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

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 psylocibin 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 psylocibin include serotonin receptors. Specifically, psylocibin 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.

Analysis of Psilocybin-Assisted Therapy in Medicine: A Narrative Review

“…These drugs are currently controversial for their hallucinogenic effects and recreational use; however, their resemblance to tryptophan enables them to act as serotonin agonists and activate 5HT receptors, mainly the 5HT-2A receptor [5]. This effect makes them promising candidates in the treatment of substance abuse disorders as well as mood disorders [6]. This is due to the fact that substance use disorder (SUD) is the manifestation of several neurophysiological mechanisms including the dopaminergic pathways of the striatum (reward center), 5-HT pathways connecting with the striatum, and the corticotropinreleasing hormone (CRH) pathway, which drives the hypothalamic-pituitary-adrenal (HPA) axis [7].…”

“…The structure of psilocybin is such that it cannot cross the blood-brain barrier. Its metabolite psilocin, however, is more lipophilic and therefore more active [6]. The active metabolite can be found 20-40 minutes after ingestion as psilocybin is quickly converted to its metabolite in the stomach acid or via first-pass metabolism with a bioavailability of around 50% and a half-life of 2.5 hours [6].…”

“…In such instances, there is a compensatory upregulation in the metabotropic glutamate receptors (mGluR2/3) due to the inverse relationship between mGluR2/3 and 5HT-2A receptors [5]. The stimulation of 5HT-2A receptors on pyramidal cells in levels V and VI in the cortex by psilocin, a metabolite, leads to the release of glutamate in the prefrontal cortex [6].…”

“…On the other hand, psilocybin's effects at the 5HT receptors are responsible for decreased depression and suicidal behaviors, as well as increased memory and learning [11]. Further, it is believed that psilocin's activation of the 5HT-2A receptor is responsible for increased release of dopamine from the striatum, which is capable of regulating the defective reward pathway in patients who suffer from depression and with suicidal ideation [6].…”

New Paradigms of Old Psychedelics in Schizophrenia

“…Psilocybin has been reported to modulate the thoughts and behavioural patterns in individuals who are at risk of suicidal behaviours. The mode of action of psilocybin is suggested to be the regulation of major pathways linked with suicidal behaviours which are affected by directly activating serotonin 5HT 2A receptors, and also, targeting the inflammatory and oxidative stress pathways leading to neuronal plasticity, and suppression of inflammation and increase in cognitive flexibility [ 77 ]. Recently, the FDA has dubbed psilocybin as a breakthrough medicine for the treatment of resistant depression [ 78 ].…”