Major interaction on record — check this product against your medications before combining. Check your meds →
Dietary supplement

Tension Relief Ingredients & Drug Interactions

by Crystal Star

Tension Relief label
See full label image
Capsule Category: Botanical
Most serious interaction: Major
Clinical methodology reviewed by · Updated Sep 9, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking Tension Relief 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

Tension Relief is a dietary supplement by Crystal Star with 11 active ingredients. Its ingredients are commonly taken for mild to moderate depression, anxiety and stress, sleep problems.Based on those ingredients, 1,466 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Kava Kava, St. John's Wort, Valerian. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

Jump to a section

Check Your Meds Against Tension Relief by Crystal Star

Ask about any prescription or over-the-counter medication and we check it for interactions with Tension Relief by Crystal Star — and tell you which ingredient is responsible.

Pharmacist-reviewed data Checks every ingredient Answer in seconds
Prefer a human? Send your question to our licensed pharmacists — free, answered by email within 24 hours.

HelloPharmacist Scorecard of Tension Relief by Crystal Star

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 11 active ingredients.
  • “Proprietary Herbal Blend (Herb/Botanical)” is a proprietary blend — the label gives one combined amount (1,000 mg) without saying how much of each component you get.

Tension Relief is a capsule containing 11 ingredients. The active herbal components are St.

John's Wort, lobelia, valerian, red raspberry leaf, Mexican wild yam, rosemary, kava kava, cramp bark, Jamaica dogwood, passion flower, and black haw, delivered in a proprietary herbal blend. The inactive ingredients are certified organic brown rice and a vegetarian capsule.

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: Tension and cramping relief.
  • We looked for evidence on: Anxiety, Dysmenorrhea, Generalized anxiety disorder (GAD), Insomnia, Muscle cramps, Myalgia — and 4 related terms.
  • The strongest evidence on file: Valerian is rated "Possibly Effective" for Insomnia (Natural Medicines).
  • Also on file: Passion Flower is rated "Possibly Effective" for Pre-procedural anxiety, Insomnia.
  • Also on file: St. John's Wort is rated "Possibly Ineffective" for Social anxiety disorder.

St. John's Wort in this product is likely effective for depression and possibly effective for somatic symptom disorder and menopausal symptoms.

Valerian is possibly effective for insomnia. Passion flower is possibly effective for insomnia and pre-procedural anxiety.

Rosemary is possibly effective for memory. Red raspberry, kava, cramp bark, Jamaica dogwood, and black haw lack reliable evidence to establish their effectiveness for the conditions they're traditionally used for in this formula.

The evidence is simply not there in the data we hold.

The evidence, ingredient by ingredient St. John's Wort Lobelia Valerian Red Raspberry Wild Yam Rosemary Kava Cramp Bark

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 11 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 11 of 11.
  • General safety write-ups exist for 11 of 11.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

St. John's Wort is generally well tolerated in the short term but has a serious track record of interactions.

It can cause sun sensitivity and, rarely, suicidal thoughts or psychosis. Valerian, passion flower, kava, and red raspberry are generally well tolerated short-term, though valerian and passion flower commonly cause drowsiness, and kava has been linked to rare cases of liver injury—over 100 reported cases worldwide.

Lobelia is particularly concerning: it can be toxic at doses of 600 mg or higher, causing sweating, rapid heart rate, seizures, dangerously low blood pressure, and even death. Doses as low as 50 mg have caused nausea, vomiting, and diarrhea.

Jamaica dogwood is also toxic at higher doses and lacks human safety data.

Side effects, ingredient by ingredient St. John's Wort Lobelia Valerian Red Raspberry Wild Yam Rosemary Kava Cramp Bark

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?
  • 9 of the 11 matched ingredients can interact with medications — Rosemary, Lobelia, Red Raspberry, St. John's Wort, Jamaican Dogwood, 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: 1,467 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 Tension Relief, check your medications against these drug types. St.

John's Wort causes Major-severity interactions with digoxin (heart medication), phenobarbital and phenytoin (seizure drugs), irinotecan and docetaxel (cancer drugs), HIV protease inhibitors, and tacrolimus (transplant drug). Kava carries a Major interaction with any CNS depressants (sedatives, sleep aids, anti-anxiety drugs).

Valerian, passion flower, and Jamaica dogwood add Moderate interactions with CNS depressants. Red raspberry and rosemary may increase bleeding risk with anticoagulants or antiplatelet drugs.

Red raspberry, rosemary, and antidiabetes medications carry Moderate interactions. Mexican wild yam may interfere with estrogen therapy.

If you're on any of these, discuss with your pharmacist before using this product.

