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Dietary supplement

Kava Cool Complex Ingredients & Drug Interactions

by Herbs Etc.

Kava Cool Complex label
See full label image
Liquid Category: Botanical
Most serious interaction: Major
Clinical methodology reviewed by · Updated Sep 16, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking Kava Cool Complex against your medications. The heart of this page is the interaction checker and the full interaction report — how this product’s ingredients may interact with prescription and over-the-counter medicines you may be taking.

Around that, we add a pharmacist’s high-level view of the product as a whole — what’s inside, the evidence for its stated use, how transparent the label is, and what safety data exists — so you can see the full picture in one place. It’s educational information from our licensed clinical databases and the clinical staff at HelloPharmacist — not medical advice — and we don’t sell or endorse products. Our editorial policy

The interaction bottom line Most serious interaction: Major

Kava Cool Complex is a dietary supplement by Herbs Etc. with 8 active ingredients. Its ingredients are commonly taken for sugar substitute / sweetener, blood sugar support in diabetes, weight management.Based on those ingredients, 1,458 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Kava root extract, St. John's Wort Herb in Bud Extract, Dry, Fresh, Chamomile flower extract. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

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Check Your Meds Against Kava Cool Complex by Herbs Etc.

Ask about any prescription or over-the-counter medication and we check it for interactions with Kava Cool Complex by Herbs Etc. — and tell you which ingredient is responsible.

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HelloPharmacist Scorecard of Kava Cool Complex by Herbs Etc.

Our pharmacy team’s full take, with four database checks built into the cards below — a summary of what is known, not a grade of the product itself.

From our pharmacy team — supplement deep dive

Generated from HelloPharmacist’s pharmacist-curated databases and editorial rules · Last generated Jul 11, 2026

What’s inside

Low disclosure
Ingredient Transparency · database check
Low

Most active ingredients don't disclose an individual amount — you can't tell how much of each you're getting.

Why this rating?
  • The label discloses an exact amount for 0 of its 8 active ingredients.
  • “Proprietary Extract Blend” is a proprietary blend — the label gives one combined amount (0.75 mL) without saying how much of each component you get.

Kava Cool Complex contains 8 ingredients total. The active herbs are stevia herb extract (a sweetener), skullcap herb extract, hops strobile extract, chamomile flower extract, passionflower herb extract, oat seed extract, kava root extract, and St.

John's Wort herb in bud extract. These are prepared in a liquid form with alcohol, purified water, and glycerin as inactive ingredients.

Does it work?

Moderate evidence
Evidence for Intended Use · database check
By FDA rules, dietary supplements can’t claim to treat, cure, or prevent disease — so labels speak in careful marketing language. We discern each product’s intended use from its name, label claims, and label statements, then grade the clinical evidence for that use. How these ratings are computed
Moderate

Some clinical evidence supports this product's ingredients for its stated purpose, but it isn't conclusive.

Why this rating?
  • The label markets this product for: Promotes a feeling of calmness.
  • We looked for evidence on: Anxiety, Generalized anxiety disorder (GAD), Insomnia, Pre-procedural anxiety, Stress, Nervousness — and 2 related terms.
  • The strongest evidence on file: Passion Flower is rated "Possibly Effective" for Pre-procedural anxiety (Natural Medicines).
  • Also on file: Passion Flower is rated "Possibly Effective" for Insomnia.
  • Also on file: St. John's Wort is rated "Possibly Ineffective" for Social anxiety disorder.

The evidence for most ingredients in this blend is limited. Passion flower is possibly effective for insomnia and pre-procedural anxiety.

Oat seed extract is likely effective for high cholesterol (dyslipidemia) and heart disease. For the other active ingredients — stevia, skullcap, hops, chamomile, kava, and St.

John's Wort — the data we hold shows either insufficient evidence or, in kava's case, possibly ineffective for generalized anxiety disorder. St.

John's Wort is likely effective for depression, but that's just one herb in a blend designed for anxiety and relaxation.

The evidence, ingredient by ingredient Stevia Skullcap Hops German Chamomile Passion Flower Oats Kava St. John's Wort

How safe is it?

Well-documented data
Safety Information · database check
Well characterized

Adverse-effect, pregnancy, and general safety data are on file for most of these ingredients.

Why this rating?
  • We hold adverse-effect (side-effect) data for 8 of the 8 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 8 of 8.
  • General safety write-ups exist for 8 of 8.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Most ingredients in this product are generally well tolerated when used short-term, though drowsiness and digestive upset (bloating, nausea, headache) are common. Stevia may cause abdominal bloating, dizziness, headache, muscle aches, nausea, and numbness in some people, though these usually fade after the first week.

Kava has been linked to over 100 cases of liver damage, mostly with heavy long-term use, but the risk exists. St.

John's Wort can cause sun sensitivity and, rarely, mood changes or psychosis. Pregnancy and breastfeeding safety is a concern: skullcap, hops, passionflower, and St.

John's Wort should all be avoided during pregnancy and breastfeeding due to insufficient safety data. Oat seed extract eaten as food is generally considered safe in pregnancy and while breastfeeding, though concentrated supplements are less studied.

No pregnancy or breastfeeding data is on file for stevia, chamomile, or kava.

Side effects, ingredient by ingredient Stevia Skullcap Hops German Chamomile Passion Flower Oats Kava St. John's Wort

Meds to double-check

Major interaction found
Known Interaction Concern · database check
Major identified

At least one ingredient has a documented Major-severity interaction. Check your medications for a personalized result.

Why this rating?
  • 8 of the 8 matched ingredients can interact with medications — St. John's Wort, Stevia, Oats, Hops, Passion Flower, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; immunosuppressants / transplant drugs; diabetes medications; heart-rhythm medications; lithium.
  • For scale: 1,459 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.

Before taking this product, double-check these medication types with your pharmacist, listed by how serious the interaction could be: blood thinners and cardiac drugs like digoxin; seizure medications like phenytoin and phenobarbital; cancer drugs like irinotecan and docetaxel; HIV protease inhibitors; transplant rejection drugs like tacrolimus; antidepressants and other mood stabilizers; anti-anxiety and sleep medications (CNS depressants); diabetes medications and insulin; blood pressure medications; any drug processed by your liver's CYP2C19, CYP2C9, CYP2E1, or CYP3A4 enzymes; haloperidol; and ropinirole.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFormula with limited ingredient disclosure with some supporting evidence for its stated purpose. Major medication interactions have been identified, and safety information is well characterized.

This blend combines multiple herbs known for sedation and relaxation, which means it carries real risks with sleep aids, anti-anxiety medications, and other CNS depressants. The St.

John's Wort and kava components have especially serious interactions with common medications. If you take any prescription drugs — especially for heart rhythm, seizures, HIV, cancer, mood, or transplant rejection — talk with your pharmacist before starting this product.

Pregnant or breastfeeding? Several of these herbs should be avoided.

Educational only — not medical advice; always confirm with your pharmacist. Our editorial policy · How we use AI

Assessment coverage: 8 of 8 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Jan 23, 2025.

This Scorecard evaluates available label information, ingredient evidence, and known medication-safety considerations. It does not independently verify product identity, purity, potency, contamination, or manufacturing quality. How these ratings are computed

At a glance

General information

Key facts about Kava Cool Complex, straight from the product label.

Brand Herbs Etc.
Barcode (UPC) 765704108512
Net contents 1 Fluid Ounce(s); 30 Milliliter(s)
Market status On market
Date entered into DSLD Jan 23, 2025
DSLD ID 320842
Product type Botanical
Supplement form Liquid
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Vegan, Vegetarian, Adult (18 - 50 Years), Women (not pregnant or lactating), Gluten Free, Dairy Free
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Kava Cool Complex by Herbs Etc., sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
30 Drop(s)
Maximum serving Sizes:
30 Drop(s)
Servings per container
40
UPC/BARCODE
765704108512
IngredientAmount% DV
Stevia herb extract0 NP--
Proprietary Extract Blend0.75 mL--
Skullcap herb extract0 NP--
Hops strobile extract0 NP--
Chamomile flower extract0 NP--
Passionflower Herb Extract, Fresh0 NP--
Oat Seed Extract, Fresh0 NP--
Kava root extract0 NP--
St. John's Wort Herb in Bud Extract, Dry, Fresh0 NP--

Other ingredients: Alcohol, Water, Purified, Glycerin

Tap any ingredient to jump to its full detail below.

Label statements
These statements are the manufacturer’s wording, reproduced from the product label — the label is saying it, not HelloPharmacist. We don’t verify or endorse them.
Formulation

Promotes a feeling of calmness

Gluten free

Vegan

Manufactured in Santa Fe, NM.

No artificial preservatives.

FDA Statement of Identity

Herbal Supplement

Formula

Kava Cool Complex is made with calmness promoting herbs, including Kava, St. John's Wort and Oat.

Suggested/Recommended/Usage/Directions

Suggested use: Take 30 drops in water as needed.

Precautions

Caution: Do not use if you have or had liver problems, frequently use alcohol or take medication.

Stop use and see a doctor if you develop these symptoms: unexplained fatigue, abdominal pain, loss of appetite, fever, vomiting, dark urine, pale stools, yellow eyes or skin.

Not for use by persons under 18, during pregnancy, while nursing, or with alcohol.

Not for use by persons under 18, during pregnancy, while nursing, or with alcohol.

Excessive use or use with products that cause drowsiness may impair ability to operate vehicles or dangerous equipment.

Notice: Do not use this product while taking any prescription drug(s) without the advice of your prescribing physician.

Avoid excessive exposure to UV irradiation (e.g. sunlight; tanning) when using this product.

FDA Disclaimer Statement

This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

General Statements

Herbal medicine

Is this label outdated? Report a formula or label change and our pharmacy team will review it.

See for yourself

Kava Cool Complex by Herbs Etc. label

The label scan from the NIH Dietary Supplement Label Database. Tap to enlarge.

Kava Cool Complex label

Label images are published by the NIH Dietary Supplement Label Database for the version of this product on file. Always read your actual product label.

View the full label (PDF)
What’s inside

The Ingredients in Kava Cool Complex by Herbs Etc.

These are the 8 active ingredients this product is made of. Select any to open its full monograph.

Serving size30 Drop(s) Dosage formLiquid Servings per container40 Amounts shown are per serving.

Most supplement products combine several ingredients, and a medication can interact with the product through any one of them. Each ingredient below shows whether it has known drug interactions.

Other (inactive) ingredients: Alcohol, Water, Purified, Glycerin. These complete the product’s ingredient list but are not active constituents.

Interaction report

Kava Cool Complex by Herbs Etc. Drug Interactions

Want to check YOUR meds against Kava Cool Complex?

Ask about interactions with your drugs in plain English — “Can I take it with lisinopril?” — and we find you the answer in seconds, ingredient by ingredient.

 Go to the checker
1,458Drugs
883 Major 515 Moderate 60 Minor

Ingredients driving the most interactions

Kava root extract 1,166
St. John's Wort Herb in Bud Extract, Dry, Fresh 1,143
Chamomile flower extract 960
Hops strobile extract 863
Passionflower Herb Extract, Fresh 836

Individual Drug Interactions

The ingredients in Kava Cool Complex interact with 1,458 drugs. Click any drug to see the details.

8 of the 8 ingredients in Kava Cool Complex interact with drugs. Each result below shows which ingredient is responsible. Kava root extract St. John's Wort Herb in Bud Extract, Dry, Fresh Chamomile flower extract Hops strobile extract Passionflower Herb Extract, Fresh Stevia herb extract Skullcap herb extract Oat Seed Extract, Fresh

Each ingredient & the kinds of drugs it affects

For each ingredient in Kava Cool Complex with known interactions, here are the types of medications they can affect. Open any type for the detail — or search your exact drug in the checker above.

Kava root extract12 drug types · 1,166 drugs

Cns Depressants

Combining kava with CNS depressants can have additive sedative effects.
Kava has CNS depressant effects. Concomitant use of kava with other CNS depressants can increase the risk of drowsiness and motor reflex depression. Clinical practice guidelines from a joint taskforce of the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) recommend that CNS depressants, including alcohol and benzodiazepines, not be used with kava.

Likelihood Probable Evidence A
Alcohol (Ethanol)

Combining kava with alcohol may increase the risk of sedation and/or hepatotoxicity.

