Research Index | Medline Index

Authors

Karler R, Borys HK, Turkanis SA

Title

Influence of 22-day treatment on the anticonvulsant properties of cannabinoids.

Source

Naunyn-Schmiedebergs Archives of Pharmacology

Date

1982 Aug

Issue

320(2)

Pages

105-9

Abstract

Mice were given delta-9-tetrahydrocannabinol (delta-9-THC) cannabidiol (CBD) or phenytoin (PHT) daily for 22 days. Drug activity was measured weekly in three different anticonvulsant tests: the maximal electroshock threshold, the 60-Hz-electroshock threshold and the 6-Hz-electroshock threshold. In order to correlate potential pharmacodynamic and pharmacokinetic changes resulting from repeated treatment, brain-drug concentrations were determined at each test time. The results from the delta-9-THC study indicate that, although tolerance developed in all three tests, there were no changes in the brain-drug concentration. For CBD the pharmacodynamics were strikingly different: an increase in sensitivity to the drug developed in two of the tests, tolerance in only one test. Here again, there were no changes in brain-drug concentrations. The results of the PHT study differed from both the cannabinoids, for tolerance developed in one test, an increase in sensitivity in one test, and the activity was unchanged in the third test. Again, the brain concentrations remained constant throughout. The results demonstrate that both tolerance and increased sensitivity can develop concomitantly with anticonvulsant effects of the cannabinoids and PHT, and that these modifications in drug activity appear to result from cellular or functional rather than dispositional changes.

Authors

Colasanti BK, Lindamood C 3d, Craig CR

Title

Effects of marihuana cannabinoids on seizure activity in cobalt-epileptic rats.

Source

Pharmacology, Biochemistry & Behavior

Date

1982 Apr

Issue

16(4)

Pages

573-8

Abstract

Rats rendered chronically epileptic by bilateral implantation of cobalt into frontal cortices were simultaneously prepared with permanent electrodes for longitudinal recording of the electroencephalogram (EEG) and electromyogram (EMG). Delta-8-tetrahydrocannabinol (delta-8-THC; 10 mg/kg), delta-9-tetrahydrocannabinol (delta-9-THC; 10 mg/kg), cannabidiol (CBD; 60 mg/kg), or polyvinylpyrrolidone (PVP) vehicle (2 ml/kg) was administered IP twice daily from day 7 through 10 after cobalt implantation, at which time generalized seizure activity in non-treated cobalt-epileptic rats was maximal. Relative to PVP-treated controls, CBD did not alter the frequency of appearance of seizures during the course of repeated administration. In contrast, both delta-8-THC and delta-9-THC markedly reduced the incidence of seizures on the first and second days of administration. Interictal spiking during this period, on the other hand, was actually enhanced. On the third and fourth days, tolerance to the effect on seizures was evident, with a return of seizure frequency of THC-treated rats to values not significantly different from those of controls. Unlike the effect on seizures, no tolerance developed to the marked suppression of rapid eye movement (REM) sleep induces by delta-8-THC and delta-9-THC. REM sleep remained reduced in the treated animals during the first 2 days after termination of THC administration. In contrast, REM sleep time was unaffected by repeated administration of CBD. These results suggest that delta-8-THC and delta-9-THC exert their initial anticonvulsant effect by limiting the spread of epileptogenic activity originating from the cobalt focus.

Authors

Karler R, Turkanis SA

Title

The cannabinoids as potential antiepileptics.

Source

Journal of Clinical Pharmacology

Date

1981 Aug-Sep

Issue

21(8-9 Suppl)

Pages

437S-448S

Abstract

Comparative studies of the anticonvulsant properties of the cannabinoids and prototype antiepileptic drugs in numerous animal seizure models demonstrate that (1) as an anticonvulsant, cannabidiol (CBD), in contrast to delta 9-tetrahydrocannabinol (THC), is relatively selective in terms of both central nervous system (CNS), depressant and excitatory properties; (2) the potency of cannabidiol, unlike that of phenytoin and phenobarbital, varies greatly with the species; (3) the large potency difference between the cannabinoids and the antiepileptics in the mouse appears to be due to dispositional differences, because brain concentrations of all the drugs are very similar; (4) tolerance to the anticonvulsant properties of cannabidiol is not a prominent feature; in three seizure models, tolerance developed in one, but "reverse tolerance" developed in the other two; and (5) the results of a study of the electrophysiologic mechanisms of action indicate that cannabidiol produces some unique effects and that its spectrum of antiepileptic activity may be different from that of the prototype drugs. The anticonvulsant nature of cannabidiol suggests that it has a therapeutic potential in at least three of the four major types of epilepsy: grand mal, cortical focal, and complex partial seizures.

