Major interaction on record — check this product against your medications before combining. Based on 5 of 7 ingredients. Check your meds →
Dietary supplement

Headache Release Ingredients & Drug Interactions

by Pacific BioLogic

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

First and foremost: checking Headache Release 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

Headache Release is a dietary supplement by Pacific BioLogic with 7 active ingredients. Its ingredients are commonly taken for pain relief, menstrual cramps, headache.Based on those ingredients, 1,417 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Corydalis yanhusuo, Citrus viride, Pueraria spp.. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

Jump to a section

Check Your Meds Against Headache Release by Pacific BioLogic

Ask about any prescription or over-the-counter medication and we check it for interactions with Headache Release by Pacific BioLogic — and tell you which ingredient is responsible.

Pharmacist-reviewed data Checks every ingredient Answer in seconds
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HelloPharmacist Scorecard of Headache Release by Pacific BioLogic

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 Aug 6, 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 7 active ingredients.
  • “Proprietary Blend” is a proprietary blend — the label gives one combined amount (525 mg) without saying how much of each component you get.

Headache Release contains 7 ingredients in a proprietary blend. The active components include Corydalis yanhusuo (a traditional Chinese herb containing berberine), Gastrodia elata, Stachys officinalis (betony), Chrysanthemum morifolium, Uncaria rhynchophylla, Pueraria spp. (kudzu), and Citrus viride (bitter orange).

The product is enclosed in plant-based capsules as its inactive ingredient.

Does it work?

Insufficient 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
Insufficient

There isn't enough reliable clinical evidence to rate this product's ingredients for its stated purpose.

Why this rating?
  • The label markets this product for: Headache relief.
  • We looked for evidence on: Cluster headache, Headache, Migraine, Tension headache, Cervicogenic headache.
  • The closest evidence on file: Corydalis Yanhusuo is rated "Insufficient Reliable Evidence To Rate" for Headache (Natural Medicines).
  • Also on file: Kudzu is rated "Insufficient Reliable Evidence To Rate" for Cluster headache.
  • Also on file: Chrysanthemum is rated "Insufficient Reliable Evidence To Rate" for Headache.

The evidence supporting Headache Release's ingredients for headache and other conditions is limited. Corydalis yanhusuo, Stachys officinalis, Chrysanthemum morifolium, and Uncaria rhynchophylla all have insufficient reliable evidence to rate their effectiveness for the conditions this product targets.

Kudzu is rated possibly effective for alcohol use disorder, but data for its use in headache relief are not established in the information we hold. Overall, reliable evidence for this product's intended use is not available in our data.

The evidence, ingredient by ingredient Corydalis Yanhusuo Betony Chrysanthemum Kudzu Bitter Orange

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 3 of the 5 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 5 of 5.
  • General safety write-ups exist for 5 of 5.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Corydalis yanhusuo carries pregnancy and lactation ratings of Likely Unsafe — the safety data advises against use during pregnancy and while breastfeeding. Stachys officinalis is traditionally avoided in pregnancy due to possible effects on the uterus, and there isn't enough safety information for breastfeeding; talk with your doctor or pharmacist about using it during these times.

Chrysanthemum is generally well tolerated as a tea but can cause allergic reactions (including urticaria, contact dermatitis, eczema, and rarely asthma) in sensitive people; safety during pregnancy and breastfeeding has not been established. Pueraria spp. and Citrus viride have not been sufficiently studied in pregnancy and breastfeeding to establish safety.

No serious adverse effects have been reported in trials, though bitter orange can raise blood pressure and heart rate, especially with caffeine, and chrysanthemum may trigger allergy symptoms in susceptible individuals.

Side effects, ingredient by ingredient Corydalis Yanhusuo Betony Chrysanthemum Kudzu Bitter Orange

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?
  • 4 of the 5 matched ingredients can interact with medications — Corydalis Yanhusuo, Betony, Kudzu, Bitter Orange.
  • 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.
  • For scale: 1,418 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.

Check with your doctor or pharmacist before taking this product if you use an MAOI (Major severity risk of dangerous blood pressure spike), midazolam or other sedatives, blood pressure medications, blood thinners, diabetes drugs, metformin, liver-toxic medications, estrogen therapy, tamoxifen, methotrexate, dextromethorphan (cough suppressant), or caffeine. Bitter orange's stimulant effects combined with these drugs can pose serious cardiovascular risks.

Check your own medication Run your meds through the checker above

The bottom line

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

Headache Release is intended to address headache using traditional ingredients, but strong evidence of effectiveness is not available. If you take blood pressure medicine, blood thinners, diabetes drugs, sedatives, or an MAOI, or if you're pregnant, nursing, or have allergies to plants in the daisy family, talk with your doctor or pharmacist before starting.

The ingredient interactions are significant enough that a conversation with your own healthcare provider or pharmacist is important before you add this to your routine.

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

Assessment coverage: 5 of 7 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Apr 23, 2020.

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 Headache Release, straight from the product label.

Brand Pacific BioLogic
Barcode (UPC) 065367401198
Net contents 90 Vegetarian Capsule(s)
Market status On market
Date entered into DSLD Apr 23, 2020
DSLD ID 218483
Product type Botanical
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years)
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 Headache Release by Pacific BioLogic, 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:
3 Capsule(s)
Servings per container
30
UPC/BARCODE
065367401198
IngredientAmount% DV
Proprietary Blend525 mg--
Corydalis yanhusuo0 NP--
Gastrodia elata0 NP--
Stachys officinalis0 NP--
Chrysanthemum morifolium0 NP--
Uncaria rhynchophylla0 NP--
Pueraria spp.0 NP--
Citrus viride0 NP--

Other ingredients: Capsules of plant origin

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.
Suggested/Recommended/Usage/Directions

Suggested dosage: 2-3 capsules 2-4 times daily between meals. Reduce the dosage and frequency as the condition improves.

Precautions

Caution: If pregnant or nursing.

Stop taking if you have symptoms of a cold or flu.

To report a serious adverse event or obtain product information, contact (800) 869-8783

Formulation

Headache Relief is a proprietary formula of Pacific BioLogic Co. manufactured in an FDA compliant facility in the United States of America from imported and domestic ingredients

Storage

Store in a cool, dry place, do not refrigerate.

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.

