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

Daily Pure Pack Healthy Sleep Ingredients & Drug Interactions

by Pure Encapsulations

Other (e.g. Tea Bag) Category: Other Combinations
Most serious interaction: Major
The interaction bottom line Most serious interaction: Major

Daily Pure Pack Healthy Sleep is a dietary supplement by Pure Encapsulations with 10 active ingredients. Its ingredients are commonly taken for trouble falling asleep (insomnia), jet lag, delayed sleep phase syndrome.Based on those ingredients, 1,627 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Melatonin, Chamomile Flower Extract, Valerian root extract. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

HelloPharmacist Scorecard of Daily Pure Pack Healthy Sleep by Pure Encapsulations

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

What’s inside

Full disclosure
Ingredient Transparency · database check
Full

Every active ingredient lists its own amount on the label.

Why this rating?
  • The label discloses an exact amount for 10 of its 10 active ingredients.
  • No proprietary blends here — you can verify the dose of every single component.

Daily Pure Pack Healthy Sleep contains 10 active ingredients designed to support sleep. The formula includes melatonin, which helps regulate sleep-wake cycles; magnesium, which plays a role in relaxation and sleep quality; and Suntheanine (a branded form of the amino acid theanine), which may support calm focus.

The botanical ingredients—chamomile flower extract, lemon balm leaf extract, hops aerial parts extract, passionflower aerial parts extract, and valerian root extract—are traditional herbal sleep and relaxation aids. Vitamin B6 is included as a supporting nutrient, and GABA (gamma-aminobutyric acid) is a neurotransmitter thought to promote relaxation.

The inactive ingredients are cellulose, water, gum arabic, maltodextrin, ascorbyl palmitate, and silica.

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: Supports sleep quality and helps you fall asleep.
  • We looked for evidence on: Anxiety, Beta blocker-induced insomnia, Insomnia, Sleep onset latency, Sleep maintenance.
  • 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: Melatonin is rated "Possibly Effective" for Pre-procedural anxiety, Beta blocker-induced insomnia.

Melatonin is likely effective for non-24-hour sleep-wake disorder and delayed sleep phase syndrome (a condition where your sleep naturally shifts later), and possibly effective for pre-procedural anxiety. Magnesium is effective for constipation and indigestion, and likely or possibly effective for high blood pressure and pregnancy-related complications.

The evidence for the botanical ingredients and other actives is less established. Chamomile, lemon balm, hops, passionflower, and valerian all show insufficient reliable evidence in our data for most of the conditions they're traditionally used for, though passionflower is possibly effective for insomnia and pre-procedural anxiety, and valerian is possibly effective for insomnia.

Suntheanine (theanine) has possibly effective evidence for cognitive function but insufficient evidence for other uses. GABA's effectiveness for any condition is not established in our data.

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 10 of the 10 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 10 of 10.
  • General safety write-ups exist for 10 of 10.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Melatonin is generally well tolerated for short-term use, though long-term safety is less certain and product quality varies. It's possibly unsafe in pregnancy and should be avoided while breastfeeding unless your doctor advises otherwise.

The most common side effects are dizziness, drowsiness, headache, and nausea; rarely, it may increase seizure risk. Magnesium is generally safe at recommended dietary amounts and supplements, with pregnancy and lactation use guided by your doctor.

Common side effects are diarrhea, nausea, and vomiting. Suntheanine is generally well tolerated short-term but long-term safety is not well studied; avoid in pregnancy and breastfeeding due to insufficient data.

Chamomile is generally well tolerated but can trigger allergic reactions in people sensitive to ragweed; avoid in pregnancy unless approved by your doctor. Vitamin B6 is safe at normal amounts, but high doses taken over time can damage nerves (sensory neuropathy).

GABA, lemon balm, hops, passionflower, and valerian all have limited long-term safety data. Lemon balm and hops may cause drowsiness; hops should be avoided in pregnancy and breastfeeding.

Passionflower is possibly unsafe in pregnancy; valerian safety is not established in pregnancy or breastfeeding. All the botanical sedating ingredients can cause drowsiness and should be used cautiously if you operate machinery or drive.

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?
  • 10 of the 10 matched ingredients can interact with medications — Lemon Balm, Gamma-aminobutyric Acid (gaba), Hops, Valerian, Passion Flower, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; seizure medications; immunosuppressants / transplant drugs; diabetes medications; heart-rhythm medications; Parkinson's medications.
  • For scale: 1,628 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.

Before taking this product, double-check with your doctor or pharmacist if you take blood pressure medications (especially nifedipine), blood thinners like warfarin, seizure medications, diabetes drugs, immunosuppressants, levodopa/carbidopa, muscle relaxants, thyroid hormone, birth control, hormone replacement therapy, tamoxifen, or any sedating medications (including sleeping pills, anti-anxiety drugs, pain relievers, or antihistamines). Magnesium and chamomile can also interfere with how your body absorbs or processes other drugs; ask your pharmacist about timing and spacing of doses.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFully disclosed formula with some supporting evidence for its stated purpose. Major medication interactions have been identified, and safety information is well characterized.

This formula is aimed at people looking for natural sleep support, combining a hormone (melatonin) with minerals, amino acids, and traditional herbal ingredients. However, if you take any prescription medications—especially blood pressure drugs, blood thinners, diabetes medications, seizure medications, thyroid replacements, birth control, or sedating drugs—you'll want to check each of your exact medications with your doctor or pharmacist before starting.

The individual ingredients are generally well tolerated short-term, but long-term safety data are limited for many of them, and the product contains multiple ingredients that can increase drowsiness.

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

Assessment coverage: 10 of 10 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Jul 18, 2023.

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 Daily Pure Pack Healthy Sleep, straight from the product label.

Brand Pure Encapsulations
Barcode (UPC) 766298023830
Net contents 30 Pack(s)
Market status On market
Date entered into DSLD Jul 18, 2023
DSLD ID 293951
Product type Other Combinations
Supplement form Other (e.g. Tea Bag)
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years), Gluten Free, Dairy Free
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Daily Pure Pack Healthy Sleep by Pure Encapsulations, 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:
3 Capsule(s)
Maximum serving Sizes:
3 Capsule(s)
Servings per container
30
UPC/BARCODE
766298023830
IngredientAmount% DV
Melatonin1 mg--
Magnesium120 mg29%
Suntheanine50 mg--
Chamomile Flower Extract100 mg--
Vitamin B63.3 mg194%
GABA300 mg--
Lemon Balm Leaf Extract150 mg--
Hops Aerial Parts Extract150 mg--
Passionflower Aerial Parts Extract100 mg--
Valerian root extract400 mg--

Other ingredients: Cellulose, Water, Cellulose, Gum Arabic, Maltodextrin, Ascorbyl Palmitate, Silica

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

Goodness encapsulated Our daily pure packs include some of our best-selling and unique formulations, carefully selected in collaboration with nutritional and medical experts to target specific health needs.

Developed by nutritional and medical experts

Visit PureEncapsulations.com for more information on our GMO policy.

Scan this QR code to learn more about our Daily Pure Packs Pills not shown to actual size.

Contents may not fill package in order to accommodate required labeling. Please rely on stated quantity.

From the premium ingredients that go into each formula to the combination of products found in each pack, we help you address your health from the inside out. #1 most recommended brand by healthcare professionals 1. Among professional supplement brands surveyed. Nutrition Business journal 2016, 2020 This paper box is recyclable

Formulation

Our supplements are made using only premium ingredients backed by verifiable science and sourced from trusted suppliers, and are carefully manufactured to ensure they are free from: Wheat, soy Except where labeled, dairy, eggs Tree nuts & peanuts Gluten Artificial colors, flavors & sweeteners Coating & shellacs GMOs Unnecessary binders, filers & preservatives Trans fats & hydrogenated oil

Supports sleep quality to help you feel rested and refreshed

Support to help you sleep Sweet dreams are made of Zzz's and your nights should be, too. Our specially developed Healthy sleep pack supports falling asleep and promotes the quality of sleep you need to feel rested, refreshed and ready to start your day.

Natural capsule color variations can occur.

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.

FDA Statement of Identity

Dietary Supplement

Formula

Each Packet Contains 2 best-rest formula 1 magnesium (glycinate)

Our Healthy Sleep pack includes. Our best-rest formula containing melatonin, I-theanine, lemon balm, chamomile and other ingredients to promote the onset of sleep as well as sleep quality Magnesium (glycinate) to promote relaxation

Suggested/Recommended/Usage/Directions

Recommendations: As a dietary supplement, take 1 packet daily (3 capsules), 30-60 minutes before bedtime.

Brand IP Statement(s)

Suntheanine is a registered trademark of Taiyo International, Inc.

Storage

Store in a cool, dry place.

Precautions

Warning: consult a healthcare professional if you are experiencing long-term sleep difficulties, before use in children, before use in pregnant or lactating women, those with a medical condition, and those taking medication.

Warning: consult a healthcare professional if you are experiencing long-term sleep difficulties, before use in children, before use in pregnant or lactating women, those with a medical condition, and those taking medication.

Do not drive or operate machinery when taking melatonin. This product may be contraindicated for individuals taking corticosteroids.

Keep out of reach of children.

This product was sealed for your protection. Do not use if box or contents are opened or damaged.

See for yourself

Daily Pure Pack Healthy Sleep by Pure Encapsulations label

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

What’s inside

The Ingredients in Daily Pure Pack Healthy Sleep by Pure Encapsulations

These are the 10 active ingredients this product is made of. Select any to open its full monograph.

Serving size3 Capsule(s) Dosage formOther (e.g. Tea Bag) 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.

Melatonin

Interacts with
1,461 drugs
1 mg per serving

Melatonin is a hormone your body makes naturally to help control your sleep-wake cycle, and the supplement form is widely used to help with sleep timi...

Melatonin monograph & interactions

Magnesium

Interacts with
295 drugs
120 mg per serving Form: Magnesium Glycinate

Magnesium is an essential mineral your body needs for muscles, nerves, blood pressure, and many other functions, and supplements are useful for preven...

Magnesium monograph & interactions

Suntheanine

Interacts with
565 drugs
50 mg per serving Form: L-Theanine

Theanine (usually L-theanine) is an amino acid found naturally in tea leaves that many people take to feel calmer and less stressed without strong dro...

Suntheanine monograph & interactions

Chamomile Flower Extract

Interacts with
960 drugs
100 mg per serving

German chamomile is a widely used herbal remedy taken mainly as a tea for calming, sleep, and digestive complaints. Early research suggests possible b...

Chamomile Flower Extract monograph & interactions

Vitamin B6

Interacts with
210 drugs
3.3 mg per serving Form: Pyridoxal 5-Phosphate

Vitamin B6 (pyridoxine) is an essential water-soluble vitamin that your body needs for metabolism, brain function, and making red blood cells. It is b...

Vitamin B6 monograph & interactions

GABA

Interacts with
419 drugs
300 mg per serving

GABA is a calming chemical messenger (neurotransmitter) that your body makes on its own, and it is sold as a supplement for stress, anxiety, and sleep...

GABA monograph & interactions

Lemon Balm Leaf Extract

Interacts with
264 drugs
150 mg per serving Form: Rosmarinic Acid

Lemon balm is a gentle, lemon-scented mint-family herb traditionally used to ease stress, support sleep, and calm digestion, and topically for cold so...

Lemon Balm Leaf Extract monograph & interactions

Hops Aerial Parts Extract

Interacts with
863 drugs
150 mg per serving

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

Hops Aerial Parts Extract monograph & interactions

Passionflower Aerial Parts Extract

Interacts with
836 drugs
100 mg per serving Form: Vitexins

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 restless...

Passionflower Aerial Parts Extract monograph & interactions

Valerian root extract

Interacts with
902 drugs
400 mg per serving Form: Valerenic Acid

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...

Valerian root extract monograph & interactions

Other (inactive) ingredients: Cellulose, Water, Cellulose, Gum Arabic, Maltodextrin, Ascorbyl Palmitate, Silica. These complete the product’s ingredient list but are not active constituents.

