The relation between naturalistic use of psychedelics and perception of emotional stimuli: An fMRI study

Abstract

Classic psychedelics, such as psilocybin, LSD (lysergic acid diethylamide), and DMT (N,N-Dimethyltryptamine), are known for inducing altered states of consciousness characterized by significant changes in sensory perception, reality perception, mood, thoughts, and sense of self. A growing body of evidence suggests that these substances can also lead to long-lasting psychological benefits, including enhanced well-being, improved quality of life, and reduced symptoms of depression and anxiety. A notable effect of psychedelics is their ability to attenuate emotional reactivity, particularly in response to negative emotions, which is linked to reduced activation of the amygdala (e.g. Kraehenmann et al., 2015; Mueller et al., 2017). This reduction in reactivity to stimuli characterized by negative valence may contribute to the observed increases in well-being and antidepressant effects. However, few studies have examined whether regular use of psychedelics leads to long-term changes in emotional processing. Our previous research (Orlowski et al., 2022) has demonstrated that regular psychedelic users exhibit greater positive emotional reactivity and lower negative emotional reactivity compared to those who have never tried psychedelics, as evidenced by a cross-sectional questionnaire study. In a 2023 study using EEG (Orlowski et al., 2024), we found that psychedelic users had significantly lower amplitudes of the N170 and N200 ERP components in response to fearful faces, indicating reduced reactivity to negative emotional stimuli at early processing stages. Beyond emotional reactivity, psychedelics are also known to induce changes in brain connectivity. Research has consistently shown that psychedelics reduce functional connectivity within associative networks, such as the Default Mode Network (DMN), while increasing connectivity within sensory and thalamocortical networks (Carhart-Harris et al., 2012; Tagliazucchi et al., 2016). These changes in brain connectivity have been correlated with subjective reports of altered consciousness, including ego dissolution and emotional modulation. Specifically, decreased connectivity within the DMN has been linked to the attenuation of rigid patterns of self-referential thinking, while changes in the Salience Network (SN) have been associated with alterations in how the brain prioritizes emotional and sensory stimuli (Lebedev et al., 2015). Moreover, recent findings suggest that psychedelics may enhance communication between large-scale networks, such as the DMN, SN, and the Central Executive Network (CEN), which could lead to greater cognitive flexibility and emotional regulation (Preller et al., 2019). Building on these findings, the present project aims to further investigate the long-term effects of regular psychedelic use on both emotional reactivity and functional connectivity using functional magnetic resonance imaging (fMRI). We will test whether regular users of classic psychedelics differ from non-users in terms of brain activity evoked by perception of emotional stimuli and changes in functional connectivity patterns.

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