General Statements

Powerful tools for gentle healing

525 mg

FDA Statement of Identity

Herbal Supplement

Seals/Symbols

Product of USA

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

See for yourself

Headache Release by Pacific BioLogic label

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

Headache Release 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 Headache Release by Pacific BioLogic

These are the 7 active ingredients this product is made of. Select any to open its full monograph.

Serving size2 Capsule(s) Dosage formCapsule Servings per container30 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 Blend

525 mg per serving

Other (inactive) ingredients: Capsules of plant origin. These complete the product’s ingredient list but are not active constituents.

Interaction report

Headache Release by Pacific BioLogic Drug Interactions

Want to check YOUR meds against Headache Release?

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
1,417Drugs
10 Major 1,407 Moderate

Ingredients driving the most interactions

Corydalis yanhusuo 1,160
Citrus viride 957
Pueraria spp. 584
Stachys officinalis 172

Individual Drug Interactions

The ingredients in Headache Release interact with 1,417 drugs. Click any drug to see the details.

4 of the 7 ingredients in Headache Release interact with drugs. Each result below shows which ingredient is responsible. Corydalis yanhusuo Citrus viride Pueraria spp. Stachys officinalis

Each ingredient & the kinds of drugs it affects

For each ingredient in Headache Release 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.

Corydalis yanhusuo14 drug types · 1,160 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, Corydalis yanhusuo might increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.
Corydalis yanhusuo contains berberine. In vitro and in vivo research suggest that berberine can inhibit platelet aggregation. Theoretically, Corydalis yanhusuo might also inhibit platelet aggregation.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, Corydalis yanhusuo may increase the risk of hypoglycemia when taken with antidiabetes drugs.
Corydalis yanhusuo contains berberine. Clinical research shows that berberine may lower blood glucose levels. Theoretically, Corydalis yanhusuo might also lower blood glucose levels.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, Corydalis yanhusuo might have additive effects with antihypertensive drugs.
Corydalis yanhusuo contains berberine. Animal research suggests that berberine can have hypotensive effects. Also, a clinical study suggests that taking berberine in combination with amlodipine can lower systolic and diastolic blood pressure when compared with amlodipine alone. Theoretically, Corydalis yanhusuo might also reduce blood pressure.

Likelihood Possible Evidence D
Cns Depressants

Theoretically, Corydalis yanhusuo might increase the sedative effects of CNS depressants.
Corydalis yanhusuo contains berberine. Animal research suggests that berberine may have sedative effects. Theoretically, Corydalis yanhusuo might also have CNS depressants effects.

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

Theoretically, Corydalis yanhusuo might increase blood levels of cyclosporine.
Corydalis yanhusuo contains berberine. Preliminary clinical research shows that berberine can reduce metabolism of cyclosporine and increase serum levels, likely through inhibition of cytochrome P450 3A4 (CYP3A4), which metabolizes cyclosporine. Theoretically, Corydalis yanhusuo might also reduce the metabolism of cyclosporine.

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

Theoretically, Corydalis yanhusuo might increase serum levels of drugs metabolized by CYP2C9.
Corydalis yanhusuo contains berberine. Preliminary clinical research shows that berberine can inhibit CYP2C9. Theoretically, Corydalis yanhusuo might also inhibit CYP2C9.

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

Theoretically, Corydalis yanhusuo might increase serum levels of drugs metabolized by CYP2D6.
Corydalis yanhusuo contains berberine. In vitro research and preliminary clinical evidence show that berberine can inhibit CYP2D6. Theoretically, Corydalis yanhusuo might also inhibit CYP2D6.

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

Theoretically, Corydalis yanhusuo might increase serum levels of drugs metabolized by CYP3A4.
Corydalis yanhusuo contains berberine. In vitro research and preliminary clinical research show that berberine moderately inhibits CYP3A4. Theoretically, Corydalis yanhusuo might also inhibit CYP3A4.

Likelihood Possible Evidence D
Dextromethorphan (Robitussin Dm, Others)

Theoretically, Corydalis yanhusuo may increase serum levels of dextromethorphan.
Corydalis yanhusuo contains berberine. Preliminary clinical research shows that berberine can inhibit cytochrome P450 2D6 (CYP2D6) activity and reduce the metabolism of dextromethorphan. Theoretically, Corydalis yanhusuo may also inhibit the metabolism of dextromethorphan.

Likelihood Possible Evidence D
Losartan (Cozaar)

Theoretically, Corydalis yanhusuo might reduce the therapeutic effects of losartan by decreasing its conversion to its active form.
Corydalis yanhusuo contains berberine. Preliminary clinical research suggests that berberine can inhibit cytochrome P450 2C9 (CYP2C9) activity and reduce metabolism of losartan. Theoretically, Corydalis yanhusuo might also inhibit the metabolism of losartan.

Likelihood Possible Evidence D
Metformin (Glucophage)

Theoretically, Corydalis yanhusuo might increase the therapeutic and adverse effects of metformin.
Corydalis yanhusuo contains berberine. In vitro and animal studies show that berberine can increase the systemic exposure and half-life of metformin, potentially increasing metformin's effects and side effects. This interaction seems to be most apparent when berberine is administered 2 hours prior to metformin. Taking berberine and metformin at the same time does not appear to increase systemic exposure to metformin. It is unclear if Corydalis yanhusuo might have this same effect.

Likelihood Possible Evidence D
Midazolam (Versed)

Theoretically, Corydalis yanhusuo might reduce metabolism of midazolam, which might increase the risk of severe adverse effects.
Corydalis yanhusuo contains berberine. Preliminary clinical research shows that berberine can inhibit cytochrome P450 3A4 (CYP3A4) activity and reduce metabolism of midazolam. Theoretically, Corydalis yanhusuo might also inhibit the metabolism of midazolam.

Likelihood Possible Evidence D
Pentobarbital (Nembutal)

Theoretically, Corydalis yanhusuo might increase the sedative effect of pentobarbital.
Corydalis yanhusuo contains berberine. Animal research shows that berberine can prolong pentobarbital-induced sleeping time. Theoretically, Corydalis yanhusuo might increase the sedative effects of pentobarbital.

