J Affect Disord
February 27, 2024
Debora Copa, David Erritzøe, Bruna Giribaldi et al.
31 citations
Brain connectivity patterns measured before psilocybin treatment can predict how much depression symptoms will improve. In people with treatment-resistant depression given two doses of psilocybin (25 mg each, one week apart), baseline resting-state functional MRI scans showed that connectivity within visual, default mode, and executive networks predicted early symptom improvement, while salience network connectivity predicted who would respond up to 24 weeks later, with about 90% accuracy. Similar patterns appeared in a separate trial comparing psilocybin to escitalopram. Fronto-occipital and fronto-temporal connections predicted early and late symptom reduction, respectively. Small sample sizes and differences between datasets limit generalizability, and the lack of a placebo arm limits specificity.
Scientific Reports
August 22, 2023
Hannes Kettner, Stephen Ross, Richard J. Zeifman et al.
31 citations
Co-using a low dose of MDMA with psilocybin or LSD is associated with less intense challenging experiences—such as grief and fear—and increased feelings of self-compassion, love, and gratitude, compared to using psilocybin or LSD alone. In a survey of 698 people planning to use these substances, the 27 who also took a low dose of MDMA reported these benefits without a reduction in mystical-type experiences or compassion. Medium-to-high MDMA doses did not show the same effects. The findings suggest MDMA may buffer against some difficult aspects of psychedelic experiences, but the study's small, non-experimental convenience sample limits certainty.
J Psychopharmacol
January 27, 2024
Jessica Barbut Siva, Tommaso Barba, Hannes Kettner et al.
29 citations
A prospective survey study examined how serotonergic antidepressants affect the acute subjective experience of classic psychedelics and subsequent well-being and depressive symptoms. People taking antidepressants reported less intense mystical-type experiences and greater anxiety during psychedelic sessions compared to those not on antidepressants. Despite this blunting, both groups showed similar improvements in well-being and reductions in depressive symptoms after the session. The findings suggest that while antidepressants may dampen the acute psychedelic experience, they do not necessarily hinder long-term mental health benefits.
Nature medicine
June 3, 2025
Chloé Pronovost-Morgan, Kyle T. Greenway, Leor Roseman et al.
26 citations
A Delphi consensus study with 89 experts from 17 countries identified 30 extra-pharmacological variables that are important or very important for reporting the setting in psychedelic clinical trials. These variables, forming the ReSPCT guidelines, cover physical environment, dosing session procedure, therapeutic framework and protocol, and subjective experiences. The findings reveal significant ambiguities in current conceptualizations of set and setting. The guidelines provide a new standard for designing and documenting contextual factors in psychedelic research.
Scientific reports
January 29, 2025
Richard J Zeifman, Meg J Spriggs, Hannes Kettner et al.
26 citations
A preliminary test of the REBUS model found that a high dose of psilocybin (25 mg) reduced confidence in negative self-beliefs in 11 healthy individuals, both during the acute experience and four weeks later. Greater brain signal entropy and stronger subjective effects under psilocybin correlated with larger decreases in negative self-belief confidence. Decreases in negative self-belief confidence were linked to increases in well-being. The findings provide initial evidence that relaxing and revising negative self-beliefs may underlie psilocybin's positive psychological effects, with increased neuronal entropy as a possible mechanism. Replication in larger clinical samples is needed.
Journal of Psychopharmacology
March 22, 2024
Tommaso Barba, David Erritzøe, Meg J. Spriggs et al.
26 citations
In a clinical trial comparing psilocybin plus psychological support to escitalopram plus psychological support for major depressive disorder, patients who discontinued their SSRI or SNRI medication before receiving psilocybin showed a reduced treatment effect on all depression severity and well-being measures compared with those who were unmedicated at trial entry. Discontinuation did not affect the intensity of the acute psychedelic experience. The findings are exploratory and hypothesis-generating, not confirmatory, and the study did not test SSRI/SNRI continuation. A controlled trial comparing discontinuation versus continuation before psilocybin is needed.
