Semester of Graduation

Spring 2021

Degree

Master of Science (MS)

Department

School of Renewable Natural Resources

Document Type

Thesis

Abstract

Epilepsy is a complex group of neurological disorders affecting approximately 65 million people worldwide. Animal models reveal the activation of cannabinoid receptor 1 and cannabinoid receptor 2 reduces the severity of seizures associated with epilepsy. Trials of phytocannabinoids in mammals demonstrate their efficacy of reducing the severity of epileptic seizures. Numerous terpenoid compounds are present in Cannabis plants but most have yet to be clinically investigated. The goal of this research was to use zebrafish (Danio rerio) to identify the potential anticonvulsive properties of phytocannabinoid and terpenoid compounds. During acute cannabinoid exposures, 7-days-post-fertilization (7 dpf) zebrafish larvae were exposed to either cannabidiol (CBD), cannabinol (CBN), tetrahydrocannabinol (∆9THC), or tetrahydrocannabivarin (THV) at concentrations of 0.125, 0.25, 0.5, or 1mg/L for 90 minutes. Epileptic-like seizures were tinduced by exposing larvae to a 10mM pentylenetetrazol (PTZ) solution for 10 minutes. After the PTZ incubation, movements were recorded for 10 minutes using a DanioVision™ recording chamber. The total distance moved and average velocity was measured using Ethovision XT™ software. Larvae exposed to phytocannabinoids had significantly reduced seizure behavior (p < 0.05) except for the 1mg/L THV treatment. The same methods and dosages were used for acute terpenoid exposures. Larvae exposed to myrcene and limonene had significantly reduced seizure behavior (p < 0.05) at all concentrations. For chronic exposures, larvae were exposed CBD or ∆9THC at 0.0625mg/L or 0.125mg/L at 24-hours-post-fertilization. Solutions were renewed every 24 hours. At 7dpf, larvae were placed into a 48-well plate and exposed to a 10mM PTZ solution for 10 minutes. Larval movement was then recorded for 10 minutes. Zebrafish embryos exposed 0.0625mg/L or 0.125mg/L of CBD or ∆9-THC for 168 hours did not see a reduction in seizure behavior. Our work has revealed an acute exposure to selected phytocannabinoids significantly reduces seizure behavior in 7dpf larval zebrafish across a range of concentrations. A chronic exposure to CBD or ∆9-THC did not yield a reduction in seizure behavior. This study indicates limonene and myrcene reduce seizure behaviors during an acute exposure. It is anticipated this research will support clinical research and use of phytocannabinoids and terpenoids increases in the future.

Committee Chair

Green, Christopher

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