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 is a multi-ingredient herbal product best suited for someone who understands the ingredient list and has checked each of their own medications against the interaction data on this page. It's not for anyone on heart drugs, seizure medications, cancer treatments, HIV medications, blood thinners, sedatives, or diabetes drugs without pharmacist review first.

Pregnant and breastfeeding women should avoid it entirely—most ingredients are rated unsafe or have insufficient safety data during pregnancy and lactation. Talk to your pharmacist before starting.

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

Assessment coverage: 11 of 11 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Feb 23, 2018.

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 Tension Relief, straight from the product label.

Brand Crystal Star
Barcode (UPC) 867499000214
Net contents 60 Vegetarian Capsule(s)
Market status On market
Date entered into DSLD Feb 23, 2018
DSLD ID 83186
Product type Botanical
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years), Gluten 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 Tension Relief by Crystal Star, 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:
2 Capsule(s)
Maximum serving Sizes:
4 Capsule(s)
Servings per container
15
UPC/BARCODE
867499000214
IngredientAmount% DV
St. John's Wort0 NP--
Proprietary Herbal Blend (Herb/Botanical)1000 mg--
Lobelia0 NP--
Valerian0 NP--
Red Raspberry0 NP--
Mexican Wild Yam0 NP--
Rosemary0 NP--
Kava Kava0 NP--
Cramp Bark0 NP--
Jamaica Dogwood0 NP--
Passion Flower0 NP--
Black Haw0 NP--

Other ingredients: certified organic Brown Rice, Vegetarian Capsule

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.
General Statements

For over 35 years, it has been my goal to help you feel better safely & naturally. Formulated by myself. Crystal Star products are the best choice. Linda Page, Ph.D, Traditional Naturopath

Plants Rule

GMP Quality Assured This product has been manufactured at a GMP registered facility certified by the NSF (The Public Health and Safety Company)

100% satisfaction guaranteed

New formula. Smaller capsule.

Herbal blend supporting the relief of muscle aches and encourages mental and physical calming.

Since 1978

Suggested/Recommended/Usage/Directions

Directions: Take 2-4 capsules for tension and cramping relief. Every 4 hours, or as needed.

Storage

Store in a cool dry place (59 - 86(0) F)

FDA Disclaimer Statement

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

Brand IP Statement(s)

Copyright 2017 Healthy HealingEnterprises LLC. All rights reserved. and denote trademarks owned by Healthy Healing Enterprises LLC.

for the whole person

Formula

Rosemary calcium rich, supports anti-inflammation Kava Kava promotes discomfort relief Valerian muscle relaxation support Cramp Bark encourages mild cramping relief

FDA Statement of Identity

Dietary Supplement

Seals/Symbols

Gluten free

Formulation

Gluten free

Precautions

Note: Do not use if the tamper proof seal is damaged or missing.

Products containing Kava Kava Root are not recommended for use by persons under the age of 18.

If pregnant, nursing, or taking a prescription drug, consult a health care practitioner prior to use.

Do not exceed recommended dose.

Excessive consumption may impair ability to drive or operate heavy equipment. Not recommended for consumption with alcoholic beverages.

Warning: Keep out of reach of children.

General

Prod #1300 REV 6/17

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

See for yourself

Tension Relief by Crystal Star label

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

Tension Relief 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 Tension Relief by Crystal Star

These are the 11 active ingredients this product is made of. Select any to open its full monograph.

Serving size2 Capsule(s) Dosage formCapsule Servings per container15 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.

Proprietary Herbal Blend (Herb/Botanical)

1000 mg per serving

Other (inactive) ingredients: Certified organic Brown Rice, Vegetarian Capsule. These complete the product’s ingredient list but are not active constituents.

Interaction report

Tension Relief by Crystal Star Drug Interactions

Want to check YOUR meds against Tension Relief?

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
1,466Drugs
883 Major 563 Moderate 20 Minor

Ingredients driving the most interactions

Kava Kava 1,166
St. John's Wort 1,143
Valerian 902
Passion Flower 836
Rosemary 372

Individual Drug Interactions

The ingredients in Tension Relief interact with 1,466 drugs. Click any drug to see the details.

