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

Br J Pharmacol. 1976 Jan;56(1):43-8. doi: 10.1111/j.1476-5381.1976.tb06957.x.


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).

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Body Temperature / drug effects
  • Body Weight / drug effects
  • Dronabinol / pharmacology*
  • Drug Tolerance
  • Heart Rate / drug effects
  • Hemodynamics / drug effects*
  • Male
  • Motor Activity / drug effects
  • Norepinephrine / pharmacology
  • Rats
  • Time Factors


  • Dronabinol
  • Norepinephrine