Cannabonoid Amelioration of Gulf War Illness
Abstract
Overarching Challenge: This project propose addressing an overarching challenge of GWIRP to develop the cannabinoid therapy as effective treatment for reducing multiple peripheral and neurological symptoms of GWI using the FDA-approved CBD product (Epidiolex). This study is consistent with the goals of the FY20 GWIRP under the Discovery (Idea Award) phase, which is intended to support exploratory, high-risk/high-reward research with the potential to yield new treatment of Gulf War Illness (GWI) in Veterans. About 250,000 Veterans who served in the Persian Gulf War have chronic multi-symptom illness that is commonly referred as GWI. Chronic pain, sleep deficits, cognitive and mood impairments are among the conspicuous symptoms in GWI Veterans. Multiple studies suggest that GWI in Veterans is linked to a combination of chemical exposures during the Gulf War, including pyridostigmine bromide (PB), DEET (a mosquito repellent) and permethrin (PM, an insecticide). Despite testing many therapeutic strategies over the past 10 years, there is currently no proven drug therapy to provide relief to GWI sufferers. The proposed studies will identify repurposed therapy for GWI, focusing on the cannabinoid system by the clinical drug CBD (Epidiolex). CBD can be very effective in treating GWI because cannabinoids play key role in pain, inflammation, neuronal excitability and memory. CBD is ideal drug for GWI therapy because it is very safe with few side effects and can be launched into the clinic sooner. Thus, CBD represents an innovative therapy for preventing multiple effects of GWI, such as pain, sleep, memory, mood and well-being. Objective and Rationale: The main goal of this project is to develop a clinically viable CBD therapy for GWI, targeting pain, insomnia, cognitive and central deficits of GWI Veterans. Experiments are designed to investigate the CBD therapy for GWI following a window of delayed (10 and 15 months) treatment protocol using neuroimaging, behavior, and neuropathology methods in an established rat model of GWI. The proposed delayed therapy (10 months = human 25 years!) closely matches 25 years that many GWI Veterans have had GWI. Since exposure to low-level nerve agents and other chemicals purportedly cause GWI, cannabinoids are proposed as effective treatment because they have been shown to be highly efficacious against acute and chronic symptoms caused by chemical exposure and bran dysfunction. This is a logical plan as per the GWI pathophysiology and CBD’s promise as new treatment. Our team is poised to lead this project as we have vast expertise and experience in GWI models. The overarching hypotheses to be tested are that exogenous supplementation of CBD restores the cannabinoid function and thereby mitigates both peripheral (pain, fatigue, fibromyalgia, sleep deficits) and central neurological (memory, headache, sleep, mood and sensorimotor) symptoms in GWI. The primary emphasis is to test the efficacy of CBD treatment in a GWI model, which will represent a landmark intervention of much higher clinical impact and application in Veterans with GWI diagnosis. We will test CBD in a valid rat model of GWI under three aims: Aim 1: To determine the protective efficacy of CBD against GWI agent-induced brain damage using MRI scanning. Aim 2: To determine the protective efficacy of CBD against GWI-induced peripheral and central deficits. Aim 3: To determine the protective efficacy of CBD against GWI agent-induced neuropathological changes. Our research team will employ standard methods and an established rat model of chronic GWI (Shetty et al., 2017). GWI will be induced in rats by exposure to mild stress and GWIR-chemicals PB, PM, and DEET for 4 weeks. CBD (50, 100 and 200 mg/kg, po) will be given for 4 weeks (at 10 and 15 months later), which is equivalent of 25-35 years that GW Veterans have had GWI. Brain neuropathology will be measured by MRI scanning. First, the therapeutic potential of CBD on multi-
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110314
Entities
People
- Samba Reddy
Organizations
- Texas A&M University
- United States Army