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PTSD clinical trials landscape

TL;DR — The registry landscape is broad but noisy: a condition query includes studies where PTSD is only an outcome, comorbidity or exploratory subgroup. This page therefore uses live ClinicalTrials.gov v2 records verified on 2026-09-02 and labels transdiagnostic designs. Current directions include digital/primary-care PE, ketamine- or esketamine-enhanced exposure, sleep intervention, moral-injury treatment, neuromodulation, implementation and measurement. Registration is evidence that a study was planned, not evidence of efficacy.

Registry method

ClinicalTrials.gov v2 was queried live for PTSD and then filtered manually for PTSD-directed eligibility/intervention. Status is a snapshot dated 2026-09-02, and every row was re-fetched on 2026-10-09 (see the sweep column below).

Interpretation

Recruiting does not mean promising; completed does not mean published; publication does not guarantee outcome concordance. Results and papers require separate verification.

Psychotherapy delivery

PE Coach, primary-care PE, internet PE, nurse-led PTSD treatment and implementation studies test reach and delivery as much as efficacy (NCT04959695; NCT03711266; NCT05560854; NCT07430657).

Drug-assisted therapy

Ketamine/esketamine plus PE studies test an interaction package rather than medication alone (NCT04560660; NCT06795659). Enrollment separates them sharply: the ketamine-enhanced PE trial randomized 73 veterans against midazolam and has a published protocol (NCT04560660; Shiroma 2024, PMID 38729297), whereas the esketamine-plus-massed-PE record closed as completed with an enrollment of 4, which cannot support an efficacy inference of any kind (NCT06795659, live 2026-09-02). The MDMA phase 3 registrations correspond to published trials (NCT03537014, n=100; NCT04077437, n=121) (Mitchell 2021, PMID 33972795) (Mitchell 2023, PMID 37709999). Two drug programmes have reported since the last sweep and belong in the landscape: the methylone (TSND-201) phase 2 trial, completed with 79 enrolled and now published (NCT05741710) (Jones 2026, PMID 41706459), and psilocybin for veterans with treatment-resistant PTSD, an open-label phase 2 study with a published pilot report (NCT05554094) (Armstrong 2026, PMID 42533157). Re-fetched on 2026-10-23, that record is completed, with an actual enrollment of 12, a last update of 16 October 2026, and no results posted. The earlier active-not-recruiting / 15-enrolled wording is superseded by this fetch. Completion agrees with the published pilot and is not a new controlled result.

Changes found at the 2026-10-09 sweep. The ketamine-enhanced PE trial posted registry results on 15 July 2026, with no journal publication found. Week-22 mean CAPS-5 was 18.8 with ketamine and 19.0 with midazolam, and 16 and 13 participants were assessed. No statistical analysis was posted, and 34 of 73 randomized did not complete (NCT04560660). The TSND-201 sponsor registered a 300-participant phase 3 trial on 23 September 2026 (NCT07836647, recruiting). Randomized psilocybin PTSD trials are now registered, though none has reported. The largest is COMPASS Pathways' 300-participant phase 2b/3 of COMP360 at 25 mg and 10 mg against 1 mg (NCT07570654, recruiting). A placebo-controlled phase 2 in PTSD with alcohol use disorder has completed recruitment (NCT06853912, n=40). One new protocol paper describes a 2:2:2:1 randomized trial of ketamine, stellate ganglion block, their combination and double sham for PTSD and/or TBI-associated headache (Cohen 2026, PMID 42817839, NCT06608277). The paper states 210 participants, but the registry records an estimated enrollment of 175 as of 2026-10-09; that discrepancy should be resolved when the trial reports.

Sleep and moral injury

A transdiagnostic sleep-health study explicitly includes PTSD but is not a PTSD-only efficacy trial (NCT06549049). Moral-injury mindfulness is adjacent to PTSD and should not be relabelled a core PTSD trial (NCT05341882).