Kava has CNS depressant effects. Concomitant use of kava with other CNS depressants can increase the risk of drowsiness and motor reflex depression. Additionally, kava has been associated with over 100 cases of hepatotoxicity. There is some concern that kava can adversely affect the liver, especially when used in combination with hepatotoxic drugs. Clinical practice guidelines from a joint taskforce of the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) recommend that alcohol not be used with kava.

Likelihood Possible Evidence A
Cytochrome P450 2C19 (Cyp2C19) Substrates

Theoretically, kava might increase levels of CYP2C19 substrates.
In vitro research shows that kava significantly inhibits CYP2C19 enzymes. This effect has not yet been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2C9 (Cyp2C9) Substrates

Theoretically, kava might increase levels of CYP2C9 substrates.
In vitro research shows that kava significantly inhibits CYP2C9 enzymes. This effect has not yet been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2E1 (Cyp2E1) Substrates

Kava might increase levels of CYP2E1 substrates.
In a clinical study in healthy volunteers, taking kava 1000 mg twice daily (containing a daily dose of 138 mg kavalactones) for 28 days inhibited the metabolism of CYP2E1 substrates.

Likelihood Probable Evidence B
Haloperidol (Haldol)

Combining kava and haloperidol might increase the risk of cardiovascular adverse effects and hypoxia.
Atrial flutter and hypoxia has been reported for a patient who received intramuscular injections of haloperidol and lorazepam after using kava orally. The side effects were attributed to kava-induced inhibition of CYP2D6, but might also have been related to additive adverse effects with the concomitant use of haloperidol, lorazepam, and kava.

Likelihood Possible Evidence D
Hepatotoxic Drugs

Theoretically, using kava with hepatotoxic drugs might increase the risk of liver damage.
Kava has been linked with over 100 cases of hepatotoxicity. Most cases occur with excessive and prolonged use. There is some concern that kava can adversely affect the liver, especially when used in combination with hepatotoxic drugs.

Likelihood Possible Evidence D
P-Glycoprotein Substrates

It is unclear if kava inhibits P-glycoprotein (P-gp); research is conflicting.
In vitro research shows that kava can inhibit P-gp efflux. However, a clinical study in healthy volunteers shows that taking kava standardized to provide 225 mg kavalactones daily for 14 days does not affect the pharmacokinetics of digoxin, a P-gp substrate. It is possible that the use of other P-gp substrates or higher doses of kava might still inhibit P-gp.

Likelihood Possible Evidence D
Ropinirole (Requip)

Taking kava with ropinirole might increase the risk for dopaminergic toxicity.
A case of visual hallucinations and paranoid delusions has been reported for a patient who used kava in combination with ropinirole. The adverse effects were attributed to kava-induced inhibition of CYP1A2, which may have reduced the metabolism of ropinirole, resulting in excessive dopaminergic stimulation.

Likelihood Possible Evidence D
Cytochrome P450 1A2 (Cyp1A2) Substrates

It is unclear if kava inhibits CYP1A2; research is conflicting.
Although in vitro research and a case report suggest that kava inhibits CYP1A2, more robust clinical evidence shows that kava has no effect on CYP1A2. In a clinical study in healthy volunteers, taking kava 1000 mg twice daily (containing a daily dose of 138 mg kavalactones) for 28 days had no effect on CYP1A2 activity.

Likelihood Unlikely Evidence B
Cytochrome P450 2D6 (Cyp2D6) Substrates

It is unclear if kava inhibits CYP1A2; research is conflicting.
In vitro research shows that kava extract significantly inhibits CYP2D6. However, clinical research shows that kava does not affect the metabolism of CYP2D6 substrates in humans.

Likelihood Unlikely Evidence B
Cytochrome P450 3A4 (Cyp3A4) Substrates

It is unclear if kava inhibits CYP3AA; research is conflicting.
Although in vitro research suggests that kava inhibits CYP3A4, more robust clinical evidence shows that kava has no effect on CYP3A4. In a clinical study in healthy volunteers, taking kava 1000 mg twice daily (containing a daily dose of 138 mg kavalactones) for 28 days had no effect on CYP3A4 activity.

Likelihood Unlikely Evidence B
Kava root extract full monograph & interactions

St. John's Wort Herb in Bud Extract, Dry, Fresh47 drug types · 1,143 drugs

Alprazolam (Xanax)

St. John's wort increases the clearance of alprazolam and decreases its effects.
Alprazolam, which is used as a probe for cytochrome P450 3A4 (CYP3A4) activity, has a two-fold increase in clearance when given with St. John's wort. St. John's wort reduces the half-life of alprazolam from 12.4 hours to 6 hours.

Likelihood Likely Evidence B
Contraceptive Drugs

St. John's wort increases the clearance of contraceptive drugs and reduces their clinical effects.
Females taking St. John's wort and oral contraceptives concurrently should use an additional or alternative form of birth control. St. John's wort can decrease norethindrone and ethinyl estradiol levels by 13% to 15%, resulting in breakthrough bleeding, irregular menstrual bleeding, or unplanned pregnancy. Bleeding irregularities usually occur within a week of starting St. John's wort and regular cycles usually return when St. John's wort is discontinued. Unplanned pregnancy has occurred with concurrent use of oral contraceptives and St. John's wort extract. St. John's wort is thought to induce the cytochrome P450 1A2 (CYP1A2), 2C9 (CYP2C9), and 3A4 (CYP3A4) enzymes, which are responsible for metabolism of progestins and estrogens in contraceptives.

Likelihood Probable Evidence B
Cyclosporine (Neoral, Sandimmune)

St. John's wort reduces the levels and clinical effects of cyclosporine.
Concomitant use can decrease plasma cyclosporine levels by 30% to 70%. Using St. John's wort with cyclosporine in patients with heart, kidney, or liver transplants can cause subtherapeutic cyclosporine levels and acute transplant rejection. This interaction has occurred with a St. John's wort extract standardized to 0.3% hypericin and dosed at 300-600 mg per day. Withdrawal of St. John's wort can result in a 64% increase in cyclosporine levels. St. John's wort induces cytochrome P450 3A4 (CYP3A4) and the multi-drug transporter, P-glycoprotein/MDR-1, which increases cyclosporine clearance.

Likelihood Probable Evidence B
Cytochrome P450 3A4 (Cyp3A4) Substrates

St. John's wort increases the metabolism and reduces the levels of CYP3A4 substrates.
St. John's wort induces CYP3A4 enzymes and increases metabolism of CYP3A4 substrates. Clinically significant interactions have been reported with St. John's wort products containing hyperforin 1 mg or more.

Likelihood Probable Evidence B
Digoxin (Lanoxin)

St. John's wort reduces the levels and clinical effects of digoxin.
St. John's wort can reduce the bioavailability, serum levels, and therapeutic effects of digoxin. Taking an extract of St. John's wort 900 mg, containing hyperforin 7.5 mg or more, daily for 10-14 days, can reduce serum digoxin levels by 25% in healthy people. St. John's wort is thought to affect the multidrug transporter, P-glycoprotein, which mediates the absorption and elimination of digoxin and other drugs. St. John's wort products providing less than 7.5 mg of hyperforin daily do not appear to affect digoxin levels.

Likelihood Likely Evidence B
Docetaxel (Taxotere)

St. John's wort reduces the levels and clinical effects of docetaxel.
Clinical research shows that taking a specific St. John's wort product (Hyperiplant, VSM) 300 mg three times daily for 14 days increases docetaxel clearance by about 14%, resulting in decreased plasma concentrations of docetaxel in cancer patients. This is most likely due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort.

Likelihood Probable Evidence B
Imatinib (Gleevec)

St. John's wort reduces the levels and clinical effects of imatinib.
Taking St. John's wort 900 mg daily for 2 weeks reduces the bioavailability and half-life of a single dose of imatinib and decreases its serum levels by 30% in healthy volunteers. This is most likely due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort, which increases clearance of imatinib.

Likelihood Likely Evidence A
Irinotecan (Camptosar)

St. John's wort reduces the levels and clinical effects of irinotecan.
St. John's wort 900 mg daily for 18 days decreases serum levels of irinotecan by at least 50%. Clearance of the active metabolite of irinotecan, SN-38, is also increased, resulting in a 42% decrease in the area under the concentration-time curve. This is thought to be due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort.

Likelihood Likely Evidence A
Mephenytoin (Mesantoin)

St. John's wort reduces the levels and clinical effects of mephenytoin.
Preliminary clinical research in healthy males shows that taking St. John's wort for 14 days induces cytochrome P450 2C19 (CYP2C19) and significantly increases metabolism of mephenytoin (Mesantoin). In people with wild-type 2C19, metabolism was almost 4-fold greater in subjects who received St. John's wort compared to placebo. In contrast, patients with 2C19*2/*2 and *2/*3 genotypes did not demonstrate a similar increase in metabolism.

Likelihood Likely Evidence B
Non-Nucleoside Reverse Transcriptase Inhibitors (Nnrtis)

St. John's wort decreases the levels and clinical effects of NNRTIs.
St. John's wort increases the oral clearance of nevirapine (Viramune) by 35%. Subtherapeutic concentrations are associated with therapeutic failure, development of viral resistance, and development of drug class resistance. St. John's wort induces intestinal and hepatic cytochrome P450 3A4 (CYP3A4) and intestinal P-glycoprotein/MDR-1, a drug transporter.

Likelihood Likely Evidence B
Omeprazole (Prilosec)

St. John's wort decreases the levels and clinical effects of omeprazole.
Taking St. John's wort, 300 mg orally three times daily for 14 days, reduces serum concentrations of omeprazole by inducing its metabolism via cytochrome P450 (CYP) 2C19 and 3A4. The reduction of omeprazole serum levels is dependent on CYP2C19 genotype, with reductions up to 50% in extensive metabolizers and 38% in poor metabolizers.

Likelihood Likely Evidence B
Oxycodone (Oxycontin)

St. John's wort decreases the levels and clinical effects of oxycodone.
St. John's wort can increase oxycodone metabolism by inducing cytochrome P450 3A4 (CYP3A4), reducing plasma levels and analgesic activity.

Likelihood Probable Evidence B
P-Glycoprotein Substrates

St. John's wort decreases the levels and clinical effects of P-glycoprotein substrates.
St. John's wort induces P-glycoprotein. P-glycoprotein is a carrier mechanism responsible for transporting drugs and other substances across cell membranes. When P-glycoprotein is induced in the gastrointestinal (GI) tract, it can prevent the absorption of some medications. In addition, induction of p-glycoprotein can decrease entry of drugs into the central nervous system (CNS) and decrease access to other sites of action.

Likelihood Probable Evidence B
Phenobarbital (Luminal)

St. John's wort decreases the levels and clinical effects of phenobarbital.
St. John's wort may increase the metabolism of phenobarbital. Plasma concentrations of phenobarbital should be monitored carefully. The dose of phenobarbital may need to be increased when St. John's wort is started and decreased when it is stopped.

Likelihood Likely Evidence B
Phenprocoumon (Marcoumar, Others)

St. John's wort decreases the levels and clinical effects of phenprocoumon.
St. John's wort appears to increase the metabolism of phenprocoumon (an anticoagulant that is not available in the US) by increasing the activity of the cytochrome P450 2C9 (CYP2C9) enzyme. This may result in decreases in the anticoagulant effect and international normalized ratio (INR).

Likelihood Likely Evidence B
Phenytoin (Dilantin)

St. John's wort decreases the levels and clinical effects of phenytoin.
St. John's wort may increase the metabolism of phenytoin. Plasma concentrations of phenytoin should be monitored closely. The dose of phenytoin may need to be increased when St. John's wort is started and decreased when it is stopped.

Likelihood Likely Evidence B
Protease Inhibitors (Pis)

St. John's wort reduces the levels and clinical effects of PIs.
In healthy volunteers, St. John's wort can reduce the plasma concentrations of indinavir (Crixivan) by inducing cytochrome P450 3A4 (CYP3A4). This might result in treatment failure and viral resistance. St. John's wort also induces P-glycoprotein, which can result in decreased intracellular protease inhibitor concentrations and increased elimination.

Likelihood Likely Evidence B
Rivaroxaban (Xarelto)

St. John's wort decreases the levels and clinical effects of rivaroxaban.
A small pharmacokinetic study in healthy volunteers shows that taking a single dose of rivaroxaban 20 mg after using a specific St. John's wort extract (Jarsin, Vifor SA) 450 mg orally twice daily for 14 days reduces the bioavailability of rivaroxaban by 24% and reduces rivaroxaban's therapeutic inhibition of factor Xa by 20%.

