medRxivFebruary 19, 2026Amanda Gow, Emily Shih, Ryan Reid et al.
preprint
Abstract Background In 2020, Oregon became the first U.S. state to establish a regulated framework for adults to access psilocybin services using naturally-derived mushroom products. No studies have examined mental health outcomes among individuals receiving psilocybin in this context. Aims To evaluate changes in self-reported symptoms of depression, anxiety, and well-being 30-days...
Major depressive disorder (MDD) is a leading cause of disability worldwide, yet many patients have inadequate responses to current treatments. Dimethyltryptamine (DMT), a serotonergic psychedelic with rapid onset and short duration, shows promise as a potential antidepressant (AD), although clinical evidence in MDD remains limited. We conducted a phase IIa, double-blind, placebo-controlled,...
Classic psychedelics typically act at the serotonin 5-HT2A receptor to profoundly alter brain function and consciousness. Research on these compounds has accelerated. Major strides have been made in understanding their unique mechanisms of action and clinical potential. This Review outlines the state of psychedelic science, spanning cellular mechanisms, systems neuroscience and clinical...
Abstract Lysergic acid diethylamide (LSD) profoundly alters conscious experience, yet the electrophysiological mechanisms by which it reshapes neural dynamics remain incompletely understood. A hallmark of psychedelic states is widespread cortical desynchronization, typically inferred from reductions in spectral power, but whether such effects reflect genuine weakening of neural oscillations or...
Classic psychedelic drugs, including psilocybin, lysergic acid diethylamide, and ayahuasca/N,N-dimethyltryptamine, are increasingly being studied as therapeutics for myriad health conditions; however, predicting individual responses is notoriously difficult. An arguably underappreciated variable potentially moderating responses to psychedelics is age. Older adults exhibit unique pathogenesis of...
Despite divergent behavioral and phenomenological profiles, both psychedelic states and reduced states of consciousness have been associated with a flattening of the brain's functional hierarchy. To address this apparent paradox, we developed a more specific definition of hierarchy based on the proximity of the brain to thermodynamic equilibrium and then applied it to investigate the changes to...
Under the influence of psychedelics, people often report encountering "entities" who seem to have their own autonomous agency. Depending on the cultural milieu, these entities are reported to take a variety of forms, including spirits, elves, ancestors, or fragments of the self. Encounters with such beings hold a central place in many traditions of psychedelic practice around the world. And...
Psychedelic compound N,N-Dimethyltryptamine (DMT) is renowned for inducing highly immersive experiences, often including encounters with seemingly sentient presences. While such phenomena are well documented, immersion under psychedelics remains conceptually underdefined and phenomenologically underexplored. Here we apply micro-phenomenology to characterize immersion under DMT as a structured...
Background:Adverse childhood experiences (ACEs) are known to contribute to mental health issues and interfere with response to mental health interventions. Psychedelics have been found to improve mental health outcomes; however, the exploration of the effects of psychedelics on mental health in those with higher ACEs remains limited. The present study aimed to examine mental health outcomes and...
Introduced in 2014 and revised in 2018, the entropic brain hypothesis has accrued a wealth of supportive evidence. The hypothesis states that-along a dimension of the size of phenomenal consciousness-expansive states reliably exhibit increased brain entropy whereas the inverse applies for states of no or reduced consciousness. Examples of expansive states include expert meditation, flicker...
Humphry Osmond coined the term ‘psychedelic’ in 1956, conjoining ‘psyche’ for ‘soul’ and ‘delic’ from ‘dêlos’ for ‘to manifest’ or ‘illuminate.’ Soul-illumination is an adjective that describes a psychological state or process. However, Osmond’s intention was to use the adjective to name— not just a state— but a category of drug that can induce the subjective effect as its principal action;...
The mechanism of psychedelic drug action is a dynamic area of neuroscience, with two major lines of investigation: (1) laboratory studies at the molecular and cellular level, and (2) human neuroimaging studies of functional brain networks. Despite considerable progress, there remains insufficient understanding of the link between molecular/cellular substrates of psychedelics and the whole-brain...