Design gaps

Small samples, inactive controls, functional unblinding, short follow-up, many outcomes and selective publication can exaggerate signals. Registry–publication concordance should be audited, and doing so on 2026-09-02 produced a concrete gap: NCT03539614, the phase 3 prazosin trial built around noradrenergic biomarkers, records an actual primary completion date of 1 January 2026 but has no results publication indexed in PubMed, so the prospective test of the pretreatment-blood-pressure responder hypothesis is complete but unreported. Re-checked 2026-10-09: the record was last updated on 14 August 2026 and is still active, not recruiting, with no results posted. Its study completion date is estimated as 31 December 2026, and a PubMed search for [NCT03539614](https://clinicaltrials.gov/study/NCT03539614){target="_blank" rel="noopener"} returns no records. The finding is still unreported, about nine months after primary completion.

Scope boundary

Studies using PTSD symptoms as a secondary outcome after ICU, pregnancy, surgery or disaster are not automatically PTSD treatment trials.

Quantitative anchors

Every row was re-fetched individually from the ClinicalTrials.gov v2 API on 2026-09-02. Enrollment is shown because a registry status alone conceals the difference between a 121-person phase 3 trial and a 4-person one.

NCT Status Phase Enrolled Intervention Source
NCT03537014 Completed 3 100 MDMA-assisted psychotherapy (MAPP1) ClinicalTrials.gov v2, live 2026-09-02; re-fetched 2026-10-09, status unchanged
NCT04077437 Completed 3 121 MDMA-assisted psychotherapy (MAPP2) ClinicalTrials.gov v2, live 2026-09-02; re-fetched 2026-10-09, status unchanged
NCT05741710 Completed 1/2 79 Methylone (TSND-201) vs placebo ClinicalTrials.gov v2, live 2026-09-02; re-fetched 2026-10-09, status unchanged
NCT04560660 Completed 2 73 Ketamine-enhanced prolonged exposure ClinicalTrials.gov v2, live 2026-09-02; re-fetched 2026-10-09: results posted 2026-07-15, no publication
NCT06795659 Completed 1/2 4 Esketamine + massed PE ClinicalTrials.gov v2, live 2026-09-02; re-fetched 2026-10-09, status unchanged
NCT03539614 Active, not recruiting 3 87 Prazosin vs placebo; noradrenergic biomarkers ClinicalTrials.gov v2, live 2026-09-02; re-fetched 2026-10-09, status unchanged
NCT05554094 Completed 2 12 (actual) Psilocybin, open-label, veterans ClinicalTrials.gov v2, re-fetched 2026-10-23: last update 2026-10-16, no results posted. Earlier fetches recorded active-not-recruiting and 15 enrolled
NCT04959695 Recruiting N/A 124 PE Coach app + PE vs PE alone ClinicalTrials.gov v2, live 2026-09-02; re-fetched 2026-10-09, status unchanged
NCT07430657 Recruiting N/A 100 Nurse-led PTSD treatment in primary care ClinicalTrials.gov v2, live 2026-09-02; re-fetched 2026-10-09, status unchanged
NCT06549049 Not yet recruiting N/A 182 Transdiagnostic sleep intervention (TranS-C) ClinicalTrials.gov v2, live 2026-09-02; re-fetched 2026-10-09, status unchanged
NCT05341882 Completed 3 75 Mindfulness vs educational support for moral injury ClinicalTrials.gov v2, live 2026-09-02; re-fetched 2026-10-09, status unchanged
NCT04007666 Completed N/A 148 CPT implementation, incarcerated population ClinicalTrials.gov v2, live 2026-09-02; re-fetched 2026-10-09, status unchanged
NCT03711266 Completed N/A 35 PE for primary care in FQHCs ClinicalTrials.gov v2, live 2026-09-02; re-fetched 2026-10-09, status unchanged
NCT05560854 Completed N/A 30 Internet-delivered prolonged exposure ClinicalTrials.gov v2, live 2026-09-02; re-fetched 2026-10-09, status unchanged
NCT07836647 Recruiting (registered 2026-09-23) 3 300 (est.) TSND-201 (methylone), two doses vs placebo ClinicalTrials.gov v2, retrieved 2026-10-09
NCT07570654 Recruiting 2b/3 300 (est.) COMP360 psilocybin 25 mg / 10 mg vs 1 mg ClinicalTrials.gov v2, retrieved 2026-10-09
NCT06853912 Active, not recruiting 2 40 (est.) Psilocybin vs placebo, PTSD + alcohol use disorder ClinicalTrials.gov v2, retrieved 2026-10-09
NCT06608277 Recruiting 2 175 (est.; protocol paper states 210) Ketamine, stellate ganglion block, combination, double sham ClinicalTrials.gov v2, retrieved 2026-10-09; (Cohen 2026, PMID 42817839)

