Placebo for PTSD

12 papers and 29 clinical trials exploring placebo as a treatment for ptsd.

CompoundComparator / Control

Placebo

Placebo is the most widely referenced comparator in psychedelic clinical research, appearing in over 500 trials. Understanding how placebos are designed, administered, and interpreted is essential to evaluating the evidence base for psychedelic-assisted therapies — and one of the field’s most contested methodological challenges.

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Indication354 million people suffering from PTSD globally.

PTSD

Posttraumatic stress disorder (PTSD) is a significant mental health challenge affecting over 354 million individuals globally. Psychedelics, particularly MDMA and psilocybin, are emerging as promising therapeutic options, offering new avenues for treatment through innovative psychotherapeutic interventions.

Full PTSD profile

Academic Research

12 papers

Paywallindividual

Changes in anxiety, quality of life, and functioning following psilocybin-assisted therapy in veterans with treatment-resistant depression

This secondary analysis of an open-label trial (n=15) examined a single 25 mg dose of psilocybin with psychological support in veterans with treatment-resistant depression, focusing on anxiety, quality of life, functioning, and PTSD symptoms. Improvements were observed across these measures, but most were no longer significant after accounting for concurrent improvements in depression.

Published: June 4, 2026
Journal: Journal of Affective Disorders
Authors: Kelly, C. M., Fradet, M., Bostian, C. M., Donnelly, A., Ellis, S., Ostacher, M., Aaronson, S., Suppes, T.

Open Accessindividual

Effects of MDMA-assisted therapy for PTSD on self-experience

This re-analysis of an RCT of MDMA-assisted therapy for PTSD finds that study participants (n=90) had significant improvements in the measures of self-experience (e.g. alexithymia -; the inability to identify & describe emotions experienced by oneself). The change in scores of self-experience correlates with recovery from PTSD.

Published: January 10, 2024
Journal: PLOS ONE
Authors: van der Kolk, B., Wang, J. B., Yehuda, R., Bedrosian, L., Cooker, A., Harrison, C., Mithoefer, M. C., Emerson, A., Doblin, R., Yazar-Klosinski, B.

Paywallindividual

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

This multi-site, randomised, double-blind, Phase IIIb trial (n=104) evaluated the efficacy and safety of MDMA-assisted therapy (MDMA-AT) for individuals with moderate to severe PTSD. The study found significant reductions in PTSD severity (CAPS-5 score) and functional impairment (SDS score) for the MDMA-AT group compared to placebo with therapy. Seven participants experienced severe treatment-emergent adverse events, but no deaths or serious adverse events were reported. The treatment was found to be generally well tolerated in a diverse population.

Published: September 14, 2023
Journal: Nature Medicine
Authors: Mitchell, J., Ot’alora G, M., van der Kolk, B., Shannon, S., Bogenschutz, M. P., Gelfand, Y., Paleos, C., Nicholas, C. R., Quevedo, S., Balliett, B., Hamilton, S., Mithoefer, A. T., Kleiman, S., Parker-Guilbert, K., Tzarfaty, K., Harrison, C., de Boer, A., Doblin, R., Yazar-Klosinski, B.

Open Accessindividual

Long term structural and functional neural changes following a single infusion of Ketamine in PTSD

This pilot RCT study (n=27) investigated the potential of a single ketamine infusion (35mg/70kg), followed by brief exposure therapy, to enhance the extinction of trauma memories in individuals diagnosed with PTSD. Participants were randomly assigned to receive either ketamine or midazolam after retrieval of the traumatic memory, and underwent trauma-focused psychotherapy 24 hours later for four days. While PTSD symptoms improved equally in both groups, post-treatment ketamine recipients showed lower amygdala and hippocampus reactivation to trauma memories than midazolam recipients, suggesting that ketamine may enhance the post-retrieval extinction of trauma memories.

Published: June 3, 2023
Journal: Neuropsychopharmacology
Authors: Duek, O., Korem, N., Li, Y., Kelmendi, B., Amen, S., Gordon, C., Milne, M., Krystal, J. H., Levy, I., Harpaz-Rotem, I.

Open Accessmeta

International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators

This meta-analysis (n=809, s=17) finds robust effects of ketamine for relieving depression (at 24 hours and seven days). Moderators of this effect were the level of treatment resistance (i.e. more failed SSRIs) and studies that used a cross-over design (smaller placebo effect). Other moderators were found, but all were modest and clinically irrelevant (i.e. age or sex doesn't moderate treatment effect).

