Codeine–guaifenesin

A cough syrup combining codeine, an opioid cough suppressant, with guaifenesin, an expectorant, for cough from colds or inhaled irritants.

psilodex.org/m/codeine-guaifenesin · data v2026.10.05

Clinical contraindication: None listed; No label contraindication covering psilocybin was found. This is not a finding that the combination has been shown to be without risk.
Psilocybin evidence: No psilocybin data
Half-life: Not stated in label or references

Named in state rules?

Not namedColorado

Not namedOregon

PendingNew Mexico

Cite asPsilodex, “Codeine–guaifenesin”, v2026.10.05. psilodex.org/m/codeine-guaifenesin

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

Carries over-the-counter Drug Facts labeling under FDA's cough and cold monograph.

FDA-approved for

Cough from minor throat and bronchial irritation (colds, inhaled irritants)
Loosening phlegm (mucus) in the chest

Sources [1]

Other safety

Boxed warning: addiction, abuse and misuse; life-threatening respiratory depression; and profound sedation, respiratory depression, coma and death when combined with benzodiazepines or other CNS depressants, including alcohol.

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

Sources [2]

01 Interaction with psilocybin

Codeine's sedation and nausea may add to psilocybin's nausea. Stopping it suddenly after regular use can cause withdrawal.

Detail Codeine is an opioid agonist. Its sedation and nausea may add to psilocybin's nausea and to other sedatives. Psilocybin does not depress breathing, but codeine can, especially at higher doses or with other sedatives. The codeine label reports serotonin syndrome when opioids are combined with serotonergic (serotonin-boosting) drugs; there are no psilocybin data. Also, the label reports severe hypotension (low blood pressure) and more frequent seizures in people with seizure disorders. Codeine's conversion to morphine varies with CYP2D6 genotype (genetic makeup). Stopping after regular use can cause withdrawal. Guaifenesin alone has no known interaction. Sources [2]

Human data with psilocybin: No psilocybin data; based on how it works and its label

Evidence types on this record

No psilocybin dataNo psilocybin data: no human data with psilocybin or another classic psychedelic; the text draws on the medication's own pharmacology and its label or reference facts

02 Pharmacology relevant to psilocybin

6 listed · counted on reports

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 [2]
Withdrawal or rebound if stopped abruptly: Stopping suddenly can cause withdrawal or a rebound of symptoms. Sources [2]
Lowers blood pressure or causes orthostasis: Lowers blood pressure, or causes a drop on standing (orthostasis) that can bring dizziness or fainting. Sources [2]
Opioid: Activates opioid receptors, causing pain relief, sedation and slowed breathing at higher doses. Psilocybin does not slow breathing, but stopping an opioid suddenly can cause withdrawal. Sources [2]
Lowers seizure threshold or carries seizure risk: Makes a seizure more likely, or has been linked to seizures. Sources [2]
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 named

No provision names this medication or its class.

Colorado · checked 2026-10-04

OROAR 333-333

Not named

No provision names this medication or its class.

Oregon · checked 2026-10-04

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 2026-10-04

04 Conditions to ask about

None linked

No condition named in state rules is linked to this medication.

05 Sources

Codeine-Guaifenesin Oral Solution (Method Pharmaceuticals) - Drug Facts · FDA label (DailyMed) — Uses: "cough due to minor throat and bronchial irritation as may occur with a cold or inhaled irritants" | Purpose: codeine phosphate "Antitussive"; guaifenesin "Expectorant"
Codeine Sulfate Tablets (codeine component) · FDA label (DailyMed) — Opioid: 12.1 "Codeine sulfate is an opioid agonist relatively selective for the mu-opioid receptor" | Sedating or CNS depressant: Boxed Warning "Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death." | Serotonergic: 7 Drug Interactions "The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome." | Lowers blood pressure or causes orthostasis: 5.12 "Codeine sulfate tablets may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients." | Lowers seizure threshold or carries seizure risk: 5.15 "may increase the frequency of seizures in patients with seizure disorders" | Withdrawal or rebound if stopped abruptly: 5.16 "Do not rapidly reduce or abruptly discontinue codeine sulfate tablets in a patient physically dependent on opioids." | 5.6 "Codeine is subject to variability in metabolism based upon CYP2D6 genotype"
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
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.
2026-10-04Last reviewed against its sources.

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