Volume 355, Number 9198 8 January 2000
Herb-drug interactions

Adriane Fugh-Berman

Lancet 2000 (Jan 8); 355 (9198): 134-138

George Washington University School of Medicine and Health Sciences, Department of Health Care Sciences, 2150 Pennsylvania Avenue, NW 2B-417, Washington, DC 20037, USA (A Fugh-Berman MD) (e-mail:

Source and extent of review
Misidentification, adulteration, and contamination
Counselling of patients about herb-drug interactions

Concurrent use of herbs may mimic, magnify, or oppose the effect of drugs. Plausible cases of herb-drug interactions include: bleeding when warfarin is combined with ginkgo (Ginkgo biloba), garlic (Allium sativum), dong quai (Angelica sinensis), or danshen (Salvia miltiorrhiza); mild serotonin syndrome in patients who mix St John's wort (Hypericum perforatum) with serotonin-reuptake inhibitors; decreased bioavailability of digoxin, theophylline, cyclosporin, and phenprocoumon when these drugs are combined with St John's wort; induction of mania in depressed patients who mix antidepressants and Panax ginseng; exacerbation of extrapyramidal effects with neuroleptic drugs and betel nut (Areca catechu); increased risk of hypertension when tricyclic antidepressants are combined with yohimbine (Pausinystalia yohimbe); potentiation of oral and topical corticosteroids by liquorice (Glycyrrhiza glabra); decreased blood concentrations of prednisolone when taken with the Chinese herbal product xaio chai hu tang (sho-saiko-to); and decreased concentrations of phenytoin when combined with the Ayurvedic syrup shankhapushpi. Anthranoid-containing plants (including senna [Cassia senna] and cascara [Rhamnus purshiana]) and soluble fibres (including guar gum and psyllium) can decrease the absorption of drugs. Many reports of herb-drug interactions are sketchy and lack laboratory analysis of suspect preparations. Health-care practitioners should caution patients against mixing herbs and pharmaceutical drugs.

"Poisons and medicines are oftentimes the same substances given with different intents."

Peter Mere Latham (1789-1875)

Many medicinal herbs and pharmaceutical drugs are therapeutic at one dose and toxic at another. Interactions between herbs and drugs may increase or decrease the pharmacological or toxicological effects of either component. Synergistic therapeutic effects may complicate the dosing of long-term medications--eg, herbs traditionally used to decrease glucose concentrations in diabetes1 could theoretically precipitate hypoglycaemia if taken in combination with conventional drugs.

Eleutherococcus senticosis (Siberian ginseng)

Herbal medicines are ubiquitous: the dearth of reports of adverse events and interactions probably reflects a combination of under-reporting and the benign nature of most herbs used. Experimental data in the field of herb-drug interactions are limited, case reports scarce, and case series rare. This lack of data is also true of drug-drug interactions: published clinical studies are mainly case reports (controlled trials are scarce, since the random assignment of patients to trials that examine unintended effects is not ethical). The true prevalence of drug interactions is substantial but unknown. One study of 1000 elderly people admitted to a hospital from the emergency department found that 538 patients were exposed to 1087 drug-drug interactions; 30 patients experienced adverse effects as a consequence of these interactions.2 In clinical practice, polypharmacy is common, and to the mixture physicians prescribe, patients add various over-the-counter medications, vitamins, herbs, and foods. All ingested substances have the potential to interact.  

Source and extent of review

Sources for this review include MEDLINE 1966-98 (searched under MeSH terms "drug interactions" combined with "herbal medicine", "traditional medicine", "Chinese traditional medicine", "African traditional medicine", "Ayurvedic medicine", "Oriental traditional medicine", "Unani medicine", and "Arabic medicine"); EMBASE 1994-99 (searched under the same terms); reference dredging; and my own files on the subject.

Many reports of herb-induced interactions lack crucial documentation on temporal relations and concomitant drug use. Perhaps the most serious problem encountered in analysing such reports is the consistent absence of any effort (beyond that of reading the label) to establish a positive identification of the herb involved, and to exclude the effect of contaminants or adulterants. Unless noted otherwise, the reports mentioned herein did not include chemical analyses.