Registry re-check, 2026-10-16. All 22 NCT records cited in this condition were retrieved individually from ClinicalTrials.gov v2. No status or results-posting change was identified relative to the 2026-10-09 sweep. The prazosin biomarker trial remains active, not recruiting, with no posted results (NCT03539614); the ketamine-plus-PE results remain posted without a PubMed record returned by the exact identifier search (NCT04560660). The four tracked randomized psilocybin registrations still have no posted results (NCT07570654, NCT06853912, NCT06885996, NCT06407635). These are dated registry observations, not claims of absence across every publication or registry. Query details and per-record update dates are preserved in the 2026-10-16 sweep manifest.

Registry re-check, 2026-10-23. All 22 cited NCT records were retrieved again from ClinicalTrials.gov v2. One status change: the open-label veteran psilocybin record is now completed, actual enrollment 12, last update 16 October 2026, with no results posted (NCT05554094). The four randomized psilocybin records still have no posted results. COMP360 remains recruiting, estimated enrollment 300, phases 2 and 3, primary completion estimated November 2028, last update 21 October 2026 (NCT07570654). The fields changed on that date were not identified, so no protocol amendment is inferred. The PTSD-plus-alcohol-use-disorder trial remains active, not recruiting, estimated n = 40, estimated primary completion November 2026 (NCT06853912). The prazosin biomarker trial remains active, not recruiting, last update 14 August 2026, with no posted results (NCT03539614). The ketamine-plus-PE record remains completed, with results first posted 15 July 2026 (NCT04560660). Exact PubMed searches for [NCT03539614](https://clinicaltrials.gov/study/NCT03539614){target="_blank" rel="noopener"} and [NCT04560660](https://clinicaltrials.gov/study/NCT04560660){target="_blank" rel="noopener"} again returned zero records. Per-record dates are in the 2026-10-23 sweep manifest.

Evidence ledger

The ledger lists the live-retrieved records used to bound this page. Inclusion does not make every record equally probative; design, population and comparator remain decisive.

