Role of the central autonomic nervous system in the hypotension and bradycardia induced by (-)-Δ9-trans-tetrahydrocannabinol

Abstract

( -)-A9-t~ans-Tetrahydrocannabinol (A9-THC), when given intravenously (2 mg kg-I) to cats, produced marked decreases in blood pressure and heart rate which developed gradually and were of prolonged duration. Cervical spinal transection (Cl-C,) abolished these effects whereas surgical removal of neurogenic tone to the myocardium selectively eliminated the bradycardia. Bilateral vagotomy alone did not modify the action of AS-THC upon heart rate or blood pressure. Recordings of spontaneous sympathetic outflow in the inferior cardiac nerve indicated a rapid reduction in neural discharge rate after AS-THC administration. These observations support the hypothesis that AS-THC produces a cardiodecellerator and hypotensive effect by acting at some level within the sympathetic nervous system. Experiments conducted to investigate transmission in the superior cervical and stellate ganglia demonstrated that AS-THC did not alter ganglionic function. Also, responses to intravenous isoprenaline and noradrenaline were unchanged which suggested that AS-THC did not interact with a-or p-adrenoceptors. The possible action of Ag-THC on central sympathetic structures was investigated by perfusion of As-THC into the lateral cerebral ventricle. AS-THC so administered produced a significant reduction in heart rate without a substantial lowering of blood pressure. Tritiated or 14C-A9-THC perfused into the lateral ventricle demonstrated that the amount of radioactive compound passing into the peripheral circulation was insignificant and could not account for the decrease in heart rate. The current data are in agreement with the proposal that A9-THC produces cardiovascular alterations by an action on the central nervous system which results in a decrease in sympathetic tone.(-)-As-trans-Tetrahydrocannabinol (A9-THC), a psychoactive constituent of marihuana, and several other tetrahydrocannabinols produce cardiovascular alterations in man (Hollister,

Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice

“…The reason for this increased mortality is currently unknown and needs to be determined in future experiments. As cannabinoids can cause pronounced hypotension and bradycardia (33,34), probably through activation of the CB1 receptor (35,36), it is conceivable that CB1 knockout mice may succumb to latent cardiovascular problems. Alternatively, CB1 Ϫ/Ϫ mice have an increased risk of developing neurological problems such as seizures.…”

G Protein-coupled Endothelial Receptor for Atypical Cannabinoid Ligands Modulates a Ca2+-dependent K+ Current

“…In addition to displaying well described neurobehavioral effects (6), cannabinoid receptor agonists elicit prolonged hypotension and bradycardia (7). These effects are mediated by the CB 1 receptor as shown by the use of the selective CB 1 antagonist SR141716 (8), or CB 1 receptor-deficient mice (9,10).…”

Endocannabinoids Acting at Cannabinoid-1 Receptors Regulate Cardiovascular Function in Hypertension

“…1 Effective treatment of hypertension reduces complications and improves life expectancy; however, side effects of available antihypertensive medications and differences in their efficacy in preventing end-organ damage justify the search for antihypertensive agents that act through novel mechanisms of action. ⌬ 9 -Tetrahydrocannabinol, the psychoactive ingredient of marijuana, lowers blood pressure and heart rate in experimental animals, 2,3 and hypotension has been reported after chronic marijuana use in humans. 4 The endogenous cannabinoid ligands arachidonoyl ethanolamide (anandamide) and 2-arachidonoylglycerol (2-AG) also lower blood pressure and heart rate in rodents.…”