In a phase 2 randomized clinical trial, TSND-201 (methylone) reduced PTSD symptoms more than placebo in adults aged 18 to 65. Over 10 weeks, 65 participants received either TSND-201 or placebo in four weekly oral sessions. The drug group showed a significantly greater improvement in the primary measure of PTSD severity (CAPS-5) than placebo, with a difference of about 10 points. Secondary measures of PTSD-related distress, disability, and depression also improved more with the drug. Common side effects included headache, nausea, and increased blood pressure. The results suggest TSND-201 is a well-tolerated, rapid-acting treatment for PTSD.
Methylone, a monoamine uptake inhibitor and releaser currently in clinical development for PTSD, produced rapid changes in gene expression in rat brain areas linked to PTSD and major depressive disorder. In the amygdala, methylone regulated myelin-related genes; in the frontal cortex, it upregulated genes involved in neuroplasticity. Unlike MDMA, methylone showed no off-target activity at 168 tested GPCRs, including 5HT2A and 5HT2C receptors. These results suggest methylone acts as a rapid-acting neuroplastogen with higher specificity and fewer off-target effects than MDMA, supporting its potential for treating PTSD and possibly other neuropsychiatric disorders.