AdolescentsMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Depressive DisordersSuicidalityImmunology & InflammationInterpersonal Functioning & Social ConnectednessPublic Health, Prevention & Behaviour ChangePsilocybin

Psilocybin, a Naturally Occurring Indoleamine Compound, Could Be Useful to Prevent Suicidal Behaviors

This review (2021) presents a framework to understand the basis for using psilocybin to treat individuals with suicidal behaviours. The positive effects psilocybin has on suicidal behaviours are discussed, specifically its role as a 5-HT2A receptor agonist and its ability to increase neuroplasticity and suppress inflammation.

Authors

  • Strumila, R.
  • Guillaume, S.

Published

Pharmaceuticals
meta Study

Abstract

The available interventions for people who are at risk of suicide have limited efficacy. Recently, research on new mental health treatments has started to consider psychedelic compounds, particularly psilocybin, a molecule with a few thousand years of history of use in human societies. The possible effects of psilocybin on suicidal ideation and behaviors have not been specifically studied yet; however, the current knowledge on the suicidal process and the available data on es/ketamine suggest that psilocybin could be used to modulate the thoughts and behavioral patterns in individuals who are at risk of suicidal behaviors. Here, we summarize the available evidence on the possible mechanisms underlying psilocybin positive effects on suicide risk. Major pathways related to suicidal behaviors that might be modulated by psilocybin include serotonin receptors. Specifically, psilocybin directly stimulates the serotonin 2A receptor (5HT2A), targeting the inflammatory and oxidative stress pathways and leading to a rapid increase in brain plasticity and inflammation suppression and increases in cognitive flexibility, spirituality, and empathy. We also present preliminary epidemiological data and provide a rationale for studying psilocybin in individuals with suicidal ideation or who are at risk of suicidal behaviors. This review presents a framework to understand the basis for psilocybin use in individuals who are at risk of suicidal behaviors and calls for clinical studies.

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Research Summary of 'Psilocybin, a Naturally Occurring Indoleamine Compound, Could Be Useful to Prevent Suicidal Behaviors'

Introduction

Research interest in psychedelic treatments has resurged over recent decades, with psilocybin emerging as one of the most intensively studied compounds. Earlier clinical work has associated psilocybin with rapid and sometimes sustained remission of depressive symptoms, prompting the United States Food and Drug Administration to designate psilocybin a “breakthrough therapy” for treatment‑resistant depression. Despite this progress, suicidal behaviours (suicide, suicide attempt) and suicidal ideation are generally treated as manifestations of other psychiatric disorders (most often major depressive disorder), and standard prevention strategies rely on antidepressants and psychotherapy. These approaches have limitations in suicidal populations: suicidal patients often respond less well to classic antidepressants, a minority experience treatment‑emergent or worsening suicidal ideation, some continue to have suicidal ideation despite improvement in depressive symptoms, and effective psychotherapy can be slow, costly, and difficult to access in crisis situations. Strumila and colleagues set out to review the evidence linking psilocybin’s pharmacology and psychological effects to pathophysiological systems implicated in suicidal behaviours, and to present a rationale for studying psilocybin as an intervention to reduce suicidal ideation and prevent suicidal acts. The review focuses on psilocybin’s actions on the serotonergic system (notably 5‑HT2A receptors), neuroplasticity (including BDNF and mTOR pathways), inflammatory and oxidative stress processes, and the psychological changes (e.g., cognitive flexibility, connectedness, autobiographical recall, mystical/quantum experiences) that might mediate clinical benefit. The authors also summarise preliminary epidemiological and clinical findings and outline priorities for future clinical trials.

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