PsilodexMedication × psilocybin
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Supplements and over the counter
Brand names
Excedrin Extra Strength, Excedrin Migraine
Reviewed 2026-10-03

Acetaminophen / aspirin / caffeine

An over-the-counter combination of acetaminophen, aspirin (an NSAID) and caffeine, FDA-approved for headache and minor aches (Extra Strength) and migraine (Migraine).

psilodex.org/m/acetaminophen-aspirin-caffeine · data v2026.10.04

Clinical contraindication
None listed
No clinical contraindication identified.
Psilocybin evidence
Mechanism only
Half-life
Not stated in label or references
Components differ (see acetaminophen and aspirin records).
Named in state rules?
Not namedColorado Condition rules (3)
Not namedOregon
PendingNew Mexico
Cite asPsilodex, “Acetaminophen / aspirin / caffeine”, v2026.10.04. psilodex.org/m/acetaminophen-aspirin-caffeine

Clinical data and state rules are separate facts. Both are shown; neither is a decision.

What it is used for

FDA status

FDA-approved

Excedrin Migraine is FDA-approved; Excedrin Extra Strength and similar products are sold under FDA's OTC monograph for internal analgesics (M013).

Availability

OTC

FDA-approved for
  • Minor aches and pains (headache, colds, arthritis, muscular aches, toothache, menstrual cramps)
  • Migraine
Sources [1][2]
Other safety

Its Drug Facts carry a liver warning: severe liver damage can occur above the maximum daily amount, with other acetaminophen-containing products, or with 3 or more alcoholic drinks a day. A stomach bleeding warning covers the aspirin component, with higher chance at age 60 or older, with prior ulcers, or with blood thinners or steroids.

About the medication itself, separate from any interaction with psilocybin.

Sources [1]

01 Interaction with psilocybin

Th

In theory its caffeine may add to psilocybin's transient heart rate rise; acetaminophen and aspirin have no known interaction with psilocybin.

Detail No known interaction for acetaminophen or aspirin. The label states too much caffeine may cause nervousness, irritability, sleeplessness and occasionally rapid heartbeat; psilocybin also transiently raises heart rate and blood pressure. Sources [2]

No reported interaction is not a finding of safety: most combinations with psilocybin have never been studied.

Human data with psilocybin
None known: no published human data with psilocybin
Evidence types on this record
Mechanism onlyMechanism only (theoretical)

02 Pharmacology relevant to psilocybin

2 listed · counted on reports
Liver injury
The label or source warns of liver injury, from raised liver enzymes to liver failure. Liver disease also affects how the body clears psilocin. Sources [1]
Raises blood pressure or heart rate
Raises blood pressure or heart rate. Psilocybin raises both for several hours, so the effects can add. Sources [1]

03 State rules

Plain-language summary · official text governs
CO4 CCR 755-1
Not namedCondition rules (3)

No provision names this medication or its class.

Colorado · checked 2026-09-30
OROAR 333-333
Not named

No provision names this medication or its class.

Oregon · checked 2026-09-30
NM7.35.3 NMAC (proposed)
Pending

New Mexico's clinical rules (proposed 7.35.3 NMAC) are not final. No provision naming this medication has been found.

New Mexico · checked 2026-10-02

04 Conditions to ask about

Screening items in state rules

This medication is usually taken for a condition. State rules screen for some conditions directly, so the medication is a prompt to ask about them. Confirm with the participant; never assume a condition from the medication.

  • Liver disease if heavy use
    • CO 2.5(A)(2) · Clinical Facilitator licensees
    • CO 6.16(F)(2)(a) · Facilitators without a clinical facilitator license
    • CO 6.16(F)(1) · All licensees

05 Sources

4
  1. EXCEDRIN MIGRAINE (acetaminophen, aspirin, caffeine) Drug Facts (Haleon) · FDA label (DailyMed) — revised 2025-03-11 | raises_bp_hr: "too much caffeine may cause nervousness, irritability, sleeplessness, and, occasionally, rapid heart beat" | liver_injury: Warnings: Liver warning "Severe liver damage may occur if you take •more than 2 caplets in 24 hours, which is the maximum daily amount"
  2. Excedrin Extra Strength Pain Reliever (acetaminophen, aspirin, caffeine) Drug Facts (Haleon) · FDA label (DailyMed) — revised 2024-04-05 | interaction: "too much caffeine may cause nervousness, irritability, sleeplessness"
  3. Halman A, Kong G, Sarris J, Perkins D. Drug–drug interactions involving classic psychedelics: a systematic review. J Psychopharmacol 2024;38(1):3–18. — no reported interaction
  4. Sarparast A, Thomas K, Malcolm B, Stauffer CS. Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review. Psychopharmacology 2022;239(6):1945–1976. — no reported interaction

Record history

  • v2026.10.02First published.
  • 2026-10-03Last reviewed against its sources.

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Before you startTerms 2026-10-01

What Psilodex is, and isn't.

  1. 01Psilodex summarizes published evidence and public state rules. It does not decide whether you can safely use psilocybin or take part in services, and it is not medical advice.
  2. 02Psilodex presents information only. Do not stop or change a medication without talking with the prescriber. Bring the report to them.
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