Convulsant-anticonvulsant properties of delta-9-tetrahydrocannabinol in rabbits

Fish, Barbara Schneiderman; Consroe, Paul; Fox, R. R.

doi:10.1007/bf01065669

Cited by 9 publications

(7 citation statements)

References 8 publications

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“…Cannabis has been reported to exert both pro‐ and anticonvulsant effects, as has its principal psychoactive constituent Δ 9 ‐THC (Chiu et al, 1979; Turkanis & Karler, 1981; Colasanti et al, 1982; Fish et al, 1983; Wallace et al, 2003). Δ 9 ‐THC acts as a partial agonist at CB1 receptors (Shen & Thayer, 1999), implicating CB1 as a potential therapeutic target in epilepsy.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, radioligand binding data indicate that, as has been previously reported in mouse cortical membranes (Dennis et al, 2008), D 9 -THCV acts as a relatively high affinity CB1-receptor ligand in rat cortical brain membranes, a property that could underlie the antiepileptiform and anticonvulsant effects described. Cannabis has been reported to exert both pro-and anticonvulsant effects, as has its principal psychoactive constituent D 9 -THC (Chiu et al, 1979;Turkanis & Karler, 1981;Colasanti et al, 1982;Fish et al, 1983;Wallace et al, 2003). D 9 -THC acts as a partial agonist at CB1 receptors (Shen & Thayer, 1999), implicating CB1 as a potential therapeutic target in epilepsy.…”

Section: Discussionmentioning

confidence: 99%

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Δ⁹‐Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats

et al. 2010

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-THCV (0.025-2.5 mg/kg) on pentylenetetrazole (PTZ)-induced seizures in adult rats were also assessed. Results: After induction of stable spontaneous epileptiform activity, acute D 9 -THCV application ( ‡20 lM) significantly reduced burst complex incidence and the amplitude and frequency of paroxysmal depolarizing shifts (PDSs). Furthermore, slices pretreated with 10 lM D 9 -THCV prior to induction of epileptiform activity exhibited significantly reduced burst complex incidence and PDS peak amplitude. In radioligand-binding experiments, -THCV exerts antiepileptiform and anticonvulsant properties, actions that are consistent with a CB1 receptor-mediated mechanism and suggest possible therapeutic application in the treatment of pathophysiologic hyperexcitability states.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Δ⁹‐Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats

et al. 2010

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“…9 -THC clearly affects seizure states and susceptibility in preclinical models (Lutz, 2004;Boggan et al, 1973) via well-known effects at central CB 1 receptors (Shen & Thayer, 1999). However, 9 -THC (and other CB 1 agonists) often exhibit contradictory pro-and anti-convulsant effects in clinical cases (Table 1) and preclinical models (Karler & Turkanis, 1980;Turkanis & Karler, 1981b;Turkanis & Karler, 1982;Consroe & Mechoulam, 1987;Wallace et al, 2001;Fish et al, 1983). Together with psychotropic side effects, such contradictory effects likely limit or prohibit 9 -THC"s widespread therapeutic use as an isolated agent.…”

Section: 11historical Backgroundmentioning

confidence: 99%

Phytocannabinoids as novel therapeutic agents in CNS disorders

Hill

Whalley

et al. 2012

Pharmacology & Therapeutics

280

248

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The Cannabis sativa herb contains over 100 phytocannabinoid (pCB) compounds and has been used for thousands of years for both recreational and medicinal purposes. In the past two decades, characterisation of the body's endogenous cannabinoid (CB) (endocannabinoid, eCB) system (ECS) has highlighted activation of central CB(1) receptors by the major pCB, Δ(9)-tetrahydrocannabinol (Δ(9)-THC) as the primary mediator of the psychoactive, hyperphagic and some of the potentially therapeutic properties of ingested cannabis. Whilst Δ(9)-THC is the most prevalent and widely studied pCB, it is also the predominant psychotropic component of cannabis, a property that likely limits its widespread therapeutic use as an isolated agent. In this regard, research focus has recently widened to include other pCBs including cannabidiol (CBD), cannabigerol (CBG), Δ(9)tetrahydrocannabivarin (Δ(9)-THCV) and cannabidivarin (CBDV), some of which show potential as therapeutic agents in preclinical models of CNS disease. Moreover, it is becoming evident that these non-Δ(9)-THC pCBs act at a wide range of pharmacological targets, not solely limited to CB receptors. Disorders that could be targeted include epilepsy, neurodegenerative diseases, affective disorders and the central modulation of feeding behaviour. Here, we review pCB effects in preclinical models of CNS disease and, where available, clinical trial data that support therapeutic effects. Such developments may soon yield the first non-Δ(9)-THC pCB-based medicines.

