[Illicit use of classic psychedelics and suicidality: A systematic literature review]. (Phase 2) — Given the contrasting results available in the literature, the objective of this systematic review was to investigate the specific impact of illicit use of classic psychedelics (psilocybin, LSD, DMT, mescaline) on suicidality (suicidal ideation, suicide planning, suicide attempts, suicides).…
Precision Functional Brain Mapping in Psilocybin (Observational, Washington University School of Medicine, n=11, completed) — This project will employ functional brain imaging to study the mechanism and immediate and long-term effects of psilocybin, a serotonin receptor 2A agonist, on cortical and cortico-subcortical brain networks in healthy adults.
Open-Label Psilocybin Study in Transdiagnostic Population (Phase 1, Yale University, n=50, recruiting) — The primary objective of this study is to investigate the safety, feasibility, and tolerability of psilocybin treatment in individuals with functional impairment due to psychiatric symptoms.…
Efficacy and Safety of Psilocybin in Treatment-Resistant Major Depression (Phase 2, Central Institute of Mental Health, Mannheim, n=144, completed) — The study aims to investigate the safety and efficacy of oral psilocybin administered under supportive conditions in treatment-resistant major depression (TRD).…
Two Doses of Psilocybin for the Treatment of MDD in Adults With Cancer (Phase 2, Sunstone Medical, n=56, active) — This is a Phase 2, single-center study to explore the efficacy, safety, and tolerability of up to two 25-mg doses of psilocybin administered at an interval of 9 to 10 weeks in patients with MDD and cancer.…
Safety and Tolerability of Psilocybin in Post-Traumatic Stress Disorder (Phase 1, Johns Hopkins University, completed) — The purpose of this study is to evaluate the safety, tolerability, and potential efficacy of psilocybin-assisted psychotherapy to reduce post-traumatic stress disorder (PTSD) severity in a sample of individuals with PTSD.
Wellcome Leap Psilocybin for OUD (Phase 2, Anna Rose Childress, Ph.D., n=36, recruiting) — Investigators will recruit 36 individuals on MAT for OUD for a double-blind, placebo-controlled design to determine whether PEX010 (25-mg/d) shows preliminary efficacy on neural correlates of neurocognition and on clinical outcomes.…
Compass Pathways to Announce New Clinical Data from Two Ongoing Phase 3 Trials (Phase 3, Compass Pathways plc, active) — Compass Pathways will report new clinical data from two ongoing Phase 3 trials evaluating COMP360, a synthetic formulation of psilocybin, for treatment-resistant depression. Data from Part A and Part B of COMP005 and Part A of COMP006 will be disclosed.
For veterans with severe PTSD, psilocybin-assisted therapy may help (Phase 2, The Ohio State University, n=12) — A pilot clinical trial with 12 veterans found that 75% were in remission from PTSD one month after psilocybin-assisted therapy. The treatment was safe, with no serious adverse events or increases in suicidal thinking.
Efficacy and Safety of a Single Dose of Psilocybin for Chronic Suicidal Ideation: An Open-Label Trial (Phase 2, n=20, completed) — This open-label, single-arm study evaluated a single 25-mg dose of psilocybin with psychological support in 20 adults with chronic suicidal ideation and treatment-resistant depression. The primary outcome was the change from baseline in the Modified Scale for Suicidal Ideation (MSSI) at week 3.
Psilocybin Failed to Live Up to Hype for Treatment-Resistant Depression (Phase 2, Heidelberg University) — The phase IIb EPISODE trial found that psilocybin plus psychotherapy showed limited efficacy for easing depressive symptoms in individuals with treatment-resistant depression. While secondary outcomes showed some improvement, the primary outcome was not statistically significant, leading to inconclusive findings.
Compass says its psilocybin drug helped patients with severe depression in two trials (Phase 3, Compass Pathways) — Compass Pathways' COMP360 psilocybin therapy showed positive results in two Phase 3 trials for severe depression, meeting primary endpoints and demonstrating significant reductions in depressive symptoms. The company plans to submit these findings to regulatory authorities.
