Acetaminophen / dextromethorphan / doxylamine

An over-the-counter nighttime cold and flu combination of acetaminophen, dextromethorphan (a cough suppressant) and doxylamine (a sedating antihistamine).

psilodex.org/m/acetaminophen-dextromethorphan-doxylamine · 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: doxylamine ~12 h, dextromethorphan ~2–3 h (see dextromethorphan record).

Named in state rules?

Not namedColorado Condition rules (3)

Not namedOregon

PendingNew Mexico

Cite asPsilodex, “Acetaminophen / dextromethorphan / doxylamine”, v2026.10.04. psilodex.org/m/acetaminophen-dextromethorphan-doxylamine

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

What it is used for

FDA status

Over the counter under an FDA monograph

Sold over the counter under FDA's OTC monograph for cough, cold and allergy products (M012), not individually approved.

Availability

OTC

FDA-approved for

Common cold and flu symptoms: cough, sore throat, headache, minor aches and pains, fever, runny nose and sneezing

Sources [1]

01 Interaction with psilocybin

In theory its dextromethorphan adds serotonin and dissociative effects, and its doxylamine adds sedation and possible confusion, alongside psilocybin.

Detail Dextromethorphan is serotonergic and an NMDA antagonist, adding serotonin and dissociative effects in theory. Doxylamine is sedating and anticholinergic, with confusion or delirium possible in an altered state. Acetaminophen has no known interaction. Acetaminophen labels 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.

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

5 listed · counted on reports

Anticholinergic: Blocks acetylcholine. Can cause a fast heart rate, dry mouth, reduced sweating and heat intolerance, and confusion, more so at high doses or in combination. Sources [4]
Sedating or CNS depressant: Slows the central nervous system: drowsiness, slower reactions and impaired coordination, and slowed breathing at high doses. Effects add with other sedating substances. Sources [1]
Dissociative (NMDA antagonist): Blocks NMDA receptors and can cause dissociation: feeling detached from the body or surroundings. Effects can add to psilocybin’s. Sources [3]
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]
Serotonergic: Increases serotonin activity, for example by blocking its reuptake or releasing it. Psilocybin acts on serotonin receptors, so effects can add together. With antidepressant use, the psilocybin response can be weaker. Sources [2]

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

Vicks NyQuil Cold & Flu LiquiCaps (acetaminophen 325 mg, dextromethorphan HBr 15 mg, doxylamine succinate 6.25 mg) Drug Facts · FDA label (DailyMed) — revised 2025-12-01 | cns_depressant: "marked drowsiness may occur" | liver_injury: Warnings: Liver warning "Severe liver damage may occur if you take • more than 8 LiquiCaps in 24 hours, which is the maximum daily amount for this product"
NUEDEXTA (dextromethorphan/quinidine) — section 10 Overdosage · FDA label (DailyMed) — revised 2026-01-22 | serotonergic: "Dextromethorphan may cause serotonin syndrome, and this risk is increased by overdose, particularly if taken with other serotonergic agents, SSRIs or tricyclic antidepressants."
AUVELITY (dextromethorphan–bupropion) — section 12.1 · FDA label (DailyMed) — revised 2026-08-17 | dissociative: "Dextromethorphan is an uncompetitive antagonist of the NMDA receptor"
DICLEGIS (doxylamine/pyridoxine) — section 5.1 · FDA label (DailyMed) — revised 2025-12-03 | anticholinergic: "DICLEGIS may cause somnolence due to the anticholinergic properties of doxylamine succinate, an antihistamine."

Record history

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

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