Emotions and brain function are altered up to one month after a single high dose of psilocybin

Frederick S Barrett,Manoj K Doss,Nathan D Sepeda,James J Pekar,Roland R Griffiths

doi:10.1038/s41598-020-59282-y

Frederick S Barrett, Manoj K Doss + Show 3 more

Open Access

https://doi.org/10.1038/s41598-020-59282-y

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Abstract

Psilocybin is a classic psychedelic compound that may have efficacy for the treatment of mood and substance use disorders. Acute psilocybin effects include reduced negative mood, increased positive mood, and reduced amygdala response to negative affective stimuli. However, no study has investigated the long-term, enduring impact of psilocybin on negative affect and associated brain function. Twelve healthy volunteers (7F/5M) completed an open-label pilot study including assessments 1-day before, 1-week after, and 1-month after receiving a 25 mg/70 kg dose of psilocybin to test the hypothesis that psilocybin administration leads to enduring changes in affect and neural correlates of affect. One-week post-psilocybin, negative affect and amygdala response to facial affect stimuli were reduced, whereas positive affect and dorsal lateral prefrontal and medial orbitofrontal cortex responses to emotionally-conflicting stimuli were increased. One-month post-psilocybin, negative affective and amygdala response to facial affect stimuli returned to baseline levels while positive affect remained elevated, and trait anxiety was reduced. Finally, the number of significant resting-state functional connections across the brain increased from baseline to 1-week and 1-month post-psilocybin. These preliminary findings suggest that psilocybin may increase emotional and brain plasticity, and the reported findings support the hypothesis that negative affect may be a therapeutic target for psilocybin.

Highlights

Psilocybin is a classic psychedelic compound that may have efficacy for the treatment of mood and substance use disorders
Post-hoc tests demonstrated that DASS stress, PANAS negative affect, State and Trait Anxiety Inventory (STAI) state anxiety, and Profile of Mood States (POMS) tension, depression, and total mood disturbance scale scores were significantly lower 1 week after psilocybin compared to baseline and returned towards baseline ratings 1 month after psilocybin (Table 1)
The current open-label pilot study identified four key sustained effects of a single high dose of psilocybin on affect and the neural correlates of affective processing

Summary

Introduction

Psilocybin is a classic psychedelic compound that may have efficacy for the treatment of mood and substance use disorders. The number of significant resting-state functional connections across the brain increased from baseline to 1-week and 1-month post-psilocybin These preliminary findings suggest that psilocybin may increase emotional and brain plasticity, and the reported findings support the hypothesis that negative affect may be a therapeutic target for psilocybin. Areas within the anterior cingulate cortex (ACC) are understood to monitor cognitive conflict[19,20,21,22], are involved in the appraisal and expression of negative emotion[22], respond to distress levels associated with pain[23] and negative social affect[24], and have been implicated in negative rumination and depression[25] Both amygdala and ACC dysfunction have been implicated in the pathophysiology of substance use disorders[12] and have been implicated in supporting aberrant negative affect in these disorders. Other reports identify increased “connection to life,” increased meaning-making[36], and changes in other higher-level psychological factors[37], as well as engagement with music[38], as potential mechanisms underlying treatment efficacy

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