PMID Year Evidence contribution Scope caution
33972795 2021 MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. PTSD-specific record; inspect design and population
37709999 2023 MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. PTSD-specific record; inspect design and population
39741438 2025 MDMA and MDMA-Assisted Therapy. PTSD-specific record; inspect design and population
29728331 2018 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. PTSD-specific record; inspect design and population
41926191 2026 Comparing dropout from cognitive processing therapy versus prolonged exposure: Results from a randomized clinical trial. PTSD-specific record; inspect design and population
32063234 2020 Psychological treatments for post-traumatic stress disorder in adults: a network meta-analysis. Synthesis: preserve included-population and certainty limits
32284821 2020 Psychological therapies for post-traumatic stress disorder in adults: systematic review and meta-analysis. Synthesis: preserve included-population and certainty limits
34954460 2022 Exposure therapy for PTSD: A meta-analysis. Synthesis: preserve included-population and certainty limits
32813696 2020 Psychological and pharmacological interventions for posttraumatic stress disorder and comorbid mental health problems following complex traumatic events: Systematic review and component network meta-analysis. Synthesis: preserve included-population and certainty limits
29414272 2018 Trial of Prazosin for Post-Traumatic Stress Disorder in Military Veterans. PTSD-specific record; inspect design and population
30688367 2019 Moral Injury: An Integrative Review. Synthesis: preserve included-population and certainty limits
39630422 2025 Psychological Interventions for Pediatric Posttraumatic Stress Disorder: A Systematic Review and Network Meta-Analysis. Synthesis: preserve included-population and certainty limits
40308104 2025 An Update on Psychotherapy for the Treatment of PTSD. PTSD-specific record; inspect design and population
38198456 2024 Effects of MDMA-assisted therapy for PTSD on self-experience. PTSD-specific record; inspect design and population
39078646 2024 Psychedelic Therapy Scrutinized by FDA Advisory Committee? PTSD-specific record; inspect design and population
33517752 2021 Ketamine for PTSD: Well, Isn't That Special. PTSD-specific record; inspect design and population
35688992 2022 Pharmacological Management of Nightmares Associated with Posttraumatic Stress Disorder. PTSD-specific record; inspect design and population
38795401 2024 Pharmacotherapy for sleep disturbances in post-traumatic stress disorder (PTSD): A network meta-analysis. Synthesis: preserve included-population and certainty limits
34992738 2021 Pharmacological therapy for post-traumatic stress disorder: a systematic review and meta-analysis of monotherapy, augmentation and head-to-head approaches. Synthesis: preserve included-population and certainty limits
36613097 2022 The Effects of Pharmacological Treatment of Nightmares: A Systematic Literature Review and Meta-Analysis of Placebo-Controlled, Randomized Clinical Trials. Synthesis: preserve included-population and certainty limits
26808441 2016 Revisiting propranolol and PTSD: Memory erasure or extinction enhancement? PTSD-specific record; inspect design and population
21352105 2007 Early intervention for post-traumatic stress disorder. PTSD-specific record; inspect design and population
26574151 2016 Psychological treatments for adults with posttraumatic stress disorder: A systematic review and meta-analysis. Synthesis: preserve included-population and certainty limits
29451967 2018 Cognitive behavioral therapy for anxiety and related disorders: A meta-analysis of randomized placebo-controlled trials. Synthesis: preserve included-population and certainty limits
34477098 2021 Comparing treatments for post-traumatic stress disorder - a systematic review. Synthesis: preserve included-population and certainty limits
38729297 2024 Ketamine-enhanced prolonged exposure therapy in veterans with PTSD: A randomized controlled trial protocol. Protocol; not a results paper
41706459 2026 Efficacy and Safety of the Neuroplastogen TSND-201 for the Treatment of PTSD: A Randomized Clinical Trial. Phase 2; sponsor-employed authors; 90% CIs
42533157 2026 Safety, feasibility, and preliminary clinical outcomes of psilocybin-assisted therapy for veterans with severe, treatment-resistant PTSD: an open-label pilot clinical trial. n=12; open-label pilot

Interpretation guardrails

  • Trauma exposure, post-traumatic symptoms, acute stress disorder, DSM-5 PTSD, ICD-11 PTSD and ICD-11 complex PTSD are not interchangeable populations.
  • A mixed-anxiety or transdiagnostic estimate is labelled as such; only a source’s PTSD stratum can be treated as a PTSD effect.
  • Comorbid depression is measured separately and cross-linked to the depression condition; it is not absorbed into PTSD.
  • Waitlist, treatment-as-usual, attention control and active treatment answer different causal questions.
  • Registration, statistical significance and diagnostic loss do not respectively prove completion, clinical importance or functional recovery.
  • This page synthesizes research and does not provide individual medical advice.

