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PTSD (Post-traumatic stress disorder)

A central target for MDMA-assisted therapy and related trauma-focused interventions.

State of the evidence

Synthesized

Synthesized from 25 studies in the library · AI-generated, grounded in the abstracts below

Found by searching the library for PTSD, post-traumatic stress disorder, traumatic stress, then ranked by relevance.

Research indicates that MDMA-assisted therapy and ketamine can reduce PTSD symptoms, with MDMA showing consistent, large effects in phase 2 and 3 trials, and ketamine showing rapid but less durable effects. However, evidence is limited by small sample sizes, short follow-up durations, and the need for more diverse populations and long-term safety data.

Evidence by study

Direction is which way each study's own result points, not our rating of the study.

What the directions mean
Supports:
the study found the intervention worked, or its hypothesis held.
Opposes:
it found the opposite, no benefit or a harm.
No effect:
no significant difference either way.
Mixed:
effects in both directions within the same study.
Unclear:
the abstract does not report a direction.
MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. 2021
Supports

MDMA-assisted therapy significantly reduced PTSD symptoms (CAPS-5) and functional impairment (SDS) compared to placebo, with large effect sizes.

RCT Sample size: 90

The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future. 2017
Unclear

This review discusses the therapeutic potential of psychedelic drugs but does not provide specific findings on PTSD.

review

The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. 2010
Supports

This pilot study found MDMA-assisted psychotherapy to be safe and efficacious in treatment-resistant PTSD.

RCT

Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder 2014
Supports

A single intravenous ketamine infusion significantly reduced PTSD symptom severity compared to midazolam at 24 hours post-infusion.

RCT Sample size: 41

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. 2018
Supports

MDMA-assisted psychotherapy showed dose-dependent efficacy for PTSD in first responders and military personnel.

RCT

A randomized, controlled pilot study of MDMA (±3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD) 2012
Mixed

MDMA-assisted psychotherapy did not show statistically significant reductions on the clinician-rated CAPS but did show significant self-reported improvement on the PDS.

RCT Sample size: 12

MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. 2023
Supports

MDMA-assisted therapy significantly reduced PTSD symptoms and functional impairment compared to placebo with therapy, with a large effect size.

RCT Sample size: 104

Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study. 2013
Supports

Long-term follow-up (mean 45.4 months) showed that most participants maintained clinically significant symptom relief from MDMA-assisted psychotherapy, though two relapsed.

observational Sample size: 19

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. 2019
Supports

Pooled analysis of six phase 2 trials showed MDMA-assisted psychotherapy significantly reduced PTSD symptoms compared to control, with a large effect size.

pooled analysis Sample size: 103

Theorizing that Psychedelic Assisted Therapy May Play a Role in the Treatment of Trauma-Induced Personality Disorders. 2024
Unclear

This theoretical paper proposes that psychedelic-assisted therapy may be useful for trauma-induced personality disorders, but does not provide empirical data.

theoretical

Psychedelic Psychiatry's Brave New World. 2020
Unclear

This review discusses the potential of psychedelic psychiatry but does not provide specific findings on PTSD.

review

Reviewing the Potential of Psychedelics for the Treatment of PTSD 2020
Unclear

This review discusses the potential of MDMA, ketamine, classical psychedelics, and cannabinoids for PTSD, but does not provide specific quantitative findings.

review

A PILOT STUDY OF GROUP MINDFULNESS-BASED COGNITIVE THERAPY (MBCT) FOR COMBAT VETERANS WITH POSTTRAUMATIC STRESS DISORDER (PTSD) 2013
Supports

Mindfulness-based cognitive therapy (MBCT) significantly improved PTSD symptoms compared to treatment-as-usual in combat veterans.

RCT Sample size: 37

A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder. 2021
Supports

Repeated intravenous ketamine infusions over 2 weeks significantly reduced PTSD symptoms compared to midazolam, with a large effect size at week 2.

