This systematic review and dose-response meta-analysis (n=489) aimed to determine the optimal dosage of psilocybin for depression treatment. Seven studies were included, with four focusing on primary depression (n=366) and three on secondary depression (n=123). Specific 95% effective daily doses (ED95) were identified for each group, revealing different dose-response associations and side effects.
Abstract of Psilocybin-assisted therapy for depression dose-response
“Psilocybin is increasingly studied for its antidepressant effect, but its optimal dosage for depression remains unclear. We conducted a systematic review and a dose-response meta-analysis to find the optimal dosage of psilocybin to reduce depression scores.
Following our protocol (CRD 42022220190) multiple electronic databases were searched from their inception until February 2023, to identify double-blind randomized placebo-controlled (RCTs) fixed-dose trials evaluating the use of psilocybin for adult patients with primary or secondary depression. A one-stage dose-response meta-analysis with restricted cubic splines was used. Cochrane risk of bias was used to assess risk of bias.
Our analysis included seven studies with a total of 489 participants. Among these, four studies focused on primary depression (N = 366), including one study with patients suffering from treatment-resistant depression. The remaining three studies examined secondary depression (N = 123). The determined 95% effective doses per day (ED95) were 8.92, 24.68, and 36.08 mg/70 kg for patients with secondary depression, primary depression, and both subgroups, respectively. We observed significant dose-response associations for all curves, each plateauing at different levels, except for the bell-shaped curve observed in the case of secondary depression. Additionally, we found significant dose-response associations for various side effects, including physical discomfort, blood pressure increase, nausea/vomiting, headache/migraine, and the risk of prolonged psychosis.
In conclusion, we discovered specific ED95 values for different populations, indicating higher ED95 values for treatment-resistant depression, primary depression, and secondary depression groups. Further RCTs are necessary for each population to determine the optimal dosage, allowing for maximum efficacy while minimizing side effects.”
Authors: Natacha Perez, Florent Langlest, Luc Mallet, Marco De Pieri, Othman Sentissi, Gabriel Thorens, Federico Seragnoli, Daniele Zullino, Matthias Kirschner, Stefan Kaiser, Marco Solmi & Michel Sabé
Summary of Psilocybin-assisted therapy for depression dose-response
Depression is a prevalent mental disorder affecting more than 300 million people worldwide. Half of patients with depressive disorder lack adherence to antidepressants as soon as six months after initiation of treatment. Most prescribed antidepressants are superior to placebo in adults but have a small effect size, limited tolerability, and high relapse rates. Hence, in recent years, renewed interest in psychedelic-assisted therapy has emerged mainly with lysergic acid diethylamide (LSD) and psilocybin.
Although the exact physiopathology of MDD has not been fully understood, it is widely accepted that dysregulation of the monoaminergic system contributes to affective symptoms.
Psilocybin use in the treatment of mood disorders has shown promising effects. It has a low addiction and physical dependence potential, and is well-tolerated in the long term.
Find this paper
https://doi.org/10.1016/j.euroneuro.2023.07.011
Paywall | Google Scholar | Backup | 🕊
Cite this paper (APA)
Perez, N., Langlest, F., Mallet, L., De Pieri, M., Sentissi, O., Thorens, G., Seragnoli, F., Zullino, D., Kirschner, M., Kaiser, S., Solmi, M., & Sabé, M. (2023). Psilocybin-assisted therapy for depression: A systematic review and dose-response meta-analysis of human studies. European Neuropsychopharmacology, 76, 61–76.
Study details
Compounds studied
Psilocybin
Topics studied
Depression
Treatment-Resistant Depression
Study characteristics
Meta-Analysis
Literature Review
Participants
489
Humans