9 of the 11 ingredients in Tension Relief interact with drugs. Each result below shows which ingredient is responsible. Kava Kava St. John's Wort Valerian Passion Flower Rosemary Jamaica Dogwood Red Raspberry Mexican Wild Yam Lobelia

Each ingredient & the kinds of drugs it affects

For each ingredient in Tension Relief 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 Kava12 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 Kava full monograph & interactions

St. John's Wort47 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 full monograph & all 47 interactions

Valerian6 drug types · 902 drugs

Alcohol (Ethanol)

Valerian can have additive sedative effects when used concomitantly with alcohol.
Valerian has sedative effects. Theoretically, valerian might have an additive sedative effect when combined with alcohol. Excessive sedation has been reported in an alcohol-abusing individual who took valerian and Gingko biloba. However, the potential interaction between valerian and alcohol has been disputed in other research. Limited evidence suggests that a combination of valerian 160 mg and lemon balm 80 mg (Euvegal) does not cause further deterioration in reaction ability and reaction rate when taken with alcohol as compared to the effects of alcohol alone.

Likelihood Possible Evidence B
Alprazolam (Xanax)

Valerian can have additive sedative effects when used with alprazolam. Also, valerian in high doses might modestly increase alprazolam levels, though this is not likely to be clinically significant.
Valerian has sedative effects. Theoretically, valerian might cause additive sedation when combined with alprazolam. Also, a small pharmacokinetic study shows that taking valerian extract 1000 mg daily (providing 11 mg valerenic acid) might increase alprazolam levels by about 19%. This might be due to valerian's mild inhibition of cytochrome P450 3A4 (CYP3A4). Despite being statistically significant, this increase is not likely to be clinically significant.

Likelihood Possible Evidence B
Cns Depressants

Valerian can have additive sedative effects when used concomitantly with CNS depressant drugs.
Theoretically, concomitant use of valerian and drugs with sedative and anesthetic properties may cause additive therapeutic and adverse effects.

Likelihood Possible Evidence D
Glucuronidated Drugs

Valerian might weakly inhibit glucuronidation and increase concentrations of drugs metabolized by UGT1A1 and UGT2B7.
In vitro research shows that methanolic valerian extract and valerenic acid might competitively inhibit UDP-glucuronosyltransferase (UGT) 1A1 (UGT1A1) and UGT2B7.

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

Valerian does not seem to have a clinically relevant effect on levels of drugs metabolized by CYP2D6.
Although some in vitro evidence suggests that valerian affects CYP2D6, clinical pharmacokinetic (PK) studies show that valerian is unlikely to affect the CYP2D6 enzyme. In one PK study, taking valerian 1000 mg (providing about 11 mg valerenic acid) nightly for 14 days did not affect the metabolism of dextromethorphan, a CYP2D6 substrate. In another PK study, taking valerian 125 mg three times daily for 28 days did not affect metabolism of debrisoquine, an accepted CYP2D6 probe-substrate.

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

Valerian does not seem to have a clinically relevant effect on levels of drugs metabolized by CYP3A4.
Although some in vitro evidence suggests that valerian extract might inhibit or induce CYP3A4, clinical pharmacokinetic (PK) studies show that valerian does not have a clinically significant effect on the CYP3A4 enzyme. In one PK study, taking valerian 125 mg three times daily for 28 days did not affect metabolism of midazolam, an accepted CYP3A4 probe-substrate. In another PK study, taking valerian 1000 mg (providing about 11 mg valerenic acid) nightly for 14 days modestly increases levels of alprazolam, a CYP3A4 substrate, suggesting mild inhibition of CYP3A4. However, this mild inhibition is unlikely to be clinically relevant.

Likelihood Possible Evidence B
Valerian full monograph & interactions

Passion Flower3 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
Passion Flower full monograph & interactions

Rosemary6 drug types · 372 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, rosemary may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro and animal research suggests that rosemary inhibits platelet aggregation.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, taking rosemary with antidiabetes drugs might increase the risk of hypoglycemia.
Animal research shows that rosemary extract can decrease blood glucose levels in diabetic models. However, research in humans is conflicting. Although rosemary powder decreased blood glucose levels in healthy adults, no change in blood glucose levels was seen in adults with type 2 diabetes, most of whom were taking antidiabetes drugs.

Likelihood Possible Evidence B
Aspirin

Theoretically, rosemary might have additive effects with salicylate-containing drugs such as aspirin.
Rosemary is reported to contain salicylates.

Likelihood Possible Evidence D
Choline Magnesium Trisalicylate (Trilisate)

Theoretically, rosemary might have additive effects with salicylate-containing drugs such as choline magnesium trisalicylate.
Rosemary is reported to contain salicylate.

Likelihood Possible Evidence D
Salsalate (Disalcid)

Theoretically, rosemary might have additive effects with salicylate-containing drugs such as salsalate.
Rosemary is reported to contain salicylate.

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

Theoretically, rosemary might decrease the levels and clinical effects of CYP1A2 substrates.
In vitro research shows that rosemary induces CYP1A2 enzymes. This effect has not been reported in humans.

