“Cannabinoid receptors have been shown to interact with other receptors, including Tumor Necrosis Factor Receptor Superfamily (TNFRS) members, to induce cancer cell death. When cannabinoids and death-inducing ligands (including TRAIL) are administered together, they have been shown to synergize and demonstrate enhanced antitumor activity in vitro. Certain cannabinoid ligands have been shown to sensitize cancer cells and synergistically interact with members of the TNFRS, thus suggesting that the combination of cannabinoids with death receptor (DR) ligands induces additive or synergistic tumor cell death. This review summarizes recent findings on the interaction of the cannabinoid and DR systems and suggests possible clinical co-application of cannabinoids and DR ligands in the treatment of various malignancies.” https://www.ncbi.nlm.nih.gov/pubmed/28948607 http://onlinelibrary.wiley.com/doi/10.1002/1873-3468.12863/abstract?systemMessage=Wiley+Online+Library+will+be+unavailable+on+Saturday+7th+Oct+from+03.00+EDT+%2F+08%3A00+BST+%2F+12%3A30+IST+%2F+15.00+SGT+to+08.00+EDT+%2F+13.00+BST+%2F+17%3A30+IST+%2F+20.00+SGT+and+Sunday+8th+Oct+from+03.00+EDT+%2F+08%3A00+BST+%2F+12%3A30+IST+%2F+15.00+SGT+to+06.00+EDT+%2F+11.00+BST+%2F+15%3A30+IST+%2F+18.00+SGT+for+essential+maintenance.+Apologies+for+the+inconvenience+caused+.]]>
Efficacy and Tolerability of Phytomedicines in Multiple Sclerosis Patients: A Review.
“Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disorder of the central nervous system (CNS) that can cause cognition, mobility, and sensory impairments. It is considered one of the most common non-traumatic causes of disability in the world.
The aim of the present article was to review the clinical evidence related to medicinal plants in the management of MS symptoms.
Electronic databases, including the Cochrane Library, Pubmed, and Scopus, were searched for entries from 1966 to February 2017. Only clinical studies were included in this review. Different medicinal plants have positive effects on MS, including Andrographis paniculata, Boswellia papyrifera, Ruta graveolens, Vaccinium spp., Camellia sinensis, Panax ginseng, Aloysia citrodora, Ginkgo biloba, Oenothera biennis, and Cannabis sativa.
C. sativa had the highest level of clinical evidence, supporting its efficacy in MS symptoms.
Proanthocyanidins, ginkgo flavone glycosides, ginsenosides, epigallocatechin-3-gallate, cannabinoids (including delta-9-tetrahydrocannabinol and cannabidiol), boswellic acid, and andrographolide were presented as the main bioactive components of medicinal plants with therapeutic benefits in MS.
The main complications of MS in which natural drugs were effective include spasticity, fatigue, scotoma, incontinence, urinary urgency, nocturia, memory performance, functional performance, and tremor. Herbal medicines were mostly well tolerated, and the adverse effects were limited to mild to moderate. Further well-designed human studies with a large sample size and longer follow-up period are recommended to confirm the role of medicinal plants and their metabolites in the management of MS.”
https://www.ncbi.nlm.nih.gov/pubmed/28948486
Cannabinoid CB1 Discrimination: Effects of Endocannabinoids and Catabolic Enzyme Inhibitors.
