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Effects of acetaminophen on risk taking

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Abstract

Acetaminophen, an analgesic and antipyretic available over-the-counter and used in over 600 medicines, is one of the most consumed drugs in the USA. Recent research has suggested that acetaminophen's effects extend to the blunting of negative as well as positive affect. Because affect is a determinant of risk perception and risk taking, we tested the hypothesis that acute acetaminophen consumption (1000 mg) could influence these important judgments and decisions. In three double-blind, placebo-controlled studies, healthy young adults completed a laboratory measure of risk taking (Balloon Analog Risk Task) and in Studies 1 and 2 completed self-report measures of risk perception. Across all studies (total n = 545), acetaminophen increased risk-taking behavior. On the more affectively stimulating risk perception measure used in Study 2, acetaminophen reduced self-reported perceived risk and this reduction statistically mediated increased risk-taking behavior. These results indicate that acetaminophen can increase risk taking, which may be due to reductions in risk perceptions, particularly those that are highly affect laden.
Effects of acetaminophen on risk taking
Alexis Keaveney1, Ellen Peters2and Baldwin Way1
1Department of Psychology, The Ohio State University, Columbus, OH 43210, USA and 2School of Journalism
and Communication, University of Oregon Eugene, OR 97403, USA
Correspondence should be addressed to Baldwin M. Way, Department of Psychology, The Ohio State University, 1835 Neil Avenue, Columbus, OH 43210,
USA. E-mail: way.37@osu.edu
Abstract
Acetaminophen, an analgesic and antipyretic available over-the-counter and used in over 600 medicines, is one of the most
consumed drugs in the USA. Recent research has suggested that acetaminophen’s effects extend to the blunting of negative as
well as positive affect. Because affect is a determinant of risk perception and risk taking, we tested the hypothesis that acute
acetaminophen consumption (1000 mg) could inuence these important judgments and decisions. In three double-blind,
placebo-controlled studies, healthy young adults completed a laboratory measure of risk taking (Balloon Analog Risk Task)
and in Studies 1 and 2 completed self-report measures of risk perception. Across all studies (total n=545), acetaminophen
increased risk-taking behavior. On the more affectively stimulating risk perception measure used in Study 2, acetaminophen
reduced self-reported perceived risk and this reduction statistically mediated increased risk-taking behavior. These results
indicate that acetaminophen can increase risk taking, which may be due to reductions in risk perceptions, particularly those
that are highly affect laden.
Key words: NSAID; decision-making; risk perception; anti-inammatory
Acetaminophen, the active ingredient in Tylenol®and nearly 600
other medicines, is taken each week by an estimated 23% of
the US adult population (Kaufman et al., 2002). Recent research
has demonstrated that acetaminophen’s effects on pain and
fever reduction extend to psychological processes. For example,
acetaminophen reduces hurt feelings (Dewall et al., 2010), mean-
ing threats (Randles et al., 2013), distress over another’s suffering
(Mischkowski et al., 2016), loss aversion (DeWall et al., 2014) and
affective reactivity to negatively valenced images (Durso et al.,
2015). In this latter study, acetaminophen also blunted affec-
tive reactivity to positively valenced images, suggesting that
it may reduce affective reactivity more generally, rather than
solely inuencing negative experiences. Because risk judgments
and decisions rely on both positive and negative affect
(Loewenstein et al., 2001;Slovic et al., 2004), it is rea-
sonable to hypothesize that acetaminophen may inuence
them.
Affect and decision-making
Work on the ‘affect-heuristic’ and ‘risk-as-feelings’ hypothe-
sis have demonstrated a key role for affect in risk judgments
and decisions (Loewenstein et al., 2001;Slovic et al., 2004). In
particular, when faced with a complex decision, people often
use their feelings about an option as information, substituting
it for the more difcult probabilities and outcomes that accu-
rately describe risks. This affect then serves as a simple cue,
allowing people to avoid hazards quickly and efciently. As a
result, affect manipulations, perhaps including acetaminophen,
should inuence decisions about risks.
Received: 19 October 2019; Revised: 28 May 2020; Accepted: 24 June 2020
© The Author(s) 2020. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/
licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
For commercial re-use, please contact journals.permissions@oup.com
Social Cognitive and Affective Neuroscience, 2020, 725–732
doi: 10.1093/scan/nsaa108
Advance Access Publication Date:
Original Manuscript
30 July 2020
725
Affect heuristic and risk taking
The affect heuristic predicts that individuals will use affect as
information to guide decisions, especially in risky tasks that are
affectively stimulating and experientially engaging (Figner and
Weber, 2011). The Balloon Analog Risk Task (BART; (Lejuez et al.,
2002)), for example, is such an experiential task; performance on
it predicts drug and alcohol use, delinquent behavior and risky
sexual behavior (e.g. (Lejuez et al., 2004 2007;Aklin et al., 2005)).