Likelihood Possible Evidence D
Tacrolimus (Prograf)

Theoretically, Corydalis yanhusuo might increase blood levels of tacrolimus.
Corydalis yanhusuo contains berberine. In a 16-year-old patient with idiopathic nephrotic syndrome who was being treated with tacrolimus 6.5 mg twice daily, intake of berberine 200 mg three times daily increased the blood concentration of tacrolimus from 8 to 22 ng/mL. Following a reduction of the tacrolimus dose to 3 mg daily, blood levels of tacrolimus decreased to 12 ng/mL. It is unclear if Corydalis yanhusuo might have this same effect.

Likelihood Possible Evidence D
Corydalis yanhusuo full monograph & interactions

Citrus viride13 drug types · 957 drugs

Midazolam (Versed)

Bitter orange might increase blood levels of midazolam.
One small clinical study shows that bitter orange juice can increase midazolam levels, likely through inhibition of cytochrome P450 3A4 (CYP3A4). Theoretically, bitter orange might increase the risk of midazolam-related adverse effects.

Likelihood Probable Evidence B
Monoamine Oxidase Inhibitors (Maois)

Theoretically, taking MAOIs with synephrine-containing bitter orange preparations might increase the hypertensive effects of synephrine, potentially leading to hypertensive crisis.
Bitter orange contains tyramine, octopamine, and synephrine, which are MAO substrates.

Likelihood Probable Evidence D
Antidiabetes Drugs

Theoretically, bitter orange might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Some clinical research shows that drinking a tea containing bitter orange and Indian snakeroot reduces fasting and postprandial glucose levels in patients with type 2 diabetes who are using antidiabetes drugs. However, it is unclear if these effects are due to bitter orange, Indian snakeroot, or the combination. An animal study also shows that p-synephrine in combination with gliclazide , a sulfonylurea, causes an additional 20% to 44% decrease in glucose levels when compared with gliclazide alone.

Likelihood Possible Evidence B
Caffeine

Bitter orange might increase blood pressure and heart rate when taken with caffeine.
Small clinical studies show that taking bitter orange in combination with caffeine can increase blood pressure and heart rate in otherwise healthy normotensive adults. Theoretically, this might increase the risk of serious cardiovascular adverse effects.

Likelihood Possible Evidence B
Colchicine

Bitter orange might affect colchicine levels.
Colchicine is a substrate of P-glycoprotein and cytochrome P450 3A4 (CYP3A4). Bitter orange has been reported to inhibit CYP3A4 and increase levels of CYP3A4 substrates. However, one small clinical study in healthy adults shows that drinking bitter orange juice 240 mL twice daily for 4 days and taking a single dose of colchicine 0.6 mg on the 4th day decreases colchicine peak serum levels by 24%, time to peak serum level by 1 hour, and overall exposure to colchicine by 20%. The clinical significance of this finding is unclear.

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

Bitter orange might increase levels of drugs metabolized by CYP3A4.
Small clinical studies suggest that single or multiple doses of freshly squeezed bitter orange juice 200-240 mL can inhibit CYP3A4 metabolism of drugs, causing increased drug levels and potentially increasing the risk of adverse effects. However, the extent of the effect of bitter orange on CYP3A4-mediated drug interactions is unknown. Some evidence suggests that bitter orange selectively inhibits intestinal CYP3A4, but not hepatic CYP3A4. Its effect on P-glycoprotein, which strongly overlaps with CYP3A4 interactions, is unclear. One small clinical study shows that drinking 8 ounces of freshly squeezed bitter orange juice has no effect on cyclosporine, which seems to be more dependent on hepatic CYP3A4 and P-glycoprotein than intestinal CYP3A4.

Likelihood Possible Evidence B
Dextromethorphan (Robitussin Dm, Others)

Bitter orange might increase blood levels of dextromethorphan.
One small clinical study shows that bitter orange juice increases dextromethorphan levels, likely through cytochrome P450 3A4 (CYP3A4) inhibition. Theoretically, bitter orange might increase the risk for dextromethorphan-related adverse effects.

Likelihood Possible Evidence B
Felodipine (Plendil)

Bitter orange might increase blood levels of felodipine.
One small clinical study shows that bitter orange juice increases felodipine levels, likely through cytochrome P450 3A4 (CYP3A4) inhibition. Theoretically, bitter orange might increase the risk for felodipine-related adverse effects.

Likelihood Probable Evidence B
Indinavir (Crixivan)

Bitter orange might increase blood levels of indinavir.
One small clinical study shows that bitter orange juice slightly increases indinavir levels, but this effect is likely to be clinically insignificant. Bitter orange selectively inhibits intestinal cytochrome P450 3A4 (CYP3A4); however, the metabolism of indinavir seems to be more dependent on hepatic CYP3A4. The effect of bitter orange on other protease inhibitors has not been studied.

Likelihood Possible Evidence B
Qt Interval-Prolonging Drugs

Theoretically, bitter orange might have an additive effect when combined with drugs that prolong the QT interval, potentially increasing the risk of ventricular arrhythmias.
One case report suggests that taking bitter orange in combination with other stimulants such as caffeine might prolong the QT interval in some patients.

Likelihood Possible Evidence D
Sildenafil (Viagra)

Bitter orange juice might increase blood levels of sildenafil.
A small clinical study in healthy adult males shows that drinking freshly squeezed bitter orange juice 250 mL daily for 3 days and taking a single dose of sildenafil 50 mg on the 3rd day increases the peak plasma concentration of sildenafil by 18% and the overall exposure to sildenafil by 44%. Theoretically, this may be due to inhibition of cytochrome P450 3A4 by bitter orange.

Likelihood Probable Evidence B
Stimulant Drugs

Theoretically, bitter orange might increase the risk of hypertension and adverse cardiovascular effects when taken with stimulant drugs.
Bitter orange appears to have stimulant effects.

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

Theoretically, bitter orange might increase levels of drug metabolized by CYP2D6.
In vitro research shows that octopamine, a constituent of bitter orange, weakly inhibits CYP2D6 enzymes. This effect has not been reported in humans.

Likelihood Possible Evidence D
Citrus viride full monograph & interactions

Pueraria spp.7 drug types · 584 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, kudzu may increase the risk of bleeding if used with antiplatelet or anticoagulant drugs.
Kudzu isoflavones are reported to have antiplatelet activity.

