Treatment-resistant depression psychedelic and ketamine research trials
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Data as of 11 October 2026. Source: ClinicalTrials.gov records held by PsychoactiveMap, refreshed from a reviewed snapshot.
146 registered studies are counted for treatment-resistant depression. By compound: 34 psilocybin, 1 LSD, 3 DMT, 2 5-MeO-DMT, 1 ayahuasca and 110 ketamine. By registry status: 32 recruiting, 7 not yet recruiting, 1 enrolling by invitation, 9 active, not recruiting, 67 completed, 4 terminated, 10 withdrawn and 16 status not reported. By phase: 2 early phase 1, 13 phase 1, 51 phase 2, 25 phase 3, 17 phase 4, 21 not applicable and 17 not reported. Reported start years run from 2008 (earliest) to 2026 (latest).
Studies are matched when the title pairs treatment resistance or refractoriness with depression, major depression or MDD. Treatment-resistant PTSD or OCD is not included. Studies are matched by keyword on the title as registered, so a study can be missed and a study that mentions the condition only in passing can be included. A study tagged with more than one compound is counted under each compound. Ketamine studies are counted only when PsychoactiveMap classifies them as psychiatric research; anaesthesia, sedation and pain studies are left out.
Educational information, not medical advice. A registry listing is not evidence of safety, benefit or results, and it is not a recommendation. PsychoactiveMap does not recruit, screen or refer participants. Status and other details are copied from the registry and can be out of date, so check the registry record and speak to a qualified health professional before any decision. Read the full disclaimer.
At a glance
- 146 registered studies are counted on this page.
By compound
| Compound hub | Studies |
|---|---|
| Psilocybin | 34 |
| LSD | 1 |
| DMT | 3 |
| 5-MeO-DMT | 2 |
| Ayahuasca | 1 |
| Ketamine | 110 |
By registry status
| Status | Studies | Share |
|---|---|---|
| Recruiting | 32 | 22% |
| Not yet recruiting | 7 | 5% |
| Enrolling by invitation | 1 | 1% |
| Active, not recruiting | 9 | 6% |
| Completed | 67 | 46% |
| Terminated | 4 | 3% |
| Withdrawn | 10 | 7% |
| Status not reported | 16 | 11% |
By phase
| Phase | Studies | Share |
|---|---|---|
| Early Phase 1 | 2 | 1% |
| Phase 1 | 13 | 9% |
| Phase 2 | 51 | 35% |
| Phase 3 | 25 | 17% |
| Phase 4 | 17 | 12% |
| Not applicable | 21 | 14% |
| Not reported | 17 | 12% |
Countries
Country is taken from the study's linked research site. 1 of 146 records have no country on file. The top 10 countries are shown.
| Country | Studies | Share |
|---|---|---|
| United States | 68 | 47% |
| Canada | 26 | 18% |
| United Kingdom | 5 | 3% |
| Israel | 5 | 3% |
| Mexico | 4 | 3% |
| Poland | 4 | 3% |
| Austria | 3 | 2% |
| Belgium | 3 | 2% |
| Brazil | 3 | 2% |
| France | 3 | 2% |
When studies started
| Start year | Studies |
|---|---|
| 2024 to 2026 | 46 |
| 2020 to 2023 | 47 |
| 2015 to 2019 | 34 |
| 2010 to 2014 | 16 |
| Before 2010 | 2 |
| Start date not reported | 1 |
Study design
- 129 interventional and 16 observational studies.
- Median planned or actual enrolment is 50 participants (range 1 to 1,148, across 135 records that report it).
Registered studies
The 50 studies with the latest start dates, newest first. The order is not a ranking and says nothing about quality. Titles are quoted from the registry. Each ID links to its own ClinicalTrials.gov record, which has the eligibility criteria and contacts.
