Neural Mechanisms and Psychology of Psychedelic Ego Dissolution

Abstract

Neuroimaging studies of psychedelics have advanced our understanding of hierarchical brain organisation and the mechanisms underlying their subjective and therapeutic effects. The primary mechanism of action of classic psychedelics is binding to serotonergic 5HT2A receptors. Agonist activity at these receptors leads to neuromodulatory changes in synaptic efficacy that can have a profound effect on hierarchical message passing in the brain. Here, we review the cognitive and neuroimaging evidence for the effects of psychedelics; in particular, their influence on selfhood and subject-object boundaries—known as ego dissolution—surmised to underwrite their subjective and therapeutic effects. Agonist of 5HT2A receptors, located at the apex of the cortical hierarchy may have a particularly powerful effect on sentience and consciousness. These effects can endure well after the pharmacological half life, suggesting that psychedelics may have long-term effects on neural plasticity – that may play a role in their therapeutic efficacy. Psychologically, this may be accompanied by a surrender of ego resistance that increases the repertoire of perceptual hypotheses, including those that undergird selfhood. We consider the interaction between serotonergic neuromodulation and sentience through the lens of hierarchical predictive coding, which speaks to the value of psychedelics in understanding how we make sense of the world—and specific predictions about effective connectivity in cortical hierarchies that can be tested using functional neuroimaging.

Changes in both top-down and bottom-up effective connectivity drive visual hallucinations in Parkinson’s disease

“…Interestingly, changes in thalamic resting state functional connectivity 58 , as well as changes in thalamocortical effective connectivity 59 may also underlie hallucinations during exposure to LSD, consistent with a more general role for changes in thalamic connectivity in hallucinations in other contexts 60 .…”

“…Two separate pathways may exist for this, with low-signal-related uncertainty (as would be expected with reduced bottom-up sensory input) resolved by dopaminergic projections from medial thalamus that increase prefrontal output 57 . Interestingly, changes in thalamic resting state functional connectivity 58 , as well as changes in thalamocortical effective connectivity 59 may also underlie hallucinations during exposure to LSD, consistent with a more general role for changes in thalamic connectivity in hallucinations in other contexts 60 .…”

Reduced Precision Underwrites Ego Dissolution and Therapeutic Outcomes Under Psychedelics

“…Classic psychedelics, including psilocybin and lysergic diethylamide acid (LSD), at sufficient doses, can induce a range of subjective effects that include visual alterations ( Studerus et al, 2012 ), altered perception of time ( Wittmann et al, 2007 ) and shifts in attention and perspective that reframe the relationship of self with the world ( Swanson, 2018 ). This latter phenomenon, known as ego dissolution , is suggested to be the fundamental feature of classic psychedelic psychoactive effects ( Stoliker et al, 2021 ). Ego dissolution, or the shift in sense of self and dissolution of boundary between the self and world ( Lebedev et al, 2015 ; Millière, 2017 ), has been validated as a measurable construct on the Ego Dissolution Inventory 1 ( Nour et al, 2016 ), with evidence suggesting that therapeutic outcomes are tied to its occurrence 2 ( Garcia-Romeu et al, 2014 ; Majic et al, 2015 ; Carhart-Harris and Goodwin, 2017 ; Roseman et al, 2018 ; Yaden and Griffiths, 2020 ).…”

Psychedelic replications in virtual reality and their potential as a therapeutic instrument: an open-label feasibility study

“…There was a significant decrease in EST-Q2 scores at the two week follow-up (M = 10.73, SD = 3.66; paired samples t-test, t( 10 One important facet of subjective experiences that could be instrumental for therapeutic benefits is the insight experience 5,32,40,41 . The Psychological Insight Questionnaire 40 Another aspect of subjective experience that has been suggested to underlie the beneficial effects of psychedelic therapy is ego dissolution 32,38,114 , measured here by the Ego-Dissolution Inventory 109 (EDI). EDI scores increased from M = 34.81 (SD = 20.42) at baseline to M = 42.66 (SD = 28.23) post-experiment, but the change was not statistically significant (t(11) = 1.34, p = 0.207, Cohen's d = 0.39).…”

“…As the demonstrative VR was in a small room with a balcony view onto a mountain range the participant felt it to be very personally meaningful. Third, one of the potential mediators of the beneficial effects of psychedelic experiences as well as a crucial element of mystical experiences 32,38,114 egodissolution, might be induced to some degree in any VR experience with an altered image of the body 156,157 . While the EDI did not show a significant change from baseline, half of the participants showed relatively high (a score of over 40) results even after the demo experience on the first day and several participants mentioned alterations in their sense of self during the integrative sessions.…”