“Cannabis sativa L. (Cannabaceae) is one of the first plants cultivated by man and one of the oldest plant sources of fibre, food and remedies. Cannabinoids comprise the plant‐derived compounds and their synthetic derivatives as well as endogenously produced lipophilic mediators. Phytocannabinoids are terpenophenolic secondary metabolites predominantly produced in CannabissativaL. The principal active constituent is delta‐9‐tetrahydrocannabinol (THC), which binds to endocannabinoid receptors to exert its pharmacological activity, including psychoactive effect. The other important molecule of current interest is non‐psychotropic cannabidiol (CBD). Since 1970s, phytocannabinoids have been known for their palliative effects on some cancer‐associated symptoms such as nausea and vomiting reduction, appetite stimulation and pain relief. More recently, these molecules have gained special attention for their role in cancer cell proliferation and death. A large body of evidence suggests that cannabinoids affect multiple signalling pathways involved in the development of cancer, displaying an anti‐proliferative, proapoptotic, anti‐angiogenic and anti‐metastatic activity on a wide range of cell lines and animal models of cancer.” https://www.intechopen.com/books/natural-products-and-cancer-drug-discovery/phytochemical-aspects-and-therapeutic-perspective-of-cannabinoids-in-cancer-treatment]]>
Tag Archives: therapeutic
Targeting the endocannabinoid system as a potential anticancer approach.
“The endocannabinoid system is currently under intense investigation due to the therapeutic potential of cannabinoid-based drugs as treatment options for a broad variety of diseases including cancer.
Besides the canonical endocannabinoid system that includes the cannabinoid receptors CB1 and CB2 and the endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol, recent investigations suggest that other fatty acid derivatives, receptors, enzymes, and lipid transporters likewise orchestrate this system as components of the endocannabinoid system when defined as an extended signaling network.
As such, fatty acids acting at cannabinoid receptors (e.g. 2-arachidonoyl glyceryl ether [noladin ether], N-arachidonoyldopamine) as well as endocannabinoid-like substances that do not elicit cannabinoid receptor activation (e.g. N-palmitoylethanolamine, N-oleoylethanolamine) have raised interest as anticancerogenic substances.
Furthermore, the endocannabinoid-degrading enzymes fatty acid amide hydrolase and monoacylglycerol lipase, lipid transport proteins of the fatty acid binding protein family, additional cannabinoid-activated G protein-coupled receptors, members of the transient receptor potential family as well as peroxisome proliferator-activated receptors have been considered as targets of antitumoral cannabinoid activity. Therefore, this review focused on the antitumorigenic effects induced upon modulation of this extended endocannabinoid network.” https://www.ncbi.nlm.nih.gov/pubmed/29390896 http://www.tandfonline.com/doi/abs/10.1080/03602532.2018.1428344?journalCode=idmr20
“Anticancer mechanisms of cannabinoids” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791144/
“Cannabinoids as Anticancer Drugs.”
]]>
Cannabis Use, Lung Cancer, and Related Issues.
“The cannabis plant and its derivatives have been exploited for centuries for recreational and medicinal purposes with millions of regular users around the world. The recreational use of cannabis is reflective of its neuropsychiatric effects such as anxiolysis and euphoria. However, cannabis appears to have an emerging therapeutic role, especially in chronic disease and as an adjunct to cancer treatment. Increasing evidence supports cannabis in the management of chemotherapy induced nausea and vomiting and for pain management, but studies are limited particularly by difficulties associated with standardized dosing estimates and inability to accurately assess biologic activities of compounds in cannabis and derivative products. Smoking cannabis has not been proven to be a risk factor in the development of lung cancer but the data are limited by small studies, misclassification due to self-reporting of usage, small numbers of heavy cannabis smoking and confounding of risk associated with known causative agents for lung cancer such as parallel chronic tobacco use. Cannabis and its biologically effective derivatives warrant additional research, ideally controlled trials where the CBD and the THC strength and usage are controlled and documented.” https://www.ncbi.nlm.nih.gov/pubmed/29374567
“Good News: There’s No Definitive Link Between Marijuana Use and Lung Cancer” http://www.esquire.com/lifestyle/health/news/a52634/marijuana-lung-cancer/
“Study Shows No Proven Link Between Weed-Smoking and Lung Cancer” http://www.complex.com/life/2017/01/weed-study-lung-cancer
]]>Cannabinoid CB1 and CB2 Receptors, and Monoacylglycerol Lipase Gene Expression Alterations in the Basal Ganglia of Patients with Parkinson's Disease.
