Psilocybin

What it is

Psilocybin is a naturally occurring compound found in certain mushrooms, often called "magic mushrooms" [1]. In research it is given as a single oral dose - commonly 25 mg - inside a supervised session with psychological support before, during and after [2][3]. It is a controlled substance and is illegal in many countries outside approved research [4].

How it might work

Psilocybin acts mainly on serotonin 5-HT2A receptors in the brain; researchers propose that this increases neuroplasticity and helps loosen rigid patterns of thought [1].

What the research says

A 2024 BMJ systematic review pooled seven randomised trials (436 people) and found psilocybin reduced depression scores more than placebo or non-psychoactive controls (Hedges' g 0.66, 95% CI 0.46 to 0.86); all included studies were at moderate risk of bias [5]. A 2025 review of six RCTs found a similar effect up to six weeks (standardised mean difference -0.72 across five pooled trials, 403 people) and higher response and remission rates than comparators [6].

In the 233-person COMP360 trial of treatment-resistant depression, a single 25 mg dose lowered MADRS scores by 12.0 points at week 3 versus 5.4 with a 1 mg control; 10 mg did not clearly separate from control [2]. A 104-person trial in major depression found MADRS scores fell 12.3 points more than with a niacin placebo by day 43 [3].

An NHS feasibility trial (60 people) found MADRS scores 10.4 points better than placebo at week 3, sustained at week 6 [7]; a 35-person trial found significant effects from day 2 to day 42 that had faded by one year [8]. Not all trials agree: psilocybin matched escitalopram rather than beating it on the primary measure in a 59-person trial [9], and the 144-person EPISODE trial missed its primary response end point (17.0% vs 10.6% response with active placebo) while secondary measures favoured 25 mg [10].

In people with life-threatening illness, a 2024 Cochrane review found classical psychedelics may reduce anxiety and depression (five trials, 122 people; low-certainty evidence) [4]; two older psilocybin trials in 51 and 29 cancer patients found large, sustained improvements [11][12].

For alcohol use disorder, a 95-person trial found heavy drinking days fell to 9.7% (from 23.6%) over 32 weeks [13], while a later 37-person trial found no significant difference in abstinence or drinking [14]. Microdosing has not shown benefits in controlled trials: three small trials found no effect on mood, anxiety or wellbeing [15][16][17].

Doses used in studies

Trials used single oral doses of 25 mg [2][3], weight-based doses of about 20-30 mg per 70 kg [18][11], or 0.3 mg/kg [12], always with psychological support. Benefits were usually strongest in the first weeks and faded over months [8][2]. A 2026 review found larger effects in trials using weight-based dosing and longer therapy sessions, but these subgroup differences were not statistically significant [19].

Safety and interactions

Common short-term effects are headache, nausea, dizziness, anxiety and a temporary rise in blood pressure; they usually settle within 48 hours [20]. In a review of 114 studies (3,504 people), serious adverse events occurred in about 4% of participants who had existing neuropsychiatric conditions and in none of the healthy volunteers [21]. Manic or hypomanic symptoms were reported in 5.8% of controlled depression trials and up to 30% of observational studies in people with bipolar disorder, usually briefly [22]. The EPISODE trial reported higher suicidal ideation on dosing days (4% vs 1-2%) and one case of hallucinogen persisting perception disorder [10]. Trials excluded people with psychosis or mania histories, so risk in them is unknown [3]. Psilocybin can interact with psychiatric medications, including serotonergic antidepressants [23]. No studies in pregnancy or breastfeeding were found in the evidence reviewed.

Caveats and open questions

The main caveat is blinding: participants can usually tell whether they received a full dose, which may inflate reported benefits, and one review judged the certainty of evidence low [4]. Most trials are small and some are funded by companies developing psilocybin medicines [2]. How well it compares with standard antidepressants and whether repeated dosing extends benefits are still open questions [9].