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

Andrew Gallup,Gillian Perry,Brianda Gagnon,Omar Eldakar

doi:10.5178/lebs.2021.84

Abstract

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.

Highlights

Painkilling medications can profoundly improve human welfare by minimizing physical discomfort and suffering
Research shows that common OTC medications like acetaminophen can produce a variety of additional unintended psychological effects that could result in further mismatch with our evolved psychology (Ratner et al, 2018)
Numerous studies have examined the psychoactive effects of acetaminophen (Ratner et al, 2018), with most attention paid towards aspects of social pain (DeWall et al, 2010; Slavich et al, 2019) and basic affective processes (Durso et al, 2015; Gallup et al, 2020; Mischkowski et al, 2019)

Summary

Introduction

Painkilling medications can profoundly improve human welfare by minimizing physical discomfort and suffering. Research shows that common OTC medications like acetaminophen (paracetamol, Tylenol) can produce a variety of additional unintended psychological effects that could result in further mismatch with our evolved psychology (Ratner et al, 2018). Research suggests that the painkilling properties of acetaminophen are largely attributed to the activation of the descending inhibitory serotoninergic pathways (e.g., Graham & Scott 2005; Pickering et al, 2008). It remains unclear as to the precise mechanisms by which acetaminophen exerts an analgesic effect, involving serotonergic, opioid and cannabinoid systems (Graham et al, 2013), it is widely accepted that this drug reduces pain through central, rather than peripheral, nervous system mechanisms (Anderson 2008; Courade et al, 2001; Pickering et al, 2006; Smith 2009). Acetaminophen has the potential to alter varied forms of perception, mood, cognition, and behavior

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