Drug & supplement interaction

St. John's Wort + Olanzapine

Olanzapine brand name: Zyprexa.

Moderate Interaction
The bottom line Moderate

Olanzapine falls into 2 drug categories that St. John's Wort can interact with; the most serious is rated moderate. Theoretically, St. John's wort might inhibit reuptake and increase levels of serotonin, resulting in additive effects with serotonergic drugs.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

St. John's Wort and Olanzapine

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

St. John's Wort interacts with whole categories of medication. Olanzapine falls into 2 of those categories, so it can interact with St. John's Wort in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

SEROTONERGIC DRUGS

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Why this applies to Olanzapine

Olanzapine falls under SEROTONERGIC DRUGS — the group St. John's Wort interacts with.

Theoretically, St. John's wort might inhibit reuptake and increase levels of serotonin, resulting in additive effects with serotonergic drugs.
Concomitant use of serotonergic drugs with St. John's wort can lead to increased adverse effects and increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstriction disorders.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the thing to know about pairing St. John's wort with olanzapine (Zyprexa). St. John's wort can nudge up serotonin activity in the brain, and olanzapine itself touches serotonin pathways too. Putting them together could add up, in theory, and slightly raise the odds of too much serotonin. That can look like restlessness, sweating, shakiness, a fast heartbeat, or confusion. A full-blown reaction called serotonin syndrome is rare but worth knowing about.

I'll be honest that this concern is mostly theoretical, based on how the two work rather than strong real-world reports, so I don't want to alarm you. Olanzapine is not a prodrug, so this isn't about it being weakened. Before adding St. John's wort, please check with your pharmacist or doctor first.

References
  1. Miller LG. Herbal Medicinals: Selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med 1998;158:2200-11.
  2. Gordon JB. SSRIs and St. John's Wort: possible toxicity? Am Fam Physician 1998;57:950, 953.
  3. Beckman SE, Sommi RW, Switzer J. Consumer use of St. John's wort: A survey of effectiveness, safety, and tolerability. Pharmacotherapy 2000;20:568-74.
  4. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3. PubMed
  5. Sarris J, Ravindran A, Yatham LN, et al. Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety T
Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

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Olanzapine also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

St. John's wort may increase the metabolism and reduce the levels of CYP1A2 substrates.
Clinical and in vitro research shows that St. John's wort induces CYP1A2, but to a lesser extent than CYP3A4.
Severity Moderate Likelihood Possible Evidence B

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for olanzapine (Zyprexa): your liver clears it partly through an enzyme called CYP1A2. St. John's wort can rev that enzyme up, which means your body may break olanzapine down faster than usual. When that happens, the level in your blood can drop, and you may not get the full benefit you're counting on.

For something treating schizophrenia or bipolar disorder, weaker coverage can matter. You might notice mood symptoms, racing thoughts, or other signs creeping back. This effect is considered possible rather than guaranteed, and St. John's wort nudges this particular enzyme less than others. Still, please don't add or stop either one on your own. Check with your pharmacist or doctor first so they can watch how you're doing.

References
  1. Henderson L, Yue QY, Bergquist C, et al. St John's wort (Hypericum perforatum): drug interactions and clinical outcomes. Br J Clin Pharmacol 2002;54:349-56..
  2. Foster BC, Vandenhoek S, Hana J, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine 2003;10:334-42.. PubMed
  3. Van Strater, A. C. and Bogers, J. P. Interaction of St John's wort (Hypericum perforatum) with clozapine. Int.Clin.Psychopharmacol. 2012;27(2):121-124. PubMed
  4. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

St. John's Wort Also Interacts With Other Medications

St. John's Wort has 755 major, 387 moderate known drug interactions in our database — the Olanzapine one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against St. John's Wort

Covers the 2,830 medications we’ve checked against St. John's Wort. Pick one to open its full report.

From our Q&A

Questions About St. John's Wort or Olanzapine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers St. John's Wort or Olanzapine, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Olanzapine

This page covers St. John's Wort only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Olanzapine page lists 160 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Indian Snakeroot (major), Lithium (major), Rauvolfia Vomitoria (major) and 1,3-dmaa (moderate).

By severity: 4 major · 118 moderate · 38 minor.

From our pharmacist’s overview on the Olanzapine page

“Olanzapine (Zyprexa) is an antipsychotic prescribed for schizophrenia and bipolar disorder, and adding supplements to it warrants genuine care. Four of the 160 ingredients on file rate major, and those four deserve your attention before anything else: lithium supplements raise the risk of serotonin syndrome, activated charcoal can trap…”

Reviewed by 2 · Jul 18, 2026

Open the Olanzapine interaction page

One more smart check

Taking St. John's Wort as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,159 real supplement products containing St. John's Wort, each one broken down to its full ingredient list — and combination products often carry several ingredients besides St. John's Wort. Your product may carry other ingredients that interact with Olanzapine too, on top of St. John's Wort — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where St. John's Wort and Olanzapine Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement St. John's Wort
Top 25%

#156 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Olanzapine
Top 25%

#332 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About St. John's Wort

What is St. John's Wort?

St. John's Wort
  • Mild to moderate depression
  • Anxiety and stress
  • Sleep problems
  • Menopausal symptoms
  • Wound healing (topical)

St. John's wort is a well-studied herb most often used for mild to moderate depression, and some research suggests it may help with this. However, it has many serious interactions with prescription medicines and is not safe for everyone, so always talk to your pharmacist or doctor before taking it.

Read the full St. John's Wort monograph & all interactions
Medication

About Olanzapine

What Is Olanzapine Used For?

Brand name: Zyprexa

Olanzapine treats schizophrenia and the manic or mixed episodes of bipolar I disorder in both adults and adolescents (ages 13–17). It can also be used alongside valproate or lithium to treat manic or mixed episodes in adults. When combined with fluoxetine, olanzapine tablets and orally disintegrating tablets are used to treat depressive episodes associated with bipolar I disorder and treatment-resistant depression in adults.

Olanzapine intramuscular injection (short-acting) is used by healthcare providers to quickly calm acute agitation in adults with schizophrenia or bipolar I mania. Zyprexa Relprevv — a separate, long-acting intramuscular formulation available only through a restricted program — is indicated specifically for the treatment of schizophrenia in adults.

See full Olanzapine drug information
Keep checking

Other Drugs & St. John's Wort

Browse every other medication we’ve checked against St. John's Wort — both the ones with a known interaction and the ones without. Select any drug for the full detail.

755Major
387Moderate
0Minor
1,687No known interaction
Major

755 interactions

Showing 60 of 755 major interactions — see all 755 on the St. John's Wort page.

Moderate

387 interactions

Showing 60 of 387 moderate interactions — see all 387 on the St. John's Wort page.

No interaction 1,687 drugs checked — show the list
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Pharmacist Counseling Corner

Taking St. John's Wort and Olanzapine Together: Common Questions

Can you take St. John's Wort with Olanzapine?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for St. John's Wort and Olanzapine?
Olanzapine belongs to more than one drug category, and St. John's Wort interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the St. John's Wort and Olanzapine interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Olanzapine and St. John's Wort?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.