“Cannabidiol (CBD) is a major nonpsychoactive cannabinoid of marijuana. Based on reports indicating possible efficacy of CBD in dystonic movements, we tried CBD in three patients with Huntington’s disease (HD). The patients;, aged 30 to 56, had HD of 7 to 12 years’ duration. Their condition has been slowly progressive and unresponsive to prior therapy with neuroleptics. Orally administered CBD was initiated at 300 mg/d and increased 1 week later to 600 mg/d for the next 3 weeks. Mild improvement ( 5 to 15%) in the choreic movements was documented using the tongueprotrusion test and a chorea severity evaluation scale after the first week. Further improvement (20 to 40%) was noticed after the second week of CBD, and this remained stable for the following 2 weeks. Except for transient, mild hypotension, no side effects were recorded, and laboratory tests were normal. Withdrawal of CBD after 48 hours resulted in return of choreic movements to the pre-CBD state.” http://www.druglibrary.org/schaffer/hemp/medical/hunting1.htm]]>
It’s Colorectal Cancer Awareness Month. Please Be Aware:
“Loss of cannabinoid receptor 1 accelerates intestinal tumor growth” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2561258/
“Turned-off Cannabinoid Receptor Turns On Colorectal Tumor Growth” https://www.sciencedaily.com/releases/2008/08/080801074056.htm
“Turning CB1 back on and then treating with a cannabinoid agonist could provide a new approach to colorectal cancer treatment or prevention. Cannabinoids are a group of ligands that serve a variety of cell-signaling roles. Some are produced by the body internally (endocannabinoids). External cannabinoids include manmade versions and those present in plants, most famously the active ingredient in marijuana (THC).” http://www.news-medical.net/news/2008/08/03/40485.aspx
“Cannabinoid Receptor Activation Induces Apoptosis through Tumor Necrosis Factor α–Mediated Ceramide De novo Synthesis in Colon Cancer Cells. The present study shows that either CB1 or CB2 receptor activation induces apoptosis through ceramide de novo synthesis in colon cancer cells. ” http://clincancerres.aacrjournals.org/content/14/23/7691.long
“The cannabinoid delta(9)-tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival signalling and induces BAD-mediated apoptosis in colorectal cancer cells. Here, we report that CB1 and CB2 cannabinoid receptors are expressed in human colorectal adenoma and carcinoma cells, and show for the first time that THC induces apoptosis in colorectal cancer cells. The use of THC, or selective targeting of the CB1 receptor, may represent a novel strategy for colorectal cancer therapy.” http://www.ncbi.nlm.nih.gov/pubmed/17583570
“Programmed Cell Death (Apoptosis)” http://www.ncbi.nlm.nih.gov/books/NBK26873/
“Cannabis-Linked Cell Receptor Might Help Prevent Colon Cancer” http://www.medicinenet.com/script/main/art.asp?articlekey=91511
“Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer. Cannabidiol, a safe and non-psychotropic ingredient of Cannabis sativa, exerts pharmacological actions (antioxidant and intestinal antinflammatory) and mechanisms (inhibition of endocannabinoid enzymatic degradation) potentially beneficial for colon carcinogenesis. It is concluded that cannabidiol exerts chemopreventive effect in vivo and reduces cell proliferation through multiple mechanisms.” https://www.ncbi.nlm.nih.gov/pubmed/22231745
“CBD-Rich Marijuana Fights Colon Cancer, New Study Finds” http://blog.sfgate.com/smellthetruth/2014/01/06/cbd-rich-marijuana-fights-colon-cancer-new-study-finds/
“Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol. Cannabis-based medicines are useful adjunctive treatments in cancer patients.” http://www.ncbi.nlm.nih.gov/pubmed/24373545
“Cannabigerol (CBG) is a safe non-psychotropic Cannabis-derived cannabinoid. CBG hampers colon cancer progression in vivo and selectively inhibits the growth of colorectal cancer cells. CBG should be considered translationally in colorectal cancer prevention and cure.” http://www.ncbi.nlm.nih.gov/pubmed/25269802
“According to researchers at the University of Texas in Houston chemicals in marijuana could be a potential cure in the treatment of colon cancer.” http://www.digitaljournal.com/article/258161
“Cannabis compound clue to colon cancer” https://www.newscientist.com/article/mg19926685.000-cannabis-compound-clue-to-colon-cancer/
“Marijuana takes on colon cancer” https://www.newscientist.com/article/dn14451-marijuana-takes-on-colon-cancer/
“Cannabinoids appear to kill tumor cells but do not affect their nontransformed counterparts and may even protect them from cell death. Tumor specimens revealed that THC had antiangiogenic and antiproliferative effects. CBD has also been demonstrated to exert a chemopreventive effect in a mouse model of colon cancer. In in vitro experiments involving colorectal cancer cell lines, the investigators found that CBD protected DNA from oxidative damage, increased endocannabinoid levels, and reduced cell proliferation. In addition, both plant-derived and endogenous cannabinoids have been studied for anti-inflammatory effects. A mouse study demonstrated that endogenous cannabinoid system signaling is likely to provide intrinsic protection against colonic inflammation. As a result, a hypothesis that phytocannabinoids and endocannabinoids may be useful in the risk reduction and treatment of colorectal cancer has been developed.” http://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq#section/_7
Co-localization of the cannabinoid type 1 receptor with corticotropin-releasing factor-containing afferents in the noradrenergic nucleus locus coeruleus: implications for the cognitive limb of the stress response.
