The short answer
Kratom warrants review with the clozapine team because of its own sedative and seizure concerns and its demonstrated interaction with a different drug metabolized by CYP3A. The size and clinical effects of a clozapine-kratom interaction remain unknown; separating doses is not an established solution.
What this answer covers
Oral Mitragyna speciosa products. A single low-dose leaf tea study does not represent concentrated alkaloid products or prolonged use.
- Supplement or preparation
- Mitragyna speciosa
- Medication ingredient
- clozapine
Overlapping concerns
Clozapine can cause sedation, instability and dose-related seizures. NCCIH reports drowsiness and rare serious seizures with kratom. These separate observations justify caution, but do not prove that combining them increases seizures or causes dangerous central nervous system depression.
What the metabolism study showed
In 12 healthy adults, a single kratom tea increased exposure to midazolam, a CYP3A probe, while leaving the CYP2D6 probe dextromethorphan unchanged. Clozapine uses several metabolic pathways. The result raises a possible interaction concern but does not predict a clozapine level change or justify a numerical dose adjustment.
A case report needs context
One report linked heavy kratom use with psychiatric deterioration in a person also using cannabis and inconsistently taking antipsychotics. Clozapine was introduced weeks after hospital admission. This was not a demonstrated clozapine-kratom toxicity case.
Review the actual product
Discuss kratom use, changes in use, and the product label with the clozapine team. Current evidence does not establish a safe dose or protective interval. New marked sleepiness or unsteadiness needs prompt assessment; a seizure requires emergency care. Do not change prescribed clozapine dosing yourself.
Evidence and practical considerations
Side effects & toxicity
Intrinsic sedative and seizure reports plus an indirect CYP3A probe signal do not prove the compound clozapine toxicity statement or validate separation or universal avoidance.
- Exact scope
- Oral Mitragyna speciosa products. A single low-dose leaf tea study does not represent concentrated alkaloid products or prolonged use. with Oral clozapine, RxNorm 2626 IN.
- Medication form and route
- oral clozapine; oral supplement
What remains uncertain
- No quantified clozapine-specific interaction or validated spacing intervention.
Factors that may matter: Exact preparation; Other medicines and baseline clinical status.
Read the supporting source summaries
Source 1: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed clozapine.
Clozapine causes sedation and impaired performance, can contribute to falls, and carries dose-related seizure risk. CYP1A2, CYP3A4 and CYP2D6 participate in metabolism. Proposed therapeutic activity includes dopamine D2 and serotonin 5-HT2A receptor antagonism.
How this applies: Medication-specific safety context only; no direct botanical interaction or automatic dose change is established.
No named interaction with these counterparties or measured combined risk.
Source 2: federal supplement safety guidance
nccih.nih.gov · Source check Sep 10, 2026
Population: Users of the named supplement.
Reports stimulant-like and opioid/sedative-like effects, drowsiness and rare serious seizures. More research on interactions is needed.
How this applies: Supplement-specific guidance interpreted alongside the clozapine label.
General guidance does not quantify a clozapine interaction or establish protective spacing.
Source 3: original human clinical study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: 12 healthy adults.
Kratom increased midazolam AUC 1.39-fold and peak concentration 1.50-fold, but did not change dextromethorphan exposure. Unchanged midazolam half-life suggests intestinal CYP3A inhibition.
How this applies: Interpret only within the stated preparation, population and endpoints.
Clozapine not tested. Single low-dose tea and probe effects cannot quantify clozapine exposure or chronic/high-strength product effects. Full-text access failed; original abstract read.
Source 4: original human clinical study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: One man with schizoaffective disorder, inconsistent antipsychotic use and cannabis co-use.
Psychiatric deterioration followed escalating reported kratom use; clozapine was introduced three weeks after admission.
How this applies: Interpret only within the stated preparation, population and endpoints.
Not evidence of a concurrent clozapine-kratom interaction, seizure or excess sedation. Confounding and unconfirmed dose limit attribution.
Research assessment: · Open full citations ↗
Side effects & toxicity
Possible additional impairment warrants individual review because clozapine causes sedation and the supplement has sedative effects or a stated theoretical sedative-interaction concern; clinical magnitude is unmeasured.
- Exact scope
- Oral Mitragyna speciosa products. A single low-dose leaf tea study does not represent concentrated alkaloid products or prolonged use. with Oral clozapine, RxNorm 2626 IN.
- Medication form and route
- oral clozapine; oral supplement
What remains uncertain
- No quantified clozapine-specific interaction or validated spacing intervention.
Factors that may matter: Exact preparation; Other medicines and baseline clinical status.
Read the supporting source summaries
Source 1: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed clozapine.
Clozapine causes sedation and impaired performance, can contribute to falls, and carries dose-related seizure risk. CYP1A2, CYP3A4 and CYP2D6 participate in metabolism. Proposed therapeutic activity includes dopamine D2 and serotonin 5-HT2A receptor antagonism.
How this applies: Medication-specific safety context only; no direct botanical interaction or automatic dose change is established.
No named interaction with these counterparties or measured combined risk.
Source 2: federal supplement safety guidance
nccih.nih.gov · Source check Sep 10, 2026
Population: Users of the named supplement.
Reports stimulant-like and opioid/sedative-like effects, drowsiness and rare serious seizures. More research on interactions is needed.
How this applies: Supplement-specific guidance interpreted alongside the clozapine label.
General guidance does not quantify a clozapine interaction or establish protective spacing.
Source 3: original human clinical study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: 12 healthy adults.
Kratom increased midazolam AUC 1.39-fold and peak concentration 1.50-fold, but did not change dextromethorphan exposure. Unchanged midazolam half-life suggests intestinal CYP3A inhibition.
How this applies: Interpret only within the stated preparation, population and endpoints.
Clozapine not tested. Single low-dose tea and probe effects cannot quantify clozapine exposure or chronic/high-strength product effects. Full-text access failed; original abstract read.
Source 4: original human clinical study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: One man with schizoaffective disorder, inconsistent antipsychotic use and cannabis co-use.
Psychiatric deterioration followed escalating reported kratom use; clozapine was introduced three weeks after admission.
How this applies: Interpret only within the stated preparation, population and endpoints.
Not evidence of a concurrent clozapine-kratom interaction, seizure or excess sedation. Confounding and unconfirmed dose limit attribution.
Research assessment: · Open full citations ↗
Review and change history
- Publication status
- Published research summary
- Clinical review
- Not yet recorded
| Date | Update |
|---|---|
| Article prepared | |
| Prepared evidence-based article with explicit preparation and endpoint limits. | |
| Research summary published |
Article revision: 4d17f3417b53f671
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.