OHSU-led research initiative examines supervised psilocybin (Observational, Oregon Health & Science University, active) — A five-year, $3.3 million federally funded research initiative led by OHSU will assess the safety and effectiveness of state-regulated psilocybin services in community settings, aiming to inform other states considering similar legal frameworks.
Connecticut moves to expand psychedelic-assisted therapy study for PTSD, depression (Observational, State of Connecticut, active) — Connecticut is expanding a pilot program for psychedelic-assisted therapy using MDMA or psilocybin for PTSD and depression. The program, initially limited to veterans and first responders, will now be open to qualifying patients 18 and older. The legislation also removes a sunset clause, allowing the program to continue even if MDMA and psilocybin are approved for medical use by the DEA.
MDMA
Pharmacological Interaction Between Pindolol and MDMA (3,4-Methylenedioxymethamphetamine) (Phase 1, University Hospital, Basel, Switzerland, n=16, completed) — MDMA (3,4-Methylenedioxymethamphetamine, "Ecstasy") produces tachycardia, hypertension, hyperthermia, and other acute adverse effects. Ecstasy use has also been associated with rare cardio- and cerebrovascular complications.…
New VA Trial of MDMA Psychedelic for PTSD: What Veterans Need to Know (Phase 2, Department of Veterans Affairs, n=80, recruiting) — The VA began enrolling veterans in its first-ever clinical trial of therapy assisted by MDMA for treatment-resistant PTSD and alcohol use disorder in May 2026. Approximately 80 veterans will be enrolled in this randomized, placebo-controlled, double-blind study, with results expected in May 2030.
Trump throws support behind psychedelics with executive order (Regulatory, approved) — President Donald Trump signed an executive order to accelerate the development of and facilitate broader access to psychedelic therapies for serious mental health conditions. The order directs the FDA to grant Commissioner's National Priority Vouchers to appropriate psychedelic drugs with breakthrough designation, potentially shortening review periods.
MDMA Therapy in Australia Shows Results, but the Cost Is Limiting Access (Regulatory, Therapeutic Goods Administration, n=200, active) — In Australia, MDMA-assisted therapy for PTSD has shown striking early results, with over half of patients reporting significant relief and no serious adverse events recorded among nearly 200 participants. However, the high cost and limited access pose significant barriers to widespread adoption.
VA Launches MDMA Clinical Trial to Measure Effects on PTSD, Mental Health (Phase 3, Department of Veterans Affairs (VA), n=80, recruiting) — The VA is launching a randomized controlled trial to evaluate the safety and efficacy of MDMA-assisted therapy for PTSD and alcohol use disorder in approximately 80 veterans. Results will compare outcomes between those receiving MDMA-assisted therapy and those receiving psychotherapy with an active placebo.
Ketamine
Ketamine for substance use disorders: a systematic review and meta-analysis. (Phase 2) — Substance use disorder (SUD) is a major global health issue, contributing significantly to the disease burden. Despite this, effective treatments for SUD remain limited. Ketamine has shown potential as a treatment, yet no meta-analysis has assessed its efficacy for SUD.…
Ketamine persists within neuronal compartments long after systemic clearance. (Phase 2) — Ketamine produces rapid and sustained antidepressant effects after a single dose. Plasma membrane NMDA receptors are the presumptive primary molecular targets, yet how ketamine distributes, localizes, and engages neurons across cellular and subcellular compartments remains largely unknown.…
Treatment-resistant Depression in the Post-ketamine Era: Unmet Needs beyond Rapid Response. (Meta-analysis) — The introduction of ketamine and its S-enantiomer, esketamine, has been one of the most consequential advances in treatment-resistant depression (TRD) in recent decades, demonstrating that rapid and clinically meaningful antidepressant effects can occur within hours, even in patients who have not responded to conventional treatments.…
Esketamine in Treatment-Resistant Depression: Clinical and Translational Perspectives. (Phase 2) — Esketamine, an intranasally administered N-methyl-D-aspartate (NMDA) receptor antagonist, represents a significant advancement in the treatment of Major Depressive Disorder (MDD), particularly among patients with Treatment-Resistant Depression (TRD).…
The functional role of ERK activity in esketamine's antidepressant effects. (Phase 2) — Esketamine has been approved for the treatment of treatment-resistant depression. However, there is an unmet clinical need to extend the duration of esketamine's action to reduce the high recurrence rate after drug withdrawal and the potential side effects of repeated esketamine use.…
The UTHealth Ketamine Project (Phase 2, The University of Texas Health Science Center, Houston, n=10, completed) — The primary objective of this study is to determine the effectiveness of serial infusions of intravenous (IV) ketamine in adults with treatment resistant depression (TRD).
