Psychedelic · TSND-201
Methylone (TSND-201)
- Breakthrough Therapy
- Commissioner's National Priority Voucher
Methylone (3,4-methylenedioxy-N-methylcathinone, bk-MDMA), an entactogen/neuroplastogen developed as TSND-201 for PTSD. Releases serotonin, norepinephrine and dopamine without direct 5-HT2A agonism, producing shorter, milder effects than MDMA. Transcend was acquired by Otsuka (completed 15 Jun 2026).
- Modality
- Psychedelic
- Chemical class
- Substituted cathinone, Methylenedioxyphenethylamine
- DEA schedule
- Schedule I
- Chemistry
- Racemic
- Mechanism
- SERT releaser
- Highest phase
- Phase 3
- Lead indication
- Post-traumatic stress disorder
- Developer
- Transcend Therapeutics, Inc.
- Designations
- Breakthrough Therapy, Commissioner's National Priority Voucher
- Trials
- 3 tracked · 1 recruiting · 60 sites
Mechanism of action
Methylone is a substrate-type releaser at the serotonin, norepinephrine and dopamine transporters (SERT/NET/DAT) with no direct 5-HT2A/2C activity; downstream it engages BDNF/mTOR signaling ('neuroplastogen'), enhancing fear-extinction learning.
| Target | Action | Affinity |
|---|---|---|
| SERTprimarySLC6A4 | Releaser | —ⓘ |
| DATSLC6A3 | Releaser | —ⓘ |
| NETSLC6A2 | Releaser | —ⓘ |
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| TSND-201 oral (IMPACT-1)proprietary oral formulation of methylone Four once-weekly oral dosing sessions (150 mg on day 1, then 100 mg on days 8, 15, 22) in the Phase 2 IMPACT-1 PTSD trial | Oral | Once weekly | t½ 6.4 h · Tmax 2 h |
Development timeline
- Otsuka completed acquisition of Transcend Therapeutics; program continues under Otsuka.↗
- Phase 3 EMPOWER-1 (NCT07456696) initiated/recruiting for PTSD.
- FDA granted Breakthrough Therapy Designation for TSND-201 in PTSD.↗
- IMPACT-1 (NCT05741710) met primary endpoint: placebo-adjusted CAPS-5 -9.64 at Day 64 (p=0.011).↗
Methylone (TSND-201) for Post-traumatic stress disorder
Phase 3RecruitingPost-traumatic stress disorder indication →
TSND-201 (methylone) for PTSD. Phase 1/2 IMPACT-1 met its primary endpoint (placebo-adjusted CAPS-5 -9.64 at Day 64, p=0.011; published in JAMA Psychiatry). FDA Breakthrough Therapy granted 10 Jul 2025; pivotal Phase 3 EMPOWER-1 began enrolling Apr 2026. Otsuka completed acquisition of Transcend 15 Jun 2026.
Clinical trials
NCT07456696EMPOWER-1Phase 3Recruitingn=300
Phase 3 Evaluation of TSND-201 for the Treatment of PTSD (EMPOWER-1)
NCT06215261IMPACT-2Phase 2Completedn=62
Safety and Efficacy of Methylone for PTSD (IMPACT-2)
NCT05741710IMPACT-1Phase 1/2Completedn=79
A Study to Assess Methylone in the Treatment of PTSD (IMPACT-1)
metprimaryCAPS-5 change at Day 64 (placebo-adjusted) — -9.64 points (0.011)
Response 57.1% vs 19.2% (p=0.002), remission 32.1% vs 11.5%, loss of diagnosis 60.7% vs 30.8%. Published in JAMA Psychiatry.
Conference coverage
TSND-201 appears in 3 CNS Pulse conference abstracts:
Identifiers
- ChEMBL CHEMBL3604010
- PubChem CID 45789647
- FDA UNII L4I4B1R01F
Sources
- An Evaluation of the Safety and Efficacy of TSND-201 for the Treatment of PTSD (EMPOWER-1) — ClinicalTrials.gov
- Efficacy and Safety of the Neuroplastogen TSND-201 for the Treatment of PTSD: A Randomized Clinical Trial (IMPACT-1) — JAMA Psychiatry / PMC
- clinicaltrials.gov — ClinicalTrials.gov
- transcendtherapeutics.com — Reference
- transcendtherapeutics.com — Reference
- transcendtherapeutics.com — Reference
- IMPACT-1 (NCT05741710) — ClinicalTrials.gov
- Otsuka Pharmaceutical Completes Acquisition of Transcend Therapeutics — Otsuka Pharmaceutical
- Transcend Therapeutics Receives Breakthrough Therapy Designation for TSND-201 (methylone) for PTSD — Transcend Therapeutics