Evidence

Research

What the trials actually show, how far along each one is, and where the claims run ahead of the evidence.

Blinding doesn’t work. Participants know whether they got a psychedelic within about half an hour, and so do the people rating them. Every trial here is affected, and expectancy is a powerful confound in a field full of enthusiasts. Active-placebo designs help but don’t solve it. It doesn’t make the findings wrong, but read the effect sizes as upper bounds.

By indication

Treatment-resistant depression

Phase IIb complete

The largest trial to date randomised 233 people to 25 mg, 10 mg or 1 mg of synthetic psilocybin with psychological support. The 25 mg group showed a significantly greater reduction in depression scores at three weeks than the 1 mg comparator. Phase III is under way.

Caveat: The separation narrowed by twelve weeks. Suicidal ideation and self-injury were reported in all three arms. This is a signal worth taking seriously, not a settled treatment.

Major depressive disorder

Phase II

Smaller randomised trials have reported substantial and rapid reductions in depression scores, sustained at one-year follow-up in an open-label extension.

Caveat: Small samples, highly selected participants, and an unusually enthusiastic population. Long-term follow-up without a control arm cannot separate drug effect from regression to the mean.

Depression and anxiety in life-threatening illness

Phase II, replicated

Two independent randomised trials found large, rapid reductions in depression and anxiety among patients with cancer, sustained at six months in a substantial majority.

Caveat: The strongest evidence base of any indication here, and still on the order of eighty participants across both trials.

Alcohol use disorder

Phase II

A randomised trial found two psilocybin sessions alongside psychotherapy reduced heavy drinking days significantly more than an active placebo over eight months.

Caveat: Single trial, 93 participants. Not yet replicated independently.

Tobacco dependence

Pilot

A small open-label pilot reported unusually high abstinence rates at long-term follow-up.

Caveat: Fifteen participants, no control group, and the investigators themselves describe it as preliminary. Frequently cited as though it were more than that.

Anorexia nervosa, OCD, chronic pain

Early

Small feasibility and safety studies exist.

Caveat: No efficacy evidence worth summarising yet. These are pilot studies; read the claims accordingly.

What has not been shown

That psilocybin outperforms existing antidepressants. Only one head-to-head trial exists, it was small, and its primary outcome did not separate.
That benefits persist without ongoing support. Follow-up beyond a year is almost entirely uncontrolled.
That recreational or unsupervised use produces the outcomes seen in trials. Trial participants are screened, prepared, supervised for the whole session and followed up. Almost none of that describes anybody reading this.
That it is safe for people with a psychosis or bipolar history. Those people are excluded from every trial, so there is no evidence either way, and the exclusion exists because of a real concern.

The microdosing evidence is much weaker than the clinical-dose evidence and often gets discussed as if it were the same body of work. It has its own page.