“Gulf War Illness (GWI) is a chronic disorder characterized by a heterogeneous set of symptoms that include pain, fatigue, anxiety, and cognitive impairment. These are thought to stem from damage caused by exposure under unpredictable stress to toxic Gulf War (GW) chemicals, which include pesticides, nerve agents, and prophylactic drugs.
We hypothesized that GWI pathogenesis might be rooted in long-lasting disruption of the endocannabinoid (ECB) system, a signaling complex that serves important protective functions in the brain.
Using a mouse model of GWI, we found that tissue levels of the ECB messenger, anandamide, were significantly reduced in the brain of diseased mice, compared to healthy controls. In addition, transcription of the Faah gene, which encodes for fatty acid amide hydrolase (FAAH), the enzyme that deactivates anandamide, was significant elevated in prefrontal cortex of GWI mice and brain microglia.
Behavioral deficits exhibited by these animals, including heightened anxiety-like and depression-like behaviors, and defective extinction of fearful memories, were corrected by administration of the FAAH inhibitor, URB597, which normalized brain anandamide levels. Furthermore, GWI mice displayed unexpected changes in the microglial transcriptome, implying persistent dampening of homeostatic surveillance genes and abnormal expression of pro-inflammatory genes upon immune stimulation.
Together, these results suggest that exposure to GW chemicals produce a deficit in brain ECB signaling which is associated with persistent alterations in microglial function. Pharmacological normalization of anandamide-mediated ECB signaling may offer an effective therapeutic strategy for ameliorating GWI symptomology.”
https://pubmed.ncbi.nlm.nih.gov/39241906/
“A mouse model for Gulf War Illness (GWI) displays deficits in brain anandamide.
Normalization of endocannabinoid signaling may offer a therapeutic strategy for GWI.”
https://www.sciencedirect.com/science/article/pii/S0028390824003113?via%3Dihub
“FDA-approved cannabidiol [Epidiolex®] alleviates Gulf War Illness-linked cognitive and mood dysfunction, hyperalgesia, neuroinflammatory signaling, and declined neurogenesis”
https://pubmed.ncbi.nlm.nih.gov/39169440/
“CBD formulation improves energetic homeostasis in dermal fibroblasts from Gulf War Illness patients. Our data provide new evidence that will validate the potential of cannabinoids as a therapeutic strategy to mitigate energy imbalance that may contribute to detrimental symptomatology (i.e., chronic fatigue, brain fog, cognitive dysfunction, etc.) in GWI patients.”
“One endocannabinoid, anandamide, and an endocannabinoid analog N-oleoylethanolamine (OEA) were decreased in veterans with GWI [Gulf War Illness]”. [OEA, is also an endocannabinoid]
-The Mitochondrial and Metabolic Disease Center, University of California San Diego School of Medicine, San Diego, California, USA.
-Dept. of Medicine, Division of Medical Genetics, University of California San Diego School of Medicine, San Diego, California, USA.
-Dept. of Pathology, Division of Comparative Pathology,
-Dept. of Neurosciences, Division of Pediatric Neurology,
-Dept. of Medicine, Division of General Internal Medicine, University of California San Diego School of Medicine, San Diego, California, USA.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660083/
“Recently, an accumulating body of evidence has implicated the endocannabinoid system [ECS] in the etiology of PTSD, and targets within this system are believed to be suitable for treatment development.“. . .
“There is convincing evidence from multiple studies for reduced endocannabinoid availability in PTSD.“…
“Of particular relevance is evidence showing reduced levels of the endocannabinoid anandamide”…
– Department of Psychiatry, New York University School of Medicine
– United States Department of Veterans Affairs National Center for Posttraumatic Stress Disorder
http://www.ncbi.nlm.nih.gov/pubmed/25456347
“…..NYU School of Medicine, and colleagues are the first to demonstrate through brain imaging that people with PTSD have markedly lower concentrations of at least one of these neurotransmitters — an endocannabinoid known as anandamide — than people without PTSD. Their study, which was supported by three grants from the National Institutes of Health, illuminates an important biological fingerprint of PTSD that could help improve the accuracy of PTSD diagnoses, and points the way to medications designed specifically to treat trauma.”
https://www.sciencedaily.com/releases/2013/05/130514085016.htm
“The empirical evidence reviewed strongly supports the role for dysregulated cannabinoid signaling in the pathophysiology of social functioning deficits observed in brain disorders, such as autism spectrum disorder, schizophrenia, major depressive disorder, posttraumatic stress disorder and bipolar disorder. Moreover, these findings indicate that the endogenous cannabinoid system holds exceptional promise as a biological marker of, and potential treatment target for, neuropsychiatric and neurodevelopmental disorders characterized by impairments in social functioning.”
– Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences / Division of Child and Adolescent Psychiatry, Department of Psychiatry and Behavioral Sciences Stanford University School of Medicine
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5048207/