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MDMA and psychedelic-assisted therapy for PTSD

TL;DR — Two sponsor-linked phase 3 trials found MDMA-assisted therapy superior to therapy with inactive placebo: d=.91 in 90 severe-PTSD participants and d=.70 in 104 moderate–severe participants (Mitchell 2021, PMID 33972795) (Mitchell 2023, PMID 37709999). These are efficacy signals, not regulatory approval. As of live PubMed searches on 2026-09-02, the FDA declined to approve MDMA-assisted therapy in August 2024 for insufficient evidence and required a further phase 3 trial, and no approval has been reported since (Wolfgang 2025, PMID 39741438) (Morland 2026, PMID 41820235). Functional unblinding, expectancy, therapist effects, misconduct and the inseparability of drug from psychotherapy remain central interpretive issues. The misconduct is no longer only an allegation. In 2024 Psychopharmacology retracted three pooled phase 2 analyses after protocol violations at one study site that the authors had not disclosed (see Conflicts and independence below). Psilocybin and depression/pooled anxiety findings are not PTSD evidence.

What was tested

The phase 3 package tested MDMA plus a manualized therapeutic program against identical therapy plus inactive placebo, not MDMA alone (Mitchell 2021, PMID 33972795) (Mitchell 2023, PMID 37709999). Attribution to drug, psychotherapy, interaction and expectancy remains difficult.

Efficacy

MAPP1 mean CAPS-5 change among completers was −24.4 versus −13.9 and between-group d=.91 (Mitchell 2021, PMID 33972795). MAPP2 least-squares changes were −23.7 versus −14.8 and d=.70 (Mitchell 2023, PMID 37709999). A conjoint-therapy variant was piloted open-label in 8 veteran–partner dyads (N=16). MDMA was added to brief cognitive-behavioral conjoint therapy, and veterans' pre–post PTSD change was d=1.25, with no serious adverse events (Morland 2026, PMID 42693902; registered as NCT05979844). It has no control arm, so it shows feasibility rather than efficacy.

Blinding

Acute subjective effects make functional unblinding likely. Blinded independent outcome assessors reduce but do not eliminate expectancy transmitted through participants and therapists; the 2026 state-of-the-science review names blinding failure, absent active comparators, no head-to-head comparison of therapy models, inadequate safety monitoring and limited sample generalizability as the five limitations the field must resolve (Morland 2026, PMID 41820235). The FDA advisory committee's deliberations turned on the same benefit–risk questions (Marks 2024, PMID 39078646). Active-placebo and expectancy measurement strategies remain underdeveloped.

Safety

Controlled settings include medical screening, monitored dosing and integration. Small trials cannot precisely estimate rare harms; protocol deviations and therapist conduct are part of intervention safety, not externalities.

Regulation

FDA advisory review concerned benefit–risk (Marks 2024, PMID 39078646). MDMA-assisted therapy received FDA Breakthrough Therapy designation for PTSD in 2017; the agency then declined to approve it in August 2024 on grounds of insufficient evidence and required an additional phase 3 trial (Wolfgang 2025, PMID 39741438) (Morland 2026, PMID 41820235). No approval should be inferred from breakthrough designation or positive trials. A 2026 meta-analysis pooling eight randomized trials (k=24 comparisons) estimated MDMA-assisted therapy reduced PTSD symptom severity by SMD −1.19 (95% CI −1.95 to −0.42; n=298, k=9; I²=68.8%), reduced dissociative symptoms (SMD −0.37, 95% CI −0.70 to −0.04) and may improve functioning (SMD −0.83, 95% CI −1.47 to −0.19), with no clear benefit for depressive symptoms; most studies were at high risk of bias in outcome measurement (Fares-Otero 2026, PMID 41825162). A second 2026 meta-analysis, of seven published and unpublished RCTs, reached the same direction for CAPS, dissociation, depression and functional impairment, but not for sleep quality. Its authors list "a common sponsor for all trials" among the limitations and state that the included studies "were not included in recent article retractions" (Green 2026, PMID 42708350). Two meta-analyses of one sponsor's trials are not independent replication.

