JAMA
August 31, 2023
Charles L Raison, Gerard Sanacora, Joshua Woolley et al.
493 citations
A single 25-mg dose of synthetic psilocybin, administered with psychological support, produced a clinically significant and sustained reduction in depressive symptoms and functional disability over 43 days in adults with major depressive disorder. In a phase 2 trial of 104 participants, those receiving psilocybin showed a mean 12.3-point greater improvement on the Montgomery-Asberg Depression Rating Scale at day 43 compared with those receiving a niacin placebo. Psilocybin also improved daily functioning and led to more sustained response, though not remission. No serious adverse events occurred, but psilocybin was associated with more overall and severe adverse events.
JAMA Network Open
December 5, 2024
Anthony L Back, Timara K Freeman-Young, Ladybird Morgan et al.
37 citations
A double-blind randomized trial tested psilocybin therapy against niacin in 30 US clinicians (physicians, advanced practice practitioners, and nurses) who developed depression, burnout, or PTSD from frontline COVID-19 pandemic work. Participants had no prepandemic mental health diagnoses but had moderate or severe depression at enrollment. After one medication session, depression symptoms (measured by the Montgomery-Asberg Depression Rating Scale) improved significantly more with psilocybin (mean decrease of 21.33 points) than with niacin (mean decrease of 9.33 points), a difference of 12.00 points. Burnout and PTSD symptoms showed numerically larger improvements with psilocybin, but these differences were not statistically significant. The findings suggest psilocybin therapy can reduce depression in this postpandemic condition.
Progress in brain research
January 1, 2018
Joseph P Barsuglia, Martin Polanco, Robert Palmer et al.
37 citations
A 31-year-old male military veteran with moderate alcohol use disorder received sequential treatment with ibogaine hydrochloride (1550mg, 17.9mg/kg) on day 1 and vaporized 5-MeO-DMT (bufotoxin source 50mg, estimated 5-7mg) on day 3 at an inpatient clinic in Mexico. SPECT neuroimaging before and 3 days after treatment showed increased brain perfusion in bilateral caudate nuclei, left putamen, right insula, and temporal, occipital, and cerebellar regions. The patient reported improved mood, cessation of alcohol use, and reduced cravings at 5 days, sustained at 1 month, with partial return to mild alcohol use at 2 months. The findings suggest short-term therapeutic outcomes and warrant further investigation.
Heliyon
December 1, 2022
Benjamin Kelmendi, Giuliana DePalmer, Gayle Maloney et al.
34 citations
A patient with treatment-resistant obsessive-compulsive disorder received psilocybin and was followed for a year. His OCD symptoms markedly improved, with the YBOCS score dropping from 24 to between 0 and 2. Broader gains included better emotional connection, social and work functioning, and quality of life. This individual was an early participant in an ongoing controlled study. The results are preliminary but suggest that carefully monitored and supported psychedelic treatment may hold therapeutic potential for obsessions and compulsions.
Frontiers in Psychiatry
February 6, 2023
Candace R. Lewis, Joseph Tafur, Sophie Spencer et al.
29 citations
Epigenetic changes in hypothalamic-pituitary-adrenal (HPA) axis genes may predict successful psychotherapy for post-traumatic stress disorder (PTSD). In a pilot sub-study of a Phase 3 clinical trial, 23 participants (16 receiving MDMA-assisted therapy, 7 receiving placebo with therapy) provided saliva samples. Methylation at 259 CpG sites across three HPA genes (CRHR1, FKBP5, NR3C1) was measured before and after treatment. Methylation changes across both groups significantly predicted symptom reduction on 37 of the sites, with two surviving false discovery rate correction. The MDMA group showed greater methylation change on one NR3C1 site compared to placebo. Therapy-related PTSD symptom improvements may be linked to DNA methylation changes in HPA genes, and such changes may be larger with MDMA-assisted therapy.
Frontiers in Psychiatry
April 25, 2023
Rachael Grazioplene, Calvin Bohner, Giuliana DePalmer et al.
27 citations
A randomized, double-blind, placebo-controlled trial tests whether a single dose of psilocybin (0.25 mg/kg) is safe, tolerable, and effective for obsessive-compulsive disorder (OCD) symptoms. Thirty adults who have not responded to at least one standard treatment will receive either psilocybin or an active placebo (niacin). OCD symptoms are assessed by blinded raters at 48 hours post-dosing, with 12 weeks of follow-up. Resting-state neuroimaging explores neural mechanisms. The study aims to provide preliminary evidence for psilocybin's effects on OCD and pave the way for future research on neurobiological mechanisms.
