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

¹ University of Queensland, ² University Hospital of Psychiatry, Zurich, Switzerland, ³ Instituto di Neuroscienze del CNR, Pisa, Italy

Reprint requests should be sent to Olivia Carter, Vision Science Lab, Harvard University, 33 Kirkland St., Rm 702, Cambridge, MA 02138, or via e-mail: o.carter{at}wjh.harvard.edu.

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. Eight healthy human volunteers were tested on a multiple-object tracking task and spatial working memory task under the four conditions: placebo, psilocybin (215 µg/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-HT_1A 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.

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