Psychedelics for major depressive disorder (MDD): what the evidence shows

In the Phase 3 Emerge trial (149 adults), one 100 µg dose cut depression scores by 8.1 points more than placebo at week 6. 24% reached remission, versus 3% on placebo.¹

A second pivotal trial, Ascend, is part of the programme; its results aren't out yet.¹

An academic Swiss trial (61 people) compared high and low doses of LSD with therapy. The high dose did better on the clinician-rated scale, but the self-rated measure just missed significance, and neither result held after adjusting for how depressed people were at the start.²

In a Phase 2 trial of 104 adults with major depression, one dose of psilocybin cut depression scores by about 12 points more than an active placebo at six weeks.³

An earlier Johns Hopkins trial (27 people) compared two psilocybin sessions with a waiting list: 71% responded at four weeks. A waiting list isn't a placebo, so this overstates the drug's own effect.⁴

Head-to-head against the antidepressant escitalopram, psilocybin was not significantly better on the main measure, though some secondary results favoured it.⁵

Usona Institute is running a Phase 3 trial (uAspire). The FDA gave this programme a national priority voucher in April 2026. No Phase 3 results have been published.⁶⁷

A related molecule, HLP003 (Helus Pharma), finished enrolling its first Phase 3 trial in 2026, with results expected in Q4 2026. It isn't psilocybin itself.⁸

In a 34-person Phase 2a trial, one intravenous DMT session (about 10 minutes) with therapy cut depression scores by 7.4 points more than placebo at two weeks.⁹

In an open-label study of 12 adults with major depression, 9 responded after two MDMA sessions with therapy. The authors themselves say this can't establish efficacy.¹⁰

In an online survey of 452 people who had used mescaline, most of those with a past depression diagnosis said it improved afterwards. Surveys like this can't show cause and effect.¹¹

A Lancet Psychiatry review of 83 studies found very little, very low-quality evidence that cannabinoids improve depression.¹²