The short answer
St. John’s wort warrants review before use with cyclobenzaprine because of a possible serotonin-related interaction. There is no established exact-pair risk estimate or protective short dosing interval.
What this answer covers
Hypericum perforatum oral supplements; extract composition differs.
- Supplement or preparation
- Hypericum perforatum
- Medication ingredient
- cyclobenzaprine
The current medication warning is relevant
Cyclobenzaprine labels describe serotonin syndrome with other serotonergic medicines. Supplement guidance raises a similar concern for this product, supporting review before co-use rather than assuming safety.
The clinical cases involved different medicines
Two postoperative cases involved cyclobenzaprine with phenelzine or duloxetine. Laboratory work also supports serotonergic activity, but neither source measures this supplement combination’s risk.
Contraindications and precautions differ
Cyclobenzaprine is formally contraindicated with MAO inhibitors and for 14 days after stopping them. The labels call for careful observation when other serotonergic co-use is clinically warranted. Do not apply the MAOI interval as a proven supplement washout rule.
Review all products before changing use
Tell the prescriber the supplement, cyclobenzaprine formulation and other medicines. A few hours of separation is not established protection. Agitation with fever, tremor, stiffness or confusion needs urgent medical assessment.
Evidence and practical considerations
Side effects & toxicity
Conditional serotonergic review precaution from exact current labels, original other-drug cases and supplement guidance; no exact-pair incidence or blanket herb contraindication. Short spacing not established.
- Exact scope
- Hypericum perforatum oral supplements; extract composition differs. with Cyclobenzaprine21949 IN; hydrochloride swallowed IR/ER and sublingual products with formulation-specific indications.
- Medication form and route
- oral medication; sublingual 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 cyclobenzaprine
CNS-depressant and serotonin-syndrome warnings; concomitant MAOIs and14days after stopping contraindicated.
How this applies: Exact cyclobenzaprine RxCUI 21949 IN, with stated salt/formulation/route bridge.
Not extended-release or sublingual dosing; supplement-specific risk unmeasured.
Source 2: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed cyclobenzaprine
CNS-depressant and serotonergic precautions; MAOI contraindication.
How this applies: Exact cyclobenzaprine RxCUI 21949 IN, with stated salt/formulation/route bridge.
Different release/directions from immediate-release and sublingual products.
Source 3: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed cyclobenzaprine
CNS depression and serotonergic precautions; MAOI contraindication retained.
How this applies: Exact cyclobenzaprine RxCUI 21949 IN, with stated salt/formulation/route bridge.
Not swallowed-tablet dosing; sublingual product administration instructions are not a universal supplement-separation rule.
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 cyclobenzaprine only within the stated preparation and endpoint limits.
Not a direct cyclobenzaprine combination trial; original preparation, dose and endpoint limits apply. No exact-pair adverse-event rate or protective spacing established.
Source 5: original case reports
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Two postoperative patients.
Severe serotonin-syndrome features arose within hours and resolved after stopping implicated medicines.
How this applies: Two other-drug cases; not St John’s wort or SAMe; no supplement-specific incidence.
Two other-drug cases; not St John’s wort or SAMe; no supplement-specific incidence.
Source 6: original laboratory pharmacology investigation
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Laboratory pharmacology with clinical context.
Evidence of serotonin/noradrenaline transporter blockade and serotonin-receptor binding; clinical causal association described as debated.
How this applies: Original abstract used after fullXML404; laboratory activity cannot establish exact supplement toxicity or frequency.
Original abstract used after fullXML404; laboratory activity cannot establish exact supplement toxicity or frequency.
Research assessment: · Open full citations ↗
Timing & monitoring
Conditional serotonergic review precaution from exact current labels, original other-drug cases and supplement guidance; no exact-pair incidence or blanket herb contraindication. Short spacing not established.
- Exact scope
- Hypericum perforatum oral supplements; extract composition differs. with Cyclobenzaprine21949 IN; hydrochloride swallowed IR/ER and sublingual products with formulation-specific indications.
- Medication form and route
- oral medication; sublingual 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 cyclobenzaprine
CNS-depressant and serotonin-syndrome warnings; concomitant MAOIs and14days after stopping contraindicated.
How this applies: Exact cyclobenzaprine RxCUI 21949 IN, with stated salt/formulation/route bridge.
Not extended-release or sublingual dosing; supplement-specific risk unmeasured.
Source 2: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed cyclobenzaprine
CNS-depressant and serotonergic precautions; MAOI contraindication.
How this applies: Exact cyclobenzaprine RxCUI 21949 IN, with stated salt/formulation/route bridge.
Different release/directions from immediate-release and sublingual products.
Source 3: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed cyclobenzaprine
CNS depression and serotonergic precautions; MAOI contraindication retained.
How this applies: Exact cyclobenzaprine RxCUI 21949 IN, with stated salt/formulation/route bridge.
Not swallowed-tablet dosing; sublingual product administration instructions are not a universal supplement-separation rule.
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 cyclobenzaprine only within the stated preparation and endpoint limits.
Not a direct cyclobenzaprine combination trial; original preparation, dose and endpoint limits apply. No exact-pair adverse-event rate or protective spacing established.
Source 5: original case reports
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Two postoperative patients.
Severe serotonin-syndrome features arose within hours and resolved after stopping implicated medicines.
How this applies: Two other-drug cases; not St John’s wort or SAMe; no supplement-specific incidence.
Two other-drug cases; not St John’s wort or SAMe; no supplement-specific incidence.
Source 6: original laboratory pharmacology investigation
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Laboratory pharmacology with clinical context.
Evidence of serotonin/noradrenaline transporter blockade and serotonin-receptor binding; clinical causal association described as debated.
How this applies: Original abstract used after fullXML404; laboratory activity cannot establish exact supplement toxicity or frequency.
Original abstract used after fullXML404; laboratory activity cannot establish exact supplement toxicity or frequency.
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 cyclobenzaprine article with formulation-specific evidence and uncertainty. | |
| Research summary published |
Article revision: f664cc5ef3b31eba
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?
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Open the interaction checkerInformation, not medical advice. Do not change prescribed treatment based on this guide.