Major depressive disorder (MDD) shows marked sex differences in prevalence, symptomatology, and treatment response. However, females remain underrepresented in many clinical trials, and sex-specific treatment outcomes are rarely examined. This study reanalyzed data from a randomized controlled trial comparing psilocybin and escitalopram for MDD to evaluate sex differences across multiple...
Neuroplasticity, the brain's capacity to reorganise its structure and function, is a transdiagnostic feature across psychiatric and neurodegenerative diseases and a putative mechanism of action for pharmacological interventions. [11C]-UCBJ positron emission tomography (PET), which quantifies synaptic vesicle glycoprotein 2A (SV2A) density, offers the most direct in vivo measure of human...
PsychopharmacologySeptember 29, 2026Praneet Suresh, Josie Kins, Lex Levkovskyy et al.
Psychedelics exhibit rapid, durable therapeutic effects across diverse psychiatric conditions, yet their broad-spectrum psychoactivity poses challenges for clinical translation. As a proof-of-concept, we aimed to quantify associations between 19 neurotransmitter receptors and the subjective effects of 21 psychedelic drugs with broadly assayed binding profiles. We used a custom Global Vectors...
Brain ResearchSeptember 7, 2026Eleni Kroupi, Helena Araujo, Cas Oosterveld et al.
N,N-Dimethyltryptamine (DMT), a potent serotonin-2A receptor agonist, elicits intense psychedelic experiences and has become a focus of interest in neuroscience and mental health research. While EEG studies of psychedelics typically report reduced alpha power, increased delta power, and enhanced signal complexity-primarily assessed using Lempel-Ziv complexity (LZc)-less is known about DMT's...
Abstract Psychiatric trials typically define success as symptom reduction, yet patients prioritize meaning, vitality, and functioning. This imbalance undervalues experiential benefits, distorting clinical, policy, and FDA decisions. Psychedelic trials illustrate this, where robust well-being gains sometimes accompany modest symptom effects. We argue well-being should be elevated to co-primary...
The contribution of patient support to psilocybin's antidepressant effects remains uncertain. Relationships between therapeutic alliance (Scale to Assess Therapeutic Relationship-Patient version; STAR-P), psychedelic experience (Five-Dimensional Altered States of Consciousness Questionnaire and Emotional Breakthrough Inventory; 5D-ASC and EBI) and clinical outcomes (Montgomery-Åsberg Depression...
Abstract Psychedelic drugs exert rapid and profound effects on human consciousness [1–7] and are increasingly being investigated for their therapeutic potential [8–14]. Yet the transcriptional programs through which they may reshape brain function and structure remain incompletely understood, in part because the available evidence is heterogeneous and largely preclinical [15, 16]. In a...
Background Anorexia nervosa is a debilitating eating disorder with high mortality and chronicity rates owing to the paucity of effective existing treatments. Several clinical trials using psilocybin therapy have demonstrated therapeutic efficacy and safety in psychiatric conditions, including anorexia nervosa. Aims This study aimed to further assess the safety, feasibility and potential...
Psilocybin has been shown to induce fast and sustained symptoms improvements across various psychiatric conditions, yet its long-term mechanisms of action are not fully understood. Initial evidence suggests that longitudinal functional and structural brain changes implicate fronto-striatal-thalamic (FST) circuitry, a broad system involved in goal-directed behavior and motivational states. Here,...
Abstract A central challenge in neuroscience is understanding how the human brain is organised to support optimal functioning and adaptability. One approach to characterise complex brain dynamics is by artificially perturbing whole-brain models. Here, we asked whether whole-brain organisation under perturbation in major depressive disorder (MDD) changes after intervention with psilocybin and...
Abstract Rationale: Major depressive disorder (MDD) shows marked sex differences in prevalence, symptomatology, and treatment response. However, women remain underrepresented in many clinical trials, and sex-specific treatment outcomes are rarely examined. Objectives This study reanalyzed data from a randomized controlled trial comparing psilocybin and escitalopram for MDD to evaluate sex...
Abstract In recent decades, the psychedelic psilocybin has been studied as a potential treatment for major depressive disorder (MDD), offering an alternative to traditional antidepressants. However, the brain changes underlying the clinical effects of different interventions remain unclear. Here, we investigated the effects of psilocybin and a conventional antidepressant, escitalopram, from the...
