The pharmacological activity of inhalation exposure to marijuana smoke in mice

Although the majority of cannabinoid users smoke marijuana, the preponderan ce of laboratory animal research is based on administration of Delta (9)-te lrahydrocannabinol (Delta (9)-THC) or other cannabinoid agents via injectio n. The aim of the present study was to evaluate the impact of inhaling mari juana, or ethanol-extracted placebo smoke in the mouse model of cannabinoid activity by assessing inhibition of spontaneous activity, antinociception, catalepsy, and body temperature. In order to determine dosimetry, blood le vels of Delta (9)-THC were obtained following either marijuana exposure or intravenous injection of Delta (9)-THC. Inhalation exposure to marijuana pr oduced dose-related increases in antinociception and catalepsy, with estima ted ED50 doses of Delta (9)-THC of 2.4 and 3.8 mg/kg, respectively. However , hypothermia and locomotor depression occurred in both the placebo- and ma rijuana-exposed mice. The CB1 receptor antagonist, SR 141716A antagonized t he antinociceptive effects of marijuana (AD(50) = 0.6 mg/kg), but only slig htly decreased marijuana-induced catalepsy, and failed to alter either the hypothermic or locomotor depressive effects. In contrast, SR 141716A antago nized the antinociceptive, cataleptic, and hypothermic effects of intraveno usly administered Delta (9)-THC in mice that were exposed to air alone, tho ugh all subjects exhibited locomotor depression, possibly related to the re straint. In accordance with reports of others, these data suggest that expo sure to smoke alone has pharmacological consequences. Our findings also ind icate that marijuana-induced antinociception is mediated through a CB1-rece ptor mechanism of action and are consistent with the notion that Delta (9)- THC is mainly responsible for this effect. (C) 2001 Elsevier Science Irelan d Ltd. All rights reserved.