Living review, 2026-10-16. A new synthesis of six published randomized trials reports Hedges’ g=−0.71 (95% CI −0.95 to −0.47) for PTSD symptoms; the primary-endpoint analysis includes 242 participants, whereas Table 1 describes 286 randomized participants in the selected trial arms. Supplementary Table 10 explicitly excludes pooled secondary reports containing MP4 data, and MP4 is absent from the six primary trials in Table 1. This partly answers the contamination question: a benefit remains in this synthesis without those pooled reports. It does not provide independent trial replication: all six trials used the MAPS treatment model, and the authors rate overall certainty low, citing functional unblinding and indirectness (Sevchik 2026, PMID 42860436; full text, Figure 1, Table 1 and supplementary Table 10 checked).

Other psychedelics and ketamine

Psilocybin. A 2022 review stated that no study had then investigated psilocybin or psilocybin-assisted psychotherapy as a treatment for PTSD (Khan 2022, PMID 35711024). That absence has since closed, and re-running the search on 2026-09-02 is what establishes the current position. Two uncontrolled PTSD trials are now published: a phase 2, non-randomized, open-label multicentre trial of single-dose psilocybin in 22 participants, which reported 117 treatment-emergent adverse events (none serious), and a mean CAPS-5 change of −29.9 (SD 14.06) at week 4 and −29.5 (SD 15.43) at week 12 (McGowan 2026, PMID 40883964); and an open-label pilot of psilocybin-assisted therapy in 12 US veterans with severe treatment-resistant PTSD, reporting a mean clinician-rated reduction of 27.5 points (95% CI 19.9–35.1; d=2.30, P<0.001) at one month with 75% in remission and no increase in suicidal ideation (Armstrong 2026, PMID 42533157, NCT05554094). Re-fetched on 2026-10-23, that registry record is completed, with an actual enrollment of 12, a last update of 16 October 2026, and no results section posted. Completion agrees with the published open-label pilot. It adds no control arm. Both are single-arm designs with no control condition, so the dated evidence gap is now narrower and more specific: as of 2026-09-02 no randomized, controlled trial of psilocybin for PTSD has been published, and the two open-label studies together enrolled 34 participants. Re-run 2026-10-09: the PubMed search psilocybin AND (PTSD OR posttraumatic OR "post-traumatic") AND (randomized controlled trial[pt] OR randomi*[ti]) still returns no randomized psilocybin trial in a PTSD population. The registry has moved, though. ClinicalTrials.gov v2 now lists randomized psilocybin PTSD trials that are recruiting or have completed dosing. The largest is a 300-participant, quadruple-masked phase 2b/3 trial of COMP360 at 25 mg and 10 mg against a 1 mg comparator (NCT07570654, sponsor COMPASS Pathways, recruiting, estimated primary completion November 2028). Others are a 40-participant placebo-controlled phase 2 trial in PTSD with alcohol use disorder (NCT06853912, active not recruiting, estimated primary completion November 2026), a 76-participant high- versus low-dose trial in intimate-partner-violence survivors (NCT06885996, not yet recruiting), and a 20-participant Johns Hopkins pilot randomizing psilocybin with trauma-focused psychotherapy against psilocybin with standard support (NCT06407635, active not recruiting, primary completion March 2026). None has posted results. ISRCTN returned no psilocybin PTSD trial, and the EU CTIS public search returned none. WHO ICTRP could not be queried programmatically. So the gap is now one of reporting, not of design. A pooled psychedelic meta-analysis across mental disorders still cannot supply a PTSD-specific psilocybin effect (Yao 2024, PMID 38574699).

Media versus trials, search through 10 October 2024. A systematic review of English-language psilocybin trials published from 1 January 2014 to 10 October 2024 (n = 70; Medline, Embase, PsycInfo and CENTRAL) and of media articles through 22 April 2025 (n = 172) found that no included trial examined PTSD. Media articles named PTSD as a clinical indication in 74 of 172 articles (43%) (Madden 2026, PMID 42900476; full text, Table 3). That search closed before the two uncontrolled 2026 trials already cited on this page. The review dates a mismatch between media claims and the trial literature inside its own window. It is not an efficacy estimate, and it does not describe the 2026 publications.

Ketamine. Depression findings should not be imported (Stein 2021, PMID 33517752), but PTSD-specific randomized evidence exists and disagrees with itself. Six ketamine (0.5 mg/kg) versus midazolam infusions over two weeks in 30 adults with chronic PTSD reduced CAPS-5 by 11.88 points more than midazolam (SE 3.96; d=1.13, 95% CI 0.36–1.91), with 67% versus 20% responders (Feder 2021, PMID 33397139). Eight infusions of placebo, 0.2 mg/kg or 0.5 mg/kg ketamine in 158 antidepressant-resistant veterans and service members produced no significant group-by-time effect on PCL-5 or CAPS-5, while the standard dose still improved MADRS depression scores (Abdallah 2022, PMID 35046508). Population, dose schedule and comparator all differ; the discrepancy is unresolved.