Interaction report

Daily Pure Pack Healthy Sleep by Pure Encapsulations Drug Interactions

Want to check YOUR meds against Daily Pure Pack Healthy Sleep?

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
1,627Drugs
6 Major 1,583 Moderate 38 Minor

Each ingredient & the kinds of drugs it affects

For each ingredient in Daily Pure Pack Healthy Sleep 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.

Melatonin18 drug types · 1,461 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, melatonin may have anticoagulant effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
There are isolated case reports of minor bleeding and decreased prothrombin activity in people taking melatonin with warfarin (Coumadin). The mechanism, if any, of this interaction is unknown. Taking melatonin orally seems to decrease coagulation activity within one hour of dosing in healthy men.

Likelihood Possible Evidence B
Anticonvulsants

Theoretically, melatonin may reduce the effects of anticonvulsants. Some clinical research suggests that melatonin may increase the frequency of seizures in certain patients, particularly children with neurological impairment.

Likelihood Possible Evidence B
Antidiabetes Drugs

Theoretically, taking melatonin with antidiabetes drugs might increase the risk of hypoglycemia.
Some clinical research shows that melatonin reduces levels of fasting blood glucose and improves glycemic control. However, other research suggests that melatonin might impair glucose utilization and increase insulin resistance, while other research has found no effect on glucose levels. Until more is known, use melatonin cautiously in combination with antidiabetes drugs.

Likelihood Possible Evidence B
Antihypertensive Drugs

Theoretically, taking melatonin with antihypertensive drugs might increase the risk of hypotension or hypertension.
Some clinical research suggests that taking melatonin decreases blood pressure in healthy adults. Also, melatonin seems to lower systolic and diastolic blood pressure in individuals with high blood pressure at nighttime or untreated essential hypertension. However, melatonin seems to worsen blood pressure in patients who are taking antihypertensive medications. Immediate-release melatonin 5 mg at night in combination with nifedipine GITS (Procardia XL) increases systolic blood pressure an average of 6.5 mmHg, diastolic blood pressure by an average of 4.9 mmHg, and heart rate by 3.9 bpm. Also, results from animal research suggest that melatonin reduces the effectiveness of certain antihypertensive drugs, including methoxamine and clonidine.

Likelihood Possible Evidence A
Caffeine

Theoretically, taking caffeine with melatonin might increase levels of melatonin.
Some evidence suggests that caffeine consumption can decrease endogenous melatonin levels, while other evidence suggests that caffeine increases endogenous melatonin levels. When administered in combination with melatonin supplements, caffeine seems to increase melatonin effects and levels. The reason for this discrepancy is not completely clear. Part of the discrepancy may result from the fact that caffeine can inhibit melatonin synthesis as well as inhibit melatonin metabolism. By functioning as an adenosine receptor antagonist, caffeine may indirectly inhibit the synthesis of melatonin. Conversely, because melatonin and caffeine are both metabolized by cytochrome P450 1A2 (CYP1A2) enzyme, concomitant use of melatonin and caffeine may reduce the metabolism of melatonin, resulting in higher serum levels.

Likelihood Probable Evidence B
Cns Depressants

Theoretically, taking melatonin might increase the sedative effects of CNS depressants.
Melatonin has sedative effects. Theoretically, concomitant use of melatonin with alcohol, benzodiazepines, or other sedative drugs might cause additive sedation.

Likelihood Possible Evidence D
Contraceptive Drugs

Theoretically, taking contraceptive drugs with melatonin might increase the effects and adverse effects of melatonin.
Contraceptive drugs can increase the levels of endogenous melatonin. Theoretically, these drugs may increase the effects and adverse effects of oral melatonin.

Likelihood Probable Evidence B
Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, melatonin might increase levels of drugs metabolized by CYP1A2. Also, other CYP1A2 substrates might decrease the metabolism of melatonin, increasing melatonin levels.
Melatonin is metabolized in the liver primarily by the CYP2C19 and CYP1A2 enzymes. Theoretically, combined administration of melatonin with drugs metabolized by the CYP1A2 enzyme might reduce the metabolism of these drugs, resulting in increased serum levels. Conversely, some drugs metabolized by CYP1A2 may inhibit the metabolism of melatonin, resulting in increased serum levels of melatonin. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.

Likelihood Probable Evidence D
Cytochrome P450 2C19 (Cyp2C19) Substrates

Theoretically, melatonin might increase levels of drugs metabolized by CYP2C19. Also, other CYP2C19 substrates might decrease the metabolism of melatonin, increasing melatonin levels.
Melatonin is metabolized in the liver primarily by the CYP2C19 and CYP1A2 enzymes. Theoretically, combined administration of melatonin with certain drugs metabolized by the CYP2C19 enzyme may reduce the metabolism of these drugs, resulting in increased serum levels. Conversely, some drugs metabolized by CYP2C19 may inhibit the metabolism of melatonin, resulting in increased serum levels of melatonin. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.

Likelihood Probable Evidence D
Fluvoxamine (Luvox)

Theoretically, taking fluvoxamine with melatonin might increase levels of melatonin.
Fluvoxamine can significantly increase melatonin levels. In some cases, fluvoxamine might increase bioavailability of exogenously administered melatonin by up to 20 times. Some researchers think this might be a beneficial interaction and be potentially useful for cases of refractory insomnia. However, this interaction might also cause unwanted excessive drowsiness and possibly other adverse effects. Fluvoxamine is known to increase endogenous melatonin secretion. It seems to increase serum levels of exogenously administered melatonin possibly by decreasing melatonin metabolism by inhibiting cytochrome P450 (CYP450) 1A2 and 2C19 or by inhibiting melatonin elimination. This effect has been found in healthy people taking fluvoxamine 50-75 mg and melatonin 5 mg.

Likelihood Probable Evidence B
Immunosuppressants

Theoretically, melatonin might interfere with immunosuppressive therapy.
Melatonin can stimulate immune function. Theoretically, melatonin might interfere with immunosuppressive therapy.

Likelihood Possible Evidence B
Methamphetamine (Desoxyn)

Theoretically, taking melatonin with methamphetamine may increase the adverse effects of methamphetamine.
Animal research suggests that melatonin exacerbates the adverse effects of methamphetamine, resulting in greater depression of tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) activity, as well as a significant reduction in dopamine levels. This has not been shown in humans.

Likelihood Possible Evidence D
Nifedipine Gits (Procardia Xl)

Theoretically, taking melatonin with extended release nifedipine reduces the effects of nifedipine.
Melatonin can decrease the effectiveness of extended release nifedipine (GITS). Immediate-release melatonin 5 mg at night in combination with nifedipine GITS 30-60 mg daily increases systolic and blood pressure by an average of 6.5 mmHg and 4.9 mmHg, respectively. Concomitant use with melatonin also increases heart rate by 3.9 bpm. The mechanism of this interaction is not known.

Likelihood Probable Evidence B
Seizure Threshold Lowering Drugs

Theoretically, taking melatonin with drugs that lower the seizure threshold might increase the risk of seizure activity.
Some clinical evidence suggests that melatonin may increase the frequency of seizures in certain patients, particularly children with neurological disabilities.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, melatonin may have antiplatelet effects and may increase the risk of bleeding with warfarin.
Three cases of increased prothrombin time have been reported for patients aged 48-72 years who took melatonin orally in combination with warfarin. However, three cases of decreased prothrombin time have also been reported for patients aged 51-84 years who took melatonin orally in combination with warfarin. Until more is known, use melatonin cautiously in patients taking warfarin.

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

Theoretically, melatonin might increase levels of drugs metabolized by CYP2D6.
Laboratory research suggests that certain lots of melatonin inhibit CYP2D6. Theoretically, combined administration of melatonin with certain drugs metabolized by the CYP2D6 enzyme may reduce the metabolism of these drugs, resulting in increased serum levels. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.

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

Theoretically, melatonin might increase levels of drugs metabolized by CYP3A4.
Laboratory research shows that certain lots of melatonin inhibit CYP3A4. Theoretically, combined administration of melatonin with certain drugs metabolized by CYP3A4 may reduce the metabolism of these drugs, resulting in increased serum levels. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.

Likelihood Possible Evidence D
Flumazenil (Romazicon)

Theoretically, taking flumazenil with melatonin might reduce the effects of melatonin.
Animal research shows that flumazenil may inhibit the effect of melatonin.

Likelihood Possible Evidence D

Chamomile Flower Extract9 drug types · 960 drugs

Cns Depressants

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

Likelihood Possible Evidence D
Contraceptive Drugs

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

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

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

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

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

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

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

Likelihood Possible Evidence D
Estrogens

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

Likelihood Possible Evidence D
Tamoxifen (Nolvadex)

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

Likelihood Possible Evidence D
Warfarin (Coumadin)

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

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

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

Likelihood Possible Evidence D

Valerian root extract6 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

Hops Aerial Parts Extract4 drug types · 863 drugs

Cns Depressants

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

Likelihood Possible Evidence D
Estrogens

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

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

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

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

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

Likelihood Possible Evidence D

Passionflower Aerial Parts Extract3 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

Suntheanine3 drug types · 565 drugs

Antihypertensive Drugs

Theanine might lower blood pressure, potentiating the effects of antihypertensive drugs.
Animal research shows that theanine can lower blood pressure in spontaneously hypertensive animals. Theoretically, concomitant use of theanine and antihypertensive drugs might potentiate the antihypertensive activity.

Likelihood Possible Evidence D
Cns Depressants

Theoretically, theanine might have additive sedative effects when used in conjunction with CNS depressants. However, it is unclear if this concern is clinically relevant.
Theoretically, theanine may compete with glutamate and/or increase plasma gamma-aminobutyric acid (GABA) levels, which could cause CNS depression. In one clinical study, some subjects taking oral theanine reported drowsiness.

Likelihood Unlikely Evidence D
Serotonergic Drugs

Clinical studies regarding the effects of L-theanine on serotonin levels are conflicting. Some studies suggest it can increase serotonin levels in the brain while others report that it may decrease them. Nevertheless, there have been no reports of l-theanine being a causative agent in serotonergic-related side effects or serotonin syndrome.

Likelihood Unlikely Evidence C

GABA2 drug types · 419 drugs

Antihypertensive Drugs

Theoretically, taking GABA with antihypertensive drugs might increase the risk of hypotension.
Some clinical research shows that GABA can decrease blood pressure in patients with hypertension.

Likelihood Possible Evidence B
Cns Depressants

Theoretically, GABA might have additive sedative effects when used in conjunction with CNS depressants. However, it is unclear if this concern is clinically relevant.
Endogenous GABA has well-established relaxant effects and GABA(A) receptors have an established physiological role in sleep. However, the effects of GABA supplements are unclear, as it is unknown whether exogenous GABA crosses the blood-brain barrier. Although there have been limited reports of drowsiness or tiredness with GABA supplements, these effects have not been widely reported in clinical studies. Additionally, intravenous GABA 0.1-1 mg/kg has been shown to induce anxiety in a dose-dependent manner.

Likelihood Unlikely Evidence D

Magnesium15 drug types · 295 drugs

Levodopa/Carbidopa (Sinemet)

Magnesium can reduce the bioavailability of levodopa/carbidopa.
Clinical research in healthy volunteers shows that taking magnesium oxide 1000 mg with levodopa 100 mg/carbidopa 10 mg reduces the area under the curve (AUC) of levodopa by 35% and of carbidopa by 81%. In vitro and animal research shows that magnesium produces an alkaline environment in the digestive tract, which might lead to degradation and reduced bioavailability of levodopa/carbidopa.

Likelihood Probable Evidence B
Aminoglycoside Antibiotics

Concomitant use of aminoglycoside antibiotics and magnesium can increase the risk for neuromuscular weakness.
Both aminoglycosides and magnesium reduce presynaptic acetylcholine release, which can lead to neuromuscular blockade and possible paralysis. This is most likely to occur with high doses of magnesium given intravenously.