RCT Sample size: 30

Novel psychopharmacological therapies for psychiatric disorders: psilocybin and MDMA. 2016
Unclear

This review discusses psilocybin and MDMA for psychiatric disorders but does not provide specific findings on PTSD.

review

Trauma re-experiencing episodes during esketamine treatment in patients with treatment-resistant depression and comorbid PTSD: a retrospective case series. 2026
Mixed

In patients with TRD and comorbid PTSD, esketamine treatment led to trauma re-experiencing episodes; in most cases these resolved, but in some treatment was stopped.

observational Sample size: 22

A neurocognitive account of complex PTSD: self-modelling, affective dysregulation, and implications for MDMA-assisted and targeted psychotherapies. 2026
Unclear

This narrative review develops a neurocognitive account of C-PTSD and discusses MDMA-assisted psychotherapy as a potential intervention, but does not provide empirical data.

theoretical

Changes in trauma symptoms of discrimination after MDMA-assisted psychotherapy for posttraumatic stress disorder. 2026
Supports

MDMA-assisted therapy significantly reduced discrimination-related trauma symptoms, with a large effect size, but the sample was very small.

observational Sample size: 5

Dissociation and PTSD in women with a history of childhood sexual abuse: a pilot examination of a specialized inpatient unit 2026
Supports

In a specialized inpatient unit, PTSD symptoms significantly decreased after treatment, and reductions in dissociative symptoms were associated with improvements in PTSD.

observational Sample size: 108

Ketamine effects on EEG and their links to therapy differ across treatment-resistant major depression, post-traumatic stress disorder, and obsessive-compulsive disorder 2026
Unclear

Ketamine produced dose- and band-frequency-dependent EEG power changes in TR-PTSD patients, which differed from TR-MDD and TR-OCD patients.

observational Sample size: 22

MDMA-assisted PTSD and Alcohol Therapy Trial (MPATHY): study protocol for a double-blind, randomised, controlled outpatient trial of MDMA-assisted integrated exposure-based therapy for comorbid post-traumatic stress disorder and alcohol use disorder 2026
Unclear

This is a study protocol for a trial of MDMA-assisted integrated exposure therapy for comorbid PTSD and AUD; no results are reported.

protocol

Making a case for using MDMA-assisted psychotherapy for borderline personality disorder and complex PTSD: a descriptive systematic review of the literature 2026
Supports

This systematic review found that MDMA-assisted psychotherapy reduced PTSD symptoms across studies, with some evidence for decreased dissociative symptoms at higher doses.

systematic review Sample size: 335

Ketamine-assisted psychotherapy for posttraumatic stress disorder: a systematic review and individual participant data meta-analysis of predictors of treatment effects. 2026
Supports

Individual participant data meta-analysis found that more psychotherapy sessions, more ketamine sessions, higher baseline severity, and shorter treatment duration predicted greater PTSD symptom improvement with ketamine-assisted psychotherapy.

meta-analysis Sample size: 533

At-Home Telehealth-Supported Subcutaneous Ketamine Therapy in Adults With Moderate to Severe Depression, Anxiety, or PTSD: A Real-World Observational Study of Safety, Feasibility, and Clinical Outcomes in a Large, Heterogeneous Cohort in the United States. 2026
Supports

At-home telehealth-supported subcutaneous ketamine therapy was associated with significant reductions in PTSD symptoms (PCL-5) over 6 weeks in a large real-world cohort.

observational Sample size: 3870

Acute pretrauma ethanol exacerbates PTSD-like phenotype in rats and is reversed by early intranasal ketamine 2026
Unclear

In rats, acute ethanol exposure before trauma exacerbated PTSD-like symptoms, and early intranasal ketamine reversed this effect.

preclinical

Points of agreement

  • MDMA-assisted therapy consistently reduces PTSD symptoms across multiple RCTs and a pooled analysis.
  • Ketamine, both single and repeated infusions, rapidly reduces PTSD symptoms.
  • Both MDMA and ketamine show large effect sizes in reducing PTSD symptoms.
  • Long-term follow-up of MDMA-assisted therapy suggests durability of symptom relief.

Conflicts

  • One early MDMA trial (article_id 22029) found non-significant results on the clinician-rated CAPS but significant self-reported improvement, while later trials found significant effects on both.
  • Esketamine treatment for comorbid TRD and PTSD led to trauma re-experiencing episodes in some patients, which is a potential adverse effect not reported in other ketamine studies.
  • The durability of ketamine's effects is less established compared to MDMA, with most studies focusing on short-term outcomes.