Likelihood Probable Evidence B
Tacrolimus (Prograf)

St. John's wort decreases the levels and clinical effects of tacrolimus.
Taking a St. John's wort extract (Jarsin) 600 mg daily significantly decreases tacrolimus serum levels. Dose increases of 60% may be required to maintain therapeutic tacrolimus levels in patients taking St. John's wort. St. John's wort is thought to lower tacrolimus levels by inducing cytochrome P450 3A4 (CYP3A4) enzymes. A small clinical study in healthy adults also shows that taking St. John's wort 300 mg three times daily for 10 days decreases the total systemic exposure to tacrolimus by 27% and 33% after taking a single 5 mg dose of immediate-release or prolonged-release tacrolimus, respectively.

Likelihood Likely Evidence B
Warfarin (Coumadin)

St. John's wort decreases the levels and clinical effects of warfarin.
Taking St. John's wort significantly increases clearance of warfarin, including both its R- and S-isomers. This is likely due to induction of cytochrome P450 (CYP) 1A2 and CYP3A4. St. John's wort can also significantly decrease International Normalized Ratio (INR) in people taking warfarin. In addition, taking warfarin at the same time as St. John's wort might reduce warfarin bioavailability. When a dried extract is mixed with warfarin in an aqueous medium, up to 30% of warfarin is bound to particles, reducing its absorption.

Likelihood Likely Evidence B
Aminolevulinic Acid

St. John's wort might have additive phototoxic effects with aminolevulinic acid.
Concomitant use with St. John's wort extract may cause synergistic phototoxicity. Delta-aminolevulinic acid can cause a burning erythematous rash and severe swelling of the face, neck, and hands when taken with St. John's wort.

Likelihood Possible Evidence D
Bupropion (Wellbutrin)

St. John's wort might reduce the levels and effects of bupropion.
Clinical research shows that taking St. John's wort 325 mg three times daily for 14 days along with bupropion reduces the area under the concentration-time curve by approximately 14% and increases the clearance of bupropion by approximately 20%. This effect is attributed to the induction of cytochrome P450 2B6 (CYP2B6) by St. John's wort.

Likelihood Probable Evidence B
Clopidogrel (Plavix)

St. John's wort might increase the levels and effects of clopidogrel.
Taking St. John's wort with clopidogrel seems to increase the activity of clopidogrel. In clopidogrel non-responders, taking St. John's wort seems to induce metabolism of clopidogrel to its active metabolite by cytochrome P450 enzymes 3A4 and 2C19. This leads to increased antiplatelet activity. Theoretically, this might lead to an increased risk of bleeding in clopidogrel responders.

Likelihood Possible Evidence B
Clozapine (Clozaril)

St. John's wort might decrease the levels and clinical effects of clozapine.
A case report describes a female with schizophrenia controlled on clozapine who had a return of symptoms when she started taking St. John's wort. The plasma concentration of clozapine was reduced, likely because its clearance was increased due to induction of the cytochrome P450 enzymes 3A4, 1A2, 2C9, and 2C19 by St. John's wort.

Likelihood Possible Evidence D
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.

Likelihood Possible Evidence B
St. John's Wort Herb in Bud Extract, Dry, Fresh full monograph & all 47 interactions

Chamomile flower extract9 drug types · 960 drugs

Cns Depressants

Theoretically, German chamomile might have additive effects when used with CNS depressants.
German chamomile has mild sedative effects. Theoretically, concomitant use with drugs with sedative properties can cause additive effects and side effects.

Likelihood Possible Evidence D
Contraceptive Drugs

Theoretically, large amounts of German chamomile might reduce the effectiveness of oral contraceptives.
In vitro, German chamomile has demonstrated antiestrogenic activity. Theoretically, concomitant use of large amounts of German chamomile might interfere with contraceptive drugs through competition for estrogen receptors.

Likelihood Possible Evidence D
Cytochrome P450 2C9 (Cyp2C9) Substrates

Theoretically, German chamomile might inhibit CYP2C9 and increase levels of drugs metabolized by these enzymes.
In vitro evidence shows that German chamomile might inhibit CYP2C9. So far, this interaction has not been reported in humans. However, there might be an increase in the levels of drugs metabolized by CYP2C9 in patients taking German chamomile.

Likelihood Possible Evidence D
Cytochrome P450 2D6 (Cyp2D6) Substrates

Theoretically, German chamomile might inhibit CYP2D6 and increase levels of drugs metabolized by these enzymes.
In vitro evidence shows that German chamomile might inhibit CYP2D6. So far, this interaction has not been reported in humans. However, there might be an increase in the levels of drugs metabolized by CYP2D6 in patients taking German chamomile.

Likelihood Possible Evidence D
Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, German chamomile might inhibit CYP3A4 and increase levels of drugs metabolized by these enzymes.
In vitro evidence shows that German chamomile might inhibit CYP3A4. So far, this interaction has not been reported in humans. However, there might be an increase in the levels of drugs metabolized by CYP3A4 in patients taking German chamomile.

Likelihood Possible Evidence D
Estrogens

Theoretically, large amounts of German chamomile might reduce the effectiveness of estrogens.
In vitro, German chamomile has demonstrated antiestrogenic activity. Theoretically, large amounts of German chamomile might interfere with hormone replacement therapy through competition for estrogen receptors.

Likelihood Possible Evidence D
Tamoxifen (Nolvadex)

Theoretically, large amounts of German chamomile might interfere with the activity of tamoxifen.
In vitro, German chamomile has demonstrated antiestrogenic activity.

Likelihood Possible Evidence D
Warfarin (Coumadin)

German chamomile might increase the effects of warfarin and increase the risk of bleeding.
In one case, a 70-year-old female taking warfarin developed retroperitoneal hematoma and bilateral recti muscle bleeding along with an INR of 7.9 following ingestion of German chamomile tea 4-5 cups daily and use of a topical chamomile-based lotion applied 4-5 times daily.

Likelihood Possible Evidence D
Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, German chamomile might inhibit CYP1A2 and increase levels of drugs metabolized by these enzymes.
In vitro and animal research shows that German chamomile might inhibit CYP1A2. So far, this interaction has not been reported in humans. However, there might be an increase in the levels of drugs metabolized by CYP1A2 in patients taking German chamomile.

Likelihood Possible Evidence D
Chamomile flower extract full monograph & interactions

Hops strobile extract4 drug types · 863 drugs

Cns Depressants

Theoretically, concomitant use of hops with sedative drugs might cause additive sedation.
Some animal research shows that hops has sedative effects.

Likelihood Possible Evidence D
Estrogens

Theoretically, concomitant use of large amounts of hops might interfere with hormone replacement therapy due to competition for estrogen receptors.
In vitro research suggests that certain hops constituents can competitively bind to estrogen receptors. However, most hops extracts contain very small amounts of these constituents.

Likelihood Possible Evidence D
Cytochrome P450 1A2 (Cyp1A2) Substrates

Hops extract does not seem to affect the metabolism of CYP1A2 substrates.
In vitro research suggests that flavonoid constituents of hops inhibit CYP1A2 enzyme activity. However, a pharmacokinetic study in healthy postmenopausal patients shows that taking a standardized extract of spent hops containing prenylated phenols, as 59.5 mg twice daily for 2 weeks, does not affect levels of caffeine, a CYP1A2 probe substrate.

Likelihood Unlikely Evidence D
Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, hops extract might alter metabolism of CYP3A4 substrates; however, this effect may not be clinically significant.
Animal research suggests that specific constituents of hops, called lupulones, can induce hepatic CYP3A4 enzyme activity. However, a pharmacokinetic study in healthy postmenopausal patients with normal metabolism shows that taking a standardized extract of spent hops containing prenylated phenols, as 59.5 mg twice daily for 2 weeks, decreases the concentration of alprazolam, a CYP3A4 probe substrate, by 7.6%. This reduction is unlikely to be clinically relevant.

Likelihood Possible Evidence D
Hops strobile extract full monograph & interactions

Passionflower Herb Extract, Fresh3 drug types · 836 drugs

Cns Depressants

Concomitant use of passion flower with sedative drugs might cause additive effects and side effects.
Research in animals and humans shows that passion flower has sedative effects which can be additive when used with sedative medications like lorazepam.

Likelihood Possible Evidence D
Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, passion flower might decrease the effects of CYP3A4 substrates.
In vitro research suggests that passion flower can induce CYP3A4 enzymes, albeit to a much lower degree than rifampin, a known CYP3A4 inducer.

Likelihood Possible Evidence D
Organic Anion-Transporting Polypeptide Substrates (Oatp)

Theoretically, passion flower might reduce the bioavailability of OATP2B1 and OATP1A2 substrates.
In vitro research shows that the passion flower constituents apigenin and vitexin inhibit OATP2B1 and OATP1A2. This inhibition may be dose-dependent. One specific high-flavonoid passion flower extract (Valverde) seems to inhibit OATP2B1 and OATP1A2, while another extract with a lower flavonoid concentration (Arkocaps) shows less potent inhibition. OATPs are responsible for the uptake of drugs and other compounds into the body; however, the specific activities of OATP2B1 and OATP1A2 are not well characterized.

Likelihood Possible Evidence D
Passionflower Herb Extract, Fresh full monograph & interactions

Stevia herb extract3 drug types · 259 drugs

Lithium

Theoretically, stevia might decrease clearance and increase levels of lithium.
Animal research suggests that stevia extracts might have diuretic activity. Theoretically, increased reabsorption of lithium along with sodium might reduce excretion and increase levels of lithium.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, stevia might increase the risk for hypoglycemia when combined with antidiabetes drugs.
Preliminary clinical research in patients with type 2 diabetes suggests that taking a single dose of stevia extract 1000 mg reduces postprandial blood glucose levels when taken with a meal. However, other clinical research in patients with type 1 or type 2 diabetes suggests that taking stevioside 250 mg three times daily does not significantly affect blood glucose levels or glycated hemoglobin (HbA1C) after three months of treatment.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, combining stevia or stevia constituents with antihypertensive agents might increase the risk of hypotension.
Stevia extract and stevioside might lower blood pressure in patients with hypertension. However, other clinical research suggests that stevioside does not significantly lower blood pressure in patients with hypertension.

Likelihood Possible Evidence D
Stevia herb extract full monograph & interactions

Skullcap herb extract1 drug type · 248 drugs

Cns Depressants

Theoretically, skullcap can have additive effects when used with other CNS depressants.
Animal and clinical research suggests that skullcap can cause sedation and cognitive impairment.

Likelihood Possible Evidence D
Skullcap herb extract full monograph & interactions

Oat Seed Extract, Fresh2 drug types · 86 drugs

Antidiabetes Drugs

Theoretically, oats may have additive effects with antidiabetic agents and might increase the risk of hypoglycemia.
Consuming oats can decrease blood glucose in patients with diabetes. In those who require insulin, taking oats 100 grams daily for 2 days reduces the insulin dose required to achieve metabolic control.

Likelihood Possible Evidence D
Insulin

Concomitant use of oats and insulin might increase the risk of hypoglycemia.
In patients with insulin-dependent type 2 diabetes, taking oats 100 grams daily for 2 days reduces the insulin dose required to achieve metabolic control.

Likelihood Possible Evidence B
Oat Seed Extract, Fresh full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Kava Cool Complex, from the product label.

Herbs Etc.