International Journal of Mental Health and Addiction
March 7, 2024
Brandon Weiss, Leor Roseman, Bruna Giribaldi et al.
26 citations
Acute psychological experiences, particularly mystical experience and ego dissolution, partially account for how psilocybin therapy improves depression compared to escitalopram. In a phase 2 trial of patients with moderate-to-severe major depressive disorder, mystical experience and ego dissolution uniquely mediated the effect of treatment on depressive response. Higher levels of mystical experience, emotional breakthrough, and intense music-listening responses were also linked to greater antidepressant improvement. These findings suggest that acute psychological experiences play a causal mechanistic role in psilocybin therapy for depression.
Brain
January 1, 2024
Andrea I Luppi, Manesh Girn, Fernando E Rosas et al.
25 citations
Serotonin 2A receptor (5-HT2AR) signaling drives both the evolutionary expansion and ongoing modulation of the human cerebral cortex's most complex cognitive centers. The cortex is organized along a gradient from simple sensory processing to high-level integration, with the transmodal cortex at the apex—a region disproportionately enlarged in humans and rich in 5-HT2AR expression. During early brain development, 5-HT2AR signaling on neural progenitor cells stimulates their proliferation, contributing to cortical expansion. In the adult brain, 5-HT2AR agonism promotes neuroplasticity, learning, and cognitive flexibility with therapeutic potential. The receptor thus plays a dual role in enabling cortical growth and sophisticated functioning.
Psychiatry and Clinical Neurosciences
October 1, 2024
Shakila Meshkat, Fatemeh Gholaminezhad, Eric Vermetten et al.
24 citations
A systematic review of 20 studies with 2,959 participants found that psilocybin's effects on cognitive function are mixed. Global cognitive function and processing speed remained mostly unchanged in healthy individuals, while improvements in sustained attention, working memory, and executive function were reported in patients with treatment-resistant depression. Emotional processing and empathy were positively modified, especially in these patients, but cognitive empathy and social cognition were not significantly altered. Cognitive flexibility and creative cognition initially declined but could improve over time. Psilocybin improved semantic associations and associative learning, but effects on episodic and verbal memory were less pronounced than with other cognitive enhancers.
Scientific Reports
February 7, 2024
Tommaso Barba, Hannes Kettner, Caterina Radu et al.
24 citations
Psychedelics may improve sexual functioning and satisfaction days or weeks after use, according to two studies. In a large naturalistic study, people who used psychedelics reported greater pleasure, communication during sex, and satisfaction with their partner and appearance. A controlled clinical trial comparing psilocybin therapy with the SSRI escitalopram for depression found that those given psilocybin reported positive changes in sexual functioning after treatment, while those given escitalopram did not. This is the first quantitative investigation of psychedelics' post-acute effects on sexual functioning, suggesting a potential benefit and a need for further research.
Psychiatry Research
July 23, 2023
Otto Simonsson, Per Carlbring, Robin Carhart-Harris et al.
24 citations
In a meta-analysis of three psilocybin trials for depression involving 102 participants, clinically significant symptom worsening occurred for a minority of those receiving psilocybin or escitalopram (about 10%) and for a majority of those in the waitlist condition (63.6%). The psilocybin arm showed a lower likelihood of symptom worsening compared to waitlist and no difference compared to escitalopram. The authors note the limitation of a relatively small sample size.
Journal of Psychopharmacology
April 25, 2023
Brandon Weiss, David Erritzøe, Bruna Giribaldi et al.
24 citations
A reanalysis of data from a trial comparing psilocybin therapy (PT) to escitalopram (ET) for major depressive disorder found that 14 of 16 outcome measures favored PT, but the QIDS-SR-16 did not. The QIDS-SR-16 showed higher variance, imprecision from compound items and sum-scoring, vague response options, and lack of focus on a core depression factor. When the trial data were examined at item, facet, and factor levels, results suggested PT was superior in reducing depressed mood, anhedonia, a core depression factor, and specific symptoms like sexual dysfunction. This raises concerns about relying on individual scales that miss depression's multidimensional structure.