The BART is a computerized task in which participants inate
balloons to earn money, but each pump risks them losing all of
their prior earnings. The task is probabilistic although it does not
provide explicit information about the probability of loss events.
It is also visual and experiential, making it a strong candidate for
a task in which participants are likely to use the affect heuristic.
Indeed, experimentally induced increases to participant’s
negative affect have reduced risk taking on the BART (Yuen
and Lee, 2003;Heilman et al., 2010;Parkinson et al., 2012).
This research suggests that negative affect experienced during
the BART signals one to engage in less risk taking. Because
the BART negative loss events are more visually and audito-
rily salient than its win events and because manipulations of
negative affect had signicant inuences on task performance,
it seems likely that negative affect toward potential or expe-
rienced losses exerts a stronger inuence on BART decisions
than does positive affect toward potential or experienced gains.
Therefore, acetaminophen’s blunting of negative affect may lead
to a reduction in this negative affect signal and an increase
in risk taking. These considerations led to our rst hypoth-
esis: Acetaminophen will increase risk taking on the BART
(Hypothesis 1).
Affect heuristic and risk and benet
judgments
Affect-heuristic use also has also been explored in the context
of risk and benet judgments (Slovic and Peters, 2006). Individu-
als appear to rely on affect to infer the risks and benets offered
by activities and hazards. Objects that elicit positive affect, say
alcoholic beverages, tend to be judged as having high benets
and low risks. Conversely, objects that elicit negative affect, say
nuclear power, tend to be judged as low in benet and high
in risk. Because acetaminophen appears to reduce the extrem-
ity of affective reactions to stimuli, it may reduce perceived
risk and perceived benet of a behavior or policy. Therefore,
our second hypothesis is: acetaminophen will reduce the neg-
ative affect elicited when considering potential risk, leading to
reduced risk perception (Hypothesis 2A). The corollary of this
hypothesis is that acetaminophen will reduce the positive affect
elicited when considering potential benets, leading to reduced
benet perception (Hypothesis 2B).
To test these hypotheses, we used an acute, double-blind,
placebo-controlled, parallel-arm design with acute adminis-
tration of the standard extra-strength dosage (1000 mg) of
acetaminophen.
Study 1
Method
Participants. Participants were 142 undergraduate volunteers
(76 men, 64 women, 2 nonresponses) with a mean age of 19.36
years (s.d. =1.68). Sample size was determined a priori based
on the expectation of a similar effect size as that found in pre-
vious acetaminophen and affect research (Durso et al., 2015)
and acetaminophen and decision-making research (DeWall et
al., 2014). All research reported herein was approved by the Ohio
State University Institutional Review Board.
Acetaminophen. A double-blind, placebo-controlled design was
used. Participants were randomly assigned to drug condi-
tion using a random number generator (n=69 placebo, n=73
acetaminophen). Participants were given a placebo or 1000 mg
of acetaminophen, the recommended extra strength dosage
for a headache and the dosage commonly used in studies
of acetaminophen’s psychological effects (Durso et al., 2015).
Acetaminophen and placebo solutions were prepared by Phar-
macy Specialists Compounding Pharmacy (Altamonte Springs,
Florida; http://www.makerx.com/). The drug solution consisted
of acetaminophen (100 mg/ml) suspended in Ora-Plus suspen-
sion liquid and avored with Fagron Simple Syrup. The placebo
solution consisted of Avicel Microcrystalline powder (100 mg/ml)
dissolved in Ora-Plus suspension liquid and avored with Ora-
Sweet Syrup. After consuming the assigned solution, partici-
pants were given a small cup of water to wash it down. At the
conclusion of the experiment, participants were asked to guess
which drug condition they were in (acetaminophen, placebo, or
‘no idea’); thus, participants could opt out of guessing their con-
dition, or guess between drug and placebo conditions, a 50%
chance of guessing correctly. In the acetaminophen condition,
46.6% of participants correctly guessed which condition they
were in (i.e. choosing ‘acetaminophen’ and not ‘placebo’ or ‘no
idea’). A one-sample t-test for proportions reveals that this was
not signicantly different from chance, t=0.58, P=0.56. In
the placebo condition, 34.8% of participants correctly guessed
which condition they were in (i.e. selecting ‘placebo’ and not
‘acetaminophen’ or ‘no idea’), a proportion that was signicantly
worse than chance, t=2.64, P=0.01, suggesting that partic-
ipants did not accurately predict their experimental condition
(the most common response in this group was ‘no idea’, 41%).