“The noradrenergic system has been shown to play a key role in the regulation of stress responses, arousal, mood, and emotional states. Corticotropin-releasing factor (CRF) is a primary mediator of stress-induced activation of noradrenergic neurons in the nucleus locus coeruleus (LC).
The endocannabinoid (eCB) system also plays a key role in modulating stress responses, acting as an “anti-stress” neuro-mediator.
In the present study, we investigated the cellular sites for interactions between the cannabinoid receptor type 1 (CB1r) and CRF in the LC.
Taken together, these results indicate that the eCB system is poised to directly modulate stress-integrative heterogeneous CRF afferents in the LC, some of which arise from limbic sources.”
The current status of artisanal cannabis for the treatment of epilepsy in the United States.
“The widespread patient use of artisanal cannabis preparations has preceded quality validation of cannabis use for epilepsy. Neurologists and cannabinoid specialists are increasingly in a position to monitor and guide the use of herbal cannabis in epilepsy patients. We report the retrospective data on efficacy and adverse effects of artisanal cannabis in Patients with medically refractory epilepsy with mixed etiologies in Washington State, California, and Maine. Clinical considerations, including potential risks and benefits, challenges related to artisanal preparations, and cannabinoid dosing, are discussed.
RESULTS:
Of 272 combined patients from Washington State and California, 37 (14%) found cannabis ineffective at reducing seizures, 29 (15%) experienced a 1-25% reduction in seizures, 60 (18%) experienced a 26-50% reduction in seizures, 45 (17%) experienced a 51-75% reduction in seizures, 75 (28%) experienced a 76-99% reduction in seizures, and 26 (10%) experienced a complete clinical response. Overall, adverse effects were mild and infrequent, and beneficial side effects such as increased alertness were reported. The majority of patients used cannabidiol (CBD)-enriched artisanal formulas, some with the addition of delta-9-tetrahydrocannabinol (THC) and tetrahydrocannabinolic acid (THCA). Four case reports are included that illustrate clinical responses at doses <0.1mg/kg/day, biphasic dose-response effects, the use of THCA for seizure prevention, the use of THC for seizure rescue, and the synergy of cannabinoids and terpenoids in artisanal preparations. This article is part of a Special Issue entitled “Cannabinoids and Epilepsy”.” https://www.ncbi.nlm.nih.gov/pubmed/28254350]]>The role of exercise training and the endocannabinoid system in atherosclerotic plaque burden and composition in Apo-E-deficient mice.
“We investigated the effect of combining exercise training and treatment with an endocannabinoid receptor 1 inhibitor (Rimonabant) on atherosclerosis burden and composition. Both exercise and rimonabant treatments induced plaque regression and promoted plaque stability. The combined treatment failed to show additive or synergistic benefits relative to either intervention alone.” https://www.ncbi.nlm.nih.gov/pubmed/28254386]]>
CB1 receptor-mediated respiratory depression by endocannabinoids.
“Endocannabinoids (ECs) are bioactive lipid mediators acting on two distinct cannabinoid receptors (CB1 and CB2), which are ubiquitously expressed in many tissues including the respiratory system. Despite numerous experimental data showing that cannabinomimetics influence respiration, the role of endogenously produced ECs in respiratory control has not been verified yet. Pulse oximetry was used in the present study to directly measure changes in respiratory parameters during elevation of EC levels. The cannabinoid reuptake inhibitor AM-404 (10mgkg-1, i.v.), but not its vehicle, induced a transient reduction of respiratory rate with a concomitant depression of arterial oxygen saturation and increase in breath distension in wild-type mice. In contrast, CB1 knock-out mice showed no alteration in any of these parameters upon administration of AM-404. Our results imply that the EC system has an important role in the physiological control of respiration by modulating the respiratory rate and consequently influencing arterial oxygen saturation. Furthermore, this mechanism is entirely dependent on CB1 receptors.” https://www.ncbi.nlm.nih.gov/pubmed/28254562]]>
CB2 cannabinoid receptors modulate HIF-1α and TIM-3 expression in a hypoxia-ischemia mouse model.