Other rapid-acting agents. A phase 2 randomized, placebo-controlled trial across 16 sites in the US, UK and Ireland tested the neuroplastogen TSND-201 (methylone) in 65 adults with PTSD without any psychotherapy component and found a least-squares mean CAPS-5 difference of 9.64 favouring drug (90% CI −16.48 to −2.80; P=.01), with PCL-5, SDS and MADRS moving in the same direction (Jones 2026, PMID 41706459, NCT05741710). It is sponsor-run, reports 90% rather than 95% intervals, and has not been replicated — but it separates a rapid-acting drug effect from a therapy package in a way the MDMA programme has not. A 300-participant, two-dose, placebo-controlled phase 3 trial was registered on 23 September 2026 and is recruiting (NCT07836647; estimated primary completion February 2028).

Conflicts and independence

Sponsor involvement and a specialised therapy ecosystem heighten the need for independent replication, transparent adverse-event adjudication and fidelity monitoring.

Retractions and expressions of concern (identified at the 2026-10-09 sweep). Three sponsor-authored secondary analyses of the phase 2 programme carry the PubMed publication type Retracted Publication, and Crossref records a retraction update for each:

  • the pooled six-trial analysis used to design the phase 3 trials (Mithoefer 2019, PMID 31065731);
  • the long-term follow-up pooled analysis (Jerome 2020, PMID 32500209);
  • the reuptake-inhibitor taper analysis (Feduccia 2021, PMID 33221932).

The retraction notices were published in November 2024 (PMIDs: 39126501, 39126500, 39126502). The notice for the design paper, read in full, gives the reason. The editors acted "after they were informed of protocol violations amounting to unethical conduct at the MP4 study site", and "the authors have subsequently confirmed that they were aware of these violations at the time of submission of this article, but did not disclose this information to the journal or remove data generated by this site from their analysis". The notice also cites an undeclared potential competing interest (Mithoefer 2024, PMID 39126501).

Separately, the Journal of Traumatic Stress issued expressions of concern, dated 3 December 2024, on two further secondary analyses: posttraumatic growth (Gorman 2020, PMID 32073177; EoC PMID 39627911) and sleep quality (Ponte 2021, PMID 34114250; EoC PMID 39627875). Their texts are PDF-only, so the stated grounds were not read this session.

None of these five records is cited as evidence anywhere in this condition. All 385 PMIDs cited here were re-checked on 2026-10-09 for retraction and expression-of-concern flags in PubMed, and none carries one. The two phase 3 papers have no retraction in Crossref; MAPP2 (Mitchell 2023, PMID 37709999) carries a correction, published in November 2024 (PMID 39375459). The phase 2 trial cited on this page (Mithoefer 2018, PMID 29728331) is not flagged either. Not yet checked: whether any meta-analysis cited on this page pooled data from the MP4 site. That needs each review's included-studies table (Smith 2022, PMID 34708874; Shahrour 2024, PMID 39381877; Fares-Otero 2026, PMID 41825162).

