The New England journal of medicine
November 3, 2022
Guy M. Goodwin, Scott T Aaronson, Oscar Alvarez et al.
1,095 citations
A single 25 mg dose of psilocybin, but not 10 mg, reduced depression scores more than a 1 mg control dose over three weeks in adults with treatment-resistant depression. In this phase 2 trial, 233 participants were randomly assigned to 25 mg, 10 mg, or 1 mg of synthetic psilocybin with psychological support. The 25 mg group showed an average 12-point drop on the MADRS depression scale versus a 5.4-point drop in the 1 mg group, a significant difference. The 10 mg group did not differ significantly from control. Response and remission rates at three weeks supported the primary result, but sustained response at 12 weeks was not significantly different.
Journal of Affective Disorders
February 3, 2023
Guy M. Goodwin, Scott T Aaronson, Oscar Alvarez et al.
168 citations
Three weeks after a single dose, 25 mg of psilocybin, and to a lesser extent 10 mg, improved patient-reported measures of depression severity, anxiety, affect, and functioning in people with treatment-resistant depression. These findings extend the primary results from the largest randomized clinical trial of psilocybin for TRD, highlighting outcomes that matter to patients.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
September 1, 2023
Guy M. Goodwin, Megan Croal, David Feifel et al.
166 citations
A single 25 mg dose of synthetic psilocybin (COMP360) given alongside psychological support to adults with treatment-resistant depression who continued taking a selective serotonin reuptake inhibitor led to a mean reduction of 14.9 points on the Montgomery-Åsberg Depression Rating Scale at three weeks. Twelve of nineteen participants (63.2%) experienced mild treatment-emergent adverse events that resolved the same day, with no serious events or increased suicidal ideation. Response and remission occurred in 8 participants (42.1%). The authors suggest larger controlled trials are needed to determine whether this approach can benefit patients who cannot safely withdraw from antidepressants.
Irish Journal of Medical Science (1971 -)
June 15, 2021
Kate Corrigan, Maeve Haran, Conor Mccandliss et al.
79 citations
A survey of 99 mental health service users (52% female, average age 42) found that 72% supported further research into psilocybin therapy and 59% supported psilocybin as a medical treatment. 27% had previously used recreational psilocybin, more often men. Younger people, those with prior psychedelic experience, and those with non-religious beliefs held more favorable attitudes. 55% would accept psilocybin therapy if a doctor recommended it, while 20% would not. People with depression or anxiety were less likely to have used recreational psychedelics but more likely to support government-funded studies. Only 5% of those with conditions like psychosis or bipolar disorder thought psilocybin would be useful for them.
Frontiers in Psychiatry
December 17, 2021
John R. Kelly, Claire M. Gillan, Jack Prenderville et al.
66 citations
Psychedelic therapy, combining psychedelic drugs with psychological support, shows promise for treating disorders marked by rigid and unhealthy patterns of emotion, thought, and behavior, including depression, treatment-resistant depression, addiction, and potentially anxiety, OCD, PTSD, and eating disorders. This review examines preclinical and clinical evidence through the Research Domain Criteria (RDoC) framework, mapping the drugs' effects across molecular, cellular, and network levels to RDoC constructs like negative and positive valence, arousal, social processing, cognition, and sensorimotor systems. The goal is to clarify the specific clinical dimensions psychedelics affect and their underlying neurobiology, aiming toward a mechanistic understanding and personalized psychedelic therapy.
Journal of Affective Disorders
March 1, 2025
Guy M. Goodwin, Scott T Aaronson, Oscar Alvarez et al.
35 citations
In treatment-resistant depression, a single dose of 25 mg of psilocybin produced stronger correlations between certain psychedelic experiences and depression improvement three weeks later than lower doses. The intensity of psychedelic effects was dose-related, but scores for different doses overlapped considerably. At the 25 mg dose, dimensions of oceanic boundlessness and visual restructuralization, along with emotional breakthrough, showed the strongest correlations with reduced depression scores. The study does not establish causation and requires replication. The overlap in experience intensity across doses suggests unblinding to dose is less likely. Correlations between psychedelic experience and outcome indicate specificity in psilocybin's mechanism of action.
International journal of clinical and health psychology : IJCHP
January 1, 2023
John R. Kelly, Gerard Clarke, Andrew Harkin et al.