Likelihood Possible Evidence D
Caffeine

Theoretically, taking kudzu with caffeine might increase levels of caffeine.
In healthy males injected with the kudzu constituent puerarin, caffeine clearance and metabolism is inhibited. This effect has been attributed to inhibition of cytochrome P450 1A2 (CYP1A2) enzyme, which is involved in caffeine metabolism. It is unclear if taking kudzu orally would have this same effect.

Likelihood Probable Evidence D
Estrogens

Theoretically, kudzu might alter the effects of estrogen therapy.
Some research suggests that kudzu has estrogenic effects. This may enhance or inhibit the effects of estrogen therapy.

Likelihood Possible Evidence B
Hepatotoxic Drugs

Theoretically, concomitant use might have additive hepatotoxic effects.
There is some concern that kudzu can adversely affect the liver.

Likelihood Possible Evidence D
Methotrexate (Trexall, Others)

Theoretically, taking kudzu with methotrexate might increase the risk of methotrexate toxicity.
Preclinical research suggests that kudzu extract greatly reduces the elimination and increases the toxicity of methotrexate. Kudzu might inhibit organic anion transporters (OATs) that are responsible for hepatobiliary and renal excretion of anions, similar to the interaction between methotrexate and non-steroidal anti-inflammatory drugs (NSAIDs).

Likelihood Possible Evidence D
Tamoxifen (Nolvadex)

Theoretically, kudzu might interfere with tamoxifen activity.
Some research suggests that kudzu may have estrogenic effects.

Likelihood Possible Evidence B
Antidiabetes Drugs

Theoretically, taking kudzu with antidiabetes drugs might increase the risk of hypoglycemia.
Kudzu might lower blood glucose levels and have additive effects in patients treated with antidiabetic agents. The dose of diabetes medications might need to be adjusted.

Likelihood Unlikely Evidence D
Pueraria spp. full monograph & interactions

Stachys officinalis1 drug type · 172 drugs

Antihypertensive Drugs

Theoretically, betony might have additive effects with blood pressure lowering drugs due to hypotensive activity of the glycosides found in betony. It might also interfere with the activity of pressor drugs. Some antihypertensive drugs include captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), Amlodipine (Norvasc), hydrochlorothiazide (HydroDiuril), furosemide (Lasix), and many others.

Likelihood Possible Evidence D
Stachys officinalis full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Headache Release, from the product label.

Pacific BioLogic

See all Pacific BioLogic products
Name
Pacific BioLogic Co.
City
Concord
State
CA
ZipCode
94521
Phone Number
800 869-8783
Web Address
www.pacificbiologic.com
Pharmacist Counseling Corner

Headache Release by Pacific BioLogic: Common Questions

Does Headache Release by Pacific BioLogic interact with any medications?
Yes. Based on its ingredients, Headache Release has a known interaction with 1,417 medications, including 10 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Headache Release contains 7 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.
Can I take this if I'm pregnant or breastfeeding?
Corydalis yanhusuo is rated Likely Unsafe during pregnancy and lactation, so the safety data advises against it. Stachys officinalis is traditionally avoided in pregnancy and lacks safety information for breastfeeding. Chrysanthemum, kudzu, and bitter orange have not been studied enough to establish safety. Talk with your doctor or pharmacist before use during pregnancy or while breastfeeding.
What does each ingredient do in this product?
Corydalis yanhusuo, Stachys officinalis, Chrysanthemum morifolium, Uncaria rhynchophylla, Pueraria spp., and Citrus viride are traditional herbal components used in formulas aimed at headache relief, though reliable clinical evidence for their effectiveness in this product is not established in our data.
Can this cause allergic reactions?
Chrysanthemum can cause allergic reactions in sensitive people, including urticaria (hives), contact dermatitis, eczema, and rarely asthma. Bitter orange and kudzu have also been associated with allergic reactions in some individuals. If you have known allergies to plants in the daisy family or to any ingredient listed, avoid this product or consult your doctor first.
Is there enough evidence that this works for headaches?
The evidence supporting the ingredients in Headache Release for headache relief is insufficient to rate their effectiveness. While these herbs have traditional use, clinical research specifically for this product and indication has not been established in our data.
What should I do before I start taking it?
Check your current medications against the interaction checker on this page. If you take any blood pressure medicine, blood thinner, diabetes drug, sedative, MAOI, heart drug, or caffeine-containing product, discuss this supplement with your doctor or pharmacist first. The ingredient interactions are significant.

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

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

Headache Release label
Go deeper

The Full Monographs Behind Headache Release’s Ingredients

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

Herb & supplement monograph

Corydalis Yanhusuo

Interacts with 1,160 drugs

Corydalis yanhusuo is a traditional Chinese herb used mainly for pain. Some early laboratory and animal research suggests its compounds may affect pain and the nervous system, but high-quali...

Read the full Corydalis Yanhusuo monograph → Herb & supplement monograph

Betony

Interacts with 172 drugs

Betony (Stachys officinalis) is a traditional European herb long used for headaches, nervous tension, and digestive complaints. Modern scientific evidence supporting these uses is very limit...

Read the full Betony monograph → Herb & supplement monograph

Chrysanthemum

Chrysanthemum flowers are most often used as a soothing tea in traditional Chinese medicine and as a folk remedy for eye irritation, colds, and minor inflammation. Solid human evidence for t...

Read the full Chrysanthemum monograph → Herb & supplement monograph

Kudzu

Interacts with 584 drugs

Kudzu is a fast-growing vine whose root has long been used in traditional Chinese medicine and is now studied mostly for reducing alcohol intake. Early research is promising for cutting back...

Read the full Kudzu monograph → Herb & supplement monograph

Bitter Orange

Interacts with 957 drugs

Bitter orange is a citrus fruit whose extracts contain synephrine, a mild stimulant often added to weight-loss and energy supplements. Evidence that it works for weight loss or performance i...

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Sources

Sources & How We Checked

Headache Release'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 116 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.

