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Cannabinoids As Novel Anti-Inflammatory Drugs

 

Key Takeaways From This Case Study:

  • Cannabinoid receptors include CB1, which is predominantly expressed in the brain, and CB2, which is primarily found on the cells of the immune system. The fact that both CB1 and CB2 receptors have been found on immune cells suggests that cannabinoids play an important role in the regulation of the immune system.

  • Administration of endocannabinoids or use of inhibitors of enzymes that break down the endocannabinoids, led to immunosuppression and recovery from immune-mediated injury to organs such as the liver. Manipulation of endocannabinoids and/or use of exogenous cannabinoids in vivo can constitute a potent treatment modality against inflammatory disorders.

  • Cannabinoids are potent anti-inflammatory agents and they exert their effects through induction of apoptosis, inhibition of cell proliferation, suppression of cytokine production and induction of T-regulatory cells (Tregs).

  • It is important to note that, unlike in immune cells, cannabinoids can protect from apoptosis in nontransformed cells of the CNS, which can play a protective role in autoimmune conditions such as multiple sclerosis.

  • Cannabinoids also exert their immunosuppressive effects on astrocytes. Astrocytes make up 60–70% of brain cells in the CNS and play important roles in neuronal growth, neuronal signaling, glucose metabolism and glutamate removal.

  • Cannabinoids have been shown to regulate the tissue response to excessive inflammation in the colon, mediated by both dampening smooth-muscular irritation caused by inflammation and suppressing proinflammatory cytokines.

  • Endocannabinoids may regulate the pathophysiology of liver diseases, including both acute forms of hepatic injury, liver fibrosis and cirrhosis. The endocannabinoids are found in low levels in normal liver, which may be due to high levels of expression of FAAH, which is responsible for the breakdown of AEA.

  • In malignancies, such as thyroid cancer, lymphoma, melanoma, pancreas and breast cancer, the levels of cannabinoid receptors are often higher in the tumor compared with normal cells of the same origin, resulting in increased sensitivity to cannabinoids in the malignancies. Thus, the role of the cannabinoid system in cancer indicates that this system is involved in regulating many of the functions that are essential in cancer development.

  • CBD treatment has been shown to significantly inhibit and delay destructive insulitis and inflammatory Th1-associated cytokine production.

  • CBD treatment inhibited specific destruction of the islets and reduced the infiltrates by mononuclear cells into the islets, thus preventing diabetes. Furthermore, cannabinoids have also been demonstrated to possess additional beneficial effects in animal models of diabetes. It has been reported that rats treated with CBD for periods of 1–4 weeks experienced significant protection from diabetic retinopathy. Cannabinoids have also been shown to alleviate neuropathic pain associated with the disease.

  • Exogenous cannabinoids have been shown to suppress T-cell-mediated immune responses by primarily inducing apoptosis and suppressing inflammatory cytokines and chemokines. Such observations indicate that targeting cannabinoid receptor–ligand interactions may constitute a novel window of opportunity to treat inflammatory and autoimmune disorders.

  • Cannabinoids suppress inflammatory response and subsequently attenuate disease symptoms. This property of cannabinoids is mediated through multiple pathways such as induction of apoptosis in activated immune cells, suppression of cytokines and chemokines at inflammatory sites and upregulation of FoxP3+ regulatory T cells.

  • Cannabinoids have been tested in several experimental models of autoimmune disorders such as multiple sclerosis, rheumatoid arthritis, colitis and hepatitis and have been shown to protect the host from the pathogenesis through induction of multiple anti-inflammatory pathways.

  • Cannabinoids may also be beneficial in certain types of cancers that are triggered by chronic inflammation. In such instances, cannabinoids can either directly inhibit tumor growth or suppress inflammation and tumor angiogenesis.

  • One major mechanism of immunosupression by cannabinoids is the induction of cell death or apoptosis in immune cell populations. Apoptosis not only eliminates pre-cancerous and virus-infected cells, but maintains the balance of cells in the human body too.

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