Cannabidiol for Improving Brain Function in Gulf War Illness
Abstract
Gulf War illness (GWI) is a multi-symptom disease affecting ~26% of men (~170,000) and ~29% of the women (~14,000) who served in the first Gulf War. The symptoms related to the brain include cognitive impairment, problems with making and recalling memory, concentration issues, sleep disturbances, and chronic pain. Evidence from epidemiological and animal studies implied that exposure to GWI-related chemicals such as pyridostigmine bromide (PB, a prophylactic drug against nerve gas), and pesticides (e.g., permethrin [PER]) led to neurological problems in a significant percentage of GW Veterans. Indeed, studies in mouse models demonstrated that exposure to PB+PER for 10 consecutive days is sufficient to cause impaired learning, reduced ability for making and recalling memories, and chronic pain at extended time-points after the exposure. Moreover, these changes are associated with unremitting neuroinflammation and loss of synapses. These adverse effects in the brain likely underlie persistent cognitive and memory dysfunction and chronic pain in GWI. From this perspective, it appears that long-term treatment with a safe dose of potent anti-inflammatory and synapse promoting compounds will have multiple therapeutic benefits in Veterans with GWI. Currently, no treatment that improves cognitive and mood function or reduces chronic neuroinflammation in GWI is available. Thus, there is an urgent need to find an appropriate drug or compound that eases the debilitating symptoms of GWI. We propose to test the efficacy of cannabidiol (CBD, a non-psychotomimetic phytochemical of Cannabis sativa) for alleviating cognitive and memory impairments and neuroinflammation in a mouse model of chronic GWI. The selection of CBD is based on its robust anti-inflammatory and analgesic properties. Cannabidiol (CBD), a non-psychotomimetic phytochemical of Cannabis sativa is a promising compound for alleviating cognitive and memory impairments in GWI because of its anti-inflammatory, synapse-forming, and analgesic properties. The therapeutic efficacy of CBD has been seen in models of diverse neurodegenerative diseases. Substantiating these reports, several clinical trials and human studies have also demonstrated the promise of CBD for improving function in neurodegenerative diseases. Also, the U.S. Food and Drug Administration (FDA) has approved this drug for controlling seizures in children afflicted with Dravet syndrome. How CBD mediates therapeutic benefits include the restoration of balance between excitation and inhibition of neurons, suppression of neuroinflammation in several ways, and neuroprotective effects. These properties make CBD an attractive drug to employ for treating GWI. However, because of potential side effects reported in some studies, its efficacy to improve brain function without adverse effects will need to be tested in an animal model before its application in Veterans with chronic GWI. The studies proposed in this application will test low to moderate doses (5, 10, 20 mg/Kg) of oral CBD treatment for 8 weeks for improving cognitive and mood function, and ease pain in a mouse model of chronic GWI. Both males and female mice with chronic GWI will be examined with CBD treatment. Also, the study will determine whether the functional improvements occur in association with the alleviation of inflammation and restoration of synapses in the brain. The primary goal is to identify the lowest dose of CBD that alleviates inflammation and restores synaptic activity along with improved cognitive and mood function and reduced chronic pain. The outcome of this study would likely pave the way for a safe clinical application of CBD in Veterans with GWI. Overall, the proposed studies have considerable promise for improving the health and quality of life of Veterans with GWI in the long term.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010569
Entities
People
- Maheedhar Kodali
Organizations
- Texas A&M Health Science Center
- United States Army