33 citations
A systems psychiatry approach recognizes complex interactions across biological levels and requires integrated treatment strategies. Serotonergic psychedelics primarily target cortical 5-HT2A receptors, but their therapeutic mechanisms span molecular, cellular, and network levels, influenced by biofeedback from the periphery and environment. The gut microbiome, through the gut-brain axis, regulates host neurophysiology via unconscious parallel processing systems. Although psychedelic and microbial signaling operate on different timescales, the microbiota-gut-brain axis may contribute to the preparatory, acute, and integration phases of psychedelic therapy. This review examines the gut microbiome and mycobiome, pathways of the MGB axis, and potential interactions with psychedelic therapy, discussing implications for precision medicine.
Pharmacology & Toxicology
May 1, 1997
Ivone de Souza, John R. Kelly, Andrew Harkin et al.
29 citations
Acute oral administration of MDMA (Ecstasy) to adult female rats produced dose-related effects including hyperthermia, reduced food and water intake, and hyperactivity. Deaths occurred from 40 mg/kg upward. Lower doses (20 and 40 mg/kg) caused prolonged hyperactivity lasting about 9 hours, while higher doses led to serotonin syndrome. The likely cause of death was a combination of serotonin syndrome and hyperthermia.
Irish Journal of Psychological Medicine
September 23, 2019
John R. Kelly, Annie Baker, Mona Babiker et al.
22 citations
A growing body of preliminary clinical research indicates that psilocybin, a compound found in hallucinogenic fungi, combined with psychological support can improve mood, reduce anxiety, and enhance quality of life. An open-label study showed marked reductions in depression symptoms among participants with treatment-resistant depression. The underlying neurobiological changes include altered brain connectivity and activity in the amygdala and default mode network, as well as increased synaptogenesis and neural plasticity. A randomized, double-blind trial has recently launched across Europe and North America, including a center in Ireland, to further test psilocybin's efficacy for treatment-resistant depression.
Irish Journal of Psychological Medicine
August 19, 2020
John R. Kelly, Matthew Crockett, Laith Alexander et al.
16 citations
The medium- to long-term mental health consequences of COVID-19 are predicted to increase, requiring multidisciplinary strategies. Psilocybin therapy shows promise as a transdiagnostic treatment for disorders with maladaptive habitual patterns, such as depression, addiction, and obsessive compulsive disorder. The COMPASS Pathways phase 2b double-blind trial is testing psilocybin therapy in antidepressant-free treatment-resistant depression (TRD) to determine safety, efficacy, and optimal dose. Results from the Imperial College London Psilodep-RCT comparing psilocybin therapy to the SSRI escitalopram will soon be published. The efficacy and safety of psilocybin therapy with SSRIs in TRD is not yet known; a COMPASS study in Dublin will address this. Psilocybin therapy may play an important role in post-COVID-19 psychiatry, though it is at an early clinical stage.
Irish Journal of Psychological Medicine
November 7, 2024
Andrew Gribben, Tara Burke, Colm Harrington et al.
5 citations
A survey of 151 psychiatrists in Ireland found that most hold positive attitudes toward psilocybin therapy: 81.5% agreed it shows promise for treating psychiatric disorders, 86.8% supported funding research, 86.8% would refer a patient if licensed, and 78.1% would consider it for themselves. However, only 40.0% felt knowledgeable and just 9.9% felt adequately prepared to participate. A minority expressed concerns: 6.6% thought it unsafe under medical supervision, 21.9% considered it potentially addictive, and 15.9% reported at least one concern about evidence, effectiveness, safety, cost, or impartiality. Consultant psychiatrists were less optimistic than trainees about its role in bipolar depression and emotionally unstable personality disorder.
Acta Neuropsychiatrica
July 25, 2025
Guillaume Thuery, Christopher Sheridan, Patricia Iusan et al.
4 citations
This narrative review synthesizes clinical and preclinical research on how 5-HT2A receptor psychedelics interact with the immune system. The evidence shows these compounds have direct immunomodulatory properties, including downregulation of gene regulators like NF-κB and reduced expression of cytokines such as TNF-α, IL-6, and IL-1β in both the central and peripheral nervous systems. These effects are accompanied by modulation of corticotrophin releasing hormone, adrenocorticotrophic hormone, and cortisol. The immunomodulation occurs through pathways involving serotonin receptors, the Sigma-1 receptor, and the TrkB receptor, as well as indirectly via the HPA axis. The review identifies that modulation of brain glia and glial-neuronal interactions remains to be determined, representing a promising direction for future research on the therapeutic potential of these psychedelics for mental health and brain disorders.