Ginkgo biloba

This review was limited to the most commonly used medicinal plants, and to clinical reports (animal studies are cited where relevant). In-vitro experiments have been excluded, since extrapolation of in-vitro evidence to clinical effects is difficult. For example, St John's wort inhibits monoamine oxidase in vitro; however, in-vivo experiments have shown no such effects, and there have been no reported cases linking St John's wort with hypertensive crises associated with monoamine-oxidase inhibitors.3 However, St John's wort inhibits the uptake of serotonin, norepinephrine, and dopamine in vitro only at quite high concentrations (concentration to inhibit uptake by 50% [IC50] 2·4 mg/L, 4·5 mg/L, and 0·9 mg/L, respectively).4 That anyone could consume enough of this herb to achieve these concentrations in blood is extremely unlikely. Nevertheless, there have been six cases of serotonin syndrome caused by mixing of St John's wort with serotonin-reuptake inhibitors. The tables summarise the interactions identified by the search strategy.5-55

Table 1: Clinical reports of herb-drug interactions (B-G)
Herb and drug(s) Results of interaction Comments
Betel nut (Areca catechu)
Flupenthixol and procyclidine Rigidity, bradykinesia, jaw tremor5 Betal contains arecoline, a cholinergic alkaloid.
Fluphenazine Tremor, stiffness, akithesia5  
Prednisone and salbutamol Inadequate control of asthma Arecoline challenge caused dose-related bronchoconstriction in six asthma patients.6
Chilli pepper (Capsicum spp)
ACE inhibitor Cough7 Capsaicin depletes substance P.
Theophylline Increased absorption and bioavailability8  
Danshen (Salvia miltiorrhiza)    
Warfarin Increased INR, prolonged PT/PTT9-11 In rats, danshen decreases elimination of warfarin.12 Danshen is in at least one brand of cigarettes.13
Devil's claw (Harpagophytum procumbens)
Warfarin Purpura14  
Dong quai (Angelica sinensis)
Warfarin Increased INR15,16 and widespread bruising16 Dong quai contains coumarins.
Eleuthero or Siberian ginseng (Eleutherococcus senticocus)
Digoxin Raised digoxin concentrations17 Herb probably interfered with digoxin assay (patient had unchanged ECG
    despite digoxin concentration of 5·2 nmol/L).
Garlic (Allium sativum)
Warfarin Increased INR18 Postoperative bleeding,19,20 and spontaneous spinal epidural haematoma21 have been reported with garlic alone. Whether garlic prolongs PT is unclear, but it does cause platelet dysfunction.
Ginkgo (Ginkgo biloba)
Aspirin Spontaneous hyphema22 Ginkgolides are potent inhibitors of PAF.23,24
Paracetamol and ergotamine/caffeine Bilateral subdural haematoma25 May not be interaction but due to ginkgo alone. Subarachnoid haemorrhage26
    and subdural haematoma27 have been reported with the use of ginkgo alone.
Warfarin Intracerebral haemorrhage28  
Thiazide diuretic Hypertension18 This effect may be an unusual adverse reaction to the drug or herb; ginkgo
    alone has not been associated with hypertension.
Ginseng (Panax spp)
Warfarin Decreased INR29 In rats, concomitantly administered ginseng had no significant effect on the pharmacokinetics or pharmacodynamics of warfarin.30
Phenelzine Headache and tremor,31 mania32 Patient with mania also ingested bee pollen, and had previously had unipolar depression.
Alcohol Increased alcohol clearance33 In mice, ginseng increases the activity of alcohol dehydrogenase and aldehyde dehydrogenase.
Guar gum (Cyamopsis tetragonolobus)
Metformin, phenoxymethylpenicillin, Slows absorption of digoxin, paracetamol, Guar gum prolongs gastric retention.glibenclamide and bumetanide; decreases absorption of metformin, phenoxymethylpenicillin, and some formulations of glibenclamide18

