SUMMARY: A meta-analysis suggests that high doses of psilocybin may relieve depression symptoms similar to the SSRI drug escitalopram. Clinical trials have shown that psilocybin is superior to placebo in efficacy, although effect sizes were small. However, flaws in study design may have led to overestimation of results.
The findings suggest that psilocybin, especially at higher doses, may offer a new avenue for treating depression that is comparable to existing antidepressants.
Key Facts
High doses of psilocybin showed similar effects to escitalopram for depression. Placebo responses were low in trials of hallucinogens, affecting the overall results. Research calls for improved blinding to accurately evaluate hallucinogens.
Source: BMJ
High doses of psilocybin, the active ingredient in magic mushrooms, appear to have similar effects against depression as the selective serotonin reuptake inhibitor (SSRI) escitalopram, suggests a systematic review and meta-analysis published today in the BMJ.
In antidepressant trials, patients given high doses of psilocybin responded better than those given a placebo, although the effect size was small, according to the study.
The researchers said flaws in the study design may have led them to overestimate the effects of the hallucinogen, but that high doses of psilocybin “appear to have potential to treat symptoms of depression.”
Psychedelic treatment has been shown to be effective in reducing depressive symptoms, but to date there has been only one randomized controlled trial that has directly compared a psychedelic drug (psilocybin) with an antidepressant (escitalopram) in patients with major depressive disorder.
Furthermore, the subjective effects of hallucinogens may compromise blinding and lead to an overestimation of the treatment effect compared to placebo. Treatment with hallucinogens is usually administered with psychological support, making it difficult to isolate the direct effects of the hallucinogens.
To address these questions, the researchers searched scientific databases to identify randomized controlled trials published up to October 12, 2023 that evaluated the effects of hallucinogens or escitalopram in adults with acute depressive symptoms.
To be included, psychedelic treatments (including MDMA, LSD, psilocybin, and ayahuasca) had to be administered orally without additional antidepressants, and studies of escitalopram had to compare at least two different oral doses (up to 20 mg/day) with placebo. Trials comparing psychedelic therapy directly with escitalopram were also included.
Overall, 811 people (mean age 42 years, 54% women) participated in the 15 hallucinogen trials, and 1,968 people (mean age 39 years, 63% women) participated in the five escitalopram trials.
Effect sizes were expressed as standardized mean differences (0.2–0.5 indicates a small effect, 0.5–0.8 indicates a medium effect, and 0.8 or greater indicates a large effect).
The researchers found that placebo responses in hallucinogen trials were lower than responses in escitalopram trials. Results showed that most hallucinogens performed better than placebo in hallucinogen trials using the 17-item Hamilton Depression Rating Scale (HAMD-17), but only high-dose psilocybin performed better than placebo in escitalopram trials using the HAMD-17 scale, with a small effect size (standardized mean difference 0.3), which is similar to that of current antidepressants.
None of the interventions was associated with an increased incidence of serious adverse events (including death, hospitalization, or suicide attempts) or withdrawals compared with placebo.
The authors acknowledge some limitations of their study, including that only the acute effects of the intervention were evaluated and that the long-term effects of the hallucinogens and escitalopram are unknown. Sample sizes in the hallucinogen trials were small, and the effects of high-dose psilocybin may be slightly overestimated relative to other treatments, the authors add.
Nevertheless, they conclude: “Serotonergic hallucinogens, particularly high-dose psilocybin, appear to have potential for treating depressive symptoms. Our analyses suggest that the standardized mean difference for high-dose psilocybin is similar to that of current antidepressants, with a small effect size.”
The researchers added that “improved blinding methods and standardization of psychotherapy will enable researchers to more accurately assess the effectiveness of psychedelics for symptoms of depression and other psychiatric disorders.”
About this Psychopharmacology Research News
Author: BMJ Media Relations
Source: BMJ
Contact: BMJ Media Relations – BMJ
Image: This image is provided by Neuroscience News
Original research: The findings will be published in the BMJ