“An improved understanding of the endocannabinoid system has provided new avenues of drug discovery and development toward the management of pain and other behavioral maladies. Exogenous cannabinoid type-1 (CB1) receptor agonists such as Δ9-tetrahydrocannabinol are increasingly utilized for their medicinal actions; however, their utility is constrained by concern regarding abuse-related subjective effects. This has led to growing interest in the clinical benefit of indirectly enhancing the activity of the highly labile endocannabinoids N-arachidonoylethanolamine (anandamide; AEA) and/or 2-arachidonoylglycerol (2-AG) via catabolic enzyme inhibition. The present studies were conducted to determine whether such actions can lead to CB1 agonist-like subjective effects, as reflected in the presence or absence of CB1-related discriminative-stimulus effects in laboratory subjects. Squirrel monkeys (n=8) that discriminated the CB1 full agonist AM4054 (0.01 mg/kg) from vehicle were used to study, first, inhibitors of fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MGL) alone or in combination [FAAH (URB597, AM4303); MGL (AM4301); FAAH/MGL (AM4302)] and, second, the ability of the endocannabinoids AEA and 2-AG to produce CB1 agonist-like effects when administered alone or after enzyme inhibition. Results indicate that CB1-related discriminative-stimulus effects were produced by combined, but not selective, inhibition of FAAH and MGL, and that these effects were non-surmountably antagonized by low doses of rimonabant. Additionally, FAAH- or MGL-inhibition revealed CB1-like subjective effects produced by AEA, but not 2-AG. Taken together, the present data suggest that therapeutic effects of combined, but not selective, enhancement of AEA or 2-AG activity via enzyme inhibition may be accompanied by CB1 receptor-mediated subjective effects.” https://www.ncbi.nlm.nih.gov/pubmed/28947487 http://jpet.aspetjournals.org/content/early/2017/09/25/jpet.117.244392]]>
Do Medical Marijuana Laws Reduce Addictions and Deaths Related to Pain Killers?
“Many medical marijuana patients report using marijuana to alleviate chronic pain from musculoskeletal problems and other sources. If marijuana is used as a substitute for powerful and addictive pain relievers in medical marijuana states, a potential overlooked positive impact of medical marijuana laws may be a reduction in harms associated with opioid pain relievers, a far more addictive and potentially deadly substance. To assess this issue, we study the impact of medical marijuana laws on problematic opioid use. We use two measures of problematic use: treatment admissions for opioid pain reliever addiction from the Treatment Episode Data Set (TEDS) and state-level opioid overdose deaths in the National Vital Statistics System (NVSS). Using both standard differences-in-differences models as well as synthetic control models, we find that states permitting medical marijuana dispensaries experience a relative decrease in both opioid addictions and opioid overdose deaths compared to states that do not. We find no impact of medical marijuana laws more broadly; the mitigating effect of medical marijuana laws is specific to states that permit dispensaries. We evaluate potential mechanisms. Our findings suggest that providing broader access to medical marijuana may have the potential benefit of reducing abuse of highly addictive painkillers.” http://www.nber.org/papers/w21345.pdf “Cannabis use is associated with a substantial reduction in premature deaths in the United States. These data suggest that Cannabis use may decrease premature deaths. Overall, prohibition is estimated to lead to similar numbers of premature deaths as drunk driving, homicide, or fatal opioid overdose. Cannabis use prevents thousands of premature deaths each year, and Cannabis prohibition is revealed as a major cause of premature death in the U.S.” https://scholarworks.iu.edu/dspace/handle/2022/21632]]>
The Use of Cannabis in Response to the Opioid Crisis: A Review of the Literature
“A staggering number of Americans are dying from overdoses attributed to prescription opioid medications (POMs). In response, states are creating policies related to POM harm reduction strategies, overdose prevention, and alternative therapies for pain management, such as cannabis (medical marijuana). The purpose of this article is to examine state medical cannabis (MC) use laws and policies and their potential association with POM use and related harms. Review of the current literature suggests states that implement MC policies could reduce POM associated mortality, improve pain management, and significantly reduce health care costs. However, MC research is constrained by federal policy restrictions, and more research related to MC as a potential alternative to POM for pain management, MC harms, and its impact on POM related harms and healthcare costs should be a priority of public health, medical, and nursing research.” http://www.nursingoutlook.org/article/S0029-6554(17)30286-5/fulltext?cc=y%3D
“The use of cannabis in response to the opioid crisis: A review of the literature. Review of the current literature suggests states that implement MC policies could reduce POM-associated mortality, improve pain management, and significantly reduce health care costs.” https://www.ncbi.nlm.nih.gov/pubmed/28993073
]]>Can Cannabis be Considered a Substitute Medication for Alcohol?
