A systematic review and dose-response meta-analysis of seven double-blind randomized placebo-controlled trials involving 489 adults with depression found that the optimal daily dose of psilocybin to reduce depression scores varies by population. The 95% effective dose (ED95) was 8.92 mg/70 kg for secondary depression, 24.68 mg/70 kg for primary depression, and 36.08 mg/70 kg when combining both subgroups. Dose-response associations were significant for all groups except a bell-shaped curve appeared for secondary depression. Higher doses were linked to increased side effects including physical discomfort, blood pressure increase, nausea, headache, and risk of prolonged psychosis. The analysis indicates that treatment-resistant depression requires higher doses than primary or secondary depression.
Psychedelic-induced psychosis is rare, occurring in less than 1% of users in controlled trials, but evidence on its treatment is limited. A systematic review of 93 cases from 1955 to 2024 found that LSD (47.3%) and MDMA (38.7%) were the most common substances involved, with an average patient age of 23.7 years and 88% male. Psychosis lasted about 1.8 weeks on average. Second-generation antipsychotics had a response rate of 91.3%, significantly higher than first-generation antipsychotics at 27%. Electroconvulsive therapy also showed a 91% response rate. Follow-up revealed 34% of patients later developed schizophrenia spectrum disorders and 20.4% bipolar disorder, though limited follow-up data constrain these findings.