Methylone (TSND-201) for PTSD Shows Rapid, Sustained Symptom Improvement in Phase 2 IMPACT-1 Trial
In treatment-resistant PTSD, TSND-201 was associated with statistically significant symptom improvement as early as day 10 in the phase 2 IMPACT-1 trial.
An investigational medication for posttraumatic stress disorder (PTSD) has demonstrated significant efficacy in a phase 2 clinical trial, potentially offering hope to millions of Americans affected by this condition.
Transcend Therapeutics announced that its rapid-acting neuroplastogen TSND-201 (methylone) met its primary endpoint in the IMPACT-1 study, showing a statistically significant placebo-adjusted improvement of -9.64 points on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) on day 64 (P =.011).
Notably, TSND-201 demonstrated rapid improvements, with a statistically significant placebo-adjusted CAPS-5 improvement of -8.00 points observed as early as day 10 (-17.83 points vs -9.83 points; P =.012). These improvements remained statistically significant for the duration of the trial.
The randomized, double-blind, placebo-controlled IMPACT-1 trial enrolled 65 adults with severe PTSD (CAPS-5 equal to or greater than 35) who had previously been treated for PTSD, according to the statement. Participants received 4 oral doses of TSND-201 or placebo at weekly intervals and were followed for 64 days after the first dose.
Investigators reported significant improvements on multiple secondary endpoints as well, including response rates (50% or greater improvement from baseline on CAPS-5; 57.1% vs 19.2%; P =.002), remission (11 points or more on the CAPS-5; 32.1% vs 11.5%; P =.036), and loss of PTSD diagnosis (60.7% vs 30.8%; P = 014).
"It has been over two decades without a new treatment for PTSD. The results of this study suggest that TSND-201 may represent a significant clinical breakthrough — demonstrating clinically meaningful efficacy with a rapid onset," Murray B. Stein, MD, MPH, distinguished professor of psychiatry and public health at the University of California San Diego, said in the statement. Stein is also a staff psychiatrist at the Veteran Affairs San Diego Healthcare System, added "Rapid-acting, episodic treatments could be a paradigm shift in the treatment of PTSD, providing hope for the many patients who have struggled to find effective relief."
"Rapid-acting, episodic treatments could be a paradigm shift in the treatment of PTSD, providing hope for the many patients who have struggled to find effective relief."
The medication was generally safe and well tolerated. Most adverse events, common ones being headache, decreased appetite, nausea, dizziness, blood pressure increase, dry mouth, insomnia, muscle tightness, and feeling abnormal, were transient, the company stated, and resolved on the day of dosing. One serious adverse event of seizure occurred in the TSND-201 group, which was considered unrelated to the study drug, Transcend said.
TSND-201 is a proprietary formulation of methylone with its primary site of action at the monoamine transporters. It has no activity at 5HT-2a, meaning it is not hallucinogenic. The company is developing the drug as a rapid-acting and durable treatment for PTSD and other central nervous system conditions.
PTSD affects approximately 13 million Americans annually, with an estimated 7% of US adults being diagnosed with the condition during their lifetime.2 Only 2 medications are FDA-approved for PTSD treatment (sertraline and paroxetine), and their efficacy is described as modest at best, highlighting the significant unmet need for new treatment options.
“We are encouraged by the positive Phase 2 results demonstrating TSND-201’s potential as a rapid-acting and durable treatment for patients with PTSD,” Blake Mandell, Transcend Therapeutics co-founder and CEO said. “We look forward to working with the FDA to align on a phase 3 program in PTSD.”1
Transcend Therapeutics announces primary endpoint met in IMPACT-1 phase 2 study of TSND-102 in PTSD. News release. Transcend Therapeutics. March 31, 2025. Accessed April 1, 2025. https://transcendtherapeutics.com/impact-1-primary-endpoint-met/
2. Post-traumatic stress disorder (PTSD). National Institute of Mental Health. https://www.nimh.nih.gov/health/statistics/post-traumatic-stress-disorder-ptsd