“Previous studies suggest that the endocannabinoid system plays an important role in the neuropathological basis of Parkinson’s disease (PD). This study was designed to detect potential alterations in the cannabinoid receptors CB1 (CB1r) and CB2 (A isoform, CB2Ar), and in monoacylglycerol lipase (MAGL) gene expression in the substantia nigra (SN) and putamen (PUT) of patients with PD. The results of the present study suggest that CB1r, CB2r, and MAGL are closely related to the neuropathological processes of PD. Therefore, the pharmacological modulation of these targets could represent a new potential therapeutic tool for the management of PD.” https://www.ncbi.nlm.nih.gov/pubmed/29352424 https://link.springer.com/article/10.1007%2Fs13311-018-0603-x]]>
Cannabidiol Limits T Cell–Mediated Chronic Autoimmune Myocarditis: Implications to Autoimmune Disorders and Organ Transplantation
“Cannabidiol (CBD) is a nonpsychoactive ingredient of marijuana (Cannabis sativa). Collectively, our study demonstrates that CBD treatment markedly attenuates autoimmune myocarditis and improves myocardial dysfunction and heart failure primarily by its antiinflammatory and antifibrotic effects. These results, coupled with the proven safety of CBD in human clinical trials and its current orphan drug approval by the FDA for different neurological disorders, suggest that it has tremendous therapeutic potential in the therapy of myocarditis with different etiologies and various autoimmune disorders. The latter is also supported by beneficial effects of CBD in preventing graft versus host disease after allogeneic hematopoietic cell transplantation in a recent phase II human study, as well as in mice with arthritis. Attenuation of the T cell–mediated injury by CBD also suggests that it may have therapeutic utility in management of organ transplantation/rejection. In conclusion, CBD may represent a promising novel treatment for managing autoimmune myocarditis and possibly other autoimmune disorders and organ transplantation.” https://www.ncbi.nlm.nih.gov/pubmed/26772776 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004721/ http://static.smallworldlabs.com/molmedcommunity/content/pdfstore/16_007_Lee.pdf]]>
History of marijuana use does not affect outcomes on the liver transplant waitlist.
“Data are limited on marijuana use and its impact on liver transplant (LT) waitlist outcomes. We aimed to assess the risk of waitlist mortality/delisting and likelihood of LT among prior marijuana users, and to determine the prevalence and factors associated with marijuana use. Unlike illicit drug use, marijuana use was not associated with worse outcomes on the LT waitlist.” https://www.ncbi.nlm.nih.gov/pubmed/29319619 https://insights.ovid.com/crossref?an=00007890-900000000-96711 https://journals.lww.com/transplantjournal/Abstract/onlinefirst/History_of_marijuana_use_does_not_affect_outcomes.96711.aspx
“Do Cannabinoids have a therapeutic role in transplantation? Transplantation is one critical area of medicine that requires the use of immunosuppressants. Cannabinoids have emerged as powerful drug candidates for the treatment of inflammatory and autoimmune diseases due to their immunosuppressive properties.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923447/
“The history of donor cannabis smoking does not appear to affect early and mid-term outcomes after lung transplantation (LTx) and potentially improve the donor pool. As it does not seem to negatively affect the outcomes after LTx, it should not be per se considered a contraindication for lung donation.” https://www.ncbi.nlm.nih.gov/pubmed/28077504
“THC In Marijuana Delays Organ Transplant Rejection In Mice. A new study suggests the active ingredient in marijuana delays the rejection of incompatible organs in mice.” http://www.iflscience.com/health-and-medicine/thc-marijuana-may-delay-organ-transplant-rejection/
“Δ9-Tetrahydrocannabinol attenuates allogeneic host-versus-graft response and delays skin graft rejection through activation of cannabinoid receptor 1 and induction of myeloid-derived suppressor cells” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4541500/
“Cannabidiol Limits T Cell-Mediated Chronic Autoimmune Myocarditis: Implications to Autoimmune Disorders and Organ Transplantation. CBD may represent a promising novel treatment for management of autoimmune myocarditis and possibly other autoimmune disorders, and organ transplantation.” http://pubmedcentralcanada.ca/pmcc/articles/PMC5004721/
“Could CANNABIS help transplant patients? Drug ‘delays rejection of organs by slowing the immune system’s attack'” http://www.dailymail.co.uk/health/article-3279752/Could-CANNABIS-help-transplant-patients-Drug-delays-rejection-organs-slowing-immune-s-attack.html
Cannabis, cannabinoids, and health.
“Cannabis does have therapeutic properties for certain indications.” https://www.ncbi.nlm.nih.gov/pubmed/29302228 “The legislative policies that have been established to reduce the risks in relation to cannabis have long represented an obstacle to research concerning medical cannabis use. Improved knowledge of the endocannabinoid system and of exocannabinoids has proven that cannabis may have significant therapeutic effects.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741114/]]>
The therapeutic potential of targeting the peripheral endocannabinoid/CB1 receptor system.
“Endocannabinoids (eCBs) are internal lipid mediators recognized by the cannabinoid-1 and -2 receptors (CB1R and CB2R, respectively), which also mediate the different physiological effects of marijuana. The endocannabinoid system, consisting of eCBs, their receptors, and the enzymes involved in their biosynthesis and degradation, is present in a vast number of peripheral organs. In this review we describe the role of the eCB/CB1R system in modulating the metabolism in several peripheral organs. We assess how eCBs, via activating the CB1R, contribute to obesity and regulate food intake. In addition, we describe their roles in modulating liver and kidney functions, as well as bone remodeling and mass. Special importance is given to emphasizing the efficacy of the recently developed peripherally restricted CB1R antagonists, which were pre-clinically tested in the management of energy homeostasis, and in ameliorating both obesity- and diabetes-induced metabolic complications.”
https://www.ncbi.nlm.nih.gov/pubmed/29336868
“Sepsis is a clinical condition resulting from a dysregulated immune response to an infection that leads to organ dysfunction. Despite numerous efforts to optimize treatment, sepsis remains to be the main cause of death in most intensive care units.
The endogenous 
“Targeting the endocannabinoid system has emerged as an effective strategy for the treatment of inflammatory and neurological diseases.
Unlike the inhibition of the principal 2-arachidonyl glycerol (2-AG) hydrolytic enzyme monoacylglycerol lipase (MAGL), which leads to 2-AG overload and