Scientific reports
July 17, 2024
Sara de la Salle, Hannes Kettner, Julien Thibault Lévesque et al.
21 citations
A prospective longitudinal survey of eight Canadians with cancer who received legal psilocybin-assisted psychotherapy under Section 56 exemptions found significant improvements in anxiety, depression, pain, fear of COVID-19, quality of life, and spiritual well-being two weeks after the session. Attitudes toward death, medical assistance in dying, and desire for hastened death remained unchanged. Most participants found the sessions highly meaningful, though one reported a substantial decrease in well-being. These preliminary data suggest that real-world psilocybin-assisted psychotherapy can produce psychiatric benefits similar to those in clinical trials, but limited enrollment and negative experiences indicate a need for formal real-world evaluation programs.
Neuropsychopharmacology
March 8, 2019
M. Madsen, Patrick M. Fisher, Daniel Burmester et al.
21 citations
correction
No Summary
Neuroscience of consciousness
January 1, 2025
Christopher Timmermann, James W Sanders, David Reydellet et al.
19 citations
The psychedelic 5-MeO-DMT can, in its most extreme cases, produce a complete absence of self-experience and other perceptual content while preserving a quality of aroused, waking awareness. In an exploratory observational study in naturalistic ceremonial settings, micro-phenomenological interviews, questionnaires, and EEG recordings revealed a dynamic progression of effects, including variable disruptions of bodily and narrative self, reduced phenomenal distinctions, and visual imagery. EEG showed global alpha and posterior beta power reductions, suggesting inhibition of top-down brain models. The findings indicate 5-MeO-DMT's potential as a pharmacological model for deconstructed consciousness, though retrospective questionnaires have limitations.
The International Journal of Neuropsychopharmacology
February 14, 2014
Vibe G. Frøkjær, David Erritzøe, Klaus K. Holst et al.
19 citations
Prefrontal serotonin transporter binding is positively associated with the cortisol awakening response, a measure of hypothalamic-pituitary-adrenal-axis output, in both MDMA users and non-users. MDMA users showed a significantly higher cortisol awakening response than non-users. The findings suggest that the inhibitory control on HPA-axis output is less efficient after recent MDMA use, likely through mechanisms beyond those compensated by reduced serotonin transporter levels.
Comprehensive psychiatry
July 1, 2025
Luca Pellegrini, Naomi A Fineberg, Sorcha O'Connor et al.
17 citations
A 10 mg dose of psilocybin produced a rapid, moderate-to-large reduction in compulsive symptoms in people with obsessive-compulsive disorder (OCD), lasting up to one week after dosing. In a blinded pharmacological challenge study, 18 adults with at least moderate OCD received a 1 mg and then a 10 mg dose of oral psilocybin, separated by four weeks. One week after the 10 mg dose, scores on the compulsion subscale of the Yale-Brown Obsessive Compulsive Scale showed a significant improvement compared to the 1 mg dose (Cohen's d = 0.74). No effect on depression was detected. The drug was well tolerated with no serious adverse events.
Journal of Psychopharmacology
May 7, 2018
Balázs Szigeti, Adam Winstock, David Erritzøe et al.
17 citations
Neuroimaging studies of people who regularly use ecstasy have focused on unusually heavy users, not typical users. A systematic review of 10 imaging studies that measured serotonin transporter levels in recreational ecstasy users found that the average number of pills taken per session and sessions per month corresponded to the top 5-10% of users in the Global Drug Survey, a large international self-report database. Imaging participants consumed, on average, 720% more pills per year than the Global Drug Survey participants. This suggests that conclusions from these brain imaging studies likely overestimate the extent of serotonergic alterations experienced by the majority of people who use ecstasy.
