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CBD reduces the production of pro-angiogenic factors in gliomas in a dose-dependent fashion. THC when co-administered with CBD synergistically inhibited proliferation and caused cell cycle arrest in vitro of human glioblastoma cells . Historically, lemon products and spicy products with black pepper and cloves have been used, due to their limonene and beta caryophyllene content, respectively, for excesses of THC, panic attacks, and tachycardia. As competitive agonists for the CB1 receptor, they force THC to separate from the G-Protein receptor in the central nervous system, which reduces the influence of THC, the panic attack, and the increased heart rate. It has been theorized that certain chronic conditions, such as Post Traumatic Stress Disorder , migraine, fibromyalgia, and inflammatory bowel disease are the result of deficiencies in tonic eCB signaling.

Circulating levels of eCBs are markedly decreased in these disorders. This diminished amount of eCBs has been correlated to anxiety-like behaviors.

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It is known, for instance, that chronic environmental stress will down-regulate CB1 receptors as well as reducing levels of AEA at the same time as increasing levels of 2-AG . ) were compared to a standard CB1 ortholog in rat cerebellar tissue and were found to have high affinity binding interactions at concentrations typically found with CB1 receptors. The anatomical localization of the CB1 receptor in the normal canine nervous system has been determined through the use of immunohistochemical analysis. Currently, studies are underway using the more accurate polymerase chain reaction technology, but that data is, as yet, unpublished. Nervous systems from healthy dogs at 4 months, 6 months, and 10-year-old dogs were evaluated post-mortem.

Neutrophils of the cerebral cortex, cornu ammonis , dentate gyrus of the hippocampus, midbrain, cerebellum, medulla oblongata, and gray matter of the spinal cord were found to have strong immunoreactivity. Dense CB1 expression was found in the fibers of the globus pallidus and substantia nigra, based upon dense CB1 immunoreactivity.

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These immuno-reactive locations were surrounded by neurons with no immunoreactivity. eCBs are produced ad hoc by enzymes located in the cell membrane stimulated by the intracellular elevation of calcium ions secondary to neuronal depolarization.

The constitutive level of endocannabinoids is termed the “Endocannabinoid Tone”, and that level varies based on the specific tissue in which they are found. These levels are dependent upon their rate of production minus the rate of their enzymatic degradation. Fatty acid amide hydrolase and monoacyl-glycerol lipase are the specific enzymes involved in modulating endocannabinoid tone. AEA and 2-AG, which are the two endogenous endocannabinoids, are enzymatically metabolized by FAAH and MAGL, respectively. , the endocannabinoid system arose in the phylogeny concurrently with the development of the nervous system as multicellular animals developed increasing complexity.

This neuroprotection effect is separate from their CB receptor binding activity. THC and CBD reduce ROS in vitro when compared to common antioxidants such as ascorbate and butylated hydroxytoluene . In animal models of Alzheimer’s Disease, CBD was able to reduce Alzheimer’s-related neuro-inflammation .

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