Frontiers in Pharmacology
February 17, 2023
Lourdes Poyatos, Clara Pérez‐mañá, Olga Hladun et al.
26 citations
Methylone, a common synthetic cathinone used as a substitute for MDMA, produces similar acute effects in humans. In a controlled trial with 17 experienced psychostimulant users, a single 200 mg oral dose of methylone increased blood pressure and heart rate and induced pleasurable effects including stimulation, euphoria, wellbeing, enhanced empathy, and altered perception. Methylone's effect profile resembled MDMA's but with a faster onset and earlier disappearance of subjective effects. The findings suggest methylone's abuse potential is comparable to that of MDMA in humans.
Journal of Psychopharmacology
November 30, 2016
Benjamin Kelmendi, Philip R. Corlett, Mohini Ranganathan et al.
11 citations
No Summary
Psychedelic Medicine
January 20, 2025
Marianna Graziosi, Gabrielle Agin-Liebes, Mary P Cosimano et al.
9 citations
Psilocybin and other serotonergic psychedelics are used in research settings with safety measures including controlled environments, staff presence, screening, and psychoeducation. An analysis of study materials from psilocybin trials over the past two decades found that psychoeducation documents varied but commonly emphasized biological and physical safety, psychological safety and well-being, aspects of setting, and the potential for expectancies. The materials prioritized biological and psychological safety across all sites. The authors also identified elements unrelated to safety that may contribute to participant expectancies and suggest these extrapharmacological factors be studied systematically to maximize safety while minimizing extraneous expectancies.
Frontiers in Psychiatry
January 9, 2024
Terence H W Ching, Lucia Amoroso, Calvin Bohner et al.
9 citations
A randomized controlled trial will test whether two doses of psilocybin (25 mg followed by either 25 or 30 mg), given with non-directive support, reduce obsessive-compulsive disorder (OCD) symptoms more than a single dose or a waitlist control. Thirty adults with treatment-refractory OCD will be enrolled. OCD symptoms will be measured with the Yale-Brown Obsessive-Compulsive Scale – Second Edition by a blinded rater at baseline and after the second dosing week. Participants will be followed for up to 12 months. The trial also aims to identify psychological mechanisms that may explain psilocybin's effects on OCD.
JAMA psychiatry
May 1, 2026
Amanda Jones, Jennifer Warner-Schmidt, Hannah Kwak et al.
6 citations
In a phase 2 randomized clinical trial, TSND-201 (methylone) reduced PTSD symptoms more than placebo in adults aged 18 to 65. Over 10 weeks, 65 participants received either TSND-201 or placebo in four weekly oral sessions. The drug group showed a significantly greater improvement in the primary measure of PTSD severity (CAPS-5) than placebo, with a difference of about 10 points. Secondary measures of PTSD-related distress, disability, and depression also improved more with the drug. Common side effects included headache, nausea, and increased blood pressure. The results suggest TSND-201 is a well-tolerated, rapid-acting treatment for PTSD.
Frontiers in Neuroscience
February 7, 2024
Jennifer Warner-Schmidt, Martin Stogniew, Blake Mandell et al.
6 citations
Methylone, a monoamine uptake inhibitor and releaser currently in clinical development for PTSD, produced rapid changes in gene expression in rat brain areas linked to PTSD and major depressive disorder. In the amygdala, methylone regulated myelin-related genes; in the frontal cortex, it upregulated genes involved in neuroplasticity. Unlike MDMA, methylone showed no off-target activity at 168 tested GPCRs, including 5HT2A and 5HT2C receptors. These results suggest methylone acts as a rapid-acting neuroplastogen with higher specificity and fewer off-target effects than MDMA, supporting its potential for treating PTSD and possibly other neuropsychiatric disorders.
March 17, 2023
Terence H. W. Ching, Rachael Grazioplene, Christopher Pittenger et al.
6 citations
preprint
A randomized, waitlist-controlled study will test whether repeated oral doses of psilocybin (25 mg, with a possible second dose of 25 or 30 mg) reduce obsessive-compulsive disorder (OCD) symptoms. Participants receive either immediate treatment (two doses one week apart) or delayed treatment seven weeks later. Non-directive psychological support accompanies preparation, dosing, and integration sessions; facilitators do not provide structured therapy. The adaptive dosing strategy adjusts the second dose based on response after the first. The manual describes facilitator activities and includes updated checklists for the two-dose protocol.
