Spironolactone and Cannabis Interaction Profile

Is There a Known Interaction Between Spironolactone and Cannabis?

The Aldactone label does not list cannabis among its drug interactions [1]. The drug interactions section names specific drugs and classes: potassium supplements, salt substitutes, ACE inhibitors, angiotensin receptor blockers, NSAIDs, heparin, trimethoprim, lithium, digoxin assays, cholestyramine, aspirin, abiraterone and mitotane [1].

What the Label Says to Watch With Spironolactone Itself

Spironolactone blocks aldosterone at the kidney's sodium-potassium exchange site, so more sodium and water are excreted while potassium is retained [1].

The label says hyperkalemia risk rises with impaired renal function, potassium supplements, potassium-containing salt substitutes, and drugs that raise potassium such as ACE inhibitors and ARBs [1]. It says to monitor serum potassium within one week of initiation or titration and regularly thereafter, more often with other potassium-raising drugs or impaired kidney function, and to decrease the dose or discontinue and treat if hyperkalemia occurs [1].

The label also says excessive diuresis can cause symptomatic dehydration, hypotension and worsening renal function, particularly in salt-depleted patients or those taking ACE inhibitors or ARBs; NSAIDs, aminoglycosides and cisplatin add renal risk [1].

What Is Known About Cannabis and Cardiovascular Risk

A review of marijuana use in patients with cardiovascular disease notes cannabinoid receptors across tissue beds and cells, including platelets, adipose tissue and myocytes, and says observational data suggest associations between marijuana and a broad range of adverse cardiovascular risks [2]. It notes that marijuana is becoming more potent, that smoking marijuana carries many of the same cardiovascular hazards as smoking tobacco, and that Schedule I classification limits rigorous study of cardiovascular effects [2]. It encourages screening for marijuana use, especially in young patients presenting with cardiovascular disease [2].

Spironolactone for Acne: The Relevant Numbers

Acne is not a labeled indication; the labeled uses are heart failure, add-on hypertension, edema and primary hyperaldosteronism [1]. In the SAFA trial, 410 women with persistent facial acne took spironolactone 50 mg/day to week 6 then 100 mg/day to week 24, or placebo; the acne-specific quality of life symptom score favored spironolactone by 3.77 points (95% CI 2.50 to 5.03) at 24 weeks, and investigator-rated success at week 12 was 18.5% versus 5.6% [3].

In a retrospective study of 974 healthy young women taking spironolactone for acne, 13 of 1802 potassium measurements were abnormal (0.72%), similar to the 0.76% baseline rate in 1165 comparison women, and 6 of the 13 repeat values were normal [4]. The authors excluded women with heart or kidney disease and those taking drugs that affect the renin-angiotensin system. The Aldactone label itself still advises potassium monitoring [1].

What to Watch For

Label-listed adverse reactions include dizziness, lethargy, mental confusion, ataxia, headache, drowsiness and leg cramps, along with hyperkalemia, hyponatremia and hypovolemia [1]. Gynecomastia is the most common adverse reaction; in RALES about 9% of men developed it at a mean dose of 26 mg/day, and risk rises with dose [1].