Acetaminophen Potentiates Fear Processing: A Comparison Between Ancestral and Modern Threats

  • Andrew Gallup SUNY Polytechnic Institute
  • Brianda Gagnon SUNY Polytechnic Institute
  • Gillian Perry SUNY Polytechnic Institute
  • Omar Eldakar Nova Southeastern University
Keywords: acetaminophen, emotional processing, evolutionary mismatch, evolutionary psychopharmacology, threat detection, neuromodulation


The painkilling medication acetaminophen produces a variety of unintended psychological effects. In particular, it has been shown to diminish varied forms of psychological distress by attenuating neural activity in the cerebral cortex and enhancing the signaling of serotonin. As a result, this over-the-counter medication appears to dampen overall affective processing and has been termed “an all-purpose emotion reliever.” However, this drug may not necessarily modify all emotions in the same manner. Specifically, fear processing occurs rapidly within the amygdala and is governed by serotonin. Thus, by blunting cortical activity and facilitating serotonergic action, acetaminophen could in fact potentiate reactions to threatening stimuli. This study intersects with the fields of evolutionary psychology and psychopharmacology by investigating whether acetaminophen modulates responses to fear-inducing stimuli that vary in ancestral relevance. We hypothesized that the more subcortical and prewired mechanisms controlling responses to recurring ancestral threats (snakes and spiders) would be more affected by this drug compared to learned threats of modern environments (handguns and hypodermic needles). In a double-blind placebo-controlled design (N = 94), acetaminophen significantly enhanced participants’ evaluations and emotional reactions to threatening stimuli. In addition, ancestral threats were rated as both significantly more negative and emotionally arousing compared to modern threats. Contrary to our predictions, however, acetaminophen altered affective responses to ancestral and modern threats in a highly similar manner. We conclude that acetaminophen does not blunt overall affective processing, and call for further evolutionary-based research examining the various psychoactive effects of this commonly consumed over-the-counter painkiller.

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