Corydalis Yanhusuo 21 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. Chan E. Displacement of bilirubin from albumin by berberine. Biol Neonate 1993;63:201-8. PubMed
  3. Janbaz KH, Gilani AH. Studies on preventive and curative effects of berberine on chemical-induced hepatotoxicity in rodents. Fitoterapia 2000;71:25-33.. PubMed
  4. Wu X, Li Q, Xin H, Yu A, Zhong M. Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. Eur J Clin Pharmacol 2005;61:567-72. PubMed
  5. Zhang Y, Li X, Zou D, et al. Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocrinol Metab 2008;93:2559-65. 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. Chatterjee P, Franklin MR. Human cytochrome p450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components. Drug Metab Dispos 2003;31:1391-7. PubMed
  8. Shanbhag, S. M., Kulkarni, H. J., and Gaitonde, B. B. Pharmacological actions of berberine on the central nervous system. Jpn.J Pharmacol 1970;20(4):482-487. PubMed
  9. Wu, J. F. and Liu, T. P. [Effects of berberine on platelet aggregation and plasma levels of TXB2 and 6-keto-PGF1 alpha in rats with reversible middle cerebral artery occlusion]. Yao Xue.Xue.Bao. 1995;30(2):98-102.
  10. Peng, W. H., Hsieh, M. T., and Wu, C. R. Effect of long-term administration of berberine on scopolamine-induced amnesia in rats. Jpn J Pharmacol 1997;74(3):261-266. DOI
  11. Sabir M and Bhide NK. Study of some pharmacological actions of berberine. Ind J Physiol & Pharmac 1971;15(3):111-132.
  12. Tripathi YB and Shukla SD. Berberis artistata inhibits PAF induced aggregation of rabbit platelets. Phytotherapy Research 1996;10:628-630.
  13. Yin, J., Xing, H., and Ye, J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism 2008;57(5):712-717. PubMed
  14. Zhang, H., Wei, J., Xue, R., Wu, J. D., Zhao, W., Wang, Z. Z., Wang, S. K., Zhou, Z. X., Song, D. Q., Wang, Y. M., Pan, H. N., Kong, W. J., and Jiang, J. D. Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin re
  15. Guo, Y., Chen, Y., Tan, Z. R., Klaassen, C. D., and Zhou, H. H. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol 2012;68(2):213-217. PubMed
  16. Wei, W., Zhao, H., Wang, A., Sui, M., Liang, K., Deng, H., Ma, Y., Zhang, Y., Zhang, H., and Guan, Y. A clinical study on the short-term effect of berberine in comparison to metformin on the metabolic characteristics of women with polycystic ovary syndro
  17. Hermann, R. and von, Richter O. Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions. Planta Med 2012;78(13):1458-1477. PubMed
  18. Chun YT, Yip TT, Lau KL, and et al. A biochemical study on the hypotensive effect of berberine in rats. Gen Pharmac 1979;10:177-182. PubMed
  19. Hou Q, Han W, Fu X. Pharmacokinetic interaction between tacrolimus and berberine in a child with idiopathic nephrotic syndrome. Eur J Clin Pharmacol 2013;69(10):1861-2. PubMed
  20. Lan J, Zhao Y, Dong F, et al. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J Ethnopharmacol. 2015;161:69-81. PubMed
  21. Lyu Y, Zhang Y, Yang M, et al. Pharmacokinetic interactions between metformin and berberine in rats: Role of oral administration sequences and microbiota. Life Sci. 2019;235:116818. PubMed

See these in context on the Corydalis Yanhusuo monograph →

Betony 2 references
  1. 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.
  2. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.

See these in context on the Betony monograph →

Chrysanthemum 25 references
  1. Kuno Y, Kawabe Y, Sakakibara S. Allergic contact dermatitis associated with photosensitivity, from alantolactone in a chrysanthemum farmer. Contact Dermatitis 1999;40:224-5. PubMed
  2. deJong NW, Vermeulen AM, van Wijik RG, deGroot H. Occupational allergy caused by flowers. Allergy 1998;53:204-9. PubMed
  3. Camplimi P, Sertoli A, Fabbri P, Panconesi E. Alantolactone sensitivity in chrysanthemum contact dermatitis. Contact Dermatitis 1978;4:93-102. PubMed
  4. Bleumink E, Mitchell JC, Geismann TA, Towers GH. Contact hypersensitivity to sesquiterpene lactones in Chrysanthemum dermatitis. Contact Dermatitis 1976;2:81-8.
  5. Lamminpaa A, Estlander T, Jolanki R, Kanerva L. Occupational allergic contact dermatitis caused by decorative plants. Contact Dermatitis 1996;34:330-5. PubMed
  6. Hausen BM. The sensitizing capacity of Compositae plants. III. Test results and cross-reactions in Compositae-sensitive patients. Dermatologica 1979;159:1-11. DOI
  7. Kuno, Y., Kawabe, Y., and Sakakibara, S. Allergic contact dermatitis associated with photosensitivity, from alantolactone in a chrysanthemum farmer. Contact Dermatitis 1999;40(4):224-225. PubMed
  8. Schulz, K. H., Hausen, B. M., Wallhofer, L., and Schmidt-Loffler, P. Chrysanthemum allergy. Pt. II: Experimental studies on the causative agents. Arch.Dermatol.Forsch. 1975;251(3):235-244.
  9. Singhal, V. and Reddy, B. S. Common contact sensitizers in Delhi. J Dermatol 2000;27(7):440-445. PubMed
  10. Kuroume, T., Todokoro, M., Tomidokoro, H., Kanbe, Y., and Matsumura, T. Chrysanthemum pollinosis in Japan. Int.Arch.Allergy Appl.Immunol. 1975;48(6):800-811.
  11. Groenewoud, G. C., de Jong, N. W., Burdorf, A., de Groot, H., and van Wyk, R. G. Prevalence of occupational allergy to Chrysanthemum pollen in greenhouses in the Netherlands. Allergy 2002;57(9):835-840.
  12. Jovanovic, M. and Poljacki, M. [Compositae dermatitis]. Med Pregl. 2003;56(1-2):43-49. PubMed
  13. Hashimoto, Y., Kawada, A., Aragane, Y., and Tezuka, T. Occupational contact dermatitis from chrysanthemum in a mortician. Contact Dermatitis 2003;49(2):106-107. PubMed
  14. Groenewoud, G. C., de Groot, H., and van Wijk, R. G. Impact of occupational and inhalant allergy on rhinitis-specific quality of life in employees of bell pepper greenhouses in the Netherlands. Ann Allergy Asthma Immunol 2006;96(1):92-97. PubMed
  15. Sharma, S. C. and Kaur, S. Airborne contact dermatitis from Compositae plants in northern India. Contact Dermatitis 1989;21(1):1-5. PubMed
  16. Sharma, S. C., Tanwar, R. C., and Kaur, S. Contact dermatitis from chrysanthemums in India. Contact Dermatitis 1989;21(2):69-71. PubMed
  17. Tanaka, T., Moriwaki, S. I., and Horio, T. Occupational dermatitis with simultaneous immediate and delayed allergy to chrysanthemum. Contact Dermatitis 1987;16(3):152-154. PubMed
  18. Frain-Bell, W., Hetherington, A., and Johnson, B. E. Contact allergic sensitivity to chrysanthemum and the photosensitivity dermatitis and actinic reticuloid syndrome. Br.J.Dermatol. 1979;101(5):491-501. PubMed
  19. Diener, C., Schlenvoigt, G., Jager, L., Prater, E., and Schubert, H. Allergens of chrysanthemum pollen. Allergol.Immunopathol.(Madr.) 1986;14(1):49-53.
  20. Zeller, W., de Gols, M., and Hausen, B. M. The sensitizing capacity of Compositae plants. VI. Guinea pig sensitization experiments with ornamental plants and weeds using different methods. Arch Dermatol.Res 1985;277(1):28-35. PubMed
  21. Schmidt, R. J. When is a chrysanthemum dermatitis not a chrysanthemum dermatitis? The case for describing florists' chrysanthemums as Dendranthema cultivars. Contact Dermatitis 1985;13(2):115-119.
  22. Schmidt, R. J. and Kingston, T. Chrysanthemum dermatitis in South Wales; diagnosis by patch testing with feverfew (Tanacetum parthenium) extract. Contact Dermatitis 1985;13(2):120-121.
  23. Mitchell, J. C., Geissman, T. A., Dupuis, G., and Towers, G. H. Allergic contact dermatitis caused by Artemisia and Chrysanthemum species. The role of sesquiterpene lactones. J.Invest Dermatol. 1971;56(2):98-101. PubMed
  24. Sugai, T., Takahashi, Y., and Okuno, F. Chrysanthemum dermatitis in Japan. Contact Dermatitis 1980;6(2):155. PubMed
  25. Wakelin, S. H., Marren, P., Young, E., and Shaw, S. Compositae sensitivity and chronic hand dermatitis in a seven-year-old boy. Br J Dermatol 1997;137(2):289-291. PubMed