Risk taking. To measure risk taking, the BART was used (Lejuez
et al., 2002). In this task, participants complete 30 trials, each of
which includes 1–128 participant responses. A trial begins with
a small, uninated balloon on a computer screen. Participants
can inate the balloon, with each pump earning $0.05. Though
they played this game for imaginary money, they were told their
goal was to earn as much money as possible in the task. Partic-
ipants can collect their total trial earnings and move them to a
permanent bank at any point by pressing a button saying ‘Col-
lect $$$’. However, participants also are told that the balloon can
burst as early as the rst trial and as late as when the balloon lls
the entire computer screen. Bursts are accompanied by a burst-
ing sound and popping animation. If the balloon bursts prior to
the participants pressing the ‘Collect $$$’ button, they lose any
money earned thus far on that trial, and must move on to the
next trial having added no money to their permanent bank.
Participants are not told about the maximum number of
pumps, the likelihood of bursts, nor that, for each balloon,
the rst pump has a 1/128 probability of bursting, the second
pump 1/127, and so on until on the 128th pump there is a 1/1
probability of bursting.
Risk and benet perception. To assess acetaminophen’s impact
on use of the affect heuristic in risk judgments, participants
Social Cognitive and Affective Neuroscience, 2020, Vol. 15, No. 7726
completed the risk and benet perceptions questionnaire used
by Finucane et al. (2000). Participants were asked to make risk
and benet judgments of various activities and technologies for
US society as a whole. They made these judgments on a 7-point
scale ranging from not at all risky (benecial) to very risky (ben-
ecial). To enhance affect-heuristic use, participants were put
under time pressure with a countdown clock on the screen while
making judgments, with 5.2 s for each item (as in Finucane et al.,
2000). The scale consisted of 23 items (e.g. ‘Pesticides’, ‘Nuclear
Power Plants’), presented one at a time on the screen. Items
were presented in randomized order. After completing ratings
of all 23 items on the rst scale (either risk or benet), partici-
pants then received instructions for completing the second scale
(benet or risk), with all items presented again in a different ran-
dom order. Order of the benet and risk perception tasks was
counter-balanced.
Procedure. After signing up for the experiment, participants
received an email informing them that ‘Half of the participants
will receive a liquid dose of acetaminophen (i.e. Tylenol) and
half of the participants will receive a liquid dose of placebo
(i.e. a sugar pill or inactive liquid). Therefore, there is a 50%
chance you will be in the group that receives acetaminophen’.
The email informed them about the risk factors associated
with acetaminophen (e.g. currently taking a drug containing
acetaminophen, a history of liver disorder, an allergic reac-
tion to acetaminophen, currently taking an anticoagulant, or
a history of alcohol abuse) and asked them to refrain from
participation if they met any of these risk factors. To facil-
itate drug absorption, we also asked participants to refrain
from consuming food for three hours before the experiment.
Upon arrival at the laboratory and after providing informed con-
sent (which repeated the information in the email described
above), participants consumed either the drug or placebo, based
on random assignment. To allow for sufcient drug uptake
into the brain (Singla et al., 2012), we waited 45 min to begin
the main tasks of the study. During drug uptake, participants
completed a number of background personality and health
measures. At 45 min, participants began completing decision-
making tasks. At approximately 50 min after the drug con-
sumption, participants completed the risk and benet percep-
tion task using the online survey program Qualtrics (Qualtrics,
Provo, UT). Immediately following and approximately 60 min
after the drug consumption, participants completed the BART
task, implemented using the Psychology Experiment Building
Language (PEBL) package and prepackaged BART script (Mueller
and Piper, 2014;http://pebl.sourceforge.net/). Following the
BART, participants answered a short survey, which included
demographic information, then were debriefed and thanked.
Results
Risk-taking main effect. To analyze the BART data, we com-
puted participants’ adjusted average number of pumps across
the 30 trials, according to methods in prior work (Lejuez
et al., 2002). Specically, trials on which a balloon burst occurred
were excluded, as the number of pumps completed on this trial
reected balloon bursts rather than the participant’s desired
amount of risk taking had a burst not occurred. After those tri-
als were excluded, averages across the remaining trials were
computed.