“Substituting cannabis for alcohol may reduce drinking and related problems among alcohol-dependent individuals. Some even recommend prescribing medical cannabis to individuals attempting to reduce drinking. While more research and improved study designs are needed to better identify the extent and impact of cannabis substitution on those affected by AUD, cannabis does appear to be a potential substitute for alcohol. Perhaps more importantly, cannabis is both safer and potentially less addictive than benzodiazepines and other pharmaceuticals that have been evaluated as substitutes for alcohol.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992908/]]>
Targeting the Endocannabinoid System to Treat Sepsis
“Sepsis is a complex immune disorder that can affect the function of almost all organ systems in the body. This disorder is characterised by a malfunctioning immune response to an infection that involves both pro-inflammatory and immunosuppressive mediators. This leads to severe damage and failure of vital organs, resulting in patient death. Sepsis, septic shock, and systemic inflammatory response syndrome are the leading causes of mortality in surgical intensive care unit patients internationally. The current lack of viable therapeutic treatment options for sepsis underscores our insufficient understanding of this complex disease. The endocannabinoid system, a key regulator of essential physiological functions including the immune system, has recently emerged as a potential therapeutic target for sepsis treatment. The endocannabinoid system acquires its name from the plant Cannabis Sativa, which has been used medically to treat a variety of ailments, as well as recreationally for centuries. Cannabis Sativa contains more than 60 active phytocannabinoids with the primary phytocannabinoid Δ9-tetrahydrocannabinol (THC), (6) activating both endogenous endocannabinoid receptors. The endocannabinoid system represents a potential therapeutic target in sepsis due to the presence of cannabinoid receptors (CB2) on immune cells. In this review we discuss how various targets within the endocannabinoid system can be manipulated to treat the immune consequences of sepsis. One of the targets outlined are the endocannabinoid receptors and modulation of their activity through pharmacological agonists and antagonists. Another therapeutic target covered in this review is the modulation of the endocannabinoid degradative enzyme’s activity. Modulation of degradative enzyme activity can change the levels of endogenous cannabinoids thereby altering immune activity. Overall, activation of the CB2 receptors causes immunosuppression and can be beneficial during the hyperactivated immune state of sepsis, while suppression of the CB2 receptors may be beneficial during a hypoimmune septic state. The endocannabinoid system modulates the immune response in experimental sepsis. Manipulating the endocannabinoid system may have potential therapeutic benefit in clinical sepsis where immune and inflammatory dysfunction can be detrimental. Multiple targets exist within the endocannabinoid system, e.g. the system can be targeted at the level of receptors by administration of synthetic compounds, similar to the endocannabinoids, which either increase or inhibit receptor activation to provide the desired therapeutic effect. Alternatively, the endogenous enzymes that degrade endocannabinoids or cannabinoid-like lipids can also be targeted in order to manipulate the levels of endocannabinoids. Proper identification of the septic stage is crucial to determine the adequate therapeutic response that will be most beneficial. Due to the biphasic nature of sepsis immunopathology, immune suppression through endocannabinoid modulation can help mitigate the hyper-immune response during the early septic state, while immune activation may be beneficial in later stages.” http://www.signavitae.com/2013/05/targeting-the-endocannabinoid-system-to-treat-sepsis/ http://www.signavitae.com/2013/05/targeting-the-endocannabinoid-system-to-treat-sepsis/]]>
Treatment with cannabidiol reverses oxidative stress parameters, cognitive impairment and mortality in rats submitted to sepsis by cecal ligation and puncture.
“Oxidative stress plays an important role in the development of cognitive impairment in sepsis. Here we assess the effects of acute and extended administration of cannabidiol (CBD) on oxidative stress parameters in peripheral organs and in the brain, cognitive impairment, and mortality in rats submitted to sepsis by cecal ligation and perforation (CLP). Our data provide the first experimental demonstration that CBD reduces the consequences of sepsis induced by CLP in rats, by decreasing oxidative stress in peripheral organs and in the brain, improving impaired cognitive function, and decreasing mortality.” https://www.ncbi.nlm.nih.gov/pubmed/20561509 http://www.sciencedirect.com/science/article/pii/S0006899310013582?via%3Dihub
“Antioxidant treatment reverses mitochondrial dysfunction in a sepsis animal model.” https://www.ncbi.nlm.nih.gov/pubmed/18417427
]]>Cannabis use among patients at a comprehensive cancer center in a state with legalized medicinal and recreational use.