Likelihood Possible Evidence D
Antacids

Use of acid reducers may reduce the laxative effect of magnesium oxide.
A retrospective analysis shows that, in the presence of H2 receptor antagonists (H2RAs) or proton pump inhibitors (PPIs), a higher dose of magnesium oxide is needed for a laxative effect. This may also occur with antacids. Under acidic conditions, magnesium oxide is converted to magnesium chloride and then to magnesium bicarbonate, which has an osmotic laxative effect. By reducing acidity, antacids may reduce the conversion of magnesium oxide to the active bicarbonate salt.

Likelihood Possible Evidence D
Bictegravir/Emtricitabine/Tenofovir Alafenamide (Biktarvy)

Magnesium might decrease levels of bictegravir/emtricitabine/tenofovir alafenamide by reducing its absorption.
Advise patients that bictegravir/emtricitabine/tenofovir alafenamide should be taken at least 2 hours before or 6 hours after magnesium containing products.

Likelihood Probable Evidence D
Bisphosphonates

Magnesium can decrease absorption of bisphosphonates.
Cations, including magnesium, can decrease bisphosphonate absorption. Advise patients to separate doses of magnesium and these drugs by at least 2 hours.

Likelihood Probable Evidence B
Calcium Channel Blockers

Magnesium can have additive effects with calcium channel blockers, although evidence is conflicting.
Magnesium inhibits calcium entry into smooth muscle cells and may therefore have additive effects with calcium channel blockers. Severe hypotension and neuromuscular blockades may occur when nifedipine is used with intravenous magnesium, although some contradictory evidence suggests that concurrent use of magnesium with nifedipine does not increase the risk of neuromuscular weakness. High doses of magnesium could theoretically have additive effects with other calcium channel blockers.

Likelihood Possible Evidence D
Digoxin

Magnesium salts may reduce absorption of digoxin.
Clinical evidence suggests that treatment with oral magnesium hydroxide or magnesium trisilicate reduces absorption of digoxin from the intestines. This may reduce the blood levels of digoxin and decrease its therapeutic effects.

Likelihood Possible Evidence B
Potassium-Sparing Diuretics

Potassium-sparing diuretics decrease excretion of magnesium, possibly increasing magnesium levels.
Potassium-sparing diuretics also have magnesium-sparing properties, which can counteract the magnesium losses associated with loop and thiazide diuretics. Theoretically, increased magnesium levels could result from concomitant use of potassium-sparing diuretics and magnesium supplements.

Likelihood Probable Evidence D
Quinolone Antibiotics

Magnesium decreases absorption of quinolones.
Magnesium can form insoluble complexes with quinolones and decrease their absorption. Advise patients to take these drugs at least 2 hours before, or 4 to 6 hours after, magnesium supplements.

Likelihood Probable Evidence D
Skeletal Muscle Relaxants

Parenteral magnesium alters the pharmacokinetics of skeletal muscle relaxants, increasing their effects and accelerating the onset of effect.
Parenteral magnesium shortens the time to onset of skeletal muscle relaxants by about 1 minute and prolongs the duration of action by about 2 minutes. Magnesium potentiates the effects of skeletal muscle relaxants by decreasing calcium-mediated release of acetylcholine from presynaptic nerve terminals, reducing postsynaptic sensitivity to acetylcholine, and having a direct effect on the membrane potential of myocytes. Magnesium also has vasodilatory actions and increases cardiac output, allowing a greater amount of muscle relaxant to reach the motor end plate. A clinical study found that low-dose rocuronium (0.45 mg/kg), when given after administration of magnesium 30 mg/kg over 10 minutes, has an accelerated onset of effect, which matches the onset of effect seen with a full-dose rocuronium regimen (0.6 mg/kg). In another clinical study, onset times for rocuronium doses of 0.3, 0.6, and 1.2 mg/kg were 86, 76, and 50 seconds, respectively, when given alone, but were reduced to 66, 44, and 38 seconds, respectively, when the doses were given after a 15-minute infusion of magnesium sulfate 60 mg/kg. Giving intraoperative intravenous magnesium sulfate, 50 mg/kg loading dose followed by 15 mg/kg/hour, reduces the onset time of rocuronium, enhances its clinical effects, reduces the dose of intraoperative opiates, and prolongs the spontaneous recovery time. It does not affect the activity of subsequently administered neostigmine.

Likelihood Probable Evidence A
Sulfonylureas

Magnesium increases the systemic absorption of sulfonylureas, increasing their effects and side effects.
Clinical research shows that administration of magnesium hydroxide with glyburide increases glyburide absorption, increases maximal insulin response by 35-fold, and increases the risk of hypoglycemia, when compared with glyburide alone. A similar interaction occurs between magnesium hydroxide and glipizide. The mechanism of this effect appears to be related to the elevation of gastrointestinal pH by magnesium-based antacids, increasing solubility and enhancing absorption of sulfonylureas.

Likelihood Probable Evidence B
Tetracycline Antibiotics

Magnesium decreases absorption of tetracyclines.
Magnesium can form insoluble complexes with tetracyclines in the gut and decrease their absorption and antibacterial activity. Advise patients to take these drugs 1 hour before or 2 hours after magnesium supplements.

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, magnesium may have antiplatelet effects, but the evidence is conflicting.
In vitro evidence shows that magnesium sulfate inhibits platelet aggregation, even at low concentrations. Some preliminary clinical evidence shows that infusion of magnesium sulfate increases bleeding time by 48% and reduces platelet activity. However, other clinical research shows that magnesium does not affect platelet aggregation, although inhibition of platelet-dependent thrombosis can occur.

Likelihood Unlikely Evidence B
Gabapentin (Neurontin)

Gabapentin absorption can be decreased by magnesium.
Clinical research shows that giving magnesium oxide orally along with gabapentin decreases the maximum plasma concentration of gabapentin by 33%, time to maximum concentration by 36%, and area under the curve by 43%. Advise patients to take gabapentin at least 2 hours before, or 4 to 6 hours after, magnesium supplements.

Likelihood Unlikely Evidence B
Sevelamer (Renagel, Renvela)

Sevelamer may increase serum magnesium levels.
In patients on hemodialysis, sevelamer use was associated with a 0.28 mg/dL increase in serum magnesium. The mechanism of this interaction remains unclear.

Likelihood Possible Evidence B

Lemon Balm Leaf Extract2 drug types · 264 drugs

Cns Depressants

Theoretically, concomitant use of lemon balm might have additive effects with CNS depressant drugs.
Lemon balm seems to have CNS depressant activity in animals and in humans.

Likelihood Possible Evidence B
Thyroid Hormone

Theoretically, lemon balm might interfere with thyroid hormone replacement therapy.
In vitro, constituents of lemon balm extract bind to thyroid stimulating hormone (TSH), preventing TSH receptor-binding and leading to the inhibition of TSH-stimulated adenylate cyclase activity. In animals, lemon balm extract has been shown to decrease levels of circulating TSH and inhibit thyroid secretion.

Likelihood Possible Evidence D

Vitamin B65 drug types · 210 drugs

Amiodarone (Cordarone)

Theoretically, vitamin B6 might increase the photosensitivity caused by amiodarone.
Despite initial case reports suggesting that pyridoxine may have a protective effect against amiodarone-induced photosensitivity, preliminary clinical research suggests that pyridoxine may actually exacerbate this adverse effect.

Likelihood Possible Evidence B
Antihypertensive Drugs

Theoretically, vitamin B6 may have additive effects when used with antihypertensive drugs.
Research in hypertensive rats shows that vitamin B6 can decrease systolic blood pressure. Similarly, clinical research in patients with hypertension shows that taking high doses of vitamin B6 may reduce systolic and diastolic blood pressure, possibly by reducing plasma levels of epinephrine and norepinephrine.

Likelihood Possible Evidence B
Phenobarbital (Luminal)

High doses of vitamin B6 may reduce the levels and clinical effects of phenobarbital.
Preliminary clinical evidence suggests that vitamin B6 200 mg daily can reduce plasma levels of phenobarbital, possibly by increasing metabolism. It is not known whether lower doses have any effect. Advise people taking phenobarbital to avoid high doses of vitamin B6.

Likelihood Possible Evidence D
Phenytoin (Dilantin)

High doses of vitamin B6 may reduce the levels and clinical effects of phenytoin.
Preliminary clinical evidence suggests that vitamin B6 200 mg daily can reduce plasma levels of phenytoin, possibly by increasing metabolism. It is not known whether lower doses have any effect. Advise people taking phenytoin to avoid high doses of vitamin B6.

Likelihood Possible Evidence D
Levodopa

Vitamin B6 may increase the metabolism of levodopa when taken alone, but not when taken in conjunction with carbidopa.
Vitamin B6 (pyridoxine) enhances the metabolism of levodopa, reducing its clinical effects. However, this interaction does not occur when carbidopa is used concurrently with levodopa (Sinemet). Therefore, it is not likely to be a problem in most people.

Likelihood Unlikely Evidence D
The maker

Brand information

Manufacturer and brand details for Daily Pure Pack Healthy Sleep, from the product label.

Pure Encapsulations

See all Pure Encapsulations products
Name
Pure Encapsulations
Street Address
490 Boston Post Road
City
Sudbury
State
MA
ZipCode
01776
Phone Number
800.753.2277
Web Address
PureEncapsulations.com
Pharmacist Counseling Corner

Daily Pure Pack Healthy Sleep by Pure Encapsulations: Common Questions

Does Daily Pure Pack Healthy Sleep by Pure Encapsulations interact with any medications?
Yes. Based on its ingredients, Daily Pure Pack Healthy Sleep has a known interaction with 1,627 medications, including 6 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Daily Pure Pack Healthy Sleep contains 10 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 while pregnant?
The safety data vary by ingredient. Melatonin is possibly unsafe in pregnancy, and chamomile, suntheanine, lemon balm, hops, passionflower, and valerian all lack enough safety information, so pregnancy use is not advised unless your doctor approves. Magnesium and vitamin B6 are handled differently—magnesium is needed in pregnancy but use supplements only under your doctor's guidance, and vitamin B6 is likely safe at recommended levels for morning sickness under medical supervision. Talk with your doctor before taking this product if you're pregnant or planning to become pregnant.
Can I take this while breastfeeding?
Melatonin safety while breastfeeding has not been established and should be avoided unless your doctor directs otherwise. Suntheanine, lemon balm, hops, passionflower, valerian, and GABA also lack enough safety data for breastfeeding. Magnesium is okay at normal dietary amounts, but check with your doctor before using supplements. Vitamin B6 at normal amounts is generally considered fine, but avoid high doses. Speak with your doctor or pharmacist for personalized advice based on your situation.
Will this make me drowsy during the day?
Yes, drowsiness is possible. Melatonin, chamomile, lemon balm, hops, passionflower, and valerian all commonly cause drowsiness, especially when first starting. If you operate machinery, drive, or need to stay alert during the day, start with a low dose in the evening and see how you respond. Avoid alcohol and other sedating drugs while taking this product, as the effects can add up.
Can I take this with other sleep aids or anxiety medications?
No—not without checking with your doctor first. Multiple ingredients in this product (melatonin, theanine, chamomile, lemon balm, hops, passionflower, valerian, and GABA) can increase drowsiness and have documented interactions with sedating medications like benzodiazepines, sleep aids, and some antidepressants. Adding this to other sedating drugs could cause excessive drowsiness or other effects. Ask your pharmacist or doctor whether it's safe to combine.
Does this product really help with sleep?
Melatonin is likely effective for certain sleep disorders—specifically non-24-hour sleep-wake disorder and delayed sleep phase syndrome. Passionflower and valerian are possibly effective for insomnia. However, the evidence for the other ingredients in this formula (chamomile, lemon balm, hops, theanine, GABA, and magnesium) for sleep is not well established in our data. The product may still help you personally, but the scientific support varies by ingredient.
What are the most common side effects?
From melatonin: dizziness, drowsiness, headache, and nausea. From magnesium: diarrhea, nausea, and vomiting. From the herbal ingredients: drowsiness, dizziness, and mild gastrointestinal upset. Most people tolerate this product well short-term, but side effects can vary. If you experience persistent nausea, diarrhea, or unusual mood changes, stop taking it and talk to your pharmacist.