Quantitative anchors

Measure Estimate Population/method Source
MAPP1 n=90; CAPS-5 d=.91; SDS d=.43 Severe PTSD; NCT03537014 (Mitchell 2021, PMID 33972795)
MAPP2 n=104; CAPS-5 d=.70; SDS d=.40 Moderate–severe PTSD; NCT04077437 (Mitchell 2023, PMID 37709999)
Severe TEAEs, MAPP2 5/53 vs 2/51 No deaths or serious TEAEs reported (Mitchell 2023, PMID 37709999)
Regulatory status FDA rejected initial NDA in 2024 Additional phase 3 required (Wolfgang 2025, PMID 39741438)
Retracted phase 2 secondary analyses 3 (retraction notices November 2024) Undisclosed protocol violations at the MP4 site (Mithoefer 2024, PMID 39126501)
MDMA-bCBCT pilot veteran PTSD pre–post d=1.25 8 dyads; open-label; no SAEs (Morland 2026, PMID 42693902)
Randomized psilocybin PTSD trials 0 published; ≥4 registered (largest n=300) PubMed + ClinicalTrials.gov v2, re-checked 2026-10-23; none of the four has posted results NCT07570654, NCT06853912, NCT06885996, NCT06407635
Open-label veteran psilocybin registry Completed; actual enrollment 12; no results posted Last registry update 2026-10-16; agrees with the published pilot NCT05554094; (Armstrong 2026, PMID 42533157)
Psilocybin media mentions of PTSD 74/172 articles (43%); 0/70 trials in the review Trials published through 2024-10-10; media through 2025-04-22 (Madden 2026, PMID 42900476)
Phase 2 service population randomized dose-response Veterans, firefighters, police (Mithoefer 2018, PMID 29728331)
MDMA-AT pooled SMD −1.19 (95% CI −1.95 to −0.42); I²=68.8% 8 RCTs; n=298 for the symptom outcome (Fares-Otero 2026, PMID 41825162)
Psilocybin, open-label phase 2 CAPS-5 −29.9 (SD 14.06) at week 4 n=22; no control arm (McGowan 2026, PMID 40883964)
Psilocybin, veteran pilot −27.5 points (95% CI 19.9–35.1); d=2.30 n=12; open-label; treatment-resistant (Armstrong 2026, PMID 42533157)
Repeated ketamine vs midazolam CAPS-5 −11.88 (d=1.13, 95% CI 0.36–1.91) n=30 (Feder 2021, PMID 33397139)
Repeated ketamine, multi-site null on PCL-5 and CAPS-5 n=158 veterans/service members (Abdallah 2022, PMID 35046508)
TSND-201 (methylone) CAPS-5 LS mean difference 9.64 (90% CI −16.48 to −2.80) n=65; no psychotherapy component (Jones 2026, PMID 41706459)

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
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
39741438 2025 MDMA and MDMA-Assisted Therapy. PTSD-specific record; inspect design and population
36402502 2023 Post-traumatic Stress Disorder. PTSD-specific record; inspect design and population
37132142 2024 Treatment of Posttraumatic Stress Disorder: A State-of-the-art Review. Synthesis: preserve included-population and certainty limits
38284341 2024 The Psychedelic Future of Post-Traumatic Stress Disorder Treatment. PTSD-specific record; inspect design and population
32098487 2020 Psychedelics and Psychedelic-Assisted Psychotherapy. PTSD-specific record; inspect design and population
35711024 2022 Psilocybin for Trauma-Related Disorders. PTSD-specific record; inspect design and population
38574699 2024 Efficacy and safety of psychedelics for the treatment of mental disorders: A systematic review and 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
38795401 2024 Pharmacotherapy for sleep disturbances in post-traumatic stress disorder (PTSD): A network meta-analysis. Synthesis: preserve included-population and certainty limits
37615227 2023 Psychedelic drugs in the treatment of psychiatric disorders (Danish-language review). PTSD-specific record; inspect design and population
33517752 2021 Ketamine for PTSD: Well, Isn't That Special. PTSD-specific record; inspect design and population
39032491 2024 Ketamine ameliorates post-traumatic social avoidance by erasing the traumatic memory encoded in VTA-innervated BLA engram cells. PTSD-specific record; inspect design and population
33053043 2021 MDMA-assisted psychotherapy for the treatment of PTSD. PTSD-specific record; inspect design and population
29356590 2018 Taking Psychedelics Seriously. PTSD-specific record; inspect design and population
34708874 2022 MDMA-Assisted Psychotherapy for Treatment of Posttraumatic Stress Disorder: A Systematic Review With Meta-Analysis. Synthesis: preserve included-population and certainty limits
39381877 2024 MDMA-assisted psychotherapy for the treatment of PTSD: A systematic review and meta-analysis of randomized controlled trials (RCTs). Synthesis: preserve included-population and certainty limits
33397139 2021 A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder. 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
37991966 2023 PHARMACOLOGY OF POST-TRAUMATIC STRESS DISORDER. PTSD-specific record; inspect design and population
38941125 2024 Clonidine for post-traumatic stress disorder: a systematic review of the current evidence. Synthesis: preserve included-population and certainty limits
32063234 2020 Psychological treatments for post-traumatic stress disorder in adults: a network meta-analysis. Synthesis: preserve included-population and certainty limits
41820235 2026 State of the Science: MDMA-assisted psychotherapy for the treatment of posttraumatic stress disorder. Narrative review; records the August 2024 FDA decision
41825162 2026 Efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for posttraumatic stress disorder: A systematic review and meta-analysis of clinical and functional outcomes. High risk of bias in outcome measurement across included trials
40883964 2026 Investigating the safety and tolerability of single-dose psilocybin for post-traumatic stress disorder: A nonrandomized open-label clinical trial. Open-label, no control arm; safety was the primary outcome
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; not an efficacy estimate
33397139 2021 A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder. Small RCT; psychoactive placebo comparator
35046508 2022 Dose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial. Null primary outcome; antidepressant-resistant population
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

