Tolerance to the cardiovascular effects of delta9-tetrahydrocannabinol in the rat.

1. Daily intraperitoneal injections of delta9-tetrahydrocannabinol (delta9-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 delta9-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 delta9-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 delta9-THC was readily apparent in animals which had received daily intraperitoneal injections of delta9-THC (10 mg/kg) for 28 days. 5. Tolerance failed to develop to the pressor actions of intravenous delta9-THC after 28 days of preptreatment. 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 delta9-THC-treated animals (10 mg/kg, i.p., per day for 28 days).