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

Not sure if Daily Pure Pack Healthy Sleep 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.

Daily Pure Pack Healthy Sleep label
Go deeper

The Full Monographs Behind Daily Pure Pack Healthy Sleep’s Ingredients

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

Herb & supplement monograph

Melatonin

Interacts with 1,461 drugs

Melatonin is a hormone your body makes naturally to help control your sleep-wake cycle, and the supplement form is widely used to help with sleep timing problems and jet lag. The evidence is...

Read the full Melatonin monograph →
Herb & supplement monograph

Magnesium

Interacts with 295 drugs

Magnesium is an essential mineral your body needs for muscles, nerves, blood pressure, and many other functions, and supplements are useful for preventing or correcting deficiency. Some othe...

Read the full Magnesium monograph →
Herb & supplement monograph

Theanine

Interacts with 565 drugs

Theanine (usually L-theanine) is an amino acid found naturally in tea leaves that many people take to feel calmer and less stressed without strong drowsiness. Early research suggests it may...

Read the full Theanine monograph →
Herb & supplement monograph

German Chamomile

Interacts with 960 drugs

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

Read the full German Chamomile monograph →
Herb & supplement monograph

Vitamin B6

Interacts with 210 drugs

Vitamin B6 (pyridoxine) is an essential water-soluble vitamin that your body needs for metabolism, brain function, and making red blood cells. It is best known for helping with pregnancy-rel...

Read the full Vitamin B6 monograph →
Herb & supplement monograph

Gamma-aminobutyric Acid (gaba)

Interacts with 419 drugs

GABA is a calming chemical messenger (neurotransmitter) that your body makes on its own, and it is sold as a supplement for stress, anxiety, and sleep. The science behind oral GABA supplemen...

Read the full Gamma-aminobutyric Acid (gaba) monograph →
Herb & supplement monograph

Lemon Balm

Interacts with 264 drugs

Lemon balm is a gentle, lemon-scented mint-family herb traditionally used to ease stress, support sleep, and calm digestion, and topically for cold sores. Early studies are promising but gen...

Read the full Lemon Balm monograph →
Herb & supplement monograph

Hops

Interacts with 863 drugs

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

Read the full Hops monograph →
Herb & supplement monograph

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

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 →
Sources

Sources & How We Checked

Daily Pure Pack Healthy Sleep'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 348 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.

