Healthy VolunteersPsilocybinPlacebo

Using Psilocybin to Investigate the Relationship between Attention, Working Memory, and the Serotonin 1A and 2A Receptors

This study tested the effects of psilocybin (15mg/70kg) on attentional tracking and spatial working memory, using a placebo-controlled design and ketanserin pretreatment condition to control for the 5-HT2A specific effects. Results indicated reduced attentional tracking ability, but unimpaired working memory, which was not related to 5-HT2A activity.

Authors

  • Franz Vollenweider
  • Olivia Carter

Published

Journal of Cognitive Neuroscience
individual Study

Abstract

Introduction

Increasing evidence suggests a link between attention, working memory, serotonin (5-HT), and prefrontal cortex activity. In an attempt to tease out the relationship between these elements, this study tested the effects of the hallucinogenic mixed 5-HT1A/2A receptor agonist psilocybin alone and after pretreatment with the 5-HT2A antagonist ketanserin.

Methods

Eight healthy human volunteers were tested on a multiple-object tracking task and spatial working memory task under the four conditions: placebo, psilocybin (215 Ag/kg), ketanserin (50 mg), and psilocybin and ketanserin.

Results

Psilocybin significantly reduced attentional tracking ability, but had no significant effect on spatial working memory, suggesting a functional dissociation between the two tasks. Pretreatment with ketanserin did not attenuate the effect of psilocybin on attentional performance, suggesting a primary involvement of the 5-HT1A receptor in the observed deficit.

Discussion

Based on physiological and pharmacological data, we speculate that this impaired attentional performance may reflect a reduced ability to suppress or ignore distracting stimuli rather than reduced attentional capacity. The clinical relevance of these results is also discussed.

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Research Summary of 'Using Psilocybin to Investigate the Relationship between Attention, Working Memory, and the Serotonin 1A and 2A Receptors'

Introduction

Carter and colleagues frame the study around the intertwined roles of attention, working memory and serotonin (5-HT) signalling, with particular interest in prefrontal cortex mechanisms. The paper notes that attention must balance selectivity and breadth in dynamic environments, that multiple-object tracking demonstrates the ability to maintain several attentional foci simultaneously, and that previous imaging and pharmacological work implicates frontal regions and serotonergic receptors in both attention and working memory. Psilocybin, whose active metabolite psilocin binds to 5-HT2A (higher affinity) and 5-HT1A (lower affinity) sites, was selected as a pharmacological probe because it transiently alters perception and cognition and thus can be used to interrogate receptor-specific contributions to attentional and mnemonic processes. The study set out to test whether psilocybin impairs attentional tracking and/or spatial working memory, and whether blockade of the 5-HT2A receptor with ketanserin would attenuate any psilocybin-induced effects. The investigators used a multiple-object tracking task to measure the capacity to maintain multiple attentional foci, and a computerized Corsi-style Spatial Span task to assess spatial working memory. By comparing placebo, psilocybin, ketanserin, and ketanserin-plus-psilocybin conditions within subjects, the experiment aimed to dissociate receptor contributions and probe whether attention and working memory can be pharmacologically separated.

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Study Details

References (3)

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