Psychedelics profoundly alter subjective experience and brain dynamics. Brain oscillations express signatures of near-critical dynamics, relevant for healthy function. Alterations in the proximity to criticality have been suggested to underlie the experiential and neurological effects of psychedelics. Here, we investigate the effects of a psychedelic substance (DMT) on the criticality of brain...
Abstract Awe is a positive emotion often accompanied by sensations of vastness and unity, with known benefits for well-being and social behavior. However, its neural underpinnings remain poorly understood. We recorded electroencephalography (EEG) and autonomic physiology in 23 healthy older participants while they watched a nature-based audiovisual film and subjectively rated awe events. Awe...
Abstract Disorders of consciousness (DoC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), have limited treatment options and are characterized by low complexity of brain activity. Recent research suggests that psychedelic drugs, which enhance the complexity of brain activity, could offer promising therapies. Here, individualized whole‐brain computational...
The meta-analysis of the 11-dimensional Altered States of Consciousness (11D-ASC) included three studies that contained duplicated data from other papers: Duerler et al. (2021), Lewis et al. (2017), and Preller et al. (2017). When these studies are removed from the analysis, the results are generally similar to the previously reported findings. Out of 33 comparisons (3 doses x 11 dimensions)...
Abstract Recent clinical trial data suggests that ratings on depression scales are lowered after psilocybin therapy compared to placebo, though it is unclear what neuropsychological mechanisms underpin these effects. This study compared psilocybin, with an established antidepressant, escitalopram, to investigate whether there are shared or distinct effects on emotional information processing....
Serotonergic psychedelics and 3,4-methylendioxtmethamphetamine (MDMA) are promising treatments for mental disorders with a continuously evolving evidence base. We searched Pubmed/Scopus/clinical trial registries up to 08july2025 for double-blind randomized controlled trials (RCTs) testing MDMA or serotonergic psychedelics in patients with mental disorders. Primary outcomes were change in...
Although research shows that psychedelic use may lead to improvement in mental health and well-being, the underlying changes in psychological predictors associated with these improvements remain unclear. 161 participants were recruited in a prospective online survey assessing naturalistic psychedelic use. We used lasso regression to assess how 19 distinct changes in psychological variables...
Lysergic acid diethylamide (LSD) and 3,4-Methylenedioxymethamphetamine (MDMA) are widely used psychoactive drugs and their potential use in psychiatric medicine is currently generating interest. The mechanism by which these drugs may assist recovery in various disorders such as addiction and post-traumatic stress disorder (PTSD) is still not well understood. Most investigations of the effects...
This article presents a neuroscientific interpretation of Carl Jung's theory of archetypes and their experience in altered states of consciousness. We begin by rehearsing the Free Energy Principle and Predictive Processing as foundational frameworks that subserve and inform the thesis that follows. The following sections examine three aspects of archetypes: the affective core rooted in...
Abstract Psychedelic drugs exert rapid and profound effects on human consciousness and are increasingly explored for their clinical potential. Yet, the genetic programs through which psychedelics reshape brain function and structure remain incompletely understood, in part because most studies have been conducted in preclinical models and cell cultures. We conducted a systematic literature...
Exploring the intricate relationship between brain's structure and function, and how this affects subjective experience is a fundamental pursuit in neuroscience. Psychedelic substances offer a unique insight into the influences of specific neurotransmitter systems on perception, cognition and consciousness. Specifically, their impact on brain function propagates across the structural connectome...
Psychedelics are undergoing a clinical research renaissance, with compounds such as psilocybin advancing to Phase 3 trials for treatment-resistant depression and receiving fast-track or breakthrough designations from regulatory agencies. Despite this progress, the field lacks standardized terminology to guide clinical development, dosing, safety monitoring, and regulatory classification. Here,...