Biology subjects

Khodadadi, H.

Publications and source records attributed to Khodadadi, H..

3 recordsLinked to original sources

bioRxiv2025

Rethinking Alzheimer's: Harnessing Cannabidiol to Modulate IDO and cGAS Pathways for Neuroinflammation Control

Alzheimers disease has traditionally been associated with amyloid-{beta} plaques, but growing evidence underscores the role of neuroinflammation in disease progression. The autoimmune hypothesis of Alzheimers disease suggests chronic inflammation and immune dysfunction contribute to neuronal damage, making modulation of immune responses a promising therapeutic strategy for the disease. Cannabidiol, a phytocannabinoid with anti-inflammatory properties, may offer therapeutic potential. This study explores how cannabidiol influences the Indoleamine 2,3-dioxygenase (IDO) and cyclic GMP-AMP synthase (cGAS) pathway, a key regulator of neuroinflammation in Alzheimers disease. Using the 5XFAD transgenic mouse model of Alzheimers disease, we administered cannabidiol via inhalation. We assessed immune markers, including Indoleamine 2,3-dioxygenase and cyclic GMP-AMP synthase, through flow cytometry, immunofluorescence staining, and gene expression analysis. Cytokine levels and neuroinflammatory responses were evaluated, and protein-protein interactions within the Indoleamine 2,3-dioxygenase/cyclic GMP-AMP synthase pathway were analyzed using the STRING database. Cannabidiol treatment significantly reduced Indoleamine 2,3-dioxygenase and cyclic GMP-AMP synthase expression, correlating with lower levels of pro-inflammatory cytokines, including Tumor Necrosis Factor-alpha, Interleukin-1 beta, and Interferon-gamma. Bioinformatics analysis identified potential interactions between cannabidiol and immune targets such as Protein Kinase B (AKT1), Transient Receptor Potential Vanilloid 1, and G-protein coupled receptor 55, suggesting a multi-targeted therapeutic effect. These findings support cannabidiol as a potential monotherapy or adjunctive treatment for Alzheimers disease, targeting neuroinflammatory pathways, particularly the Indoleamine 2,3-dioxygenase/cyclic GMP-AMP synthase axis. Further studies are needed to explore its full therapeutic potential.

immunology↗

bioRxiv2024

Optimization of Seizure Prevention by Cannabidiol (CBD)

ObjectiveCannabidiol (CBD) is one of the most prominent non-psychotropic cannabinoids with known therapeutic potentials. Based on its anti-seizure efficacy, the first cannabis derived, pharmaceutical grade CBD-based medication was approved in the USA in 2018 for the treatment of seizures in patients 2 years and older. Despite the effectiveness in reducing seizures, there remain several major questions on the optimization of CBD therapy for epilepsy such as the optimal dosage, composition, and route of delivery, which are the main objective of this current study. MethodsWe evaluated the antiseizure effects of CBD through different compositions, routes of delivery, and dosages in a pre-clinical model. We used a kainic acid-induced epilepsy model in C57BL/6 mice, treated them with placebo and/or CBD through inhalation, oral and injection routes. We used CBD broad spectrum (inhaled and injection) versus CBD isolate formulations. We employed the Racine scaling system to evaluate the severity of the seizures, flow cytometry for measuring Immune biomarkers and neurotrophic factors, and histologic analysis to examine and compare the groups. ResultsOur findings showed that all forms of CBD reduced seizures severity. Among the combination of CBD tested. CBD broad spectrum via inhalation was the most effective in the treatment of epileptic seizures (p<0.05) compared to other forms of CBD treatments. ConclusionOur data suggest that route and CBD formulations affect its efficacy in the prevention of epileptic seizures. Inhaled broad spectrum CBD showed a potential superior effect compared to other delivery routes and CBD formulations in the prevention of epileptic seizures, warrants further research.

neuroscience↗

bioRxiv2024

Cannabidiol reverses fentanyl-induced addiction and modulates neuroinflammation

IntroductionFentanyl and non-pharmaceutical fentanyl use have been the leading causes of opioid-induced death worldwide. Being 50 times stronger than heroin and 100 times stronger than morphine, fentanyl is a potent opioid with overdoses causing over 250,000 deaths since 2018 in the US alone. The treatment of fentanyl addiction is a complex process and a clinical challenge. There is a dire need to find other innovative and alternative modalities in the fight against fentanyl crisis. Increasing evidence suggests a correlation between neuroinflammation and symptoms of drug abuse, opening up the possibility of immunoregulatory agents as therapy for fentanyl addiction as well as a other opioid-induced addiction. Cannabidiol (CBD) is a non-opioid, relatively safe, non-psychoactive phyto-cannabinoid produced by cannabis plants. Importantly, recent reports have documented benefits of CBD in the treatment and management of complications related to opioid withdrawal. We investigated if inhaled CBD could reverse the fentanyl addiction and whether the CBD treatment could ameliorate the addiction symptoms by regulating neuroinflammatory signals and re-establishing the homeostasis in CNS. MethodWe used a fentanyl-induced conditioned place preference (CPP) model in mouse to test whether inhaled CBD could reverse the fentanyl addiction and ameliorate the adversarial symptoms. By employing a combination of flow cytometry as well as behavioral tests, we further assessed the impact of fentanyl addiction on cells and neuroinflammatory signals in CNS and we measured the effects of CBD in the treatment of addiction symptoms and inflammatory signals. ResultsOur findings suggest that CBD inhalation could be used effectively in the treatment of fentanyl addiction. CBD mitigated the excessive fentanyl-induced neuroinflammatory responses and decreased cellular stress and senescence. Conclusioninhaled CBD could alleviate the fentanyl addiction and regulate neuroinflammatory responses. This novel approach is non-invasive, accessible, effective, and warrants further, translational and research.

animal behavior and cognition↗