A general account of how diverse states of consciousness arise from brain activity requires a quantitative framework that generalises across them. The Entropic Brain Theory proposes that states of consciousness can be ordered along a single dimension defined by the entropy of spontaneous neural activity, but this prediction has not been tested across pharmacological and clinical perturbations...
Background: Traumatic brain injury (TBI) can result in prolonged post-concussive syndrome and chronic hypoxic-ischemic brain injury (HIBI) sequelae remains therapeutically challenging with the persistence of significant neurological and cognitive impairments. While conventional treatments often provide limited relief, emerging research explores alternative therapeutic interventions, including...
Minimal Phenomenal Experiences (MPEs) are states of consciousness in which wakefulness is preserved but phenomenal content is low or absent. The Entropic Brain Hypothesis (EBH) is a model of conscious processes that regards the entropy of spontaneous brain activity as a marker of 'phenomenal richness', exemplified by high-content psychedelic experiences (HCPEs). Yet recent human neuroimaging...
First-line dictionary definitions of ‘plasticity’ describe it as the ability (of a thing) to be shaped or molded; we call this ‘plasticity proper’. In neuroscience, however, ‘neural plasticity’ or ‘neuroplasticity’ is defined as an induced change in brain function or structure. These two plasticities are not the same. Several (but not all) popular biomarkers of neuroplasticity index part of an...
Previous research suggests that psychedelics may, under certain conditions, decrease authoritarian attitudes, but larger and more rigorously designed studies are needed to confirm these findings. We aimed to examine the effects of psychedelic use on authoritarian attitudes. Using data from three separate studies with different designs and populations, we investigated the relationship between...
Philosophical PsychologyApril 10, 2026Eric Rundquist, Diego Nicolás Monasterio López, Juan Jonathan Oyarzo Alvarado et al.
This article presents the results of a Cognitive Linguistic analysis of metaphors used in a series of interviews by a single healthy volunteer following four moderate-to-high dosing sessions with psilocybin. The interviews were conducted by members of a human psychedelic research lab in a deep-sampling fMRI and EEG brain imaging study, allowing the participant to recount experiences under the...
Psychedelic drugs are re-emerging as promising scientific and clinical tools. However, despite a rapidly expanding literature on their therapeutic value, the neural mechanisms underlying psychedelic effects remain unclear. Resting-state functional magnetic resonance imaging studies of acute psychedelic effects, conducted independently by several research groups, have so far yielded fragmented...
Obsessive–compulsive disorder (OCD) is a psychiatric condition with high rates of treatment resistance. Emerging neuroimaging evidence implicates dysfunction in large-scale brain networks, particularly the cortico–striatal–thalamo–cortical (CSTC) circuit, default mode network (DMN) and salience network (SN). Lysergic acid diethylamide (LSD) and psilocybin induce acute dysregulation of the DMN...
Despite being induced by a transient pharmacological exposure, psychedelic experiences can catalyze enduring psychological transformation, presenting a central challenge for understanding the mechanism of action of psychedelic medicines. To address this challenge, the Allostatic Reset Model (ARM) of psychedelic action is proposed, which conceptualizes psychedelic therapeutic effects as a...
We investigated ketamine's neuroplastic effects in healthy human subjects using integrated Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI) measures before and 1-8 days after a single psychedelic dose of ketamine (1 mg/kg, intravenous). Eleven male participants underwent two PET/MRI scans with [11C]-UCBJ (synaptic density/plasticity), 1H-MRS (glutamate and GABA) and...
Upwards of 50% of people do not respond to the primary treatment modalities for major depressive disorder (MDD), which has led to increased attention and use of alternative methods, including exercise and psychedelics. While interventions using either exercise or psychedelics have demonstrated largely positive results in isolation, their synergistic potential has yet to be explored. As such,...
Abstract Psychedelics profoundly alter conscious experience, yet how they reshape the relationship between brain anatomy and function remains unclear. In particular, it is unknown whether psychedelic states reflect a global disruption of structure–function organization or a frequency– and network-specific reconfiguration of neural dynamics relative to the structural connectome. Here we address...
BACKGROUND: The quality and valence of psychedelic experiences are influenced by a range of psychological and contextual factors. This study examines baseline mood and the "relational triad"-comprising social connectedness, mindfulness, and spirituality-as potential predictors of the quality of naturalistic psychedelic experiences. METHODS: Data were drawn from the Predicting Responses to...