TOLERANCE TO THE CARDIOVASCULAR EFFECTS OF Δ9‐TETRAHYDROCANNABINOL IN THE RAT

Abstract

1 Daily intraperitoneal injections of Δ⁹-tetrahydrocannabinol (Δ⁹-THC, 10 mg/kg) resulted in tolerance to the effects of the cannabinoid on body weight and body temperature within 1–2 weeks of treatment. 2 Tolerance failed to develop to the suppression of spontaneous motor activity produced by Δ⁹-THC during 28 days of treatment with the cannabinoid (10 mg/kg, i.p. per day). 3 Following treatment with vehicle for 28 days, intravenous administration of Δ⁹-THC in anaesthetized rats produced a transient pressor response followed by a sustained hypotension and bradycardia. 4 Tolerance to the hypotensive and negative chronotropic responses to intravenous Δ⁹-THC was readily apparent in animals which had received daily intraperitoneal injections of Δ⁹-THC (10 mg/kg) for 28 days. 5 Tolerance failed to develop to the pressor actions of intravenous Δ⁹-THC after 28 days of pretreatment. 6 There was no difference in the pressor response to intravenous noradrenaline in vehicle-treated animals (1.0 ml/kg, i.p., per day for 28 days) and Δ⁹-THC-treated animals (10 mg/kg, i.p., per day for 28 days).