See these in context on the Chrysanthemum monograph →

Kudzu 21 references
  1. Woo J, Lau E, Ho SC, et al. Comparison of Pueraria lobata with hormone replacement therapy in treating the adverse health consequences of menopause. Menopause 2003;10:352-61. PubMed
  2. Akita H, Sowa J, Makiura M, et al. Maculopapular drug eruption due to the Japanese herbal medicine Kakkonto (kudzu or arrowroot decoction). Contact Dermatitis 2003;48:348-9. PubMed
  3. Luo ZR, Zheng B. [Effect of Puerarin on platelet activating factors CD63 and CD62P, plasminogen activator inhibitor and C-reactive protein in patients with unstable angia pectoris]. Zhongguo Zhong Xi Yi Jie He Za Zhi 2001;21:31-3 .
  4. Lee KT, Sohn IC, Kim DH, et al. Hypoglycemic and hypolipidemic effects of tectorigenin and kaikasaponin III in the streptozotocin-lnduced diabetic rat and their antioxidant activity in vitro. Arch Pharm Res 2000;23:461-6.
  5. Yu Z, Zhang G, Zhao H. [Effects of Puerariae isoflavone on blood viscosity, thrombosis and platelet function]. Zhong Yao Cai 1997;20:468-9.
  6. Hsu FL, Liu IM, Kuo DH, et al. Antihyperglycemic effect of puerarin in streptozotocin-induced diabetic rats. J Nat Prod 2003;66:788-92. PubMed
  7. Chiang HM, Fang SH, Wen KC, et al. Life-threatening interaction between the root extract of Pueraria lobata and methotrexate in rats. Toxicol Appl Pharmacol 2005;209:263-8.
  8. Zheng, J., Chen, B., Jiang, B., Zeng, L., Tang, Z. R., Fan, L., and Zhou, H. H. The effects of puerarin on CYP2D6 and CYP1A2 activities in vivo. Arch Pharm Res 2010;33(2):243-246. PubMed
  9. Hsu, H. H., Chang, C. K., Su, H. C., Liu, I. M., and Cheng, J. T. Stimulatory effect of puerarin on alpha1A-adrenoceptor to increase glucose uptake into cultured C2C12 cells of mice. Planta Med 2002;68(11):999-1003.
  10. Zheng, G., Zhang, X., Zheng, J., Meng, Q., and Zheng, D. [Estrogen-like effects of puerarin and total isoflavones from Pueraria lobata]. Zhong.Yao Cai. 2002;25(8):566-568.
  11. Qi, B. L. and Qi, B. M. [Effect of the purariae-isofiavones on estrogen level in normal and ovariectomized rats]. Zhongguo Zhong.Yao Za Zhi. 2002;27(11):850-852.
  12. Akita, H., Sowa, J., Makiura, M., Akamatsu, H., and Matsunaga, K. Maculopapular drug eruption due to the Japanese herbal medicine Kakkonto (kudzu or arrowroot decoction). Contact Dermatitis 2003;48(6):348-349. PubMed
  13. Manonai, J., Chittacharoen, A., Theppisai, U., and Theppisai, H. Effect of Pueraria mirifica on vaginal health. Menopause. 2007;14(5):919-924. PubMed
  14. Chandeying, V. and Sangthawan, M. Efficacy comparison of Pueraria mirifica (PM) against conjugated equine estrogen (CEE) with/without medroxyprogesterone acetate (MPA) in the treatment of climacteric symptoms in perimenopausal women: phase III study. J M
  15. Virojchaiwong, P., Suvithayasiri, V., and Itharat, A. Comparison of Pueraria mirifica 25 and 50 mg for menopausal symptoms. Arch.Gynecol.Obstet. 2011;284(2):411-419. PubMed
  16. Hou, Q., Ao, X., Li, G., and Zhang, Y. [Puerarin combined with avandia for diabetic nephropathy]. Zhong.Nan.Da.Xue Xue Bao Yi Xue Ban. 2012;37(1):73-77.
  17. Kim HJ, Kim H, Ahn JH, Suk JH. Liver injury induced by herbal extracts containing mistletoe and kudzu. J Altern Complement Med 2015;21(3):180-5. PubMed
  18. Santosh N, Mohan K, Royana S, Yamini TB. Hepatotoxicity of tubers of Indian Kudzu (Pueraria tuberosa) in rats. Food Chem Toxicol. 2010 Apr;48(4):1066-71. PubMed
  19. Teschke R, Zhang L, Long H, Schwarzenboeck A, Schmidt-Taenzer W, Genthner A, Wolff A, Frenzel C, Schulze J, Eickhoff A. Traditional Chinese Medicine and herbal hepatotoxicity: a tabular compilation of reported cases. Ann Hepatol. 2015 Jan-Feb;14(1):7-19. DOI
  20. Wang D, Qiu L, Wu X, Wei H, Xu F. Evaluation of kudzu root extract-induced hepatotoxicity. J Ethnopharmacol. 2015 Dec 24;176:321-6. PubMed
  21. Warinsiriruk P, Tantitham C, Cherdshewasart W, Shobeiri SA, Manonai J. Effects of Pueraria mirifica on vaginal artery vascularization in postmenopausal women with genitourinary syndrome of menopause. Maturitas 2022;160:4-10. PubMed

