Using psilocybin to investigate the relationship between attention, working memory and the Serotonin1A&2A 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 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g/kg); ketanserin (50mg); 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. 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 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 are also discussed.