Table 2: Clinical reports of herb-drug interactions (K-Y)
Herb and drug(s) Results of interaction Comments
Karela or bitter melon (Momordica charantia)
Chlorpropamide Less glycosuria34 Karela decreases glucose concentrations in blood.35
Liquorice (Glycyrrhiza glabra)
Prednisolone Glycyrrhizin decreases plasma clearance, 11ß-dehydrogenase converts endogenous cortisol to cortisone; orally
  increases AUC,36 increases plasma administered glycyrrhizin is metabolised mainly to glycyrrhetinic acid.36
  concentrations prednisolone37  
Hydrocortisone Glycyrrhetinic acid potentiates of cutaneous Glycyrrhetinic acid is a more potent inhibitor of 5-, 5ß-reductase and
  vasoconstrictor response38 11ß-dehydrogenase than is glycyrrhizin.36
Oral contraceptives Hypertension, oedema, hypokalaemia39 Oral contraceptive use may increase sensitivity to glycyrrhizin acid.39 Women are
    reportedly more sensitive than men to adverse effects of liquorice.40
Papaya (Carica papaya)
Warfarin Increased INR14  
Psyllium (Plantago ovata)
Lithium Decreased lithium concentrations41 Hydrophilic psyllium may prevent lithium from ionising.
St John's wort (Hypericum perforatum)
Paroxetine Lethargy/incoherence42  
Trazodone Mild serotonin syndrome43 A similar case is described with the use of St John's wort alone.
Sertraline Mild serotonin syndrome44  
Nefazodone Mild serotonin syndrome44  
Theophylline Decreased theophylline concentrations45  
Digoxin Decreased AUC, decreased peak and trough Most, but not all, studies indicate that St John's wort is a potent inhibitor of
  concentrations46 cytochrome P450 isoenzymes47
Phenprocoumon Decreased AUC48  
Cyclosporin Decreased concentrations in serum49  
Combined oral contraceptive (ethinyloestradiol Breakthrough bleeding49  
and desogestrel)    
Saiboku-to (Asian herbal mixture)
Prednisolone Increased prednisolone AUC50 Contains all the same herbs as sho-saiko-to, and Poria cocos,
    Magnolia officinalis, and Perillae frutescens.
Shankhapushpi (Ayurvedic mixed-herb syrup)
Phenytoin Decreased phenytoin concentrations, loss of In rats, multiple coadministered doses (but not single doses) decreased
  seizure control51 plasma phenytoin concentrations; single doses decreased the antiepileptic
    effect of phenytoin.51 Shankhapushpi is used to treat seizures.
Sho-saiko-to or xiao chai hu tang (Asian
herb mixture)
Prednisolone Decreased AUC for prednisolone50 Contains liquorice (Glycyrrhiza glabra), Bupleurum falcatum, Pinellia ternata,
    Scutellaria baicalensis, Zizyphus vulgaris, Panax ginseng, and Zingiber officinale.
Tamarind (Tamarindus indica)
Aspirin Increased bioavailability of aspirin52 Tamarind is used as a food and a medicine.
Valerian (Valeriana officinalis)
Alcohol A mixture of valepotriates reduces adverse  
  effect of alcohol on concentration53  
Yohimbine (Pausinystalia yohimbe)
Tricyclic antidepressants Hypertension54 Yohimbine alone can cause hypertension, but lower doses cause hypertension
    when combined with tricyclic antidepressants. Effect is stronger in hypertensive
    than normotensive individuals.55
ACE=angiotensin-converting enzyme; INR=international normalised ratio; PT=prothrombin time; PTT=partial thromboplastin time; ECG=electrocardiogram; PAF=platelet-activating factor; AUC=area under the concentration/time curve.


