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Research & Culture9 min readBy Shroomshack · Updated October 16, 2026

The 2026 Psilocybin Depression Trials, Explained: Compass, the NHS and EPISODE

The 2026 Psilocybin Depression Trials, Explained: Compass, the NHS and EPISODE

If you only read headlines, 2026 has been the year psilocybin "won" and the year it "flopped", depending on the week. Three large depression trials reported this year, and they point in the same direction while disagreeing on the details. Here is what each one actually measured, what the numbers say, and what it means for someone in Canada who cares about their mental health and likes mushrooms.

One thing first. Every trial below used pure, measured synthetic psilocybin, careful medical screening and trained therapists before, during and after the session. That is a different thing from a bag of dried cubensis on a Saturday. Nothing here is medical advice, and none of it means mushrooms at home treat depression. If you are struggling, please talk to a doctor. Our earlier post on the clinical research up to 2022 covers the studies these ones build on.

The short version

  • Compass Pathways finished two Phase 3 trials, the biggest psilocybin studies ever run, and both hit their main goal. The effect was real but modest on average, with about a quarter to four in ten people responding well. Six month data released by the company in July suggest that, for those who responded, the benefit largely held.
  • An NHS trial in London, published in Nature Medicine, found a much larger effect in a small group, with the researchers themselves warning that most participants could tell what they had taken.
  • A German trial called EPISODE missed its main goal at six weeks but still found a meaningful drop in depression scores, plus the clearest safety data yet on blood pressure and difficult emotions.
  • Australia, the first country to let psychiatrists prescribe psilocybin, is showing what that looks like in practice: few patients, high costs and mixed early results.

Compass: two Phase 3 trials, 839 people

In February, Compass Pathways announced that its second Phase 3 trial, COMP006, met its primary endpoint, following the first, COMP005, in 2025. Together they dosed 839 people with treatment-resistant depression across North America and Europe, which makes them the largest controlled psilocybin studies to date.

  • COMP005 gave 258 people a single 25 mg dose of psilocybin or a placebo. At six weeks the psilocybin group's depression score (the MADRS scale) had fallen 3.6 points more than placebo.
  • COMP006 gave 581 people two doses three weeks apart, either 25 mg, 10 mg or a 1 mg near-placebo. At six weeks, 25 mg beat 1 mg by 3.8 points.
  • Response, meaning at least a 25 per cent drop in score, was 25 per cent of the 25 mg group in COMP005 and 39 per cent in COMP006.
  • People who responded in COMP005 largely kept the benefit through at least week 26, and more than 40 per cent of those who improved without reaching remission did so after a second dose.

What about safety? Most side effects happened on the dosing day and were gone within a day: headache, nausea, anxiety, visual effects. Serious adverse events were 5 per cent in COMP005 and 2 per cent in COMP006. The rate of serious suicidal thoughts was under 1 per cent and, importantly, the independent safety board found no imbalance between the psilocybin and control groups. That matters because the 2022 Phase 2b trial had raised exactly this worry.

How to read a 3.6 point difference: it is statistically solid and about the size you see for many approved antidepressants against placebo. It is not a miracle. The more interesting number is the response rate, because psilocybin seems to work very well for some people and barely at all for others, and researchers still cannot predict who is who. ## Compass at six months

In May, Compass presented its Phase 3 program as posters at the American Society of Clinical Psychopharmacology meeting, summarized by Psychiatric Times. Two details stand out. The participants had long-lasting, hard-to-treat depression. And in COMP005, people who responded early after their dose tended to be the ones still doing better than placebo at 26 weeks.

In July, Compass released the 26 week results from COMP006. According to the company, people in the 25 mg group who had responded by week 6 kept that response, on average, through at least week 26, and some of those early responders went on to reach remission after another dose in the trial's second part. Most side effects were again short-lived and happened on dosing days. Compass says its rolling application to the FDA is under way and expects to complete it in the last quarter of 2026.

Two cautions. These are company announcements and conference posters, not yet full peer-reviewed papers, and detailed data beyond the press release are not yet available for independent researchers to check. And the six month figures describe the people who responded, not everyone who took part.

London: a big effect, and an honest warning about it

In August, Nature Medicine published a trial from King's College London and the South London and Maudsley NHS Trust, led by James Rucker. It was publicly funded and run inside the NHS rather than by a company, which is unusual and worth noting.

Sixty adults with treatment-resistant depression got either a single 25 mg dose or a placebo capsule, with preparation and integration sessions on both sides. At three weeks the psilocybin group scored 10.4 points lower on the MADRS than placebo, and the gap held at six weeks. That is roughly three times the Compass effect.

