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Herb drug interaction and side effects

Valerian - Clinical studies

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Herb drug interaction - As in case of drug drug interaction, herb drug interaction is an important factor in consideration of health benefits of herbal remedies. The quotations on herb-drug interaction are compiled from contemporary reviews.

: Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions.
Published in: Arch Intern Med 1998 Nov 9;158(20):2200-11
By: L.G. Miller

Echinacea: If used beyond 8 weeks, Echinacea could cause hepatotoxicity and therefore should not be used with other known hepatoxic drugs, such as anabolic steroids, amiodarone, methotrexate, and ketoconazole. Immunostimulants (eg, Echinacea and zinc) should not be given with immunosuppressants (eg, corticosteroids and cyclosporine).
Feverfew: Nonsteroidal anti-inflammatory drugs may negate the usefulness of feverfew in the treatment of migraine headaches.
Ginseng: Ginseng may cause headache, tremulousness, and manic episodes in patients treated with phenelzine sulfate. Ginseng should also not be used with estrogens or corticosteroids because of possible additive effects.
Kava when used with alprazolam has resulted in coma.
Valerian should not be used concomitantly with barbiturates because excessive sedation may occur.

Feverfew, Garlic, Ginkgo, Ginger, and Ginseng may alter bleeding time and should not be used concomitantly with warfarin.
Kyushin, Licorice, Plantain, Uzara root, Hawthorn, and Ginseng may interfere with either digoxin pharmacodynamically or with digoxin monitoring
Evening primrose oil and Borage should not be used with anticonvulsants because they may lower the seizure threshold. Kelp as a source of iodine may interfere with thyroid replacement therapies.

From: Interactions between herbal medicines and prescribed drugs: a systematic review.
Published in: Drugs 2001;61(15):2163-75
By: A.A. Izzo and E. Ernst

St John's wort (Hypericum perforatum) lowers blood concentrations of cyclosporin, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon and theophylline; furthermore it may cause intermenstrual bleeding, delirium or mild serotonin syndrome, respectively, when used concomitantly with
oral contraceptives (ethinylestradiol/desogestrel), loperamide or selective serotonin-reuptake inhibitors (sertaline, paroxetine, nefazodone).
Ginkgo (Ginkgo biloba) interactions include bleeding when combined with warfarin, raised blood pressure when combined with a thiazide diuretic and coma when
combined with trazodone.
Ginseng (Panax ginseng) lowers blood concentrations of alcohol and warfarin, and induces mania if used concomitantly with phenelzine.
Garlic (Allium sativum) changes pharmacokinetic variables of paracetamol, decreases blood concentrations of warfarin and produces hypoglycaemia when taken
with chlorpropamide.
Kava (Piper methysticum) increases 'off' periods in Parkinson patients taking levodopa and can cause a semicomatose state when given concomitantly with alprazolam.
No (drug) interactions were found for Echinacea (Echinacea angustifolia, E. purpurea, E. pallida) and Saw Palmetto (Serenoa repens).

From: Herbal remedies: adverse effects and drug interactions.
Published in: Am Fam Physician 1999 Mar 1;59(5):1239-45
By: M.J. Cupp

Ginkgo biloba extract, advertised as improving cognitive functioning, has been reported to cause spontaneous bleeding, and it may interact with anticoagulants and antiplatelet agents.
Ephedrine-containing herbal products have been associated with adverse cardiovascular events, seizures and even death.
Ginseng, widely used for its purported physical and mental effects, is generally well tolerated, but it has been implicated as a cause of decreased response to warfarin.
St. John's wort, promoted as a treatment for depression, may have monoamine oxidase-inhibiting effects or may cause increased levels of serotonin, dopamine and norepinephrine. Although St. John's wort probably does not interact with foods that contain tyramine, it should not be used with prescription antidepressants.

From: The risk-benefit profile of commonly used herbal therapies: Ginkgo, St. John's Wort, Ginseng, Echinacea, Saw Palmetto, and Kava.
Published in: Ann Intern Med 2002 Jan 1;136(1):42-53
By: E. Ernst

Ginkgo: The published evidence suggests that ginkgo is of questionable use for memory loss and tinnitus but has some effect on dementia and intermittent claudication.
Echinacea may be helpful in the treatment or prevention of upper respiratory tract infections, but trial data are not fully convincing.
Ginseng: Well-conducted clinical trials do not support the efficacy of ginseng to treat any condition.
Kava is an efficacious short-term treatment for anxiety.
Saw Palmetto has been shown in short-term trials to be efficacious in reducing the symptoms of benign prostatic hyperplasia.
St. John's wort is efficacious for mild to moderate depression, but serious concerns exist about its interactions with several conventional drugs.

