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The Antinociceptive Effects of Cannabinoids and Terpenoids on a Zebrafish Model of Nociception
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- Author / Creator
- Kim, Andrew M
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With many communities affected by the opioid crisis, it has become of paramount importance to explore methods of pain management outside of treatments with opioids. One alternative treatment that has seen a recent surge in interest is cannabis and its related phytochemical-based treatments. Indeed, some cannabinoids and terpenoids have been demonstrated to show antinociceptive effects in various model systems. However, for the vast majority of terpenoids in cannabis, these effects remain unexplored. In this study I used a zebrafish model of nociception to test the antinociceptive effects of cannabinoids, terpenoids and a combination of the two compounds. Zebrafish provides a robust and high-throughput model system for such inquiry. Using behavioural assays, I confirmed the ability of acetic acid to elicit a change in locomotion in larval zebrafish. Exposure to low concentrations of acetic acid (0.001% - 0.01%) led to a four-fold increase in mean activity levels of 5-day old larvae. When zebrafish larvae were exposed to cannabidiol (CBD) at 2.5 mg/L and 5 mg/L and the terpenoids, trans-nerolidol and caryophyllene oxide at 10mg/L, the acetic acid-induced increase in activity was prevented. However, tetrahydrocannabinol (THC) and other terpenoids failed to prevent nociception from acetic acid. Combinations of the terpenoids with CBD did not lead to a greater antinociceptive effects compared with each individual compound. Using specific blockers, I determined that the process through which CBD, trans-nerolidol, and caryophyllene oxide display antinociceptive effects involves the transient receptor potential (TRP) cation channels, specifically TRPA1 and TRPV1 channels. On the other hand, intervention with specific blockers of µ-opioid receptor, δ-opioid receptor, and cannabinoid receptor types 1 and 2 was insufficient in preventing the acetic acid-induced activity. These findings lay the foundation for a more thorough investigation of the therapeutic effects of cannabinoids, terpenoids and combinations of the two, as well as a mechanistic understanding of how such effects arise at a cellular level.
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- Subjects / Keywords
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- Graduation date
- Fall 2024
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- Type of Item
- Thesis
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- Degree
- Master of Science
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- License
- This thesis is made available by the University of Alberta Library with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.