American Journal of Psychiatry
May 7, 2025
Matthew B Wall, Lysia Demetriou, Bruna Giribaldi et al.
16 citations
Psilocybin therapy greatly improved depressive symptoms but had only a small effect on how the brain responds to emotional stimuli. This contrasts with SSRIs, which often reduce emotional responsiveness alongside their antidepressant action. The findings suggest that psychedelic therapy may work through different neural mechanisms than conventional antidepressants.
Journal of Psychopharmacology
April 12, 2024
Joseph Peill, Miriam Marguilho, David Erritzøe et al.
16 citations
In a double-blind randomized controlled trial, 59 patients with depression received either a high (25 mg) or placebo (1 mg) dose of psilocybin. Those given the high dose reported stronger perceived 'inner healing' effects, and within that group, higher inner healer scores predicted greater improvement in depressive symptoms two weeks later. The findings suggest that the concept of an intrinsic healing mechanism activated by psychedelics merits further scientific investigation, though the idea remains scientifically nascent.
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.
Journal of Psychopharmacology
November 14, 2022
Meg J Spriggs, Bruna Giribaldi, Taylor Lyons et al.
15 citations
A fixed 25 mg dose of psilocybin produces similar acute psychedelic effects and improvements in well-being regardless of body mass index (BMI). Pooling data from three therapeutic studies, results support the null hypothesis that BMI does not predict overall intensity of the altered state, mystical experiences, perceptual changes, or emotional breakthroughs. There was weak evidence that lower BMI participants reported greater 'dread of ego dissolution,' but BMI did not meaningfully add to predictions beyond age, sex, and study. Mystical-type experiences and emotional breakthroughs strongly predicted well-being improvements, but BMI did not. These findings suggest body weight-adjusted dosing may be unnecessary, supporting fixed dosing to reduce practical and financial burdens on psychedelic therapy scalability.
Psychedelic Medicine
October 28, 2022
Bruna Giribaldi, Sandeep M. Nayak, Bilal A. Bari et al.
15 citations
A Bayesian reanalysis of a trial comparing psilocybin (25 mg) to escitalopram (20 mg) over 6 weeks in 59 patients with major depressive disorder found that psilocybin outperformed escitalopram on three of four depression scales, though evidence was not uniformly clinically meaningful. Using skeptical priors that bias results toward zero, the analysis showed strong to extremely strong evidence favoring psilocybin on the BDI-1A, MADRS, and HAMD-17, while evidence on the primary outcome (QIDS SR-16) was indeterminate. For clinically meaningful superiority, evidence was moderate against it for the QIDS SR-16 but moderate to strong for the MADRS and HAMD-17. Psilocybin showed extremely strong evidence of noninferiority to escitalopram across all scales. The findings support further research on psilocybin's relative efficacy.
Nordic Journal of Psychiatry
July 20, 2017
David Erritzøe, William A. Richards
14 citations
Psychedelic therapies are being re-evaluated for treating conditions like major depression, cancer-related anxiety and depression, and alcohol use disorder. The research examines their effects and safety, suggesting potential benefits for these psychopathologies.
July 7, 2022
Richard J. Zeifman, Meg J. Spriggs, Hannes Kettner et al.
13 citations
preprint
The Relaxed Beliefs Under pSychedelics (REBUS) model suggests that psychedelics reduce the strength of deeply held beliefs. In a preliminary test of this idea, 11 healthy adults received a low (1 mg) and a high (25 mg) dose of psilocybin four weeks apart. Confidence in negative self-beliefs decreased after the high dose but not after the low dose. Greater brain signal entropy and stronger subjective effects during the high dose correlated with larger decreases in negative belief confidence, both during the session and four weeks later. Reduced confidence in negative beliefs was strongly linked to improved well-being at the four-week follow-up. These findings provide initial psychological support for the REBUS model, though replication in larger and clinical samples is needed.