The short answer
St. John’s wort can affect drug-metabolizing enzymes, but a predictable reduction in diazepam’s effect has not been established for this exact combination. Review the product before use; there is no demonstrated new supplement need or dosing schedule.
What this answer covers
Hypericum perforatum preparations; hyperforin content, duration and extract differ.
- Supplement or preparation
- Hypericum perforatum
- Medication ingredient
- diazepam
Human evidence from another sedative is indirect
Repeated St. John’s wort reduced midazolam exposure, with a much smaller effect from one low-hyperforin product. These studies did not measure diazepam or its active metabolites.
Diazepam findings in animals had another direction
Some St. John’s wort preparations increased early diazepam-related motor impairment in mice. This does not prove the human effect, but it argues against presenting a simple universal loss of effect as demonstrated.
No new need or validated timing rule
The evidence does not show that diazepam creates a need for St. John’s wort or a particular schedule. Enzyme-related effects can persist beyond a dosing gap, and active diazepam metabolites complicate predictions.
Coordinate changes with the prescriber
Disclose the exact product before starting or stopping it, especially during regular diazepam treatment. Do not adjust the medicine or delay prescribed rescue treatment on the basis of a guessed herbal interval.
Evidence and practical considerations
Absorption & effectiveness
No human exact-pair reduced efficacy/absorption or new supplement need/timing established. Midazolam induction is indirect and mouse diazepam motor impairment increased with some extracts; narrower product review warranted without a one-way claim.
- Exact scope
- Hypericum perforatum preparations; hyperforin content, duration and extract differ. with Diazepam3322 IN; oral, IV/IM and intranasal formulations, active metabolites and study-route limits.
- Medication form and route
- oral medication; intravenous medication; intramuscular medication; intranasal 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 diazepam
CNS-depressant risk; CYP3A4/2C19 formation of active metabolites with prolonged elimination.
How this applies: Exact diazepam RxCUI 3322 IN, with stated salt/formulation/route bridge.
Not midazolam metabolism or proof of exact botanical risk.
Source 2: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed diazepam
Sedation and respiratory precautions with other CNS depressants.
How this applies: Exact diazepam RxCUI 3322 IN, with stated salt/formulation/route bridge.
Bypasses intestinal absorption; oral juice exposure magnitude cannot be transferred.
Source 3: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed diazepam
CNS-depressant and metabolism-related interaction precautions; exact rescue dosing directions.
How this applies: Exact diazepam RxCUI 3322 IN, with stated salt/formulation/route bridge.
Not oral-study dosing or a basis to delay prescribed rescue treatment; rectal preparations not directly studied here.
Source 4: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: 12 healthy adults.
Short-term dosing had no measured CYP effect; repeated use reduced oral midazolam AUC more than IV AUC.
How this applies: Original source interpreted for diazepam only within the stated preparation and endpoint limits.
Not a direct diazepam combination trial; original preparation, dose and endpoint limits apply. No exact-pair adverse-event rate or protective spacing established.
Source 5: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: 20 healthy men.
Small AUC decrease considered not clinically relevant by authors; no significant Cmax or half-life change.
How this applies: Original source interpreted for diazepam only within the stated preparation and endpoint limits.
Not a direct diazepam combination trial; original preparation, dose and endpoint limits apply. No exact-pair adverse-event rate or protective spacing established.
Source 6: original animal study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Mice.
Several preparations increased early motor impairment; effects differed by extract and time.
How this applies: Animal PD endpoint, not human oral diazepam exposure or a universal direction of clinical effect.
Animal PD endpoint, not human oral diazepam exposure or a universal direction of clinical effect.
Research assessment: · Open full citations ↗
Timing & monitoring
No human exact-pair reduced efficacy/absorption or new supplement need/timing established. Midazolam induction is indirect and mouse diazepam motor impairment increased with some extracts; narrower product review warranted without a one-way claim.
- Exact scope
- Hypericum perforatum preparations; hyperforin content, duration and extract differ. with Diazepam3322 IN; oral, IV/IM and intranasal formulations, active metabolites and study-route limits.
- Medication form and route
- oral medication; intravenous medication; intramuscular medication; intranasal 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 diazepam
CNS-depressant risk; CYP3A4/2C19 formation of active metabolites with prolonged elimination.
How this applies: Exact diazepam RxCUI 3322 IN, with stated salt/formulation/route bridge.
Not midazolam metabolism or proof of exact botanical risk.
Source 2: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed diazepam
Sedation and respiratory precautions with other CNS depressants.
How this applies: Exact diazepam RxCUI 3322 IN, with stated salt/formulation/route bridge.
Bypasses intestinal absorption; oral juice exposure magnitude cannot be transferred.
Source 3: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed diazepam
CNS-depressant and metabolism-related interaction precautions; exact rescue dosing directions.
How this applies: Exact diazepam RxCUI 3322 IN, with stated salt/formulation/route bridge.
Not oral-study dosing or a basis to delay prescribed rescue treatment; rectal preparations not directly studied here.
Source 4: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: 12 healthy adults.
Short-term dosing had no measured CYP effect; repeated use reduced oral midazolam AUC more than IV AUC.
How this applies: Original source interpreted for diazepam only within the stated preparation and endpoint limits.
Not a direct diazepam combination trial; original preparation, dose and endpoint limits apply. No exact-pair adverse-event rate or protective spacing established.
Source 5: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: 20 healthy men.
Small AUC decrease considered not clinically relevant by authors; no significant Cmax or half-life change.
How this applies: Original source interpreted for diazepam only within the stated preparation and endpoint limits.
Not a direct diazepam combination trial; original preparation, dose and endpoint limits apply. No exact-pair adverse-event rate or protective spacing established.
Source 6: original animal study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Mice.
Several preparations increased early motor impairment; effects differed by extract and time.
How this applies: Animal PD endpoint, not human oral diazepam exposure or a universal direction of clinical effect.
Animal PD endpoint, not human oral diazepam exposure or a universal direction of clinical effect.
Research assessment: · Open full citations ↗
Review and change history
- Publication status
- Published research summary
- Clinical review
- Not yet recorded
| Date | Update |
|---|---|
| Research summary published | |
| Article prepared | |
| Prepared exact diazepam article with formulation-specific evidence and uncertainty. |
Article revision: a535694128ffd5a3
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.