The short answer
St. John’s wort can lower methadone exposure and may cause loss of withdrawal control. Starting or stopping it needs review by the methadone prescriber; separating the doses by a few hours is not an established solution.
What this answer covers
Hypericum perforatum oral extracts; the direct report used a specific900mg/day preparation.
- Supplement or preparation
- Hypericum perforatum
- Medication ingredient
- methadone
A small direct study found lower levels
Four patients had lower methadone concentration-to-dose ratios after starting St. John’s wort, and two reported symptoms suggesting withdrawal. The uncontrolled study supports concern but does not define the response to every product.
Metabolism is different from absorption
The methadone label names St. John’s wort among enzyme inducers that may produce withdrawal. A lower blood level does not show that less drug crossed the intestine, and methadone handling cannot be reduced to one CYP pathway.
Stopping the herb also matters
A change in enzyme induction can change methadone exposure over time. Do not increase methadone yourself or abruptly alter treatment to compensate; the prescriber should assess symptoms and the full medication list.
Review co-use rather than guessing a gap
Tell the treatment team before starting or stopping the herb. A short interval does not reliably avoid an enzyme-mediated interaction. Report withdrawal symptoms or unexpected sedation promptly.
Evidence and practical considerations
Timing & monitoring
Direct small human series and exact label support reduced methadone exposure/effect and supervised co-use review; intestinal absorption reduction and protective spacing are not established.
- Exact scope
- Hypericum perforatum oral extracts; the direct report used a specific900mg/day preparation. with Methadone6813 IN; exact oral hydrochloride preparation and injection distinguished; maintenance-study limits retained.
- Medication form and route
- oral medication; parenteral 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 methadone
Long/variable elimination, respiratory depression, CNS-depressant and QT warnings; enzyme interactions including St John’s wort can change exposure.
How this applies: Exact methadone RxCUI 6813 IN, with stated salt/formulation/route bridge.
Not interchangeable administration with swallowed tablets, concentrates or injection; opioid-use-disorder care must remain supervised.
Source 2: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed methadone
CNS-depressant and metabolic interaction precautions; individual dose and response vary.
How this applies: Exact methadone RxCUI 6813 IN, with stated salt/formulation/route bridge.
Oral grapefruit studies do not establish an injected-drug intestinal interaction.
Source 3: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Four methadone-maintenance patients.
Methadone concentration-to-dose ratios fell to a median47% of baseline; two patients reported withdrawal-like symptoms.
How this applies: Four-person uncontrolled observation, one preparation; reduced blood levels do not establish reduced intestinal absorption.
Four-person uncontrolled observation, one preparation; reduced blood levels do not establish reduced intestinal absorption.
Source 4: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Human crossover participants and laboratory enzyme systems.
Supported an important CYP2B6 role; CYP3A inhibition did not alter R- or S-methadone concentrations.
How this applies: Mechanism depends on study conditions; do not infer every botanical effect from CYP3A inhibition alone.
Mechanism depends on study conditions; do not infer every botanical effect from CYP3A inhibition alone.
Research assessment: · Open full citations ↗
Absorption & effectiveness
Direct small human series and exact label support reduced methadone exposure/effect and supervised co-use review; intestinal absorption reduction and protective spacing are not established.
- Exact scope
- Hypericum perforatum oral extracts; the direct report used a specific900mg/day preparation. with Methadone6813 IN; exact oral hydrochloride preparation and injection distinguished; maintenance-study limits retained.
- Medication form and route
- oral medication; parenteral 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 methadone
Long/variable elimination, respiratory depression, CNS-depressant and QT warnings; enzyme interactions including St John’s wort can change exposure.
How this applies: Exact methadone RxCUI 6813 IN, with stated salt/formulation/route bridge.
Not interchangeable administration with swallowed tablets, concentrates or injection; opioid-use-disorder care must remain supervised.
Source 2: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed methadone
CNS-depressant and metabolic interaction precautions; individual dose and response vary.
How this applies: Exact methadone RxCUI 6813 IN, with stated salt/formulation/route bridge.
Oral grapefruit studies do not establish an injected-drug intestinal interaction.
Source 3: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Four methadone-maintenance patients.
Methadone concentration-to-dose ratios fell to a median47% of baseline; two patients reported withdrawal-like symptoms.
How this applies: Four-person uncontrolled observation, one preparation; reduced blood levels do not establish reduced intestinal absorption.
Four-person uncontrolled observation, one preparation; reduced blood levels do not establish reduced intestinal absorption.
Source 4: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Human crossover participants and laboratory enzyme systems.
Supported an important CYP2B6 role; CYP3A inhibition did not alter R- or S-methadone concentrations.
How this applies: Mechanism depends on study conditions; do not infer every botanical effect from CYP3A inhibition alone.
Mechanism depends on study conditions; do not infer every botanical effect from CYP3A inhibition alone.
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 methadone article with formulation-specific evidence and uncertainty. | |
| Research summary published |
Article revision: 89b7a5bc465a6eed
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.