NutriStack
Metoclopramide and St. John's Wort, a caution.
Metoclopramide has rare reports of serotonin syndrome, especially when combined with serotonergic drugs. St. John's Wort has serotonergic activity and published clinical interaction reviews describe serotonin syndrome when it is combined with serotonergic medicines. The combination is not well studied directly, but the shared serotonergic risk makes it a clinically meaningful caution.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
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At a glance
- Substances
- Metoclopramide and St. John's Wort
- Pair type
- Caution
- Evidence (highest tier)
- Emerging
- Source citations
- 3 sources
- Stack Score effect
- −5 to your Stack Score (per scored caution row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Caution · Emerging evidence
Caution
What is happening. Metoclopramide has rare reports of serotonin syndrome, especially when combined with serotonergic drugs. St. John's Wort has serotonergic activity and published clinical interaction reviews describe serotonin syndrome when it is combined with serotonergic medicines. The combination is not well studied directly, but the shared serotonergic risk makes it a clinically meaningful caution.
Mechanism. Metoclopramide has serotonergic properties in addition to dopamine D2 antagonism and 5-HT4 agonism. St. John's Wort can increase serotonergic tone and also alters CYP3A4 and P-glycoprotein, creating both pharmacodynamic and pharmacokinetic uncertainty.
Recommendation. Avoid combining St. John's Wort with metoclopramide unless your prescriber specifically approves it. Stop St. John's Wort and seek urgent care for agitation, confusion, sweating, fever, diarrhea, tremor, muscle rigidity, or jerking movements after metoclopramide use. Also tell your clinician about any antidepressants, tramadol, or migraine medicines.
Sources (3)
- Fisher AA, Davis MW. Serotonin syndrome caused by selective serotonin reuptake-inhibitors-metoclopramide interaction. Ann Pharmacother. 2002;36(1):67-71. PMID 11816261
- Harada T, Hirosawa T, Morinaga K, Shimizu T. Metoclopramide-induced Serotonin Syndrome. Intern Med. 2017;56(6):737-739. PMID 28321081
- Izzo AA. Drug interactions with St. John's Wort (Hypericum perforatum): a review of the clinical evidence. Int J Clin Pharmacol Ther. 2004;42(3):139-148. PMID 15049433
Stack Score
How this pair moves the number.
Effect on the composite score
If both Metoclopramide and St. John's Wort are in the same stack, this pair applies −5 to your Stack Score (per scored caution row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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