The Effects of Acetaminophen on Fear

Behavioral Consequences of Blunting Fear With Acetaminophen

This study investigates the effects of acetaminophen on behavioral, physiological, and self-report fear responses.

Study Overview

• Status: Recruiting
• Conditions: Fear
• Intervention / Treatment: Drug: Acetaminophen; Other: Placebo

Detailed Description

As acetaminophen blunts the experience of physical, social, and empathic pain, it is important to investigate whether there are other aversive states that the drug also provides relief from. If there are others, this may suggest overlapping mechanisms involved in these affective evaluations, all of which are interrupted by acetaminophen. The emotion of fear is aversive, yet it is distinct from both physical and social pain.

The present study will investigate the effects of acetaminophen on the subjective experience of fear as well as its behavioral outcomes. While blocking adaptive behavioral responses to fear could potentially be problematic in some dangerous situations, it may also be helpful for those with anxiety-related disorders. If individuals on acetaminophen can step farther away from safety on a virtual plank 80 stories above the ground, then perhaps acetaminophen can allow anxious individuals to step farther from their comfort zone in real life. Importantly, if acetaminophen blunts the fear response, this would mean that the drug blocks aversive feelings beyond emotional and physical pain. The extent of its effects will warrant further investigation for a greater understanding of emotional evaluations.

• Study Type: Interventional
• Enrollment (Anticipated): 266
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Savannah Yerman, M.A.; Phone Number: 5197311004; Email: syerman@uoguelph.ca

Study Locations

• Canada
  • Ontario
    • Guelph, Ontario, Canada, N1G 2W1
      • Recruiting
      • University of Guelph
      • Contact: Email: reb@uoguelph.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years or older
• Literate
• Speaks English
• Does not have any risk factors associated with acetaminophen (history of liver or kidney disease, taking other products with acetaminophen, has any allergies to acetaminophen, taking blood-thinning medications, drinks more than 12 alcoholic drinks per week for females, or more than 15 alcoholic drinks per week for males, are/ could be pregnant)
• Has taken acetaminophen in the past without any adverse reactions
• Is not diabetic
• Did not have anything to eat within three hours of study time
• Did not have any acetaminophen or alcohol in the 48 hours prior to study
• Has never had an adverse reaction to virtual reality before, such as headaches or nausea

Exclusion Criteria:

• Younger than 18
• Non-literate
• Does not speak English
• Has at least one risk factor associated with acetaminophen (history of liver or kidney disease, taking other products with acetaminophen, has any allergies to acetaminophen, taking blood-thinning medications, drinks more than 12 alcoholic drinks per week for females, or more than 15 alcoholic drinks per week for males, are/ could be pregnant)
• Has never taken acetaminophen before
• Diabetic
• Had something to eat within three hours of scheduled study time
• Has had acetaminophen or alcohol in the past 48 hours
• Has had an adverse reaction to virtual reality in the past, such as headaches or nausea

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acetaminophen Condition; 1000 mg acetaminophen	Drug: Acetaminophen; 2 x 500 mg acetaminophen (one time)
Placebo Comparator: Placebo Condition; 1000 mg microcrystalline cellulose	Other: Placebo; 2 x 500 mg microcrystalline cellulose (one time)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Walking speed on plank in virtual reality	Farthest distance reached on plank / time to get there	1 hour after taking acetaminophen or placebo
Distance walked on plank	(Unless there are ceiling effects in which >90% of people make it to the end.) Measured in cm walked on a 2 m wooden plank before deciding to turn around and walk back.	1 hour after taking acetaminophen or placebo
Proportion of time spent looking down at the plank	We will record what participants see in virtual reality while doing the plank walk, and then code the footage to calculate the proportion of time on the plank participants spent looking down at the plank (indicating more anxiety about falling off).	1 hour after taking acetaminophen or placebo
Decision on whether to do the plank walk again with virtual spiders	After doing the plank walk, participants will be offered an optional second chance to try the same plank walk again but this time with virtual giant spiders around them.	1 hour after taking acetaminophen or placebo
Verbal Self-Report Fear	While participants are in virtual reality, we will ask them to rate their fear verbally twice, once when they first step onto the plank, and once when they have changed direction (during which the plank tends to shake). They will answer from 0 (no fear or anxiety) to 10 (extreme fear or anxiety). For those who decide to do the plank walk again with virtual giant spiders, they will also rate their self-reported fear in the same manner twice, once when the spiders first appear, and once when they are on their way back to the virtual elevator while surrounded by giant spiders.	1 hour after taking acetaminophen or placebo
Written Self-Report Fear	After taking off the headset, participants will answer two survey questions. The first is, "How scary do you think most people would agree the act of walking on a virtual plank is?" They will answer on an 11-point scale (0 = Not at all scary, 5 = Moderately scary, 10 = Extremely scary). They will also be asked "How fearful, scared, nervous, or anxious did you personally feel when walking on the virtual plank?" (0 = Not at all fearful or anxious, 5 = Moderately fearful or anxious, 10 = Extremely fearful or anxious). Those who choose to do the second optional plank walk with virtual spiders will answer the same questions about that experience afterwards.	1 hour after taking acetaminophen or placebo
Heart rate	Average heart rate while on the plank walk, measured with a Polar Verity Sense optical heart rate sensor on forearm.	1 hour after taking acetaminophen or placebo

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to take first step onto plank	Number of seconds it takes participants to leave the virtual elevator for the plank overlooking a virtual 80-story drop.	1 hour after taking acetaminophen or placebo
Speed towards virtual elevator after turning around on plank,	Amount of time it takes them to make it back to the starting point after turning around on the plank. It is not clear whether someone who walks faster would be doing so to get back to the feeling safety quicker or because they are less cautious due to less fear, and so this is a secondary measure.	1 hour after taking acetaminophen or placebo
Time before needing a break or quitting the virtual reality plank walk	(Unless there are ceiling effects in which >90% of participants do not quit early or need a break). Amount of time before a participant takes their headset off early, to quit or for a break, due to being overwhelmed.	1 hour after taking acetaminophen or placebo

Collaborators and Investigators

• Sponsor: University of Guelph
• Collaborators: Natural Sciences and Engineering Research Council, Canada
• Investigators: Principal Investigator: Pat Barclay, Ph.D., University of Guelph

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2022
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: May 11, 2022
• First Submitted That Met QC Criteria: May 24, 2022
• First Posted (Actual): May 31, 2022

Study Record Updates

• Last Update Posted (Actual): May 31, 2022
• Last Update Submitted That Met QC Criteria: May 24, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: acetaminophen; virtual reality; analgesics; fear; emotions
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: 21-07-024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Open Science Framework
• IPD Sharing Time Frame: Upon publication or within two years
• IPD Sharing Access Criteria: Open Access
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No