Why so much bigger? The authors say it themselves: every single person on psilocybin guessed correctly what they had taken, and so did 70 per cent of the placebo group. When you know you got the real thing, expectation does some of the lifting, and when you know you got the dud, it drags you down. The placebo group barely improved at all, which inflates the difference. This is the hardest problem in psychedelic research and this paper is refreshingly plain about it. Three serious adverse events occurred in the psilocybin group, none judged related to the drug.

Germany: the trial that "failed" and still found something

The EPISODE trial from Mannheim and Berlin, published in JAMA Psychiatry in March, enrolled 144 people and compared 25 mg of psilocybin with a 5 mg low dose and a placebo, each combined with psychotherapy.

Its primary goal was a 50 per cent drop in depression score at six weeks. At one week the high dose clearly beat placebo on that measure. By six weeks the difference was no longer statistically significant, so the trial missed its main endpoint. On the continuous score, though, the 25 mg group was still 4.6 points lower than placebo at six weeks, and by twelve weeks, once everyone had received a high dose, scores had fallen 7.5 points on average across the board.

The safety reporting is the most detailed of the three. During 25 mg sessions, 62 per cent of people had strong swings of emotion, 55 per cent had headaches, 51 per cent had raised blood pressure and 34 per cent felt nauseous. Two serious reactions occurred: one sharp blood pressure rise and one perceptual disturbance that lasted longer than expected. The researchers also found that people who reported an "emotional breakthrough" during the session improved more, which echoes the older finding that the experience itself, not just the chemistry, seems to matter.

Australia: what happens when psychiatrists can prescribe it

On 1 July 2023, Australia became the first country to let psychiatrists prescribe psilocybin outside a trial, a decision Nature reported as a world first. The Therapeutic Goods Administration allows it only for treatment-resistant depression, and only by psychiatrists approved as Authorised Prescribers.

Two years in, the picture is more modest than the 2023 headlines. A 2025 review in the Australian and New Zealand Journal of Psychiatry describes low patient uptake despite legal access. By late 2024 only 10 psychiatrists nationwide were authorised to prescribe psilocybin, and by September 2025 an advocacy group counted 13 across five states. Out-of-pocket costs for a full course exceed 20,000 to 30,000 Australian dollars, and the authors point to uneven access from region to region. Researchers writing in The Conversation raised similar concerns about cost and differing state rules.

Australia's own research is early too. A Swinburne University pilot published in 2025 gave seven people with treatment-resistant depression two 25 mg sessions with therapy. The group as a whole improved, but the individual results tell the real story: two people kept their improvement, three relapsed and two did not substantially improve. With seven people and no control group, it cannot show what psilocybin itself did, but it is a useful reminder of how much responses vary.

Australia is, in effect, the world's first real-world test of prescribed psilocybin therapy, and it is worth watching for what it reveals about cost, access and who benefits outside the tidy conditions of a trial.

So, does psilocybin work for depression?

Put the three together and a consistent picture appears:

  • A single high dose, in a clinical setting with support, produces a real reduction in depression that lasts weeks to months for a meaningful share of people.
  • The average effect is moderate. Some people get a lot, many get a little, some get nothing.
  • The experience is demanding. High blood pressure, nausea, headaches and intense emotions are the norm during the session, which is why screening and a trained sitter are not optional in these studies.
  • Expectation is part of the effect, and nobody has fully solved how to measure around it.

That is a far more useful truth than either "cure" or "hype".

What this means in Canada

Psilocybin remains a controlled substance here. Legal access for a medical need runs through Health Canada's Special Access Program, which has allowed psilocybin for individual patients since 2022, and through clinical trials. Our guide to psilocybin in Canada walks through the current routes. If Compass or others win approval in the United States, Canada will not automatically follow, but it would move the conversation here quickly. Australia's experience suggests that even once psilocybin can be prescribed, access may stay narrow and expensive for some time.

If you use mushrooms at home

You cannot recreate a clinical trial in your living room, and you should not try to treat a diagnosed condition that way. What you can borrow is the discipline. Every trial above spent more time on preparation and integration than on the dose. In everyday terms:

  • Know your dose sizes and start lower than you think.
  • Sort out your set and setting before anything else.
  • Have a sober trip sitter for any larger dose.
  • Check medication interactions. Lithium, MAOIs and tramadol are hard stops, and SSRIs blunt the experience.
  • Plan the day after and give yourself space to make sense of it.
  • Skip it entirely if you or close family have a history of psychosis or bipolar disorder, or if you have a heart condition. The blood pressure data above is a good reason to take that seriously.

We will keep following the FDA decision and Australia's prescribing program, and we will update this post when there is news.

Sources

What the research says

Research on psilocybin is still young, and most trials give a measured dose with professional support. Results don't mean any product is safe or effective for you.

This guide is general information, not medical or legal advice. If you have health questions, talk to a health professional.