Identifying Circuit Mechanisms of MDMA and Methylone to Develop Plasticity-Based PTSD Treatment
Abstract
The objectives of the proposed study in Dr. Alfred Kaye’s and Dr. Christopher Pittenger’s laboratories at Yale University are to determine the mechanisms by which MDMA and methylone may induce therapeutic plasticity in PTSD using cutting-edge neural circuits methods. MDMA is expected to be approved as a transformative treatment for PTSD, while similar compounds with distinct effects like methylone are not well understood. Methylone has been administered in two clinical studies in healthy volunteers, is well-tolerated (Poyatos, et al., 2021; Poyatos, et al., 2021b), and recently, Transcend Therapeutics, with headquarters in New York NY received authorization to proceed with an open-label PTSD study in the UK to study TSND-201. A rapid-acting (single treatment), long-lasting (durable), non-hallucinogenic treatment for psychological health condition(s) would support the DOD and/or VA goals of a rapid treatment for psychological health conditions including ASR and PTSD (Focus Area Treat 3a). To develop TSND-201 to its fullest potential and optimize a dosing regimen, additional preclinical research must be conducted to understand methylone’s mechanism of action and impact on neuroplasticity. The need for improved pharmacological treatments for PTSD has been recognized as a crisis by the VA PTSD Pharmacology Working Group (Krystal, et al 2017). While selective serotonin reuptake inhibitors are FDA-approved and show efficacy, 40% of patients may be treatment-refractory (Stein et al., 2002; Zohar et al., 2002). Recently, a phase 3 trial of MDMA augmentation of psychotherapy showed a remarkable effect (d=0.91 on CAPS-5 rating scale, Mitchell et al 2021). MDMA-assisted psychotherapy is based on its effects in enhancing the plasticity, although the precise mechanisms by which this occurs are not well understood. The broader class of potential PTSD treatments, MDMA-like compounds called entactogens, were identified based on similar biochemical effects and because they seemed to produce an enhancement of therapies for dealing with difficult memories. The entactogen methylone (TSND-201) would provide a novel therapeutic with no hallucinogenic treatment affects that would provide another therapeutic tool. A rapid-acting (single treatment), long-lasting (durable), non-hallucinogenic treatment for psychological health condition(s) would support the DOD and/or VA goals of a rapid treatment for psychological health conditions including ASR and PTSD.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310458
Entities
People
- Alfred Kaye
Organizations
- United States Army
- Yale University