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.
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.
Proceedings of the National Academy of Sciences of the United States of America
March 28, 2023
Christopher Timmermann, Leor Roseman, Sharad Haridas et al.
217 citations
Intravenous DMT, a potent psychedelic and serotonin 2A receptor agonist, profoundly alters brain function in healthy volunteers. In a placebo-controlled study with 20 participants, multimodal neuroimaging (EEG-fMRI) showed that DMT robustly increases global functional connectivity, disrupts and desegregates brain networks, and compresses the principal cortical gradient. These changes overlapped with brain regions rich in serotonin 2A receptors and associated with human-specific psychological functions. EEG and fMRI measures correlated, linking neurophysiological changes to network-level effects. The findings indicate DMT predominantly acts on the brain's transmodal association cortex, the evolutionarily recent area tied to advanced cognition and high 5-HT2A receptor density.
EClinicalMedicine
September 23, 2024
David Erritzoe, 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
September 10, 2021
Tehseen Noorani, Jonny Martell
32 citations
A Phase II trial comparing psilocybin-assisted therapy with escitalopram for depression found no statistically significant difference on the primary outcome measure (QIDS-SR16), though secondary measures favored psilocybin. Expert commentaries noted possible issues with the choice of primary outcome, statistical power, and the limitations of depression rating scales in capturing improved mood and well-being. This opinion piece, drawing on the authors' experiences in psychedelic trials and NHS psychiatry, argues that psychedelic therapies will both open new frontiers and face a bursting bubble, exploring the stakes and opportunities involved.
Cureus
January 29, 2025
Sorcha O'Connor, Kate Godfrey, Sara Reed et al.
2 citations
The study aims to uncover the neural mechanisms by which psilocybin-assisted therapy affects obsessive-compulsive disorder (OCD) and whether those brain changes align with improvements in cognitive symptoms. A secondary goal is to test whether a low, tolerable dose is both practical and effective as a clinical treatment. The results will provide essential data for designing a future randomized controlled trial.
Psychological Medicine
July 19, 2023
Brandon Weiss, Induni Ginige, Lu Shannon et al.
1 citation
No Summary
Cureus
January 1, 2025
Sorcha O'Connor, Kate Godfrey, Sara Reed et al.
correction
A protocol describes a planned study testing whether a low-moderate dose of psilocybin (10 mg), combined with non-interventional therapy, can improve cognitive flexibility and neuroplasticity in people with obsessive-compulsive disorder (OCD). Twenty blinded participants will receive an active placebo (1 mg psilocybin) in a first session and 10 mg in a second session four weeks later. Cognitive flexibility will be measured with the intradimensional-extradimensional shift task two days after each session, and neuroplasticity will be assessed via electroencephalography immediately after each session. Secondary outcomes include OCD symptom severity and patient-reported measures. The results are expected to clarify neural mechanisms and guide a future randomized controlled trial.