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-HT_2A specific effects. Results indicated reduced attentional tracking ability, but unimpaired working memory, which was not related to 5-HT_2A activity.

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-HT_1A/2A receptor agonist psilocybin alone and after pretreatment with the 5-HT_2A 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-HT_1A 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.”

Authors: Olivia L. Carter, David C. Burr, John D. Pettigrew, Guy M. Wallis, Felix Hasler, Franz X. Vollenweider