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Blake Mandell

3 papers in the library · 23 citations · publishing 2023-2026

Papers

Methylone, a rapid acting entactogen with robust anxiolytic and antidepressant-like activity

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.

Efficacy and Safety of the Neuroplastogen TSND-201 for the Treatment of PTSD: A Randomized Clinical Trial.

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.

Methylone is a rapid-acting neuroplastogen with less off-target activity than MDMA

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.