JAMA Psychiatry
March 25, 2026
Wiesław Jerzy Cubała, Malek Bajbouj, Michael Bauer et al.
3 citations
A single day of treatment with an inhaled synthetic formulation of mebufotenin (GH001) significantly reduced depression symptoms in adults with treatment-resistant depression compared to placebo. In a randomized, double-blind trial of 81 patients, those receiving up to three escalating doses of GH001 showed an average 15.5-point greater improvement on the Montgomery-Åsberg Depression Rating Scale by day 8 than those on placebo. Remission rates were 57.5% for GH001 and 0% for placebo. No severe or serious adverse events occurred. The findings suggest GH001 may be a rapid-acting, well-tolerated treatment option for treatment-resistant depression.
Journal of Affective Disorders
August 1, 2026
Guy M. Goodwin, Scott T Aaronson, Oscar Alvarez et al.
2 citations
In people with treatment-resistant depression receiving 25 mg psilocybin with monitoring and support, the therapeutic alliance before dosing had only weak correlations with improvement in depression scores at three weeks. Stronger correlations were seen with the intensity of the psychedelic experience itself, particularly emotional breakthrough and visual restructuring. Path analysis suggested that therapeutic alliance helped facilitate the psychedelic experience, but it was the psychedelic experience—not the alliance—that had stronger direct effects on clinical outcomes. The alliance's direct effect on antidepressant response was limited or absent.
Therapeutic Advances in Psychopharmacology
March 1, 2026
Guillaume Thuery, Frank Crossen, Daniel Mc Loone et al.
1 citation
About 15% of pregnant women experience postpartum depression, and many remain impaired despite available antidepressants. Serotonergic psychedelics may offer a viable therapeutic approach for postpartum depression, though the benefit-risk ratio is unclear. This review summarizes immune, endocrine, and neural pathways underlying postpartum depression and explores how psychedelics interact with these pathways in relation to maternal motivation, bonding, and caregiving. Special considerations for psychedelic therapy in the postpartum period are outlined. Further research, especially longitudinal trials with adaptations for the postpartum context, is needed to determine efficacy and safety.
The International Journal of Neuropsychopharmacology
June 2, 2026
John R. Kelly, Christopher Sheridan, Patricia Iusan et al.
Classical serotonergic psychedelics like psilocybin show emerging evidence of therapeutic potential across depression, anxiety, and substance use disorders, with indications of transdiagnostic efficacy. Early-phase studies yielded encouraging results, but recent larger-scale phase 3 trials for treatment-resistant depression have shown more modest effects. No regulatory approvals from the U.S. FDA or EMA exist, though a few countries permit psychedelic therapies in regulated clinical settings. The long-term trajectory and real-world impact within public health systems remain uncertain. This paper examines challenges for integrating psychedelic therapies into Ireland's public healthcare system, covering regulatory approval, Health Technology Assessment, service implementation, workforce capacity, and evaluation of long-term patient outcomes.
Psychedelic Medicine
December 19, 2025
Amanda Husein, Madalynn Traylor, M. Frances Vest et al.
Most Louisiana psychiatrists surveyed are open to psilocybin's medical use if backed by regulation. 82% reported some knowledge of psilocybin; 86% believed it should be researched for medicinal value; 71% would prescribe it if proven beneficial for a patient's illness. 57% thought it should be a first-line treatment for certain conditions, while 73% believed it should be used only after other treatments failed. The 10.5% response rate limits generalizability. The findings suggest a need for educational programs on psychedelics to inform clinical decisions.
Irish Journal of Psychological Medicine
December 18, 2025
Gurjot Brar, T. R. Jun. Burke, Andrew Gribben et al.
Online news coverage of psilocybin as a depression treatment increased sharply after 2022, with 43.2% of articles published between 2022 and 2024, mostly from US outlets. Although 90.4% of articles cited researchers, only 47.2% addressed risks, 46.4% discussed long-term evidence, and 25% included patient perspectives. Sentiment was very positive, averaging 2.27 on a −5 to +5 scale, and did not change significantly over time. Reporting on psilocybin's onset and duration of effects improved, but coverage remains concentrated in prominent outlets and lacks balance on risks and patient experiences.
J Affect Disord
October 10, 2025
Guy M. Goodwin, Scott T Aaronson, Oscar Alvarez et al.
correction
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