Consistent with our rst hypothesis that acetaminophen
would increase BART risk taking, a t-test revealed a signi-
cant difference in risk taking between those on acetaminophen
and those on placebo, t(140) =2.29, P=0.023, 95% CI
[10.94, 0.81], Cohen’s d=0.38 (Figure 1A, left panel). As
hypothesized, those in the placebo condition engaged in signif-
icantly less risk taking as indexed by adjusted average number
of pumps (M=33.10, s.d. =15.75) than those on acetaminophen
(M=38.98, s.d. =14.80). Hierarchical linear modeling techniques
demonstrated similar results, but did not identify further psy-
chological mechanisms driving these effects (see supplementary
material). There was also a signicant difference (t(140) =2.02,
Fig. 1. Graphs of the adjusted average number of pumps for each study (error bars denote standard error of the mean). In Studies 1, 2 and the combined analysis of
all three studies, the acetaminophen group had signicantly more adjusted average pumps.
727
A. Keaveney et al.
P=0.045, 95% CI [2.95, 0.033]) in the number of balloons that
burst as a function of drug condition with more balloons burst-
ing in the acetaminophen condition (M=10.07, s.d. =4.13) than
the placebo condition (M=8.58, s.d. =4.64).
Risk and benet perception. To assess risk perception, average
ratings were computed across the 23 items. The same pro-
cess was used for benet perception. Our second hypothesis
that acetaminophen would decrease risk and benet percep-
tions was not supported. A t-test for average risk perception
revealed no signicant difference between drug conditions,
t(140) =1.48, P=0.14, 95% CI [0.05, 0.34]. Descriptively,those on
placebo perceived more risk (M=3.93, s.d. =0.62) than those on
acetaminophen (M=3.78, s.d. =0.56). A t-test for average ben-
et perception also revealed no signicant difference between
drug conditions, t(140) =0.74, P=0.46, 95% CI [0.13, 0.28].
Descriptively, those on placebo perceived more benet (M=4.58,
s.d. =0.61) than those on acetaminophen (M=4.50, s.d. =0.62).
We also examined acetaminophen’s impact on the correla-
tion between risk and benet judgments; these analyses are
described in the supplementary online material.
Study 1 discussion
Study 1 provided initial support for our rst hypothesis; those
on acetaminophen, relative to placebo, engaged in signicantly
more risk taking on the BART. Little evidence emerged, how-
ever, for our second hypothesis that acetaminophen would
reduce risk and benet perceptions. We speculated that our
participants perceived these items to be less affectively stim-
ulating than those in the original Finucane et al. (2000) affect-
heuristic study. Indeed, in our placebo group, negative cor-
relations between risk and benet perceptions were obtained
(r=0.23), but were much weaker than those in the same time-
pressure condition of the original study (r=0.80). If partici-
pants had weaker negative affect to these risks in our study,
acetaminophen may not have exerted much effect on judgments
because acetaminophen has weaker effects on stimuli that are
less affective compared to more affective (Durso et al., 2015).
Study 2
In Study 2, we attempted a direct replication with the BART
task and used a risk-perception scale with items that may be
more affectively stimulating than those of Study 1 to re-test our
second hypothesis.
Method
Participants. One-hundred eighty-nine undergraduates volun-
teered (109 men, 79 women, 1 nonresponse) and had a mean age
of 19.49 years (s.d. =2.89). We aimed for 200 participants based
on a power analysis of Study 1 (Cohen’s d=0.38); data collection
ended at the end of the semester.
Acetaminophen. As in Study 1, we used a double-blind, placebo-
controlled design with random assignment to 1000 mg of
acetaminophen or placebo (n=95 and 94, respectively). Partic-
ipants were asked to guess which drug condition they were in
(acetaminophen or placebo). A total of 54.7% of participants in
the acetaminophen condition correctly guessed which condition
they were in, a proportion that was not signicantly different
from chance, t=0.92, P=0.36. A total of 52.1% of participants
in the placebo condition correctly guessed which condition they
were in, a proportion that was not signicantly different than
chance, t=0.41, P=0.68.
BART. The same behavioral measure of risk taking, the BART,
was used in Study 2. Participants completed 30 trials. Follow-
ing this, participants answered self-report questions about their
experience and perception of balloon bursts during the task (see
supplementary material for full materials and analysis).
Risk and benet perceptions. To examine acetaminophen’s
effect on risk and benet perceptions, we used the revised
Domain Specic Risk-Taking Scale (DOSPERT; Blais and Weber,
2006). This 30-item scale provides behavioral scenarios (e.g. ‘Bet-
ting a day’s income on the outcome of a sporting event’) for
which participants were then asked for their gut-level percep-
tion of the riskiness of each behavior as well as the expected
benets that would be obtained from enacting each behavior.
