Evidence mapPaperPMID 41706459Full record

Trial reportJAMA psychiatry2026

Efficacy and Safety of the Neuroplastogen TSND-201 for the Treatment of PTSD: A Randomized Clinical Trial.

Amanda Jones, Jennifer Warner-Schmidt, Hannah Kwak, Martin Stogniew, Blake Mandell, Terence H W Ching, Murray B Stein, Benjamin Kelmendi

Registry-linked trialAbstract readRandomized Controlled TrialMulticenter StudyClinical Trial, Phase II
In one paragraph

Trial report in JAMA psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05741710 (A Pilot Study to Assess the Use of Methylone in the Treatment of PTSD IMPACT-1), which is not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05741710 phase1 / phase2completednot on this map

A Pilot Study to Assess the Use of Methylone in the Treatment of PTSD IMPACT-1 (Investigation of Methylone for Post-Traumatic Stress Disorder [PTSD])

TypeinterventionalSponsorTranscend TherapeuticsRan2023 to 2025Enrolled79ConditionsPost Traumatic Stress DisorderArmsMethylone, Placebo
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Amanda JonesTranscend Therapeutics, New York, New York.
Jennifer Warner-SchmidtTranscend Therapeutics, New York, New York.
Hannah KwakTranscend Therapeutics, New York, New York.
Martin StogniewTranscend Therapeutics, New York, New York.
Blake MandellTranscend Therapeutics, New York, New York.
Terence H W ChingDepartment of Psychiatry, Yale School of Medicine, New Haven, Connecticut.
Murray B SteinDepartment of Psychiatry and School of Public Health, University of California San Diego, La Jolla.
Benjamin KelmendiDepartment of Psychiatry, Yale School of Medicine, New Haven, Connecticut.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Importance: The phase 2 data presented here support the development of TSND-201 for posttraumatic stress disorder (PTSD), a disorder for which there is a significant unmet need for rapid-acting and effective treatments. TSND-201 (methylone) is a highly selective, rapid-acting neuroplastogen that releases serotonin, norepinephrine, and dopamine without direct activity at 5-hydroxytryptamine (5-HT) 2A receptors that has shown rapid, robust, and long-lasting benefit for preclinical PTSD-related behaviors and has been well tolerated in phase 1 studies of healthy volunteers. Objective: To evaluate the efficacy and safety of TSND-201 vs placebo in adults with PTSD. Design, Setting, Participants: A Study to Assess the Use of Methylone in the Treatment of PTSD (IMPACT-1) part B was a phase 2, multicenter, double-blind, placebo-controlled, 10-week randomized clinical trial of TSND-201 in people with PTSD conducted between November 29, 2023, and February 19, 2025, across 16 sites in the US, UK, and Ireland. Adults aged 18 to 65 years who met DSM-5 criteria for current PTSD and 6 months or more of symptoms (Clinician-Administered PTSD Scales for DSM-5 [CAPS-5] ≥35) were eligible. Interventions: Participants were randomized 1:1 to receive TSND-201 or placebo. There were 4 once-weekly oral dosing sessions (150 mg followed by 100 mg or placebo). No psychotherapy was provided; however, dosing sessions were monitored by mental health professionals using a nondirective approach. Participants were followed up for 6 weeks after the last dose. Main Outcomes and Measures: The primary end point was change from baseline to day 64 in the CAPS-5 total severity score. Secondary end points included changes in PTSD Checklist for DSM-5 (PCL-5), Sheehan Disability Scale (SDS), and Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Other measures included response (≥50% improvement from baseline), remission (≤11 total severity score), loss of PTSD diagnosis, changes in CAPS-5 symptom clusters, and incidence of treatment-emergent adverse events (TEAEs). Safety was assessed by monitoring adverse events, vital signs, and Columbia-Suicide Severity Rating Scale. Results: Among the 65 participants (mean [SD] age, 43.7 [10.5] years; 39 female [60.0%]), TSND-201 demonstrated significantly greater improvement in CAPS-5 total score than placebo (least-squares mean difference, 9.64; 90% CI, -16.48 to -2.80; P = .01). PCL-5 (-28.46 vs -19.47; LS mean treatment difference, -8.99; 90% CI, -17.81 to -0.17), SDS (-8.29 vs -3.57; LS mean treatment difference, -4.72; 90% CI, -8.84 to -0.61), and MADRS (-13.94 vs -7.73; LS mean treatment difference, -6.21; 90% CI, -12.41 to -0.27) scores were also improved. Common TEAEs in the TSND-201 group included headache, decreased appetite, nausea, dizziness, blood pressure increased, dry mouth, insomnia. Conclusions and Relevance: Results of this randomized clinical trial reveal that TSND-201 demonstrated statistically significant efficacy and was well tolerated, supporting its potential as a rapid-acting, durable treatment for PTSD. Trial Registration: ClinicalTrials.gov Identifier: NCT05741710.

Indexed as

Azabicyclo CompoundsStress Disorders, Post-TraumaticAdultCarbamatesDouble-Blind MethodFemaleHumansMaleMiddle AgedPhenylalanineTreatment OutcomeYoung AdultAzabicyclo CompoundsCarbamatesPhenylalaninesolriamfetol

Identifiers

PMID41706459
PMCPMC12917749

What Socratic holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.