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Phytocannabinoids Reduce Seizures in Larval Zebrafish and Affect Endocannabinoid Gene Expression
Roshni Kollipara1, Evan Langille2, Cameron Tobin1
1Department of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL A1B 3V6, Canada.
Biomolecules
|September 28, 2023
Summary
Cannabis compounds like cannabidiol (CBD) and cannabichromene (CBC) effectively reduced seizures in zebrafish. This research explores their potential for epilepsy treatment, with CBC showing minimal accumulation in tissues.
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- Epilepsy affects millions, with many patients unresponsive to conventional treatments.
- Cannabis-derived compounds (cannabinoids) show promise as alternative anticonvulsant therapies.
- Zebrafish models offer a valuable platform for studying neurological disorders and drug efficacy.
Purpose of the Study:
- To investigate the anticonvulsant effects of various phytocannabinoids in a pentylenetetrazol-induced zebrafish seizure model.
- To assess the impact of cannabinoid treatment on gene expression and tissue accumulation in zebrafish.
- To explore the role of G protein-coupled receptor 55 (Gpr55) in mediating cannabinoid-induced anticonvulsant effects.
Main Methods:
- Utilized an optimized behavioral assay to evaluate seizure reduction in pentylenetetrazol-treated zebrafish larvae.
- Employed High-Performance Liquid Chromatography (HPLC) to quantify cannabinoid accumulation in zebrafish tissues.
- Conducted pharmacological manipulations targeting Gpr55 and analyzed gene expression changes post-phytocannabinoid treatment.
Main Results:
- Cannabidiol (CBD), cannabichromene (CBC), and cannabinol (CBN) demonstrated significant anticonvulsant activity at low doses with minimal sedation.
- CBC exhibited the lowest accumulation in larval tissues among the tested phytocannabinoids.
- Gpr55 was identified as a partially mediating receptor for the anticonvulsant effects of CBD.
- Treatment with endocannabinoids (2-arachidonoylglycerol and anandamide) altered larval movement and gene expression.
Conclusions:
- Phytocannabinoids like CBD, CBC, and CBN are effective in managing seizures in a zebrafish model.
- CBC presents a potentially favorable profile due to low tissue accumulation.
- Modulation of endocannabinoid pathways and Gpr55 signaling may contribute to the anticonvulsant properties of cannabinoids.
- This study supports further investigation of cannabis-based interventions for epilepsy management.
