The short answer
Goldenseal may change codeine’s effects by inhibiting drug-metabolizing enzymes. The concern is metabolism and conversion to morphine, not proven reduced intestinal absorption; the net effect of a particular product is uncertain.
What this answer covers
Hydrastis canadensis extract products; not isolated berberine or every root preparation.
- Supplement or preparation
- Hydrastis canadensis
- Medication ingredient
- codeine
Human studies show enzyme inhibition
Goldenseal inhibited CYP2D6 in a debrisoquine probe study and CYP3A in a separate midazolam study. Neither measured codeine and morphine together.
The active metabolite matters
Codeine depends partly on CYP2D6 conversion to morphine. Blocking that pathway can reduce analgesia even while codeine levels rise. CYP3A inhibition can affect a competing pathway, making a one-direction prediction unreliable.
Do not borrow the probe-drug percentage
The goldenseal studies used specific products in healthy volunteers. Their enzyme or midazolam changes cannot be assigned as a percentage change in codeine pain relief, blood levels or safety.
Review starting and stopping goldenseal
Tell the prescriber before changing use and report inadequate pain control or unusual sedation. Do not increase codeine yourself; stopping an enzyme-inhibiting product may also change the response. A short gap is not established protection.
Evidence and practical considerations
Absorption & effectiveness
Conditional metabolism/effectiveness interaction based on human goldenseal CYP2D6/CYP3A inhibition plus exact codeine active-metabolite label; no measured exact-pair absorption or net magnitude.
- Exact scope
- Hydrastis canadensis extract products; not isolated berberine or every root preparation. with Codeine RxCUI2670 IN; current oral single-ingredient sulfate label, active morphine metabolism and formulation boundaries.
- Medication form and route
- oral medication; oral supplement
What remains uncertain
- No unmeasured pair incidence, blanket class transfer or arbitrary spacing interval.
Factors that may matter: Preparation; Dose; Other medicines; Organ function.
Read the supporting source summaries
Source 1: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed codeine
Codeine is converted to active morphine via CYP2D6. CYP2D6 inhibition can reduce morphine/effect despite increased codeine; CYP3A interactions complicate disposition. CNS-depressant combinations can cause serious sedation/respiratory depression.
How this applies: Exact codeine RxCUI 2670 IN, with stated salt/formulation/route bridge.
Not cough combination products or every salt formulation. No exact botanical risk rate; genotype, age and co-medications matter.
Source 2: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: 16 healthy volunteers in the relevant study.
CYP2D6 activity decreased after goldenseal; other tested extracts, including kava and St John’s wort, did not significantly inhibit this probe measure.
How this applies: Debrisoquine, not codeine or dextromethorphan; urinary metabolic ratio not a codeine/morphine concentration change.
Debrisoquine, not codeine or dextromethorphan; urinary metabolic ratio not a codeine/morphine concentration change.
Source 3: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: 16 healthy volunteers.
Goldenseal increased midazolam exposure; kava did not significantly alter its disposition.
How this applies: Midazolam is not codeine. Inhibition of both CYP3A and CYP2D6 cannot yield a simple predicted net codeine effect.
Midazolam is not codeine. Inhibition of both CYP3A and CYP2D6 cannot yield a simple predicted net codeine effect.
Research assessment: · Open full citations ↗
Review and change history
- Publication status
- Published research summary
- Clinical review
- Not yet recorded
| Date | Update |
|---|---|
| Article prepared | |
| Prepared exact codeine article with formulation-specific evidence and uncertainty. | |
| Research summary published |
Article revision: e3f2972bfdeaf937
This guide brings together the evidence records used by our interaction checker. Each finding retains its own preparation limits, research date, and source summaries.
Full citations require verification. Reading this answer and the source summaries does not.
Taking other supplements or medications?
Use the checker to explore your other combinations. Ask a pharmacist to review the exact products, amounts and medical conditions in your complete list.
Open the interaction checkerInformation, not medical advice. Do not change prescribed treatment based on this guide.