Participants responded on a 7-point scale ranging from not at all
risky (no benets at all) to extremely risky (great benets). Because
these items are more experientially descriptive and participants
are asked to judge risk and benet personally rather than for
society, we thought they would be more affectively stimulating
than Study 1’s items. We found support for this hypothesis in
an additional study described in the supplemental materials. In
brief, the DOSPERT items were rated as signicantly more emo-
tional and negative than the Finucane items. Participants also
reported feeling more worried when thinking about those items
than the Finucane items.
The DOSPERT scale can be analyzed both for general risk and
benet perceptions as well as domain-specic perceptions in
ethical (‘passing off somebody else’s work as your own’), nan-
cial (‘betting a day’s income at a high-stake poker game’), health
(‘driving a car without a seatbelt’), recreational (‘Bungee jump-
ing off a tall bridge B’) and social (‘moving to a city far away from
your extended family’) domains. We analyzed the data for aver-
age risk/benet overall and separately within each of the ve
domains.
Procedure. Study 2’s procedure was nearly identical to Study 1
and used the same software. Participants gave informed con-
sent, consumed drug or placebo, and waited 45 min while com-
pleting background measures. Approximately 50 min after drug
administration, participants completed the DOSPERT. Following
this and approximately 60 min after drug administration, par-
ticipants completed the BART, followed by the self-report items
concerning recalled affective experience during the BART task
(see supplemental material).
Results
Risk-taking main effect. As in Study 1, we computed partici-
pants’ adjusted average number of pumps across the 30 trials.
A t-test revealed a signicant difference in risk taking between
those on placebo and those on acetaminophen, t(187) =2.14,
P=0.033, 95% CI [8.11, 0.34], Cohen’s d=0.31. Those on
acetaminophen (M=36.38, s.d. =14.79) engaged in signicantly
more risk taking than those on placebo (M=32.15, s.d. =12.14)
(Figure 1, middle panel), thus replicating Study 1’s effect. As
in Study 1, more balloons burst in the acetaminophen condi-
tion (M=9.54, s.d. =4.29) than the placebo condition (M=8.73,
Social Cognitive and Affective Neuroscience, 2020, Vol. 15, No. 7728
s.d. =4.43). However, the difference was not statistically signi-
cant (t(187) =1.27, P=0.21, 95% CI [2.06, 0.45]).
Risk and benet perception. To test the second hypothesis
that acetaminophen would decrease risk and benet percep-
tions, we used t-tests to compare placebo and acetaminophen
groups’ summed risk and summed benet perception across
all 30 DOSPERT items, as is typically done when analyzing
the DOSPERT scale. A t-test revealed a signicant difference
in risk perception between conditions, t(187) =2.72, P=0.007,
95% CI [1.93, 12.19], Cohen’s d=0.40. Those on acetaminophen
(M=133.89, s.d. =18.03) perceived signicantly less risk than
those on placebo (M=140.96, s.d. =17.71). Thus, Hypothesis 2A
was supported for risk perceptions. When analyzed separately
by domain, this effect held for risk perception in the social
(P=0.005) and recreational (P=0.025) domains was marginally
signicant in the nancial (P=0.069) domain and was nonsignif-
icant but in the hypothesized direction in the health (P=0.12)
and ethical (P=0.67) domains.
For benet perception (Hypothesis 2B), a t-test revealed no
signicant difference in summed benet perception between
conditions, t(187) =0.10, P=0.92, 95% CI [4.85, 5.35]; this null
effect existed for each of the ve domains when analyzed sepa-
rately. Thus, Hypothesis 2B was not supported.
Risk-taking mediation. The nding that acetaminophen signif-
icantly reduced perceived risk (measured with the DOSPERT)
could account for the drug’s effect on BART risk taking. We
explored whether acetaminophen’s effect on risk taking was
mediated by the drug’s effect on DOSPERT risk perception by
using PROCESS Model 4 (Hayes, 2012). This analysis revealed
a signicant indirect effect of acetaminophen on risk taking
through risk perception (point estimate: 0.88, 95% bootstrap
CI =0.14 to 2.31); acetaminophen no longer had a direct effect
on risk taking (direct effect =3.34, P=0.09, 95% CI =0.58 to
7.26). No evidence existed of an indirect effect through bene-
t perception (point estimate: 0.03, 95% bootstrap CI =0.88
to 0.66).
