Central excitatory properties of delta 9-tetrahydrocannabinol and its metabolites in iron-induced epileptic rats.
The effects of delta 9-tetrahydrocannabinol (delta 9-THC), two of its metabolites, 8 beta-hydroxy-delta 9-THC and 11-hydroxy-delta 9-THC, and cannabidiol were comparatively studied by means of an iron-induced cortical focal epilepsy in conscious rats with chronically implanted electrodes. delta 9-Tetrahydrocannabinol produced depression of the spontaneously firing epileptic focus, excitatory behavior, generalized after-discharge-like bursts of epileptiform polyspikes and frank convulsions. The pharmacological profiles of the two metabolites differed from that of the parent compound: 11-Hydroxy-delta 9-THC did not precipitate convulsions, but it did elicit all the other effects of delta 9-THC; the 8 beta-hydroxy derivative, on the other hand, exerted only two delta 9-THC-like effects; that is, it evoked polyspike bursts and convulsions. In contrast, cannabidiol, even in large doses (100 mg/kg) was devoid of all the effects of delta 9-THC. Furthermore, pretreatment with cannabidiol markedly altered the responses to delta 9-THC in the following ways: focal depression was partially blocked, polyspike activity was enhanced and convulsions abolished. Phenytoin pretreatment elicited similar effects, but it failed to block the delta 9-THC-induced convulsions. In general, the cannabinoids exhibit a wide spectrum of CNS effects ranging from focal depression to convulsions; specifically, however, the pharmacological profile of each agent can differ markedly; for example, the convulsant properties of delta 9-THC are not a universal characteristic of this class of drugs.
D000818:Animals; D002185:Cannabidiol / Q000494:pharmacology; D002490:Central Nervous System / Q000187:drug effects* / Q000503:physiopathology; D013759:Dronabinol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D004594:Electrophysiology; D004827:Epilepsy / Q000139:chemically induced* / Q000188:drug therapy; D007501:Iron / Q000494:pharmacology*; D008297:Male; D010672:Phenytoin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D002185:Cannabidiol; C001427:11-hydroxy-delta(9)-tetrahydrocannabinol; C033935:8-hydroxy-delta(9)-tetrahydrocannabinol; D010672:Phenytoin; D013759:Dronabinol; D007501:Iron