Acetaminophen, long used as a reliable pain reliever, may also reduce the brain’s ability to recognize mistakes, according to new research from the University of Toronto.
Researchers led by postdoctoral fellow Daniel Randles, together with collaborators from the University of British Columbia, conducted the first neurological investigation into how acetaminophen affects the brain’s error-detection responses. Their findings suggest the common over-the-counter drug can dampen neural signals associated with conscious awareness of mistakes.
Previous studies have shown that physical pain and social rejection share overlapping neural systems that register distress. Building on that work, and on earlier behavioral studies indicating broader evaluative blunting under acetaminophen, the team set out to identify electrical signatures in the brain that might explain these effects.
“Past research tells us physical pain and social rejection share a neural process experienced as distress, and both trace to the same brain regions,” says Randles. “Although behavioral work suggested acetaminophen affects reactions to uncertainty and evaluative processes, we wanted direct neural evidence of how the drug alters error processing.”
Sixty participants were recruited and randomly assigned, in a double-blind protocol, to receive either a single 1,000 mg dose of acetaminophen (a typical maximum over-the-counter dose) or a placebo. All participants completed a rapid target-detection Go/NoGo task while their brain activity was recorded using electroencephalography (EEG).
In the task, participants pressed a button every time the letter “F” appeared (Go trials) and withheld a response when the letter “E” appeared (No Go trials). The task emphasizes speed: because most stimuli are Go trials, participants tend to develop an automatic response tendency that must be interrupted on No Go trials—providing a reliable way to study cognitive control and error processing.
The EEG recordings focused on two well-established event-related potentials that follow errors: the error-related negativity (ERN) and the error-related positivity (Pe). The ERN is an early negative deflection detected soon after an error, often linked to automatic error detection. The Pe is a later positive wave associated with conscious evaluation and awareness of having made a mistake.
Results showed that acetaminophen significantly reduced the amplitude of the Pe but did not affect the ERN. In other words, the drug appeared to leave early automatic error signals intact while attenuating the later neural signature linked to conscious error evaluation. Participants who received acetaminophen also tended to produce more omission errors on Go trials than participants who received placebo—an unexpected finding the authors plan to investigate further.
“It looks like acetaminophen may make it harder for people to consciously recognize that they’ve made an error,” Randles explains. “That has potential implications for cognitive control in everyday situations, where recognizing and correcting mistakes quickly is important.”
Cognitive control governs the ability to interrupt automatic behaviors when circumstances change—for example, pausing a conversation to avoid stepping into traffic. The Go/NoGo paradigm simulates this requirement by creating a prepotent action tendency that must be suppressed when a No Go signal appears. By reducing Pe amplitude, acetaminophen may blunt the evaluative processes that support this adaptive interruption.
The study’s double-blind design ensured neither researchers nor participants knew who received the active drug or the placebo. The authors note that the observed reduction in conscious error processing raises questions about whether acetaminophen could increase everyday mistakes or promote mind-wandering and distraction, and they call for follow-up studies using tasks that more closely mirror real-world behavior.
The study is published in Social Cognitive and Affective Neuroscience and contributes to a growing body of evidence that acetaminophen’s effects extend beyond pain relief to broader affective and evaluative functions in the brain.
Source: Don Campbell – University of Toronto
Image Credit: University of Toronto Scarborough
Original Research: Abstract for “Acetaminophen attenuates error evaluation in cortex” by Daniel Randles, Julia W.Y. Kam, Steven J. Heine, Michael Inzlicht, and Todd C. Handy in Social Cognitive and Affective Neuroscience. Published online February 17, 2016. DOI: 10.1093/scan/nsw023
Abstract
Acetaminophen attenuates error evaluation in cortex
Recent work suggests acetaminophen influences affective processes beyond pain relief. Double-blind, placebo-controlled trials have shown reduced reactivity to social rejection, frustration, cognitive dissonance, and emotionally valenced stimuli after acetaminophen. These diverse findings have led researchers to propose that acetaminophen produces a broad dampening of evaluative processing. To test this hypothesis at the neural level, 62 participants received either acetaminophen or placebo in a double-blind protocol and completed a Go/NoGo task while event-related potentials (ERPs) were recorded. Analysis focused on error-related potentials—specifically the ERN (measured at FCz) and the Pe (measured at Pz and CPz). The results indicate that acetaminophen attenuates the Pe but not the ERN, and that individual differences in Pe amplitude correlate with omission errors, partially mediating acetaminophen’s effect on error rates. These findings support the idea that acetaminophen reduces evaluative processing and reinforce the interpretation that the Pe reflects conscious awareness of errors more so than the ERN.