Misidentification, adulteration, and contamination

Labelling of herbal products may not accurately reflect their contents, and adverse events or interactions attributed to specific herbs may actually be due to misidentified plants, pharmaceutical drugs, or heavy metals.56 For example, a "Siberian ginseng" (Eleutherococcus senticosus) product implicated in a case of neonatal androgenisation57 was found on analysis to be an unrelated species, Chinese silk vine (Periploca sepium).58 In Hong Kong, encephalopathy and neuropathy associated with a Chinese herbal preparation purportedly made from the roots of long-dan-cao (Gentiana rigescens) turned out to be due to another plant Podophyllum emodi.56 More than 48 cases of renal poisoning attributed to fang-ji (Stephania tetrandra) in a weight-loss preparation were actually caused by guang-fang-ji (Aristolochia fangchi): aristolochic acid is a known nephrotoxin.56 The confusion in the latter case seems to have arisen from the similarity of the names in Chinese.

Panax ginseng

The addition of pharmaceutical drugs to "herbal" products is a particular problem with Chinese patent medicines. Of 2609 samples of traditional Chinese medicines collected from eight hospitals in Taiwan, 23·7% contained pharmaceutical adulterants, most commonly caffeine, paracetamol, indomethacin, hydrochlorothiazide, and prednisolone.59 Non-steroidal anti-inflammatory drugs and benzodiazepines have been found in many Chinese patent medicines sold outside Asia; these compounds include Miracle Herb, Tung Shueh, and Chuifong Toukuwan.60 The latter preparation is notorious: at different times since 1974, the formulation has contained aminopyrine, phenylbutazone, indomethacin, hydrochlorothiazide, chlordiazepoxide, diazepam, corticosteroids, diclofenac, mefenamic acid, and dexamethasone.61

Valeriana officinalis

Heavy-metal contamination is not uncommon in Asian herbal products. 24 of 251 Asian patent medicines collected from herbal stores in California, USA, contained lead (at least 1 ppm); 36 products contained arsenic, and 35 contained mercury.62

Counselling of patients about herb-drug interactions

Use of herbal and dietary supplements is extremely common: in one US survey of adults who regularly take prescription medication, 18·4% reported the concurrent use of at least one herbal product or high-dose vitamin (and 61·5% of those who used unconventional therapies did not disclose such use to their physicians).63 A survey of 515 users of herbal remedies in the UK found that 26% would consult their general practitioner for a serious adverse drug reaction associated with a conventional over-the-counter medicine, but not for a similar reaction to a herbal remedy.64

Patients may not be forthcoming about the use of herbal medicine--even if it causes severe adverse effects--because they fear censure. Clinicians must ask patients about their use of herbs in a non-judgmental, relaxed way: a disapproving manner will ensure only that a patient will conceal further use. The patient should be treated as a partner in watching out for adverse reactions or interactions, and should be told about the lack of information on interactions and the need for open communication about the use of herbal remedies. Formulation, brand, dose, and reason for use of herbs should be documented on the patient's charts and updated regularly.

Any laxative or bulk-forming agents will speed intestinal transit, and thus may interfere with the absorption of almost any intestinally absorbed drug.65 The most popular stimulant laxative herbs are the anthranoid-containing senna (Cassia senna and C angustifolia) and cascara sagrada (Rhamnus purshiana). Dried exudate from the aloe vera (Aloe barbadensis) leaf (not gel) also contains anthranoids and is used as a laxative. Aloe vera gel, found within the leaves, is used topically for burns and cuts, and is sometimes recommended by herbalists for internal ingestion to treat ulcers and other disorders. The gel (or juice made from the gel) does not contain anthranoids, but some oral preparations are contaminated by the laxative leaf. Less commonly used anthranoid-containing plants are frangula (Rhamnus frangula), yellow dock (Rumex crispus), and Chinese rhubarb (Rheum officinale).

Patients with clotting disorders, those awaiting surgery, or those on anticoagulant therapy should be warned against the concurrent use of ginkgo, danshen, dong quai, papaya, or garlic. Although the combined use of anticoagulants with these herbs should be discouraged, patients who insist on the combination should have their bleeding times monitored (most of these herbs interfere with platelet function, not the coagulation cascade, and thus will not affect prothrombin time, partial thromboplastin time, or international normalised ratio [INR]). Many other herbs also contain anticoagulant substances; as a precaution, patients on warfarin should have an INR measurement within a week of starting any herbal treatment.

