“Background: Chronic Gulf War Illness (GWI) is characterized by cognitive and mood impairments, as well as persistent neuroinflammation and oxidative stress. This study aimed to investigate the efficacy of Epidiolex^®, a Food and Drug Administration (FDA)-approved cannabidiol (CBD), in improving brain function in a rat model of chronic GWI.

Methods: Six months after exposure to low doses of GWI-related chemicals [pyridostigmine bromide, N,N-diethyl-meta-toluamide (DEET), and permethrin (PER)] along with moderate stress, rats with chronic GWI were administered either vehicle (VEH) or CBD (20 mg/kg, oral) for 16 weeks. Neurobehavioral tests were conducted on 11 weeks after treatment initiation to evaluate the performance of rats in tasks related to associative recognition memory, object location memory, pattern separation, and sucrose preference. The effect of CBD on hyperalgesia was also examined. The brain tissues were processed for immunohistochemical and molecular studies following behavioral tests.

Results: GWI rats treated with VEH exhibited impairments in all cognitive tasks and anhedonia, whereas CBD-treated GWI rats showed improvements in all cognitive tasks and no anhedonia. Additionally, CBD treatment alleviated hyperalgesia in GWI rats. Analysis of hippocampal tissues from VEH-treated rats revealed astrocyte hypertrophy and increased percentages of activated microglia presenting NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) complexes as well as elevated levels of proteins involved in NLRP3 inflammasome activation and Janus kinase/signal transducers and activators of the transcription (JAK/STAT) signaling. Furthermore, there were increased concentrations of proinflammatory and oxidative stress markers along with decreased neurogenesis. In contrast, the hippocampus from CBD-treated GWI rats displayed reduced levels of proteins mediating the activation of NLRP3 inflammasomes and JAK/STAT signaling, normalized concentrations of proinflammatory cytokines and oxidative stress markers, and improved neurogenesis. Notably, CBD treatment did not alter the concentration of endogenous cannabinoid anandamide in the hippocampus.

Conclusions: The use of an FDA-approved CBD (Epidiolex^®) has been shown to effectively alleviate cognitive and mood impairments as well as hyperalgesia associated with chronic GWI. Importantly, the improvements observed in rats with chronic GWI in this study were attributed to the ability of CBD to significantly suppress signaling pathways that perpetuate chronic neuroinflammation.”

https://pubmed.ncbi.nlm.nih.gov/39169440/

“Background: The recent interest among consumers in industrial hemp due to health and wellness benefits has led to several products from industrial hemp, including cannabidiol (CBD) oil. CBD oil extraction from hemp buds and flowers generates by-product biomass (hemp flakes), often posing disposal challenges and with little or no applications. We hypothesized that hemp flakes possess residual compounds with nutritional and health value that could be used to improve utilization.

Methods: Locally sourced hemp flakes were compared to three commercial hemp protein products. The nutritional composition (proximate analysis), heavy metals (Al, Cu, As, Pb, Co, Cd), and functional composition (phenolic and antioxidant properties-total phenolic compounds (TPC), total flavonoid compounds (TFC), ferric reducing antioxidant potential (FRAP), 1,1-diphenyl-1-picrylhydrazyl (DPPH), Trolox equivalent antioxidant capacity (TEAC)), (CBD, cannabiodiolic acid-CBDA, cannabichromene-CBC, cannabigerol-CBG, and cannabinol-CBN) contents were determined and compared.

Findings: Hemp flakes had a similar nutritional composition to commercial hemp protein products, with heavy metal levels within FDA allowed limits. The by-product had significantly higher CBDA levels than commercial products. Overall, hemp flakes had comparable nutrient composition and antioxidant capabilities. Based on the protein composition of hemp flakes (31.62 %) versus the highest commercial product (43 %), hemp flakes are an acceptable functional food ingredient.”

