Administration of delta-9-tetrahydrocannabinol (THC) to the anesthetized dog produces a marked and prolonged hypotension ( 1). In normal man, marihuana extracts or THC, which produce marked psychological alterations, do not alter blood pressure in a systematic fashion (2-4).In the present experiments, the effects of THC and of marihuana extract distillate (MED) were evaluated in spontaneous hypertensive rats (SHR). This strain has been used to test the efficacy of different antihypertensive drugs (5). Because of the rapid development of tolerance (6) to many of the effects of THC, the drug was administered over a period of several days.Materials and Methods. Two groups of 12 SHR were fed through a stomach tube 5 to 25 mg/kg of THC in 3% cornstarch with Tween 80. In a first series of experiments, 5 mg/kg THC was administered to 12 hypertensive rats for 5 days. In a second series, dosage of THC was increased over a period of 10 days to 25 mg/kg. In a third group of 12 SHR, MED was administered in dosages containing 5 to 25 mg of THC. Blood pressure was measured daily by the tail plethysmography method and heart rate was computed. Measurements were made once daily in the morning for 3 days, to obtain mean control values. During the test period, measurements of blood pressure were performed once daily 24 hr after administration of the drug. The animals were also weighed daily.Results. Following administration of 5 mg/ kg THC, a significant decrease in blood pressure was observed during the first 2 days 1The THC and MED used in this study were provided by the National Institute of Mental Health. This work was supported by NIH Grant GM-09069-10 and a gift from Mr. Henri G. Dsoll.
58after treatment. The maximum decrease occurred 24 hr after the first dose (21 mm Hg t 3). However, by the third day, blood pressure was not significantly different from control. The animals lost weight significantly throughout the period of treatment (Fig. 1).In a second series of experiments, increasing the dosage of THC to 10 and 25 mg/kg produced only transient decreases in blood pressure, while weight loss was maintained throughout the period of treatment (Fig. 2). Heart rate, measured 24 hr after treatment with THC, was not signi,ficantly different from control. Significant bradycardia was only observed 3 hr after administration of the highest dose (25 mg/kg). After repeated administration of the higher dosage of THC, the animals displayed aggressive behavior, inflicting wounds upon each other.Similar results were observed when the Delta 9 THC 5 --I0
Renal studies were made on ten dogs treated with an infusion of tris(hydroxymethyl)aminomethane (THAM) during a CO2 load induced by apneic oxygenation. There was a 5 fold increase in diuresis with no significant change in inulin clearance. The urine-plasma osmolal ratio approached unity and there was a rapid elimination of the infusate demonstrating that THAM acts largely as an osmotic diuretic. The clearance of THAM was similar to that of inulin until plasma levels exceeded 19 mEq/liter. At that time the amount of THAM eliminated exceeded the filtered load indicating tubular excretion. The percentage of the filtered load of K excreted increased from 24 to more than 100% and, in spite of a rising pCO2, the tubular reabsorption of bicarbonate reached a plateau after 20 min indicating that when THAM penetrates into the tubular cell, it interferes with the (H+) – (Na+) exchange mechanism. After 1 hr 35% of the THAM given had been excreted and after 4 days up to 93% had been recovered in the urine. The amount of ionized THAM excreted approximated the cationic deficit within 10%. There was a significant net increase in H+ excretion which paralleled the elimination of ionized THAM (R.NH3+).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.