Melatonin 118 references
  1. Voordouw BC, Euser R, Verdonk RE, et al. Melatonin and melatonin-progestin combinations alter pituitary-ovarian function in women and can inhibit ovulation. J Clin Endocrinol Metab 1992;74:108-17. DOI
  2. Ellis CM, Lemmens G, Parkes JD. Melatonin and insomnia. J Sleep Res 1996;5:61-5. PubMed
  3. Petrie K, Dawson AG, Thompson L, Brook R. A double-blind trial of melatonin as a treatment for jet lag in international cabin crew. Biol Psychiatr 1993;33:526-30. PubMed
  4. Claustrat B, Brun J, David M, et al. Melatonin and jet lag: confirmatory result using a simplified protocol. Biol Psychiatr 1992;32:705-11.
  5. Fauteck J, Schmidt H, Lerchl A, et al. Melatonin in epilepsy: first results of replacement therapy and first clinical results. Biol Signals Recept 1999;8:105-10. PubMed
  6. Arangino S, Cagnacci A, Angiolucci M, et al. Effects of melatonin on vascular reactivity, catecholamine levels, and blood pressure in healthy men. Am J Cardiol 1999;83:1417-9. PubMed
  7. Pierce A. The American Pharmaceutical Association Practical Guide to Natural Medicines. New York: The Stonesong Press, 1999:19.
  8. Lancioni GE, O'Reilly MF, Basili G. Review of strategies for treating sleep problems in persons with severe or profound mental retardation or multiple handicaps. Am J Ment Retard 1999;104:170-86. PubMed
  9. Carman JS, Post RM, Buswell R, et al. Negative effects of melatonin on depression. Am J Psychiatry 1976;133:1181-1186. PubMed
  10. Hartter S, Grozinger M, Weigmann H, et al. Increased bioavailability of oral melatonin after fluvoxamine coadministration. Clin Pharmacol Ther 2000;67:1-6.
  11. Fetrow CW, Avila JR. Professional's Handbook of Complementary & Alternative Medicines. 1st ed. Springhouse, PA: Springhouse Corp., 1999.
  12. Lusardi P, et al. Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study. Br J Clin Pharmacol 2000;49:423-7. PubMed
  13. von Bahr C, Ursing C, Yasui N, et al. Fluvoxamine but not citalopram increases serum melatonin in healthy subjects – an indication that cytochrome P450 CYP1A2 and CYP2C19 hydroxylate melatonin. Eur J Clin Pharmacol 2000;56:123-7.
  14. Grozinger M, Hartter S, Wang X, et al. Fluvoxamine strongly inhibits melatonin metabolism in a patient with low-amplitude melatonin profile. Arch Gen Psychiatry 2000 Aug;57:812-3. PubMed
  15. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solic tumor patients with poor clinical status. Eur J Cancer 1999;35:1688-92.
  16. Sheldon SH. Pro-convulsant effects of oral melatonin in neurologically disabled children. Lancet 1998;351:1254. PubMed
  17. Hartter S, Grozinger M, Weigmann H, et al. Increased bioavailability of oral melatonin after fluvoxamine coadministration. Clin Pharmacol Ther 2000;67:1-6.
  18. Wright KP Jr, Myers BL, Plenzler SC, et al. Acute effects of bright light and caffeine on nighttime melatonin and temperature levels in women taking and not taking oral contraceptives. Brain Res 2000;873:310-7.
  19. Herxheimer A, Petrie KJ. Melatonin for preventing and treating jet lag. Cochrane Database Syst Rev 2001;(1):CD001520.
  20. Briggs, Freeman, Yafee. Update Drugs in Pregnancy and Lactation. Lippincott Williams & Wilkins, 2001.
  21. Suhner A, Schlagenhauf P, Johnson R, et al. Comparative study to determine the optimal melatonin dosage form for the alleviation of jet lag. Chronobiol Int 1998;15:655-66. PubMed
  22. Herxheimer A, Petrie KJ. Melatonin for the prevention and treatment of jet lag. Cochrane Database Syst Rev 2002;2:CD001520. PubMed
  23. Munoz-Hoyos A, Sanchez-Forte M, Molina-Carballo A, et al. Melatonin's role as an anticonvulsant and neuronal protector: experimental and clinical evidence. J Child Neurol 1998;13:501-9.. PubMed
  24. Sandyk R, Tsagas N, Anninos PA. Melatonin as a proconvulsive hormone in humans. Int J Neurosci 1992;63:125-35.. PubMed
  25. Golombek DA, Escolar E, Burin LJ, et al. Chronopharmacology of melatonin: inhibition by benzodiazepine antagonism. Chronobiol Int 1992;9:124-31.. PubMed
  26. Smits MG, Nagtegaal EE, van der Heijden J, et al. Melatonin for chronic sleep onset insomnia in children: a randomized placebo-controlled trial. J Child Neurol 2001;16:86-92.. PubMed
  27. Cagnacci A, Arangino S, Renzi A, et al. Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women. Clin Endocrinol (Oxf) 2001;54:339-46.. PubMed
  28. Williamson BL, Tomlinson AJ, Naylor S, Gleich GJ. Contaminants in commercial preparations of melatonin. Mayo Clin Proc 1997;72:1094-5. PubMed
  29. Williamson BL, Tomlinson AJ, Mishra PK, et al. Structural characterization of contaminants found in commercial preparations of melatonin: similarities to case-related compounds from L-tryptophan associated with eosinophilia-myalgia syndrome. Chem Res To
  30. Stewart LS. Endogenous melatonin and epileptogenesis: facts and hypothesis. Int J Neurosci 2001;107:77-85.. PubMed
  31. Molina-Carballo A, Munoz-Hoyos A, Reiter RJ, et al. Utility of high doses of melatonin as adjunctive anticonvulsant therapy in a child with severe myoclonic epilepsy: two years' experience. J Pineal Res 1997;23:97-105.. PubMed
  32. Tjon Pian Gi CV, Broeren JP, Starreveld JS, A Versteegh FG. Melatonin for treatment of sleeping disorders in children with attention deficit/hyperactivity disorder: a preliminary open label study. Eur J Pediatr 2003;162:554-5. PubMed
  33. Secreto G, Chiechi LM, Amadori A, et al. Soy isoflavones and melatonin for the relief of climacteric symptoms: a multicenter, double-blind, randomized study. Maturitas 2004;47:11-20. PubMed
  34. Weiss MD, Wasdell MB, Bomben MM, et al. Sleep hygiene and melatonin treatment for children and adolescents with ADHD and initial insomnia. J Am Acad Child Adolesc Psychiatry 2006;45:512-9. DOI
  35. Saha L, Malhotra S, Rana S, et al. A preliminary study of melatonin in irritable bowel syndrome. J Clin Gastroenterol 2007;41:29-32. PubMed
  36. Hussain, SA, Khadim, HM, Khalaf, BH, et al. Effects of melatonin and zinc on glycemic control in type 2 diabetic patients poorly controlled with metformin. Saudi Med J 2006;27:1483-8. DOI
  37. Kadhim, HM, Ismail, SH, Hussein, KI, et al. Effects of melatonin and zinc on lipid profile and renal function in type 2 diabetic patients poorly controlled with metformin. J Pineal Res 2006;41:189-93. PubMed
  38. Mutluay R. Elbeg S. Karakus R. et al. The Impact of Melatonin on Glucose Homeostasis. Turkish Journal of Endocrinology and Metabolism 2009;13:52-55.
  39. Wright KP Jr, Badia P, Myers BL, et al. Caffeine and light effects on nighttime melatonin and temperature levels in sleep-deprived humans. Brain Res. 1997;747(1):78-84. PubMed
  40. Peuhkuri K, Sihvola N, Korpela R. Dietary factors and fluctuating levels of melatonin. Food Nutr Res. 2012;56. doi: 10.3402/fnr.v56i0.17252. Epub 2012 Jul 20. PubMed
  41. Gibb JW, Bush L, Hanson GR. Exacerbation of methamphetamine-induced neurochemical deficits by melatonin. J Pharmacol Exp Ther. 1997;283(2):630-5. DOI
  42. Sunami E, Usuda K, Nishiyama Y, et al. A preliminary study of fluvoxamine maleate on depressive state and serum melatonin levels in patients after cerebral infarction. Intern Med. 2012;51(10):1187-93. PubMed
  43. Babkoff, H., French, J., Whitmore, J., and Sutherlin, R. Single-dose bright light and/or caffeine effect on nocturnal performance. Aviat.Space Environ.Med. 2002;73(4):341-350.
  44. Rossignol, D. A. Novel and emerging treatments for autism spectrum disorders: a systematic review. Ann.Clin Psychiatry 2009;21(4):213-236. DOI
  45. Yeleswaram, K., Vachharajani, N., and Santone, K. Involvement of cytochrome P-450 isozymes in melatonin metabolism and clinical implications. J Pineal Res 1999;26(3):190-191. PubMed
  46. Jan, J. E., Connolly, M. B., Hamilton, D., Freeman, R. D., and Laudon, M. Melatonin treatment of non-epileptic myoclonus in children. Dev.Med Child Neurol. 1999;41(4):255-259. PubMed
  47. Edwards, B. J., Atkinson, G., Waterhouse, J., Reilly, T., Godfrey, R., and Budgett, R. Use of melatonin in recovery from jet-lag following an eastward flight across 10 time-zones. Ergonomics 2000;43(10):1501-1513. PubMed
  48. Cagnacci, A., Arangino, S., Angiolucci, M., Melis, G. B., Facchinetti, F., Malmusi, S., and Volpe, A. Effect of exogenous melatonin on vascular reactivity and nitric oxide in postmenopausal women: role of hormone replacement therapy. Clin Endocrinol (Oxf PubMed
  49. Wakatsuki, A., Okatani, Y., Ikenoue, N., Kaneda, C., and Fukaya, T. Effects of short-term melatonin administration on lipoprotein metabolism in normolipidemic postmenopausal women. Maturitas 4-20-2001;38(2):171-177. PubMed
  50. Kitajima, T., Kanbayashi, T., Saitoh, Y., Ogawa, Y., Sugiyama, T., Kaneko, Y., Sasaki, Y., Aizawa, R., and Shimisu, T. The effects of oral melatonin on the autonomic function in healthy subjects. Psychiatry Clin Neurosci. 2001;55(3):299-300. PubMed
  51. Calvo, J. R., Guerrero, J. M., Osuna, C., Molinero, P., and Carrillo-Vico, A. Melatonin triggers Crohn's disease symptoms. J Pineal Res 2002;32(4):277-278. PubMed
  52. Luboshitzky, R., Shen-Orr, Z., Nave, R., Lavi, S., and Lavie, P. Melatonin administration alters semen quality in healthy men. J Androl 2002;23(4):572-578. DOI
  53. Rufo-Campos, M. [Melatonin and epilepsy]. Rev Neurol. 2002;35 Suppl 1:S51-S58.
  54. Ursing, C., Wikner, J., Brismar, K., and Rojdmark, S. Caffeine raises the serum melatonin level in healthy subjects: an indication of melatonin metabolism by cytochrome P450(CYP)1A2. J.Endocrinol.Invest 2003;26(5):403-406. PubMed
  55. Smits, M. G., van Stel, H. F., van der, Heijden K., Meijer, A. M., Coenen, A. M., and Kerkhof, G. A. Melatonin improves health status and sleep in children with idiopathic chronic sleep-onset insomnia: a randomized placebo-controlled trial. J Am Acad.Chi PubMed
  56. Boeve, B. F., Silber, M. H., and Ferman, T. J. Melatonin for treatment of REM sleep behavior disorder in neurologic disorders: results in 14 patients. Sleep Med. 2003;4(4):281-284. PubMed
  57. Hartter, S., Nordmark, A., Rose, D. M., Bertilsson, L., Tybring, G., and Laine, K. Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity. Br.J.Clin.Pharmacol. 2003;56(6):679-682. PubMed
  58. Scheer, F. A., Van Montfrans, G. A., van Someren, E. J., Mairuhu, G., and Buijs, R. M. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension 2004;43(2):192-197. PubMed
  59. Buscemi, N., Vandermeer, B., Pandya, R., Hooton, N., Tjosvold, L., Hartling, L., Baker, G., Vohra, S., and Klassen, T. Melatonin for treatment of sleep disorders. Evid.Rep.Technol.Assess.(Summ.) 2004;(108):1-7.
  60. Cavallo, A., Ris, M. D., Succop, P., and Jaskiewicz, J. Melatonin treatment of pediatric residents for adaptation to night shift work. Ambul.Pediatr. 2005;5(3):172-177. PubMed
  61. Faber, M. S., Jetter, A., and Fuhr, U. Assessment of CYP1A2 activity in clinical practice: why, how, and when? Basic Clin Pharmacol Toxicol. 2005;97(3):125-134. PubMed
  62. Cagnacci, A., Cannoletta, M., Renzi, A., Baldassari, F., Arangino, S., and Volpe, A. Prolonged melatonin administration decreases nocturnal blood pressure in women. Am J Hypertens. 2005;18(12 Pt 1):1614-1618. PubMed
