Neurochemical, Neurocircuitry, and Psychopathological Mechanisms of PTSD: Emerging Pharmacotherapies and Clinical Perspectives.
Santosh Kumar Prajapati, Shreyasi Majumdar, Snehapriya Murari, Kirti MachhindraVadak, Sairam Krishnamurthy
ACS chemical neuroscience June 10, 2025 DOI: 10.1021/acschemneuro.5c00335 via PubMed
Summary
AI-generated from the abstractPTSD involves complex disruptions in brain circuits, stress hormone regulation, and multiple neurotransmitter systems including serotonin, glutamate, and GABA. This review describes how the hypothalamic-pituitary-adrenal axis, monoamines, and orexinergic system contribute to the disorder. Emerging treatments discussed include MDMA, ketamine, suvorexant, and cannabinoid modulators, alongside established psychotherapies like cognitive-behavioral therapy. By integrating findings from original research, clinical trials, and reviews published between 1950 and 2025, the authors provide a consolidated framework for understanding PTSD pathophysiology and highlight potential targets for personalized therapies.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Topics | MDMA PTSD Serotonin |
| Keywords | Glutamatergic system Hypothalamic–pituitary–adrenal-axis Neurocircuitry |
| Citations | 14 |
| Key finding | PTSD involves complex neurobiological anomalies across the HPA axis, monoamines, glutamate, GABA, and orexinergic systems, with emerging pharmacological targets including MDMA, ketamine, suvorexant, and cannabinoid modulators. |
Abstract
Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition triggered by exposure to traumatic events, with complex neurobiological anomalies that remain incompletely understood. This review aims to comprehensively explore the neurocircuitry, neurochemical dysregulation, and emerging pharmacological targets associated with PTSD, offering a consolidated framework for developing more effective treatments. Particular emphasis is employed on the role of the hypothalamic-pituitary-adrenal (HPA) axis, monoamines, glutamate, GABAergic, and the orexinergic system, as well as emerging therapeutic agents such as 3,4-methylenedioxymethamphetamine (MDMA), ketamine, suvorexant, and cannabinoid modulators. Psychotherapeutic approaches including cognitive-behavioral therapy (CBT) and prolonged exposure therapy are also discussed in the context of their neurobiological effects. Articles were identified through a structured search in PubMed, Scopus, and Google Scholar, focusing on English-language publications from 1950 to 2025. Inclusion criteria encompassed original research, clinical trials, and reviews relevant to PTSD mechanisms and treatment. By integrating recent findings, this review advances the understanding of PTSD pathophysiology and highlights potential avenues for targeted, personalized therapies, thereby contributing to clinical and translational research in neuropsychiatry.