“Cannabis is purported to alleviate symptoms related to cancer treatment, although the patterns of use among cancer patients are not well known. This study was designed to determine the prevalence and methods of use among cancer patients, the perceived benefits, and the sources of information in a state with legalized cannabis.
METHODS:
A cross-sectional, anonymous survey of adult cancer patients was performed at a National Cancer Institute-designated cancer center in Washington State. Random urine samples for tetrahydrocannabinol provided survey validation.RESULTS:
Nine hundred twenty-six of 2737 eligible patients (34%) completed the survey, and the median age was 58 years (interquartile range [IQR], 46-66 years). Most had a strong interest in learning about cannabis during treatment (6 on a 1-10 scale; IQR, 3-10) and wanted information from cancer providers (677 of 911 [74%]). Previous use was common (607 of 926 [66%]); 24% (222 of 926) used cannabis in the last year, and 21% (192 of 926) used cannabis in the last month. Random urine samples found similar percentages of users who reported weekly use (27 of 193 [14%] vs 164 of 926 [18%]). Active users inhaled (153 of 220 [70%]) or consumed edibles (154 of 220 [70%]); 89 (40%) used both modalities. Cannabis was used primarily for physical (165 of 219 [75%]) and neuropsychiatric symptoms (139 of 219 [63%]). Legalization significantly increased the likelihood of use in more than half of the respondents.CONCLUSIONS:
This study of cancer patients in a state with legalized cannabis found high rates of active use across broad subgroups, and legalization was reported to be important in patients’ decision to use. Cancer patients desire but are not receiving information about cannabis use during their treatment from oncology providers.” https://www.ncbi.nlm.nih.gov/pubmed/28944449 http://onlinelibrary.wiley.com/doi/10.1002/cncr.30879/abstract;jsessionid=793E288AAC342234D14BA7C96AEEDB74.f02t04?systemMessage=Wiley+Online+Library+will+be+unavailable+on+Saturday+7th+Oct+from+03.00+EDT+%2F+08%3A00+BST+%2F+12%3A30+IST+%2F+15.00+SGT+to+08.00+EDT+%2F+13.00+BST+%2F+17%3A30+IST+%2F+20.00+SGT+and+Sunday+8th+Oct+from+03.00+EDT+%2F+08%3A00+BST+%2F+12%3A30+IST+%2F+15.00+SGT+to+06.00+EDT+%2F+11.00+BST+%2F+15%3A30+IST+%2F+18.00+SGT+for+essential+maintenance.+Apologies+for+the+inconvenience+caused+.“Study finds up to one-quarter of cancer patients use marijuana” https://medicalxpress.com/news/2017-09-one-quarter-cancer-patients-marijuana.html
“Up to one-quarter of cancer patients use marijuana” https://www.sciencedaily.com/releases/2017/09/170925095431.htm
“Cancer Patients Want to Use Marijuana, and with Good Reason” https://www.inverse.com/article/36751-cancer-patients-want-to-use-marijuana-study-fred-hutchinson-cancer-research-center
“The use of Cannabis for medicinal purposes dates back to ancient times. Cannabis has been shown to kill cancer cells in the laboratory.” http://www.cancer.gov/about-cancer/treatment/cam/patient/cannabis-pdq#section/all “Marijuana has been used in herbal remedies for centuries. More recently, scientists reported that THC and other cannabinoids such as CBD slow growth and/or cause death in certain types of cancer cells.” http://www.cancer.org/treatment/treatmentsandsideeffects/physicalsideeffects/chemotherapyeffects/marijuana-and-cancer http://www.thctotalhealthcare.com/category/cancer/]]>Preferences for Medical Marijuana over Prescription Medications Among Persons Living with Chronic Conditions: Alternative, Complementary, and Tapering Uses.
“Despite expanded legalization and utilization of medical cannabis (MC) internationally, there is a lack of patient-centered data on how MC is used by persons living with chronic conditions in tandem with or instead of prescription medications. This study describes approaches to use of MC vis-à-vis prescription medications in the treatment of selected chronic conditions.