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

A hallucinogenic drug that activates serotonin receptors, psilocybin, impaired healthy volunteers' ability to track moving objects but did not affect their spatial working memory. Blocking the 5-HT2A receptor with ketanserin before psilocybin did not prevent this attentional deficit, pointing to the 5-HT1A receptor as the likely cause. The authors suggest the impairment may stem from a reduced ability to filter out distractions rather than a loss of attentional capacity. Eight participants completed both tasks under placebo, psilocybin, ketanserin, and the combination.

Study at a glance

Abstract

Abstract 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. 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. 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. 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.