Licorice Root Drug Interactions: Blood Pressure, Diuretics, and More
Licorice root is an instructive example of a supplement with a well-understood biochemical mechanism that most users have never heard of. The compound glycyrrhizin — present in most licorice root preparations — mimics excess aldosterone in the body by blocking a critical cortisol-inactivating enzyme. The downstream effects include sodium retention, potassium excretion, and elevated blood pressure. For people taking antihypertensive medications, diuretics, or corticosteroids, this mechanism creates real drug interactions that can undermine treatment. One important exception exists and is worth knowing upfront: deglycyrrhizinated licorice (DGL), a form commonly used for GI conditions, has had glycyrrhizin removed and does not carry these risks.
The 11-beta-HSD2 mechanism
In the kidney tubule, an enzyme called 11-beta-hydroxysteroid dehydrogenase type 2 (11-beta-HSD2) converts active cortisol into inactive cortisone. This matters because cortisol and aldosterone act on the same mineralocorticoid receptors — the ones that control sodium retention and potassium excretion. Without 11-beta-HSD2 doing its job, cortisol would constantly stimulate those receptors at full strength, producing effects indistinguishable from having excess aldosterone in the blood.
Glycyrrhizin inhibits 11-beta-HSD2. The result is exactly what you'd predict from that mechanism: cortisol accumulates at mineralocorticoid receptors, causing sodium and water retention, potassium excretion, and rising blood pressure. Clinically, this produces a syndrome called pseudo-hyperaldosteronism — it looks and acts like primary aldosteronism (Conn's syndrome), but aldosterone levels themselves are actually suppressed as a feedback response. The condition has been documented in people consuming large amounts of licorice candy, licorice tea, and licorice root supplements.
Interactions with antihypertensives, diuretics, and corticosteroids
For someone taking antihypertensive medications — ACE inhibitors like lisinopril, ARBs like losartan, calcium channel blockers like amlodipine, beta-blockers, or thiazide diuretics — licorice root works in the opposite direction. These medications try to lower blood pressure through various mechanisms; licorice-induced sodium and water retention counteracts them. The interaction is pharmacodynamic, not metabolic: the two effects are simply pushing in opposite directions on the same physiological outcome. NCCIH explicitly notes that licorice root may interfere with antihypertensive treatment.
The diuretic interaction is additive rather than antagonistic. Loop diuretics like furosemide and thiazide diuretics like hydrochlorothiazide already cause potassium excretion as a side effect — they're well-known causes of hypokalemia. Licorice root produces its own potassium-wasting effect through the 11-beta-HSD2 mechanism. Combined, the two can drive potassium to significantly lower levels than either alone, with hypokalemia symptoms ranging from muscle weakness and cramps to more serious cardiac effects. People on potassium-wasting diuretics are among those most likely to be harmed by concurrent licorice root use.
Corticosteroids (prednisone, prednisolone, hydrocortisone) add a third dimension. Corticosteroids already promote sodium retention and potassium excretion at therapeutic doses. Glycyrrhizin, by slowing cortisol inactivation, effectively prolongs and amplifies the corticosteroid's mineralocorticoid activity. The result is greater sodium retention and potassium loss than the corticosteroid alone would produce.
DGL (deglycyrrhizinated licorice) is processed to remove glycyrrhizin, which is why it's commonly recommended for people with acid reflux or gastric ulcer symptoms who want to avoid these cardiovascular and electrolyte effects. If the licorice root preparation you're taking specifies that it's DGL, it should not carry these interaction risks — but most standard licorice root supplements and teas are not DGL.