The short answer
Grapefruit fruit extract should be reviewed with the methadone prescriber. Juice studies show mixed effects, including increased exposure in one small study, but they do not define the risk of every extract or a safe timing gap.
What this answer covers
Citrus paradisi fruit extract; direct evidence is from grapefruit juice, not standardized equivalence to this extract node.
- Supplement or preparation
- Citrus Paradisi (Grapefruit) Fruit Extract
- Medication ingredient
- methadone
The human studies are not uniform
One small maintenance study found a modest exposure increase without overmedication symptoms. Another study in healthy volunteers found no meaningful change in methadone concentrations or measured clinical effects. Neither tested this exact fruit extract.
A clinical case adds concern but not certainty
A patient taking methadone developed opioid toxicity after reporting several days of grapefruit juice. A single temporal association cannot define the risk or prove the magnitude for a different extract.
Do not assume a simple CYP3A explanation
Methadone metabolism involves more than CYP3A, with human evidence supporting CYP2B6. Juice effects on oral treatment cannot automatically be assigned to injection or every grapefruit formulation.
Use an individual product review
Show the prescriber the extract label before using it. A short separation interval is not established protection, and the juice trials do not supply an extract dose limit. Unexpected marked sedation, slow breathing or difficulty waking requires urgent help.
Evidence and practical considerations
Timing & monitoring
Conditional review/avoid-unsupervised-use precaution extrapolated from mixed grapefruit-juice evidence and a toxicity case; exact fruit extract equivalence and protective spacing are unproven.
- Exact scope
- Citrus paradisi fruit extract; direct evidence is from grapefruit juice, not standardized equivalence to this extract node. 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: Eight methadone-maintenance patients.
Mean methadone exposure increased modestly, with no observed or reported overmedication symptoms.
How this applies: Eight maintenance patients; fruit extract composition may differ from juice and no protective interval tested.
Eight maintenance patients; fruit extract composition may differ from juice and no protective interval tested.
Source 4: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Healthy volunteers.
No significant effect on methadone concentrations, clearance or clinical pupil effects under tested conditions.
How this applies: Healthy-volunteer design differs from steady-state maintenance; null findings cannot guarantee every juice/extract is safe.
Healthy-volunteer design differs from steady-state maintenance; null findings cannot guarantee every juice/extract is safe.
Source 5: original case report
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: One51-year-old methadone-maintenance patient.
Opioid toxidrome treated with naloxone; temporal grapefruit association reported.
How this applies: Single case, reported intake; abstract does not provide a demonstrated before/after methadone concentration or exclude every alternative cause. Fruit extract not tested.
Single case, reported intake; abstract does not provide a demonstrated before/after methadone concentration or exclude every alternative cause. Fruit extract not tested.
Source 6: 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: 7303786c54391997
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.