Likelihood Unlikely Evidence D
Rosemary full monograph & interactions

Jamaica Dogwood1 drug type · 248 drugs

Cns Depressants

Jamaican dogwood may potentiate sedative effects.

Likelihood Possible Evidence D
Jamaica Dogwood full monograph & interactions

Red Raspberry2 drug types · 135 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, taking red raspberry leaf with anticoagulant/antiplatelet drugs might increase the risk of bleeding.
In vitro research suggests that red raspberry leaf extract has antiplatelet activity and enhances the in vitro effects of the antiplatelet medication cangrelor. This interaction has not been reported in humans.

Likelihood Possible Evidence D
Insulin

Red raspberry leaf might reduce glucose levels in patients being treated with insulin.
In one case report, a 38-year-old patient with gestational diabetes, whose blood glucose was being controlled with medical nutrition therapy and insulin, developed hypoglycemia after consuming two servings of raspberry leaf tea daily for 3 days beginning at 32 weeks' gestation. The patient required an insulin dose reduction. The hypoglycemia was considered to be probably related to use of red raspberry leaf tea.

Likelihood Possible Evidence D
Red Raspberry full monograph & interactions

Mexican Wild Yam1 drug type · 41 drugs

Estrogens

Theoretically, wild yam might increase or decrease the effects of estrogen.
Wild yam root shows estrogenic and anti-estrogenic effects in vitro. Theoretically, wild yam might interfere with hormone therapy.

Likelihood Possible Evidence D
Mexican Wild Yam full monograph & interactions

Lobelia1 drug type · 1 drug

Lithium

Lobelia is thought to have diuretic properties. Theoretically, due to these potential diuretic effects, lobelia might reduce excretion and increase levels of lithium. The dose of lithium might need to be decreased.

Likelihood Probable Evidence D
Lobelia full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Tension Relief, from the product label.

Crystal Star

See all Crystal Star products
Name
Healthy Healing Enterprises LLC
Street Address
9821 Valley View Rd
City
Eden Prairie
State
MN
ZipCode
55344
Phone Number
(800) 736-6015
Web Address
www.HealthyHealing.com
Pharmacist Counseling Corner

Tension Relief by Crystal Star: Common Questions

Does Tension Relief by Crystal Star interact with any medications?
Yes. Based on its ingredients, Tension Relief has a known interaction with 1,466 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?
Tension Relief contains 11 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 product safe to take during pregnancy?
No. St. John's Wort, lobelia, kava, cramp bark, Jamaica dogwood, and black haw are all rated unsafe or possibly unsafe in pregnancy, and valerian, red raspberry, and passion flower lack sufficient safety data. Your doctor or pharmacist can discuss safer alternatives if you're pregnant or planning to be.
Can I take this while breastfeeding?
Not recommended. St. John's Wort, lobelia, kava, cramp bark, Jamaica dogwood, and black haw are all unsafe or possibly unsafe while nursing. Valerian, red raspberry, and passion flower either lack safety data or shouldn't be used. Talk to your pharmacist about other options.
What's in this product and what does it do?
Tension Relief contains 11 herbal ingredients including St. John's Wort (possibly helps depression and menopausal symptoms), valerian and passion flower (possibly help insomnia), and rosemary (possibly helps memory). Several other ingredients lack reliable evidence for their claimed uses. It's marketed for tension and stress relief, but only a few ingredients have established effectiveness.
Does lobelia work and is it safe?
There's no reliable evidence that lobelia works for smoking cessation. More importantly, it's toxic—doses as low as 50 mg cause nausea, vomiting, and diarrhea, and 600 mg or higher can cause rapid heart rate, seizures, dangerously low blood pressure, and death. Caution is strongly advised with this ingredient.
What are the common side effects?
St. John's Wort commonly causes diarrhea, dizziness, dry mouth, headache, and insomnia. Valerian and passion flower often cause drowsiness, dizziness, and confusion. Kava can cause drowsiness, dizziness, headache, and memory problems. Lobelia causes nausea, vomiting, diarrhea, and throat irritation even at low doses.
Why is kava included if it can damage the liver?
Kava has been linked to over 100 reported cases of liver injury, mostly from excessive and prolonged use. The product lists it as an active ingredient for anxiety and stress relief, but kava is actually rated possibly ineffective for anxiety disorders. The liver risk combined with the lack of proven benefit makes its inclusion questionable—discuss with your pharmacist before using.

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

Not sure if Tension Relief is safe with your meds?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.

