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Robert C. Malenka

Stanford University

7 papers in the library · 201 citations · publishing 2016-2025

Papers

Distinct neural mechanisms for the prosocial and rewarding properties of MDMA

Science Translational Medicine December 11, 2019 Boris D. Heifets, Juliana S. Salgado, Madison Taylor et al. 119 citations

MDMA's prosocial effects can be separated from its addictive properties by using fenfluramine, a selective serotonin-releasing compound. This finding reveals a conserved neuronal pathway that could be targeted to develop new therapeutics with limited abuse liability, offering a potential strategy for creating safer treatments that promote social connection without the risks of addiction.

Disruptive Psychopharmacology

JAMA Psychiatry June 26, 2019 Boris D. Heifets, Robert C. Malenka 28 citations

Methylenedioxy-methamphetamine (MDMA) and psilocybin may offer therapeutic benefits for mental health conditions, but their approval for treatment would require establishing appropriate mental health care infrastructures. This includes trained therapists, treatment protocols, and regulatory frameworks to ensure safe and effective use. The authors outline the necessary preparations for integrating these substances into clinical practice.

UNRAVELing the synergistic effects of psilocybin and environment on brain-wide immediate early gene expression in mice

bioRxiv (Cold Spring Harbor Laboratory) February 21, 2023 Daniel Ryskamp Rijsketic, Austen B. Casey, Daniel A. N. Barbosa et al. 10 citations preprint

Psilocybin, given to mice in either their home cage or an enriched environment, increased neural activity in brain regions including the neocortex, caudoputamen, central amygdala, and parasubthalamic nucleus while decreasing activity in the hypothalamus, cortical amygdala, striatum, and pallidum. The effects of both the drug and the environment were strong and widespread but largely independent, with very few interactions between context and psilocybin treatment. This suggests that the brain's response to psilocybin is not strongly modulated by environmental setting at the level of immediate early gene expression.

Psilocybin has no immediate or persistent analgesic effect in acute and chronic mouse pain models

bioRxiv (Cold Spring Harbor Laboratory) July 7, 2025 Akila Ram, Austen B. Casey, Robert C. Malenka et al. 2 citations preprint

Psilocybin does not produce direct analgesic effects in mice, despite suggestions from clinical and preclinical data that it might help chronic pain. Across multiple pain assays and models of acute and chronic inflammatory, neuropathic, and musculoskeletal pain, no dose of psilocybin was analgesic. The finding indicates that any therapeutic benefits for chronic pain syndromes are unlikely to come from direct pain relief.

CNSC-36. PSILOCYBIN INDUCES SUSTAINED GLIOMA GROWTH THROUGH SEROTONERGIC AND TRKB PATHWAYS

Neuro-Oncology November 1, 2025 Richard Drexler, Belgin Yalçın, Rebecca Mancusi et al.

High-grade gliomas integrate into serotonergic circuits via dorsal and median raphe projections, which drive calcium-mediated proliferation. Psilocybin, a serotonergic psychedelic selective for 5-HT2A with activity at TrkB, significantly increased proliferation in glioblastoma and DMG xenografts after a single dose, with effects persisting for at least two weeks. Calcium transients in glioma cells appeared within 30 minutes and remained detectable for two weeks. Genetic knockout of 5-HT2A nearly abolished psilocybin-induced proliferation, while TrkB knockout partially reduced it. These findings indicate that psilocybin promotes sustained glioma growth primarily through 5-HT2A activation, with a modulatory role for TrkB, suggesting caution for clinical use in brain tumor patients.