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Orally administered delta9-tetrahydrocannabinol (THC) produced a dose-dependent increase in urine output in hydrated rats similar in mg/kg potency and magnitude of effect to hydrochlorothiazide (HCT). Whereas HCT promoted marked excretion of Na+, K+ and Cl- and an increase in the urinary Na+/K+ at all diuretic doses (1.25-20.0 mg/kg), THC had only a slight effect on Na+ and K+ excretion but not Cl- even after the highest dose tested (20.0 mg/kg). Hypophysectomy and adrenalectomy abolished the diuretic effect of THC, thus suggesting both central and peripheral sites of action for the diuretic effect of THC. Tolerance to the effect on urine output by THC developed after 15 days of repeated dosing, while urine output and electrolyte excretion remained significantly elevated after 25 days of HCT administration.
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