Tension Relief label
Go deeper

The Full Monographs Behind Tension Relief’s Ingredients

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

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 → Herb & supplement monograph

Lobelia

Interacts with 1 drug

Lobelia is a traditional herb once used for breathing problems and to help people quit smoking, but reliable evidence supporting these uses is lacking. It can be toxic in higher amounts, cau...

Read the full Lobelia monograph → Herb & supplement monograph

Valerian

Interacts with 902 drugs

Valerian is an herb whose root is widely used as a natural sleep aid and for calming nerves. The evidence is mixed and often weak, so it may help some people sleep but does not work reliably...

Read the full Valerian monograph → Herb & supplement monograph

Red Raspberry

Interacts with 135 drugs

Red raspberry leaf is a traditional herbal remedy most often used as a tea in late pregnancy and for menstrual discomfort, but solid scientific evidence for these uses is limited. It is gene...

Read the full Red Raspberry monograph → Herb & supplement monograph

Wild Yam

Interacts with 41 drugs

Wild yam is a root traditionally used for menopausal symptoms, cramps, and as a so-called 'natural' hormone supplement, but solid human evidence for these uses is lacking. Despite popular cl...

Read the full Wild Yam monograph → Herb & supplement monograph

Rosemary

Interacts with 372 drugs

Rosemary is a fragrant Mediterranean herb that is safe and flavorful in normal food amounts. Some early research suggests possible benefits for memory, mood, and hair growth, but the evidenc...

Read the full Rosemary 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

Cramp Bark

Cramp Bark is the dried bark of Viburnum opulus, traditionally used to ease muscle and menstrual cramps. Modern, high-quality human studies are very limited, so its effectiveness is not well...

Read the full Cramp Bark monograph → Herb & supplement monograph

Jamaican Dogwood

Interacts with 248 drugs

Jamaican dogwood is a tree bark traditionally used to promote sleep and ease pain, but high-quality human studies are lacking. It can be toxic in larger amounts and should be used cautiously...

Read the full Jamaican Dogwood 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

Black Haw

Black Haw is a traditional herbal bark long used to ease menstrual cramps and uterine spasms, but modern human studies are very limited. It contains compounds that may relax smooth muscle, b...

Read the full Black Haw monograph →
Sources

Sources & How We Checked

Tension Relief'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 323 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.

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

See these in context on the St. John's Wort monograph →

Lobelia 6 references
  1. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  2. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.
  3. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  4. McChargue DE, Collins FL Jr, Cohen LM. Effect of non-nicotinic moist snuff replacement and lobeline on withdrawal symptoms during 48-h smokeless tobacco deprivation. Nicotine Tob Res 2002;4:195-200. PubMed
  5. Stead LF, Hughes JR. Lobeline for smoking cessation. Cochrane Database Syst Rev 2000;2:CD000124. PubMed
  6. Plakun, A. L., Ambrus, J., Bross, I., Graham, S., Levin, M. L., and Ross, C. A. Clinical factors in smoking withdrawal: preliminary report. Am J Public Health Nations.Health 1966;56(3):434-441. PubMed

