European Neuropsychopharmacology
August 7, 2023
Natacha Perez, Florent Langlest, Luc Mallet et al.
85 citations
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.
Molecular psychiatry
March 1, 2025
Michel Sabé, Adi Sulstarova, Alban Glangetas et al.
39 citations
A systematic review and meta-analysis assessed the risk of psychedelic-induced psychosis in people with schizophrenia. Among population studies, the incidence was 0.002%; in uncontrolled trials, 0.2%; and in randomized controlled trials, 0.6%. In uncontrolled trials that included individuals with schizophrenia, 3.8% developed long-lasting psychotic symptoms. Of those who experienced psychedelic-induced psychosis, 13.1% later developed schizophrenia. The evidence suggests schizophrenia might not be an absolute exclusion for clinical trials on psychedelics for treatment-resistant depression and negative symptoms, but low study quality and limited data warrant a conservative approach until more research is done.
Molecular psychiatry
May 29, 2026
Mickael Eskinazi, Rayan Nasserdine, Romane M Cusin et al.
A systematic review of 23 studies examined whether serotonergic psychedelics (psilocybin, LSD, mescaline, DMT/ayahuasca) or MDMA can trigger manic or hypomanic symptoms. Rates of such symptoms ranged from 5.8% in controlled trials of psilocybin-assisted therapy for depression to 30% in naturalistic studies of people with bipolar disorder. When manic symptoms occurred, they were typically acute and self-limited. Higher risks were seen in individuals with bipolar I disorder, family vulnerability, polysubstance use, or unsupervised use. Registry data showed a 4% prevalence of later transition to bipolar disorder, with little evidence for a hallucinogen-specific signal. The authors conclude that these substances pose a low but clinically meaningful relative risk of transient mood symptoms in susceptible individuals while remaining relatively safe in controlled settings.