Combined cannabinoid therapy via an oromucosal spray.

“Extensive basic science research has identified the potential therapeutic benefits of active compounds extracted from the Cannabis sativa L. plant (the cannabinoids). It is recognized that a significant proportion of patients suffering with the debilitating symptoms of pain and spasticity in multiple sclerosis or other conditions smoke cannabis despite the legal implications and stigma associated with this controlled substance. GW Pharmaceuticals have developed Sativex (GW- 1000-02), a combined cannabinoid medicine that delivers and maintains therapeutic levels of two principal cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), via an oromucosal pump spray, that aims to minimize psychotropic side effects.”  https://www.ncbi.nlm.nih.gov/pubmed/16969427 “Sativex has proved to be well tolerated and successfully self-administered and self-titrated in both healthy volunteers and patient cohorts. Clinical assessment of this combined cannabinoid medicine has demonstrated efficacy in patients with intractable pain (chronic neuropathic pain, pain due to brachial plexus nerve injury, allodynic peripheral neuropathic pain and advanced cancer pain), rheumatoid arthritis and multiple sclerosis (bladder problems, spasticity and central pain), with no significant intoxication-like symptoms, tolerance or withdrawal syndrome.”  https://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summaryn_pr?p_JournalId=4&p_RefId=1021517 “Sativex(®) (nabiximols, USAN name) oromucosal spray contains the two main active constituents of Cannabis sativa, tetrahydrocannabinol and cannabidiol in a 1:1 molecular ratio, and acts as an endocannabinoid system modulator.”  https://www.ncbi.nlm.nih.gov/pubmed/21449855

“Abuse potential and psychoactive effects of δ-9-tetrahydrocannabinol and cannabidiol oromucosal spray (Sativex), a new cannabinoid medicine. Evidence to date suggests that abuse or dependence on Sativex is likely to occur in only a very small proportion of recipients.” https://www.ncbi.nlm.nih.gov/pubmed/21542664

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The Role of Cannabinoids in the Treatment of Cancer in Pediatric Patients.

“Cannabis has been used in folk medicine to alleviate pain, depression, amenorrhea, inflammation and numerous other medical conditions. In cancer patients specifically, cannabinoids are well known to exert palliative effects; their best-established use is the inhibition of chemotherapy-induced nausea and vomiting, but they are applied also to alleviate pain, stimulate appetite, and attenuate wasting. More recently, cannabinoids have gained special attention for their role in cancer cell proliferation and death. Anti-cancer efficacy of cannabinoids: The ability of cannabinoids to reduce tumor growth was reported for the first time by Munson et al. in 1975. They showed by in vitro and in vivo experiments that several phytocannabinoids, including THC, decreased Lewis lung adenocarcinoma proliferation in a dose-dependent manner. Nevertheless, it was not until the 2000s that the interest in these compounds as anti-cancer agents was renewed, predominantly due to the work of Guzman in gliomas, and the demonstration of cannabinoids’ anti-cancer effects on various types of tumors. The anti-tumorigenic effect of the endo- and phytocannabinoids was demonstrated in several in vitro and in vivo models of a wide variety of adult tumors including glioma, prostate, breast, leukemia, lymphoma, pancreas, melanoma, thyroid, colorectal and hepatocellular carcinoma tumors. Given our positive results, we suggest that non-THC cannabinoids such as CBD might provide a basis for the development of novel therapeutic strategies without the typical psychotropic effects of THC that limit its use in pediatric patients. Overall, the cannabinoids, and specifically the non-psychoactive CBD, may show future promise in the treatment of cancer” https://www.ima.org.il/FilesUpload/IMAJ/0/228/114216.pdf https://www.ima.org.il/imaj/ViewArticle.aspx?aId=4044 https://www.ncbi.nlm.nih.gov/pubmed/28457057]]>

Anti-inflammatory effects of the cannabidiol derivative dimethylheptyl-cannabidiol – studies in BV-2 microglia and encephalitogenic T cells

“Preparations derived from Cannabis sativa (marijuana and hashish) have become widespread since ancient times, both as therapeutic agents and in recreational smoking. Among the more than 60 phytocannabinoids identified in Cannabis extracts, the two most abundant are Δ9-tetrahydrocannabinol (THC), the major psychotropic constituent, and cannabidiol (CBD), the major non-psychoactive component. Cannabinoids were shown to exert a wide range of therapeutic effects, and many of the cannabinoids, especially CBD, were shown to possess potent anti-inflammatory and immunomodulatory activities. In addition, it was shown that several cannabinoids have pro-apoptotic, neuroprotective, and antitumor properties Dimethylheptyl-cannabidiol (DMH-CBD), a non-psychoactive, synthetic derivative of the phytocannabinoid cannabidiol (CBD), has been reported to be anti-inflammatory in RAW macrophages. Here, we evaluated the effects of DMH-CBD at the transcriptional level in BV-2 microglial cells as well as on the proliferation of encephalitogenic T cells. The results show that DMH-CBD has similar anti-inflammatory properties to those of CBD. DMH-CBD downregulates the expression of inflammatory cytokines and protects the microglial cells by inducing an adaptive cellular response against inflammatory stimuli and oxidative injury. In addition, DMH-CBD decreases the proliferation of pathogenic activated TMOG cells. Several CBD derivatives were also shown to have anti-inflammatory and anti-proliferative properties. The results show that DMH-CBD induces similar anti-inflammatory, anti-proliferative, and stress response effects to those previously observed for CBD.” https://www.degruyter.com/view/j/jbcpp.2016.27.issue-3/jbcpp-2015-0071/jbcpp-2015-0071.xml]]>

Cannabinoids as Modulators of Cell Death: Clinical Applications and Future Directions.

 Image result for Rev Physiol Biochem Pharmacol. “Endocannabinoids are bioactive lipids that modulate various physiological processes through G-protein-coupled receptors (CB1 and CB2) and other putative targets. By sharing the activation of the same receptors, some phytocannabinoids and a multitude of synthetic cannabinoids mimic the effects of endocannabinoids. In recent years, a growing interest has been dedicated to the study of cannabinoids properties for their analgesic, antioxidant, anti-inflammatory and neuroprotective effects. In addition to these well-recognized effects, various studies suggest that cannabinoids may affect cell survival, cell proliferation or cell death. These observations indicate that cannabinoids may play an important role in the regulation of cellular homeostasis and, thus, may contribute to tissue remodelling and cancer treatment. For a long time, the study of cannabinoid receptor signalling has been focused on the classical adenylyl cyclase/cyclic AMP/protein kinase A (PKA) pathway. However, this pathway does not totally explain the wide array of biological responses to cannabinoids. In addition, the diversity of receptors and signalling pathways that endocannabinoids modulate offers an interesting opportunity for the development of specific molecules to disturb selectively the endogenous system. Moreover, emerging evidences suggest that cannabinoids ability to limit cell proliferation and to induce tumour-selective cell death may offer a novel strategy in cancer treatment. This review describes the main properties of cannabinoids in cell death and attempts to clarify the different pathways triggered by these compounds that may help to understand the complexity of respective molecular mechanisms and explore the potential clinical benefit of cannabinoids use in cancer therapies.” https://www.ncbi.nlm.nih.gov/pubmed/28425013
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