Gaps

  • Long-term durability of ketamine's effects on PTSD is not well studied.
  • Most studies have small sample sizes, limiting generalizability.
  • There is limited research on diverse populations, including racial/ethnic minorities and individuals with complex comorbidities.
  • The optimal dosing, number of sessions, and integration with psychotherapy for both MDMA and ketamine are not fully established.
  • Safety and efficacy in real-world settings, especially for at-home ketamine, require more research.
  • The role of psychedelic-assisted therapy for complex PTSD and borderline personality disorder is understudied.
Browse these studies in the library
How we analyze this

This synthesis reads the 15 most-cited and 10 most recent studies whose primary subject is PTSD, up to 25 in all. The most-cited set anchors the established evidence, and the recent set surfaces work that is too new to have gathered citations yet.

A study qualifies only when PTSD or a known alias appears in its title or keywords, so broad reviews that mention it only in passing are left out. Each study is read from its abstract, strongest evidence first, and the summary reports the direction of the results along with any conflicts and gaps.

Ask your own question in the Research Synthesis Tool

Latest monthly recap: June 2026 →

1,441 articles · 620 from the last two years · 654,819 participants across 552 studies reporting sample size

Common study designs

review 365 systematic review 77 observational cohort 55 randomized controlled trial 94 theoretical or philosophical paper 116

Research

Synthesize the evidence → Search all →

The efficacy and mechanism of an integrated mindfulness-based programme on posttraumatic stress disorder among people with HIV: a randomized controlled trial with 3-month follow up.

European Journal of Psychotraumatology December 1, 2026 Chulei Tang, Ting Zhao, Simin Yu et al.

An integrated mindfulness-based programme combining the Community Resiliency Model and mindfulness-based stress reduction reduced posttraumatic stress disorder symptoms and improved antiretroviral therapy adherence in people with HIV. Eighty-two participants with HIV and PTSD were assigned to either the intervention or a control group. The intervention group showed significantly greater reductions in PTSD symptoms and improvements in ART adherence immediately after the programme and at a three-month follow-up. Increased mindfulness, enhanced resilience, and decreased rumination partially explained the effect on PTSD symptoms. The authors argue the programme offers a low-resource intervention for trauma and treatment adherence in HIV-positive populations.

DOI: 10.1080/20008066.2025.2602298 (opens in new tab) Full text (opens in new tab) Hiv/aids Posttraumatic stress disorder Vih/sida Community resiliency model +2

Trauma re-experiencing episodes during esketamine treatment in patients with treatment-resistant depression and comorbid PTSD: a retrospective case series.

European Journal of Psychotraumatology December 1, 2026 Maud Rothärmel, Lila Mekaoui, François Kazour et al. 1 citation

In a retrospective study of 22 adults with treatment-resistant depression and comorbid post-traumatic stress disorder who received esketamine nasal spray, trauma re-experiencing episodes occurred during treatment sessions. For 16 patients (72.7%) these episodes disappeared as sessions progressed. Treatment was stopped for 6 patients (27.3%) due to re-experiencing. Among those who continued esketamine, depression response rate was 45.5% and remission 22.7%; PTSD improvement rate was 45.5% and remission 18.2%. The findings suggest esketamine can be safely administered in this comorbid population and that trauma re-experiencing does not prevent clinical improvement.

DOI: 10.1080/20008066.2025.2609425 (opens in new tab) Full text (opens in new tab) Treatment-resistant depression Esketamine nasal spray Post-traumatic stress disorder Real-life data +2

A neurocognitive account of complex PTSD: self-modelling, affective dysregulation, and implications for MDMA-assisted and targeted psychotherapies.

European Journal of Psychotraumatology December 1, 2026 Philip Gerrans, Hugh McGovern, Jakob Hohwy et al.

