An Evaluation of the Safety and Efficacy of Methylone for the Treatment of PTSD (IMPACT-2)

An Evaluation of the Safety and Efficacy of Methylone for the Treatment of PTSD IMPACT-2 (Investigation of Methylone for Post-Traumatic Stress Disorder [PTSD])

This study is evaluating the safety and efficacy of methylone in adults with PTSD. The study is conducted in two parts.

• Part A is open-label and will enroll up to 15 participants with PTSD
• Part B is randomized (1:1:1), single-blind and will enroll up to 45 participants with PTSD

Eligible participants will enter a 3-week Treatment Period (Part A) or 4-week Treatment Period (Part B) where they will receive methylone once weekly. Following the Treatment Period, participants will enter a 6-week Follow-up Period (Part A) or 8-week Follow-up Period (Part B).

Study Overview

• Status: Completed
• Conditions: Post Traumatic Stress Disorder
• Intervention / Treatment: Drug: Methylone

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Hawthorn, Victoria, Australia, 3122
      • Swinburne University of Technology
    • Melbourne, Victoria, Australia, 3004
      • Ramsay Clinic Albert Road
    • Melbourne, Victoria, Australia
      • Monarch Mental Health Group
• United Kingdom
  • London, United Kingdom
    • Clerkenwell Health
• United States
  • Florida
    • Lauderhill, Florida, United States, 33319
      • Segal Trials
    • Maitland, Florida, United States, 32751
      • Accel Research
    • Orlando, Florida, United States, 32801
      • CNS Healthcare
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Uptown Clinical Research
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Sunstone Medical
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Redbird Research LLC
  • Utah
    • Draper, Utah, United States, 84020
      • Numinus
  • Washington
    • Bellevue, Washington, United States, 98004
      • Seattle NTC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Meets DSM-5 criteria for severe PTSD diagnosis, with a symptom duration of at least 6 months.
• Tried at least one treatment for PTSD (either psychotherapy or pharmacological treatment).
• Proficient in reading and writing in local language sufficient to complete questionnaires.
• Free from any other clinically significant illness or disease.

Exclusion Criteria:

• Primary diagnosis of any other DSM-5 disorder.
• Body mass index (BMI) <18kg/m2 or ≥40 kg/m2.
• Smokes an average of >10 cigarettes and/or e-cigarettes per day.
• Uncontrolled hypertension at Screening.
• Use of prohibited concomitant medications or therapies.
• Current or previous history of clinically significant cardiovascular/cerebrovascular conditions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TSND-201 Low Dose; Part B only	Drug: Methylone; Methylone capsules, given orally, once a week for 3 weeks (Part A) or 4 weeks (Part B)
Experimental: TSND-201 Mid Dose; Part B only	Drug: Methylone; Methylone capsules, given orally, once a week for 3 weeks (Part A) or 4 weeks (Part B)
Experimental: TSND-201 High Dose; Part B only	Drug: Methylone; Methylone capsules, given orally, once a week for 3 weeks (Part A) or 4 weeks (Part B)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Clinician-Administered PTSD Scale for the DSM-5 (CAPS-5) total severity score	The CAPS-5 is a structured interview designed to assess PTSD symptom severity. The total severity score ranges from 0 to 80, with a higher score indicating more severe symptoms.	9 weeks (Part A) / 12 weeks (Part B)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score	The MADRS is a 10-item, clinician-rated scale designed to assess severity of depression. The total score ranges from 0 to 60, with a higher score indicating more severe depression.	9 weeks (Part A) / 12 weeks (Part B)
Change from Baseline in PTSD Checklist for DSM-5 (PCL-5)	The PCL-5 is a 20-item, patient-rated scale designed to measure severity of PTSD symptoms. The total score ranges from 0 to 80, with a higher score indicating more severe PTSD symptoms.	9 weeks (Part A) / 12 weeks (Part B)
Change from Baseline in Sheehan Disability Scale (SDS)	The SDS is a 3-item, patient-rated scale designed to measure disability and impairment across three domains: work/school, social life, and family life/home responsibilities. Each domain is scored from 0 to 10, with higher scores representing greater disability. Total scores range from 0 to 30.	9 weeks (Part A) / 12 weeks (Part B)
Incidence of treatment-emergent adverse events (TEAEs)	Types and rates of adverse events	9 weeks (Part A) / 12 weeks (Part B)

Collaborators and Investigators

• Sponsor: Transcend Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2024
• Primary Completion (Actual): September 23, 2025
• Study Completion (Actual): September 23, 2025

Study Registration Dates

• First Submitted: January 10, 2024
• First Submitted That Met QC Criteria: January 10, 2024
• First Posted (Actual): January 22, 2024

Study Record Updates

• Last Update Posted (Actual): November 25, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: PTSD; Methylone; IMPACT-2; Neuroplastogen; TSND-201
• Additional Relevant MeSH Terms: Trauma and Stressor Related Disorders; Mental Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; methylone
• Other Study ID Numbers: TSND201-PTSD-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No