See these in context on the Kudzu monograph →

Bitter Orange 47 references
  1. Penzak SR, Jann MW, Cold JA, et al. Seville (sour) orange juice: synephrine content and cardiovascular effects in normotensive adults. J Clin Pharmacol 2001;41:1059-63. PubMed
  2. Electronic Code of Federal Regulations. Title 21. Part 182 -- Substances Generally Recognized As Safe. Available at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=182
  3. Calapai G, Firenzuoli F, Saitta A, et al. Antiobesity and cardiovascular toxic effects of Citrus aurantium extracts in the rat: A preliminary report. Fitoterapia 1999;70:586-92. DOI
  4. Keogh AM, Baron DW. Sympathomimetic abuse and coronary artery spasm. Br Med J 1985;291:940.
  5. Malhotra S, Bailey DG, Paine MF, Watkins PB. Seville orange juice-felodipine interaction: comparison with dilute grapefruit juice and involvement of furocoumarins. Clin Pharmacol Ther 2001;69:14-23. PubMed
  6. Pellati F, Benvenuti S, Melegari M, Firenzuoli F. Determination of adrenergic agonists from extracts and herbal products of Citrus aurantium L. var. amara by LC. J Pharm Biomed Anal 2002;29:1113-9. . PubMed
  7. Colker CM, Kalman DS, Torina GC, et al. Effects of Citrus aurantium extract, caffeine, and St. John's wort on body fat loss, lipid levels, and mood states in overweight healthy adults. Curr Ther Res 1999;60:145-153. DOI
  8. Penzak SR, Acosta EP, Turner M, et al. Effect of Seville orange juice and grapefruit juice on indinavir pharmacokinetics. J Clin Pharmacol 2002;42:1165-70. PubMed
  9. Edwards DJ, Fitzsimmons ME, Schuetz EG, et al. 6',7'-Dihydroxybergamottin in grapefruit juice and Seville orange juice: effects on cyclosporine disposition, enterocyte CYP3A4, and P-glycoprotein. Clin Pharmacol Ther 1999;65:237-44. PubMed
  10. Di Marco MP, Edwards DJ, Wainer IW, Ducharme MP. The effect of grapefruit juice and seville orange juice on the pharmacokinetics of dextromethorphan: the role of gut CYP3A and P-glycoprotein. Life Sci 2002;71:1149-60. PubMed
  11. Visentin V, Morin N, Fontana E, et al. Dual action of octopamine on glucose transport into adipocytes: inhibition via beta3-adrenoceptor activation and stimulation via oxidation by amine oxidases. J Pharmacol Exp Ther 2001;299:96-104.
  12. Nykamp DL, Fackih MN, Compton AL. Possible association of acute lateral-wall myocardial infarction and bitter orange supplement. Ann Pharmacother 2004;38:812-6. PubMed
  13. Fugh-Berman A, Myers A. Citrus aurantium, an ingredient of dietary supplements marketed for weight loss: Current status of clinical and basic Research. Exp Biol Med 2004;229:698-704.
  14. Suzuki O, Matsumoto T, Oya M, Katsumata Y. Oxidation of synephrine by type A and type B monoamine oxidase. Experientia 1979;35:1283-4. PubMed
  15. Nasir JM, Durning SJ, Ferguson M, et al. Exercise-induced syncope associated with QT prolongation and ephedra-free Xenadrine. Mayo Clin Proc 2004;79:1059-62.. PubMed
  16. Firenzuoli F, Gori L, Galapai C. Adverse reaction to an adrenergic herbal extract (Citrus aurantium). Phytomedicine 2005;12:247-8. PubMed
  17. Bouchard NC, Howland MA, Greller HA, et al. Ischemic stroke associated with use of an ephedra-free dietary supplement containing synephrine. Mayo Clin Proc 2005;80:541-5. PubMed
  18. Haller CA, Benowitz NL, Jacob P 3rd. Hemodynamic effects of ephedra-free weight-loss supplements in humans. Am J Med 2005;118:998-1003.. PubMed
  19. Bui LT, Nguyen DT, Ambrose PJ. Blood pressure and heart rate effects following a single dose of bitter orange. Ann Pharmacother 2006;40:53-7. PubMed
  20. Min B, Cios D, Kluger J, White CM. Absence of QTc-interval-prolonging or hemodynamic effects of a single dose of bitter-orange extract in healthy subjects. Pharmacotherapy 2005;25:1719-24. PubMed
  21. Gange CA, Madias C, Felix-Getzik EM, et al. Variant angina associated with bitter orange in a dietary supplement. Mayo Clin Proc 2006;81:545-8. PubMed
  22. Jordan S, Murty M, Pilon K. Products containing bitter orange or synephrine: suspected cardiovascular adverse reactions. Canadian Adverse Reaction Newsletter 2004;14:3-4.
  23. Burke J, Seda G, Allen D, Knee TS. A case of severe exercise-induced rhabdomyolysis associated with a weight loss dietary supplement. Mil Med 2007;172:656-8. PubMed
  24. Gray, S. and Woolf, A. D. Citrus aurantium used for weight loss by an adolescent with anorexia nervosa. J Adolesc.Health 2005;37(5):414-415. PubMed
  25. Haller, C. A., Duan, M., Jacob, P., III, and Benowitz, N. Human pharmacology of a performance-enhancing dietary supplement under resting and exercise conditions. Br J Clin Pharmacol 2008;65(6):833-840. PubMed
  26. Thomas, J. E., Munir, J. A., McIntyre, P. Z., and Ferguson, M. A. STEMI in a 24-year-old man after use of a synephrine-containing dietary supplement: a case report and review of the literature. Tex.Heart Inst.J 2009;36(6):586-590.