https://pubmed.ncbi.nlm.nih.gov/39165951/

“It is predicted that by 2050, the world’s population will reach 9 billion, and a sustained food supply will be a concern; therefore, it is appropriate to examine alternatives, including the exploration of agricultural waste materials. Hemp flakes as a by-product from CBD oil extraction could be utilized due to their nutritional and functional value. The hemp flake used in this work demonstrated to hold nutritional and health components comparable to related commercial products. The antioxidant levels showed variations attributed to the source of hemp material and solvent extraction method. Hemp flakes exhibited high and similar antioxidant properties as measured by TPC, TFC, FRAP, and TEAC and possessed comparable radical scavenging properties as measured by DPPH. The hemp by-product showed comparative amounts of cannabinoids with the highest content of cannabidiolic acid, which is known to break down to cannabidiol and possess functional benefits. Further, the results of this work have exemplified that hemp flakes generated from CBD oil extraction have a considerable nutritional and functional value that supports its potential to be incorporated in food preparations as an ingredient. It was also established that the hemp flakes contained levels below the permissible levels of heavy metals in foods, according to health and environmental agencies. It is concluded that the by-product from CBD oil extraction could be utilized as an ingredient in food processing, such as a composite with other ingredients to complement nutrition and health functionality for consumers.”

https://www.cell.com/heliyon/fulltext/S2405-8440(24)11217-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2405844024112170%3Fshowall%3Dtrue

“Inflammation plays a critical role in the development of numerous diseases.

Cannabidiol (CBD), found in hemp, exhibits significant pharmacological activities. Accumulating evidence suggests that CBD has anti-inflammatory and cardiovascular protection effects, but the potential mechanisms require further exploration.

In this study, we aimed to reveal the mechanisms of CBD against high-fat, high-cholesterol (HFC) diet-induced inflammation combining metabolomics with network pharmacology.

First, plasma lipidomics results indicated that oxidized lipids could serve as potential biomarkers for HFC diet-induced inflammation, and CBD reversed the elevated levels of oxidized lipids. The HFC diet was also found to enhance intestinal permeability, facilitating the entry of lipopolysaccharides (LPSs) into the circulatory system and subsequently increasing systemic inflammation.

Additionally, cell metabolomic results indicated that CBD could reverse 10 important differential metabolites in LPS-induced RAW 264.7 cells. Using network pharmacology, we identified 49 core targets, and enrichment analysis revealed that arachidonic acid was the most significantly affected by CBD, which was closely associated with inflammation.

Further integrated analysis focused on three key targets, including PTGS2, ALOX5, and ALOX15. Molecular docking showed high affinities between key targets and CBD, and qPCR further demonstrated that CBD could reverse the mRNA expression of these key targets in RAW 264.7 cells.

Collectively, this finding integrates lipidomics and metabolomics with network pharmacology to elucidate the anti-inflammatory effects of CBD and validates key therapeutic targets.”

https://pubmed.ncbi.nlm.nih.gov/39150414/

https://pubs.acs.org/doi/10.1021/acs.jafc.4c04994

“Background: Cannabis sativa with a rich history of traditional medicinal use, has garnered significant attention in contemporary research for its potential therapeutic applications in various human diseases, including pain, inflammation, cancer, and osteoarthritis. However, the specific molecular targets and mechanisms underlying the synergistic effects of its diverse phytochemical constituents remain elusive. Understanding these mechanisms is crucial for developing targeted, effective cannabis-based therapies.

Methods: To investigate the molecular targets and pathways involved in the synergistic effects of cannabis compounds, we utilized DRIFT, a deep learning model that leverages attention-based neural networks to predict compound-target interactions. We considered both whole plant extracts and specific plant-based formulations. Predicted targets were then mapped to the Reactome pathway database to identify the biological processes affected. To facilitate the prediction of molecular targets and associated pathways for any user-specified cannabis formulation, we developed CANDI (Cannabis-derived compound Analysis and Network Discovery Interface), a web-based server. This platform offers a user-friendly interface for researchers and drug developers to explore the therapeutic potential of cannabis compounds.

Results: Our analysis using DRIFT and CANDI successfully identified numerous molecular targets of cannabis compounds, many of which are involved in pathways relevant to pain, inflammation, cancer, and other diseases. The CANDI server enables researchers to predict the molecular targets and affected pathways for any specific cannabis formulation, providing valuable insights for developing targeted therapies.

Conclusions: By combining computational approaches with knowledge of traditional cannabis use, we have developed the CANDI server, a tool that allows us to harness the therapeutic potential of cannabis compounds for the effective treatment of various disorders. By bridging traditional pharmaceutical development with cannabis-based medicine, we propose a novel approach for botanical-based treatment modalities.”

https://pubmed.ncbi.nlm.nih.gov/39149470/

https://www.researchsquare.com/article/rs-4744915/v1