“The role of CB2 cannabinoid receptors (CB2R) in global brain lesions induced by hypoxia-ischemia (HI) insult is still unresolved. The aim of this study was to evaluate the involvement of CB2R in the behavioural and biochemical underpinnings related to brain damage induced by HI in adult mice, and the mechanisms involved. Our results indicate that CB2R may have a crucial neuroprotective role following HI insult through the modulation of the inflammatory-related HIF-1α/TIM-3 signalling pathway in microglia.” https://www.ncbi.nlm.nih.gov/pubmed/28253997]]>
Potential of Cannabidiol for the Treatment of Viral Hepatitis.
“Viral hepatitis B (HBV) and hepatitis C (HCV) pose a major health problem globally and if untreated, both viruses lead to severe liver damage resulting in liver cirrhosis and cancer. While HBV has a vaccine, HCV has none at the moment. The risk of drug resistance, combined with the high cost of current therapies, makes it a necessity for cost-effective therapeutics to be discovered and developed. The recent surge in interest in Medical Cannabis has led to interest in evaluating and validating the therapeutic potentials of Cannabis and its metabolites against various diseases including viruses. Preliminary screening of cannabidiol (CBD) revealed that CBD is active against HCV but not against HBV in vitro. CBD inhibited HCV replication by 86.4% at a single concentration of 10 μM with EC50 of 3.163 μM in a dose-response assay. These findings suggest that CBD could be further developed and used therapeutically against HCV. Cannabidiol exhibited in vitro activity against viral hepatitis C.” https://www.ncbi.nlm.nih.gov/pubmed/28250664 “Cannabidiol (CBD) is a nonpsychoactive cannabinoid found in the Cannabis plants and is credited for several pharmacological properties. It is also known to have beneficial effects against inflammation/pain, neurological conditions, cancer, and other ailments. In general, with regard to antiviral activity, medical Cannabis was reported to be used as an accompanying remedy by HIV/AIDS patients to alleviate neuropathic pain, wasting, nausea, and vomiting. Given the increasing use and application of medical Cannabis along with its nonpsychoactive metabolite (CBD), and in line with our continuous effort to evaluate and validate the potential therapeutic properties of CBD, the major aim of this study was as such to evaluate the anti-HBV and anti-HCV activities of CBD in vitro. We report here for the first time in vitro studies to demonstrate the antiviral activity of CBD against HCV. CBD was shown to have activity against HCV in vitro but not against HBV. A review of the literature seems to suggest that CBD may also have activity in vivo based on its interaction with the CB2 receptor and as such using a host mechanism to indirectly slow the pathogenic process of the HBV virus. Based on these findings, CBD as such has potential to be further developed as a treatment for viral hepatitis, especially as a combination therapy with the currently existing therapies.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5330095/]]>
The Direct Actions of Cannabidiol and 2-Arachidonoyl Glycerol at GABAA Receptors.
“Cannabidiol (CBD) is a major non-intoxicating component of cannabis and possesses anti-epileptic, anxiolytic and anti-hyperalgesic properties. Despite evidence that some endogenous and synthetic cannabinoids interact with GABAA receptors, no-one has yet investigated the effects of CBD. Here we used two-electrode voltage clamp electrophysiology to compare the actions of CBD with those of the major central endocannabinoid, 2-arachidonoyl glycerol (2-AG) on human recombinant GABAA receptors (synaptic α1-6βg2 and extrasynaptic α4β2δ) expressed on Xenopus oocytes. Taken together these results reveal a mode of action of CBD on specifically configured GABAA receptors that may be relevant to the anticonvulsant and anxiolytic effects of the compound.” https://www.ncbi.nlm.nih.gov/pubmed/28249817]]>
Flexible Bionanocomposites from Epoxidised Hemp Seed Oil Thermosetting Resin Reinforced with Halloysite Nanotubes.
“Hempseed (Cannabis sativa L.) oil comprises a variety of beneficial unsaturated triglycerides with well-documented nutritional and health benefits.
However, it can become rancid over a relatively short time period leading to increased industrial costs and waste of a valuable product. The development of sustainable polymers is presented as a strategy where both the presence of unsaturation and perox-ide content could be affectively utilised to alleviate both this waste and financial burden.
After reaction with peroxyacetic acid, incorporation of halloysite nanotubes (HNTs) and sub-sequent thermal curing, without the need for organic sol-vents or interfacial modifiers, flexible transparent materials with a low glass transition temperature were developed. The improvement in thermal stability and both the static and dynamic mechanical properties of the bionanocomposites were significantly enhanced with the well-dispersed HNT filler. At an optimum concentration of 0.5 wt.% HNTs, a simultaneous increase in stiffness, strength, ductility and toughness was observed in comparison to the unfilled cured resin.
These sustainable food-waste derived bionanocompo-sites may provide an interesting alternative to petroleum-based materials, particularly for low-load bearing applica-tions, such as packaging.”
https://www.ncbi.nlm.nih.gov/pubmed/28240903