New England Journal of Medicine
April 14, 2021
Robin Carhart-Harris, Bruna Giribaldi, Rosalind Watts et al.
1,372 citations
In a selected group of patients, psilocybin did not show a significantly greater antidepressant effect than escitalopram based on depression scores at week 6. Secondary outcomes generally favored psilocybin, but these analyses were not corrected for multiple comparisons. The authors call for larger and longer trials to compare psilocybin with established antidepressants.
Frontiers in Pharmacology
March 31, 2022
Roberta Murphy, Roberta Murphy, Hannes Kettner et al.
229 citations
In a trial comparing psilocybin-assisted therapy to escitalopram for moderate-to-severe depression, a stronger therapeutic alliance with the therapist predicted greater emotional breakthrough and mystical-type experiences during psilocybin sessions, and these experiences in turn predicted larger reductions in depression symptoms six weeks after treatment. Emotional breakthrough during the first session strengthened the alliance before the second session, while a weaker alliance before the second session directly predicted higher depression scores at the endpoint, independent of the acute psychedelic experience. The findings suggest the therapeutic relationship plays a key role in shaping both the quality of the psychedelic experience and clinical outcomes.
EClinicalMedicine
September 23, 2024
David Erritzøe, Tommaso Barba, Kyle T. Greenway et al.
46 citations
In a clinical trial, psilocybin therapy showed comparable effectiveness to a common SSRI antidepressant for treating depression, with both treatments leading to significant reductions in depressive symptoms over a follow-up period. The findings suggest psilocybin may offer a viable alternative to standard antidepressant medication, though the study's design and sample size limit the strength of conclusions.
Psychological Medicine
January 1, 2024
Brandon Weiss, Induni Ginige, Lu Shannon et al.
38 citations
In a trial comparing psilocybin therapy with the antidepressant escitalopram for moderate-to-severe major depressive disorder, both treatments led to personality changes in a direction consistent with improved mental health. Psilocybin was linked to decreases in neuroticism, introversion, disagreeableness, and impulsivity, and increases in absorption, conscientiousness, and openness at six weeks, with some changes lasting six months. Escitalopram was linked to decreases in neuroticism, disagreeableness, and impulsivity, and increases in openness at six weeks, with neuroticism remaining decreased at six months. No significant differences between the two treatments were observed, except that patients' pre-trial positive expectations for escitalopram moderated personality changes after that treatment, but not after psilocybin.
Frontiers in Psychiatry
January 1, 2023
Ellen James, David Erritzøe, Tiffanie Benway et al.
16 citations
A phase 1 trial tested escalating intravenous doses of the psychedelic DMT (SPL026) in healthy volunteers who had never used psychedelics, to find a safe, tolerable dose for a future trial in people with major depressive disorder. Participants were randomly assigned to placebo or one of four doses (9, 12, 17, or 21.5 mg). The drug was well tolerated with no serious adverse events. Higher blood levels of DMT correlated with stronger ratings of mystical experience, ego dissolution, and intensity, though these trends need confirmation in larger studies. Based on safety and pharmacodynamic results, 21.5 mg given as a two-phase infusion was chosen for the patient trial.
Nat Med
February 16, 2026
David Erritzøe, Tommaso Barba, Tiffanie Benway et al.
4 citations
A single 21.5-mg intravenous dose of the psychedelic DMT, given with psychotherapeutic support, produced a rapid and significant reduction in depressive symptoms in adults with moderate-to-severe major depressive disorder. In a double-blind, placebo-controlled trial with 34 participants, those receiving DMT showed a greater decrease in depression scores at two weeks compared to placebo. Antidepressant effects persisted up to three months in an open-label phase. Adverse events were mostly mild to moderate, and no serious adverse events occurred.
Psychological Medicine
July 19, 2023
Brandon Weiss, Induni Ginige, Lu Shannon et al.
1 citation
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