Antianxiety effect of cannabis: involvement of central benzodiazepine receptors.
The present work, involving clinical, behavioral, and biochemical studies, was undertaken to elucidate the probable mechanism of the observed antianxiety effects of cannabis. The population for the clinical study consisted of 50 male chronic cannabis users who were otherwise healthy and 50 matched controls. When evaluated on Taylor's Manifest Anxiety Scale (TMA), these subjects had low anxiety scores as compared with the controls. To explore the possible interaction of cannabis with the benzodiazepine receptors, behavioral and biochemical studies in mice were devised, involving acute and chronic cannabis administration. Behavioral study revealed that mice under chronic cannabis treatment scored significantly higher on foot shock-induced aggression, but this was significantly blocked by benzodiazepine receptor antagonist. Furthermore, chronic cannabis treatment significantly (p less than 0.001) increased the frequency of licking response periodically punished by shocks. This confirms the antianxiety effect of cannabis, which also appears to be mediated through a benzodiazepine receptor, as it was reduced significantly (p less than 0.001) by a benzodiazepine receptor blocker. Specific 3H-diazepam binding was carried out in frontal cortex to assess both the population and affinity of benzodiazepine receptors. Our results indicate that acute cannabis treatment has no significant effect, whereas chronic cannabis treatment significantly increased 3H-diazepam binding as compared with controls. Scatchard analysis further reveals that increased affinity is responsible for increased binding to these receptors. It is therefore our contention that the antianxiety effect of cannabis is mediated through central benzodiazepine receptors.
D000328:Adult; D000374:Aggression / Q000187:drug effects; D000818:Animals; D001007:Anxiety / Q000188:drug therapy*; D001570:Benzodiazepinones / Q000494:pharmacology; D002186:Cannabinoids / Q000008:administration & dosage / Q000494:pharmacology*; D003975:Diazepam / Q000378:metabolism; D013759:Dronabinol / Q000494:pharmacology; D004597:Electroshock; D005260:Female; D005442:Flumazenil; D005625:Frontal Lobe / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008875:Middle Aged; D011963:Receptors, GABA-A / Q000187:drug effects*; D014316:Tritium
D001570:Benzodiazepinones; D002186:Cannabinoids; D011963:Receptors, GABA-A; D014316:Tritium; D005442:Flumazenil; D013759:Dronabinol; D003975:Diazepam