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Psilocybin acutely dissociates cognitive and affective empathy, with empathic concern predicting persisting positive psychological effects

Mason, N. L.; Mallaroni, P.; Kuypers, K. P. C.; De La Torre Fornell, R.; Reckweg, J. T.; Preller, K.; Ramaekers, J. G.

2026-08-10 neuroscience
10.64898/2026.08.04.742704 bioRxiv
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BackgroundPsychedelics have been proposed to enhance empathy and social connectedness, but it remains unclear whether these effects reflect global increases in empathic ability, whether they persist beyond the acute drug state, and whether they contribute to later psychological outcomes. MethodsIn a randomized, double-blind, placebo-controlled, parallel-group study, healthy participants received psilocybin (0.17 mg/kg) or placebo. Three dissociable components of empathy were assessed using the Multifaceted Empathy Test at baseline, during the acute drug state, and 7 days later: cognitive empathy (accuracy of emotion identification), emotional arousal (affective activation in response to anothers emotional state) and empathic concern (other-oriented compassion toward the depicted person. Persisting positive psychological effects were assessed at follow-up. Circulating oxytocin was measured, and spectral dynamic causal modeling was applied to resting-state fMRI data acquired during the acute drug state to examine effective connectivity within an empathy-relevant network. ResultsCompared with placebo, psilocybin acutely reduced cognitive empathy selectively for positive stimuli, while increasing emotional arousal for positive stimuli and empathic concern across valences. These empathy-related effects did not persist 7 days later. However, acute increases in empathic concern mediated later positive psychological changes, including improved attitudes about life and self, mood, and relationships. Psilocybin also increased circulating oxytocin compared to baseline, but oxytocin changes were not associated with empathy changes. Effective-connectivity analyses showed that empathic responding under psilocybin was associated with altered directional coupling among superior temporal and parahippocampal regions. ConclusionsPsilocybin does not simply enhance empathy, rather it impairs the identification of positive emotional states while heightening affective engagement and concern. Although these effects do not persist, acute empathic concern may contribute to later positive psychological change.

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