https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828614: Cannabinoids are a group of compounds that mediate their effects through cannabinoid receptors. The discovery of Δ9-tetrahydrocannabinol (THC) as the major psychoactive principle in marijuana, as well as the identification of cannabinoid receptors and their endogenous ligands, has led to a significant growth in research aimed at understanding the physiological functions of cannabinoids. 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. Recent studies demonstrated that administration of THC into mice triggered marked apoptosis in T cells and dendritic cells, resulting in immunosuppression. In addition, several studies showed that cannabinoids downregulate cytokine and chemokine production and, in some models, upregulate T-regulatory cells (Tregs) as a mechanism to suppress inflammatory responses. The endocannabinoid system is also involved in immunoregulation. For example, 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. This review will focus on the potential use of cannabinoids as a new class of anti-inflammatory agents against a number of inflammatory and autoimmune diseases that are primarily triggered by activated T cells or other cellular immune components.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2503660: This article reviews recent research on cannabinoid analgesia via the endocannabinoid system and non-receptor mechanisms, as well as randomized clinical trials employing cannabinoids in pain treatment. Tetrahydrocannabinol (THC, Marinol®) and nabilone (Cesamet®) are currently approved in the United States and other countries, but not for pain indications. Other synthetic cannabinoids, such as ajulemic acid, are in development. Crude herbal cannabis remains illegal in most jurisdictions but is also under investigation. Sativex®, a cannabis derived oromucosal spray containing equal proportions of THC (partial CB1 receptor agonist ) and cannabidiol (CBD, a non-euphoriant, anti-inflammatory analgesic with CB1 receptor antagonist and endocannabinoid modulating effects) was approved in Canada in 2005 for treatment of central neuropathic pain in multiple sclerosis, and in 2007 for intractable cancer pain. Numerous randomized clinical trials have demonstrated safety and efficacy for Sativex in central and peripheral neuropathic pain, rheumatoid arthritis and cancer pain. An Investigational New Drug application to conduct advanced clinical trials for cancer pain was approved by the US FDA in January 2006. Cannabinoid analgesics have generally been well tolerated in clinical trials with acceptable adverse event profiles. Their adjunctive addition to the pharmacological armamentarium for treatment of pain shows great promise.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005548: Cannabinoids have been approved in some countries for the treatment of chemotherapy-induced nausea and vomiting, and clinical trials show cannabinoids' effectiveness in pain inhibition and appetite stimulation (Guzman 2003; Tramer et al. 2001). Anti-inflammatory therapeutic potential of cannabinoids is also evident from the studies discussed in this review paper. At the optimal concentrations, cannabinoids do induce apoptosis in immune cells, alleviating inflammatory responses and protecting the host from acute and chronic inflammation. The cumulative effect of cannabinoids on all cell populations of the immune system can be beneficial, when there is a need for immune suppression. For example, in patients with autoimmune diseases such as multiple sclerosis, arthritis and lupus, or in those with septic shock, where the disease is caused by activated immune cells, targeting the immune cells via CB2 agonists may trigger apoptosis and act as anti-inflammatory therapy. CB2 select agonists are not psychoactive and because CB2 is expressed primarily in immune cells, use of CB2 agonists could provide a novel therapeutic modality against autoimmune and inflammatory diseases. Clearly, additional research is necessary to validate these studies in humans through clinical trials. However, in other instances, such as in patients with breast cancer in which cannabinoid receptors may not be expressed by the cancer cells, cannabinoids may worsen the disease, because the immune system is weakened, and the breast cancer cells are resistant to cannabinoid-induced apoptosis. Thus, it is critical to balance the immunsuppressive effects with the anticancer properties, which require careful dose–response studies on these clinical outcomes. Overall, there exists a biphasic role for cannabinoids, and it depends on three key factors: (1) the type of cannabinoid, (2) the dose of cannabinoid, and (3) the type of cell that the cannabinoid is acting on. The degree of cannabinoid receptor expression may play role in some cases; however, the receptor-independent mechanism of action is evident for cannabinoids in some cell populations. In addition to the use of exogenous cannabinoids, in vivo manipulation of endocannabinoids may also offer novel treatment opportunities against cancer and autoimmune diseases.
Cannabis -vs- Lupus