Dissertation
Investigating the therapeutic potential of cannabinoids in pre-clinical models of migraine
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Autumn 2024
DOI: 10.25820/etd.007600
Abstract
Migraine is a complex and debilitating neurological condition with significant social and economic consequences worldwide. Although recent advances in treatments such as CGRP monoclonal antibodies and triptans have improved care for some, many migraine patients continue to experience insufficient relief, side effects, or dissatisfaction with current options. This unmet need highlights the urgency for alternative treatments. Cannabinoids, specifically CBD and THC, have gained attention as promising candidates due to their anti-inflammatory and analgesic properties, as well as their interactions with the trigeminovascular system, a key player in migraine pathophysiology. This thesis investigates the potential of cannabinoids to alleviate migraine symptoms, focusing on their efficacy and safety.
Using well-established rodent models of migraine, this research examines the impact of cannabinoids on both peripheral and central mechanisms underlying migraine. The migraine triggers employed in this study include CGRP (both centrally and peripherally administered) and the nitric oxide donor sodium nitroprusside (peripherally administered). Cannabinoids were tested in a range of assays that assessed symptom relief and behavioral responses related to pain, light aversion, and adverse effects.
Our results demonstrate that combined CBD and THC therapy, rather than individual cannabinoid administration, offers relief from migraine-like symptoms of pain and light aversion with minimal adverse effects. Additionally, the thesis explores the effects of a third migraine trigger, amylin, on migraine-like symptoms when administered centrally. In recent years, the primary focus in migraine drug development has been CGRP. Our findings indicate that amylin can produce light aversion by acting on central sites, suggesting its potential as an additional therapeutic target other than CGRP.
This research adds to the growing body of migraine studies by highlighting cannabinoids as potential adjunct or alternative therapies for migraine management. Future directions for research include further investigation into how cannabinoids modulate immune responses and their impact on neuroinflammatory pathways related to migraine. Additional studies are needed to refine dosage, administration routes, and cannabinoid ratios to enhance therapeutic outcomes in human populations. This work highlights the potential of cannabinoids to address a critical gap in migraine treatment, providing new options for those who do not respond to conventional therapies.
Details
- Title: Subtitle
- Investigating the therapeutic potential of cannabinoids in pre-clinical models of migraine
- Creators
- Erik Zorrilla
- Contributors
- Andrew F. Russo (Advisor)Yuriy M. Usachev (Committee Member)Rainbo C. K. Hultman (Committee Member)Alan K. Johnson (Committee Member)Michael E. Dailey (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Neuroscience
- Date degree season
- Autumn 2024
- DOI
- 10.25820/etd.007600
- Publisher
- University of Iowa
- Number of pages
- xix, 244 pages
- Copyright
- Copyright 2024 Erik Zorrilla
- Translated title
- Investigando el potencial terapéutico de los cannabinoides en modelos preclínicos de migraña
- Language
- English
- Date submitted
- 12/09/2024
- Description illustrations
- illustrations, graphs, tables
- Description bibliographic
- Includes bibliographical references (pages 209-244).
- Public Abstract (ETD)
- Migraine is a neurological condition that affects millions worldwide, imposing significant health and economic burdens on individuals and societies. Although treatments have advanced with options like CGRP monoclonal antibodies, gepants, and triptans, many people with migraine still find these medications ineffective or unsatisfactory. This unmet need highlights the urgency to explore alternative therapies. This thesis investigates cannabinoids, specifically CBD and THC, as potential treatments for migraine. Using rodent models, the research focuses on how these compounds influence both peripheral and central triggers of migraine, including key migraine triggers like CGRP, SNP, and amylin, known to initiate or exacerbate migraine symptoms. Experiments were conducted to observe the effects of cannabinoids on migraine-related symptoms, assessing their potential to provide relief while minimizing adverse effects. Our results indicate that the combination of CBD and THC show promise in reducing migraine symptoms without significant side effects. This suggests cannabinoids may offer an alternative approach for managing migraine, especially for those unresponsive to current treatments. Beyond the potential therapeutic benefits, this research contributes to the understanding of the role of cannabinoids in modulating peripheral and central mechanisms of migraine pathogenesis. Future studies are encouraged to delve deeper into cannabinoid-based therapies and their interactions with migraine-related immune activity, aiming to offer more effective, patient-centered treatment options for this complex disorder.
- Academic Unit
- Interdisciplinary Graduate Program in Neuroscience; Craniofacial Anomalies Research Center
- Record Identifier
- 9984774457702771
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