| Title as registered | Registry ID | Status | Phase | Start | Compound |
|---|---|---|---|---|---|
| Behavioural Activation Therapy and Ketamine for Treatment-Resistant Depression | NCT07801703 | Not yet recruiting | Phase 2 | 2026-09-01 | Ketamine |
| Ketamine Treatment for Treatment-Resistant Depression - the Role of Framing | NCT07824973 | Not yet recruiting | Not applicable | 2026-09-01 | Ketamine |
| A Study of Esketamine Nasal Spray Versus Placebo Spray in Adult Participants With Treatment-resistant Depression | NCT07716098 | Recruiting | Phase 3 | 2026-08-03 | Ketamine |
| Psilocybin Assisted Psychotherapy for Treatment Resistant Depression and Co-occurring Substance Use Disorder | NCT07499583 | Not yet recruiting | Phase 1 | 2026-08-01 | Psilocybin |
| Biomarker-Guided Antidepressant Selection | NCT07680140 | Recruiting | Phase 4 | 2026-07-01 | Ketamine |
| Psilocybin-Assisted Group Integration Psychotherapy for Treatment-Resistant Depression | NCT07737990 | Enrolling by invitation | Not applicable | 2026-07-01 | Psilocybin |
| Psilocybin Intervention for Veterans Overcoming Treatment-Resistant Depression | NCT07226232 | Recruiting | Phase 3 | 2026-06-01 | Psilocybin |
| Ketamine With Dialectical Behavioural Therapy (DBT) for Suicidality in Individuals With Treatment-Resistant Depression and Borderline Personality Disorder (KET-DBT) | NCT07569198 | Recruiting | Phase 2 | 2026-06-01 | Ketamine |
| InTRavenous kEtAmine and immerSive virtUal Reality to Treat dEpression | NCT06781697 | Recruiting | Phase 3 | 2026-05-01 | Ketamine |
| Understanding Music and Mindfulness Preferences in Psilocybin-Assisted Psychotherapy | NCT07373535 | Not yet recruiting | Phase 2 | 2026-05-01 | Psilocybin |
| Evaluating the Role of Psilocybin Monitors in Psilocybin Therapy for Treatment Resistant Depression | NCT07211438 | Recruiting | Phase 2 | 2026-04-01 | Psilocybin |
| Coaching as an Adjunct to Ketamine Therapy for Treatment-Resistant Depression | NCT07563868 | Recruiting | Not applicable | 2026-04-01 | Ketamine |
| Esketamine With or Without Integration Therapy for Treatment-Resistant Depression | NCT07369102 | Recruiting | Phase 4 | 2026-02-01 | Ketamine |
| Ketamine-Assisted Psychotherapy for Treatment-Resistant Depression | NCT07247006 | Not yet recruiting | Phase 2 | 2026-01-01 | Ketamine |
| Ketamine Biomarker Validation | NCT07307768 | Not yet recruiting | Phase 1 | 2025-12-20 | Ketamine |
| Psilocybin Microdosing With Psychotherapy for Treatment-Resistant Depression | NCT07183748 | Recruiting | Phase 2 | 2025-12-01 | Psilocybin |
| Efficacy of Psilocybin and Trazodone Combination in Treatment-resistant Depression: a Randomized Controlled Proof-of-concept Study (PSILOTRAZ) | NCT07210112 | Recruiting | Phase 2 | 2025-10-08 | Psilocybin |
| Psilocybin-Assisted Therapy for Treatment-Resistant Depression in Bipolar II Disorder | NCT06943573 | Recruiting | Phase 3 | 2025-10-01 | Psilocybin |
| Virtual Reality-Based Mindfulness as an Adjunct to Treatment as Usual in Treatment-Resistant Depression | NCT07422519 | Recruiting | Not applicable | 2025-09-18 | Ketamine |
| Comparison of Esketamine Nasal Spray vs.Aripiprazole in Treat.Resistant Major Depressive Disorder in Elderly Patients | NCT07153406 | Not yet recruiting | Phase 3 | 2025-09-15 | Ketamine |
| Ketamine Augmentation of ECT in Treatment-Resistant Depression | NCT07088380 | Recruiting | Phase 3 | 2025-07-10 | Ketamine |
| Electroconvulsive Therapy Versus Intravenous Ketamine in Treatment-Resistant Major Depressive Disorder | NCT07526454 | Completed | Not applicable | 2025-07-01 | Ketamine |
| A Study of Esketamine Nasal Spray in Korean Participants With Treatment-resistant Depression | NCT07053345 | Completed | Phase 4 | 2025-06-09 | Ketamine |
| Working Mechanisms and Effectiveness of IV Ketamine-assisted Psychotherapy on Depression in TRD Clients | NCT07706478 | Recruiting | Not reported | 2025-06-01 | Ketamine |
| Imaging the Effects of Serotonin 2A Receptor Modulation on Synaptic Density in Treatment-resistant Depression (SYNVEST) | NCT06512220 | Recruiting | Phase 2 | 2025-04-21 | Psilocybin |
| Treatment With Psilocybin for Chronic Neuropathic Pain and Depression (TRANSCEND) | NCT06518720 | Recruiting | Phase 2 | 2025-04-01 | Psilocybin |