Esketamine as Treatment for Chronic Pain Due to Endometriosis: a RCT Study (Phase 3, Reinier de Graaf Groep, n=56, recruiting) — The goal of this randomized controlled trial is to investigate the effect of esketamine versus placebo on the NRS score for chronic pelvic pain. Secondary endpoints are to assess pain scores, side-effects, quality of life, depressive symptoms and pain coping.
Using Virtual Reality to Control the Audio-visual Inputs During Ketamine/Esketamine Treatment (Observational, Yale University, n=7, completed) — Investigators aim to examine the role of audiovisual inputs during treatment with ketamine/esketamine in affecting tolerability and effectiveness of treatment of depressive episodes, by providing patients with a relaxing environment using virtual reality goggles and noise cancelling headphones, and assessing whether these tools can improve the tolerability and effectiveness of treatment with ketamine/esketamine
Efficacy of Repeated Ketamine Infusions for Treatment-resistant Depression (Phase 2, VA Office of Research and Development, n=62, completed) — About one-third of depressed patients will not get better after multiple antidepressant treatments. This situation put a high burden on patients with depression due to worsening quality of life and increasing health care costs.…
Ketamine For Suicidal Ideation (Observational, James Murrough, n=24, completed) — This study will examine the effects of Intravenous (IV) ketamine both in an outpatient population and with subjects on the inpatient unit with suicidal ideation (SI).
The Effects of Ketamine and Guanfacine on Working Memory in Healthy Subjects (Observational, Yale University, n=16, completed) — The purpose of the study is 1. To establish the feasibility of fMRI studies of the interaction of guanfacine and ketamine. 2. To explore the possibility that guanfacine can ameliorate the negative effects of ketamine on task-related prefrontal activation. 3.…
Low-dose Ketamine Infusion Among Adolescents With Treatment-resistant Depression (Observational, Taipei Veterans General Hospital, Taiwan, n=12, completed) — In the past decades, the prevalence of adolescent depression and suicide increased significantly in Taiwan and worldwide. To date, the suicide mortality is the second mortality cause in the adolescent and young adult population in Taiwan.…
Ketamine as an Alternative Treatment to ECT in Major Depressive Disorder (Phase 2, Pouya Movahed Rad, n=198, completed) — Developing more effective and faster acting antidepressant is of outmost clinical importance. Available antidepressant therapies have a delayed therapeutic effect. It typically takes several weeks before symptom relief is evident.…
Effectiveness of Ketamine Administered by Mesotherapy in Complex Regional Pain Syndrome Type 1 (CRPS1) (Phase 2, Hospices Civils de Lyon, n=31, completed) — Complex Regional Pain Syndrome type 1 (CRPS1) is a disabling pain syndrome. Its definitive treatment has not been established and the results of current treatments are often unsatisfactory. The prognosis is difficult to establish because the vast majority of CRPS regresses within a few weeks.…
Reverse Engineering Ketamine’s Effects May Lead to New Antidepressants (News, Weill Cornell Medicine) — Weill Cornell Medicine investigators have "reverse engineered" ketamine’s antidepressant effects to identify potential new strategies for treating depression. Ketamine can provide immediate relief to some patients with treatment-resistant depression, but the effects are often short-lived and it has serious side effects.