  63. Weekley, L. B. Melatonin-induced relaxation of rat aorta: interaction with adrenergic agonists. J Pineal Res 1991;11(1):28-34. PubMed
  64. Grossman, E., Laudon, M., Yalcin, R., Zengil, H., Peleg, E., Sharabi, Y., Kamari, Y., Shen-Orr, Z., and Zisapel, N. Melatonin reduces night blood pressure in patients with nocturnal hypertension. Am J Med 2006;119(10):898-902. PubMed
  65. van der Heijden, K. B., Smits, M. G., van Someren, E. J., Ridderinkhof, K. R., and Gunning, W. B. Effect of melatonin on sleep, behavior, and cognition in ADHD and chronic sleep-onset insomnia. J Am Acad.Child Adolesc.Psychiatry 2007;46(2):233-241. PubMed
  66. Klupinska, G., Poplawski, T., Drzewoski, J., Harasiuk, A., Reiter, R. J., Blasiak, J., and Chojnacki, J. Therapeutic effect of melatonin in patients with functional dyspepsia. J.Clin.Gastroenterol. 2007;41(3):270-274. PubMed
  67. Bjorvatn, B., Stangenes, K., Oyane, N., Forberg, K., Lowden, A., Holsten, F., and Akerstedt, T. Randomized placebo-controlled field study of the effects of bright light and melatonin in adaptation to night work. Scand.J Work Environ.Health 2007;33(3):204 PubMed
  68. Wirtz, P. H., Spillmann, M., Bartschi, C., Ehlert, U., and von Kanel, R. Oral melatonin reduces blood coagulation activity: a placebo-controlled study in healthy young men. J Pineal Res 2008;44(2):127-133. PubMed
  69. Bendz, L. M. and Scates, A. C. Melatonin treatment for insomnia in pediatric patients with attention-deficit/hyperactivity disorder. Ann.Pharmacother. 2010;44(1):185-191. PubMed
  70. Elkhayat, H. A., Hassanein, S. M., Tomoum, H. Y., Abd-Elhamid, I. A., Asaad, T., and Elwakkad, A. S. Melatonin and sleep-related problems in children with intractable epilepsy. Pediatr.Neurol. 2010;42(4):249-254. PubMed
  71. van Geijlswijk, I. M., van der Heijden, K. B., Egberts, A. C., Korzilius, H. P., and Smits, M. G. Dose finding of melatonin for chronic idiopathic childhood sleep onset insomnia: an RCT. Psychopharmacology (Berl) 2010;212(3):379-391. PubMed
  72. Wade AG, Ford I, Crawford G, et al. Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety. BMC Med 2010;8:51. PubMed
  73. Al-Aama, T., Brymer, C., Gutmanis, I., Woolmore-Goodwin, S. M., Esbaugh, J., and Dasgupta, M. Melatonin decreases delirium in elderly patients: a randomized, placebo-controlled trial. Int.J.Geriatr.Psychiatry 2011;26(7):687-694. PubMed
  74. Alstadhaug, K. B., Odeh, F., Salvesen, R., and Bekkelund, S. I. Prophylaxis of migraine with melatonin: a randomized controlled trial. Neurology 10-26-2010;75(17):1527-1532. PubMed
  75. Wade, A. G., Crawford, G., Ford, I., McConnachie, A., Nir, T., Laudon, M., and Zisapel, N. Prolonged release melatonin in the treatment of primary insomnia: evaluation of the age cut-off for short- and long-term response. Curr.Med.Res.Opin. 2011;27(1):87 PubMed
  76. van Geijlswijk, I. M., Korzilius, H. P., and Smits, M. G. The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis. Sleep 2010;33(12):1605-1614. PubMed
  77. Guenole, F., Godbout, R., Nicolas, A., Franco, P., Claustrat, B., and Baleyte, J. M. Melatonin for disordered sleep in individuals with autism spectrum disorders: systematic review and discussion. Sleep Med.Rev. 2011;15(6):379-387. PubMed
  78. Rossignol, D. A. and Frye, R. E. Melatonin in autism spectrum disorders: a systematic review and meta-analysis. Dev.Med.Child Neurol. 2011;53(9):783-792. PubMed
  79. Eryilmaz, O. G., Devran, A., Sarikaya, E., Aksakal, F. N., Mollamahmutoglu, L., and Cicek, N. Melatonin improves the oocyte and the embryo in IVF patients with sleep disturbances, but does not improve the sleeping problems. J.Assist.Reprod.Genet. 2011;28 PubMed
  80. Batioglu, A. S., Sahin, U., Gurlek, B., Ozturk, N., and Unsal, E. The efficacy of melatonin administration on oocyte quality. Gynecol.Endocrinol. 2012;28(2):91-93.
  81. Grossman, E., Laudon, M., and Zisapel, N. Effect of melatonin on nocturnal blood pressure: meta-analysis of randomized controlled trials. Vasc.Health Risk Manag. 2011;7:577-584. PubMed
  82. Nickelsen, T., Demisch, L., Demisch, K., Radermacher, B., and Schoffling, K. Influence of subchronic intake of melatonin at various times of the day on fatigue and hormonal levels: a placebo-controlled, double-blind trial. J Pineal Res 1989;6(4):325-334. PubMed
  83. Wright, J., Aldhous, M., Franey, C., English, J., and Arendt, J. The effects of exogenous melatonin on endocrine function in man. Clin Endocrinol (Oxf) 1986;24(4):375-382. PubMed
  84. Papavasiliou, P. S., Cotzias, G. C., Duby, S. E., Steck, A. J., Bell, M., and Lawrence, W. H. Melatonin and parkinsonism. JAMA 7-3-1972;221(1):88-89. DOI
  85. Middleton, B. A., Stone, B. M., and Arendt, J. Melatonin and fragmented sleep patterns. Lancet 8-24-1996;348(9026):551-552. PubMed
  86. Holliman, B. J. and Chyka, P. A. Problems in assessment of acute melatonin overdose. South.Med J 1997;90(4):451-453. PubMed
  87. Hong, Y. G. and Riegler, J. L. Is melatonin associated with the development of autoimmune hepatitis? J Clin Gastroenterol 1997;25(1):376-378. PubMed
  88. Cagnacci, A., Arangino, S., Angiolucci, M., Maschio, E., and Melis, G. B. Influences of melatonin administration on the circulation of women. Am J Physiol 1998;274(2 Pt 2):R335-R338. PubMed
  89. U.S.Food and Drug Administration. Special Nutritionals Adverse Events Monitoring System: registered case reports.
  90. Brueske V, Allen J, Kepic T, and et al. Melatonin inhibition of seizure activity in man [abstract]. Electroencephalog Clin Neurophysiol 1981;51:20P.
  91. Siddiqui MA, Nazmi AS, Karim S, and et al. Effect of melatonin and valproate in epilepsy and depression. Indian J Pharmacol 2001;33:378-381.
  92. Appleton RE, Jones AP, Gamble C, et al. The use of MElatonin in children with neurodevelopmental disorders and impaired sleep: a randomised, double-blind, placebo-controlled, parallel study (MENDS). Health Technol Assess. 2012;16(40):i-239. PubMed
  93. Bardazzi F, Placucci F, Neri I, D'Antuono A, Patrizi A. Fixed drug eruption due to melatonin. Acta Derm Venereol. 1998 Jan;78(1):69-70. PubMed
  94. Eckerberg B, Lowden A, Nagai R, Akerstedt T. Melatonin treatment effects on adolescent students' sleep timing and sleepiness in a placebo-controlled crossover study. Chronobiol Int. 2012;29(9):1239-48.
  95. Khezri MB, Merate H. The effects of melatonin on anxiety and pain scores of patients, intraocular pressure, and operating conditions during cataract surgery under topical anesthesia. Indian J Ophthalmol. 2013;61(7):319-24. PubMed
  96. Khezri MB, Oladi MR, Atlasbaf A. Effect of melatonin and gabapentin on anxiety and pain associated with retrobulbar eye block for cataract surgery: a randomized double-blind study. Indian J Pharmacol. 2013;45(6):581-6. PubMed
  97. Nishihara T, Hashimoto S, Ito K, et al. Oral melatonin supplementation improves oocyte and embryo quality in women undergoing in vitro fertilization-embryo transfer. Gynecol Endocrinol. 2014;30(5):359-62.
  98. De Bleecker JL, Lamont BH, Verstraete AG, Schelfhout VJ. Melatonin and painful gynecomastia. Neurology. 1999 Jul 22;53(2):435-6. PubMed
  99. Waldron DL, Bramble D, Gringras P. Melatonin: prescribing practices and adverse events. Arch Dis Child. 2005 Nov;90(11):1206-7. PubMed
  100. Chojnacki C, Walecka-Kapica E, Lokiec K, et al. Influence of melatonin on symptoms of irritable bowel syndrome in postmenopausal women. Endokrynol Pol. 2013;64(2):114-20.
  101. Kim MK, Park EA, Kim HJ, et al. Does supplementation of in-vitro culture medium with melatonin improve IVF outcome in PCOS? Reprod Biomed Online. 2013;26(1):22-9. PubMed
  102. Silman RE. Melatonin: a contraceptive for the nineties. Eur J Obstet Gynecol Reprod Biol. 1993;49(1-2):3-9. PubMed
  103. Briggs GG, Freeman RK, Forinash AB, Towers CV. Drugs in Pregnancy and Lactation. 11th ed. Philadelphia, PA: Wolters Kluwer, 2017.
  104. Onseng K, Johns NP, Khuayjarernpanishk T, et al. Beneficial Effects of Adjuvant Melatonin in Minimizing Oral Mucositis Complications in Head and Neck Cancer Patients Receiving Concurrent Chemoradiation. J Altern Complement Med 2017;23(12):957-63. PubMed
  105. Foster BC, Cvijovic K, Boon HS, et al. Melatonin Interaction Resulting in Severe Sedation. J Pharm Pharm Sci 2015;18(2):124-31. PubMed
  106. Gonçalves AL, Martini Ferreira A, Ribeiro RT, Zukerman E, Cipolla-Neto J, Peres MF. Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention. J Neurol Neurosurg Psychiatry 2016;87(10):1127-32. PubMed
  107. Gringras P, Nir T, Breddy J, Frydman-Marom A, Findling RL. Efficacy and Safety of Pediatric Prolonged-Release Melatonin for Insomnia in Children With Autism Spectrum Disorder. J Am Acad Child Adolesc Psychiatry 2017;56(11):948-57.e4. PubMed
  108. Baandrup L, Lindschou J, Winkel P, Gluud C, Glenthoj BY. Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia or bipolar disorder: A randomised, placebo-controlled, blinded trial. World J Biol Psychi PubMed
  109. Lui MFG, Chow HKD, Wong WMK, Tsang WNW. Melatonin affects postural control in community-dwelling older adults while dual-tasking: a randomized observation study. J Aging Phys Act. 2018 May 29:1-24. PubMed
  110. Fallah R, Shoroki FF, Ferdosian F. Safety and efficacy of melatonin in pediatric migraine prophylaxis. Curr Drug Saf. 2015;10(2):132-5. PubMed
  111. Scheuer C, Pommergaard HC, Rosenberg J, Gogenur I. Effect of topical application of melatonin cream 12.5% on cognitive parameters: a randomized, placebo-controlled, double-blind crossover study in healthy volunteers. J Dermatolog Treat. 2016 Nov;27(6):488 PubMed
  112. Doosti-Irani A, Ostadmohammadi V, Mirhosseini N et al. The effects of melatonin supplementation on glycemic control: A systematic review and meta-analysis of randomized controlled trials. Horm Metab Res. 2018;50(11):783-790. PubMed
  113. Farrokhian A, Tohidi M, Ahanchi NS, et al. Effect of bedtime melatonin administration in patients with type 2 diabetes: A triple-blind, placebo-controlled, randomized trial. Iran J Pharm Res. 2019;18(Suppl1):258-268.
  114. Hayashi M, Mishima K, Fukumizu M, et al. Melatonin treatment and adequate sleep hygiene interventions in children with autism spectrum disorder: A randomized controlled trial. J Autism Dev Disord 2021. PubMed
  115. Esmaeili A, Nassiri Toosi M, Taher M, et al. A pilot randomized, clinical trial of the anti-pruritus effect of melatonin in patients with chronic liver disease. Iran J Pharm Res 2021;20(2):462-472.
  116. Yan W, Li C, Song X, Zhou W, Chen Z. Prophylactic melatonin for delirium in critically ill patients: A systematic review and meta-analysis with trial sequential analysis. Medicine (Baltimore) 2022;101(43):e31411. PubMed
  117. Ameri A, Frouz Asadi M, Ziaei A, et al. Efficacy and safety of oral melatonin in patients with severe COVID-19: a randomized controlled trial. Inflammopharmacology 2023;31(1):265-274. PubMed
  118. Ha M, Yoon D, Lee CY, et al. Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase. J Pineal Res 2024;76(2):e12949. PubMed