  27. Campbell-Tofte, J. I., Molgaard, P., Josefsen, K., Abdallah, Z., Hansen, S. H., Cornett, C., Mu, H., Richter, E. A., Petersen, H. W., Norregaard, J. C., and Winther, K. Randomized and double-blinded pilot clinical study of the safety and anti-diabetic ef
  28. Seifert, J. G., Nelson, A., Devonish, J., Burke, E. R., and Stohs, S. J. Effect of acute administration of an herbal preparation on blood pressure and heart rate in humans. Int J Med Sci 2011;8(3):192-197. PubMed
  29. Stohs, S. J., Preuss, H. G., Keith, S. C., Keith, P. L., Miller, H., and Kaats, G. R. Effects of p-synephrine alone and in combination with selected bioflavonoids on resting metabolism, blood pressure, heart rate and self-reported mood changes. Int J Med
  30. Wason, S., DiGiacinto, J. L., and Davis, M. W. Effects of grapefruit and Seville orange juices on the pharmacokinetic properties of colchicine in healthy subjects. Clin Ther 2012;34(10):2161-2173. PubMed
  31. Kaats, G. R., Miller, H., Preuss, H. G., and Stohs, S. J. A 60day double-blind, placebo-controlled safety study involving Citrus aurantium (bitter orange) extract. Food Chem Toxicol. 2013;55:358-362.
  32. Calapai, G., Firenzuoli, F., Saitta, A., Squadrito, F. R., Arlotta, M., Costantino, G., and Inferrera, G. Antiobesity and cardiovascular toxic effects of Citrus aurantium extracts in the rat: a preliminary report. Fitoterapia 12-1-1999;70(6):586-592. DOI
  33. Colker, C., Kalman, D., and Torina, G. Effects of Citrus aurantium extract, caffeine, and St. John's Wort on body fat loss, lipid levels, and mood states in overweight healthy adults. Curr Ther Res 1999;60:145-153. DOI
  34. Shara M, Stohs SJ. Safety evaluation of Bitter orange extract (p-synephrine) in healthy volunteers. J.Amer.Coll.Nutr. 2011;30:358.
  35. Lynch B. Review of the safety of p-synephrine and caffeine. Intertek-Cantox Report, 2013;1-20.
  36. Smith TB, Staub BA, Natarajan GM, et al. Acute myocardial infarction associated with dietary supplements containing 1,3-dimethylamylamine and Citrus aurantium. Tex Heart Inst J 2014;41(1):70-2. PubMed
  37. Shara M, Stohs SJ, Mukattash TL. Cardiovascular safety of oral p-synephrine (bitter orange) in healthy subjects: a randomized placebo-controlled cross-over clinical trial. Phytother Res. 2016;30(5):842-7.
  38. Liu Y, Santillo MF. Cytochrome P450 2D6 and 3A4 enzyme inhibition by amine stimulants in dietary supplements. Drug Test Anal. 2016;8(3-4):307-10. PubMed
  39. Abdelkawy KS, Donia AM, Turner RB, Elbarbry F. Effects of Lemon and Seville Orange Juices on the Pharmacokinetic Properties of Sildenafil in Healthy Subjects. Drugs R D. 2016 Sep;16(3):271-278. PubMed
  40. Gutiérrez-Hellín J, Salinero JJ, Abían-Vicen J, Areces F, Lara B, Gallo C, et al. Acute consumption of p-synephrine does not enhance performance in sprint athletes.J. Appl Physiol Nutr Metab. 2016;41(1):63-9. doi: 10.1139/apnm-2015-0299.
  41. Jung YP, Earnest CP, Koozehchian M, et al. Effects of ingesting a pre-workout dietary supplement with and without synephrine for 8 weeks on training adaptations in resistance-trained males. J Int Soc Sports Nutr. 2017;3;14:1. doi: 10.1186/s12970-016-0158- PubMed
  42. Jung YP, Earnest CP, Koozehchian M, et al. Effects of acute ingestion of a pre-workout dietary supplement with and without synephrine on resting energy expenditure, cognitive function and exercise performance. J Int Soc Sports Nutr. 2017;14:3. doi: 10.118
  43. Vatsavai LK, Kilari EK. Interaction of p-synephrine on the pharmacodynamic and pharmacokinetics of gliclazide in animal models. J Ayurveda Integr Med 2017; S0975-9476(16)30487-9. doi: 10.1016/j.jaim.2017.04.010.
  44. Ratamess NA, Bush JA, Stohs SJ, et al. Acute cardiovascular effects of bitter orange extract (p-synephrine) consumed alone and in combination with caffeine in human subjects: A placebo-controlled, double-blind study. Phytother Res. 2018;32(1):94-102.
  45. Gutiérrez-Hellín J, Ruiz-Moreno C, Del Coso J. Acute p-synephrine ingestion increases whole-body fat oxidation during 1-h of cycling at Fatmax. Eur J Nutr. 2019 Nov 5. PubMed
  46. Karimzadeh Z, Azizzadeh Forouzi M, Tajadini H, Ahmadinejad M, Roy C, Dehghan M. Effects of lavender and Citrus aurantium on pain of conscious intensive care unit patients: a parallel randomized placebo-controlled trial. J Integr Med 2021:S2095-4964(21)000 PubMed
  47. Koncz D, Tóth B, Bahar MA, Roza O, Csupor D. The Safety and Efficacy of Citrus aurantium (Bitter Orange) Extracts and p-Synephrine: A Systematic Review and Meta-Analysis. Nutrients 2022;14(19):4019. PubMed

See these in context on the Bitter Orange monograph →

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

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