Complex post-traumatic stress disorder (C-PTSD) involves lasting difficulties with emotions, self-concept, and relationships, beyond typical PTSD symptoms. This review proposes a neurocognitive explanation based on predictive processing and self-modelling, focusing on how the brain's insula integrates bodily signals, emotions, and self-awareness. The authors suggest that C-PTSD arises from maladaptive predictions shaped by prolonged interpersonal trauma, leading to unstable self-regulation. They examine MDMA-assisted psychotherapy as one intervention that may temporarily alter emotional salience, trust, and self-related thinking. The framework generates testable hypotheses about self-modelling in C-PTSD and offers guidance for developing treatments that target affective regulation and self-referential processing.

DOI: 10.1080/20008066.2026.2631358 (opens in new tab) Full text (opens in new tab) 3,4-methylenedioxymethamphetamine 4-metilendioximetanfetamina C-PTSD MDMA-Assisted Psychotherapy +5

Psychedelic Therapies in the Management of Post-Traumatic Stress Disorder

Journal of Education Health and Sport July 16, 2026 Jakub Bajer, Aleksandra Włodarczyk, Hubert Kulawinek et al.

Psychedelic therapies, especially MDMA-assisted therapy, show promise for treating PTSD by targeting underlying causes rather than just symptoms. A review of studies found that MDMA-assisted therapy led to 67% of participants no longer meeting PTSD criteria at the study endpoint. Psilocybin effectively treats common comorbidities like anxiety and treatment-resistant depression, while ketamine offers rapid symptom relief for treatment-resistant cases with high risk of self-harm. These treatments work by inducing neuroplasticity and augmenting fear extinction through specific biological pathways. Despite regulatory challenges, standardized protocols are needed to ensure safety and reproducibility in future research.

DOI: 10.12775/jehs.2026.94.73071 (opens in new tab) Traumatic stress Ketamine Psilocybin Anxiety disorder +7

Silence is golden: Documenting the speech production of participants and support providers in psilocybin administration sessions for the treatment of post-traumatic stress disorder

Journal of Psychopharmacology July 16, 2026 Robert F. Dougherty, Nadav Liam Modlin, Niall M. Mcgowan et al.

In a 12-week clinical trial of 25 mg COMP360 psilocybin for 22 participants with post-traumatic stress disorder, audio recordings showed that during drug-administration sessions speech by either party was rare: silence filled 78% of the time on average, compared to 25% to 30% in non-administration sessions. Thematic analysis of post-dosing interviews revealed that support was minimally enacted but experientially salient, autonomy was promoted through the introspective state and non-directive support, and primary modes of support during altered states included reassurance and validation. The minimal verbal interaction distinguishes this monitoring and support from conventional psychotherapies and MDMA-assisted therapy.

DOI: 10.1177/02698811261464988 (opens in new tab) Psilocybin Context archaeology Thematic analysis Focus group +6

Mindfulness Processes and User Experiences in a Randomized Controlled Trial of the Mindfulness Coach App for Veterans with Posttraumatic Stress Disorder

Mindfulness July 11, 2026 Shilpa Hampole, Haijing Wu Hallenbeck, Joseph Wielgosz et al.

Veterans with PTSD who used the Mindfulness Coach mobile app for 8 weeks showed improvements in two facets of mindfulness—describing and nonjudgment—compared to a waitlist control group, and both groups improved in psychological flexibility. Qualitative interviews indicated positive experiences, perceived reductions in stress, PTSD symptoms, and sleep problems, but also barriers to use. High attrition limited the findings' generalizability, highlighting challenges in sustaining engagement with self-guided digital interventions. The app is described as a low-cost, scalable tool that may extend access to mindfulness-based strategies for veterans with PTSD.

DOI: 10.1007/s12671-026-02930-7 (opens in new tab) Full text (opens in new tab) Mindfulness Meditation Randomized controlled trial Psychological intervention +10

Temporal associations between nightmares and PTSD symptoms in the acute post-sexual assault period: An ecological momentary assessment study

Journal of Mood and Anxiety Disorders July 10, 2026 Ashby Boland, Lauren D Reyes, Jenny Black et al.

