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Investigating Emotional Reactivity in Experienced Users of Psychedelics: A Cross‐Sectional fMRI Study

Paweł Orłowski, Aleksandra Domagalik, Michał Bola

Human Brain Mapping April 1, 2026 DOI: 10.1002/hbm.70522 (opens in new tab)

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Characteristics Cross-sectional fMRI study Preregistered Peer reviewed
Sample size 67
Population Experienced psychedelic users (≥ 10 lifetime uses) and matched nonusers
Topics Default mode network
Keywords Precuneus Facial expression Anger Reactivity psychology Emotional expression Salience neuroscience Emotion perception Feeling Cognitive psychology Neuroimaging Emotional valence Dissociation chemistry Developmental psychology Subliminal stimuli Emotional behavior Emotional regulation
Key findings Experienced psychedelic users showed enhanced behavioral recognition of angry expressions and altered neural responses to emotional faces, including reduced limbic and salience network activation to anger and increased sensorimotor responses to happiness.

Abstract

Classic psychedelics profoundly alter emotional states, inducing intense acute experiences lasting hours, followed by subtler, longer-lasting changes in emotional reactivity that can persist for weeks. While experimental and clinical studies document these prolonged effects, the highly context-dependent nature of psychedelic experiences leaves open the question of whether naturalistic, nonclinical use similarly modulates emotional processing. To investigate this, we conducted a preregistered, cross-sectional fMRI study comparing experienced psychedelic users (≥ 10 lifetime uses; N = 33) with closely matched nonusers (N = 34). Participants performed an emotional face recognition task, and we examined behavioral performance and neural responses to angry, happy, and fearful facial expressions. Behavioral results revealed that psychedelic users recognized angry expressions more quickly and accurately, indicating enhanced processing efficiency for threat-related stimuli. Consistent with this, whole-brain fMRI analyses showed reduced activation to anger in key limbic and salience network regions. Psychedelic users also exhibited heightened responses to happy expressions in parietal and sensorimotor cortices-aligning with prior clinical observations-as well as increased precuneus activation to fearful expressions. Region-of-interest analyses further demonstrated reduced differentiation between emotional categories in two default mode network nodes: the frontal medial cortex and parahippocampal gyrus. These findings provide a nuanced characterization of neurofunctional changes in emotional processing linked to repeated naturalistic psychedelic use. By bridging clinical and real-world contexts, this work deepens our understanding of the potential long-term consequences of psychedelics and complements existing evidence from controlled therapeutic settings.

Comparable studies

Other experimental studies on default mode network, most cited first.

Study Year Design Participants
Functional connectivity of default mode network components: Correlation, anticorrelation, and causality Healthy subjects 2008 Observational study using resting-state fMRI and seed correlation analysis
Patterns of Brain Activity Supporting Autobiographical Memory, Prospection, and Theory of Mind, and Their Relationship to the Default Mode Network Healthy subjects 2009 Experimental study using fMRI
Dynamic reconfiguration of the default mode network during narrative comprehension Human subjects 2016 Experimental study
Broadband Cortical Desynchronization Underlies the Human Psychedelic State Healthy human participants 2013 Experimental study
The brain on art: intense aesthetic experience activates the default mode network Human observers 2012 Observational study with fMRI and behavioral analysis

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