Subacute cannabinoid treatment: anticonvulsant activity and withdrawal excitability in mice.
1 The effects of subacute treatment with cannabidiol, delta 9-tetrahydrocannabinol (delta 9-THC), phenytoin and phenobarbitone on anticonvulsant activity and on withdrawal excitability in mice were compared in three electrically induced seizure-threshold tests. 2 In the maximal electroshock-threshold test, subacute treatment did not alter the anticonvulsant activity of cannabidiol, phenytoin or phenobarbitone, but tolerance developed to delta 9-THC. 3 In the 60 Hz electroshock-threshold test, the activity of delta 9-THC and cannabidiol did not change, but tolerance developed to phenobarbitone, and there was an increase in sensitivity to phenytoin. 4 In the 6 Hz electroshock-threshold test, there was an increase in sensitivity to both delta 9-THC and cannabidiol, there was tolerance to phenobarbitone, while the activity of phenytoin did not change. 5 Although tolerance developed in some of the seizure-threshold tests to delta 9-THC and phenobarbitone, tolerance to cannabidiol and phenytoin did not develop in any of the tests. 6 Hyperexcitability followed withdrawal from only delta 9-THC (6 Hz and 60 Hz electroshock-threshold tests) and phenobarbitone (maximal electroshock-threshold and 60 Hz electroshock-threshold tests). 7 The delta 9-THC withdrawal hyperexcitability suggests that the use of marihuana may jeopardize the control of seizures in epileptics.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002185:Cannabidiol / Q000494:pharmacology; D002186:Cannabinoids / Q000009:adverse effects / Q000494:pharmacology*; D013759:Dronabinol / Q000494:pharmacology; D004361:Drug Tolerance; D004597:Electroshock; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013375:Substance Withdrawal Syndrome
D000927:Anticonvulsants; D002186:Cannabinoids; D002185:Cannabidiol; D013759:Dronabinol