See these in context on the Lobelia monograph →

Valerian 37 references
  1. Willey LB, Mady SP, Cobaugh DJ, Wax PM. Valerian overdose: a case report. Vet Hum Toxicol 1995;37:364-5.
  2. Kuhlmann J, Berger W, Podzuweit H, Schmidt U. The influence of valerian treatment on "reaction time, alertness and concentration" in volunteers. Pharmacopsychiatry 1999;32:235-41. PubMed
  3. Klepser TB, Klepser ME. Unsafe and potentially safe herbal therapies. Am J Health Syst Pharm 1999;56:125-38. PubMed
  4. Houghton PJ. The scientific basis for the reputed activity of Valerian. J Pharm Pharmacol 1999;51:505-12. PubMed
  5. Garges HP, Varia I, Doraiswamy PM. Cardiac complications and delirium associated with Valerian root withdrawal. [Letter to the Editor]. JAMA 1998;280:1566-7. PubMed
  6. 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
  7. MacGregor FB, Abernethy VE, Dahabra S, et al. Hepatotoxicity of herbal remedies. BMJ 1989;299:1156-7. PubMed
  8. Leathwood PD, Chauffard F. Aqueous extract of valerian reduces latency to fall asleep in man. Planta Med 1985;2:144-8. PubMed
  9. Hadley S, Petry JJ. Valerian. Am Fam Physician 2003;67:1755-8..
  10. Glass JR, Sproule BA, Herrmann N, et al. Acute pharmacological effects of temazepam, diphenhydramine, and valerian in healthy elderly subjects. J Clin Psychopharmacol 2003;23:260-8. PubMed
  11. Lefebvre T, Foster BC, Drouin CE, et al. In vitro activity of commercial valerian root extracts against human cytochrome P450 3A4. J Pharm Pharmaceut Sci 2004;7:265-73.
  12. Yuan CS, Mehendale S, Xiao Y, et al. The gamma-aminobutyric acidergic effects of valerian and valerenic acid on rat brainstem neuronal activity. Anesth Analg 2004;98:353-8. PubMed
  13. Donovan JL, DeVane CL, Chavin KD, et al. Multiple night-time doses of valerian (Valeriana officinalis) had minimal effects on CYP3A4 activity and no effect on CYP2D6 activity in healthy volunteers. Drug Metab Dispos 2004;32:1333-6. PubMed
  14. 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
  15. Gutierrez S, Ang-Lee MK, Walker DJ, Zacny JP. Assessing subjective and psychomotor effects of the herbal medication valerian in healthy volunteers. Pharmacol Biochem Behav 2004;78:57-64. PubMed
  16. Jacobs BP, Bent S, Tice JA, et al. An internet-based randomized, placebo-controlled trial of kava and valerian for anxiety and insomnia. Medicine (Baltimore) 2005;84:197-207. PubMed
  17. National Toxicology Program, US Department of Health and Human Services. Chemical Information Review Document for Valerian (Valeriana officinalis L.) [CAS No. 8057-49-6] and Oils [CAS No. 8008-88-6]. Supporting Nomination for Toxicological Evaluation by t
  18. Fernández-San-Martín MI, Masa-Font R, Palacios-Soler L, et al. Effectiveness of Valerian on insomnia: a meta-analysis of randomized placebo-controlled trials. Sleep Med. 2010 Jun;11:505-11. PubMed
  19. Coxeter PD, Schluter PJ, Eastwood HL, et al. Valerian does not appear to reduce symptoms for patients with chronic insomnia in general practice using a series of randomised n-of-1 trials. Complement Ther Med. 2003 Dec;11:215-22. PubMed
  20. Diaper A, Hindmarch I. A double-blind, placebo-controlled investigation of the effects of two doses of a valerian preparation on the sleep, cognitive and psychomotor function of sleep-disturbed older adults. Phytother Res. 2004 Oct;18:831-6. PubMed
  21. Cuellar NG, Ratcliffe SJ. Does valerian improve sleepiness and symptom severity in people with restless legs syndrome? Altern Ther Health Med 2009;15:22-8.
  22. Chen D, Klesmer J, Giovanniello A, et al. Mental status changes in an alcohol abuser taking valerian and gingko biloba. Am J Addict. 2002 Winter;11:75-7. PubMed
  23. Albrecht M, Berger W, Laux P, Schmidt U, et al. Psychopharmaka und Verkehrssicherheit. Der Einfluß von Euvegal® - Dragees forte auf die Fahrtüchtigkeit und Kombinationswirkungen mit Alkohol Z Allg Med 1995;71:1215-25.
  24. 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.
  25. Hellum BH, Nilsen OG. The in vitro inhibitory potential of trade herbal products on human CYP2D6-mediated metabolism and the influence of ethanol. Basic Clin Pharmacol Toxicol. 2007 Nov;101:350-8.
  26. Hellum BH, Hu Z, Nilsen OG. The induction of CYP1A2, CYP2D6 and CYP3A4 by six trade herbal products in cultured primary human hepatocytes. Basic Clin Pharmacol Toxicol. 2007 Jan;100:23-30. PubMed
  27. Alkharfy, K. M. and Frye, R. F. Effect of valerian, valerian/hops extracts, and valerenic acid on glucuronidation in vitro. Xenobiotica 2007;37(2):113-123.
  28. Vassiliadis, T., Anagnostis, P., Patsiaoura, K., Giouleme, O., Katsinelos, P., Mpoumponaris, A., and Eugenidis, N. Valeriana hepatotoxicity. Sleep Med 2009;10(8):935. PubMed
  29. Muller, Z., Sarkany, A., Altorjay, A., Szilagyi, A., Tura, T., and Ozsvar, Z. [Liver failure a la Eastern Europe]. Orv.Hetil. 3-22-2009;150(12):555-557. PubMed
  30. National Toxicology Program, US Department of Health and Human Services. Chemical Information Review Document for Valerian (Valeriana officinalis L.) [CAS No. 8057-49-6] and Oils [CAS No. 8008-88-6]. 2009;
  31. Wells SR. International intravenous administration of a crude valerian root extract. NACCT 1995;33:542.
  32. Aydinoglu U, Özcan H, Yücel A, Yücel N, Mutlu M. Valerian induced hypomania: a case report. Bull Clin Psychopharma 2012;22(Suppl. 1):S63.
  33. Mirabi P, Mojab F. The effects of valerian root on hot flashes in menopausal women. Iran J Pharm Res 2013;12(1):217-22.
  34. Thomas K, Canedo J, Perry PJ, et al. Effects of valerian on subjective sedation, field sobriety testing and driving simulator performance. Accid Anal Prev. 2016 Jul;92:240-4. PubMed
  35. Kia YH, Alexander S, Dowling D, Standish R. A case of steroid-responsive valerian-associated hepatitis. Intern Med J. 2016 Jan;46(1):118-9. PubMed
  36. Burke H, Jiang S, Chatham P, Stern TA. Delirium After Withdrawal From Valerian Root: A Case Report. Psychosomatics. 2020;61(6):787-790. PubMed
  37. Hajizadeh I, Jamshidi M, Kazemi M, Kargar H, Sadeghi T. Comparison the effect of valerian and gabapentin on RLS and sleep quality in hemodialysis patients: A randomized clinical trial. Ther Apher Dial 2023.