Name
Herbs, Etc., Inc.
Street Address
1340 Rufina Circle
City
Santa Fe
State
NM
ZipCode
87507
Web Address
www.herbsetc.com
Pharmacist Counseling Corner

Kava Cool Complex by Herbs Etc.: Common Questions

Does Kava Cool Complex by Herbs Etc. interact with any medications?
Yes. Based on its ingredients, Kava Cool Complex has a known interaction with 1,458 medications, including 883 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Kava Cool Complex contains 8 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.
Is this safe if I'm pregnant or breastfeeding?
Several ingredients — skullcap, hops, passionflower, and St. John's Wort — should be avoided during pregnancy and breastfeeding because safety data is not adequate. The oat seed extract in food form is considered safe during pregnancy and breastfeeding, but concentrated supplements are less studied. Talk with your doctor or pharmacist before using this product during pregnancy or while nursing.
Does passion flower in this product actually help with sleep?
Yes, passion flower is rated possibly effective for insomnia based on our data. However, this is a blend of eight ingredients with different purposes, so the effect depends on the full formula, not just one herb.
What are the most common side effects?
Drowsiness, dizziness, headache, nausea, bloating, and digestive upset are the most common side effects across these ingredients. Most minor effects fade after the first week of use, but if they persist or worsen, stop the product and talk with a pharmacist.
Why does the label say this product has kava if kava has liver problems?
Kava is a traditional herbal relaxant, but it has been linked to rare liver injury, especially with heavy or prolonged use. The risk is lower with short-term use, but it's real. If you use this product, limit it to short-term use and avoid it if you drink alcohol regularly or have liver disease.
Is oat seed extract the same as oatmeal?
Oat seed extract is a concentrated form of oats, while oatmeal is the whole grain you eat for breakfast. Both are from oats and are safe to eat, but the extract is stronger. Both may lower blood sugar, so be cautious if you take diabetes medications or insulin.
Why do I need to check my medications with a pharmacist?
St. John's Wort and kava in this blend interact with many common drugs — heart medications, seizure drugs, cancer treatments, HIV drugs, and others. St. John's Wort can make some drugs stop working, and kava can make others build up to dangerous levels. Your pharmacist can check your exact medications and tell you if it's safe to mix them with this product.

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

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Label information is sourced from the NIH Dietary Supplement Label Database and reflects the product version on file; always read your actual product label. This page is for education only and is not a substitute for professional medical advice. Confirm with your pharmacist or doctor before combining supplements and medications.

Kava Cool Complex label
Go deeper

The Full Monographs Behind Kava Cool Complex’s Ingredients

Every ingredient we hold a full HelloPharmacist monograph for — uses, evidence, safety, and the complete interaction list.

Herb & supplement monograph

Stevia

Interacts with 259 drugs

Stevia is a plant-based, calorie-free sweetener that is widely used as a sugar alternative and is considered safe in normal food amounts by major regulators. Purified stevia extracts have a...

Read the full Stevia monograph → Herb & supplement monograph

Skullcap

Interacts with 248 drugs

American skullcap is an herb traditionally used to calm anxiety and promote relaxation, but solid human evidence is very limited. It is generally considered relatively safe for short-term us...

Read the full Skullcap monograph → Herb & supplement monograph

Hops

Interacts with 863 drugs

Hops are most often used for sleep and mild anxiety, frequently combined with valerian, but the human evidence is limited and not very strong. They are generally well tolerated when used sho...

Read the full Hops monograph → Herb & supplement monograph

German Chamomile

Interacts with 960 drugs

German chamomile is a widely used herbal remedy taken mainly as a tea for calming, sleep, and digestive complaints. Early research suggests possible benefits for mild anxiety and some skin o...

Read the full German Chamomile monograph → Herb & supplement monograph

Passion Flower

Interacts with 836 drugs

Passion flower is a traditional calming herb that many people use for anxiety and sleep. Early studies hint it may help with mild anxiety and restlessness, but the evidence is limited and mo...

Read the full Passion Flower monograph → Herb & supplement monograph

Oats

Interacts with 86 drugs

Oats are a well-studied whole grain whose soluble fiber (beta-glucan) can help lower cholesterol and support heart health when eaten regularly. As a food, oats are safe for most people, and...

Read the full Oats monograph → Herb & supplement monograph

Kava

Interacts with 1,166 drugs

Kava is a Pacific Island plant traditionally used to promote relaxation and ease anxiety, and some studies suggest it may help mild anxiety. However, kava has been linked to rare but serious...

Read the full Kava monograph → Herb & supplement monograph

St. John's Wort

Interacts with 1,143 drugs

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 presc...

Read the full St. John's Wort monograph →
Sources

Sources & How We Checked

Kava Cool Complex's label data comes from the NIH Dietary Supplement Label Database; the ingredient interaction data is from the Natural Medicines database, reviewed by our pharmacists.

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

The 298 references behind this product’s interaction data

Every citation that drives the interaction findings for this product’s ingredients, from the evidence-graded Natural Medicines (TRC Healthcare) database. Open an ingredient to browse its citations — links open the study on PubMed or the publisher’s site.

Stevia 10 references
  1. Chan P, Xu DY, Liu JC, et al. The effect of stevioside on blood pressure and plasma catecholamines in spontaneously hypertensive rats. Life Sci 1998;63:1679-84. PubMed
  2. Melis MS. A crude extract of Stevia rebaudiana increases the renal plasma flow of normal and hypertensive rats. Braz J Med Biol Res 1996;29:669-75.
  3. Melis MS. Chronic administration of aqueous extract of Stevia rebaudiana in rats: renal effects. J Ethnopharmacol 1995;47:129-34. PubMed
  4. Melis MS, Sainati AR. Effect of calcium and verapamil on renal function of rats during treatment with stevioside. J Ethnopharmacol 1991;33:257-622. PubMed
  5. Hsieh MH, Chan P, Sue YM, et al. Efficacy and tolerability of oral stevioside in patients with mild essential hypertension: a two-year, randomized, placebo-controlled study. Clin Ther 2003;25:2797-808. PubMed
  6. Chan P, Tomlinson B, Chen YJ, et al. A double-blind placebo-controlled study of the effectiveness and tolerability of oral stevioside in human hypertension. Br J Clin Pharmacol 2000;50:215-20. PubMed
  7. Gregersen S, Jeppesen PB, Holst JJ, Hermansen K. Antihyperglycemic effects of stevioside in type 2 diabetic subjects. Metabolism 2004;53:73-6. PubMed
  8. Barriocanal LA, Palacios M, Benitez G, et al. Apparent lack of pharmacological effect of steviol glycosides used as sweeteners in humans. A pilot study of repeated exposures in some normotensive and hypotensive individuals and in Type 1 and Type 2 diabeti
  9. Ferri LA, Alves-Do-Prado W, Yamada SS, et al. Investigation of the antihypertensive effect of oral crude stevioside in patients with mild essential hypertension. Phytother Res 2006;20:732-6. PubMed
  10. Almiron-Roig E, Navas-Carretero S, Castelnuovo G, et al. Impact of acute consumption of beverages containing plant-based or alternative sweetener blends on postprandial appetite, food intake, metabolism, and gastro-intestinal symptoms: Results of the SWEE

See these in context on the Stevia monograph →

Skullcap 3 references
  1. Wolfson P, Hoffmann DL. An investigation into the efficacy of Scutellaria lateriflora in healthy volunteers. Altern Ther Health Med 2003;9:74-8.
  2. Awad, R., Arnason, J. T., Trudeau, V., Bergeron, C., Budzinski, J. W., Foster, B. C., and Merali, Z. Phytochemical and biological analysis of skullcap (Scutellaria lateriflora L.): a medicinal plant with anxiolytic properties. Phytomedicine. 2003;10(8):6 PubMed
  3. Brock C, Whitehouse J, Tewfik I, Towell T. American skullcap (Scutellaria lateriflora): a randomised, double-blind placebo-controlled crossover study of its effects on mood in healthy volunteers. Phytother Res 2014;28(5):692-8.

See these in context on the Skullcap monograph →

Hops 15 references
  1. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  2. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  3. Zava DT, Dollbaum CM, Blen M. Estrogen and progestin bioactivity of foods, herbs, and spices. Proc Soc Exp Biol Med 1998;217:369-78. PubMed
  4. Milligan SR, Kalita JC, Heyerick A, et al. Identification of a potent phytoestrogen in hops (Humulus lupulus L.) and beer. J Clin Endocrinol Metab 1999;84:2249-52.. PubMed
  5. Milligan SR, Kalita JC, Pocock V, et al. The endocrine activities of 8-prenylnaringenin and related hop (Humulus lupulus L.) flavonoids. J Clin Endocrinol Metab 2000;85:4912-5.. DOI
  6. Henderson MC, Miranda CL, Stevens JF, et al. In vitro inhibition of human P450 enzymes by prenylated flavonoids from hops, Humulus lupulus. Xenobiotica 2000;30:235-51.. PubMed
  7. Mannering, G. J., Shoeman, J. A., and Deloria, L. B. Identification of the antibiotic hops component, colupulone, as an inducer of hepatic cytochrome P-4503A in the mouse. Drug Metab Dispos 1992;20(2):142-147. DOI
  8. Skorska, C., Mackiewicz, B., Gora, A., Golec, M., and Dutkiewicz, J. Health effects of inhalation exposure to organic dust in hops farmers. Ann.Univ Mariae.Curie Sklodowska [Med] 2003;58(1):459-465.
  9. Schiller, H., Forster, A., Vonhoff, C., Hegger, M., Biller, A., and Winterhoff, H. Sedating effects of Humulus lupulus L. extracts. Phytomedicine. 2006;13(8):535-541. PubMed
  10. van Hunsel, F. P. and Kampschoer, P. [Postmenopausal bleeding and dietary supplements: a possible causal relationship with hop- and soy-containing preparations]. Ned.Tijdschr.Geneeskd. 2012;156(41):A5095.
  11. Fenselau, C. and Talalay, P. Is oestrogenic activity present in hops? Food Cosmet.Toxicol. 1973;11(4):597-602. PubMed
  12. Godnic-Cvar, J., Zuskin, E., Mustajbegovic, J., Schachter, E. N., Kanceljak, B., Macan, J., Ilic, Z., and Ebling, Z. Respiratory and immunological findings in brewery workers. Am J Ind Med 1999;35(1):68-75. DOI
  13. Lee KM, Jung JS, Song DK, and et al. Effects of Humulus lupulus extract on the central nervous system in mice. Planta Med 1993;59(Suppl):A691.
  14. Assessment report on Humulus lupulus L., flos. European Medicines Agency, 2014. Available at: https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-humulus-lupulus-l-flos_en.pdf. Accessed September 29, 2021.
  15. van Breemen RB, Chen L, Tonsing-Carter A, et al. Pharmacokinetic Interactions of a Hop Dietary Supplement with Drug Metabolism in Perimenopausal and Postmenopausal Women. J Agric Food Chem. 2020;68(18):5212-5220. PubMed

See these in context on the Hops monograph →

German Chamomile 15 references
  1. Subiza J, Subiza JL, Hinojosa M, et al. Anaphylactic reaction after the ingestion of chamomile tea; a study of cross-reactivity with other composite pollens. J Allergy Clin Immunol 1989;84:353-8. PubMed
  2. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82. PubMed
  3. Viola H, Wasowski C, Levi de Stein M, et al. Apigenin, a component of Matricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects. Planta Med 1995;61:213-6.
  4. van Ketel WG. Allergy to Matricaria chamomilla. Contact Dermatitis 1982;8:143. PubMed
  5. van Ketel WG. Allergy to Matricaria chamomilla. Contact Dermatitis 1987;16:50-1. PubMed
  6. Hormann HP, Korting HC. Evidence for the efficacy and safety of topical herbal drugs in dermatology: part I: anti-inflammatory agents. Phytomedicine 1994;1:161-71. PubMed
  7. Avallone R, Zanoli P, Puia G, et al. Pharmacological profile of apigenin, a flavonoid isolated from Matricaria chamomilla. Biochem Pharmacol 2000;59:1387-94. PubMed
  8. Kassi E, Papoutsi Z, Fokialakis N, et al. Greek plant extracts exhibit selective estrogen receptor modulator (SERM)-like properties. J Agric Food Chem 2004;52:6956-61. PubMed
  9. Maliakal PP, Wanwimolruk S. Effect of herbal teas on hepatic drug metabolizing enzymes in rats. J Pharm Pharmacol 2001;53:1323-9. PubMed
  10. Segal R, Pilote L. Warfarin interaction with Matricaria chamomilla. CMAJ 2006;174:1281-2. PubMed
  11. Loggia RD, Traversa U, Scarcia V, et al. Depressive effects of Chamomilla recutita (L.) Rausch, tubular flowers, on central nervous system in mice. Pharmacol Res Commun 1982;14(2):153-162. PubMed
  12. Ganzera M, Schneider P, Stuppner H. Inhibitory effects of the essential oil of chamomile (Matricaria recutita L.) and its major constituents on human cytochrome P450 enzymes. Life Sci 2006;78(8):856-861. PubMed
  13. Benito P, Rodríguez-Perez R, García F, Juste S, Moneo I, Caballero ML. Occupational allergic rhinoconjunctivitis induced by Matricaria chamomilla with tolerance of chamomile tea. J Investig Allergol Clin Immunol. 2014;24(5):369-70. No abstract available.
  14. Braga FT, Santos AC, Bueno PC, et al. Use of Chamomilla recutita in the prevention and treatment of oral mucositis in patients undergoing hematopoietic stem cell transplantation: a randomized, controlled, phase II clinical trial. Cancer Nurs 2015;38(4):32 PubMed
  15. 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