From: Herbal medication: potential for adverse interactions with analgesic drugs.
Published in: J Clin Pharm Ther 2002 Dec;27(6):391-401
By: Abebe W.

Non-steroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, have the potential to interact with herbal supplements that are known to possess antiplatelet activity (ginkgo, garlic, ginger, bilberry, dong quai, feverfew, ginseng, turmeric, meadowsweet and willow), with those containing coumarin (chamomile, motherworth, horse chestnut, fenugreek and red clover) and with tamarind, enhancing the risk of bleeding.
Acetaminophen may also interact with ginkgo and possibly with at least some of the above herbs to increase the risk of bleeding.
The incidences of hepatotoxicity and nephrotoxicity may be augmented by acetaminophen when concomitantly used with the potentially hepatotoxic herbs Echinacea and kava, and with herbs containing salicylate (willow, meadowsweet), respectively.
The concomitant use of opioid analgesics with the sedative herbal supplements, valerian, kava and chamomile, may lead to increased central nervous system (CNS) depression. The analgesic effect of opioids may also be inhibited by ginseng.

From: Drug-herb interaction among commonly used conventional medicines: a compendium for health care professionals.
Published in: Am J Ther. 2003; 10(3):163-9.
By: Brazier NC, Levine MA.

Warfarin is the most common drug and St. John's wort was the most common herbal product reported in drug-herb interactions.



Clinical trials of Valerian. Valerian root is traditionall used in teas, tinctures and other herbal medicines to help combat stress, reduce excessive anxiety, restlessness and reverse insomnia. In medieval Europe it was called "all-heal" and it's potency was considered unsurpassed. Modern studies have identified at least three groups of ingredients with potentially beneficial effect on nervous system in Valerian root. A selection of quotations from contemporatry scientific publications confirms and expands traditional applications of Valerian.

Valerian has been shown to decrease sleep latency and nocturnal awakenings and improve subjective sleep quality, but placebo effects were marked in some studies, and in some cases the beneficial effects were not seen until two to four weeks of therapy. From: Beaubrun G, Gray GE. A review of herbal medicines for psychiatric disorders. Psychiatr Serv. 2000; 51(9): 1130-4

The effect of an aqueous extract of valerian root on sleep was studied in two groups of healthy, young subjects. The results indicate that the aqueous valerian extract exerts a mild hypnotic action.
From: Balderer G, Borbely AA.: Psychopharmacology (Berl) 1985;87(4):406-9. Effect of valerian on human sleep.

Different herbal remedies are recommended, but only for extracts of valerian a sleep-inducing effect can be assumed. From: Balogh A. Z Arztl Fortbild Qualitatssich 2001;95(1):11-6. Drug for the treatment of sleep disorders-review.

The clinical features and risk of hepatotoxicity … were determined in 23 patients. There was no clinical evidence of acute hepatitis after taking an average of 2.5 g of valerian (range 0.5 to 12 g). There was no evidence of subclinical liver damage in 12 patients who had routine liver function tests performed approximately 6-12 hours after ingestion. From: Chan TY, Tang CH, Critchley JA.: Postgrad Med J 1995;71(834):227-8. Poisoning due to an over-the-counter hypnotic

This study investigated whether kava or valerian could moderate the effects of psychological stress induced under laboratory conditions in a group of healthy volunteers. The results suggest that kava and valerian may be beneficial to health by reducing physiological reactivity during stressful situations. From: Cropley M, Cave Z, Ellis J, Middleton RW., Phytother Res 2002;16(1):23-7. Effect of Kava and Valerian on human physiological and psychological responses to mental stress assessed under laboratory conditions.