October 5, 2022
Terence H. W. Ching, Stephen A. Kichuk, Giuliana DePalmer et al.
5 citations
preprint
A single 0.25 mg/kg dose of psilocybin, given with non-directive psychological support in a controlled clinical setting, is being tested for safety and efficacy in treating obsessive-compulsive disorder. Monitors accompany participants before, during, and after dosing to prepare them, ensure safety, and provide an unstructured context for processing the experience. Although no formal therapy is delivered, the supportive presence of monitors may be experienced as therapeutic. This manual outlines monitor activities across the three phases of the dosing session.
Journal of Psychedelic Studies
May 15, 2025
Terence H. W. Ching, Benjamin Kelmendi
4 citations
A primer for culturally attuned psychedelic clinical trials narratively reviews psychological and pragmatic barriers to diversity—including stigma, medical mistrust, history of psychedelic-assisted conversion therapy, income disparities, schedule inflexibilities, and transportation inaccessibility—and proposes strategies for culturally attuned recruitment, assessment, and retention of Black, Indigenous, and Peoples of Color (BIPOC) and sexual- and gender-diverse populations. Strategies include diversifying the study team, debinarizing the therapist dyad, using culturally attuned language and flyers, community outreach, improving transportation access, diversifying room setup, and using culturally attuned assessments. The authors encourage research groups to adapt these recommendations to improve accessibility to innovative mental health treatments for diverse populations.
Psychiatry research
June 1, 2024
Gayle Maloney, Terence Ching, Stephen A Kichuk et al.
3 citations
About 30-50% of people with obsessive-compulsive disorder do not respond to standard treatments. Recent pilot data suggest benefit from both psilocybin-assisted psychotherapy and imagery rescripting. Both interventions appear to allow reprocessing of negative emotions and core beliefs linked to past aversive events. The authors propose that basing psilocybin-assisted psychotherapy on an imagery rescripting framework may provide synergistic benefits in reducing symptoms, modifying core beliefs, and supporting value-based living.
February 11, 2026
Sarah Shnayder, Gabrielle Agin-Liebes, Troy Hubert et al.
preprint
In people with treatment-resistant obsessive-compulsive disorder (OCD), greater mystical-type experiences during psilocybin sessions—especially feelings of unity, sacredness, and transcendence—were linked to lower OCD symptom severity at 1-week and 12-week follow-ups, even after accounting for baseline severity and treatment condition. The Mystical subscale of the Mystical Experience Questionnaire showed the strongest and most consistent associations. The Space–Time subscale was related to lower OCD severity only at 12 weeks. Positive mood, ineffability, and challenging experiences were not significantly tied to post-treatment OCD severity. These results suggest that the quality of subjective experience during psilocybin sessions may help optimize treatment outcomes.
January 15, 2026
Benjamin Kelmendi, Thomas G. Adams, Terence H. W. Ching et al.
preprint
A single dose of psilocybin (0.25 mg/kg) produced rapid and sustained reductions in obsessive-compulsive disorder (OCD) symptoms among adults with treatment-resistant OCD. In a randomized, double-blind trial, 28 adults received either psilocybin or niacin (250 mg). At 48 hours, OCD severity scores dropped by about 10 points more in the psilocybin group than in the niacin group, a large effect. At one week, 69% of psilocybin participants achieved a clinically meaningful response, compared with none in the niacin group. Benefits lasted through 12 weeks. One serious adverse event occurred. Open-label psilocybin given later also reduced symptoms. The findings suggest psilocybin may offer a new treatment approach for treatment-resistant OCD, but larger confirmatory trials are needed.
Frontiers in Psychiatry
February 16, 2024
Terence H W Ching, Lucia Amoroso, Calvin Bohner et al.
correction
A correction notice addresses an error in a previously published article on psilocybin therapy for obsessive-compulsive disorder. The notice specifies that the original article's DOI is 10.3389/fpsyt.2023.1278823 and provides the necessary correction. No findings, methods, or results are presented in this text.
Elsevier eBooks
January 1, 2024
Alfred P. Kaye, Benjamin Kelmendi, Merangely N. Rivera et al.
No Summary