Patients on serotonin-reuptake inhibitors, cyclosporin, digoxin, phenprocoumon, or any critical chronic medication should avoid St John's wort; those on phenelzine should avoid ginseng; and those on tricyclic antidepressants should avoid yohimbine. Patients taking phenytoin should avoid Ayurvedic herbal mixtures for seizures. Liquorice (a very common ingredient in Chinese herb mixtures) may potentiate the action of corticosteroids, and betel nuts have pronounced cholinergic effects. There are doubtless many as yet undiscovered interactions.

I thank Dennis Awang and Ted Kaptchuk for helpful comments on the paper.


1 Bailey CJ, Day C. Traditional plant medicines as treatments for diabetes. Diabetes Care 1989; 12: 553-64.

2 Doucet J, Chassagne P, Trivalle C, et al. Drug-drug interactions related to hospital admissions in older adults: a prospective study of 1000 patients. J Am Geriatr Soc 1996; 44: 944-48.

3 Fugh-Berman A, Cott JM. Dietary supplements and natural products as psychotherapeutic agents. Psychosom Med 1999; 61: 712-28.

4 Cott JM, Fugh-Berman A. Is St John's Wort (Hypericum perforatum) an effective antidepressant? J Nerv Ment Dis 1998; 186: 500-01.

5 Deahl M. Betel nut-induced extrapyramidal syndrome: an unusual drug interaction. Mov Disord 1989; 4: 330-33.

6 Taylor RFH, Al-Jarad N, John LME. Betel-nut chewing and asthma. Lancet 1992; 339: 1134-36.

7 Hakas JF. Topical capsaicin induces cough in patient receiving ACE inhibitor. Ann Allergy 1990; 65: 322.

8 Bouraoui A, Toum A, Bouchoucha S, et al. Influence de l'alimentation épicéé et piquante sur l'absorption de la théophylline. Thérapie 1986; 41: 467-71.

9 Tam LS, Chan TYK, Leung WK, Critchley JAJH. Warfarin interactions with Chinese traditional medicines; danshen and methyl salicylate medicated oil. Aust NZ J Med 1995; 25: 257.

10 Yu CM, Chan JCN, Sanderson JE. Chinese herbs and warfarin potentiation by 'danshen'. J Intern Med 1997; 241: 337-39.

11 Izzat MB, Yim APC, El-Zufari MH. A taste of Chinese medicine. Ann Thorac Surg 1998; 66: 941-42.

12 Chan K, Lo AC, Yeung JH, Woo KS. The effects of danshen (Salvia miltiorrhiza) on warfarin pharmacodynamics and pharmacokinetics of warfarin enantiomers in rats. J Pharm Pharmacol 1995; 47: 402-06.

13 Cheng TO. Warfarin danshen interaction. Ann Thorac Surg 1999; 67: 892-96.

14 Shaw D, Leon C, Kolev S, Murray V. Traditional remedies and food supplements: a five year toxicological study (1991-1995). Drug Saf 1997; 17: 342-56.

15 Page RL, Lawrence JD. Potentiation of warfarin by dong quai. Pharmacotherapy 1999; 19: 870-76.

16 Ellis GR, Stephens MR. Untitled (photograph and brief case report). BMJ 1999; 319: 650.

17 McRae S. Elevated serum digoxin levels in a patient taking digoxin and Siberian ginseng. Can Med Assoc J 1996; 155: 293-95.

18 De Smet PAGM, D'Arcy PF. Drug interactions with herbal and other non-toxic remedies. In: D'Arcy PF, McElnay JC, Welling PG, eds. Mechanisms of drug interactions. Berlin: Springer-Verlag, 1996.

