Same old

Potentiation of electrical and chemical synaptic transmission mediated by endocannabinoids.

Potentiation of electrical and chemical synaptic transmission mediated by endocannabinoids.

Neuron. 2007 Dec 20;56(6):1034-47

Authors: Cachope R, Mackie K, Triller A, O'Brien J, Pereda AE

Endocannabinoids are well established as inhibitors of chemical synaptic transmission via presynaptic activation of the cannabinoid type 1 receptor (CB(1)R). Contrasting this notion, we show that dendritic release of endocannabinoids mediates potentiation of synaptic transmission at mixed (electrical and chemical) synaptic contacts on the goldfish Mauthner cell. Remarkably, the observed enhancement was not restricted to the glutamatergic component of the synaptic response but also included a parallel increase in electrical transmission. This effect involved the activation of CB(1) receptors and was indirectly mediated via the release of dopamine from nearby varicosities, which in turn led to potentiation of the synaptic response via a cAMP-dependent protein kinase-mediated postsynaptic mechanism. Thus, endocannabinoid release can potentiate synaptic transmission, and its functional roles include the regulation of gap junction-mediated electrical synapses. Similar interactions between endocannabinoid and dopaminergic systems may be widespread and potentially relevant for the motor and rewarding effects of cannabis derivatives.

PMID: 18093525 [PubMed - in process]

Prolonged CNS hyperexcitability in mice after a single exposure to delta-9-tetrahydrocannabinol.

Prolonged CNS hyperexcitability in mice after a single exposure to delta-9-tetrahydrocannabinol.

Neuropharmacology. 1986 Apr;25(4):441-6

Authors: Karler R, Calder LD, Turkanis SA

A single exposure to delta-9-tetrahydrocannabinol (THC) resulted in a "rebound" hyperexcitability in the CNS in mice, which was assessed in terms of the susceptibility of the CNS to electrically-induced convulsions. The magnitude of the hyperexcitability was dose-related (25-150 mg/kg, i.p.), as measured 24 hr after treatment. The time-course study of the effect indicated a peak-effect at 24 hr after administration of the drug, with a duration of the effect for as long as 196 hr. The time course of the rebound hyperexcitability to THC was compared to that for phenobarbital, which peaked at 48 hr after administration of the drug and returned to the control value by 96 hr. Tolerance developed rapidly to the motor-toxic effect of THC, but after 23 days of daily treatment there was no evidence of tolerance to the rebound hyperexcitability. The functional significance of the hyperexcitable state was assessed in two tests; electrical kindling to minimal convulsions was enhanced, even when the kindling procedure was initiated 120 hr after exposure to the drug; and the anticonvulsant activity of phenytoin was blocked when mice were treated with the anticonvulsant 96 hr after a single exposure to THC. The results suggest that the rebound response from a single exposure to THC represents a functionally significant prolonged increase in excitability of the CNS.

PMID: 3012403 [PubMed - indexed for MEDLINE]

Different cannabinoids exhibit different pharmacological and toxicological properties.

Different cannabinoids exhibit different pharmacological and toxicological properties.

NIDA Res Monogr. 1987;79:96-107

Authors: Karler R, Turkanis SA

PMID: 3125482 [PubMed - indexed for MEDLINE]

Structure-anticonvulsant activity relationships of cannabidiol analogs.

Structure-anticonvulsant activity relationships of cannabidiol analogs.

NIDA Res Monogr. 1987;79:48-58

Authors: Martin AR, Consroe P, Kane VV, Shah V, Singh V, Lander N, Mechoulam R, Srebnik M

Cannabidiol (CBD) exhibits anticonvulsant activity in experimental animals and in man. As part of a structure-activity study, analogs were prepared wherein the terpene unit, the aryl unit, and/or the side chain were modified. Thus, several pinenyl and carenyl derivatives, aryl ethers and acetates, and a variety of 1",1"-dialkylhexyl and 1",1"-dialkylheptyl analogs were synthesized. The compounds were evaluated for anti-convulsant activity in seizure susceptible (AGS) rats and for neurotoxicity in the rat rotorod (ROT) test. Comparisons of stereoisomers of CBD and several analogs revealed a general lack of stereoselectivity for anticonvulsant and other CNS properties of this class of compounds.

PMID: 3125480 [PubMed - indexed for MEDLINE]

Anticonvulsant and neurotoxic effects of tetrahydrocannabinol stereoisomers.

Anticonvulsant and neurotoxic effects of tetrahydrocannabinol stereoisomers.

NIDA Res Monogr. 1987;79:59-66

Authors: Consroe P, Mechoulam R

Enantiomers of delta-6-tetrahydrocannabinol (THC), delta-6-THC-1'', 1''-dimethylheptyl (DMHP), and 7-OH-delta-6-THC-1'',1''-DMHP were assessed for their ability to block audiogenic seizures in genetically epilepsy-prone rats. The stereoisomers were evaluated also for their ability to produce differential neurotoxicity in the rat rotorod (ROT) paradigm. Potency comparisons among the compounds revealed modest to profound stereoselectivity for anticonvulsant and neurotoxic activities, a general increase in both activities with the DMHP and 7-OH modifications of delta-6-THC, and some favorable separation between anticonvulsant and neurotoxic activities with selected THC analogs.

PMID: 2830538 [PubMed - indexed for MEDLINE]

Marijuana use and the risk of new onset seizures.

Marijuana use and the risk of new onset seizures.

Trans Am Clin Climatol Assoc. 1992;103:176-81

Authors: Brust JC, Ng SK, Hauser AW, Susser M

PMID: 1413377 [PubMed - indexed for MEDLINE]

The autism-epilepsy connection.

The autism-epilepsy connection.

Epilepsia. 2007;48 Suppl 9:33-5

Authors: Levisohn PM

The high prevalence of epilepsy in children with autism supports a neurobiologic etiology for autism. It remains unclear whether seizures and epileptiform activity on the EEG are causative or comorbid. It is also uncertain if focal epileptiform EEG abnormalities may be associated with stable cognitive impairment. Even less clear is whether these EEG abnormalities can result in the combination of language and social dysfunction seen in autistic spectrum disorders.

PMID: 18047599 [PubMed - in process]