Id Code

76043607

Authors

Wada JA, Osawa T, Corcoran ME

Title

Effects of tetrahydrocannabinols on kindled amygdaloid seizures and photogenic seizures in Senegalese baboons, Papio papio.

Source

Epilepsia

Date

1975 Sep

Issue

16(3)

Pages

439-48

Abstract

Intraperitoneal injections of delta 8-tetrahydrocannabinol (THC) and delta 9-THC failed to affect myoclonic response to photic stimulation in Senegalese baboons (Papio papio). However, both isomers of THC exerted dose-related antiepileptic effects upon established kindled convulsions provoked by electrical stimulation of amygdala in the same species. Delta 9-THC was more potent than delta 8-THC, in terms of both antiepileptic effects and general toxicity. The antiepileptic effects of the THC isomers appear to be due mainly to the suppression of propagation of the induced afterdischarge to distant cerebral structures, although high doses also seem to suppress afterdischarge at the site of stimulation.

Id Code

76162638

Authors

Johnson DD, McNeill JR, Crawford RD, Wilcox WC

Title

Epileptiform seizures in domestic fowl. V. The anticonvulsant activity of delta9-tetrahydrocannabinol.

Source

Canadian Journal of Physiology & Pharmacology

Date

1975 Dec

Issue

53(6)

Pages

1007-13

Abstract

The anticonvulsant activity of delta9-tetrahydrocannabinol (delta9-THC) has been determined against seizures induced in epileptic chickens by intermittent photic stimulation (IPS) and in epileptic and nonepileptic chickens by Metrazol. Intravenous administration of the drug reduced both the severity and incidence of seizures evoked by IPS in epileptic chickens. This anticonvulsant action was accompanied by a reduction in frequency of inter-ictal slow-wave high-voltage electroencephalographic activity and by the absence of spiking during IPS. delta9-THC did not affect the incidence of Metrazol-induced seizures in epileptic or nonepileptic chickens.

Id Code

76043617

Authors

Wada JA, Wake A, Sato M, Corcoran ME

Title

Antiepileptic and prophylactic effects of tetrahydrocannabinols in amygdaloid kindled cats.

Source

Epilepsia

Date

1975 Sep

Issue

16(3)

Pages

503-10

Abstract

Acute administration of delta8-tetrahydrocannabinol (delta8-THC) or delta9-THC failed to affect partially developed or fully developed kindled amygdaloid seizures in cats. However, delta9-THC was quite effective in suppressing focal AD in the stimulated amygdala when administered very early in kindling, before the development of any clinical manifestations. This finding suggested that chronic administration of delta9-THC during kindling might block the process of seizure development, which was supported by the observation that three of four cats failed to kindle when treated with the drug. The cat that failed to be protected by delta9-THC was also insensitive to the general electroclinical effects of moderately high doses of delta9-THC. The prophylactic activity of delta9-THC is in contrast to the ineffectiveness of diphenylhydantoin, a drug whose anticonvulsant activity is often compared with that of THC.

Id Code

80003560

Authors

Chiu P, Olsen DM, Borys HK, Karler R, Turkanis SA

Title

The influence of cannabidiol and delta 9-tetrahydrocannabinol on cobalt epilepsy in rats.

Source

Epilepsia

Date

1979 Aug

Issue

20(4)

Pages

365-75

Abstract

The mechanisms of the anticonvulsant activity of cannabidiol (CBD) and the central excitation of delta 9-tetrahydrocannabinol (delta 9-THC) were investigated electrophysiologically with conscious, unrestrained cobalt epileptic rats. The well-known antiepileptics, trimethadione (TMO), ethosuximide (ESM), and phenytoin (PHT), were included as reference drugs. Direct measurements were made of spontaneously firing, epileptic potentials from a primary focus on the parietal cortex and convulsions were monitored visually. ESM and TMO decreased the frequency of focal potentials, but PHT and CBD exerted no such effect. Although CBD did not suppress the focal abnormality, it did abolish jaw and limb clonus; in contrast, delta 9-THC markedly increased the frequency of focal potentials, evoked generalized bursts of polyspikes, and produced frank convlusions. 11-OH-delta 9-THC, the major metabolite of delta 9-THC, displayed only one of the excitatory properties of the parent compound: production of bursts of polyspikes. In contrast to delta 9-THC and its 11-OH metabolite, CBD, even in very high doses, did not induce any excitatory effects or convulsions. The present study provides the first evidence that CBD exerts anticonvulsant activity against the motor manifestations of a focal epilepsy, and that the mechanism of the effect may involve a depression of seizure generation or spread in the CNS.

