Neural Mechanisms and Psychology of Psychedelic Ego Dissolution

Abstract

Classic psychedelics bind to serotonergic 5-HT2A receptors. Their agonist activity at these receptors leads to neuromodulatory changes in synaptic efficacy, resulting in a profound effect on information processing in the brain. Here, we synthesize an abundance of brain imaging research with pharmacological and psychological interpretations informed by the framework of predictive coding. Moreover, predictive coding is suggested to offer more sophisticated interpretations of neuroimaging findings by bridging the role between the 5-HT2A receptors and large-scale brain networks.

Default Mode Network Modulation by Psychedelics: A Systematic Review

“…It has been hypothesized that ego dissolution can be therapeutic because an individual’s cognitive attributions and affect are viewed with a greater distance and objectivity ( Letheby and Gerrans, 2017 ; Mason et al, 2020 ). Psychedelic-induced ego dissolution may be precipitated via Bayesian belief updating wherein reduced precision of previously held beliefs lends to revision of the self and world, as hypothesized by Stolicker and colleagues (2022) . This has parallels with the practice of meditation, which is also associated with decreased activity of the DMN and alterations to precision-weighting of beliefs and attention ( Brewer et al, 2011 ; Palhano-Fontes et al, 2015 ; Letheby and Gerrans, 2017 ; Millière et al, 2018 ).…”

Effective connectivity of emotion and cognition under psilocybin

“…Agonism of the 5-HT2A receptor is primarily responsible for psychedelic subjective effects that can cause powerful changes to subjective experience (Vollenweider et al 1998; (Kometer et al, 2012) Kometer et al 2013; Preller et al 2017; Kraehenmann et al 2017). Psychedelics can also produce feelings of subjective wellbeing (Hirschfeld & Schmidt, 2020) and profound changes in self-awareness and perception, including visual hallucinations and synaesthesia, and a sense of transcendence of time and space (Studerus, Gamma, & Vollenweider, 2010; Swanson, 2018; Wittmann et al, 2007; (Stoliker, Egan, Friston, & Razi, 2022). Altered (self-)perception and self-awareness are unique effects of serotonergic psychedelics and may involve an experience of ego dissolution, defined as a loss of self-boundaries and sense of unity between the self and the environment (Stoliker, Egan, Friston, & Razi, 2021; Stoliker, Egan, Friston, et al, 2022)Lebedev et al, 2015).…”

“…Psychedelics can also produce feelings of subjective wellbeing (Hirschfeld & Schmidt, 2020) and profound changes in self-awareness and perception, including visual hallucinations and synaesthesia, and a sense of transcendence of time and space (Studerus, Gamma, & Vollenweider, 2010; Swanson, 2018; Wittmann et al, 2007; (Stoliker, Egan, Friston, & Razi, 2022). Altered (self-)perception and self-awareness are unique effects of serotonergic psychedelics and may involve an experience of ego dissolution, defined as a loss of self-boundaries and sense of unity between the self and the environment (Stoliker, Egan, Friston, & Razi, 2021; Stoliker, Egan, Friston, et al, 2022)Lebedev et al, 2015). Although complete ego dissolution is rare at the medium dose potency used in clinical trials, several studies have found that overall blissful ego dissolution (as measured by the total mystical score or oceanic self-boundlessness) is associated with better long-term outcomes in healthy subjects (Griffiths et al, 2011) and reduced symptoms of depression (Griffiths et al, 2016; Roseman, Nutt, & Carhart-Harris, 2018; Ross et al, 2016) and addiction (Bogenschutz et al, 2015; Garcia-Romeu, Griffiths, & Johnson, 2014).…”

“…The dorsal ACC region of the SN is activated in response to social pain (Rotge et al, 2015) that has been associated with changes in self-processing (Smigielski et al 2019; Smigielski et al, 2020) as well as reduced sense of social exclusion under psilocybin (Preller et al, 2016; Preller et al, 2015). Observations under psilocybin have also shown reduced SN integrity (Lebedev et al, 2015) and changes to effective connectivity from the SN to the DMN under LSD (Stoliker, Novelli, et al, 2021). Psychedelics may alter salience functions that select the pre-reflective channels of attention and modulate amygdala connectivity involved in emotional attention and appraisal (Kapur, 2003; Stoliker, Egan, et al, 2021).…”

“…Observations under psilocybin have also shown reduced SN integrity (Lebedev et al, 2015) and changes to effective connectivity from the SN to the DMN under LSD (Stoliker, Novelli, et al, 2021). Psychedelics may alter salience functions that select the pre-reflective channels of attention and modulate amygdala connectivity involved in emotional attention and appraisal (Kapur, 2003; Stoliker, Egan, et al, 2021).…”