Cannabichromene, Related Phytocannabinoids, and 5-Fluoro-cannabichromene Have Anticonvulsant Properties in a Mouse Model of Dravet Syndrome.
Lyndsey L AndersonAdam AmetovskiJia Lin LuoDeclan Everett-MorganIain S McGregorSamuel D BanisterJonathon C ArnoldPublished in: ACS chemical neuroscience (2021)
Cannabis-based products are increasingly being used to treat refractory childhood epilepsies such as Dravet syndrome. Cannabis contains at least 140 terpenophenolic compounds known as phytocannabinoids. These include the known anticonvulsant compound cannabidiol (CBD) and several molecules showing emergent anticonvulsant properties in animal models. Cannabichromene (CBC) is a phytocannabinoid frequently detected in artisanal cannabis oils used in the community by childhood epilepsy patients. Here we examined the brain and plasma pharmacokinetic profiles of CBC, cannabichromenic acid (CBCA), cannabichromevarin (CBCV), and cannabichromevarinic acid (CBCVA) following intraperitoneal administration in mice. The anticonvulsant potential of each was then tested against hyperthermia-induced seizures in the Scn1a+/- mouse model of Dravet syndrome. All phytocannabinoids within the CBC series were readily absorbed and showed substantial brain penetration (brain-plasma ratios ranging from 0.2 to 5.8). Anticonvulsant efficacy was evident with CBC, CBCA, and CBCVA, each significantly increasing the temperature threshold at which Scn1a+/- mice had a generalized tonic-clonic seizure. We synthesized a fluorinated derivative of CBC (5-fluoro-CBC), which showed improved brain penetration relative to the parent CBC molecule but not any greater anticonvulsant effect. Since CBC and derivatives are anticonvulsant in a model of intractable pediatric epilepsy, they may constitute part of the mechanism through which artisanal cannabis oils are anticonvulsant in patients.
Keyphrases
- mouse model
- end stage renal disease
- resting state
- ejection fraction
- chronic kidney disease
- peritoneal dialysis
- healthcare
- prognostic factors
- case report
- mental health
- type diabetes
- functional connectivity
- cerebral ischemia
- patient reported outcomes
- oxidative stress
- climate change
- computed tomography
- multiple sclerosis
- adipose tissue
- skeletal muscle
- risk assessment
- blood brain barrier
- early life
- high glucose