The 5-HT2A/1A Agonist Psilocybin Disrupts Modal Object Completion Associated with Visual Hallucinations

The hallucinogenic compound psilocybin, which activates 5-HT2A/1A serotonin receptors, alters how the brain processes visual information. In a placebo-controlled experiment with 17 healthy volunteers, psilocybin dose-dependently reduced the N170 brain response, especially when viewing incomplete object figures, while slightly enhancing the P1 component over occipital areas. The reduction in N170-related brain activity in the right extrastriate and posterior parietal regions correlated with the intensity of visual hallucinations. These findings point to a central role of 5-HT2A/1A receptors in visual processing and suggest that a diminished N170 response may be a key mechanism underlying visual hallucinations.

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Abstract

BackgroundRecent findings suggest that the serotonergic system and particularly the 5-HT2A/1A receptors are implicated in visual processing and possibly the pathophysiology of visual disturbances including hallucinations in schizophrenia and Parkinson's disease.MethodsTo investigate the role of 5-HT2A/1A receptors in visual processing the effect of the hallucinogenic 5-HT2A/1A agonist psilocybin (125 and 250 μg/kg vs. placebo) on the spatiotemporal dynamics of modal object completion was assessed in normal volunteers (n = 17) using visual evoked potential recordings in conjunction with topographic-mapping and source analysis. These effects were then considered in relation to the subjective intensity of psilocybin-induced visual hallucinations quantified by psychometric measurement.ResultsPsilocybin dose-dependently decreased the N170 and, in contrast, slightly enhanced the P1 component selectively over occipital electrode sites. The decrease of the N170 was most apparent during the processing of incomplete object figures. Moreover, during the time period of the N170, the overall reduction of the activation in the right extrastriate and posterior parietal areas correlated positively with the intensity of visual hallucinations.ConclusionsThese results suggest a central role of the 5-HT2A/1A-receptors in the modulation of visual processing. Specifically, a reduced N170 component was identified as potentially reflecting a key process of 5-HT2A/1A receptor-mediated visual hallucinations and aberrant modal object completion potential.