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

  • Can an independently funded phase 3 trial replicate benefit with credible expectancy measurement? (Wolfgang 2025, PMID 39741438)
  • Which part of the package—drug, therapy, interaction or context—drives durable benefit? (Mitchell 2021, PMID 33972795)
  • What are rare and long-term harms under real-world delivery? (Mitchell 2023, PMID 37709999)

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. 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
  4. Wolfgang AS, et al. MDMA and MDMA-Assisted Therapy. Am J Psychiatry. 2025;182(1):79-103. PMID 39741438
  5. Merians AN, et al. Post-traumatic Stress Disorder. Med Clin North Am. 2023;107(1):85-99. PMID 36402502
  6. Burback L, et al. Treatment of Posttraumatic Stress Disorder: A State-of-the-art Review. Curr Neuropharmacol. 2024;22(4):557-635. PMID 37132142
  7. Zaretsky TG, et al. The Psychedelic Future of Post-Traumatic Stress Disorder Treatment. Curr Neuropharmacol. 2024;22(4):636-735. PMID 38284341
  8. Reiff CM, et al. Psychedelics and Psychedelic-Assisted Psychotherapy. Am J Psychiatry. 2020;177(5):391-410. PMID 32098487
  9. Khan AJ, et al. Psilocybin for Trauma-Related Disorders. Curr Top Behav Neurosci. 2022;56:319-332. PMID 35711024
  10. Yao Y, et al. Efficacy and safety of psychedelics for the treatment of mental disorders: A systematic review and meta-analysis. Psychiatry Res. 2024;335:115886. PMID 38574699
  11. Rothbaum BO, et al. An Update on Psychotherapy for the Treatment of PTSD. Am J Psychiatry. 2025;182(5):424-437. PMID 40308104
  12. van der Kolk BA, et al. Effects of MDMA-assisted therapy for PTSD on self-experience. PLoS One. 2024;19(1):e0295926. PMID 38198456
  13. Marks M Psychedelic Therapy Scrutinized by FDA Advisory Committee? JAMA. 2024;332(12):963-964. PMID 39078646
  14. 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
  15. Ibrahim IB, et al. Psychedelic drugs in the treatment of psychiatric disorders. [Danish] Ugeskr Laeger. 2023;185(32):V01230066. PMID 37615227
  16. Stein MB, et al. Ketamine for PTSD: Well, Isn't That Special. Am J Psychiatry. 2021;178(2):116-118. PMID 33517752
  17. Li M, et al. Ketamine ameliorates post-traumatic social avoidance by erasing the traumatic memory encoded in VTA-innervated BLA engram cells. Neuron. 2024;112(18):3192-3210.e6. PMID 39032491
  18. Reiff CM, et al. MDMA-assisted psychotherapy for the treatment of PTSD. Braz J Psychiatry. 2021;43(2):123-124. PMID 33053043
  19. Byock I Taking Psychedelics Seriously. J Palliat Med. 2018;21(4):417-421. PMID 29356590
  20. Smith KW, et al. MDMA-Assisted Psychotherapy for Treatment of Posttraumatic Stress Disorder: A Systematic Review With Meta-Analysis. J Clin Pharmacol. 2022;62(4):463-471. PMID 34708874
  21. Shahrour G, et al. MDMA-assisted psychotherapy for the treatment of PTSD: A systematic review and meta-analysis of randomized controlled trials (RCTs). Neuropsychopharmacol Rep. 2024;44(4):672-681. PMID 39381877
  22. Feder A, et al. A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder. Am J Psychiatry. 2021;178(2):193-202. PMID 33397139
  23. Geldenhuys C, et al. Pharmacological Management of Nightmares Associated with Posttraumatic Stress Disorder. CNS Drugs. 2022;36(7):721-737. PMID 35688992
  24. Tregub T, et al. PHARMACOLOGY OF POST-TRAUMATIC STRESS DISORDER. Georgian Med News. 2023;(342):122-124. PMID 37991966
  25. Marchi M, et al. Clonidine for post-traumatic stress disorder: a systematic review of the current evidence. Eur J Psychotraumatol. 2024;15(1):2366049. PMID 38941125
  26. 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
  27. Morland LA, et al. State of the Science: MDMA-assisted psychotherapy for the treatment of posttraumatic stress disorder. J Trauma Stress. 2026;39(2):173-187. PMID 41820235