The study showed no differences in the efficacy for valerian and oxazepam. Because of the more favourable adverse effect profile of valerian compared to oxazepam, this hypothesis should be analysed confirmatorily in an equivalence study. From: Dorn M. Forsch Komplementarmed Klass Naturheilkd 2000;7(2):79-84. Efficacy and tolerability of Baldrian versus oxazepam in non-organic and non-psychiatric insomniacs: a randomised, double-blind, clinical, comparative study

A comprehensive review of the constituents of the Valerianaceae is presented with particular reference to the sedative activity of extracts from various constituent species. The sedative activity can be ascribed to the valepotriates present and to a lesser extent to the sesquiterpene constituents of the volatile oils. From: Houghton PJ.: J Ethnopharmacol 1988;22(2):121-42 . The biological activity of Valerian and related plants.

Valeriana officinalis is the species most commonly used in northern Europe and still retains its official pharmacopoeial status although it is most commonly encountered as an ingredient of herbal medicines. This plant is still the subject of considerable research aimed at establishing the chemical and pharmacological basis of the activity which has been clearly shown in a number of animal and clinical studies. Valerian is a good example of both the negative and positive aspects of herbal drugs. The considerable variation in its composition and content as well as the instability of some of its constituents pose serious problems for standardization but the range of components which contribute to its overall activity suggest that it may correct a variety of underlying causes of conditions which necessitate a general sedative or tranquilizing effect. From: Houghton PJ. J Pharm Pharmacol 1999;51(5):505-12. The scientific basis for the reputed activity of Valerian.

A randomised, controlled, double-blind trial was performed on 102 male and female volunteers to determine whether reaction time, alertness and concentration might be impaired by treatment with a native valerian root extract. It is concluded that neither single nor repeated evening administrations of 600 mg of Valerian root extract have a relevant negative impact on reaction time, alertness and concentration the morning after intake.
Kuhlmann J, Berger W, Podzuweit H, Schmidt U. Pharmacopsychiatry 1999 Nov;32(6):235-41. The influence of valerian treatment on "reaction time, alertness and concentration" in volunteers.

Aqueous extract of valerian reduces latency to fall asleep in man.
Leathwood PD, Chauffard F. Planta Med 1985;(2):144-8. Aqueous extract of valerian reduces latency to fall asleep in man.

A questionnaire analysis on a mild sedative (400 mg of an aqueous extract of Valeriana officinalis L.) showed that by subjective criteria it is sedative (i.e. it significantly decreased perceived sleep latencies and night awakenings, and improved sleep quality). In an EEG study on the same preparation the pattern of results tended to confirm the subjective evaluation (i.e. shorter mean sleep latency, increased mean latency to first awakening) but the changes did not reach statistical significance.
Leathwood PD, Chauffard F: J Psychiatr Res 1982-83;17(2):115-22. Quantifying the effects of mild sedatives.

Phytopharmacons are widely used in Germany. Whereas kava-kava is prescribed for unspecified anxiety syndromes, hop, balm, lavender, passiflora and valerian are traditionally administered against nervousness and sleep disturbances.
Volz HP.Z Arztl Fortbild Qualitatssich 2001;95(1):33-4. Phytochemicals as means to induce sleep

Kava and valerian are herbal remedies, claimed to have anxiolytic and sedative properties respectively, without dependence potential or any appreciable side-effects. In this pilot study, 24 patients suffering from stress-induced insomnia were treated for 6 weeks with kava 120 mg daily. This was followed by 2 weeks off treatment and then, 5 having dropped out, 19 received valerian 600 mg daily for another 6 weeks. Total stress severity was significantly relieved by both compounds (p < 0.01) with no significant differences between them; as was also insomnia (p < 0.01). The proportion of patients with no side-effects was 58% with each drug respectively and the 'commonest' effect was vivid dreams with valerian (16%), followed by dizziness with kava (12% ). These compounds may be useful in the treatment of stress and insomnia but further studies are required to determine their relative roles for such indications. From: Wheatley D. Phytother Res 2001;15(6):549-51. Kava and valerian in the treatment of stress-induced insomnia.

We present the first reported case of valerian (Valeriana officianalis) overdose. This herb is popular as a sedative but little is known about its toxic effects. The patient presented with mild symptoms, all of which resolved within 24 h. Valerian overdose, at approximately 20 times the recommended therapeutic dose, appears to be benign. From: Willey LB, Mady SP, Cobaugh DJ, Wax PM.: Vet Hum Toxicol 1995;37(4):364-5. Valerian overdose: a case report.


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