See these in context on the Valerian monograph →

Red Raspberry 8 references
  1. Eagon PK, Elm MS, Hunter DS, et al. Medicinal herbs: modulation of estrogen action. Era of Hope Mtg, Dept Defense; Breast Cancer Res Prog, Atlanta, GA 2000;Jun 8-11.
  2. Parsons M, Simpson M, Ponton T. Raspberry leaf and its effects on labour: safety and efficacy. Aust Coll Midwives Inc J 1999;12:20-5.
  3. Simpson M, Parsons M, Greenwood J, Wade K. Raspberry leaf in pregnancy: its safety and efficacy in labor. J Midwifery Womens Health 2001;46:51-9.. PubMed
  4. Mullen W, McGinn J, Lean ME, et al. Ellagitannins, flavonoids, and other phenolics in red raspberries and their contribution to antioxidant capacity and vasorelaxation properties. J Agric Food Chem 2002;50:5191-6.. PubMed
  5. Sherson, D., Andersen, B., Hansen, I., and Kjoller, H. Occupational asthma due to freeze-dried raspberry. Ann Allergy Asthma Immunol. 2003;90(6):660-663. PubMed
  6. Cheang KI, Nguyen TT, Karjane NW, Salley KE. Raspberry Leaf and Hypoglycemia in Gestational Diabetes Mellitus. Obstet Gynecol. 2016;128(6):1421-4. PubMed
  7. Dudzinska D, Bednarska K, Boncler M, Luzak B, Watala C. The influence of Rubus idaeus and Rubus caesius leaf extracts on platelet aggregation in whole blood. Cross-talk of platelets and neutrophils. Platelets. 2016;27(5):433-9.
  8. Henrotin Y, Cozannet RL, Fança-Berthon P, et al. Rubus idaeus extract improves symptoms in knee osteoarthritis patients: results from a phase II double-blind randomized controlled trial. BMC Musculoskelet Disord 2022;23(1):650. PubMed

See these in context on the Red Raspberry monograph →

Wild Yam 7 references
  1. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  2. Eagon PK, Elm MS, Hunter DS, et al. Medicinal herbs: modulation of estrogen action. Era of Hope Mtg, Dept Defense; Breast Cancer Res Prog, Atlanta, GA 2000;Jun 8-11.
  3. Cheong JL, Bucknall R. Retinal vein thrombosis associated with a herbal phytoestrogen preparation in a susceptible patient. Postgrad Med J 2005;81:266-7.. PubMed
  4. Rosenberg Zand, R. S., Jenkins, D. J., and Diamandis, E. P. Effects of natural products and nutraceuticals on steroid hormone-regulated gene expression. Clin Chim.Acta 2001;312(1-2):213-219. PubMed
  5. Araghiniknam M, Chung S, Nelson-White T, and et al. Antioxidant activity of Dioscorea and dehydroepiandrosterone (DHEA) in older humans. Life Sciences 1996;59:L147-L157.
  6. Zeng M, Zhang L, Li M, et al. Estrogenic effects of the extracts from the Chinese Yam (Dioscorea opposite Thunb.) and its effective compounds in vitro and in vivo. Molecules. 2018 Jan 23;23(2). Pii: E11. PubMed
  7. Lu J, Wong RN, Zhang L, et al. Comparative analysis of proteins with stimulating activity on ovarian estradiol biosynthesis from four different Dioscorea species in vitro using both phenotypic and target-based approaches: implication for treating menopaus