19 Burnham BE. Garlic as a possible risk for postoperative bleeding. Plast Reconstruc Surg 1995; 95: 213.

20 German K, Kumar U, Blackford HN. Garlic and the risk of TURP bleeding. Br J Urol 1995; 76: 518.

21 Rose KD, Croissant PD, Parliament CF, Levin MB. Spontaneous spinal epidural hematoma with associated platelet dysfunction from excessive garlic consumption: a case report. Neurosurgery 1990; 26: 880-82.

22 Rosenblatt M, Mindel J. Spontaneous hyphema associated with ingestion of ginkgo biloba extract. N Engl J Med 1997; 336: 1108.

23 Lamant V, Mauco G, Braquet P, Chap H, Douste-Blazy L. Inhibition of the metabolism of platelet activating factor (PAF-acether) by three specific antagonists from Ginkgo biloba. Biochem Pharmacol 1987; 36: 2749-52.

24 Chung KF, McCusker M, Page CP, et al. Effect of a ginkgolide mixture (BN 52063) in antagonizing skin and platelet responses to platelet activating factor in man. Lancet 1987; i: 248-50.

25 Rowin J, Lewis SL. Spontaneous bilateral subdural hematomas associated with chronic Ginkgo biloba ingestion. Neurology 1996; 46: 1775-76.

26 Vale S. Subarachnoid haemorrhage associated with ginkgo biloba. Lancet 1998; 352: 36.

27 Gilbert GJ. Ginkgo biloba. Neurology 1997; 48: 1137.

28 Matthews MK. Association of Ginkgo biloba with intracerebral hemorrhage. Neurology 1998; 50: 1933.

29 Janetzky K, Morreale AP. Probable interaction between warfarin and ginseng. Am J Health Syst Pharm 1997; 54: 692-93.

30 Zhu M, Chan KW, Ng LS, et al. Possible influences of ginseng on the pharmacokinetics and pharmacodynamics of warfarin in rats. J Pharm Pharmacol 1999; 51: 175-80.

31 Shader RI, Greenblatt DJ. Phenelzine and the dream machine--ramblings and reflections. J Clin Psychopharmacol 1985; 5: 65.

32 Jones BD, Runikis AM. Interaction of ginseng with phenelzine. J Clin Psychopharmacol 1987; 7: 201-02.

33 Lee FC, Ko JH, Park JK, Lee JS. Effects of Panax ginseng on blood alcohol clearance in man. Clin Exp Pharmacol Physiol 1987; 14: 543-46.

34 Aslam M, Stockley IH. Interaction between curry ingredient (karela) and drug (chlorpropamide). Lancet 1979; i: 607.

35 Leatherdale BA, Panesar RK, Singh G, et al. Improvement in glucose tolerance due to Momordica charantia (karela). BMJ 1981; 282: 1823-24.

36 Chen M-F, Shimada F, Kato H, et al. Effect of oral administration of glycyrrhizin on the pharmacokinetics of prednisolone. Endocrinol Jpn 1991; 38: 167-75.

37 Chen M-F, Shimada F, Kato H, et al. Effect of glycyrrhizin on the pharmacokinetics of prednisolone following low dosage of prednisolone hemisuccinate. Endocrinol Jpn 1990; 37: 331-41.

38 Teelucksingh S, Mackie ADR, Burt D, et al. Potentiation of hydrocortisone activity in skin by glycyrrhetinic acid. Lancet 1990; 335: 1060-63.

39 De Klerk GJ, Nieuwenhuis MG, Beutle JJ. Hypokalaemia and hypertension associated with use of liquorice flavoured chewing gum. BMJ 1997; 314: 731-32.

40 Bernardi M, D'Intino PE, Trevisani F, et al. Effects of prolonged graded doses of licorice by healthy volunteers. Life Sci 1994; 55: 863-72.

41 Perlman BB. Interaction between lithium salts and ispaghula husk. Lancet 1990; 335: 416.

42 Gordon JB. SSRIs and St John's wort: possible toxicity? Am Fam Phys 1998; 57: 950.

43 Demott K. St John's wort tied to serotonin syndrome. Clin Psychiatry News 1998; 26: 28.

44 Lantz MS, Buchalter E, Giambanco V. St John's Wort and antidepressant drug interactions in the elderly. J Geriatr Psychiatr Neurol 1999; 12: 7-10.