Published: September 7, 2022
Journal: Molecular Psychiatry
Authors: Price, R., Kissel, N., Baumeister, A., Rohac, R., Woody, M. L., Ballard, E. D., Zarate, C. A., Deakin, W., Abdallah, C. G., Feder, A., Charney, D. S., Grunebaum, M. F., Mann, J. J., Mathew, S. J., Gallagher, B., McLoughlin, D. M., Murrough, J. W., Muthukumaraswamy, S., McMillan, R., Sumner, R. L., Papakostas, G. I., Fava, M., Hock, R. S., Phillips, J. L., Blier, P., Shiroma, P. R., Sos, P., Chen, M. H., Tiger, M., Lundberg, J., Wilkinson, S. T., Wallace, M. L., Su, T. P.

Paywallmeta

MDMA-assisted therapy for posttraumatic stress disorder: A pooled analysis of ethnoracial differences in efficacy and safety from two Phase 2 open-label lead-in trials and a Phase 3 randomized, blinded placebo-controlled trial

This study (2022) analysed data from two Phase II and one Phase III trials from MAPS where MDMA-assisted therapy (MDMA-AT) was used to treat PTSD in order to compare the efficacy and safety of MDMA-AT between Black, Indigenous, and People of Color (BIPOC) and non-Hispanic White participants. No significant ethnoracial difference in CAPS-5 scores was observed while BIPOC participants trended toward greater reductions following MDMA-AT.

Published: June 21, 2022
Journal: Journal of Psychopharmacology
Authors: Ching, T. H., Williams, M. T., Wang, J. B., Jerome, L., Yazar-Klosinski, B., Emerson, A., Doblin, R.

Clinical Trials

29 trials

CompletedPhase II

A Study to Assess the Use of Methylone in the Treatment of PTSD (IMPACT-1)

This Phase II, two-part, multicentre trial (n=64) will assess methylone as a treatment for adults with post-traumatic stress disorder (PTSD). It is designed to evaluate the drug’s safety, tolerability, and efficacy in participants aged 18–65 years in the UK, including people who have previously tried at least one PTSD treatment without sufficient benefit.

Type: interventional
Blinding: double
Randomized: Yes

Not yet recruitingPhase NA

Intra-Sessional Autonomic Arc Detection in Ketamine-Assisted Therapy for PTSD: A Signal Characterisation Pilot Study

This prospective observational pilot study (n=5) will assess whether continuous wearable physiological monitoring can characterise an intra-sessional autonomic arc during ketamine-assisted therapy in adults with post-traumatic stress disorder (PTSD). It will evaluate the feasibility of detecting a consistent autonomic trajectory, using continuous heart rate variability (HRV) and electrodermal activity (EDA) data collected during independently arranged ketamine sessions. Participants aged 19 years or older with confirmed PTSD will wear an EmbracePlus wrist-worn biosensor across a 3–7 day pre-session baseline period, the full ketamine-assisted therapy session, and 3–5 day follow-up monitoring windows at 1, 2 and 4 weeks after the session. The study also includes a structured pre-session interview within 48 hours before treatment and a structured post-session interview within 4 hours after session end, including administration of the Post-Session Subjective Integration Scale. Ketamine is administered solely by the participant’s licensed treating provider, and no drug is given by the researcher. The primary outcome is intra-sessional autonomic arc trajectory characterisation during the ketamine session, with sessions showing EDA channel loss exceeding 15% of the recording window excluded from primary analysis.

Started: July 15, 2026
Type: observational
Blinding: none
Randomized: No
Registry ID: NCT07614581

WithdrawnPhase II

Precision Phenotyping of Behavioral Risk and Response to Electromagnetic and Psychedelic Therapies

This Phase II, non-randomised, open-label, parallel-group trial (n=150) will study response to three neuroplasticity-enhancing interventions in civilian and Veteran adults (aged 18–69) at low, intermediate or high risk for self-harm. The study will evaluate clinical change in suicidal ideation (Scale of Suicidal Ideation from baseline to the post‑treatment visit at Month 6) and aim to characterise neurobiological and blood-based markers associated with risk and treatment response. Participants are allocated to one of three experimental arms: two sessions of fMRI neurofeedback targeting amygdala activity, an accelerated theta burst stimulation programme of 50 sessions delivered to the dorsolateral prefrontal cortex, or psilocybin‑assisted therapy comprising three preparation sessions, two psilocybin administration sessions and two integration sessions. Baseline and post‑treatment assessments include clinical measures, structural and functional MRI and blood sampling for circular RNA (circRNA); an artificial intelligence analytic team will use these multimodal data to develop predictive models of behavioural risk and treatment response.

