Possible mediation of catecholaminergic pathways in the antinociceptive effect of an extract of Cannabis sativa L.

Abstract

An extract of cannabis (5 and 15 mg/kg expressed as delta 9-THC) orally administered to rats caused an elevation of the nociceptive threshold (tail-flick latency and vocalization tests). Naloxone and naltrexone (blockers of mu-type opiate receptors) as well as MR 1452 (blocker of kappa opiate receptors) did not prevent the antinociceptive effect of cannabis when used at the dose of 2 mg/kg SC; only a high dose (10 mg/kg SC) of these narcotic antagonists partially blocked cannabis antinociception. ICI 154, 129, an antagonist of delta-type opiate receptors, failed to prevent the cannabis-induced rise in nociceptive threshold when used at a dose of 2 mg/kg SC but produced a significant effect at 10 mg/kg SC. While the role of opiate receptors does not seem fundamental to cannabis antinociception, the clear-cut effectiveness shown by 6-hydroxydopamine (a neurotoxin which causes a degeneration of catecholamine-containing terminals) in reducing cannabis antinociception is indicative of a participation of catecholamines in the phenomenon.

Suppression of Noxious Stimulus-Evoked Activity in the Ventral Posterolateral Nucleus of the Thalamus by a Cannabinoid Agonist: Correlation between Electrophysiological and Antinociceptive Effects

“…These findings provide a strong basis for the conclusion that the actions of WIN 55,212-2 on pain and movement are mediated by separate processes and suggest that the decreased behavioral responsiveness to noxious stimuli does not result merely from a disruption of motor function. This conclusion is supported by studies that demonstrated antinociceptive actions of cannabinoids in a test (vocalization to shock) that does not require a gross motor response (Ferri et al, 1981(Ferri et al, , 1986.…”

The Future of Cannabinoids as Analgesic Agents: A Pharmacologic, Pharmacokinetic, and Pharmacodynamic Overview

“…28,29 Relation of cannabinoids to dopaminergic neurotransmitters Six-hydroxydopamine produces degeneration in catecholamine terminals that block THC antinociception effects. 30 Cannabimimetic agents cause ''inhibition of the dopaminergic nigrostriatal system.'' 31 Cannabinoid receptors are colocalized with dopamine D 1 receptors on striatonigral dynorphin/substance-P-containing neurones and with dopamine D 2 -receptors on striatopallidal enkephalinergic neurons.…”