Using psilocybin to investigate the relationship between attention, working memory and the serotonin 5-HT1A and 5-HT2A receptors

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 5-HT1A/2A receptor agonist psilocybin alone and after pretreatment with the 5-HT2A antagonist ketanserin on multiple object tracking and spatial working memory, in eight healthy human volunteers. Psilocybin significantly reduced attentional tracking ability, but had no significant effect on spatial working memory, suggesting a functional dissociation between the two tasks. In line with the 5-HT1A receptor's known role in modulating prefrontal activity, 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 propose that this impaired attentional performance may reflect reduced ability to suppress or ignore distracting stimuli rather than reduced attentional capacity.