Nightmares are common after sexual assault and may contribute to posttraumatic stress disorder (PTSD) development, but daily links between nightmares and PTSD symptoms in the acute aftermath are not well understood. In 54 women sexual assault survivors followed with daily surveys for six weeks, most had clinically significant PTSD symptoms and frequent nightmares (42.8% of days). At the within-person level, nightmares predicted next-survey PTSD symptoms and vice versa, but these effects disappeared after adjusting for how symptoms carried over from one time to the next. Between individuals, those with more frequent nightmares had higher PTSD symptoms, with models accounting for 43-44% of the variance. Short-term nightmare fluctuations may not drive PTSD changes once stability is considered; nightmares may instead indicate overall PTSD severity.

DOI: 10.1016/j.xjmad.2026.100191 (opens in new tab) Ecological validity Ecological study Poison control Disease +4

Dissociation and PTSD in women with a history of childhood sexual abuse: a pilot examination of a specialized inpatient unit

Frontiers in Psychiatry July 8, 2026 Lotem Zvi, Jonathan E. Handelzalts, Danny Horesh et al.

Women with histories of childhood sexual abuse (CSA) and co-occurring psychiatric disorders admitted to a specialized integrative inpatient unit in Israel showed that dissociative symptoms, particularly maladaptive absorption, were strongly linked to PTSD severity. In a cross-sectional phase with 108 women, all facets of dissociation correlated positively with PTSD symptoms. In a smaller treatment phase with 28 women, PTSD symptoms decreased after the program, and reductions in absorption were tied to improvements in overall PTSD and hyperarousal. The findings suggest dissociation should be a key therapeutic target, though larger controlled trials are needed.

DOI: 10.3389/fpsyt.2026.1855046 (opens in new tab) Dissociative experiences scale Dissociative disorders Dissociation chemistry Sexual abuse +6

Ketamine effects on EEG and their links to therapy differ across treatment-resistant major depression, post-traumatic stress disorder, and obsessive-compulsive disorder

The International Journal of Neuropsychopharmacology July 6, 2026 Shabah M. Shadli, Neda Nasrollahi, Calvin K. Young et al.

Ketamine at low doses (0.5-1.0 mg/kg I.M.) quickly reduces symptoms in treatment-resistant major depressive disorder (TR-MDD), post-traumatic stress disorder (TR-PTSD), and obsessive-compulsive disorder (TR-OCD), but its neural effects differ by diagnosis. EEG recordings of resting frontal activity before and after ketamine or fentanyl showed that TR-PTSD patients had dose- and band-frequency-dependent power changes (especially alpha at 0.5 mg/kg), while TR-MDD patients showed no such changes. TR-OCD responses differed qualitatively from both. Correlations between EEG power changes and symptom scale improvements varied by band and electrode across different disorder-specific scales. Ketamine's effects and their therapeutic links vary by brain site and frequency band depending on the DSM diagnosis, suggesting disorder-specific systems require a ketamine-sensitive factor to generate the disorder.

DOI: 10.1093/ijnp/pyag037 (opens in new tab) Full text (opens in new tab) Panic disorder Ketamine Anxiety disorder Major depressive disorder +12

Making a case for using MDMA-assisted psychotherapy for borderline personality disorder and complex PTSD: a descriptive systematic review of the literature

Therapeutic Advances in Psychopharmacology July 1, 2026 Karthika Kasiviswanathan, Dinuli Nilaweera, M Morando et al.

MDMA-assisted psychotherapy (MDMA-AP) may help treat not only PTSD but also complex PTSD and borderline personality disorder. A systematic review of 24 studies involving 335 participants found that most reported reduced PTSD symptoms after MDMA-AP, with some noting decreased dissociative symptoms at higher doses. Although no studies directly assessed MDMA-AP for complex PTSD or borderline personality disorder, improvements in emotional regulation, interpersonal functioning, identity coherence, and abandonment concerns were reported. Adverse drug reactions were mild to moderate, though specific safety concerns remain. These findings offer preliminary insights for future research and clinical considerations.

DOI: 10.1177/20451253251408626 (opens in new tab) Ecstasy Borderline personality disorder Psycinfo Abandonment legal +11

Clinical trials

All PTSD trials →