See these in context on the German Chamomile monograph →

Passion Flower 19 references
  1. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  2. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
  3. Fisher AA, Purcell P, Le Couteur DG. Toxicity of Passiflora incarnata L. J Toxicol Clin Toxicol 2000;38:63-6.
  4. Akhondzadeh S, Naghavi HR, Shayeganpour A, et al. Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam. J Clin Pharm Ther 2001;26:363-7. PubMed
  5. Farnsworth N, Bingel A, Cordell G, et al. Potential value of plants as sources of new antifertility agents I. J Pharm Sci 1975;64:535-98. DOI
  6. Mori A, Hasegawa K, Murasaki M, et al. Clinical evaluation of Passiflamin (passiflora extract) on neurosis - multicenter double blind study in comparison with mexazolam. Rinsho Hyoka (Clinical Evaluation) 1993;21:383-440.
  7. Miyasaka LS, Atallah AN, Soares BG. Passiflora for anxiety disorder. Cochrane Database Syst Rev 2007;(1):CD004518. DOI
  8. Speroni E., Minghetti A. Neuropharmacological activity of extracts from Passiflora incarnata. Planta Med. 1988;54:488-91.
  9. Capasso A., Sorrentino L. Pharmacological studies on the sedative and hypnotic effect of Kava kava and Passiflora extracts combination. Phytomedicine. 2005;12:39-45. PubMed
  10. Carrasco MC, Vallejo JR, Pardo-de-Santayana M, et al. Interactions of Valeriana officinalis L. and Passiflora incarnata L. in a patient treated with lorazepam. Phytother Res. 2009 Dec;23:1795-6.
  11. Smith, G. W., Chalmers, T. M., and Nuki, G. Vasculitis associated with herbal preparation containing Passiflora extract. Br J Rheumatol. 1993;32(1):87-88.
  12. Soulimani, R., Younos, C., Jarmouni, S., Bousta, D., Misslin, R., and Mortier, F. Behavioural effects of Passiflora incarnata L. and its indole alkaloid and flavonoid derivatives and maltol in the mouse. J Ethnopharmacol. 1997;57(1):11-20. PubMed
  13. Nojoumi M, Ghaeli P, Salimi S, Sharifi A, Raisi F. Effects of Passion Flower Extract, as an Add-On Treatment to Sertraline, on Reaction Time in Patients ?with Generalized Anxiety Disorder: A Double-Blind Placebo-Controlled Study. Iran J Psychiatry. 2016;1
  14. Rokhtabnak F, Ghodraty MR, Kholdebarin A, et al. Comparing the Effect of Preoperative Administration of Melatonin and Passiflora incarnata on Postoperative Cognitive Disorders in Adult Patients Undergoing Elective Surgery. Anesth Pain Med. 2016;7(1):e4123 PubMed
  15. Dantas LP, de Oliveira-Ribeiro A, de Almeida-Souza LM, Groppo FC. Effects of passiflora incarnata and midazolam for control of anxiety in patients undergoing dental extraction. Med Oral Patol Oral Cir Bucal. 2017;22(1):e95-e101. PubMed
  16. Ozturk Z, Kalayci CC. Pregnancy outcomes in psychiatric patients treated with passiflora incarnata. Complement Ther Med. 2018 Feb;36:30-32. PubMed
  17. da Cunha RS, Amorim KS, Gercina AC, et al. Herbal medicines as anxiolytics prior to third molar surgical extraction. A randomized controlled clinical trial. Clin Oral Investig. 2020. PubMed
  18. Schäfer AM, Gilgen PM, Spirgi C, et al. Constituents of Passiflora incarnata, but Not of Valeriana officinalis, Interact with the Organic Anion Transporting Polypeptides (OATP)2B1 and OATP1A2. Planta Med. 2021. PubMed
  19. Mazzari ALDA, Lacerda MG, Milton FA, et al. In vitro effects of European and Latin-American medicinal plants in CYP3A4 gene expression, glutathione levels, and P-glycoprotein activity. Front Pharmacol 2022;13:826395. PubMed

See these in context on the Passion Flower monograph →

Oats 13 references
  1. Cooper SG, Tracey EJ. Small-bowel obstruction caused by oat-bran bezoar. N Engl J Med 1989;320:1148-9. DOI
  2. Pick ME, Hawrysh ZJ, Gee MI, et al. Oat bran concentrate bread products improve long-term control of diabetes: a pilot study. J Am Diet Assoc 1996;96:1254-61. PubMed
  3. Braaten JT, Scott FW, Wood PJ, et al. High beta-glucan oat bran and oat gum reduce postprandial blood glucose and insulin in subjects with and without type 2 diabetes. Diabet Med 1994;11:312-8.
  4. Rosario PG, Gerst PH, Prakash K, Albu E. Dentureless distention: oat bran bezoars cause obstruction. J Am Geriatr Soc 1990;38:608. PubMed
  5. Food and Drug Administration. Food labeling: health claims: oats and coronary heart disease. Fed Regist 1996;61:296-313.
  6. Foulke J. FDA Allows Whole Oat Foods To Make Health Claim on Reducing the Risk of Heart Disease. FDA Talk Paper. 1997. Available at: http://www.fda.gov/bbs/topics/ANSWERS/ANS00782.html.
  7. Chandalia M, Garg A, Lutjohann D, et al. Beneficial effects of high dietary fiber intake in patients with type 2 diabetes mellitus. N Engl J Med 2000;342:1392-8. PubMed
  8. Lembo A, Camilleri M. Chronic constipation. N Engl J Med 2003;349:1360-8. . PubMed
  9. De Paz Arranz S, Perez Montero A, Remon LZ, Molero MI. Allergic contact urticaria to oatmeal. Allergy 2002;57:1215. . PubMed
  10. Delgado G, Kleber ME, Krämer BK, et al. Dietary intervention with oatmeal in patients with uncontrolled type 2 diabetes mellitus - A crossover study. Exp Clin Endocrinol Diabetes. 2019;127(9):623-629. PubMed
  11. Sobhan M, Hojati M, Vafaie SY, Ahmadimoghaddam D, Mohammadi Y, Mehrpooya M. The efficacy of colloidal oatmeal cream 1% as add-on therapy in the management of chronic irritant hand eczema: A double-blind study. Clin Cosmet Investig Dermatol. 2020;13:241-25
  12. Hou Q, Li Y, Li L, Cheng G, Sun X, Li S, Tian H. The metabolic effects of oats intake in patients with type 2 diabetes: A systematic review and meta-analysis. Nutrients. 2015;7(12):10369-87. PubMed
  13. González-Afonso M, Cañas JA, Sastre B, et al. A Case of Anaphylaxis After Ingestion of Oats: Research Into New Allergens. J Investig Allergol Clin Immunol 2022;32(6):506-508. PubMed

