Electronic Theses and Dissertations

Date of Award

1-1-2017

Document Type

Dissertation

Degree Name

Ph.D. in Pharmaceutical Sciences

Department

Biomolecular Sciences

First Advisor

Kristine L Willett

Second Advisor

Tracy A. Brooks

Third Advisor

Ikhlas A. Khan

Relational Format

dissertation/thesis

Abstract

Medical marijuana is legal in twenty-nine of the United States and an additional nineteen states have passed legislation for cannabidiol (CBD) treatment of drug-resistant epilepsy, such as Dravet Syndrome (DS) which is diagnosed in children as young as two months. While CBD has shown anecdotal and recently clinical trial efficacy in reducing seizure frequency in DS patients, little is known about the potential adverse side-effects on child physiology, brain development, adult disease, or subsequent generations. Moreover, CBD is rarely administered without including low concentrations of Δ9-tetrahydrocannabinol (THC). The goal of this project is to characterize the relative morphological, behavioral, reproductive, and multigenerational toxicities following a developmental F0 exposure to 0.024–5 mg/L (0.08–16 µM) THC or 0.006–1.2 mg/L (0.02–4 µM) CBD. In this study, THC was used as a positive control due to its established developmental toxicities. An additional goal of this project was to analytically confirm THC and CBD concentrations during waterborne exposure as well as the bioconcentration in zebrafish. Following a developmental exposure, CBD posed similar risk to development, reproduction, and behavior as THC, but at much lower concentrations. Also, CBD bioconcentrated in zebrafish more readily than THC. To our knowledge, this is the first study to systematically compare the harmful effects on development and behavior of the two most prevalent and widely used phytocannabinoids. While most patients with drug-resistant forms of epilepsy and debilitating seizures choose cannabinoids in desperation, more research is necessary into their developmental toxicity to better understand both their therapeutic and toxic mechanisms of action.

Concentration/Emphasis

Emphasis: Environmental Toxicology

Included in

Biology Commons

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