Drug–drug interaction between clobazam and cannabidiol in children with refractory epilepsy

Geffrey, Alexandra L.; Pollack, Sarah F.; Bruno, Patricia; Thiele, Elizabeth A.

doi:10.1111/epi.13060

Cited by 431 publications

(374 citation statements)

References 25 publications

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“…The clinical relevance for such indirect effects of CBD on circulating AED levels has recently been highlighted in the case of clobazam co-administration [161].…”

Section: Cbd Enzyme Targets In Epilepsymentioning

confidence: 99%

Molecular Targets of Cannabidiol in Neurological Disorders

Bih

Chen

Nunn³

et al. 2015

Neurotherapeutics

462

323

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Cannabis has a long history of anecdotal medicinal use and limited licensed medicinal use. Until recently, alleged clinical effects from anecdotal reports and the use of licensed cannabinoid medicines are most likely mediated by tetrahydrocannabinol by virtue of: 1) this cannabinoid being present in the most significant quantities in these preparations; and b) the proportion:potency relationship between tetrahydrocannabinol and other plant cannabinoids derived from cannabis. However, there has recently been considerable interest in the therapeutic potential for the plant cannabinoid, cannabidiol (CBD), in neurological disorders but the current evidence suggests that CBD does not directly interact with the endocannabinoid system except in vitro at supraphysiological concentrations. Thus, as further evidence for CBD's beneficial effects in neurological disease emerges, there remains an urgent need to establish the molecular targets through which it exerts its therapeutic effects. Here, we conducted a systematic search of the extant literature for original articles describing the molecular pharmacology of CBD. We critically appraised the results for the validity of the molecular targets proposed. Thereafter, we considered whether the molecular targets of CBD identified hold therapeutic potential in relevant neurological diseases. The molecular targets identified include numerous classical ion channels, receptors, transporters, and enzymes. Some CBD effects at these targets in in vitro assays only manifest at high concentrations, which may be difficult to achieve in vivo, particularly given CBD's relatively poor bioavailability. Moreover, several targets were asserted through experimental designs that demonstrate only correlation with a given target rather than a causal proof. When the molecular targets of CBD that were physiologically plausible were considered for their potential for exploitation in neurological therapeutics, the results were variable. In some cases, the targets identified had little or no established link to the diseases considered. In others, molecular targets of CBD were entirely consistent with those already actively exploited in relevant, clinically used, neurological treatments. Finally, CBD was found to act upon a number of targets that are linked to neurological therapeutics but that its actions were not consistent withmodulation of such targets that would derive a therapeutically beneficial outcome. Overall, we find that while >65 discrete molecular targets have been reported in the literature for CBD, a relatively limited number represent plausible targets for the drug's action in neurological disorders when judged by the criteria we set. We conclude that CBD is very unlikely to exert effects in neurological diseases through modulation of the endocannabinoid system. Moreover, a number of other molecular targets of CBD reported in the literature are unlikely to be of relevance owing to effects only being observed at supraphysiological concentrations. Of interest and after excludin...

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“…The clinical relevance for such indirect effects of CBD on circulating AED levels has recently been highlighted in the case of clobazam co-administration [161].…”

Section: Cbd Enzyme Targets In Epilepsymentioning

confidence: 99%

Molecular Targets of Cannabidiol in Neurological Disorders

Bih

Chen

Nunn³

et al. 2015

Neurotherapeutics

462

323

View full text Add to dashboard Cite

show abstract

“…29 CBD inhibits the CYP2C19 metabolic receptors, which are used by several other AEDs to enter the central nervous system and neuronal pathways. 30 Some studies have linked CBD to increased inhibition of GABA receptors and regulation of calcium channels, which could also result in an anticonvulsant effect. 21 Underlying neural mechanisms of epilepsy are often related to increased glutamate/GABA activity, which sometimes results in excitotoxicity, or overactivity, that can cause eccentric neuronal connectivity with resulting seizure and behavior deficit.…”

Section: Mechanisms Of Action Of Cannabinoidsmentioning

confidence: 99%

Untitled

2017

J Pediatr Neurol

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“…Although it has been praised as a natural remedy, lack of oversight and regulation may lead to contamination with pesticides and heavy metals [93]. There are also concerns for known and unknown drug interactions with current anticonvulsant medications which may lead to dangerous adverse drug events or poor control of epilepsy [94]. Furthermore, caregivers may adjust or change their own medication regimen without recommendations from a neurologist, which can have dangerous consequences for a patient's seizure control.…”

Section: Medical Use In Pediatricsmentioning

confidence: 99%

Pediatric Concerns Due to Expanded Cannabis Use: Unintended Consequences of Legalization

Wang

2016

J. Med. Toxicol.

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An "unintended consequence" of marijuana legalization is the impact on the pediatric population. From prenatal exposure to unintentional childhood exposures, through concerns of adolescence abuse and marijuana use for medicinal indications in children, marijuana exposure can affect pediatric patients at every stage in childhood. Regardless of the stage or reason of exposure, concerns exist about short-term and long-term consequences in a child's physical and mental health. The use of cannabidiol (CBD) may have some benefit for the treatment of epilepsy, but emphasis needs to be on rigorous clinical trials to evaluate efficacy and safety. As more states allow both medical and recreational marijuana, availability and prevalence of use will likely increase and more surveillance and research is needed to evaluate the consequences on the pediatric population.

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Drug–drug interaction between clobazam and cannabidiol in children with refractory epilepsy

Cited by 431 publications

References 25 publications

Molecular Targets of Cannabidiol in Neurological Disorders

Molecular Targets of Cannabidiol in Neurological Disorders

Untitled

Pediatric Concerns Due to Expanded Cannabis Use: Unintended Consequences of Legalization

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