Psilocybin for Treatment-Resistant Depression: What the New NHS Trial Actually Found

By Joseph Santiago, founder of Microdose Bros. Connect with me on LinkedIn

A new trial in Nature Medicine tested psilocybin-assisted therapy inside England’s National Health Service, on people who had been depressed for about 20 years on average and hadn’t been helped by the usual treatments. The headline numbers are striking. The paper is also unusually honest about why you shouldn’t take them at face value, and that’s the part I want to spend time on.

What the researchers did

Researchers at King’s College London and the South London and Maudsley NHS Foundation Trust recruited 60 adults with treatment-resistant major depression. To qualify, people had to have had an inadequate response to at least two antidepressants, or one antidepressant plus one course of psychotherapy.

Half were randomly assigned to a single 25 mg dose of pharmaceutical-grade synthetic psilocybin, and half to an inactive placebo. Nobody was handed a capsule and sent home. Participants had preparation sessions beforehand, spent about six hours in a quiet room with a therapist and a chaperone (eye mask and a curated music playlist available), and came back for follow-up and integration sessions over the next six weeks.

So what was tested was psilocybin-assisted therapy, not psilocybin on its own. That distinction runs through everything below.

The results

Depression was measured with the MADRS, a clinician-rated scale. At week three:

  • 43% of the psilocybin group had a clinical response, meaning their score dropped by at least half, compared with 3% of the placebo group
  • 40% were in remission (a score of 10 or lower), compared with 3% on placebo
  • The average difference between groups was about 10 points on the scale

At week six, 50% of the psilocybin group met the response threshold, and the gap between groups had widened to nearly 13 points. Anxiety, wellbeing and overall health ratings also favored the psilocybin group. On the anxiety screener, 17% of the psilocybin group still scored in the moderate range at week six, versus 62% of the placebo group.

“Response” and “remission” are clinical definitions. They mean a big drop in symptoms, not that depression is gone for good, and nobody in this paper calls it a cure.

The catch: almost everyone knew what they got

This is the most important thing to understand about the study. The trial was double-blind on paper, but psilocybin is hard to hide. When researchers later asked a subset of 23 participants to guess their group, all 13 who got psilocybin guessed right, and 7 of the 10 on placebo did too.

That’s called functional unblinding, and it matters because expectation is powerful in depression research. If you know you got the real thing, you may feel hopeful. If you know you got placebo, you may feel let down. The authors say plainly that expectancy likely explains some of the gap between groups, and that part of the very large effect comes from the placebo group barely improving at all.

They also make a point I find fair: in psychedelic therapy, the experience itself is part of the treatment model, so expectation and subjective effects can’t be cleanly separated from the drug’s action. That makes these trials genuinely hard to design, and it’s a good reason to treat any single result with caution.

This was a feasibility trial

The main goal wasn’t to prove psilocybin works. It was to find out whether a trial like this could be run in the NHS at all: could they recruit, keep people in, and collect the data? The answer was yes. 62 of 75 screened people were eligible, everyone randomized showed up for the dosing day, and 59 of 60 completed the depression assessments at every visit.

The researchers didn’t run formal hypothesis tests, and the effect sizes are described as preliminary. The conclusion is that the findings support a larger confirmatory trial. That’s a more modest claim than most headlines made.

Safety, and who was in the room

There were 287 non-serious adverse events during the randomized phase (164 in the psilocybin group, 123 in the placebo group). Most were mild and had resolved by the end of the trial. Four serious adverse events were recorded across the whole study, including the open-label phase: three in people who had received psilocybin, which the researchers judged unrelated to treatment, and one in the placebo group, judged possibly related.

The people in this trial were also carefully screened and carefully supported. If you take one thing from this section, take this one:

  • People with bipolar disorder, psychotic disorders, substance dependence, personality disorder, dementia, or a suicide attempt in the past year were excluded
  • Participants were withdrawn from antidepressants, antipsychotics and mood stabilizers before dosing, under clinical supervision
  • A doctor decided when each person was fit to leave at the end of the dosing day

That second point is worth a pause. Combining psilocybin with some medications changes the picture, and stopping prescribed medication abruptly can be risky on its own. If you take antidepressants or any psychiatric medication, don’t change anything on your own because of a study. Talk to the prescriber first.

It’s also worth knowing that an earlier, larger trial of psilocybin for treatment-resistant depression (Goodwin et al., 2022) reported more suicidal ideation and behavior events in the higher-dose groups than in the 1 mg group, although that wasn’t statistically tested. In this NHS trial, suicidality measures didn’t show substantial change in either direction. The authors are open that people at high suicide risk were excluded, which limits what can be seen. The evidence here is still developing.

Who this doesn’t tell us about

Participants were highly educated, and the authors acknowledge they fell short of their recruitment target for Black participants, so the results may not generalize equally to everyone. Follow-up in the randomized phase was only six weeks. A two-year follow-up is underway and will say more about how long any effect lasts.

For disclosure, the psilocybin and placebo capsules were supplied by COMPASS Pathways, which the paper says had no role in design, analysis, or the decision to publish. The trial itself was funded by the UK’s National Institute for Health and Care Research.

This is not microdosing

I want to be direct about this one, since it’s the question we get most. 25 mg of psilocybin, taken once with therapeutic support, is built to produce a full psychedelic experience. Microdosing means much smaller amounts, chosen so you don’t feel an obvious “trip.” They’re different practices, and this study says nothing about whether microdosing helps with depression. If you want to read more on the difference, our Psilocybin FAQ is a good place to start.

What it means in practice

I find it encouraging that a public health system ran a placebo-controlled psilocybin trial and published it in a top journal. It’s also a reminder of how much structure sits around the substance: screening, preparation, six hours of supervised support, integration afterwards. And cost-effectiveness hasn’t been worked out, which the authors flag as essential before this could be offered more widely.

It also doesn’t mean psilocybin therapy is available on the NHS. It isn’t. If you’re living with long-term depression, the practical step today is to talk with a doctor or mental health professional about what’s available to you. If you’re ever in crisis or thinking about harming yourself, please contact local emergency services or a crisis line right away.

For more context on where psychedelics sit in medicine, read Are Psychedelics Medicine? It’s Complicated.

Source

Rucker, J.J., Mantingh, T., Kerr-Gaffney, J. et al. Psilocybin-assisted therapy for treatment-resistant major depressive disorder in a public healthcare setting: a randomized controlled trial. Nature Medicine 32, 3430–3437 (2026). Read the full paper | DOI: 10.1038/s41591-026-04541-0

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This article is for education only and isn’t medical advice. It reports on published research and isn’t a recommendation to use psilocybin, change prescribed medication, or treat depression on your own. Microdose Bros products are not intended to diagnose, treat, cure or prevent any condition.

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