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Cannabichromene, Related Phytocannabinoids, and 5-Fluoro-cannabichromene Have Anticonvulsant Properties in a Mouse Model of Dravet Syndrome
- Source :
- ACS chemical neuroscience. 12(2)
- Publication Year :
- 2021
-
Abstract
- 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.
- Subjects :
- Physiology
Cognitive Neuroscience
medicine.medical_treatment
Epilepsies, Myoclonic
Pharmacology
Biochemistry
03 medical and health sciences
Cannabichromene
chemistry.chemical_compound
Mice
0302 clinical medicine
Dravet syndrome
Pharmacokinetics
parasitic diseases
medicine
Animals
Humans
In patient
Child
030304 developmental biology
Pediatric epilepsy
0303 health sciences
biology
business.industry
Cannabinoids
Cell Biology
General Medicine
medicine.disease
biology.organism_classification
NAV1.1 Voltage-Gated Sodium Channel
Anticonvulsant
chemistry
Anticonvulsants
Cannabis
business
Cannabidiol
Spasms, Infantile
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 19487193
- Volume :
- 12
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- ACS chemical neuroscience
- Accession number :
- edsair.doi.dedup.....a6c86fb92f8c1040b9103c639435dece