What happens when you take MAOIs with St. John's Wort?
St. John's Wort (Hypericum perforatum) looks like a gentle tea-aisle herb, but pharmacologically it behaves like a prescription antidepressant. Stacked on top of an MAOI, the two raise brain monoamines through overlapping mechanisms, and standard references treat the pair as one to avoid entirely.
- St. John's Wort raises monoamines on its own. Hyperforin and hypericin, its main active constituents, inhibit the reuptake of serotonin, norepinephrine, dopamine, GABA, and glutamate. That alone lifts synaptic monoamine levels in a way comparable to a prescription antidepressant.
- The MAOI blocks the cleanup crew. Prescription MAOIs such as phenelzine and tranylcypromine block the enzyme that breaks serotonin, norepinephrine, and dopamine back down. St. John's Wort also shows weak MAO inhibition in laboratory studies, so the combination stacks degradation blockade on top of reuptake inhibition at the same synapses.
- Monoamines can climb too high. With both the reuptake route and the breakdown route impaired, synaptic serotonin and norepinephrine can rise toward toxic concentrations. That is the setup for serotonin syndrome, and the added noradrenergic load also raises the risk of a hypertensive crisis.
Why is this important?
This is not a problem you can manage by spacing doses apart. Reference sources including the StatPearls MAOI monograph list St. John's Wort among the agents to avoid with MAOIs, and a systematic review of St. John's Wort drug interactions reaches the same conclusion, because the consequences of being wrong are serious.
Serotonin syndrome. Early signs include agitation, sweating, shivering, dilated pupils, a racing heart, and overactive reflexes. Severe cases can progress to high fever, muscle rigidity, muscle breakdown, seizures, and clotting problems. There is no specific antidote; care is supportive, and onset can be within hours of combining the two.
Hypertensive crisis. The residual MAO-inhibiting activity of St. John's Wort layered on a prescription MAOI can drive blood pressure into an emergency range, with risk of stroke or cardiac complications.
Loss of control over your other medicines. Separately, St. John's Wort is a strong inducer of the CYP3A4 enzyme and P-glycoprotein, speeding up the clearance of many drugs including oral contraceptives, blood thinners, digoxin, transplant anti-rejection drugs, and HIV medicines. People have experienced transplant rejection, contraceptive failure, and loss of HIV viral control after adding it to a stable regimen.
What should you do?
Treat this as a hard rule rather than a balancing act, and plan any switch with your prescriber.
Before any change: Tell every prescriber and pharmacist that you take an MAOI before starting any new supplement. If your prescriber wants to start an MAOI while you take St. John's Wort, stop the herb first and allow a washout of roughly a couple of weeks before the first MAOI dose. Going the other way, allow a full medication-free interval after your last MAOI dose before starting St. John's Wort. Your doctor will confirm the right gap for your specific medicine.
Every day you are on an MAOI: Do not take St. John's Wort in any form, including capsules, tablets, teas, tinctures, topical products, or multi-herb mood and sleep blends. Read every supplement facts panel, since St. John's Wort is often listed only as Hypericum perforatum or buried in a blend.
After a change or accidental exposure: If you accidentally take both, stop them and seek emergency care, watching for agitation, sweating, tremor, muscle twitching or clonus, overactive reflexes, fever, or confusion. Bring all your bottles, including the supplement, so clinicians can see everything you have taken. After stopping St. John's Wort, the enzyme induction it caused takes time to fade, so any other medicines whose levels depend on that enzyme may need review with your doctor.
Which specific products are affected?
Prescription MAOIs and MAOI-like drugs:
- Phenelzine (Nardil)
- Tranylcypromine (Parnate)
- Isocarboxazid (Marplan)
- Selegiline (Emsam patch, oral Eldepryl, Zelapar)
- Rasagiline (Azilect)
- Linezolid (Zyvox) and tedizolid (Sivextro)
- Intravenous methylene blue
- Procarbazine (Matulane)
St. John's Wort products and blends to watch for:
- Single-ingredient St. John's Wort capsules and tablets
- St. John's Wort tinctures and teas
- Combination mood, calm, happy, or serotonin-support blends
- Multi-herb sleep formulas
- Any product labeled Hypericum perforatum
St. John's Wort is sometimes listed only under its Latin name, so always check the supplement facts panel.
The science behind it
The StatPearls monograph on monoamine oxidase inhibitors lists St. John's Wort among the agents contraindicated with MAOIs because of serotonin syndrome risk, reflecting standard clinical guidance to keep the two apart.
A systematic review of St. John's Wort adverse effects and drug interactions, written for consultation psychiatrists, likewise identifies MAOI co-use as contraindicated and describes the serotonin syndrome and hypertensive crisis concerns that drive that recommendation.
It is worth being honest about the evidence base: documented case reports are thinner for MAOI plus St. John's Wort than for SSRIs plus St. John's Wort. The contraindication rests on consistent pharmacology, every mechanism by which the two raise monoamine signaling is additive, combined with consequences severe enough that no clinician runs the experiment.
Sources: Patel P, Saadabadi A. Monoamine Oxidase Inhibitors (MAOI). StatPearls (https://www.ncbi.nlm.nih.gov/books/NBK539848/). Hammerness P, et al. St. John's Wort: A Systematic Review of Adverse Effects and Drug Interactions for the Consultation Psychiatrist. Psychosomatics. 2003;44(4):271-82.
Frequently Asked Questions
Can I take St. John's Wort if I am on an MAOI?
No. The combination is contraindicated because it can cause serotonin syndrome and raise blood pressure dangerously. This applies to every form of St. John's Wort, including teas and multi-herb blends.
Is St. John's Wort safer than a prescription antidepressant here?
No. Despite its tea-aisle image, it acts pharmacologically like an antidepressant and carries the same combination risks with an MAOI. Treat it as off limits while on an MAOI.
How long should I wait when switching between them?
You need a full medication-free washout in both directions, not just a few hours' gap. The exact interval depends on your specific MAOI, so confirm the timing with your doctor or pharmacist.
What are the warning signs I should watch for?
Agitation, sweating, tremor, muscle twitching, overactive reflexes, a racing heart, dilated pupils, fever, or confusion can signal serotonin syndrome. Stop both and seek emergency care.
How would I know if a supplement secretly contains St. John's Wort?
Read the supplement facts panel on every product. St. John's Wort is often listed only by its Latin name, Hypericum perforatum, or folded into mood, calm, happy, or sleep blends.
Does St. John's Wort affect my other medications too?
Yes. It speeds up the breakdown of many drugs, including birth control, blood thinners, and transplant and HIV medicines, which can make them stop working. Tell your pharmacist about every medicine you take before adding it.
Key takeaways
- Do not combine St. John's Wort with any MAOI in any form; the pair is contraindicated.
- Both raise brain monoamines, so stacking them risks serotonin syndrome and hypertensive crisis, which can begin within hours.
- Spacing doses apart is not enough; switching between them requires a full medication-free washout planned with your doctor.
- St. John's Wort is often hidden in blends or listed only as Hypericum perforatum, so read every supplement facts panel.
- St. John's Wort can also weaken many other medicines by speeding their clearance, so review your full list with a pharmacist.