The short answer
Repeated St. John's wort use may lower bupropion exposure, although the small human study did not establish reduced antidepressant benefit. Discuss starting or stopping it with the prescriber; monitoring treatment response is supported, while simple dose spacing is not an established solution.
What this answer covers
Applies to oral bupropion and oral St. John's wort products; formulations and indications have different dosing constraints.
- Supplement or preparation
- St. John's wort
- Medication ingredient
- bupropion
Evidence and practical considerations
Absorption & effectiveness
An exact-pair human pharmacokinetic study and government clinical guidance support reduced bupropion exposure or effect during St. John's wort use. Evidence is moderate and conditional because the human study is small, the observed parent-drug AUC change is modest, clinical effectiveness was not directly measured, and botanical products vary.
- Exact scope
- St. John's wort (Hypericum perforatum) with bupropion
- Medication form and route
- systemic oral bupropion formulations; formulation-specific dose limits remain separate
- Timing or duration
- Enzyme induction requires repeated St. John's wort exposure; the captured human study evaluated supplementation rather than a single dose, but no universal onset or washout interval is established.
What remains uncertain
- The exact human study demonstrates a modest pharmacokinetic change, not proven antidepressant treatment failure.
- St. John's wort products vary substantially in hyperforin content and induction potential.
- Bupropion salts, combinations, and finished products are not silently collapsed into RxCUI 42347.
Factors that may matter: St. John's wort extract composition and hyperforin content; supplement dose and duration; bupropion formulation and indication; baseline treatment response; concomitant enzyme-modifying agents.
Read the supporting source summaries
Source 1: human pharmacokinetic study
hero.epa.gov · Source check Jul 25, 2026
Population: Healthy male Chinese volunteers.
The captured study report states that bupropion AUC decreased from 1.4 to 1.2 microgram-hour/mL and metabolite formation changed, without a change in bupropion half-life or time to peak concentration.
Small healthy-volunteer pharmacokinetic study; the capture does not establish a clinical antidepressant-effect size, and results can vary by extract composition.
Source 2: United States government clinical information
nccih.nih.gov · Source check Jul 25, 2026
Population: People considering or using St. John's wort with prescription medicines.
NCCIH explicitly includes bupropion among medicines whose effects St. John's wort can weaken.
Clinical guidance rather than a quantified exact-pair effectiveness trial.
Source 3: systematic review of clinical interaction trials
pmc.ncbi.nlm.nih.gov · Source check Jul 25, 2026
Population: Participants in prospective clinical pharmacokinetic interaction trials involving St. John's wort and conventional medicines.
The review supports induction-mediated reductions in exposure for susceptible medicines and identifies extract composition and steady-state exposure as important determinants.
The review spans multiple medicines; only exact bupropion evidence is transferred to this record.
Research assessment: · Open full citations ↗
Timing & monitoring
The exact-pair Q2 pharmacokinetic signal and authoritative clinical guidance justify a management record: patients should not independently start or stop St. John's wort while taking bupropion. The evidence supports clinician review and response monitoring, not a universal dose-separation interval or automatic medication adjustment.
- Exact scope
- St. John's wort (Hypericum perforatum) with bupropion
- Medication form and route
- systemic oral bupropion with oral St. John's wort products
- Timing or duration
- The interaction reflects enzyme induction from repeated use; simple same-day dose separation is not an adequate mitigation, and no universal washout period is established.
What remains uncertain
- No evidence supports a simple hour-based separation interval because the concern is enzyme induction rather than immediate binding in the gut.
- Avoidance is framed as avoiding unsupervised co-use; a specialist may make an individualized decision.
- Bupropion products and indications have different dosing constraints and are not silently merged.
Factors that may matter: St. John's wort extract composition and hyperforin content; supplement start or stop; bupropion treatment response; concomitant enzyme-modifying medicines; formulation and dose.
Read the supporting source summaries
Source 1: United States government clinical information
nccih.nih.gov · Source check Jul 25, 2026
Population: People taking bupropion or other interacting medicines.
NCCIH explicitly says St. John's wort can weaken bupropion and advises discussion with a health care provider before combining it with medicines.
Does not specify a universal timing interval or dose-adjustment algorithm.
Source 2: Australian product information
safetyandquality.gov.au · Source check Jul 25, 2026
Population: Patients using sustained-release bupropion for smoking cessation.
The product information states that an interaction with St. John's wort is possible and can increase undesirable effects.
Formulation- and indication-specific product information; it does not quantify risk or establish a separation interval.
Source 3: Australian regulatory health-professional guidance
tga.gov.au · Source check Jul 25, 2026
Population: Patients taking medicines susceptible to St. John's wort interactions.
The guidance emphasizes medication review and monitoring when St. John's wort is initiated or discontinued.
General St. John's wort management guidance rather than an exact bupropion dosing protocol.
Research assessment: · Open full citations ↗
Review and change history
- Publication status
- Published research summary
- Clinical review
- Not yet recorded
| Date | Update |
|---|---|
| Article prepared | |
| Research summary published |
Article revision: dbab85997edff14b
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.