The short answer
St. John’s wort can raise a serotonin-related interaction concern with dextromethorphan. Have the combination reviewed before use; the evidence does not establish a safe supplement dose or a protective short interval.
What this answer covers
Hypericum perforatum oral supplements; extract constituents and strength vary.
- Supplement or preparation
- Hypericum perforatum
- Medication ingredient
- dextromethorphan
Why serotonin matters
Dextromethorphan inhibits the serotonin transporter in laboratory experiments. Federal St. John’s wort guidance warns about serious serotonin-related effects with other medicines acting on serotonin.
The risk cannot be assigned a percentage
The inspected sources do not establish an exact-pair event rate at ordinary cough doses. Other serotonergic medicines, supplement strength and the amount of dextromethorphan affect the assessment. Mechanistic concern is not a measured probability.
The MAOI rule has a specific scope
The cough labels prohibit use with prescription MAO inhibitors and for two weeks after stopping those drugs. This is not a validated two-week rule for every supplement, and a shorter gap has not been shown to prevent this pair’s concern.
Review the combination and recognize symptoms
Ask the pharmacist or prescriber before combining them. Agitation with fever, tremor, muscle stiffness, unusual sweating or confusion warrants urgent assessment. Do not exceed the cough product directions.
Evidence and practical considerations
Side effects & toxicity
Conditional serotonin-related precaution based on dextromethorphan transporter activity plus supplement-specific official guidance, not exact-pair incidence; no universal herbal washout or protective spacing inferred.
- Exact scope
- Hypericum perforatum oral supplements; extract constituents and strength vary. with Dextromethorphan3289 IN; oral cough hydrobromide/polistirex formulations, not codeine or other pain opioids; psychiatric combinations explicitly limited.
- Medication form and route
- oral 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 dextromethorphan
Cough suppressant with age-specific directions, overdose precautions and prohibition during prescription MAOI use or within2weeks after stopping that drug.
How this applies: Exact dextromethorphan RxCUI 3289 IN, with stated salt/formulation/route bridge.
Not a pain opioid label, not a sedating antihistamine combination, and MAOI interval cannot be assigned to every herb.
Source 2: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed dextromethorphan
Different age-specific schedule and release duration from caplets; MAOI prohibition and overdose precautions.
How this applies: Exact dextromethorphan RxCUI 3289 IN, with stated salt/formulation/route bridge.
Not interchangeable dosing with immediate-release products or psychiatric combinations containing a CYP2D6 inhibitor.
Source 3: national medication patient information
medlineplus.gov · Source check Sep 10, 2026
Population: People using dextromethorphan cough medicines
Possible dizziness and drowsiness; disclose supplements and other medicines; overdose can cause serious neurologic and breathing problems.
How this applies: Exact medication effects and review advice.
No exact supplement interaction incidence; overdose outcomes are not routine therapeutic-dose event rates.
Source 4: federal supplement safety guidance
nccih.nih.gov · Source check Sep 10, 2026
Population: Users of the named oral supplement
Possible serious serotonin-related effects with other serotonin-active drugs.
How this applies: Original source interpreted for dextromethorphan only within the stated preparation and endpoint limits.
Not a direct dextromethorphan combination trial; original preparation, dose and endpoint limits apply. No exact-pair adverse-event rate or protective spacing established.
Source 5: original transporter experiment
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Cell-based human transporter experiments; not a supplement co-use trial.
Dextromethorphan inhibited the human serotonin transporter in transfected-cell experiments, unlike several other tested opioids.
How this applies: Original source interpreted for dextromethorphan only within the stated preparation and endpoint limits.
Mechanistic evidence, not exact supplement incidence or proof of toxicity at a particular cough dose.
Research assessment: · Open full citations ↗
Timing & monitoring
Conditional serotonin-related precaution based on dextromethorphan transporter activity plus supplement-specific official guidance, not exact-pair incidence; no universal herbal washout or protective spacing inferred.
- Exact scope
- Hypericum perforatum oral supplements; extract constituents and strength vary. with Dextromethorphan3289 IN; oral cough hydrobromide/polistirex formulations, not codeine or other pain opioids; psychiatric combinations explicitly limited.
- Medication form and route
- oral 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 dextromethorphan
Cough suppressant with age-specific directions, overdose precautions and prohibition during prescription MAOI use or within2weeks after stopping that drug.
How this applies: Exact dextromethorphan RxCUI 3289 IN, with stated salt/formulation/route bridge.
Not a pain opioid label, not a sedating antihistamine combination, and MAOI interval cannot be assigned to every herb.
Source 2: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed dextromethorphan
Different age-specific schedule and release duration from caplets; MAOI prohibition and overdose precautions.
How this applies: Exact dextromethorphan RxCUI 3289 IN, with stated salt/formulation/route bridge.
Not interchangeable dosing with immediate-release products or psychiatric combinations containing a CYP2D6 inhibitor.
Source 3: national medication patient information
medlineplus.gov · Source check Sep 10, 2026
Population: People using dextromethorphan cough medicines
Possible dizziness and drowsiness; disclose supplements and other medicines; overdose can cause serious neurologic and breathing problems.
How this applies: Exact medication effects and review advice.
No exact supplement interaction incidence; overdose outcomes are not routine therapeutic-dose event rates.
Source 4: federal supplement safety guidance
nccih.nih.gov · Source check Sep 10, 2026
Population: Users of the named oral supplement
Possible serious serotonin-related effects with other serotonin-active drugs.
How this applies: Original source interpreted for dextromethorphan only within the stated preparation and endpoint limits.
Not a direct dextromethorphan combination trial; original preparation, dose and endpoint limits apply. No exact-pair adverse-event rate or protective spacing established.
Source 5: original transporter experiment
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Cell-based human transporter experiments; not a supplement co-use trial.
Dextromethorphan inhibited the human serotonin transporter in transfected-cell experiments, unlike several other tested opioids.
How this applies: Original source interpreted for dextromethorphan only within the stated preparation and endpoint limits.
Mechanistic evidence, not exact supplement incidence or proof of toxicity at a particular cough dose.
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 dextromethorphan article with formulation-specific evidence and uncertainty. | |
| Research summary published |
Article revision: 103df3554374741b
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.