45 Nebel A, Schneider BJ, Baker RK, Kroll DJ. Potential metabolic interaction between St John's Wort and theophylline. Ann Pharmacother 1999; 33: 502.

46 Johne A, Brockmöller J, Bauer S, et al. Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum). Clin Pharmacol Ther 1999; 66: 338-45.

47 Ernst E. Second thoughts about safety of St John's wort. Lancet 1999; 354: 2014-15.

48 Maurer A, Johne A, Bauer S, et al. Interaction of St John's wort extract with phenprocoumon. Eur J Clin Pharmacol 1999; 55: A22.

49 Bon S, Hartmann K, Kuhn M. Schweitzer Apothekerzeitung 1999; 16: 535-36.

50 Homma M, Oka K, Ikeshima K, et al. Different effects of traditional Chinese medicines containing similar herbal constituents on prednisolone pharmacokinetics. J Pharm Pharmacol 1995; 47: 687-92.

51 Dandekar UP, Chandra RS, Dalvi S, et al. Analysis of clinically important interaction between phenytoin and Shankhapushpi, an Ayurvedic preparation. J Ethnopharm 1992; 35: 285-88.

52 Mustapha A, Yakasai IA, Aguye IA. Effect of Tamarindus indica L on the bioavailability of aspirin in healthy human volunteers. Eur Drug Metab Pharmacokinet 1996; 21: 223-26.

53 Bos R, Woerdenberg HJ, De Smet PAGM, Scheffer JJC. Valeriana species. In: De Smet PAGM, Keller K, Hansel R, Chandler RF, eds. Adverse effects of herbal drugs, vol 3. Berlin: Springer, 1997: 165-80.

54 Lacombiez L, Bensimon G, Isnard F, et al. Effect of yohimbine on blood pressure in patients with depression and orthostatic hypertension induced by clomipramine. Clin Pharmacol Ther 1989; 45: 241-51.

55 De Smet PAGM. Yohimbe alkaloids--general discussion. In: De Smet PAGM, Keller K, Hansel R. Chandler RF, eds. Adverse effects of herbal drugs, volume 3. Berlin: Springer, 1997: 181-206.

56 But PP-H. Herbal poisoning caused by adulterants or erroneous substitutes. J Trop Med Hyg 1994; 97: 371-74.

57 Koren G, Randor S, Martin S, Danneman D. Maternal ginseng use associated with neonatal androgenization. JAMA 1990; 264: 2866.

58 Awang DVC. Maternal use of ginseng and neonatal androgenization. JAMA 1991; 266: 363.

59 Huang WF, Wen K-C, Hsiao M-L. Adulteration by synthetic therapeutic substances of traditional Chinese medicines in Taiwan. J Clin Pharmacol 1997; 37: 344-50.

60 Gertner E, Marshall PS, Filandrinos D, et al. Complications resulting from the use of Chinese herbal medications containing undeclared prescription drugs. Arthritis Rheum 1995; 38: 614-17.

61 Vander Stricht BI, Parvais OE, Vanhaelen-Fastre RJ. Remedies may contain cocktail of active drugs. BMJ 1994; 308: 1162.

62 Ko RJ. Adulterants in Asian patent medicines. N Engl J Med 1998; 339: 847.

63 Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative medicine use in the United States, 1990-97. JAMA 1998; 280: 1569-75.

64 Barnes J, Mills SY, Abbott NC, et al. Different standards for reporting ADRs to herbal remedies and conventional OTC medicines: face to face interviews with 515 users of herbal remedies. Br J Clin Pharmacol 1998; 45: 496-500.

65 Westendorf J. Anthranoid derivatives--general discussion. In: De Smet PAGM, Keller K, Hansel R, Chandler RF. Adverse effects of herbal drugs, vol 2: 105-08.