Minimum extraction frame for studies on this topic

Field What must be retained Why it changes interpretation
Diagnostic system DSM version, ICD version, full/subthreshold Case mix is not interchangeable
Diagnostic method Structured interview, clinician judgment, self-report cutoff Screening is not diagnosis
Index trauma Type, timing, repetition, direct/indirect/occupational Conditional risk and phenotype differ
Population Civilian, veteran, refugee, child/adolescent, mixed Transportability is empirical
Baseline severity Mean, SD, range and exclusion threshold Ceiling and floor effects alter change
CPTSD status ITQ/ICD-11 definition and DSO score Complexity cannot be inferred from trauma count
Comorbidity Depression, GAD, SUD, pain, TBI measured separately Shared symptoms can distort effects
Comparator Waitlist, usual care, attention, active treatment The estimand changes with comparator
Treatment dose Sessions offered/attended, duration, homework Assignment is not exposure
Outcome Symptoms, diagnosis, response, function, sleep Outcomes are not interchangeable
Time point End point and prespecified follow-up windows Acute benefit may not persist
Missing data Denominator, reasons, imputation and estimand Attrition can bias rank and magnitude
Adverse events Definitions, ascertainment and arm-level counts Absence of reporting is not absence of harm
Therapist/context Training, fidelity, allegiance, setting Delivery is part of the intervention
Funding/conflicts Sponsor role and analytic independence Especially material for proprietary packages

Claims this page does not make

  • It does not infer PTSD from trauma exposure alone.
  • It does not treat a self-report cutoff as equivalent to a structured diagnosis.
  • It does not convert a pooled anxiety-disorder effect into a PTSD effect.
  • It does not convert a depression outcome in a comorbid sample into a PTSD outcome.
  • It does not infer superiority from a statistically significant within-group change.
  • It does not infer equivalence from a non-significant between-group test.
  • It does not infer effectiveness from trial registration or mechanistic plausibility.
  • It does not assume military, civilian, refugee and pediatric estimates transport unchanged.
  • It does not average conflicting estimates that use different definitions.
  • It does not treat lack of adverse-event reporting as evidence of safety.

Evidence-updating triggers

Trigger Required response
New diagnostic revision Recalculate which populations prior estimates represent
New head-to-head RCT Compare against active treatment, not only waitlist
New individual-participant synthesis Revisit effect modifiers and transportability
Registry status change Verify results and linked publication before changing conclusions
Guideline update Separate evidence review from panel recommendation
Regulatory decision Record decision date and source; do not infer from efficacy papers
Safety signal Re-extract denominator, ascertainment and exposure time by arm
Contradictory replication Display estimates side by side; do not average definitions

Evidence updates should preserve the prior estimate and explain why the new study changes—or does not change—the inference.

Open questions

  • Which completed PTSD-directed registrations remain unpublished after 24 months?
  • Which trials include function, adverse events and post-dropout outcome collection? (Harper 2026, PMID 41926191)
  • Will independent MDMA replication address expectancy and therapist effects? (Wolfgang 2025, PMID 39741438)

