The short answer
St. John's wort can increase the risk of serotonin syndrome when used with amphetamine aspartate. If co-use is necessary, the prescriber may need a lower stimulant starting dose and monitoring, especially when starting or increasing treatment. Do not adjust an existing dose yourself.
What this answer covers
Applies to amphetamine aspartate with St. John's wort products; the risk concerns overlapping effects on serotonin. Evidence includes a mixed-salt product containing this ingredient, with the finding limited to its documented active-ingredient mechanism.
- Supplement or preparation
- St. John's wort
- Medication ingredient
- amphetamine aspartate
Evidence and practical considerations
Side effects & toxicity
Current amphetamine labeling explicitly names St. John's wort as a serotonergic agent and provides management, supporting a clinically major conditional serotonin-toxicity interaction. Exact amphetamine-aspartate labeling or an explicit noncausal-aspartate active-moiety bridge supports the PIN applicability stated here. Exact amphetamine aspartate identity is retained; the component-containing product bridge is explicit and limited to an amphetamine-moiety mechanism with a noncausal aspartate counterion.
- Exact scope
- St. John's wort with amphetamine aspartate
- Medication form and route
- systemic amphetamine
- Timing or duration
- Risk is most relevant during overlapping systemic serotonergic exposure and dose initiation or escalation.
What remains uncertain
- Pair-specific incidence and dose-response are unknown.
- A distinct cardiovascular or neuropsychiatric interaction beyond serotonin toxicity was not independently established.
- St. John's wort enzyme induction is not assumed to change amphetamine exposure without exact evidence.
- Active-moiety evidence was bridged to RxCUI 221057 only where sulfate is noncausal; mixed salts, other salts, combinations, prodrugs, brands, and formulation-specific effects were not transferred.
- No standalone amphetamine-aspartate finished-product effect was assumed.
- The component-containing product bridge is allowed only because the adjudicated mechanism concerns amphetamine and the aspartate counterion is noncausal; other components and formulation effects are excluded.
Factors that may matter: higher stimulant dose; other serotonergic drugs or supplements; CYP2D6 inhibitors; history of serotonin toxicity; product variability.
Read the supporting source summaries
Source 1: FDA prescribing information (amphetamine-aspartate-containing product)
dailymed.nlm.nih.gov · Source check Jul 24, 2026
Population: Patients receiving an oral mixed-amphetamine product containing amphetamine aspartate.
St. John's wort is explicitly listed as a serotonergic drug; lower initial doses and monitoring are instructed when co-use is warranted.
The finished product also contains amphetamine sulfate and dextroamphetamine salts. Applicability to RxCUI 221057 is limited to the label's amphetamine-moiety mechanism; formulation-specific magnitude and other-component effects are not transferred.
Source 2: United States government supplement safety resource
nccih.nih.gov · Source check Jul 24, 2026
Population: Users of St. John's wort and medicines affecting serotonin.
NCCIH warns that combining St. John's wort with serotonin-affecting medicines can cause serious serotonin-related effects.
Not an exact-amphetamine pair study.
Research assessment: · Open full citations ↗
Timing & monitoring
Exact government and regulatory sources support disclosure, avoidance when feasible, and monitoring if concomitant use is clinically warranted. Exact amphetamine-aspartate labeling or an explicit noncausal-aspartate active-moiety bridge supports the PIN applicability stated here. Exact amphetamine aspartate identity is retained; the component-containing product bridge is explicit and limited to an amphetamine-moiety mechanism with a noncausal aspartate counterion.
- Exact scope
- St. John's wort with amphetamine aspartate
- Medication form and route
- systemic amphetamine
- Timing or duration
- During overlapping systemic exposure; timing separation is not an adequate risk-control strategy.
What remains uncertain
- This is a pharmacodynamic risk; time separation is not a reliable workaround.
- Use is not automatically prohibited in every circumstance, but requires clinician judgment.
- Enzyme-induction hypotheses are not used for management here.
- Active-moiety evidence was bridged to RxCUI 221057 only where sulfate is noncausal; mixed salts, other salts, combinations, prodrugs, brands, and formulation-specific effects were not transferred.
- No standalone amphetamine-aspartate finished-product effect was assumed.
- The component-containing product bridge is allowed only because the adjudicated mechanism concerns amphetamine and the aspartate counterion is noncausal; other components and formulation effects are excluded.
Factors that may matter: other serotonergic agents; higher amphetamine dose; CYP2D6 inhibitors; product variability.
Read the supporting source summaries
Source 1: FDA prescribing information (amphetamine-aspartate-containing product)
dailymed.nlm.nih.gov · Source check Jul 24, 2026
Population: Patients receiving an oral mixed-amphetamine product containing amphetamine aspartate.
St. John's wort is named and should not be started without discussion.
The finished product also contains amphetamine sulfate and dextroamphetamine salts. Applicability to RxCUI 221057 is limited to the label's amphetamine-moiety mechanism; formulation-specific magnitude and other-component effects are not transferred.
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: 9f1cb1a0666f7d4b
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.