See these in context on the Wild Yam monograph →

Rosemary 20 references
  1. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  2. Foster S, Tyler VE. Tyler's Honest Herbal: A Sensible Guide to the Use of Herbs and Related Remedies. 3rd ed., Binghamton, NY: Haworth Herbal Press, 1993.
  3. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
  4. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  5. Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 1st ed. Montvale, NJ: Medical Economics Company, Inc., 1998.
  6. Cartier LC, Lehrer A, Malo JL. Occupational asthma caused by aromatic herbs. Allergy 1996;51:647-9. DOI
  7. Burkhard PR, Burkhardt K, Haenggeli CA, Landis T. Plant-induced seizures: reappearance of an old problem. J Neurol 1999;246:667-70. PubMed
  8. Swain AR, Dutton SP, Truswell AS. Salicylates in foods. J Am Diet.Assoc 1985;85(8):950-60. DOI
  9. Zhu BT, Loder DP, Cai MX, et al. Dietary administration of an extract from rosemary leaves enhances the liver microsomal metabolism of endogenous estrogens and decreases their uterotropic action in CD-1 mice. Carcinogenesis 1998;19(10):1821-7. PubMed
  10. Debersac P, Heydel JM, Amiot MJ, et al. Induction of cytochrome P450 and/or detoxication enzymes by various extracts of rosemary: description of specific patterns. Food Chem Toxicol 2001;39(9):907-18. PubMed
  11. Debersac P, Vernevaut MF, Amiot MJ, et al. Effects of a water-soluble extract of rosemary and its purified component rosmarinic acid on xenobiotic-metabolizing enzymes in rat liver. Food Chem Toxicol 2001;39(2):109-17. PubMed
  12. Lee JJ, Jin YR, Lee JH, et al. Antiplatelet activity of carnosic acid, a phenolic diterpene from Rosmarinus officinalis. Planta Med 2007;73(2):121-7.
  13. Yamamoto J, Yamada K, Naemura A, et al. Testing various herbs for antithrombotic effect. Nutrition 2005;21(5):580-7. PubMed
  14. Naemura A, Ura M, Yamashita T, et al. Long-term intake of rosemary and common thyme herbs inhibits experimental thrombosis without prolongation of bleeding time. Thromb Res 2008;122(4):517-22. PubMed
  15. Lee JJ, Jin YR, Lim Y, et al. Antiplatelet activity of carnosol is mediated by the inhibition of TXA2 receptor and cytosolic calcium mobilization. Vascul Pharmacol 2006;45:148-53. PubMed
  16. Bakirel, T., Bakirel, U., Keles, O. U., Ulgen, S. G., and Yardibi, H. In vivo assessment of antidiabetic and antioxidant activities of rosemary (Rosmarinus officinalis) in alloxan-diabetic rabbits. J Ethnopharmacol 2-28-2008;116(1):64-73. PubMed
  17. Erenmemisoglu, A., Saraymen, R., and Ustun, S. Effect of a Rosmarinus officinalis leave extract on plasma glucose levels in normoglycaemic and diabetic mice. Pharmazie 1997;52(8):645-646.
  18. Valones MAA, Silva ICG, Gueiros LAM, Leão JC, Caldas AF Jr, Carvalho AAT. Clinical assessment of rosemary-based toothpaste (Rosmarinus officinalis Linn.): A randomized controlled double-blind study. Braz Dent J. 2019;30(2):146-151. PubMed
  19. Quirarte-Báez SM, Zamora-Perez AL, Reyes-Estrada CA, et al. A shortened treatment with rosemary tea (rosmarinus officinalis) instead of glucose in patients with diabetes mellitus type 2 (TSD). J Popul Ther Clin Pharmacol. 2019;26(4):e18-e28.
  20. Al Jamal A. Effect of rosemary (Rosmarinus officinalis) on lipid profiles and blood glucose in human diabetic patients (type-2). African J. Biochem. Res. 2014;8(8):147-50. DOI

See these in context on the Rosemary 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 →

Jamaican Dogwood 2 references
  1. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  2. Della, Loggia R., Tubaro, A., and Redaelli, C. [Evaluation of the activity on the mouse CNS of several plant extracts and a combination of them]. Riv.Neurol. 1981;51(5):297-310.

See these in context on the Jamaican Dogwood 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 →

Black Haw 1 reference
  1. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.

See these in context on the Black Haw monograph →

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

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

© 2021 Therapeutic Research Center, LLC

Keep exploring
Supplement interaction checker › Check any supplement or product against your medications Drug–drug interactions › Check two or more of your medications against each other Browse medications A–Z › Every drug we've checked against herbs & supplements NDC & pricing lookup › Find a drug’s NDCs, packaging and costs Ask a pharmacist › Free, personal answer from our licensed team