Started: May 1, 2026
Type: interventional
Blinding: none
Randomized: No
Registry ID: NCT07484906

RecruitingPhase II

MDMA-Assisted Massed Exposure Therapy for PTSD

This Phase II, randomised, triple‑blind, parallel trial (n=200) will evaluate whether a single 100 mg oral dose of MDMA given adjunctively with massed Prolonged Exposure (PE) therapy improves PTSD symptom severity and related neural measures in adults with post‑traumatic stress disorder (age 21–70 years), with the primary outcome being change in Clinician‑Administered PTSD Scale for DSM‑5‑Revised (CAPS‑5‑R) score from baseline to one month post‑treatment. Participants will be randomised to MDMA + massed PE or placebo + massed PE; MDMA is administered as a 100 mg capsule under supervision at Visit 2 of a course of 10 daily PE sessions delivered over two weeks (11 therapy sessions total, including an additional session during Visit 2), and the placebo visually matches the three MDMA capsules (40mg, 40mg, and 20mg). The study will also assess response efficiency and durability of symptom improvement and explore extinction retention and amygdala threat reactivity (neuroimaging), with safety and blinded independent evaluator CAPS‑5‑R assessments at the one‑month post‑treatment follow‑up; the trial is sponsored by Emory University with an anticipated start in January 2026 and completion in January 2030.

Started: January 1, 2026
Type: interventional
Blinding: triple
Randomized: Yes
Registry ID: NCT07288151

Temporarily not availablePhase II

Department of Defense PTSD Adaptive Platform Trial – Intervention D – SLS-002

This Phase II randomised, quadruple-blind, placebo-controlled trial (n=200) will assess the safety and efficacy of intranasal SLS-002 (ketamine, 78mg) for post-traumatic stress disorder (PTSD) in active-duty service members and veterans.

Started: June 1, 2025
Type: interventional
Blinding: quadruple
Randomized: Yes
Registry ID: NCT06816433

RecruitingPhase II

Psilocybin with Psychological Support (Psi-PS) for Military Veterans and First Responders with Co-occurring PTSD & Alcohol Use Disorder (AUD) (Psi-PS)

This Phase II, double-blind, placebo-controlled trial (n=40) will investigate the safety, effectiveness, and lasting effects of psilocybin (25mg) combined with psychological support (Psi-PS) in military veterans and first responders with both alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD).

Started: March 1, 2025
Type: interventional
Blinding: double
Randomized: Yes
Registry ID: NCT06853912

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Search all Placebo papers Search all PTSD trials Full Placebo profile Full PTSD profile

Placebo for PTSD

Placebo

PTSD

Academic Research

Changes in anxiety, quality of life, and functioning following psilocybin-assisted therapy in veterans with treatment-resistant depression

Effects of MDMA-assisted therapy for PTSD on self-experience

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

Long term structural and functional neural changes following a single infusion of Ketamine in PTSD

International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators

MDMA-assisted therapy for posttraumatic stress disorder: A pooled analysis of ethnoracial differences in efficacy and safety from two Phase 2 open-label lead-in trials and a Phase 3 randomized, blinded placebo-controlled trial

Clinical Trials

A Study to Assess the Use of Methylone in the Treatment of PTSD (IMPACT-1)

Intra-Sessional Autonomic Arc Detection in Ketamine-Assisted Therapy for PTSD: A Signal Characterisation Pilot Study

Precision Phenotyping of Behavioral Risk and Response to Electromagnetic and Psychedelic Therapies

MDMA-Assisted Massed Exposure Therapy for PTSD

Department of Defense PTSD Adaptive Platform Trial – Intervention D – SLS-002

Psilocybin with Psychological Support (Psi-PS) for Military Veterans and First Responders with Co-occurring PTSD & Alcohol Use Disorder (AUD) (Psi-PS)

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Placebo for PTSD

Placebo

PTSD

Academic Research

Changes in anxiety, quality of life, and functioning following psilocybin-assisted therapy in veterans with treatment-resistant depression

Effects of MDMA-assisted therapy for PTSD on self-experience

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

Long term structural and functional neural changes following a single infusion of Ketamine in PTSD

International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators

MDMA-assisted therapy for posttraumatic stress disorder: A pooled analysis of ethnoracial differences in efficacy and safety from two Phase 2 open-label lead-in trials and a Phase 3 randomized, blinded placebo-controlled trial

Clinical Trials

A Study to Assess the Use of Methylone in the Treatment of PTSD (IMPACT-1)

Intra-Sessional Autonomic Arc Detection in Ketamine-Assisted Therapy for PTSD: A Signal Characterisation Pilot Study

Precision Phenotyping of Behavioral Risk and Response to Electromagnetic and Psychedelic Therapies

MDMA-Assisted Massed Exposure Therapy for PTSD

Department of Defense PTSD Adaptive Platform Trial – Intervention D – SLS-002

Psilocybin with Psychological Support (Psi-PS) for Military Veterans and First Responders with Co-occurring PTSD & Alcohol Use Disorder (AUD) (Psi-PS)

Explore further