Pharmacological Reviews
September 9, 2022
Devon Stoliker, Adeel Razi, Gary F. Egan et al.
83 citations
Classic psychedelics work primarily by binding to serotonergic 5-HT2A receptors, and their agonist activity at these receptors changes synaptic efficacy, profoundly affecting hierarchical message-passing in the brain. This review synthesizes cognitive and neuroimaging evidence showing that psychedelics influence selfhood and subject-object boundaries—a phenomenon called ego dissolution—which may underlie their subjective and therapeutic effects. Because 5-HT2A receptors sit at the apex of the cortical hierarchy, their agonism may powerfully affect sentience and consciousness. Effects can last beyond the pharmacological half-life, suggesting psychedelics promote neural plasticity. Psychologically, they may disarm ego resistance, expanding the repertoire of perceptual hypotheses and enabling alternate pathways for thought and behavior. The authors interpret these effects through hierarchical predictive coding, offering testable predictions about effective connectivity in cortical hierarchies.
Biological Psychiatry
January 5, 2024
Devon Stoliker, Leonardo Novelli, Adeel Razi et al.
42 citations
Temporary reduction in amygdala signaling is linked to changes in how brain networks connect at rest. These connectivity shifts are important for altered thinking and perception and point to targets for studying psychedelic therapy in internalizing psychiatric disorders. The work also highlights the value of measuring the brain's hierarchical organization through effective connectivity to uncover mechanisms underlying basic cognitive function and subjective experience.
bioRxiv (Cold Spring Harbor Laboratory)
March 11, 2025
Devon Stoliker, Leonardo Novelli, Moein Khajehnejad et al.
8 citations
preprint
Psychedelics like psilocybin alter consciousness by reorganizing brain connectivity in a context-sensitive way. In the largest psychedelic neuroimaging dataset to date, 62 adults underwent functional MRI and EEG before and after ingesting 19 mg of psilocybin, during rest and naturalistic stimuli. Under psilocybin, brain signals during eyes-closed conditions became similar to those during eyes-open conditions, with increased global functional connectivity in associative regions and decreased connectivity in sensory areas. Machine learning linked subjective effects to structured neural activity patterns. Stronger self-dissolving effects were associated with more distinct neural representations and next-day mindset changes, revealing a state of 'embeddedness' where networks that usually segregate internal and external processing integrate coherently, aligning neural dynamics with context.
medRxiv
September 9, 2022
Devon Stoliker, Katrin H. Preller, Leonardo Novelli et al.
5 citations
preprint
A double-blind, placebo-controlled study of 24 healthy adults found that psilocybin, the active compound in magic mushrooms, alters visual brain connectivity in ways consistent with preclinical models. Under psilocybin, early visual and higher visual-association regions showed increased self-inhibition, while top-down feedback from association areas to earlier visual regions was enhanced. These connectivity changes were linked to decreased sensitivity to neural inputs and the perception of eyes-closed visual imagery. The findings suggest that psilocybin-induced visual imagery arises from reduced bottom-up gain and strengthened top-down influences, informing basic and clinical understanding of visual perception.
medRxiv
September 9, 2022
Devon Stoliker, Leonardo Novelli, Franz X. Vollenweider et al.
4 citations
preprint
Psilocybin reduces the brain's top-down control from resting state networks to the amygdala, which is involved in emotion appraisal and regulation. In a randomized, double-blind, placebo-controlled trial of 24 healthy adults given 0.215 mg/kg psilocybin, effective connectivity decreased from the default mode network and salience network to the amygdala, and within the DMN and SN, while connectivity within the central executive network increased. These changes were linked to altered emotion and meaning under the drug, suggesting that attenuation of the amygdala signal may serve as a biomarker for psilocybin's therapeutic effects in conditions like addiction and depression.