Potential therapeutical effects of cannabidiol in children with pharmacoresistant epilepsy

Cortesi, Mariachiara; Fusar‐Poli, Paolo

doi:10.1016/j.mehy.2006.09.030

Cited by 23 publications

(15 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the CNS, CBD has been reported to have anti‐inflammatory properties, thus being useful for neuroinflammatory disorders [5], including multiple sclerosis for which CBD combined with Δ 9 ‐THC (Sativex®) has been recently licenced as a symptom‐relieving agent for the treatment of spasticity and pain [6]. Based on its anticonvulsant properties, CBD has been proposed for the treatment of epilepsy [7–9], and also for the treatment of sleep disorders based on its capability to induce sleep [10]. CBD is also anti‐emetic, as are most of the cannabinoid agonists, but its effects are independent of CB 1 receptors and are possibly related to its capability to modulate serotonin transmission (see [11] and below).…”

Section: Overview On the Therapeutic Properties Of Cbdmentioning

confidence: 99%

Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid?

Fernández‐Ruiz

Sagredo

Pazos

et al. 2013

Brit J Clinical Pharma

283

196

View full text Add to dashboard Cite

Cannabidiol (CBD) is a phytocannabinoid with therapeutic properties for numerous disorders exerted through molecular mechanisms that are yet to be completely identified. CBD acts in some experimental models as an anti‐inflammatory, anticonvulsant, anti‐oxidant, anti‐emetic, anxiolytic and antipsychotic agent, and is therefore a potential medicine for the treatment of neuroinflammation, epilepsy, oxidative injury, vomiting and nausea, anxiety and schizophrenia, respectively. The neuroprotective potential of CBD, based on the combination of its anti‐inflammatory and anti‐oxidant properties, is of particular interest and is presently under intense preclinical research in numerous neurodegenerative disorders. In fact, CBD combined with Δ9‐tetrahydrocannabinol is already under clinical evaluation in patients with Huntington's disease to determine its potential as a disease‐modifying therapy. The neuroprotective properties of CBD do not appear to be exerted by the activation of key targets within the endocannabinoid system for plant‐derived cannabinoids like Δ9‐tetrahydrocannabinol, i.e. CB1 and CB2 receptors, as CBD has negligible activity at these cannabinoid receptors, although certain activity at the CB2 receptor has been documented in specific pathological conditions (i.e. damage of immature brain). Within the endocannabinoid system, CBD has been shown to have an inhibitory effect on the inactivation of endocannabinoids (i.e. inhibition of FAAH enzyme), thereby enhancing the action of these endogenous molecules on cannabinoid receptors, which is also noted in certain pathological conditions. CBD acts not only through the endocannabinoid system, but also causes direct or indirect activation of metabotropic receptors for serotonin or adenosine, and can target nuclear receptors of the PPAR family and also ion channels.

show abstract

Section: Overview On the Therapeutic Properties Of Cbdmentioning

confidence: 99%

Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid?

Fernández‐Ruiz

Sagredo

Pazos

et al. 2013

Brit J Clinical Pharma

283

196

View full text Add to dashboard Cite

show abstract

“…see Ross, 2007), or targeting more subtle CB1R independent effects of endogenous, synthetic, and phytocannabinoids. In this last regard it is worth noting that Δ 9 -THC has been noted to be an effective GABA uptake blocker in some preparations (Maneuf et al ., 1996; Coull et al ., 1997), that WIN55,212-2 and AEA have recently been shown to facilitate action potential independent synaptic transmission via a CB1R independent mechanism (Sang et al ., 2010; Hofmann et al ., 2011), and that cannabidiol (a prominent phytocannabinoid with minimal psychoactive properties and poor affinity for CB1Rs) has shown significant potential for CB1R independent antiepileptic effects (Cortesi & Fusar-Poli, 2007; Jones et al ., 2010). Overall, it is clear that significant additional effort and time will be required to develop appropriately selective therapeutic interventions for epilepsy that more precisely target specific aspects of endogenous cannabinoid systems, however appropriate tools for ever more selective manipulation of brain systems continue to develop, and thus basic science should continue to strive to provide detailed mechanistic insights that will be appropriate to guide the use of future therapeutic tools.…”

