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

  • Carter O
  • Burr D
  • Pettigrew J
 et al. 
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& Increasing evidence suggests a link between attention, working memory, serotonin (5-HT), and prefrontal cortex ac-tivity. 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 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 dis-sociation between the two tasks. Pretreatment with ketanserin did not attenuate the effect of psilocybin on attentional per-formance, 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 atten-tional performance may reflect a reduced ability to suppress or ignore distracting stimuli rather than reduced attentional capac-ity. The clinical relevance of these results is also discussed. &

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  • Olivia L Carter

  • David C Burr

  • John D Pettigrew

  • Guy M Wallis

  • Felix Hasler

  • Franz X Vollenweider

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