The short answer
Kratom may add to methadone-related impairment, but its effect on methadone blood levels or absorption has not been established. Do not use it to replace, boost or adjust methadone treatment without the treatment team’s review.
What this answer covers
Mitragyna speciosa leaf tea, powder or extracts; not interchangeable with isolated7-hydroxymitragynine or semisynthetic derivatives.
- Supplement or preparation
- Mitragyna speciosa
- Medication ingredient
- methadone
Sedating effects can overlap
Kratom constituents act at opioid receptors and drowsiness is reported. Methadone’s CNS-depressant warning therefore supports caution, without establishing a measured risk for this exact pair.
The human metabolism study used other drugs
Low-dose kratom tea increased midazolam exposure but did not change dextromethorphan exposure. These findings cannot be converted into a methadone dose change or claim of altered absorption.
Methadone has its own metabolism
Human studies support an important CYP2B6 role in methadone handling. A botanical CYP3A result alone does not establish its overall interaction, particularly with repeated or concentrated kratom use.
Keep withdrawal treatment supervised
Tell the treatment team about the actual kratom product and frequency. Do not adjust or discontinue methadone yourself. Marked sedation, slow breathing or unusual difficulty waking requires emergency help.
Evidence and practical considerations
Absorption & effectiveness
No exact-pair human exposure/absorption study; other probe-drug kratom findings and CYP3A theory cannot establish methadone direction or magnitude.
- Exact scope
- Mitragyna speciosa leaf tea, powder or extracts; not interchangeable with isolated7-hydroxymitragynine or semisynthetic derivatives. 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: 12 healthy adults.
Midazolam exposure modestly increased; dextromethorphan exposure and peak concentration were unchanged.
How this applies: Not methadone or chronic/high-dose kratom; CYP3A result cannot establish a methadone exposure change. Full-text endpoint returned404, abstract used.
Not methadone or chronic/high-dose kratom; CYP3A result cannot establish a methadone exposure change. Full-text endpoint returned404, abstract used.
Source 4: federal supplement guidance
nccih.nih.gov · Source check Sep 10, 2026
Population: Kratom users
Opioid-receptor effects and drowsiness reported; combination harms noted; safety/effectiveness for opioid withdrawal not established.
How this applies: Supplement-specific PD concern, not exact methadone PK proof.
No isolated methadone-pair rate; high-potency derivatives and leaf products differ.
Source 5: 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 ↗
Side effects & toxicity
Conditional additive CNS-effect concern from methadone label and kratom opioid-like/drowsiness effects; no exact-pair incidence or proven pharmacokinetic toxicity.
- Exact scope
- Mitragyna speciosa leaf tea, powder or extracts; not interchangeable with isolated7-hydroxymitragynine or semisynthetic derivatives. 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: 12 healthy adults.
Midazolam exposure modestly increased; dextromethorphan exposure and peak concentration were unchanged.
How this applies: Not methadone or chronic/high-dose kratom; CYP3A result cannot establish a methadone exposure change. Full-text endpoint returned404, abstract used.
Not methadone or chronic/high-dose kratom; CYP3A result cannot establish a methadone exposure change. Full-text endpoint returned404, abstract used.
Source 4: federal supplement guidance
nccih.nih.gov · Source check Sep 10, 2026
Population: Kratom users
Opioid-receptor effects and drowsiness reported; combination harms noted; safety/effectiveness for opioid withdrawal not established.
How this applies: Supplement-specific PD concern, not exact methadone PK proof.
No isolated methadone-pair rate; high-potency derivatives and leaf products differ.
Source 5: 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: c993da80d4b90751
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.