Uses of this Herb
Peptic Ulcer
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  Drugs that Interact
Angiotensin-Converting Enzyme (ACE) Inhibitors
Aspirin-containing Medications
Hydrocortisone-containing Medications
Loop Diuretics
Oral Contraceptives
Prednisolone-containing Medications
Thiazide Diuretics
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Look Up > Herbs > Licorice > Interactions
Interactions with Licorice
Angiotensin-Converting Enzyme (ACE) Inhibitors

ACE inhibitors enhance the dehydrogenase activity of 11b-hydroxysteroiddehydrogenase (11b-HSD), which is thought to contribute to their ability to cause sodium excretion by the kidneys (Kerstens and Dullaart 1999). Licorice reduces the action of 11b-HSD; in so doing, licorice may oppose some of the antihypertensive effects of ACE inhibitors.


Deglycyrrhizinated licorice (DGL) (100 mg, 300 mg, or 500 mg) administered with aspirin (60 mg po) reduced ulcer formation and blood loss in rats (Rees et al. 1979). The effects of licorice on aspirin-induced gastric mucosal injury also were evaluated in a double-blind cross-over study with nine healthy male volunteers. Less blood loss was associated with aspirin ingestion (325 mg tid) when administered concurrently with DGL (175 mg). It has also been shown that licorice-coated aspirin significantly reduced the number and size of ulcers in the gastric mucosa of animals compared to aspirin alone (Dehpour et al. 1994).


In rats, low doses of cimetidine taken with DGL (50 mg) provided greater protection against aspirin-induced gastric mucosal damage than either deglycyrrhizinated licorice or cimetidine alone (Bennett et al. 1980).


Licorice not only induces high blood pressure in some patients but also causes clinically significant hypokalemia, resulting in myopathy and arrhythmia (Sailler et al. 1993; Shintani et al. 1992). Patients with hypokalemia may be predisposed to development of digoxin toxicity due to sensitization of the myocardium to digoxin in the setting of low serum potassium (Physicians' Desk Reference 1999). Although licorice-induced hypokalemia and its subsequent effects on digoxin are not well documented, the known effect described raise a theoretical concern.

Hydrocortisone; Prednisolone

A study conducted with volunteers and patients with psoriasis and eczema demonstrated that application of glycyrrhetinic acid enhanced vasoconstriction and glucocorticoid activity in skin by local inhibition of 11b-HSD (Teelucksingh et al. 1990). This report also noted that in vitro studies in nude mice confirmed the inhibition of this enzyme in skin. The report also suggested that topical application of glycyrrhetinic acid significantly enhanced the anti-inflammatory activity of topical hydrocortisone compared to hydrocortisone alone.

Systemic administration of glycyrrhizin with prednisolone to humans was shown to alter the pharmacokinetic parameters of prednisolone by significantly increasing the concentrations of both total and free prednisolone in plasma (Chen et al. 1990; Chen et al. 1991). These results suggest that ingestion of licorice could interact with corticosteroid treatment. Similarly, in early animal studies of rats and rabbits, glycyrrhizin exhibited an ability to enhance the immunosuppressive effects of cortisone (Kumagai et al. 1967).

Loop Diuretics; Thiazide Diuretics

When licorice-containing substances were combined with diuretics, patients were at increased risk of developing glycyrrhizin-induced hypokalemic myopathy (GIHM) (Shintani et al. 1992). In 96.6% of the cases studied, GIHM resolved completely by supplementing with potassium and discontinuing the glycyrrhizin.

Ingestion of licorice (200 g/day) for 10 weeks concurrent with a thiazide diuretic for two weeks resulted in the development of severe hypokalemia, arterial hypertension, edema, and rhabdomyolysis in a 38-year-old man (Folkersen et al. 1996). A hypertensive 70-year-old man who ingested licorice candy (100 g/day) for 4 to 5 years became pathologically hypokalemic when treated with thiazide diuretics (Farese et al. 1990). (Note: these doses greatly exceed the amounts of licorice recommended to avoid side effects and toxicity; see sections entitled "Dosage Ranges and Duration of Administration" and "Side Effects/Toxicology.")