See these in context on the Oats monograph →

Kava 71 references
  1. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
  2. Strahl S, Ehret V, Dahm HH, Maier KP. [Necrotizing hepatitis after taking herbal medication]. Dtsch Med Wochenschr 1998;123:1410-4.
  3. Spillane PK, et al. Neurological manifestations of kava intoxication. Med J Aust 1997;167:172-3. PubMed
  4. Swensen JN. Man convicted of driving under the influence of kava. Salt Lake City, UT: Deseret News, 1996.
  5. Pittler MH, Ernst E. Efficacy of kava extract for treating anxiety: systematic review and meta-analysis. J Clin Psychopharmacol 2000;20:84-9. PubMed
  6. Volz HP, Kieser M. Kava-kava extract WS 1490 versus placebo in anxiety disorders--a randomized placebo-controlled 25-week outpatient trial. Pharmacopsychiatry 1997;30:1-5. PubMed
  7. Heinze HJ, Munthe TF, Steitz J, Matzke M. Pharmacopsychological effects of oxazepam and kava-extract in a visual search paradigm assessed with event-related potentials. Pharmacopsychiatry 1994;27:224-30. PubMed
  8. Munte TF, Heinze HJ, Matzke M, Steitz J. Effects of oxazepam and an extract of kava roots (Piper methysticum) on event-related potentials in a word recognition task. Neuropsychobiology 1993;27:46-53.
  9. Wheatley D. Stress-induced insomnia treated with kava and valerian: singly and in combination. Hum Psychopharmacol 2001;16:353-6. PubMed
  10. Schelosky L, Raffaup C, Jendroska K, Poewe W. Kava and dopamine antagonism. J Neurol Neurosurg Psychiatry 1995;58:639-40. PubMed
  11. Norton SA, Ruze P. Kava dermopathy. J Am Acad Dermatol 1994;31:89-97.
  12. Pizzorno JE, Murray MT, eds. Textbook of Natural Medicine. 2nd ed. Edinburgh:Churchill Livingstone, 1999.
  13. Mathews JD, Riley MD, Fejo L, et al. Effects of heavy usage of kava on physical health: Summary of a pilot survey in an aboriginal community. Med J Aust 1988;148:548-55.
  14. Escher M, Desmeules J, Giostra E, Mentha G. Hepatitis associated with Kava, a herbal remedy for anxiety. BMJ 2001;322:139.
  15. Russmann S, Lauterburg BH, Helbling A. Kava hepatotoxicity [letter]. Ann Intern Med 2001;135:68-9.
  16. Liver Toxicity With Kava. Pharmacist's Letter/Prescriber's Letter. January 2001.
  17. Consultation letter MLX 286: Proposals to prohibit the herbal ingredient Kava-Kava (Piper methysticum) in unlicensed medicines. Medicines Control Agency, United Kingdom, July 19, 2002.
  18. Meseguer E, Taboada R, Sanchez V, et al. Life-threatening parkinsonism induced by kava-kava. Mov Disord 2002;17:195-6. PubMed
  19. Ruze P. Kava-induced dermopathy: a niacin deficiency? Lancet 1990;335:1442-5. PubMed
  20. Singh YN. Kava: an overview. J Ethnopharmacol 1992;37:13-45.
  21. Bilia AR, Gallori S, Vincieri FF. Kava-kava and anxiety: growing knowledge about the efficacy and safety. Life Sci 2002;70:2581-97. PubMed
  22. Wooltorton E. Herbal kava: reports of liver toxicity. CMAJ 2002;166:777.
  23. Mathews JM, Etheridge AS, Black SR. Inhibition of human cytochrome P450 activities by kava extract and kavalactones. Drug Metab Dispos 2002;30:1153-7. PubMed
  24. Logan JL, Ahmed J. Critical hypokalemic renal tubular acidosis due to Sjogren's syndrome: association with the purported immune stimulant echinacea. Clin Rheumatol 2003;22:158-9.
  25. Teschke R, Gaus W, Loew D. Kava extracts: safety and risks including rare hepatotoxicity. Phytomedicine 2003;10:440-6. PubMed
  26. Schmidt P, Boehncke WH. Delayed-type hypersensitivity reaction to kava-kava extract. Contact Dermatitis 2000;42:363-4.
  27. Schulze J, Raasch W, Siegers CP. Toxicity of kava pyrones, drug safety and precautions--a case study. Phytomedicine 2003;10:68-73.. PubMed
  28. Pittler MH, Ernst E. Kava extract for treating anxiety. Cochrane Database Syst Rev 2003;(1):CD003383.
  29. Cairney S, Maruff P, Clough AR, et al. Saccade and cognitive impairment associated with kava intoxication. Hum Psychopharmacol 2003;18:525-33. PubMed
  30. Moulds RF, Malani J. Kava: herbal panacea or liver poison? Med J Aust 2003;178:451-3. PubMed
  31. Gow PJ, Connelly NJ, Hill RL, et al. Fatal fulminant hepatic failure induced by a natural therapy containing kava. Med J Aust 2003;178:442-3. PubMed
  32. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  33. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77:415-26. PubMed
  34. Weiss J, Sauer A, Frank A, Unger M. Extracts and kavalactones of Piper methysticum G. Forst (kava-kava) inhibit P-glycoprotein in vitro. Drug Metab Dispos 2005;33:1580-3. PubMed
  35. Gurley BJ, Swain A, Barone GW, et al. Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans. Drug Metab Dispos 2007;35:240-5. PubMed
  36. Gurley BJ, Swain A, Hubbard MA, et al. Clinical assessement of CYP2D6-mediated herb-drug interactions in humans: Effects of milk-thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea. Mol Nutr Food Res 2008;52:755-63.
  37. Li XZ, Ramzan I. Role of ethanol in kava hepatotoxicity. Phytother Res 2010;24:475-80. PubMed
  38. Bodkin R, Schneider S, Rekkerth D, et al. Rhabdomyolysis associated with kava ingestion. Am J Emerg Med 2012;30:635.el-3. PubMed
  39. Donadio V, Bonsi P, Zele I, et al. Myoglobinuria after ingestion of extracts of guarana, Ginkgo biloba and kava. Ginkgo biloba and kava. Neurol Sci 2000;21:124. PubMed
  40. Sarris J, Kavanagh DJ, Byrne G, et al. The Kava Anxiety Depression Spectrum Study (KADSS): a randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum. Psychopharmacology 2009;205:399-407. PubMed
  41. Hannam S, Murray M, Romani L, Tuicakau M, J Whitfeld M. Kava dermopathy in Fiji: an acquired ichthyosis? Int J Dermatol 2014;53(12):1490-4. PubMed
  42. Huynh JC, Asgari MM, Moore MM. Sebotropic eruption associated with use of oral kava kava supplement. Clin Exp Dermatol 2014;39(7):816-8. PubMed
  43. Teschke R, Sarris J, Schweitzer I. Kava hepatotoxicity in traditional and modern use: the presumed Pacific kava paradox hypothesis revisited. Br J Clin Pharmacol 2012;73(2):170-4. PubMed
  44. Scherer, J. Kava-kava extract in anxiety disorders: an outpatient observational study. Adv.Ther. 1998;15(4):261-269.
  45. Humberston, C. L., Akhtar, J., and Krenzelok, E. P. Acute hepatitis induced by kava kava. J Toxicol.Clin Toxicol. 2003;41(2):109-113. PubMed
  46. Schmidt, M. Are kavalactones the hepatotoxic principle of kava extracts? The pitfalls of the glutathione theory. J Altern Complement Med 2003;9(2):183-187. PubMed
  47. Stickel, F., Baumuller, H. M., Seitz, K., Vasilakis, D., Seitz, G., Seitz, H. K., and Schuppan, D. Hepatitis induced by Kava (Piper methysticum rhizoma). J Hepatol. 2003;39(1):62-67. PubMed
  48. Grace, R. Kava-induced urticaria. J Am Acad Dermatol 2005;53(5):906. PubMed
  49. Christl, S. U., Seifert, A., and Seeler, D. Toxic hepatitis after consumption of traditional kava preparation. J.Travel.Med. 2009;16(1):55-56. PubMed
  50. Teschke, R., Genthner, A., and Wolff, A. Kava hepatotoxicity: comparison of aqueous, ethanolic, acetonic kava extracts and kava-herbs mixtures. J.Ethnopharmacol. 6-25-2009;123(3):378-384. PubMed
  51. Jappe, U., Franke, I., Reinhold, D., and Gollnick, H. P. Sebotropic drug reaction resulting from kava-kava extract therapy: a new entity? J Am Acad Dermatol. 1998;38(1):104-106. PubMed
  52. Gessner B and Cnota P. Extract of the kava-kava rhizome in comparison with diazepam and placebo. Z Phytother 1994;15(1):30-37.
  53. Johnson D, Frauendorf A, Stecker K, and et al. Neurophysiological active profile and tolerance of kava extract WS 1490, A pilot study with randomized evaluation. TW Neurolgie Psychiatrie 1991;5(6):349-354.
  54. Keller F and Klohs M. A review of the chemistry and pharmacology of the constituents of Piper methysticum. Lloydia 1963;26:1-15.
  55. Siegers CP, Honold E, Krall B, and et al. Results of the drug monitoring L 1090 with Laitan capsules. Arztl Forsch 1992;39:7-11.
  56. Chanwai, L. G. Kava toxicity. Emergency Medicine 2002;12:142-145.
  57. Leung, N. Acute urinary retention secondary to kava ingestion. Emerg Med Australas 2004;16(1):94. PubMed
  58. Teschke R. Kava hepatotoxicity: pathogenetic aspects and prospective considerations. Liver Int 2010;30(9):1270-9. PubMed
  59. Toohey TP, Lu BY, Wada C. Toxic effects of psychotropics related to possible p450 enzyme inhibition by kava:report of 2 cases. Prim Care Companion CNS Disord 2013;15(5). PubMed
  60. Ostermayer D. News: Kava, Popular as Alcohol Alternative, May Cause Toxicity. Emerg Med News. 2016;38(1B).
  61. Kuchta K, Schmidt M, Nahrstedt A. German Kava Ban Lifted by Court: The Alleged Hepatotoxicity of Kava (Piper methysticum) as a Case of Ill-Defined Herbal Drug Identity, Lacking Quality Control, and Misguided Regulatory Politics. Planta Med. 2015;81(18):16 PubMed
  62. Schmidt M. German Court Ruling Reverses Kava Ban; German Regulatory Authority Appeals Decision. HerbalEGram. 2014;11(7).
  63. Wainiqolo I, Kool B, Nosa V, Ameratunga S. Is driving under the influence of kava associated with motor vehicle crashes? A systematic review of the epidemiological literature. Aust N Z J Public Health 2015;39(5):495-9. PubMed
  64. Wainiqolo I, Kafoa B, Kool B, et al. Driving following kava use and road traffic injuries: a population-based case-control study in Fiji (TRIP 14). PLoS One 2016;11(3):e0149719. PubMed
  65. Asher GN, Corbett AH, Hawke RL. Common Herbal Dietary Supplement-Drug Interactions. Am Fam Physician. 2017;96(2):101-107.
  66. Sarris J, Byrne GJ, Bousman CA, et al. Kava for generalised anxiety disorder: A 16-week double-blind, randomised, placebo-controlled study. Aust N Z J Psychiatry. 2020 Mar;54(3):288-297. PubMed
  67. Aporosa AS, Atkins M, Brunton R. Kava drinking in traditional settings: towards understanding effects on cognitive function. Hum Psychopharmacol. 2020;35(2):e2725. PubMed
  68. 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
  69. Aporosa S', Ballard H, Pandey R, McCarthy MJ. The impact of traditional kava (Piper methysticum) use on cognition: Implications for driver fitness. J Ethnopharmacol 2022;291:115080. PubMed
  70. Savage K, Sarris J, Hughes M, et al. Neuroimaging insights: Kava's (Piper methysticum) effect on dorsal anterior cingulate cortex GABA in generalized anxiety disorder. Nutrients 2023;15(21):4586. PubMed
  71. du Plessis Nisbet J, Xie D, Thompson R, Wark K, Lamrock E, Scurry J. Kava-induced dermatitis: A detailed histopathological analysis. Australas J Dermatol 2024. PubMed