References

  1. Mitchell JM, et al. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med. 2021;27(6):1025-1033. PMID 33972795
  2. Mitchell JM, et al. MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nat Med. 2023;29(10):2473-2480. PMID 37709999
  3. Wolfgang AS, et al. MDMA and MDMA-Assisted Therapy. Am J Psychiatry. 2025;182(1):79-103. PMID 39741438
  4. Mithoefer MC, et al. 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. Lancet Psychiatry. 2018;5(6):486-497. PMID 29728331
  5. Harper KL, et al. Comparing dropout from cognitive processing therapy versus prolonged exposure: Results from a randomized clinical trial. J Consult Clin Psychol. 2026;94(3):140-150. PMID 41926191
  6. Mavranezouli I, et al. Psychological treatments for post-traumatic stress disorder in adults: a network meta-analysis. Psychol Med. 2020;50(4):542-555. PMID 32063234
  7. Lewis C, et al. Psychological therapies for post-traumatic stress disorder in adults: systematic review and meta-analysis. Eur J Psychotraumatol. 2020;11(1):1729633. PMID 32284821
  8. McLean CP, et al. Exposure therapy for PTSD: A meta-analysis. Clin Psychol Rev. 2022;91:102115. PMID 34954460
  9. Coventry PA, et al. Psychological and pharmacological interventions for posttraumatic stress disorder and comorbid mental health problems following complex traumatic events: Systematic review and component network meta-analysis. PLoS Med. 2020;17(8):e1003262. PMID 32813696
  10. Raskind MA, et al. Trial of Prazosin for Post-Traumatic Stress Disorder in Military Veterans. N Engl J Med. 2018;378(6):507-517. PMID 29414272
  11. Griffin BJ, et al. Moral Injury: An Integrative Review. J Trauma Stress. 2019;32(3):350-362. PMID 30688367
  12. Hoppen TH, et al. Psychological Interventions for Pediatric Posttraumatic Stress Disorder: A Systematic Review and Network Meta-Analysis. JAMA Psychiatry. 2025;82(2):130-141. PMID 39630422
  13. Rothbaum BO, et al. An Update on Psychotherapy for the Treatment of PTSD. Am J Psychiatry. 2025;182(5):424-437. PMID 40308104
  14. van der Kolk BA, et al. Effects of MDMA-assisted therapy for PTSD on self-experience. PLoS One. 2024;19(1):e0295926. PMID 38198456
  15. Marks M Psychedelic Therapy Scrutinized by FDA Advisory Committee? JAMA. 2024;332(12):963-964. PMID 39078646
  16. Stein MB, et al. Ketamine for PTSD: Well, Isn't That Special. Am J Psychiatry. 2021;178(2):116-118. PMID 33517752
  17. Geldenhuys C, et al. Pharmacological Management of Nightmares Associated with Posttraumatic Stress Disorder. CNS Drugs. 2022;36(7):721-737. PMID 35688992
  18. Lappas AS, et al. Pharmacotherapy for sleep disturbances in post-traumatic stress disorder (PTSD): A network meta-analysis. Sleep Med. 2024;119:467-479. PMID 38795401
  19. Hoskins MD, et al. Pharmacological therapy for post-traumatic stress disorder: a systematic review and meta-analysis of monotherapy, augmentation and head-to-head approaches. Eur J Psychotraumatol. 2021;12(1):1802920. PMID 34992738
  20. Skeie-Larsen M, et al. The Effects of Pharmacological Treatment of Nightmares: A Systematic Literature Review and Meta-Analysis of Placebo-Controlled, Randomized Clinical Trials. Int J Environ Res Public Health. 2022;20(1):777. PMID 36613097
  21. Giustino TF, et al. Revisiting propranolol and PTSD: Memory erasure or extinction enhancement? Neurobiol Learn Mem. 2016;130:26-33. PMID 26808441
  22. Bryant RA Early intervention for post-traumatic stress disorder. Early Interv Psychiatry. 2007;1(1):19-26. PMID 21352105
  23. Cusack K, et al. Psychological treatments for adults with posttraumatic stress disorder: A systematic review and meta-analysis. Clin Psychol Rev. 2016;43:128-41. PMID 26574151
  24. Carpenter JK, et al. Cognitive behavioral therapy for anxiety and related disorders: A meta-analysis of randomized placebo-controlled trials. Depress Anxiety. 2018;35(6):502-514. PMID 29451967
  25. Storm MP, et al. Comparing treatments for post-traumatic stress disorder - a systematic review. Dan Med J. 2021;68(9):A09200643. PMID 34477098
  26. Shiroma PR, et al. Ketamine-enhanced prolonged exposure therapy in veterans with PTSD: A randomized controlled trial protocol. Contemp Clin Trials. 2024;143:107569. PMID 38729297
  27. Jones A, et al. Efficacy and Safety of the Neuroplastogen TSND-201 for the Treatment of PTSD: A Randomized Clinical Trial. JAMA Psychiatry. 2026;83(5):469-477. PMID 41706459
  28. Armstrong SB, et al. Safety, feasibility, and preliminary clinical outcomes of psilocybin-assisted therapy for veterans with severe, treatment-resistant PTSD: an open-label pilot clinical trial. Commun Med (Lond). 2026;6(1):411. PMID 42533157
  29. Cohen SP, Smolynets R, Wood J, et al. Multi-center, randomized controlled efficacy and comparative-effectiveness study evaluating ketamine, stellate ganglion blocks, combination treatment, and sham treatments for posttraumatic stress disorder and traumatic brain injury-associated headache: a study protocol. Pain Manag. 2026:1-11. PMID 42817839