Evidence map›Paper›PMID 40849539›Full record

ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2026

Methylone promotes neurite outgrowth and has long-lasting effects on fear extinction learning.

Jennifer Warner-Schmidt, Martin Stogniew, Blake Mandell, Benjamin Kelmendi

Abstract read
In one paragraph

Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Trial
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Jennifer Warner-SchmidtTranscend Therapeutics, New York, NY, USA. jennifer@transcendtherapeutics.com.
Martin StogniewTranscend Therapeutics, New York, NY, USA.
Blake MandellTranscend Therapeutics, New York, NY, USA.
Benjamin KelmendiTranscend Therapeutics, New York, NY, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Post-traumatic stress disorder (PTSD) is a prevalent and debilitating disorder, and available treatments are limited. TSND-201 (methylone) is in clinical trials for PTSD, showing potential to have rapid, robust and long-lasting benefit without direct agonist/antagonist activity at 5HT2A. Alterations in structural neuroplasticity are a well-studied mechanism that may underlie both the pathophysiology and treatment of PTSD. Previous work showed that methylone rapidly induced neuroplasticity-related factors in PTSD-relevant brain areas. The current study was undertaken to determine whether methylone affected structural neuroplasticity (e.g., neurite outgrowth) and whether its effects may also be long-lasting. Methylone stimulated neurite outgrowth, specifically increasing the number of branches and the length of the longest neurite per cell in cultured cortical neurons. Methylone's effect on neurite branching was blocked by inhibitors of monoamine transporters (reboxetine, escitalopram, JHW-007) whereas its effects on the length of the longest neurite per cell were mediated by trkB receptors or mTor signaling. RNA-seq and functional enrichment analyses suggest that methylone has long-lasting effects on factors that mediate neurite outgrowth. Rapid and long-lasting effects of methylone on fear extinction learning and memory were also observed, consistent with the rapid and long-lasting neuroplasticity effects. Reboxetine blocked methylone's improvement of extinction recall memory, suggesting NET activity is required for methylone's behavioral effect. Together, this work provides insight into methylone's mechanism of action and evidence that rapid-acting pharmacotherapies that induce structural neuroplasticity may have potential to treat PTSD.

Indexed as

Extinction, PsychologicalFearNeuronal OutgrowthAnimalsCells, CulturedMaleMiceMice, Inbred C57BLRatsRats, Sprague-DawleyReceptor, trkBReceptor, trkB

Identifiers

PMID40849539
PMCPMC12823647

What Socratic holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.