Oral Contraceptives

A healthy female volunteer taking oral contraceptives developed hypertension, hypokalemia, and peripheral edema after four weeks of ingestion of dried, aqueous extract of licorice root at doses up to 814 mg (Bernardi et al. 1994). There are two other case reports cited in the literature involving women who also developed hypokalemia and hypertension when they used licorice chewing gum while on oral contraceptives (de Klerk et al. 1997). Symptoms resolved upon discontinuation of the licorice chewing gum.


Bennett A, Clark-Wibberley T, Stamford IF, Wright JE. Aspirin-induced gastric mucosal damage in rats: cimetidine and deglycyrrhizinated liquorice together give greater protection than low doses of either drug alone. J Pharm Pharmacol. 1980;32(2):150.

Bernardi M, D'Intino PE, Trevisani F, et al. Effects of prolonged ingestion of graded doses of licorice by healthy volunteers. Life Sci. 1994;55(11):863-872.

Chen MF, Shimada F, Kato H, Yano S, Kanaoka M. Effect of glycyrrhizin on the pharmacokinetics of prednisolone following low dosage of prednisolone hemisuccinate. Endocrinol Jpn. 1990;37(3):331-341.

Chen MF, Shimada F, Kato H, Yano S, Kanaoka M. Effect of oral glycyrrhizin on the pharmacokinetics of prednisolone. Endocrinol Jpn. 1991;38(2):167-174.

de Klerk GJ, Nieuwenhuis C, Beutler JJ. Hypokalemia and hypertension associated with use of liquorice flavoured chewing gum. BMJ. 1997;314:731-732.

Dehpour AR, Zolfaghari ME, Samadian T. The protective effect of liquorice components and their derivatives against gastric ulcer induced by aspirin in rats. J PharmPharmacol. 1994;46(2):148-149.

Farese RV, Biglieri EG, Shakelton CHL, et al. Licorice-induced hypermineralcorticoidism. N Engl J Med. 1990;325(17):1223-1227.

Folkersen L, Knudsen NA, Teglbjaerg PS. [Licorice. A basis for precautions one more time!]. Ugeskr Laeger. 1996;158(51):7420-7421.

Kerstens MN, Dullaart R. 11 Beta-hydroxysteroid dehydrogenase: characteristics and the clinical significance of a key enzyme in cortisol metabolism [in Dutch]. Ned Tijdschr Geneeskd. 1999;143(10):509-514.

Kumagai A, Nanaboshi M, Asanuma Y, Yagura T, Nishino K, Yamamura Y. Effects of glycyrrhizin on thymolytic and immunosuppressive action of cortisone. Endocrinol Jpn. 1967;14(1):39-42.

Physicians' Desk Reference. 53rd ed. Montvale, NJ: Medical Economics Company, Inc.; 1999.

Rees WD, Rhodes J, Wright JE, Stamford LF, Bennett A. Effect of deglycyrrhizinated liquorice on gastric mucosal damage by aspirin. Scand J Gastroenterol. 1979;14:605-607.

Sailler L, Juchet H, Ollier S, Nicodeme R, Arlet P. Potassium loss may increase effects, especially of digitalis and related glycosides. [Generalized edema caused by licorice: a new syndrome. Apropos of 3 cases.] Rev Med Interne. 1993;14(10):984.

Shintani S, Murase H, Tsukagoshi H, Shiigai T. Glycyrrhizin (licorice)-induced hypokalemic myopathy. Eur Neuro. 1992;32:44-51.

Teelucksingh S, Mackie ADR, Burt D, McIntyre MA, Brett L, Edwards CR. Potentiation of hydrocortisone activity in skin by glycyrrhetinic acid. Lancet. 1990;335:1060-1063.

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