See these in context on the Melatonin monograph →

Magnesium 82 references
  1. Rodin SM, Johnson BF. Pharmacokinetic interactions with digoxin. Clin Pharmacokinet 1988;15:227-44.
  2. Covington TR, et al. Handbook of Nonprescription Drugs. 11th ed. Washington, DC: American Pharmaceutical Association, 1996.
  3. Dahle LO, Berg G, Hammar M, et al. The effect of oral magnesium substitution on pregnancy-induced leg cramps. Am J Obstet Gynecol 1995;173:175-80. PubMed
  4. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  5. Peikert A, Wilimzig C, Kohne-Volland R. Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study. Cephalalgia 1996;16:257-63. PubMed
  6. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academy Press, 1999. Available at: http://books.nap.edu/books/0309063507/html/index.html.
  7. Birrer RB, Shallash AJ, Totten V. Hypermagnesemia-induced fatality following epsom salt gargles. J Emerg Med 2002;22:185-8. PubMed
  8. Ryan MP. Diuretics and potassium/magnesium depletion. Directions for treatment. Am J Med 1987;82:38-47.. PubMed
  9. Hollifield JW. Magnesium depletion, diuretics, and arrhythmias. Am J Med 1987;82:30-7.. PubMed
  10. Heidenreich O. Mode of action of conventional and potassium-sparing diuretics--aspects with relevance to Mg-sparing effects. Magnesium 1984;3:248-56..
  11. Pfaffenrath V, Wessely P, Meyer C, et al. Magnesium in the prophylaxis of migraine--a double-blind placebo-controlled study. Cephalalgia 1996;16:436-40.. PubMed
  12. Wang F, Van Den Eeden SK, Ackerson LM, et al. Oral magnesium oxide prophylaxis of frequent migrainous headache in children: a randomized, double-blind, placebo-controlled trial. Headache 2003;43:601-10.. PubMed
  13. Sompolinsky D, Samra Z. Influence of magnesium and manganese on some biological and physical properties of tetracycline. J Bacteriol 1972;110:468-76.. PubMed
  14. Jeyabalan A, Caritis SN. Pharmacologic inhibition of preterm labor. Clin Obstet Gynecol 2002;45:99-113. PubMed
  15. Mittendorf R, Dambrosia J, Pryde PG, et al. Association between the use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants. Am J Obstet Gynecol 2002;186:1111-8.. PubMed
  16. Witlin AG, Sibai BM. Magnesium sulfate therapy in preeclampsia and eclampsia. Obstet Gynecol 1998;92:883-9.. DOI
  17. Crowther CA, Hiller JE, Doyle LW. Magnesium sulphate for preventing preterm birth in threatened preterm labour. Cochrane Database Syst Rev 2002;4:CD001060. . PubMed
  18. Davey MJ, Teubner D. A randomized controlled trial of magnesium sulfate, in addition to usual care, for rate control in atrial fibrillation. Ann Emerg Med 2005;45:347-53.. PubMed
  19. L'Hommedieu CS, Nicholas D, Armes DA, et al. Potentiation of magnesium sulfate--induced neuromuscular weakness by gentamicin, tobramycin, and amikacin. J Pediatr 1983;102:629-31..
  20. Dunn CJ, Goa KL. Risedronate: a review of its pharmacological properties and clinical use in resorptive bone disease. Drugs 2001;61:685-712..
  21. Kass L, Weekes J, Carpenter L. Effect of magnesium supplementation on blood pressure: a meta-analysis. Eur J Clin Nutr 2012;66:411-8. PubMed
  22. Koontz SL, Friedman SA, Schwartz ML. Symptomatic hypocalcemia after tocolytic therapy with magnesium sulfate and nifedipine. Am J Obstet Gynecol. 2004;190(6):1773-6. PubMed
  23. Snyder SW, Cardwell MS. Neuromuscular blockade with magnesium sulfate and nifedipine. Am J Obstet Gynecol. 1989;161(1):35-6. PubMed
  24. Waisman GD, Mayorga LM, Cámera MI, et al. Magnesium plus nifedipine: potentiation of hypotensive effect in preeclampsia? Am J Obstet Gynecol. 1988;159(2):308-9. PubMed
  25. Brown DD, Juhl RP. Decreased bioavailability of digoxin due to antacids and kaolin-pectin. N Engl J Med. 1976;295(19):1034-7. PubMed
  26. Allen MD, Greenblatt DJ, Harmatz JS, et al. Effect of magnesium--aluminum hydroxide and kaolin--pectin on absorption of digoxin from tablets and capsules. J Clin Pharmacol. 1981;21(1):26-30. PubMed
  27. Ravn HB, Vissinger H, Kristensen SD, et al. Magnesium inhibits platelet activity--an in vitro study. Thromb Haemost. 1996;76(1):88-93. DOI
  28. Ravn HB, Kristensen SD, Vissinger H, et al. Magnesium inhibits human platelets. Blood Coagul Fibrinolysis. 1996;7(2):241-4. PubMed
  29. Ravn HB, Vissinger H, Kristensen SD, et al. Magnesium inhibits platelet activity--an infusion study in healthy volunteers. Thromb Haemost. 1996;75(6):939-44. DOI
  30. Neuvonen PJ, Kivistö KT. The effects of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations. Br J Clin Pharmacol. 1991;32(2):215-20. PubMed
  31. Kivistö KT, Neuvonen PJ. Enhancement of absorption and effect of glipizide by magnesium hydroxide. Clin Pharmacol Ther. 1991;49(1):39-43. PubMed
  32. Neuvonen PJ, Kivistö KT. Enhancement of drug absorption by antacids. An unrecognised drug interaction. Clin Pharmacokinet. 1994;27(2):120-8. PubMed
  33. Shechter, M., Merz, C. N., Paul-Labrador, M., Meisel, S. R., Rude, R. K., Molloy, M. D., Dwyer, J. H., Shah, P. K., and Kaul, S. Beneficial antithrombotic effects of the association of pharmacological oral magnesium therapy with aspirin in coronary heart
  34. Ganzevoort, J. W., Hoogerwaard, E. M., and van der Post, J. A. [Hypocalcemic delirium due to magnesium sulphate therapy in a pregnant woman with pre-eclampsia]. Ned.Tijdschr.Geneeskd. 8-3-2002;146(31):1453-1456.
  35. Horner, S. M. Efficacy of intravenous magnesium in acute myocardial infarction in reducing arrhythmias and mortality. Meta-analysis of magnesium in acute myocardial infarction. Circulation 1992;86(3):774-779. PubMed
  36. Azria, E., Tsatsaris, V., Goffinet, F., Kayem, G., Mignon, A., and Cabrol, D. [Magnesium sulfate in obstetrics: current data]. J Gynecol.Obstet.Biol.Reprod.(Paris) 2004;33(6 Pt 1):510-517.
  37. Magee, L. A., Miremadi, S., Li, J., Cheng, C., Ensom, M. H., Carleton, B., Cote, A. M., and von Dadelszen, P. Therapy with both magnesium sulfate and nifedipine does not increase the risk of serious magnesium-related maternal side effects in women with p
  38. Henyan, N. N., Gillespie, E. L., White, C. M., Kluger, J., and Coleman, C. I. Impact of intravenous magnesium on post-cardiothoracic surgery atrial fibrillation and length of hospital stay: a meta-analysis. Ann.Thorac.Surg. 2005;80(6):2402-2406. PubMed
  39. Li, J., Zhang, Q., Zhang, M., and Egger, M. Intravenous magnesium for acute myocardial infarction. Cochrane.Database.Syst.Rev. 2007;(2):CD002755. PubMed
  40. Doyle, L. W., Crowther, C. A., Middleton, P., Marret, S., and Rouse, D. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane.Database.Syst.Rev. 2009;(1):CD004661. PubMed
  41. Han, S., Crowther, C. A., and Moore, V. Magnesium maintenance therapy for preventing preterm birth after threatened preterm labour. Cochrane.Database.Syst.Rev. 2010;(7):CD000940. PubMed
  42. Duley, L., Gulmezoglu, A. M., Henderson-Smart, D. J., and Chou, D. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane.Database.Syst.Rev. 2010;(11):CD000025. PubMed
  43. Conde-Agudelo, A., Romero, R., and Kusanovic, J. P. Nifedipine in the management of preterm labor: a systematic review and metaanalysis. Am J Obstet.Gynecol. 2011;204(2):134-20. PubMed
  44. Wong, G. K., Boet, R., Poon, W. S., Chan, M. T., Gin, T., Ng, S. C., and Zee, B. C. Intravenous magnesium sulphate for aneurysmal subarachnoid hemorrhage: an updated systemic review and meta-analysis. Crit Care 2011;15(1):R52. PubMed
  45. Magee, L., Sawchuck, D., Synnes, A., and von, Dadelszen P. SOGC Clinical Practice Guideline. Magnesium sulphate for fetal neuroprotection. J Obstet.Gynaecol.Can. 2011;33(5):516-529.
  46. Doyle, L. W. Antenatal magnesium sulfate and neuroprotection. Curr Opin Pediatr 2012;24(2):154-159. PubMed
  47. McDonald, S. D., Lutsiv, O., Dzaja, N., and Duley, L. A systematic review of maternal and infant outcomes following magnesium sulfate for pre-eclampsia/eclampsia in real-world use. Int J Gynaecol.Obstet. 2012;118(2):90-96. PubMed
  48. Gordon, M., Naidoo, K., Akobeng, A. K., and Thomas, A. G. Osmotic and stimulant laxatives for the management of childhood constipation. Cochrane.Database.Syst.Rev. 2012;7:CD009118. PubMed
  49. Dodd, J. M., Crowther, C. A., and Middleton, P. Oral betamimetics for maintenance therapy after threatened preterm labour. Cochrane.Database.Syst.Rev. 2012;12:CD003927. PubMed
  50. Wu, X., Wang, C., Zhu, J., Zhang, C., Zhang, Y., and Gao, Y. Meta-analysis of randomized controlled trials on magnesium in addition to beta-blocker for prevention of postoperative atrial arrhythmias after coronary artery bypass grafting. BMC.Cardiovasc.D PubMed
  51. Thorp, J. M., Jr., Katz, V. L., Campbell, D., and Cefalo, R. C. Hypersensitivity to magnesium sulfate. Am.J.Obstet.Gynecol. 1989;161(4):889-890. PubMed
  52. Duley L and Gulmezoglu AM. Magnesium sulphate versus lytic cocktail for eclampsia. Cochrane Database of Systematic Reviews 2000;(3) PubMed
  53. Gibbins KJ, Browning KR, Lopes VV, Anderson BL, Rouse DJ. Evaluation of the clinical use of magnesium sulfate for cerebral palsy prevention. Obstet Gynecol 2013;121(2 Pt 1):235-40. PubMed
  54. Ji D. Oral magnesium sulfate causes perforation during bowel preparation for fiberoptic colonoscopy in patients with colorectal cancer. J Emerg Med 2012;43(4):716-7. PubMed
  55. Yagi T, Naito T, Mino Y, Umemura K, Kawakami J. Impact of concomitant antacid administration on gabapentin plasma exposure and oral bioavailability in healthy adult subjects. Drug Metab Pharmacokinet 2012;27(2):248-54. PubMed
  56. Yamasaki M, Funakoshi S, Matsuda S, Imazu T, Takeda Y, Murakami T, Maeda Y. Interaction of magnesium oxide with gastric acid secretion inhibitors in clinical pharmacotherapy. Eur J Clin Pharmacol 2014;70(8):921-4. PubMed
  57. Choi ES, Jeong WJ, Ahn SH, Oh AY, Jeon YT, Do SH. Magnesium sulfate accelerates the onset of low-dose rocuronium in patients undergoing laryngeal microsurgery. J Clin Anesth. 2017 Feb;36:102-106. PubMed
  58. Ikee R, Toyoyama T, Endo T, Tsunoda M, Hashimoto N. Impact of sevelamer hydrochloride on serum magnesium concentrations in hemodialysis patients. Magnes Res. 2016 Apr 1;29(4):184-90. PubMed
  59. Miller ES, Sakowicz A, Leger E. Lange E, Yee LM. The association between receipt of intrapartum magnesium and postpartum hemorrhage. Am J Obstet Gynecol 2018;218(1 Suppl):S165.
  60. Rodríguez-Rubio L, Solis Garcia Del Pozo J, Nava E, Jordán J. Interaction between magnesium sulfate and neuromuscular blockers during the perioperative period. A systematic review and meta-analysis. J Clin Anesth. 2016;34:524-34. PubMed
  61. Brown RS. Magnesium Sulfate: Another Cause of a Solute Diuresis. Am J Kidney Dis. 2017;69(4):550-551. PubMed
  62. Park H, Qin R, Smith TJ, et al. North Central Cancer Treatment Group N10C2 (Alliance): a double-blind placebo-controlled study of magnesium supplements to reduce menopausal hot flashes. Menopause. 2015;22(6):627-32. PubMed
  63. Sakanoue M, Sanada J, Kanekura T. Skin eruption elicited by magnesium oxide (Maglax). J Dermatol. 2016;43(2):221-2.
  64. Iwamuro M, Saito S, Yoshioka M, et al. A Magnesium Oxide Bezoar. Intern Med. 2018;57(21):3087-3091. PubMed
  65. Vilchez G, Dai J, Kumar K, Mundy D, Kontopoulos E, Sokol RJ. Racial/ethnic disparities in magnesium sulfate neuroprotection: a subgroup analysis of a multicenter randomized controlled trial. J Matern Fetal Neonatal Med. 2018;31(17):2304-2311. PubMed
  66. Drug Safety Communication: FDA Recommends Against Prolonged Use of Magnesium Sulfate to Stop Pre-term Labor Due to Bone Changes in Exposed Babies. U.S. Food and Drug Administration (FDA), May 30, 2013. https://www.fda.gov/downloads/Drugs/DrugSafety/UCM353
  67. Committee Opinion: Magnesium Sulfate Use in Obstetrics. The American College of Obstetricians and Gynecologists Committee on Obstetric Practice Society for Maternal-Fetal Medicine, Number 652, January 2016. https://www.acog.org/Clinical-Guidance-and-Publi
  68. Kashihara Y, Terao Y, Yoda K, et al. Effects of magnesium oxide on pharmacokinetics of L-dopa/carbidopa and assessment of pharmacodynamic changes by a model-based simulation. Eur J Clin Pharmacol. 2019;75(3):351-361. PubMed
  69. Shepherd E, Salam RA, Manhas D, et al. Antenatal magnesium sulphate and adverse neonatal outcomes: A systematic review and meta-analysis. PLoS Med. 2019;16(12):e1002988. PubMed
  70. Hong JY, Hong JY, Choi YS, et al. Antenatal magnesium sulfate treatment and risk of necrotizing enterocolitis in preterm infants born at less than 32 weeks of gestation. Sci Rep. 2020;10(1):12826. PubMed
  71. Schuh S, Sweeney J, Rumantir M, et al. Effect of nebulized magnesium vs placebo added to albuterol on hospitalization among children with refractory acute asthma treated in the emergency department: a randomized clinical trial. JAMA. 2020;324(20):2038-20 PubMed
  72. Almeida CED, Carvalho LR, Andrade CVC, Nascimento PD Jr, Barros GAM, Modolo NSP. Effects of magnesium sulphate on the onset time of rocuronium at different doses: a randomized clinical trial. Braz J Anesthesiol. 2021;71(5):482-8. PubMed
  73. Gochi Valdovinos A, Arriaga-Redondo M, Dejuan Bitriá E, Pérez Rodríguez I, Márquez Isidro E, Blanco Bravo D. Prenatal therapy with magnesium sulphate and intestinal obstruction due to meconium in preterm newborns. An Pediatr (Engl Ed). 2022 Feb;96(2):138- PubMed
  74. Iio K, Kondo E, Shibata E, et al. Long-term tocolysis with magnesium sulfate as a risk factor for low bone mass: a case series. J Med Cases. 2022 Feb;13(2):47-50. PubMed
  75. Eiraku K, Uozumi Y, Hieda M, Maruyama T, Nomura H. A senile case of heart failure associated with hypermagnesemia induced by magnesium-containing laxative agent. Geriatr Gerontol Int. 2022;22(10):897-899.
  76. Enayati A, Gin JH, Sajeev JK, et al. Efficacy of intravenous magnesium for the management of non-post operative atrial fibrillation with rapid ventricular response: A systematic review and meta-analysis. J Cardiovasc Electrophysiol 2023;34(5):1286-1295. PubMed
  77. Su YH, Luo DC, Pang Y. Effects of intraoperative Magnesium sulfate infusion on emergency agitation during general anesthesia in patients undergoing radical mastectomy: a randomized controlled study. BMC Anesthesiol 2023;23(1):326. PubMed
  78. Han J, Park HY, Shin HJ, Chung SH, Do SH. Effects of magnesium sulphate on neostigmine-induced recovery from moderate neuromuscular blockade with rocuronium: a randomized controlled trial. Magnes Res 2023;36(2):31-39. PubMed
  79. Lee AT, Cordova JC, Jamplis RP, Pomicter GR. Posterior Reversible Encephalopathy Syndrome and Eclampsia in the Setting of Magnesium Toxicity: A Case Report. A A Pract 2023;17(11):e01726. PubMed
  80. Darmawan D, Rengganis I, Rumende CM, et al. Effectiveness and Safety of Nebulized Magnesium as Last Line Treatment in Adults with Acute Asthma Attack: A Systematic Review and Meta-Analysis. Acta Med Indones 2024;56(1):3-12.
  81. Shepherd ES, Goldsmith S, Doyle LW, et al. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev 2024;5(5):CD004661. PubMed
  82. US Food and Drug Administration (FDA). Biktarvy Prescribing Information. October 2024. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/210251Orig1s020lbl.pdf. Accessed July 16, 2025.

