PUBLICATION

Phytocannabinoids Reduce Seizures in Larval Zebrafish and Affect Endocannabinoid Gene Expression

Authors
Kollipara, R., Langille, E., Tobin, C., French, C.R.
ID
ZDB-PUB-231002-153
Date
2023
Source
Biomolecules   13(9): (Journal)
Registered Authors
French, Curtis R.
Keywords
GPR55, cannabis, endocannabinoid, epilepsy, phytocannabinoid, seizure, zebrafish
MeSH Terms
  • Animals
  • Anticonvulsants/pharmacology
  • Cannabidiol*/pharmacology
  • Cannabinoid Receptor Agonists
  • Cannabinol
  • Cannabis*
  • Endocannabinoids
  • Gene Expression
  • Humans
  • Seizures/chemically induced
  • Seizures/drug therapy
  • Seizures/genetics
  • Zebrafish
PubMed
37759798 Full text @ Biomolecules
Abstract
Cannabis has demonstrated anticonvulsant properties, and about thirty percent of epileptic patients do not have satisfactory seizure management with standard treatment and could potentially benefit from cannabis-based intervention. Here, we report the use of cannabinoids to treat pentylenetetrazol (PTZ)-induced convulsions in a zebrafish model, their effect on gene expression, and a simple assay for assessing their uptake in zebrafish tissues. Using an optimized behavioral assay, we show that cannabidiol (CBD) and cannabichromene (CBC) and cannabinol (CBN) are effective at reducing seizures at low doses, with little evidence of sedation, and our novel HPLC assay indicates that CBC is effective with the lowest accumulation in larval tissues. All cannabinoids tested were effective at higher concentrations. Pharmacological manipulation of potential receptors demonstrates that Gpr55 partially mediates the anticonvulsant effects of CBD. Treatment of zebrafish larvae with endocannabinoids, such as 2-arachidonoylglycerol (2-AG) and anandamide (AEA), altered larvae movement, and the expression of genes that regulate their metabolism was affected by phytocannabinoid treatment, highlighting the possibility that changes to endocannabinoid levels may represent one facet of the anticonvulsant effect of phytocannabinoids.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping