Psychedelic therapy, described accurately.

Depression, particularly treatment-resistant depression, has the most substantial randomized evidence for a classic psychedelic. A phase 2 trial of single-dose psilocybin in treatment-resistant depression reported greater reductions in depression scores at three weeks in the 25 mg group than in the 1 mg comparator, with effects attenuating over twelve weeks. A separate trial comparing psilocybin with escitalopram found no statistically significant difference on its primary outcome measure.

Read together, those two results are the honest summary of the field: a real and rapid signal, not an established superiority over existing antidepressant treatment.

Cautions specific to depression

Suicidal ideation and self-injurious behaviour were reported in psilocybin trial participants, including in treatment groups. Active suicidality is a reason for intensive conventional care, not a reason to accelerate into an experimental session.

Existing antidepressant medication complicates matters in both directions: discontinuation carries its own risks, and some combinations carry interaction risk. Medication decisions are made by a physician, gradually, and never as a precondition imposed by a marketing promise.

Integration is the work of turning an acute experience into changed behaviour. In the trials with the most credible results, dosing sessions were embedded in a course of psychological support, and the therapy component cannot be separated from the reported effect.

Here, integration runs across the remaining weeks of residency: psychological sessions, sleep and nutrition, movement, and concrete planning for the environment a person is returning to. Continuing care after discharge is arranged rather than assumed.

Why it is the part most often skipped

Integration is slow, unglamorous, and difficult to market. It is also the part most likely to determine whether anything durable comes of a session, which is why a single-session model with no follow-up should be treated with scepticism.

A fair summary in one paragraph: psilocybin has repeatedly produced rapid, clinically meaningful reductions in depression scores in small randomized trials, without demonstrating superiority to an established antidepressant on a primary outcome. MDMA-assisted therapy produced positive phase 3 results for PTSD that the FDA judged insufficient for approval. Ayahuasca and 5-MeO-DMT rest on small early trials and observational data. Ibogaine has no completed randomized trials and a documented cardiac risk. None of these compounds is approved for these uses.

The methodological problems are shared across the field: small samples, participants who can usually tell whether they received the active compound, strong expectancy effects, highly selected volunteers, short follow-up, and outcome measures that rely on self-report or unblinded raters.

What does not count as evidence

Commercial investment does not. Acquisitions, valuations and funding rounds in the psychedelic sector reflect expectations about future markets and regulatory outcomes; they are not clinical findings and they say nothing about whether a compound works.

Language we avoid

We do not say that a psychedelic "resets" the brain, repairs neurochemistry, cures a diagnosis, or works for everyone. Those claims outrun the published data. Where a mechanism is a hypothesis under investigation, this page says so.