  28. Fares-Otero NE, et al. Efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for posttraumatic stress disorder: A systematic review and meta-analysis of clinical and functional outcomes. Eur Neuropsychopharmacol. 2026;107:112802. PMID 41825162
  29. McGowan NM, et al. Investigating the safety and tolerability of single-dose psilocybin for post-traumatic stress disorder: A nonrandomized open-label clinical trial. J Psychopharmacol. 2026;40(1):139-148. PMID 40883964
  30. 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
  31. Abdallah CG, et al. Dose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial. Neuropsychopharmacology. 2022;47(8):1574-1581. PMID 35046508
  32. 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
  33. Morland LA, Khalifian CE, Perivoliotis D, et al. Healing together: Results from a pilot trial of 3,4-Methylenedioxymethamphetamine-enhanced cognitive-behavioral conjoint therapy for posttraumatic stress disorder. J Trauma Stress. 2026 (online ahead of print). doi:10.1002/jts.70126. PMID 42693902
  34. Green WM, Raut SB, James FLJ, et al. MDMA-Assisted Therapy May Decrease PTSD Symptoms, Dissociation, Depression, and Functional Disability: A Systematic Review and Meta-Analysis. Harv Rev Psychiatry. 2026 (online ahead of print). doi:10.1097/HRP.0000000000000478. PMID 42708350
  35. Mithoefer MC, Feduccia AA, Jerome L, et al. MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology (Berl). 2019;236(9):2735-2745. PMID 31065731 — RETRACTED (cited only to document the retraction)
  36. Jerome L, Feduccia AA, Wang JB, et al. Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials. Psychopharmacology (Berl). 2020;237(8):2485-2497. PMID 32500209 — RETRACTED (cited only to document the retraction)
  37. Feduccia AA, Jerome L, Mithoefer MC, et al. Discontinuation of medications classified as reuptake inhibitors affects treatment response of MDMA-assisted psychotherapy. Psychopharmacology (Berl). 2021;238(2):581-588. PMID 33221932 — RETRACTED (cited only to document the retraction)
  38. Mithoefer MC, Feduccia AA, Jerome L, et al. Retraction Note: MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology (Berl). 2024;241(11):2405. PMID 39126501
  39. Jerome L, Feduccia AA, Wang JB, et al. Retraction Note: Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials. Psychopharmacology (Berl). 2024;241(11):2407. PMID 39126500
  40. Feduccia AA, Jerome L, Mithoefer MC, et al. Retraction Note: Discontinuation of medications classified as reuptake inhibitors affects treatment response of MDMA-assisted psychotherapy. Psychopharmacology (Berl). 2024;241(11):2403. PMID 39126502
  41. Gorman I, Belser AB, Jerome L, et al. Posttraumatic Growth After MDMA-Assisted Psychotherapy for Posttraumatic Stress Disorder. J Trauma Stress. 2020;33(2):161-170. PMID 32073177 — subject to an Expression of Concern (PMID 39627911)
  42. Ponte L, Jerome L, Hamilton S, et al. Sleep Quality Improvements After MDMA-Assisted Psychotherapy for the Treatment of Posttraumatic Stress Disorder. J Trauma Stress. 2021;34(4):851-863. PMID 34114250 — subject to an Expression of Concern (PMID 39627875)
  43. Expression of Concern: Posttraumatic Growth After MDMA-Assisted Psychotherapy for Posttraumatic Stress Disorder. J Trauma Stress. 2025;38(3):556. PMID 39627911
  44. Expression of Concern: Sleep Quality Improvements After MDMA-Assisted Psychotherapy for the Treatment of Posttraumatic Stress Disorder. J Trauma Stress. 2025;38(3):555. PMID 39627875 Sevchik BL, et al. A living systematic review, meta-analysis, and open data resource of trials of MDMA-assisted therapy for PTSD. Neuropsychopharmacology. 2026 (published online 11 October). doi:10.1038/s41386-026-02575-z. PMID 42860436. Madden K, Flood B, Kashir I, et al. Clinical Evidence on Psilocybin and Its Representation in Media Reporting: A Systematic Review. JAMA Netw Open. 2026;9(10):e2638843. doi:10.1001/jamanetworkopen.2026.38843. PMID 42900476.