Healthy VolunteersPsilocybin

Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience

This double-blind, placebo-controlled, randomised, within-subject study (n=36) with four experimental drug conditions, investigated the effects of psilocybin (11.9mg/70kg) in combination with the selective 5-HT1A agonist buspirone (20mg/70kg) and non-hallucinogenic 5-HT2A/1A agonist ergotamine (3mg/70kg), to investigate how the interaction of these serotonin receptor subtypes affect altered states of consciousness. While ergotamine exerted no effect, buspirone selectively inhibited psilocybin-induced visual hallucinations, affective changes, derealization, and depersonalization via activation of 5 -HT1A and/or an interaction between 5-HT1A and 5-HT2A receptors.

Authors

  • Franz Vollenweider
  • Katrin Preller
  • Rafael Kraehenmann

Published

European Neuropsychopharmacology
individual Study

Abstract

Introduction

The mixed serotonin (5-HT) 1A/2A/2B/2C/6/7 receptor agonist psilocybin dose-dependently induces an altered state of consciousness (ASC) that is characterized by changes in sensory perception, mood, thought, and the sense of self. The psychological effects of psilocybin are primarily mediated by 5-HT2A receptor activation. However, accumulating evidence suggests that 5-HT1A or an interaction between 5-HT1A and 5-HT2A receptors may contribute to the overall effects of psilocybin.

Methods

Therefore, we used a double-blind, counterbalanced, within-subject design to investigate the modulatory effects of the partial 5-HT1A agonist buspirone (20 mg p.o.) and the non-hallucinogenic 5-HT2A/1A agonist ergotamine (3 mg p.o.) on psilocybin-induced (170 µg/kg p.o.) psychological effects in two groups (n=19, n=17) of healthy human subjects. Psychological effects were assessed using the Altered State of Consciousness (5D-ASC) rating scale.

Results

Buspirone significantly reduced the 5D-ASC main scale score for Visionary Restructuralization (VR) (p<0.001), which was mostly driven by a reduction of the VR item cluster scores for elementary and complex visual hallucinations. Further, buspirone also reduced the main scale score for Oceanic Boundlessness (OB) including derealisation and depersonalisation phenomena at a trend level (p=0.062), whereas ergotamine did not show any effects on the psilocybin-induced 5D-ASC main scale scores.

Discussion

The present finding demonstrates that buspirone exerts inhibitory effects on psilocybin-induced effects, presumably via 5-HT1A receptor activation, an interaction between 5-HT1A and 5-HT2A receptors, or both. The data suggest that the modulation of 5-HT1A receptor activity may be a useful target in the treatment of visual hallucinations in different psychiatric and neurological diseases.

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Research Summary of 'Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience'

Introduction

Serotonergic hallucinogens such as psilocybin produce an altered state of consciousness (ASC) characterised by marked changes in perception, emotion, thought, and sense of self. Converging human and animal evidence indicates that many core psychological effects of psilocybin are primarily mediated by 5-HT2A receptor activation, yet these compounds also bind to other serotonin receptor subtypes including 5-HT1A. Animal studies and limited human data suggest that 5-HT1A receptor activity can modulate behaviours and subjective effects associated with 5-HT2A agonists, but the role of 5-HT1A receptors in shaping psychedelic symptom formation in humans is not well defined. Pokorny and colleagues set out to test whether pretreatment with a partial 5-HT1A agonist (buspirone) or a non-hallucinogenic 5-HT1A/2A agonist (ergotamine) alters the subjective effects of psilocybin in healthy volunteers. The study specifically examined whether these pretreatments reduce psilocybin-induced alterations in perception, emotion, thought, and self-experience as measured by the Altered State of Consciousness (5D-ASC) rating scale.

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Study Details

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