Study 2 discussion
Study 2 replicated and extended Study 1’s risk-taking result:
Again, acetaminophen increased risk taking, supporting our rst
hypothesis. Furthermore, there was also support for hypothe-
sis 2A: acetaminophen reduced risk perceptions (but not benet
perceptions) on the DOSPERT. These effects of acetaminophen
on risk perceptions in Study 2, but not Study 1, are likely due
to the greater negative emotion elicited by the DOSPERT items
than Finucane et al. (2000) items (see supplementary material
for the aforementioned additional study demonstrating greater
emotionality of the DOSPERT items).
In addition, the acetaminophen-caused reduction in risk per-
ceptions mediated increased risk taking on the BART,suggesting
that acetaminophen may reduce negative affect to options and
thereby how risky they seem.
Study 3
The goal of Study 3 was to replicate and extend Study 2.
Method
Participants. Two-hundred fteen undergraduates volunteered
(91 men, 122 women, 1 selected ‘prefer not to answer’) and had
a mean age of 19.49 years (s.d. =2.89). Like in Study 2, we aimed
for 200 participants; data collection ended at the end of the
semester. The sample was 69% white, 10% Asian, 8% Black or
African American, and 14% Mixed race or some other origin.
Drug preparation. As in the prior studies, we used a double-
blind, placebo-controlled design with random assignment to
1000 mg of acetaminophen or placebo (n=109 and 106, respec-
tively). It should be noted that a different preparation procedure
and vehicle were used for acetaminophen administration than
in the prior studies. Drug suspension was prepared in the labora-
tory by adding 40g of acetaminophen powder with 0.6 g Vivasol®
GF to 400 ml of Flavor Blendsuspending vehicle from which 10
ml (1000 mg) aliquots were administered to participants. Placebo
solutions were prepared in the same manner by adding 40 g
of Avicel® PH-105 microcrystalline cellulose powder with 0.6
g Vivasol®GF to 400 ml of Flavor Blendsuspending vehicle.
All products were prepared and provided by Pharmacy Spe-
cialists Compounding Pharmacy (Altamonte Springs, Florida;
http://www.makerx.com/).
Procedure. The procedure was similar to prior studies. After
consenting and consuming drug or placebo, participants com-
pleted background questionnaires. At least 45 min later, partic-
ipants completed two tasks (Columbia Card Task (Figner et al.,
2009) and the Iowa Gambling task (Bechara et al., 1994); these
data have not been analyzed and will be reported separately)
followed by the BART. A different software platform (Inquisit,
www.millisecond.com) was used to implement the BART. An
additional change in procedure was that after the rst 15 bal-
loons, participants completed the same self-report items as in
Study 2, which were repeated after the nal 15 balloons. Partic-
ipants did not complete any self-reported risk perception items
in this study.
Results and discussion
Unlike the prior studies, participants in the acetaminophen con-
dition were better at guessing their condition; 61.2% correctly
guessed their condition, a proportion signicantly better than
chance, t=2.45, P=0.02.
As measured by the average number of pumps on nonburst-
ing trials, we did not nd a signicant difference in risk taking
on the BART between the acetaminophen (M=24.13, s.d. =12.56)
and placebo condition (M=24.49, s.d.=13.30), t(213) =0.20,
P=0.84, 95% CI [3.11, 3.83] in this study (Figure 1, right panel).
Although we thought it plausible that guessed drug condition
might have predicted performance, according to an ANOVA, no
main effect existed of guessed drug condition (F(l,210) =1.59,
P=0.21) nor was there an interaction effect of guessed drug con-
dition (F(1,210) =0.32, P=0.57) with actual drug condition (one
subject did not guess condition). There was a greater number
of balloon bursts in the acetaminophen (M=6.56, s.d. =3.60)
than the placebo condition (M=6.17, s.d.=3.47); however,
the difference was not signicant (t(213) =.81, P=0.42, 95%
CI [1.34, 0.56]).
It should be noted that the average number of pumps in this
study (across both conditions), which used the Inquisit software
(M=24.31, s.d. =12.90) was signicantly less (F(2,543) =39.88,
729
A. Keaveney et al.
P< 0.0001) than that from the prior two studies that used the
PEBL software (Study 1, M=36.12 s.d. =15.50; Study 2 M=34.28,
s.d. =13.66). Similarly, the number of bursts in this study
(M=6.37, s.d. =3.53) was signicantly lower (F(2,543) =2185.73,
P< 0.001) than those in the prior two studies (Study 1: M=9.35,
s.d. =4.34; Study 2: M=9.14, s.d. =4.37). Consistent with
these differences, signicant differences existed in earnings
(F(2,545) =31.5, P< 0.001), with lower earnings in Study 3 (Study
1: M=$34.27, s.d. =10.14 Study 2: M=$34.02, s.d. =10.37; Study
3: M=$26.53, s.d. =11.95).
