J Pharmacol Exp Ther. 2024 Sep 16:JPET-MR-2024-002237. doi: 10.1124/jpet.124.002237. Online ahead of print.

ABSTRACT

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition that develops following exposure to a traumatic event. Individuals with this condition experience numerous physiological and behavioral alterations, including intrusive memories, avoidance of trauma-related stimuli, heightened anxiety, hypervigilance, impaired cognition, elevated resting heart rate and blood pressure, and altered neuroendocrine function, to name a few. In most patients, currently available pharmacological and psychological treatments are insufficient to alleviate the array of symptoms associated with the disorder. Thus, novel treatment options that can more effectively target the core etiology of PTSD are desperately needed. Recent work demonstrating the psychoplastogenic effects of psychedelics has reinvigorated research to examine their therapeutic potential in psychiatric conditions. Psilocybin, one psychedelic found in the Psilocybe genus of mushrooms, has exhibited promising antidepressant and anxiolytic effects in preclinical and clinical studies. The purpose of this review is to summarize the existing research that has examined the behavioral effects of psilocybin and link it to potential efficacy in treating PTSD-related symptoms. The proposed mechanisms for psilocybin’s effects are then explored, as are the benefits and drawbacks for the agent’s therapeutic use. Finally, the challenges faced by investigators aiming to study psilocybin as a therapeutic aid in future studies are discussed in order to shed light on this budding area of research. Significance Statement Current pharmacotherapy for PTSD is insufficient. Traditional antidepressants and anxiolytics help reduce symptom severity, but nonresponse rates often reach levels greater than 50%, emphasizing the need for more effective treatment options. The goal of this review is to summarize the existing evidence for and the potential mechanisms of the antidepressant and anxiolytic effects of psilocybin, a psychedelic compound found in the Psilocybe genus of mushrooms. We then relate the observed effects to psilocybin’s potential use as a treatment for PTSD.

PMID:39284623 | DOI:10.1124/jpet.124.002237