Section: The (Basic Science) Case For the Endocannabinoid System As Amentioning

confidence: 99%

Marijuana, endocannabinoids, and epilepsy: Potential and challenges for improved therapeutic intervention

Hofmann

Frazier

2013

Experimental Neurology

View full text Add to dashboard Cite

Phytocannabinoids isolated from the cannabis plant have broad potential in medicine that has been well recognized for many centuries. It is presumed that these lipid soluble signaling molecules exert their effects in both the central and peripheral nervous system in large part through direct interaction with metabotropic cannabinoid receptors. These same receptors are also targeted by a variety of endogenous cannabinoids including 2-arachidonoyl glycerol and anandamide. Significant effort over the last decade has produced an enormous advance in our understanding of both the cellular and the synaptic physiology of endogenous lipid signaling systems. This increase in knowledge has left us better prepared to carefully evaluate the potential for both natural and synthetic cannabinoids in the treatment of a variety of neurological disorders. In the case of epilepsy, long standing interest in therapeutic approaches that target endogenous cannabinoid signaling systems are, for the most part, not well justified by available clinical data from human epileptics. Nevertheless, basic science experiments have clearly indicated a key role for endogenous cannabinoid signaling systems in moment to moment regulation of neuronal excitability. Further it has become clear that these systems can both alter and be altered by epileptiform activity in a wide range of in vitro and in vivo models of epilepsy. Collectively these observations suggest clear potential for effective therapeutic modulation of endogenous cannabinoid signaling systems in the treatment of human epilepsy, and in fact, further highlight key obstacles that would need to be addressed to reach that goal.

show abstract

“…Pure CBD appears to be an excellent candidate among phytocannabinoids to evaluate in patients with treatmentresistant epilepsy. 9,24 Its lack of THC and therefore of the risks associated with the use of marijuana in the young age, 25,26 its excellent safety profile in humans, as well as its efficacy in preclinical studies suggest that it could be a safe and effective drug for epilepsy. The anecdotal human experiences reported in patients with Dravet syndrome and Lennox-Gastaut syndrome 19 are with products containing primarily CBD, often with CBD:THC ratios as high as >20:1.…”

Section: Discussionmentioning

confidence: 99%

“…Pure CBD appears to be an excellent candidate among phytocannabinoids to evaluate in patients with treatment‐resistant epilepsy . Its lack of THC and therefore of the risks associated with the use of marijuana in the young age, its excellent safety profile in humans, as well as its efficacy in preclinical studies suggest that it could be a safe and effective drug for epilepsy.…”

mentioning

confidence: 99%

The case for assessing cannabidiol in epilepsy

2014

View full text Add to dashboard Cite

SUMMARYIntractable epilepsies have an extraordinary impact on cognitive and behavioral function and quality of life, and the treatment of seizures represents a challenge and a unique opportunity. Over the past few years, considerable attention has focused on cannabidiol (CBD), the major nonpsychotropic compound of Cannabis sativa. Basic research studies have provided strong evidence for safety and anticonvulsant properties of CBD. However, the lack of pure, pharmacologically active compounds and legal restrictions have prevented clinical research and confined data on efficacy and safety to anecdotal reports. Pure CBD appears to be an ideal candidate among phytocannabinoids as a therapy for treatment-resistant epilepsy. A first step in this direction is to systematically investigate the safety, pharmacokinetics, and interactions of CBD with other antiepileptic drugs and obtain an initial signal regarding efficacy at different dosages. These data can then be used to plan double-blinded placebo-controlled efficacy trials.

show abstract

Potential therapeutical effects of cannabidiol in children with pharmacoresistant epilepsy

Cited by 23 publications

References 5 publications

Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid?

Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid?

Marijuana, endocannabinoids, and epilepsy: Potential and challenges for improved therapeutic intervention

The case for assessing cannabidiol in epilepsy

Contact Info

Product

Resources

About