Combined analysis of studies 1, 2 and 3
As compilation of results across studies can lead to improved
interpretation of effects (Braver et al., 2014;Fabrigar and
Wegener, 2016), we combined data from all three studies.
In this compilation, there was a signicant main effect of
acetaminophen on BART risk taking (t(544) =2.26, P=0.024,
95% CI [5.35, 0.38], Cohen’s d=0.19) with a greater
average number of pumps on nonbursting balloons in the
acetaminophen condition (M=32.24, s.d. =15.40) than the
placebo condition (M=29.37, s.d. =14.11). Consistent with
the acetaminophen group engaging in greater risk taking,
there was a greater number of balloon bursts (t(544) =2.237,
P=0.026, 95% CI [1.543, 0.100]) in the acetaminophen condi-
tion (M=8.51, s.d. =4.28) than the placebo condition (M=7.68,
s.d. =4.30). This provides strong evidence that acetaminophen
increases risk-taking on the BART.
General discussion
Across three separate studies, acetaminophen increased risk
taking on the BART. In Study 2, acetaminophen also reduced
perceived risk on the DOSPERT, and this experimentally induced
reduction in perceived risk accounted for increased risk taking
on the BART, suggesting acetaminophen may reduce negative
affect and risk perception in turn and, thereby, increase risk
taking.
Acetaminophen did not reduce risk perceptions using the
Finucane items (Study 1) in contrast to the effects seen with
the DOSPERT risk perception items (Study 2). Motivated by
prior work showing that acetaminophen has greater effects on
affective stimuli rated to be more extreme in negative or posi-
tive valence than less extreme stimuli (Durso et al., 2015), our
additional online study (see supplementary material) provided
evidence that Study 2’s items were more affectively stimulat-
ing (e.g. they were rated more emotional and negative) than
Study 1’s items These ndings provide initial evidence that
acetaminophen can inuence risk judgments, especially for
more affectively stimulating stimuli.
Interestingly, although acetaminophen signicantly reduced
perceived risk in Study 2, it did not reduce perceived benet. One
potential explanation for the lack of effect on benet items is
that their phrasing may have elicited more cognitive evaluation,
whereas the risk questions may have been moreaffectively stim-
ulating. The risk questionnaire asked participants to rate ‘your
gut level assessment of how risky each situation or behavior is’
whereas the benet scale asks for ‘the benets you would obtain
from each situation’. An emphasis on gut level risk assessment
may increase reliance on the affect heuristic. This difference
may account for Study 2’s acetaminophen-caused reduced risk
perceptions and its lack of effect on perceived benets.
Although not all studies were independently signicant,
when treated in aggregate, a signicant relation emerged
between taking acetaminophen and choosing more risk. Mul-
tiple studies with effects in the same direction, even if not
signicant, reduce the probability that the population effect is
zero (Braver et al., 2014;Fabrigar and Wegener, 2016), suggest-
ing that this is a reliable effect. Potential factors contributing
to the lack of an effect in Study 3 could be the different drug
formulation that led to greater awareness of drug condition as
well as the differences in software used to implement the BART.
Each ination of the balloon using the software in Study 3 was
larger, leading to fewer pumps being necessary to ll the screen
and thus less overall pumps and bursts. Such reduced range may
have impaired the ability to detect a drug effect.
Another consideration is whether or not playing the BART
with actual money would have changed the results. Although
some controversy exists about the differential role of hypothet-
ical relative to monetary reinforcers on decision-making tasks
(Johnson and Bickel, 2002;Madden et al., 2003;Hinvest and
Anderson, 2010), it appears that when real monetary reinforcers
have differential effects they tend to amplify the differences
between conditions (Bowman and Turnbull, 2003). For exam-
ple, large monetary losses in a modied form of the BART
led to greater neural reactivity and reductions in risk behav-
ior than hypothetical losses (Xu et al., 2018). Thus, employing
a BART with real money could potentially enhance the effects of
acetaminophen.
Future directions
In addition to decreases in risk perception, other psychologi-
cal processes are likely involved in acetaminophen’s effects on
risk taking. One possible unexplored mechanism is anticipatory
experienced anxiety. It may be that as the balloon increases in
size, those on placebo feel increasing amounts of anxiety about
a potential burst. When the anxiety becomes too much, they
end the trial. Acetaminophen may reduce this anxiety, thus
leading to greater risk taking. As indicated in the supplement,
self-reported affective experiences to the BART did not differ
between conditions, but these recalled emotions may not reect
affective responses experienced in the moment.