| Intravenous Ketamine for Treatment-Resistant Depression | NCT06668571 | Recruiting | Phase 2 | 2025-02-10 | Ketamine |
| Psilocybin rTMS for Treatment Resistant Depression | NCT06132178 | Recruiting | Phase 2 | 2025-01-10 | Psilocybin |
| Personalized DBS Targeting for Treating Depression | NCT06784388 | Recruiting | Early Phase 1 | 2025-01-05 | Ketamine |
| Effect of Psilocybin on the Positive Valence System in Treatment-resistant Depression | NCT06650800 | Completed | Not applicable | 2024-11-19 | Psilocybin |
| FMRI of Patients Receiving IV Ketamine for Treatment Resistant Bipolar Depression | NCT06620042 | Completed | Phase 2 | 2024-11-12 | Ketamine |
| Investigation of the Antidepressant Effects of (2R,6R)-HNK, an Enhancer of Synaptic Glutamate Release, in Treatment-Resistant Depression | NCT06511908 | Recruiting | Phase 2 | 2024-11-06 | Ketamine |
| Psilocybin for Treatment-Resistant Depression in Autism | NCT06731621 | Active, not recruiting | Phase 1 | 2024-11-01 | Psilocybin |
| Neurobiological Effects of Psilocybin in Treatment Resistant Bipolar Depression | NCT06506019 | Active, not recruiting | Phase 1 | 2024-10-09 | Psilocybin, LSD |
| Psilocybe Cubensis Mushrooms With or Without Fluoxetine for Refractory Depression: a Phase 2a Pilot Randomized Clinical Trial (COGUNILA) | NCT06898606 | Recruiting | Phase 1 | 2024-09-05 | Psilocybin |
| The Effect of a Six Week Intensified Pharmacological Treatment for Major Depressive Disorder Compared to Treatment as Usual in Subjects Who Had a First-time Treatment Failure on Their First-line Treatment. | NCT05973851 | Recruiting | Phase 3 | 2024-08-31 | Ketamine |
| Psilocybin for Treatment-Resistant Depression | NCT06230757 | Completed | Phase 2 | 2024-07-08 | Psilocybin |
| Behavioural Activation Therapy and Esketamine for Resistant Depression | NCT06431386 | Terminated | Not applicable | 2024-06-11 | Ketamine |
| Comparative Effectiveness Study of Two Forms of Ketamine for Treatment-resistant Depression | NCT06278779 | Recruiting | Phase 4 | 2024-06-03 | Ketamine |
| Psilocybin for Hospitalized Patients with Treatment-resistant Depression | NCT06378229 | Recruiting | Phase 2 | 2024-05-21 | Psilocybin |
| Belief Updating in Treatment Resistant Depression | NCT05577247 | Recruiting | Not reported | 2024-05-13 | Ketamine |
| Psilocybin-Assisted Therapy in Treatment-Resistant Depression | NCT06303739 | Active, not recruiting | Phase 3 | 2024-04-19 | Psilocybin |
| Psilocybin-Assisted Psychotherapy for Treatment-Resistant Depression: Comparing One Versus Two Doses of Psilocybin | NCT06341426 | Active, not recruiting | Phase 2 | 2024-02-05 | Psilocybin |
| Predictors of Intravenous Ketamine Response in TRD | NCT05625555 | Active, not recruiting | Phase 3 | 2024-01-19 | Ketamine |
| i-CBT and IV Ketamine for Suicidality in Treatment-Resistant Depression: A Randomized, Midazolam-Controlled Clinical Trial | NCT06480500 | Active, not recruiting | Phase 2 | 2024-01-02 | Ketamine |
| Gamma Oscillations as a Prognostic Marker for Ketamine Therapy in Treatment Resistant Depression | NCT06480201 | Recruiting | Phase 1 | 2024-01-01 | Ketamine |
| VA Aripiprazole vs Esketamine for Treatment Resistant Depression | NCT05554627 | Withdrawn | Phase 4 | 2023-10-27 | Ketamine |
| KET-RO Plus RO DBT for Treatment Resistant Depression | NCT06138691 | Completed | Phase 1 | 2023-10-04 | Ketamine |
| Does Psilocybin Require Psychedelic Effects to Treat Depression? | NCT05710237 | Completed | Phase 2 | 2023-07-01 | Psilocybin |
| A Trial of GH001 in Patients With Treatment-resistant Depression | NCT05800860 | Completed | Phase 2 | 2023-05-24 | DMT, 5-MeO-DMT |
About this data
Compound tags come from automated matching of the registry search term and have not been checked record by record. Counts are of registered studies, not of people, results or approvals. A registry listing is not evidence of safety, benefit or results.
Substance hubs for these compounds
Psilocybin | LSD | DMT | 5-MeO-DMT | Ayahuasca | Ketamine
Other condition hubs
Depression | Bipolar disorder | Post-traumatic stress disorder | Alcohol use disorder | Opioid use disorder | Tobacco and nicotine use | Cocaine and methamphetamine use | Anxiety | Cancer and end-of-life distress | Obsessive-compulsive disorder | Eating disorders | Headache and migraine | Chronic pain | Suicidal ideation and suicide risk