Chronic marijuana smoke exposure in the rhesus monkey. IV: Neurochemical effects and comparison to acute and chronic exposure to delta-9-tetrahydrocannabinol (THC) in rats.
S F Ali, Glenn D. Newport, Andrew C. Scallet, Merle G. Paule, J R Bailey, William Slikker
Pharmacology, Biochemistry, and Behavior November 1991 DOI: 10.1016/0091-3057(91)90381-b (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study (in vitro binding assays plus acute and chronic in vivo exposure in rats and monkeys) Peer reviewed |
|---|---|
| Population | Rat brain membranes and live rats; rhesus monkeys exposed to marijuana smoke |
| Interventions | THC Marijuana smoke Cannabidiol Cannabinol |
| Dose | 1-100 nM in vitro; 1, 3, 10, or 30 mg THC/kg IP acutely; 10 or 20 mg THC/kg daily, 5 days/week for 90 days; 2.6% THC cigarette smoke |
| Duration | 2 h after acute injection; 90 days chronic rat dosing with sacrifice at 24 h or 2 months; 1 year monkey smoke exposure with sacrifice about 7 months after last exposure |
| Measures | Muscarinic cholinergic receptor binding, neurotransmitter receptor binding, neurotransmitter concentrations |
| Topics | Cannabis |
| Key findings | THC inhibited muscarinic cholinergic receptor binding in isolated rat brain membranes in a dose-dependent manner, but cannabidiol and cannabinol did the same, suggesting the effect is not specific to THC's psychoactivity. In living rats and monkeys, acute or chronic THC or marijuana smoke exposure produced no significant changes in receptor binding or neurotransmitter concentrations. |
Abstract
THC is the major psychoactive constituent of marijuana and is known to produce psychopharmacological effects in humans. These studies were designed to determine whether acute or chronic exposure to marijuana smoke or THC produces in vitro or in vivo neurochemical alterations in rat or monkey brain. For the in vitro study, THC was added (1-100 nM) to membranes prepared from different regions of the rat brain and muscarinic cholinergic (MCh) receptor binding was measured. For the acute in vivo study, rats were injected IP with vehicle, 1, 3, 10, or 30 mg THC/kg and sacrificed 2 h later. For the chronic study, rats were gavaged with vehicle or 10 or 20 mg THC/kg daily, 5 days/week for 90 days and sacrificed either 24 h or 2 months later. Rhesus monkeys were exposed to the smoke of a single 2.6% THC cigarette once a day, 2 or 7 days a week for 1 year. Approximately 7 months after the last exposure, animals were sacrificed by overdose with pentobarbital for neurochemical analyses. In vitro exposure to THC produced a dose-dependent inhibition of MCh receptor binding in several brain areas. This inhibition of MCh receptor binding, however, was also observed with two other nonpsychoactive derivatives of marijuana, cannabidiol and cannabinol. In the rat in vivo study, we found no significant changes in MCh or other neurotransmitter receptor binding in hippocampus, frontal cortex or caudate nucleus after acute or chronic exposure to THC. In the monkey brain, we found no alterations in the concentration of neurotransmitters in caudate nucleus, frontal cortex, hypothalamus or brain stem.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.