Frontiers in Psychiatry
January 10, 2023
Jennifer Warner-Schmidt, Christopher Pittenger, Martin Stogniew et al.
11 citations
Methylone, a rapid-acting entactogen, produced a stronger and more durable antidepressant-like effect in rats than the standard SSRI fluoxetine. A single dose of methylone reduced immobility in the Forced Swim Test by nearly 95% compared to controls, with effects lasting at least 72 hours, whereas three doses of fluoxetine caused a 50% reduction lasting less than 24 hours. Methylone also showed anxiolytic effects, increasing time spent in the center of an open field. Fluoxetine pretreatment did not alter methylone's effects, suggesting possible co-administration. These results indicate methylone may have potential for treating depression and anxiety.
JAMA Psychiatry
May 1, 2026
Amanda Jones, Jennifer Warner-Schmidt, Hannah Kwak et al.
6 citations
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.
Frontiers in Neuroscience
February 7, 2024
Jennifer Warner-Schmidt, Martin Stogniew, Blake Mandell et al.
6 citations
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.
Mol Psychiatry
July 7, 2026
Axel F. Rosado, Abigail L. Yu, Jen-Hau Yang et al.
Psilocybin and MDMA are both psychedelic drugs but produce different behavioral effects. MDMA, but not psilocybin, raises both serotonin and norepinephrine in the medial prefrontal cortex. Blocking norepinephrine release reveals head-twitch responses (a rodent correlate of psychedelic effects) from MDMA, suggesting that noradrenergic signaling opposes serotonin 2A receptor effects. Artificially raising norepinephrine also reduces psilocybin-induced head-twitch responses. Activating the noradrenergic alpha-2 receptor alone suppresses these responses, even in mice lacking the locus coeruleus, indicating action via heteroreceptors. Importantly, alpha-2 receptor activation does not block psilocybin's antidepressant-like effects in the forced swim test. This suggests that side effects of serotonin 2A activation can be reduced without losing therapeutic benefits.