SUBACUTE CANNABINOID TREATMENT: ANTICONVULSANT ACTIVITY AND WITHDRAWAL EXCITABILITY IN MICE

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Abstract
1 The effects of subacute treatment with cannabidiol, Δ9-tetrahydrocannabinol (Δ9-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 Δ9-THC. 3 In the 60 Hz electroshock-threshold test, the activity of Δ9-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 Δ9-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 Δ9-THC and phenobarbitone, tolerance to cannabidiol and phenytoin did not develop in any of the tests. 6 Hyperexcitability followed withdrawal from only Δ9-THC (6 Hz and 60 Hz electroshock-threshold tests) and phenobarbitone (maximal electroshock-threshold and 60 Hz electroshock-threshold tests). 7 The Δ9-THC withdrawal hyperexcitability suggests that the use of marihauana may jeopardize the control of seizures in epileptics.