See these in context on the Kava monograph →

St. John's Wort 152 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. Gulick RM, McAuliffe V, Holden-Wiltse J, et al. Phase I studies of hypericin, the active compound in St. John's Wort, as an antiretroviral agent in HIV-infected adults. AIDS Clinical Trials Group Protocols 150 and 258. Ann Intern Med 1999;130:510-4. PubMed
  3. O'Breasail AM, Argouarch S. Hypomania and St John's wort. Can J Psychiatry 1998;43:746-7.
  4. Johne A, Brockmoller J, Bauer S, et al. Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum). Clin Pharmacol Ther 1999;66:338-45.
  5. Gordon JB. SSRIs and St. John's Wort: possible toxicity? Am Fam Physician 1998;57:950, 953.
  6. Golsch S, Vocks E, Rakoski J, et al. [Reversible increase in photosensitivity to UV-B caused by St. John's wort extract]. Hautarzt 1997;48:249-52.
  7. Bove GM. Acute neuropathy after exposure to sun in a patient treated with St. John's Wort. Lancet 1998;352:1121-2. PubMed
  8. Brockmoller J, Reum T, Bauer S, et al. Hypericin and pseudohypericin: pharmacokinetics and effects on photosensitivity in humans. Pharmacopsychiatry 1997;30:94-101. PubMed
  9. Upton R, ed. St. John's wort, Hypericum perforatum: Quality control, analytical and therapeutic monograph. Santa Cruz, CA: American Herbal Pharmacopoeia 1997;1-32.
  10. Muller WE, Singer A, Wonnemann M, et al. Hyperforin represents the neurotransmitter reuptake inhibiting constituent of hypericum extract. Pharmacopsychiatry 1998;31:16-21.
  11. Abul-Ezz SR, Barone GW, Gurley BJ, et al. Effect of herbal supplements on cyclosporine blood levels and associated acute rejection. Am Soc of Nephrol Ann Mtg, Toronto, CAN 2000;Oct. 11-16:abstract A3754.
  12. Piscitelli SC, Burstein AH, Chaitt D, et al. Indinavir concentrations and St John's wort. Lancet 2000;355:547-8. PubMed
  13. Yue QY, Bergquist C, Gerden B. Safety of St. John's wort (Hypericum perforatum). Lancet 2000;355:576-7. PubMed
  14. Ruschitzka F, Meier PJ, Turina M, et al. Acute heart transplant rejection due to Saint John's wort. Lancet 2000;355:548-9. PubMed
  15. Roberts JE, Wang RH, Tan IP, et al. Hypericin (active ingredient in St. John's wort) photo-oxidation of lens proteins. Photochem Photobiol 1999;69:42S.
  16. Gurley BJ, Barone GW. Herb-drug interaction involving St. John's wort and cyclosporine. AAPS Ann Mtg & Expo Indianapolis, IN:2000;Oct 29- Nov 2: presentation #3443.
  17. Durr D, Stieger B, Kullak-Ublick GA, et al. St. John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin Pharmacol Ther 2000;68:598-604. PubMed
  18. Lee A, Minhas R, Ito S, et al. Safety of St. John's wort during breastfeeding. Clin Pharmacol Ther 2000;67:130, abstract PII-64.
  19. Schneck C. St. John's wort and hypomania. J Clin Psychiatry 1998;59:689. PubMed
  20. Nierenberg AA, Burt T, Matthews J, et al. Mania associated with St. John's wort. Biol Psychiatry 1999;46:1707-8. PubMed
  21. Nebel A, Schneider BJ, Baker RA, et al. Potential metabolic interaction between St. John's wort and theophylline. Ann Pharmacother 1999;33:502. PubMed
  22. Moses EL, Mallinger AG. St. John's wort: Three cases of possible mania induction. J Clin Psychopharmacol 2000;20:115-7. PubMed
  23. 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.
  24. Peirce A. The American Pharmaceutical Association Practical Guide to Natural Medicines. New York, NY: William Morrow and Co., 1999.
  25. Mai I, Kruger H, Budde K, et al. Hazardous pharmacokinetic interaction of Saint John's wort (Hypericum perforatum) with the immunosuppressant cyclosporin. Int J Clin Pharmacol Ther 2000;38:500-2. PubMed
  26. Schempp CM, Muller K, Winghofer B, et al. Single-dose and steady-state administration of Hypericum perfotatum extract (St. John's wort) does not influence skin sensitivity to UV radiation, visible light, and solar-stimulated radiation. Arch Dermatol 2001;
  27. Schempp CM, Ludtke R, Winghofer B, Simon JC. Effect of topical application of hypericum perforatum extract on skin sensitivity to solar simulated radiation. Photodermatol Photoimmunol Photomed 2000;16:125-8.
  28. Jacobson JM, Feinman L, Liebes L, et al. Pharmacokinetics, safety, and antiviral effects of hypericin, a derivative of St. John's Wort plant, in patients with chronic hepatitis C virus infection. Antimicrob Agents Chemother 2001;45:517-24. PubMed
  29. Moschella C, Jaber BL. Interaction between cyclosporine and Hypericum perforatum (St. John's wort) after organ transplantation. Amer J Kidney Dis 2001;38:1105-7. PubMed
  30. Karliova M, Treichel U, Malago M, et al. Interaction of Hypericum perforatum (SJW) with cyclosporin A metabolism in a patient after liver transplantation. J Hepatol 2000;33:853-5.
  31. Mandelbaum A, Pertzborn F, Martin-Facklam M, Wiesel M. Unexplained decrease of cyclosporin trough levels in a compliant renal transplant patient. Nephrol Dial Transplant 2000;15:1473-4. PubMed
  32. Assalian P. Sildenafil for SJW-induced sexual dysfunction. J Sex Marital Ther 2000;26:357-8.
  33. de Maat M, Hoetelmans R, Mathot R, et al. Drug interaction between St. John's wort and nevirapine. AIDS 2001;15:420-1. PubMed
  34. Schrader E. Equivalence of St. John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression. Int Clin Psychopharmacol 2000;15:61-8.
  35. Ernst E, Rand JI, Barnes J, Stevinson C. Adverse effects profile of the herbal antidepressant St. John's wort (Hypericum perforatum L.). Eur J Clin Pharmacol 1998;54:589-94. PubMed
  36. Shelton RC, Keller MB, Gelenberg A, et al. Effectiveness of St. John's wort in major depression: A randomized, placebo-controlled trial. JAMA 2001;285:1978-86. DOI
  37. Breidenbach T, Hoffmann MW, Becker T, et al. Drug interaction of St. John's wort with cyclosporin. Lancet 2000;355:1912.
  38. Brown TM. Acute St. John's wort toxicity. Am J Emerg Med 2000;18:231-2. PubMed
  39. Kleber E, Obry T, Hippeli S, et al. Biochemical activities of extracts from Hypericum perforatum L. 1st Communication: inhibition of dopamine-beta-hydroxylase. Arzneimittelforschung 1999;49:106-9.
  40. Barone GW, Gurley BJ, Ketel BL, et al. Drug interaction between St. John's wort and cyclosporin. Ann Pharmacother 2000;34:1013-6.
  41. Cheng TO. St. John's wort interaction with digoxin [letter]. Arch Intern Med 2000;160:2548. PubMed
  42. Lane-Brown MM. Photosensitivity associated with herbal preparations of St. John's wort (Hypericum perforatum). Med J Aust 2000;172:302.
  43. Mathijssen RHJ, Verweij J, De Bruijn P, et al. Modulation of irinotecan (CPT-11) metabolism by St. John's wort in cancer patients. American Association for Cancer Research Annual Meeting, San Francisco, April 2002. Abstract 2443.
  44. Mai I, Bauer S, Krueger H, et al. Wechselwirkungen von Johaniskraut mit tacrolismus bei nierentransplantierten patienten. Symposium Phytopharmaka VII. Forschung und Klinische Anwendung, Berlin, October, 2001.
  45. Bhopal JS. St John's wort-induced sexual dysfunction. Can J Psychiatry 2001;46:456-457. PubMed
  46. Schulz V. Incidence and clinical relevance of the interactions and side effects of Hypericum preparations. Phytomedicine 2001;8:152-60.
  47. Gorski JC, Hamman MA, Wang Z, et al. The effect of St. John's wort on the efficacy of oral contraceptives (abstract MPI-80). Clin Pharmacol Ther 2001;71:P25.
  48. Hennessy M, Kelleher D, Spiers JP, et al. St Johns wort increases expression of P-glycoprotein: implications for drug interactions. Br J Clin Pharmacol 2002;53:75-82.
  49. Parker V, Wong AH, Boon HS, Seeman MV. Adverse reactions to St John's Wort. Can J Psychiatry 2001;46:77-9. PubMed
  50. Patel S, Robinson R, Burk M. Hypertensive crisis associated with St. John's Wort. Am J Med 2002;112:507-8. PubMed
  51. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3. PubMed
  52. Holme SA, Roberts DL. Erythroderma associated with St John's wort. Br J Dermatol 2000;143:1127-8. PubMed
  53. Irefin S, Sprung J. A possible cause of cardiovascular collapse during anesthesia: long-term use of St. John's Wort. J Clin Anesth 2000;12:498-9. PubMed
  54. Calapai G, Crupi A, Firenzuoli F, et al. Serotonin, norepinephrine and dopamine involvement in the antidepressant action of hypericum perforatum. Pharmacopsychiatry 2001;34:45-9. PubMed
  55. 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..
  56. Mathijssen RH, Verweij J, de Bruijn P, et al. Effects of St. John's wort on irinotecan metabolism. J Natl Cancer Inst 2002;94:1247-9.. PubMed
  57. Ladner DP, Klein SD, Steiner RA, Walt H. Synergistic toxicity of delta-aminolaevulinic acid-induced protoporphyrin IX used for photodiagnosis and hypericum extract, a herbal antidepressant. Br J Dermatol 2001;144:916-8. PubMed
  58. Ernst E. St. John's Wort supplements endanger the success of organ transplantation. Arch Surg 2002;137:316-9. PubMed
  59. Wang Z, Hamman MA, Huang SM, et al. Effect of St. John's wort on the pharmacokinetics of fexofenadine. Clin Pharmacol Ther 2002;71:414-20.. PubMed
  60. Chan LY, Chiu PY, Lau TK. A study of hypericin-induced teratogenicity during organogenesis using a whole rat embryo culture model. Fertil Steril 2001;76:1073-4. PubMed
  61. Schwarz UI, Buschel B, Kirch W. Unwanted pregnancy on self-medication with St John's wort despite hormonal contraception. Br J Clin Pharmacol 2003;55:112-3. PubMed
  62. Logan JL, Ahmed J. Critical hypokalemic renal tubular acidosis due to Sjogren's syndrome: association with the purported immune stimulant echinacea. Clin Rheumatol 2003;22:158-9.
  63. Mai I, Stormer E, Bauer S, et al. Impact of St John's wort treatment on the pharmacokinetics of tacrolimus and mycophenolic acid in renal transplant patients. Nephrol Dial Transplant 2003;18:819-22.. PubMed
  64. Groning R, Breitkreutz J, Muller RS. Physico-chemical interactions between extracts of Hypericum perforatum L. and drugs. Eur J Pharm Biopharm 2003;56:231-6.. PubMed
  65. Sugimoto K, Ohmori M, Tsuruoka S, et al. Different effects of St John's wort on the pharmacokinetics of simvastatin and pravastatin. Clin Pharmacol Ther 2001;70:518-24.. DOI
  66. Bauer S, Stormer E, Johne A, et al. Alterations in cyclosporin A pharmacokinetics and metabolism during treatment with St John's wort in renal transplant patients. Br J Clin Pharmacol 2003;55:203-11.. PubMed
  67. Markowitz JS, Donovan JL, DeVane CL, et al. Effect of St. John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA 2003;290:1500-4.. PubMed
  68. Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St. John's wort) in major depressive disorder: a randomized controlled trial. JAMA 2002;287:1807-14. PubMed
  69. Hammerness P, Basch E, Ulbricht C, et al. St. John's wort: a systematic review of adverse effects and drug interactions for the consultation psychiatrist. Psychosomatics 2003;44:271-82. PubMed
  70. Gurley BJ, Gardner SF, Hubbard MA, et al. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther 2002;72:276-87.. PubMed
  71. 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
  72. Kim RB. Drugs as P-glycoprotein substrates, inhibitors, and inducers. Drug Metab Rev 2002;34:47-54. PubMed
  73. Dean AJ, Moses GM, Vernon JM. Suspected withdrawal syndrome after cessation of St. John's wort. Ann Pharmacother 2003;37:150. PubMed
  74. Morimoto T, Kotegawa T, Tsutsumi K, et al. Effect of St. John's wort on the pharmacokinetics of theophylline in healthy volunteers. J Clin Pharmacol 2004;44:95-101. PubMed
  75. Pfrunder A, Schiesser M, Gerber S, et al. Interaction of St John's wort with low-dose oral contraceptive therapy: a randomized controlled trial. Br J Clin Pharmacol 2003;56:683-90. PubMed
  76. Hall SD, Wang Z, Huang SM, et al. The interaction between St John's wort and an oral contraceptive. Clin Pharmacol Ther 2003;74:525-35. PubMed
  77. Frye RF, Fitzgerald SM, Lagattuta TT, et al. Effect of St. John's wort on imatinib mesylate pharmacokinetics. Clin Pharmacol Ther 2004;76:323-9. PubMed
  78. Komoroski BJ, Zhang S, Cai H, et al. Induction and inhibition of cytochromes P450 by the St. John's wort constituent hyperforin in human hepatocyte cultures. Drug Metab Dispos 2004;32:512-8. PubMed
  79. Jiang X, Williams KM, Liauw WS, et al. Effect of St John's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 2004;57:592-9. PubMed
  80. Shimizu K, Nakamura M, Isse K, Nathan PJ. First-episode psychosis after taking an extract of Hypericum perforatum (St John's Wort). Hum Psychopharmacol 2004;19:275-6.
  81. Szegedi A, Kohnen R, Dienel A, Kieser M. Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine. BMJ 2005;330:503. PubMed
  82. Lau WC, Carville DGM, Guyer KE, et al. St. John's Wort Enhances the Platelet Inhibitory Effect of Clopidogrel in Clopidogrel "Resistant" Healthy Volunteers. American College of Cardiology Annual Meeting, Orlando, FL 2005: Presentation 1043-129.
  83. Murphy PA, Kern SE, Stanczyk FZ, Westhoff CL. Interaction of St. John's Wort with oral contraceptives: effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding. Contraception 2005;71:402-8. PubMed
  84. Linde K, Knuppel L. Large-scale observational studies of hypericum extracts in patients with depressive disorders - a systematic review. Phytomedicine 2005;12:148-57. PubMed
  85. Dasgupta A, Hovanetz M, Olsen M, et al. Drug-herb interaction: effect of St John's wort on bioavailability and metabolism of procainamide in mice. Arch Pathol Lab Med 2007;131:1094-8. PubMed