Id Code

77234937

Authors

Turkanis SA, Chiu P, Borys HK, Karler R

Title

Influence of delta9-tetrahydrocannabinol and cannabidiol on photically evoked after-discharge potentials.

Source

Psychopharmacology

Date

1977 Apr 29

Issue

52(2)

Pages

207-12

Abstract

Two cannabinoids, delta9-tetrahydrocannabinol and cannabidiol, and several reference drugs were compared relative to their effects in a recently developed anticonvulsant test system, the after-discharge potentials of the visually evoked response; the potentials were recorded electrophysiologically from electrodes permanently mounted over the visual cortices of conscious rats. In anticonvulsant doses, trimethadione and ethosuximide produced an extensive depression of after-discharge activity, whereas diphenylhydantoin and cannabidiol exerted no such effect. In contrast, anticonvulsant doses of delta9-tetrahydrocannabinol and subconvulsant doses of pentylenetetrazol markedly increased after-discharge activity, which may represent a manifestation of their central nervous system excitatory properties. The data from the present study support our previously published ovservations from several other anticonvulsant tests that indicate the anticonvulsant characteristics of cannabidiol resemble those of diphenylhydantoin rather than those of trimethadione and that the central excitatory properties of delta9-tetrahydrocannabinol distinguish it from cannabidiol. The results consistently suggest that the cannabinoids will be effective against grand mal but not absence seizures.

Id Code

80003559

Authors

Turkanis SA, Smiley KA, Borys HK, Olsen DM, Karler R

Title

An electrophysiological analysis of the anticonvulsant action of cannabidiol on limbic seizures in conscious rats.

Source

Epilepsia

Date

1979 Aug

Issue

20(4)

Pages

351-63

Abstract

The effects of cannabidiol (CBD) on electrically evoked kindled seizures were studied in conscious, unrestrained rats with chronically implanted cortical and limbic electrodes, and the results were compared with those of delta 9-tetrahydrocannabinol (delta 9-THC), phenytoin (PHT), and ethosuximide (ESM). All drugs were anticonvulsant, but there were marked differences in their effects on afterdischarge (AD) threshold, duration, and amplitude. CBD, like PHT and delta 9-THC, elevated the AD threshold; in contrast, ESM decreased the threshold but suppressed AD spread. CBD, however, also resembled ESM inasmuch as both drugs decreased AD duration and amplitude. Electrophysiologically, the antiseizure effects of CBD were a combination of those of PHT and ESM. The combination of effects may account for the observation that CBD was the most efficacious of the drugs tested against limbic ADs and convulsions. Other properties of CBD were also noted: For example, compared with delta 9-THC, it is a much more selective anticonvulsant vis-a-vis motor toxicity. CBD also lacks the CNS excitatory effects produced by delta 9-THC, PHT, and ESM. These characteristics, combined with its apparently unique set of electrophysiological properties, support the suggestion that CBD has therapeutic potential as an antiepileptic.

Id Code

91078286

Authors

Maurer M, Henn V, Dittrich A, Hofmann A

Title

Delta-9-tetrahydrocannabinol shows antispastic and analgesic effects in a single case double-blind trial.

Source

European Archives of Psychiatry & Neurological Sciences

Date

1990

Issue

240(1)

Pages

1-4

Abstract

A double-blind study was performed comparing 5 mg delta-9-tetrahydrocannabinol (THC) p.o., 50 mg codeine p.o., and placebo in a patient with spasticity and pain due to spinal cord injury. The three conditions were applied 18 times each in a randomized and balanced order. Delta-9-THC and codeine both had an analgesic effect in comparison with placebo. Only delta-9-THC showed a significant beneficial effect on spasticity. In the dosage of THC used no altered consciousness occurred.