Structural imaging predictors of ketamine response in treatment-resistant depression: a machine learning approach (Phase 3, n=99) — A machine-learning model using pre-treatment structural MRI data predicted antidepressant response to ketamine in adults with treatment-resistant depression with a balanced accuracy of 72.2% in the discovery sample and 60.0% in external validation. Greater gray matter volume in frontal regions predicted response, while greater cerebellar volume predicted non-response.
Advancing the Treatment of Depression (Meta-analysis, UConn School of Medicine) — Two studies evaluated existing drugs used in new ways to treat major depression. One found intravenous ketamine was more effective than placebo in the short term for depression and rapidly reduced suicidal impulses. The other meta-analysis found some antipsychotics were more likely to decrease depression symptoms, but the most effective one, lumapeterone, also had the most side effects.
Is Ketamine for Depression Moving Too Fast on Weak Data? (Observational, Trinity College Dublin) — A study investigating racemic ketamine infusions for depression found no additional benefit compared to a placebo when added to usual inpatient care, leading researchers to question if ketamine's efficacy for depression has been overstated.
Ketamine: How Yale Redefined Depression Treatment (News, Yale) — Yale researchers have been instrumental in redefining depression treatment through their work with ketamine, exploring its rapid antidepressant effects and mechanisms.
Ketamine Therapy (News, Cleveland Clinic) — Ketamine therapy uses a low dose of an anesthetic to treat depression, anxiety and some chronic pain by blocking certain brain signals and helping nerve cells form new connections, potentially improving mood quickly. Treatment is given by IV or nasal spray under medical supervision and may require multiple sessions.
LSD
Neuronal Correlates of Altered States of Consciousness (Observational, University Hospital, Basel, Switzerland, n=24, completed) — The aim of the present study is to assess the neuronal correlates of alterations in waking consciousness pharmacologically induced by a 5-hydroxytryptamine (HT)2A receptor agonist in healthy subjects using functional magnetic resonance imaging (fMRI).
DMT
Safety of GH001 in Healthy Volunteers (Phase 1, GH Research Ireland Limited, n=22, completed) — The aim of the study is to investigate the safety of GH001 (containing 5-methoxy-dimethyltryptamine; 5-MeO-DMT), and its dose-related psychoactive effects in healthy volunteers.…
Pharmacokinetics of GH001 Delivered Via a Proprietary Aerosol Delivery Device in Healthy Subjects (Phase 1, GH Research Ireland Limited, n=52, recruiting) — The primary objectives of this trial are to determine the pharmacokinetic (PK) profile and the safety and tolerability of GH001 delivered via a proprietary aerosol delivery device in healthy subjects after single-dose administration and a single-day individualized dosing regimen (IDR).…
The NeXT Study; The Netherlands XTC Toxicity Study (Observational, UMC Utrecht, n=225, completed) — The purpose of this study is to investigate the possible neurotoxic effects of the party-drug Ecstasy (MDMA)on brain and brain function in humans. Main research questions concern the causality, course and clinical relevance of the neurotoxicity of ecstasy
Functional Brain Imaging in Recreational Users of Ecstasy (Observational, Hadassah Medical Organization, n=18, completed) — Recreational use of "ecstasy" (MDMA; 3,4-methylenedioxymethamphetamine) is associated with long-lasting effects on metabolism in the human brain.…
Multimodal Pharmacological Study of Clinical Cohorts for Major Depressive Disorder (Observational, Shanghai Mental Health Center, n=130, recruiting) — This study focuses on the neurobiological changes in MDD patients with high suicidal risk during rapid antidepressant treatments, such as Esketamine and Electroconvulsive Therapy (ECT).…
Final psychedelics guidance suggests FDA is ‘receptive’ to helping companies succeed (Regulatory, FDA) — The FDA released final guidance for developers of psychedelic drugs, updating its 2023 draft recommendations and providing a framework for future regulatory action. This guidance suggests the agency is receptive to helping sponsors succeed in developing these compounds for mental health.