  86. Dugoua JJ, Mills E, Perri D, Koren G. Safety and efficacy of St. John's wort (hypericum) during pregnancy and lactation. Can J Clin Pharmacol 2006;13:e268-76.
  87. Jiang X, Blair EY, McLachlan AJ. Investigation of the effects of herbal medicines on warfarin response in healthy subjects: a population pharmacokinetic-pharmacodynamic modeling approach. J Clin Pharmacol 2006;46:1370-8. PubMed
  88. Niederhofer H. St. John's wort may diminish methylphenidate's efficacy in treating patients suffering from attention deficit hyperactivity disorder. Med Hypotheses 2007;68:1189. PubMed
  89. Bell EC, Ravis WR, Lloyd KB, Stokes TJ. Effects of St. John's wort supplementation on ibuprofen pharmacokinetics. Ann Pharmacother 2007;41:229-34. PubMed
  90. Booth JN, McGwin G. The association between self-reported cataracts and St. John's Wort. Curr Eye Res 2009;34:863-6. PubMed
  91. Samadi S, Khadivzadeh T, Emami A, et al. The effect of Hypericum perforatum on the wound healing and scar of cesarean. J Altern Complement Med 2010;16:113-7.
  92. Wang LS, Zhu B, Abd El-Aty A, et al. The influence of St. John's wort on CYP2C19 activity with respect to genotype. J Clin Pharmacol 2004;44:577-81. PubMed
  93. Weber W, Vander Stoep A, McCarty RL, et al. Hypericum perforatum (St John's wort) for attention-deficit/hyperactivity disorder in children and adolescents: a randomized controlled trial. JAMA 2008;299:2633-41. PubMed
  94. Lee, A., Minhas, R., Matsuda, N., Lam, M., and Ito, S. The safety of St. John's wort (Hypericum perforatum) during breastfeeding. J Clin Psychiatry 2003;64(8):966-968.
  95. Eich-Hochli, D., Oppliger, R., Golay, K. P., Baumann, P., and Eap, C. B. Methadone maintenance treatment and St. John's Wort - a case report. Pharmacopsychiatry 2003;36(1):35-37. PubMed
  96. Smith M, Lin KM, and Zheng YP. PIII-89 an open trial of nifedipine-herb interactions: Nifedipine with St. John's wort, ginseng or ginkgo biloba. Clin Pharm Ther 2001;69:P86.
  97. Kawaguchi, A., Ohmori, M., Tsuruoka, S., Nishiki, K., Harada, K., Miyamori, I., Yano, R., Nakamura, T., Masada, M., and Fujimura, A. Drug interaction between St John's Wort and quazepam. Br.J.Clin Pharmacol. 2004;58(4):403-410. PubMed
  98. Dresser, G. K., Schwarz, U. I., Wilkinson, G. R., and Kim, R. B. Coordinate induction of both cytochrome P4503A and MDR1 by St John's wort in healthy subjects. Clin Pharmacol Ther 2003;73(1):41-50. PubMed
  99. Patel, J., Buddha, B., Dey, S., Pal, D., and Mitra, A. K. In vitro interaction of the HIV protease inhibitor ritonavir with herbal constituents: changes in P-gp and CYP3A4 activity. Am.J.Ther. 2004;11(4):262-277. PubMed
  100. Xu, H., Williams, K. M., Liauw, W. S., Murray, M., Day, R. O., and McLachlan, A. J. Effects of St John's wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide. Br.J.Pharmacol. 2008;153(7):1579-1586.
  101. Wang, L. S., Zhou, G., Zhu, B., Wu, J., Wang, J. G., Abd El-Aty, A. M., Li, T., Liu, J., Yang, T. L., Wang, D., Zhong, X. Y., and Zhou, H. H. St John's wort induces both cytochrome P450 3A4-catalyzed sulfoxidation and 2C19-dependent hydroxylation of omepr
  102. Hojo, Y., Echizenya, M., Ohkubo, T., and Shimizu, T. Drug interaction between St John's wort and zolpidem in healthy subjects. J.Clin.Pharm.Ther. 2011;36(6):711-715. PubMed
  103. Izzo, A. A. and Ernst, E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs 2009;69(13):1777-1798. PubMed
  104. Barbenel, D. M., Yusufi, B., O'Shea, D., and Bench, C. J. Mania in a patient receiving testosterone replacement postorchidectomy taking St John's wort and sertraline. J Psychopharmacol 2000;14(1):84-86.
  105. Ratz, A. E., von Moos, M., and Drewe, J. [St. John's wort: a pharmaceutical with potentially dangerous interactions]. Schweiz Rundsch.Med Prax. 5-10-2001;90(19):843-849.
  106. Guzelcan, Y., Scholte, W. F., Assies, J., and Becker, H. E. [Mania during the use of a combination preparation with St. John's wort (Hypericum perforatum)]. Ned.Tijdschr.Geneeskd. 10-6-2001;145(40):1943-1945.
  107. van Gurp, G., Meterissian, G. B., Haiek, L. N., McCusker, J., and Bellavance, F. St John's wort or sertraline? Randomized controlled trial in primary care. Can Fam Physician 2002;48:905-912.
  108. Lecrubier, Y., Clerc, G., Didi, R., and Kieser, M. Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial. Am J Psychiatry 2002;159(8):1361-1366. PubMed
  109. Schempp, C. M., Winghofer, B., Muller, K., Schulte-Monting, J., Mannel, M., Schopf, E., and Simon, J. C. Effect of oral administration of Hypericum perforatum extract (St. John's Wort) on skin erythema and pigmentation induced by UVB, UVA, visible light
  110. Zullino, D. and Borgeat, F. Hypertension induced by St. John's Wort - a case report. Pharmacopsychiatry 2003;36(1):32. PubMed
  111. Nanayakkara, P. W., Meijboom, M., and Schouten, J. A. [Suicidal and aggressive thoughts as a result of taking a Hypericum preparation (St. John's wort)]. Ned.Tijdschr.Geneeskd. 6-11-2005;149(24):1347-1349.
  112. Fava, M., Alpert, J., Nierenberg, A. A., Mischoulon, D., Otto, M. W., Zajecka, J., Murck, H., and Rosenbaum, J. F. A Double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder. J.Clin.Psychopharmacol. 2005;25(5 PubMed
  113. Gastpar, M., Singer, A., and Zeller, K. Comparative efficacy and safety of a once-daily dosage of hypericum extract STW3-VI and citalopram in patients with moderate depression: a double-blind, randomised, multicentre, placebo-controlled study. Pharmacops PubMed
  114. Cappuzzo, K. A. Herbal product use in a patient with polypharmacy. Consult Pharm. 2006;21(11):911-915. PubMed
  115. Papakostas, G. I., Crawford, C. M., Scalia, M. J., and Fava, M. Timing of clinical improvement and symptom resolution in the treatment of major depressive disorder. A replication of findings with the use of a double-blind, placebo-controlled trial of Hyp DOI
  116. Sardella, A., Lodi, G., Demarosi, F., Tarozzi, M., Canegallo, L., and Carrassi, A. Hypericum perforatum extract in burning mouth syndrome: a randomized placebo-controlled study. J.Oral Pathol.Med. 2008;37(7):395-401.
  117. Etogo-Asse, F., Boemer, F., Sempoux, C., and Geubel, A. Acute hepatitis with prolonged cholestasis and disappearance of interlobular bile ducts following tibolone and Hypericum perforatum (St. John's wort). Case of drug interaction? Acta Gastroenterol.Be
  118. Andreescu, C., Mulsant, B. H., and Emanuel, J. E. Complementary and alternative medicine in the treatment of bipolar disorder--a review of the evidence. J.Affect.Disord. 2008;110(1-2):16-26. PubMed
  119. Kasper, S., Volz, H. P., Moller, H. J., Dienel, A., and Kieser, M. Continuation and long-term maintenance treatment with Hypericum extract WS 5570 after recovery from an acute episode of moderate depression--a double-blind, randomized, placebo controlled
  120. Al-Akoum, M., Maunsell, E., Verreault, R., Provencher, L., Otis, H., and Dodin, S. Effects of Hypericum perforatum (St. John's wort) on hot flashes and quality of life in perimenopausal women: a randomized pilot trial. Menopause. 2009;16(2):307-314. PubMed
  121. Brattstrom, A. Long-term effects of St. John's wort (Hypericum perforatum) treatment: a 1-year safety study in mild to moderate depression. Phytomedicine. 2009;16(4):277-283. PubMed
  122. Canning, S., Waterman, M., Orsi, N., Ayres, J., Simpson, N., and Dye, L. The efficacy of Hypericum perforatum (St John's wort) for the treatment of premenstrual syndrome: a randomized, double-blind, placebo-controlled trial. CNS.Drugs 2010;24(3):207-225. PubMed
  123. 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
  124. Sultana D, Peindl KS Wisner KL. Rash associated with St. John's wort treatment in premenstrual dysphoric disorder. Arch Women Ment Health 2000;3:99-101. DOI
  125. Bernd A, Ramirez-Bosca A, Kippenberger S, and et al. Phototoxic effects of Hypericum extract in cultures of human keratinocytes compared with those of psoralen. Photochem Photobiol 1999;2(69):218-221.
  126. Woelk H, Burkard G, and Grunwald J. Nutzen und Risikobewertung des Hypericum-extraktes LI 160 auf der Basis einer Drug-Monitoring-Studie mit 3250 patienten. Nervenheilkunde 1993;12:308-313.
  127. Schakau D, Hiller K, Schultz-Zehden W, and et al. Risk/benefit profile of St.John's wort extract: STEI 300 in 2404 patients with various degrees of psychiatric disturbance. Psychopharmakotherapie 1996;3:116-122.
  128. Laird RD and Webb M. Psychotic episode during use of St John's wort. J Herbal Pharmacother 2001;1(2):81-87. DOI
  129. Schrader E, Meier B, and Brattstrom A. Hypericum treatment of mild-moderate depression in a placebo-controlled study. A prospective, double-blind, randomized, placebo-controlled, multicentre study. Human Psychopharm 1998;13:163-169. DOI
  130. Dolton MJ, Mikus G, Weiss J, et al. Understanding variability with voriconazole using a population pharmacokinetic approach: implications for optimal dosing. J Antimicrob Chemother 2014;69(6):1633-41. PubMed
  131. Goey AK, Meijerman I, Rosing H, et al. The effect of St John's wort on the pharmacokinetics of docetaxel. Clin Pharmacokinet 2014;53(1):103-10. PubMed
  132. Lei HP, Yu XY, Xie HT, et al. Effect of St. John's wort supplementation on the pharmacokinetics of bupropion in healthy male Chinese volunteers. Xenobiotica 2010;40(4):275-81. PubMed
  133. Gurok MG, Mermi O, Kilic F, et al. Psychotic episode induced by St. John's wort (Hypericum perforatum): a case report. J Mood Dis 2014;4(1):38-40. DOI
  134. Yildirim O, Canan F. A case of panic attack induced by St John's wort. Prim Care Companion CNS Disord 2013;15(1). pii: PCC.12l01453. PubMed
  135. Abdali K, Khajehei M, Tabatabaee HR. Effect of St John's wort on severity, frequency, and duration of hot flashes in premenopausal, perimenopausal and postmenopausal women: a randomized, double-blind, placebo-controlled study. Menopause 2010;17(2):326-31. PubMed
  136. Trana C, Toth G, Wijns W, Barbato E. St. John's Wort in patients non-responders to clopidogrel undergoing percutaneous coronary intervention: a single-center randomized open-label trial (St. John's Trial). J Cardiovasc Transl Res 2013;6(3):411-4. PubMed
  137. Agollo MC, Miszputen SJ, Diament J. Hypericum perforatum-induced hepatotoxicity with possible association with copaiba (copaifera langsdorffii desf): a case report. Einstein (Sao Paulo) 2014;12(3):355-7.
  138. Hohmann N, Maus A, CarlsA, Haefeli WE, Mikus G. St. John's wort treatment in women bears risks beyond pharmacokinetic drug interactions. Arch Toxico. 2016;90(4):1013-15. doi:10.1007/s00204-015-1532-7. PubMed
  139. Jackson A, D'Avolio A, Moyle G, et al. Pharmacokinetics of the co-administration of boceprevir and St. John's wort to male and female healthy volunteers. J Antimicrob Chemother 2014;69:1911-1915. PubMed
  140. Jones D. Tourian LT, Margolese H. Possible association of syndrome of Inappropriate secretion of antidiuretic hormone with St. John's wort use. J of Clin Psychopharmacol 2014:34(6):759-60. PubMed
  141. Soleymani S, Bahramsoltani R, Rahimi R, Abdollahi M. Clinical risks of St John's Wort (Hypericum perforatum) co-administration. Expert Opin Drug Metab Toxicol. 2017;13(10):1047-62.
  142. Chrubasik-Hausmann S, Vlachojannis J, McLachlan AJ. Understanding drug interactions with St John's wort (Hypericum perforatum L.): impact of hyperforin content. J Pharm Pharmacol. 2018.
  143. Market C, Kastner IM, Hellwig, et al. The effect of induction of CYP3A4 by St. John's wort on ambrisentan plasma kinetics in volunteers of known CY2C19 genotype. Basic & Clinical Pharmacology & Toxicology 2015;116:423-428.
  144. Loughren MJ, Kharasch ED, Kelton-Rehkopf MC, Syrjala KL, Shen DD. Influence of St. John's wort on intravenous fentanyl pharmacokinetics, pharmacodynamics, and clinical effects: a randomized clinical trial. Anesthesiology 2020;132(3):491-503. PubMed
  145. Scholz I, Liakoni E, Hammann F, et al. Effects of Hypericum perforatum (St. John's wort) on the pharmacokinetics and pharmacodynamics of rivaroxaban in humans. Br J Clin Pharmacol. 2020. doi: 10.1111/bcp.14553.
  146. Fisher KA, Patel P, Abualula S, Concepion L. St. John's Wort-Induced Supraventricular Tachycardia. Cureus. 2021 Apr 7;13(4):e14356. PubMed
  147. Schäfer W, Wentzell N, Schink T, Haug U. Characterization of pregnancies exposed to St. John's wort and their outcomes: A claims data analysis. Reprod Toxicol. 2021 Jun;102:90-97. PubMed
  148. Adibelli Z, Karacay I, Demir M, Duran C. St. John's Wort (Hypericum perforatum)-related acute kidney injury. Blood Purif. 2021 Aug 24:1-3. doi: 10.1159/000518349.
  149. 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
  150. 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
  151. Pochet S, Lechon AS, Lescrainier C, et al. Herb-anticancer drug interactions in real life based on VigiBase, the WHO global database. Sci Rep 2022;12(1):14178. PubMed
  152. Gümüs KS, Teegelbekkers A, Sauter M, et al. Effect of Tacrolimus Formulation (Prolonged-Release vs Immediate-Release) on Its Susceptibility to Drug-Drug Interactions with St. John's Wort. Clin Pharmacol Drug Dev 2024. PubMed

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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

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