades. That is why almost every study below was published after 2005, and why so many questions are still open.

Psilocybin and meaningful experiences (2006)

The study that restarted mainstream interest came from Johns Hopkins. Thirty-six healthy adults who had never taken a hallucinogen, and who all took part regularly in religious or spiritual activities, received psilocybin in one session and a stimulant, methylphenidate, in another, without knowing which was which. Sessions were eight hours long, one person at a time, with monitors present.

Psilocybin produced experiences that scored high on questionnaires measuring mystical-type experience. Two months later, volunteers rated the session as having substantial personal meaning and spiritual significance, and friends and family reported positive changes in their attitudes and behavior. Psilocybin also produced anxiety in some sessions.

The limits: 36 people, chosen partly because they were already spiritually engaged, in an unusually supportive setting. It showed that such experiences can be produced in a lab. It wasn’t a treatment study.

Psilocybin and cancer-related distress (2016)

Two trials published together, from Johns Hopkins and New York University, gave psilocybin to people with cancer who were also living with depression or anxiety. The Hopkins trial had 51 participants and the NYU trial 29. Both used a crossover design: everyone eventually received both psilocybin and a comparison (a very low dose of psilocybin at Hopkins, niacin at NYU), in a random order, alongside psychotherapy.

Both reported large drops in depression and anxiety after the psilocybin session. At six months, about 80% of the Hopkins participants and about 60 to 80% of the NYU participants still showed clinically meaningful improvement. In both, the strength of the mystical-type experience during the session predicted how much people improved.

The limits: small samples, a very specific group of patients, and the crossover design, which means the long-term follow-up had no untreated comparison group because by then everyone had received psilocybin.

Early depression and addiction studies (2014 to 2016)

A 2016 study from Imperial College London gave psilocybin to 12 people with treatment-resistant depression, with psychological support before, during and after. Depression scores fell sharply at one week and three months. There was no control group; the study was designed to test whether this was feasible and safe. Every patient had short-lived anxiety as the effects began, and nine had brief confusion or disordered thinking.

A 2014 Johns Hopkins pilot gave psilocybin within a 15-week program to quit smoking. Twelve of 15 participants had not smoked in the week before their six-month check, confirmed by biological tests. The authors noted that an open-label study, where everyone knows what they’re getting, can’t settle whether psilocybin was the reason.

Psilocybin for major depression (2021)

A Johns Hopkins trial randomly assigned 27 adults with major depression to start psilocybin treatment right away or after an eight-week wait. Twenty-four completed it. Treatment meant two psilocybin sessions with around 11 hours of supportive therapy. Four weeks after treatment, depression scores in the treated group were far lower than in the group still waiting.

The limits: a waiting list is a weak comparison, because the people waiting know they haven’t been treated yet. The study also excluded anyone with a history of psychotic disorder, a serious suicide attempt or a psychiatric hospital stay, and anyone taking antidepressants.

Psilocybin against a standard antidepressant (2021)

This trial, published in the New England Journal of Medicine, is often cited as showing psilocybin beat an antidepressant. It’s more accurate to say it didn’t show a difference on the measure it was designed to test.

Fifty-nine people with moderate to severe depression were randomly assigned to psilocybin or to escitalopram, a common antidepressant, over six weeks, with psychological support for everyone. On the main measure of depression, the two groups weren’t significantly different. Several secondary measures, such as the share of people in remission, looked better in the psilocybin group, but the authors pointed out that these weren’t corrected for the number of comparisons made and called for larger, longer trials.

The larger psilocybin trial (2022)

A larger phase 2 trial included 233 people with treatment-resistant depression, randomly given a single session at one of three strengths of a synthetic psilocybin: high, medium or a very low comparison dose, with psychological support. After three weeks, the high dose had lowered depression scores significantly more than the very low dose. The medium dose had not.

Adverse events were common: 77% of participants had at least one, including headache, nausea and dizziness. Suicidal thoughts or behavior, or self-harm, occurred in all three groups. The authors concluded that larger and longer trials, including comparisons with existing treatments, were needed.

Larger phase 3 trials of the same synthetic psilocybin have since reported results, and the company developing it has said it is seeking approval from the US Food and Drug Administration. As of October 2026, no psilocybin medicine had been approved in the US.

Psilocybin and alcohol use disorder (2022)

This trial randomly assigned 95 adults with alcohol dependence to psilocybin or an active placebo (the antihistamine diphenhydramine, which has noticeable effects of its own), in two day-long sessions, within 12 weeks of structured psychotherapy. Over the 32 weeks after the first session, the psilocybin group drank heavily on 9.7% of days and the placebo group on 23.6%. No serious adverse events occurred among those who received psilocybin.

The limits: people with major psychiatric conditions, other drug use disorders and past hallucinogen use were excluded, and an active placebo still doesn’t fully disguise a psilocybin session.

MDMA for PTSD, and the 2024 decision

A phase 3 trial published in 2021 randomly assigned 90 people with severe PTSD to MDMA or placebo, each combined with a structured course of therapy: three preparation sessions, three eight-hour medication sessions and nine integration sessions. PTSD symptoms fell considerably more in the MDMA group two months after the last session.

When the sponsor applied for approval, an FDA advisory committee voted 9 to 2 in June 2024 that the data didn’t show the treatment worked, and 10 to 1 that its benefits didn’t outweigh its risks. One concern raised was functional unblinding, meaning participants could tell whether they’d received MDMA. In August 2024 the FDA declined to approve it and asked for another phase 3 trial.

Ayahuasca (2019)

The only placebo-controlled trial of ayahuasca for depression included 29 people with treatment-resistant depression and followed them for one week. Our guide on ayahuasca and mental health research covers it, and the wider ayahuasca evidence, in detail.

Problems that run through the whole field

A 2021 review of psychedelic trials argued that their effect sizes are probably overestimated. When a substance produces strong effects, most participants can tell whether they got it, and people who sign up for these trials often expect a lot from them. The review found that trials had generally not measured either of these problems and urged caution in reading the results.

Other limits come up again and again:

  • Samples are small. Most trials above had fewer than 100 people.
  • Participants are carefully selected. People with psychosis, bipolar disorder, serious suicide risk or certain medicines are usually excluded.
  • The substance comes with many hours of therapy, so it’s hard to know how much each part contributes.
  • Follow-up is often short, from a week to a few months.
  • Several trials are funded by companies hoping to sell the treatment, which doesn’t make them wrong, and is worth knowing.

What this means if you’re considering a ceremony

The research describes something quite different from most ceremonies. Trial participants are screened by doctors, take a known amount of a pure compound, sit with trained staff who usually outnumber them, and have therapy before and after. People at high risk are turned away. Even under those conditions, trials record anxiety, nausea, headaches and in some cases suicidal thoughts.

So when a center points to “the research,” you can ask a few questions. Which study? Who took part? Does the center screen for the conditions those studies excluded? Does it offer anything like the preparation and follow-up the trial participants got? And does it tell you about the side effects the same studies recorded?

If you’re struggling after any psychedelic experience, Fireside Project’s free peer support line, 62-FIRESIDE (623-473-7433), takes calls and texts. In the US, the 988 Suicide & Crisis Lifeline is available by call or text at 988.

More guides

Research can’t tell you how a particular center treats people. Reviews from past participants can. You can search the Safe Ceremonies listings, including psychedelic-assisted therapy and psilocybin and mushroom providers, and read what people say about screening, staffing and follow-up.

Sources

Photo: Library Books by Aleksi Tappura, CC0 1.0.

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