Additionally, there are many potentially interesting ways in
which we might examine the impact of risk taking on tasks
that involve stronger positive affect. It may be the case that
risk-taking tasks that focus on the positive affect associated
with gains may actually show reverse effects of acetaminophen
due to acetaminophen’s affect-blunting effects. For instance, if
we manipulated the BART to make gain events more salient
(adding sounds and visuals) or more intense (larger payoffs),
acetaminophen may decrease risk taking.
Alternatively, acetaminophen’s effects on risk taking may
be driven less by affective inuences on judgment than by
effects on another psychological process such as learning dur-
ing the task (Pearson et al., 2018) or error monitoring. Event-
related potentials (ERPs) recorded during a Go/No-Go task, for
example, showed that acetaminophen reduced the error pos-
itivity (Pe), which partially mediated acetaminophen-induced
increases in omission errors (Randles et al., 2016). The Pe is a
signal that appears to be associated with the emergence of con-
scious awareness of committing an error (Nieuwenhuis et al.,
2001;Murphy et al., 2012) and highly correlated with activity in
the anterior insula (Ullsperger et al., 2010). Of note, the associa-
tion of greater anterior insula activation with anticipated risk is
one of the most reliable ndings in the neural decision-making
literature (Knutson and Huettel, 2015). Because acetaminophen
Social Cognitive and Affective Neuroscience, 2020, Vol. 15, No. 7730
blunts activity in the anterior insula (Dewall et al., 2010) as
well as the Pe, it may be inuencing risk-related processing
particularly at a conscious level. Dissecting such inuences on
the BART could provide insight into additional psychological
mechanisms accounting for the drug-induced increase in risk
taking.
Another question for future research will be identifying
the biological mechanisms responsible for these effects of
acetaminophen. Like more conventional nonsteroidal anti-
inammatory drugs (NSAIDs) such as ibuprofen and aspirin,
acetaminophen inhibits the production of prostaglandins in
the brain (Flower and Vane, 1972). The administration of such
drugs might provide insight into whether the prostaglandins
are involved in risk judgments as well as which enzymes
producing prostaglandins (cyclooxygenase 1 and cyclooxyge-
nase 2) are greater contributors to the effect. Alternatively,
acetaminophen may exert its effects on risk taking through a dif-
ferent biological pathway than the prostaglandins, potentially
through the vanilloid, cannabinoid or serotoninergic systems
(Graham et al., 2013).
Potential implications
With nearly 25% of the population consuming acetaminophen
each week (Kaufman et al., 2002), reduced risk perceptions
and increased risk taking could have important societal effects.
Many areas of daily life require making decisions that involve
the processes examined here. For example, many patients in
the hospital have acetaminophen in their systems when pre-
sented with risk information and asked to make potentially
life-changing risk assessments such as whether or not to do an
invasive surgery. Similarly, when driving, one is regularly
presented with decisions that involve risk perception and
assessment. Thus, it is imperative that we understand
acetaminophen’s effects on choices made and risks taken. Risk
perception and risk taking are judgments and decisions that can
affect many aspects of our lives, and this common, over-the-
counter drug may inuence this process, unbeknownst to the
millions taking the drug.
Acknowledgements
We would like to acknowledge the helpful assistance of Liv Bobb,
Amanda Brown, Brittany Boltz, Michael Butrey, Japera Benson,
Nicole Hadjisofocli, Catie Johnson, Elianna Miller, Cori O’Boyle,
Maggie Walsh and Zachary Weisenseel.
Supplementary data
Supplementary data are available at SCAN online.
Open practices
The consent form completed by participants in these studies
stated, ‘Only the investigators and their research assistants will
have access to the original research data’. As a consequence, we
cannot share the original data publicly at this time. However, for
anyone interested in accessing the data for verifying our analy-
ses, please contact the authors. Study 1 (https://osf.io/p2e5c/)
and the online study reported in the supplemental material
(https://osf.io/496rc/) were preregistered with the Open Science
Framework.
Funding
This research was generously supported by funds from the Ohio
State University as well as the National Science Foundation
(Award #1558230; Peters (PI), Way (Co-I)). The funders had no
inuence on the design, collection, analysis and interpretation
of the data, writing of the report and decision to submit this
article for publication.
Conict of interest
The authors do not have any conicts of interest.
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