The Effects of Acetaminophen on Fear

Overseen By Savannah Yerman, M.A.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Guelph

Must not be taking: Blood thinners

Disqualifiers: Liver disease, Kidney disease, Pregnancy, others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 hour

266 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial investigates whether acetaminophen can reduce fear responses in people. It aims to see if the drug can help those with anxiety by making them feel less scared, similar to how it reduces other types of pain.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking blood-thinning medications or other products with acetaminophen.

What data supports the effectiveness of the drug acetaminophen?

Research shows that acetaminophen is effective in reducing pain in children after ear, nose, and throat surgeries when given before the procedure. It is also widely used to relieve mild-to-moderate pain and reduce fever. ^{1 2 3 4 5}

Is acetaminophen (paracetamol) generally safe for humans?

Acetaminophen (paracetamol) is widely used and has a consistent safety profile with a very low incidence of side effects. However, there are rare cases of skin reactions and fixed drug eruptions associated with its use. ^{6 7 8 9 10}

How does the drug acetaminophen differ from other treatments for pain and fever?

Acetaminophen is unique because it is an analgesic (pain reliever) and antipyretic (fever reducer) that does not have anti-inflammatory effects, unlike many other pain medications such as NSAIDs (non-steroidal anti-inflammatory drugs). It is also known for having a low rate of adverse hypersensitivity reactions, making it a safer option for individuals who may have skin reactions to other pain medications. ^{1 6 11 12 13}

Research Team

Pat Barclay, Ph.D.

Principal Investigator

University of Guelph

Eligibility Criteria

Inclusion Criteria

Literate

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either 1000 mg acetaminophen or 1000 mg placebo and engage in virtual reality tasks to assess fear responses

1 hour

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

Treatment Details

Interventions

• Acetaminophen
• Placebo

Participant Groups

Group I: Acetaminophen Condition Experimental Treatment 1 Intervention

1000 mg acetaminophen

Group II: Placebo Condition Placebo Group 1 Intervention

1000 mg microcrystalline cellulose

Acetaminophen is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Tylenol for:

• Pain relief
• Fever reduction

Approved in European Union as Paracetamol for:

• Pain relief
• Fever reduction

Approved in Canada as Tylenol for:

• Pain relief
• Fever reduction

Who Is Running the Clinical Trial?

University of Guelph

Lead Sponsor

Trials

87

Recruited

15,100+

Natural Sciences and Engineering Research Council, Canada

Collaborator

Trials

63

Recruited

3,000+

Findings from Research

Paracetamol, first marketed in the U.K. in 1956, is widely used as an analgesic (pain reliever) and antipyretic (fever reducer).

It has gained popularity among both healthcare professionals and the public as a safer alternative to aspirin for pain and fever management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paracetamol. Meredith, TJ., Goulding, R.[2019]

The new fast-dissolving acetaminophen tablet formulation (FD-APAP) disintegrates significantly faster than standard acetaminophen tablets, with a mean disintegration time of 12.9 minutes compared to 69.6 minutes (P < 0.0001).

FD-APAP also shows a quicker absorption rate, with a median time to peak concentration (Tmax) of 0.50 hours versus 0.67 hours for standard acetaminophen (P < 0.01), potentially leading to improved pain relief outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of a novel fast-dissolving acetaminophen tablet formulation (FD-APAP) and standard acetaminophen tablets using gamma scintigraphy and pharmacokinetic studies. Wilson, CG., Clarke, CP., Starkey, YY., et al.[2022]

In a study of 57 malaria patients, the combination of Artemisinin-Based Combination Therapies (ACTs) with paracetamol significantly altered 24 out of 37 evaluated toxicity markers, indicating potential safety concerns with this treatment regimen.

The findings suggest that careful selection of ACTs plus paracetamol is crucial, especially for patients with existing health conditions, due to the observed changes in various biochemical and haematological indices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicological effect of Artemisinin-Based Combination Therapies plus Paracetamol in malaria patients. Aghahowa, SE., Ozolua, RI., Bafor, EE., et al.[2023]

Ibuprofen has been shown to be effective for treating acute migraine attacks in children, providing pain relief at 2 hours compared to a placebo, with no significant difference in adverse events reported.

Paracetamol did not demonstrate a significant difference in efficacy compared to placebo, and there was no notable difference in effectiveness between ibuprofen and paracetamol for treating migraines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of acute migraine attacks in children with analgesics on the World Health Organization Essential Medicines List: A systematic review and GRADE evidence synthesis. Jeric, M., Surjan, N., Jelicic Kadic, A., et al.[2019]

In a survey of 5000 patients, nearly 50% were found to have contraindications for ibuprofen, suggesting that many individuals may not safely use this common over-the-counter pain reliever, while only 6.8% had contraindications for paracetamol.

The findings indicate that the results of the PAIN study, which suggested similar tolerability for ibuprofen and paracetamol, may not apply to the general population, as the study excluded many patients who could be at risk when using ibuprofen without medical supervision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective survey to compare the suitability profiles of over-the-counter ibuprofen and paracetamol use in a French general practitioner-controlled population. Pigeon, P., Robillard, E., Clarke, GD., et al.[2018]

In a study involving 97 children aged 6 to 12 with pharyngotonsillitis, paracetamol syrup was found to be significantly more effective than placebo in reducing pain, as reported by both children and parents.

Both paracetamol and ketoprofen lysine salt were shown to be safe and effective analgesics for treating sore throat in children, with no significant adverse effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled trial of paracetamol and ketoprofren lysine salt for pain control in children with pharyngotonsillitis cared by family pediatricians. Ruperto, N., Carozzino, L., Jamone, R., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Treatment with paracetamol in infants. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Paracetamol. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

The Effect of Pre-Emptive Analgesia on the Postoperative Pain in Pediatric Otolaryngology: A Randomized, Controlled Trial. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Comparison of a novel fast-dissolving acetaminophen tablet formulation (FD-APAP) and standard acetaminophen tablets using gamma scintigraphy and pharmacokinetic studies. [2022]

5. France pubmed.ncbi.nlm.nih.gov

[Paracetamol and other antipyretic analgesics: optimal doses in pediatrics]. [2013]

6. Spain pubmed.ncbi.nlm.nih.gov

Safety of celecoxib in patients with adverse skin reactions to acetaminophen (paracetamol) and other non-steroidal anti-inflammatory drugs. [2015]

7. Ireland pubmed.ncbi.nlm.nih.gov

Toxicological effect of Artemisinin-Based Combination Therapies plus Paracetamol in malaria patients. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Cellulitis-like fixed drug eruption attributed to paracetamol (acetaminophen). [2013]

9. India pubmed.ncbi.nlm.nih.gov

Antipyretic activity of diacetyl para-amino phenol. [2013]

10. England pubmed.ncbi.nlm.nih.gov

Treatment of acute migraine attacks in children with analgesics on the World Health Organization Essential Medicines List: A systematic review and GRADE evidence synthesis. [2019]

11. New Zealand pubmed.ncbi.nlm.nih.gov

A prospective survey to compare the suitability profiles of over-the-counter ibuprofen and paracetamol use in a French general practitioner-controlled population. [2018]

12. England pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled trial of paracetamol and ketoprofren lysine salt for pain control in children with pharyngotonsillitis cared by family pediatricians. [2021]

13. Australia pubmed.ncbi.nlm.nih.gov

Systematic evaluation of the nefopam-paracetamol combination in rodent models of antinociception. [2014]