See these in context on the Magnesium monograph →

Theanine 6 references
  1. Yokogoshi H, Kobayashi M. Hypotensive effect of gamma-glutamylethylamide in spontaneously hypertensive rats. Life Sci 1998;62:1065-8.
  2. Haskell, C. F., Kennedy, D. O., Milne, A. L., Wesnes, K. A., and Scholey, A. B. The effects of L-theanine, caffeine and their combination on cognition and mood. Biol.Psychol. 2008;77(2):113-122. PubMed
  3. Yokogoshi, H., Kato, Y., Sagesaka, Y. M., Takihara-Matsuura, T., Kakuda, T., and Takeuchi, N. Reduction effect of theanine on blood pressure and brain 5-hydroxyindoles in spontaneously hypertensive rats. Biosci.Biotechnol.Biochem. 1995;59(4):615-618. PubMed
  4. Lyon MR, Kapoor MP, Juneja LR. The effects of L-theanine (Suntheanine®) on objective sleep quality in boys with attention deficit hyperactivity disorder (ADHD): a randomized, double-blind, placebo-controlled clinical trial. Altern Med Rev. 2011;16(4):348-
  5. Hidese S, Ota M, Wakabayashi C, et al. Effects of chronic l-theanine administration in patients with major depressive disorder: an open-label study. Acta Neuropsychiatr 2017;29(2):72-9.
  6. Tsuchiya T, Honda H, Oikawa M, et al. Oral administration of the amino acids cystine and theanine attenuates the adverse events of S-1 adjuvant chemotherapy in gastrointestinal cancer patients. Int J Clin Oncol 2016;21(6):1085-90. PubMed

See these in context on the Theanine monograph →

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

See these in context on the German Chamomile monograph →

Vitamin B6 32 references
  1. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  2. Yates AA, Schlicker SA, Suitor CW. Dietary reference intakes: The new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 1998;98:699-706. PubMed
  3. Geerling BJ, Dagnelie PC, Badart-Smook A, et al. Diet as a risk factor for the development of ulcerative colitis. Am J Gastroenterol 2000;95:1008-13. PubMed
  4. South M. Neonatal seizures after pyridoxine use -- reply. Lancet 1999;354:2083. PubMed
  5. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (2000). Washington, DC: National Academy Press, 2000. Available at: http://b
  6. Baxter P, Aicardi J. Neonatal seizures after pyridoxine use. Lancet 1999;354:2082-3. PubMed
  7. Bendich A, Cohen M. Vitamin B6 safety issues. Ann N Y Acad Sci 1990;585:321-30.
  8. Schaumburg H, Kaplan J, Windebank A. Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome. N Engl J Med 1983;309:445-8. PubMed
  9. Gordon N. Pyridoxine dependency: an update. Dev Med Child Neurol 1997;39:63-5. PubMed
  10. Lewis PJ. Pain in the hand and wrist. Pyridoxine supplements may help patients with carpal tunnel syndrome. BMJ 1995;310:1534. PubMed
  11. Kaufman G. Pyridoxine against amiodarone-induced photosensitivity (letter). Lancet 1984;1:51-2. PubMed
  12. Mulrow JP, Mulrow CD, McKenna WJ. Pyridoxine and amiodarone-induced photosensitivity. Ann Intern Med 1985;103:68-9. PubMed
  13. Kawada A, Kashima A, Shiraishi H, et al. Pyridoxine-induced photosensitivity and hypophosphatasia. Dermatology 2000;201:356-60.. PubMed
  14. Vasile A, Goldberg R, Kornberg B. Pyridoxine toxicity: report of a case. J Am Osteopath Assoc 1984;83:790-1. DOI
  15. Hansson O, Sillanpaa M. Pyridoxine and serum concentration of phenytoin and phenobarbitone. Lancet 1976;1:256. DOI
  16. Jansen T, Romiti R, Kreuter A, Altmeyer P. Rosacea fulminans triggered by high-dose vitamins B6 and B12. J Eur Acad Dermatol Venereol 2001;15:484-5..
  17. Chittumma P, Kaewkiattikun K, Wiriyasiriwach B. Comparison of the effectiveness of ginger and vitamin B6 for treatment of nausea and vomiting in early pregnancy: a randomized double-blind controlled trial. J Med Assoc Thai 2007;90:15-20.
  18. Hatzitolios, A., Iliadis, F., Katsiki, N., and Baltatzi, M. Is the anti-hypertensive effect of dietary supplements via aldehydes reduction evidence based? A systematic review. Clin Exp.Hypertens. 2008;30(7):628-639. PubMed
  19. Vasdev, S., Ford, C. A., Parai, S., Longerich, L., and Gadag, V. Dietary vitamin B6 supplementation attenuates hypertension in spontaneously hypertensive rats. Mol.Cell Biochem. 1999;200(1-2):155-162.
  20. de, Vogel S., Dindore, V., van, Engeland M., Goldbohm, R. A., van den Brandt, P. A., and Weijenberg, M. P. Dietary folate, methionine, riboflavin, and vitamin B-6 and risk of sporadic colorectal cancer. J Nutr 2008;138(12):2372-2378. PubMed
  21. Hagen, I., Nesheim, B. I., and Tuntland, T. No effect of vitamin B-6 against premenstrual tension. A controlled clinical study. Acta Obstet.Gynecol.Scand. 1985;64(8):667-670. PubMed
  22. Aybak, M., Sermet, A., Ayyildiz, M. O., and Karakilcik, A. Z. Effect of oral pyridoxine hydrochloride supplementation on arterial blood pressure in patients with essential hypertension. Arzneimittelforschung. 1995;45(12):1271-1273.
  23. Lal, K. J., Dakshinamurti, K., and Thliveris, J. The effect of vitamin B6 on the systolic blood pressure of rats in various animal models of hypertension. J Hypertens. 1996;14(3):355-363. PubMed
  24. Lauritzen CH, Reuter HD, Repges R, Bohnert K, and Schmidt U. Treatment of premenstrual tension syndrome with Vitex agnus castus. Controlled, double-blind study versus pyridoxine. Phytomed 1997;4(3):183-189. PubMed
  25. Fonseca VA, Lavery LA, Thethi TK, et al. Metanx in type 2 diabetes with peripheral neuropathy: A randomized trial. Am J Med 2013;126(2):141-9. PubMed
  26. Hankey GJ, Eikelboom JW, Yi Q, et al. Treatment with B vitamins and incidence of cancer in patients with previous stroke or transient ischemic attack: Results of a randomized placebo-controlled trial. Stroke 2012;43(6):1572-7. PubMed
  27. Hoyer-Kuhn H, Kohbrok S, Volland R, Franklin J, Hero B, Beck BB, Hoppe B. Vitamin B6 in primary hyperoxaluria I: first prospective trial after 40 years of practice. Clin J Am Soc Nephrol. 2014 Mar;9(3):468-77. PubMed
  28. Mahmoud A, Tabassum S, Al Enazi S, et al. Amelioration of levetiracetam-induced behavioral side effects by pyridoxine. A randomized double blind controlled study. Pediatr Neurol 2021;119:15-21. PubMed
  29. Gupta M, Gallante B, Bamberger JN, et al. Prospective randomized evaluation of idiopathic hyperoxaluria treatments. J Endourol 2021;35(12):1844-1851. PubMed
  30. Li H, Chen M, Liang S, et al. Excessive vitamin B6 during treatment is related to poor prognosis of patients with nasopharyngeal carcinoma: A U-shaped distribution suggests low dose supplement. Clin Nutr 2021;40(4):2293-2300. PubMed
  31. Tanigawa J, Nabatame S, Tominaga K, et al. High-dose pyridoxine treatment for inherited glycosylphosphatidylinositol deficiency. Brain Dev 2021;43(6):680-687. PubMed
  32. Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy. Obstet Gynecol. 2018;131(1):e15-e30. PubMed

See these in context on the Vitamin B6 monograph →

Gamma-aminobutyric Acid (gaba) 12 references
  1. Cavagnini F, Invitti C, Pinto M, et al. Effect of acute and repeated administration of gamma aminobutyric acid (GABA) on growth hormone and prolactin secretion in man. Acta Endocrinol (Copenh) 1980;93:149-54.
  2. Nurnberger JI Jr, Berrettini WH, Simmons-Alling S, et al. Intravenous GABA administration is anxiogenic in man. Psychiatry Res 1986;19:113-7. PubMed
  3. Gershman RN, Vasilenko MA, Iliushina GG, et al. [Gammalon in the rehabilitation in infantile cerebral palsy]. Pediatr.Akus.Ginekol. 1977;(6):26-7.
  4. Loeb C, Benassi E, Bo, GP, et al. Preliminary evaluation of the effect of GABA and phosphatidylserine in epileptic patients. Epilepsy Res. 1987;1:209-12 . PubMed
  5. Inoue K, Shirai T, Ochiai H, et al. Blood-pressure-lowering effect of a novel fermented milk containing gamma-aminobutyric acid (GABA) in mild hypertensives. Eur J Clin Nutr 2003;57:490-95.
  6. ELLIOTT, K. A. and JASPER, H. H. Gammaaminobutyric acid. Physiol Rev. 1959;39(2):383-406.
  7. Winsky-Sommerer, R. Role of GABAA receptors in the physiology and pharmacology of sleep. Eur.J.Neurosci. 2009;29(9):1779-1794.
  8. Meldrum, B. S. GABAergic mechanisms in the pathogenesis and treatment of epilepsy. Br.J.Clin.Pharmacol. 1989;27 Suppl 1:3S-11S. PubMed
  9. Loeb, C., Marinari, U. M., Benassi, E., Besio, G., Cottalasso, D., Cupello, A., Maffini, M., Mainardi, P., Pronzato, M. A., and Scotto, P. A. Phosphatidylserine increases in vivo the synaptosomal uptake of exogenous GABA in rats. Exp.Neurol. 1988;99(2):4 PubMed
  10. Melis, G. B., Paoletti, A. M., Mais, V., and Fioretti, P. Interference of dopamine infusion on gamma-amino butyric acid (GABA)-stimulated prolactin increase. J.Endocrinol.Invest 1980;3(4):445-448.
  11. Boonstra E, de Kleijn R, Colzato LS, Alkemade A, Forstmann BU, Nieuwenhuis S. Neurotransmitters as food supplements: the effects of GABA on brain and behavior. Front Psychol. 2015 Oct 6;6:1520. doi: 10.3389/fpsyg.2015.01520. eCollection 2015. PubMed
  12. de Bie TH, Witkamp RF, Balvers MG, Jongsma MA. Effects of ?-aminobutyric acid supplementation on glucose control in adults with prediabetes: A double-blind, randomized, placebo-controlled trial. Am J Clin Nutr 2023;118(3):708-719. PubMed

See these in context on the Gamma-aminobutyric Acid (gaba) monograph →

Lemon Balm 12 references
  1. Wolbling RH, Leonhardt K. Local therapy of herpes simplex with dried extract from Melissa officinalis. Phytomedicine 1994;1:25-31.
  2. Akhondzadeh S, Noroozian M, Mohammadi M, et al. Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomised, placebo controlled trial. J Neurol Neurosurg Psychiatry 2003;74:863-6. PubMed
  3. Kennedy DO, Scholey AB, Tildesley NT, et al. Modulation of mood and cognitive performance following acute administration of Melissa officinalis (lemon balm). Pharmacol Biochem Behav 2002;72:953-64. PubMed
  4. 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.
  5. Herberg, KW. Nebenwirkungen pflanzlicher Beruhigungsmittel/ Leistung und Befinden nach Einnahme einer Baldrian-Hopfen-Kombination. Z.Allg Med 1996;72:234-240.
  6. Soulimani R, Fleurentin J, Mortier F, et al. Neurotropic action of the hydroalcoholic extract of Melissa officinalis in the mouse. Planta Med. 1991 Apr;57:105-9.
  7. Sourgens H, Winterhoff H, Gumbinger HG, et al. Antihormonal effects of plant extracts. TSH- and prolactin-suppressing properties of Lithospermum officinale and other plants. Planta Med. 1982 Jun;45:78-86. DOI
  8. Auf'mkolk M, Ingbar JC, Amir SM, et al. Inhibition by certain plant extracts of the binding and adenylate cyclase stimulatory effect of bovine thyrotropin in human thyroid membranes. Endocrinology. 1984 Aug;115:527-34. PubMed
  9. Santini F, Vitti P, Ceccarini G, et al. In vitro assay of thyroid disruptors affecting TSH-stimulated adenylate cyclase activity. J Endocrinol Invest. 2003 Oct;26:950-5. PubMed
  10. Alijaniha F, et al. Heart palpitation relief with Melissa officinalis leaf extract: double blind, randomized, placebo controlled trial of efficacy and safety. J Ethnopharmacol. 2015;164:378-384. doi: 10.1016/j.jep.2015.02.007. Epub 2015 Feb 11. PubMed
  11. Araj-Khodaei M, Noorbala AA, Yarani R, et al. A double-blind, randomized pilot study for comparison of Melissa officinalis L. and Lavandula angustifolia Mill. with Fluoxetine for the treatment of depression. BMC Complement Med Ther. 2020;20(1):207. PubMed
  12. Kucuk U, Pham M, Raza Raja MH, Saad Shaukat MH, Clark R. Transient complete atrioventricular block associated with herbal supplement use. S D Med 2023;76(7):311-313.

See these in context on the Lemon Balm monograph →

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

See these in context on the Hops monograph →

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 →

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 →

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