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“…Therefore, cannabinoids might be expected to increase network synchrony or generate excessive firing activity, in a similar manner to GABA receptors antagonists, which favor convulsive seizures (13,14). Second, several studies have reported that cannabinoids are proconvulsant in experimental models of epilepsy (15)(16)(17). The concurrent but unbalanced activation of the CB1R at the synaptic terminals of inhibitory and excitatory neurons could be one explanation for these seemingly contradictory observations.…”

mentioning

confidence: 99%

Striatal GABAergic and cortical glutamatergic neurons mediate contrasting effects of cannabinoids on cortical network synchrony

Sales-Carbonell

Rueda-Orozco

Soria-Gómez

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Activation of type 1 cannabinoid receptors (CB1R) decreases GABA and glutamate release in cortical and subcortical regions, with complex outcomes on cortical network activity. To date there have been few attempts to disentangle the region-and cell-specific mechanisms underlying the effects of cannabinoids on cortical network activity in vivo. Here we addressed this issue by combining in vivo electrophysiological recordings with local and systemic pharmacological manipulations in conditional mutant mice lacking CB1R expression in different neuronal populations. First we report that cannabinoids induce hypersynchronous thalamocortical oscillations while decreasing the amplitude of faster cortical oscillations. Then we demonstrate that CB1R at striatonigral synapses (basal ganglia direct pathway) mediate the thalamocortical hypersynchrony, whereas activation of CB1R expressed in cortical glutamatergic neurons decreases cortical synchrony. Finally we show that activation of CB1 expressed in cortical glutamatergic neurons limits the cannabinoid-induced thalamocortical hypersynchrony. By reporting that CB1R activations in cortical and subcortical regions have contrasting effects on cortical synchrony, our study bridges the gap between cellular and in vivo network effects of cannabinoids. Incidentally, the thalamocortical hypersynchrony we report suggests a potential mechanism to explain the sensory "high" experienced during recreational consumption of marijuana.annabinoids are a family of compounds that activate cannabinoid receptors, which are well known for their psychotropic effects and therapeutic potentials. The type 1 cannabinoid receptor (CB1R) is massively expressed in the brain at the synaptic terminals of excitatory and inhibitory neurons, and its activation by exogenous or endogenous cannabinoids decreases neurotransmitter release (1-3). One largely unanswered question is how the elementary decreases in excitatory and inhibitory synaptic transmissions induced by systemic intake of cannabinoids interact to produce alterations in neuronal network activity in vivo. A number of recent studies combining systemic injections of CB1R agonists and antagonists with electrophysiological recordings in the hippocampus and neocortex of awake or anesthetized rodents have shown that a hallmark of cannabinoids effects on neuronal network activity is a decrease in synchrony (4-9). Specifically, systemic CB1R activation has been shown to decrease (i) the amplitude of the hippocampal θ rhythm (4, 7, 8), (ii) the amplitude of γ oscillations in the hippocampus (4, 7, 10), enthorinal cortex (8), and prefrontal cortex (7), (iii) the incidence of hippocampal ripples (4, 6, 11), and (iv) spiking correlation in the hippocampus and prefrontal cortex (4,5,7,9).In contrast to the consistent reports that cannabinoids dampen cortical network oscillations, other findings suggest that they could also increase synchrony. First, CB1R are predominantly expressed by GABAergic forebrain neurons (12), and their activation leads to decreased GABA ...

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Convulsant-anticonvulsant properties of delta-9-tetrahydrocannabinol in rabbits

Cited by 9 publications

References 8 publications

Δ⁹‐Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats

Δ⁹‐Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats

Phytocannabinoids as novel therapeutic agents in CNS disorders

Striatal GABAergic and cortical glutamatergic neurons mediate contrasting effects of cannabinoids on cortical network synchrony

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Convulsant-anticonvulsant properties of delta-9-tetrahydrocannabinol in rabbits

Cited by 9 publications

References 8 publications

Δ9‐Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats

Δ9‐Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats

Phytocannabinoids as novel therapeutic agents in CNS disorders

Striatal GABAergic and cortical glutamatergic neurons mediate contrasting effects of cannabinoids on cortical network synchrony

Contact Info

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Δ⁹‐Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats

Δ⁹‐Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats