Tuesday, May 29, 2018

Cannabis and Diabetes


Cannabis and Diabetes


“The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014”

Diabetes is a group of metabolic conditions in which the body does not produce enough insulin or has become resistant to its effects. Insulin is a hormone required to convert sugar, starches, and other foods into energy. 



The two most common forms of diabetes are type 1 and type2. Type 1 Diabetes, where the pancreas does not produce insulin, is typically diagnosed in children and young adults. Type 2 Diabetes is much more common, normally affecting adults and is associated with obesity. In Type 2 Diabetes, the body becomes resistant to the effects of insulin, which enables glucose to accumulate to dangerous levels within the body. 
High glucose levels damage vascular and other tissues, resulting in heart disease, stroke, blindness, and kidney and nerve damage. 
Diet and Exercise is a main treatment plan for anyone with preventable diabetes. There are many other treatment plans that a trusted medical professional may recommend to you. Its important to find someone who is educated and knowledgeable about CBD and THC and how cannabis can help your diabetes conditions through the endocannabinoid system..
Cannabis is an amazing treatment to help patients suffering from diabetes. But before you start taking action with a cannabis only treatment, it is best to understand how the food we continue to eat will affect our health. Some diabetes can be controlled through a healthy lifestyle and diet.



“A diabetes diet simply means eating the healthiest foods in moderate amounts and sticking to regular mealtimes. A diabetes diet is a healthy-eating plan that's naturally rich in nutrients and low in fat and calories. Key elements are fruits, vegetables and whole grains. In fact, a diabetes diet is the best eating plan for most everyone.”
www.mayoclinic.org


How Cannabis Affects Diabetes 


The Endocannabinoid System plays a role in the development of diabetes and its complications. Diabetic complications that are linked to diabetes include: blindness, atherosclerosis, kidney failure, heart disease and neuropathic pain. Cannabis plant cannabinoids such as CBD, CBDV, and THCV (with little to no psychoactivity) may help maintain pancreatic function and insulin resistance. Research shows that CBD may prevent retinal damage by acting as an antioxidant and enhancing the retinas own defenses against inflammation. Studies are also showing THCV as a new therapeutic agent in glycemic control.
An early medical correlation study was conducted to examine the effects of Cannabis use on blood glucose level and insulin level. In the study, 579 subjects out of 4657 total participants were marijuana users. These 579 participants showed a lower tendency to have diabetes than non-marijuana users. What is even more intriguing is that the Cannabis users exhibit 16 % lower levels of fasting insulin and 17 % lower insulin resistance than subjects who do not use Cannabis. The marijuana users were also found to have lower waist circumference and higher levels of high-density lipoprotein cholesterol (commonly named as the “good cholesterol”). This discovery answers how exactly Cannabis can benefit type 2 diabetic and pre-diabetic individuals.



Recommended Cannabis Dosing


For those who regularly consume cannabis there should be no problem with dosing and medication that includes THC, seeing as how you are used to it’s effects. When trying any new forms of medication, it is best to Start Low and Go Slow! Start by consuming small amounts. Oil, Vape, Smoke, or Edibles are all ways to consume cannabis. You can take any amount of CBD you feel is necessary. However, caution must be taken when experimenting with THC. The suggested dose of cannabis for the treatment of diabetes will vary depending on the dominant cannabinoid (THC, CBD, THCV, CBDV, etc.) in each various form of medication.

Both oral (oil) and vaporized (flower or concentrate) use of high CBD, CBDV, and THCV cannabis varieties prove interest in controlling metabolic illnesses. New users to cannabis I would suggest a CBD oil and IT’S best to find one with high CBD, CBDV, and little THCV.



The Science That Proves How Cannabis Helps Diabetes


 The following articles are taken from our favorite CBD resource site: ProjectCBD.org more info at:


The endocannabinoid system and plant-derived cannabinoids in diabetes and diabetic complications.
Oxidative stress and inflammation play critical roles in the development of diabetes and its complications. Recent studies provided compelling evidence that the newly discovered lipid signaling system (ie, the endocannabinoid system) may significantly influence reactive oxygen species production, inflammation, and subsequent tissue injury, in addition to its well-known metabolic effects and functions. The modulation of the activity of this system holds tremendous therapeutic potential in a wide range of diseases, ranging from cancer, pain, neurodegenerative, and cardiovascular diseases to obesity and metabolic syndrome, diabetes, and diabetic complications. This review focuses on the role of the endocannabinoid system in primary diabetes and its effects on various diabetic complications, such as diabetic cardiovascular dysfunction, nephropathy, retinopathy, and neuropathy, particularly highlighting the mechanisms beyond the metabolic consequences of the activation of the endocannabinoid system. The therapeutic potential of targeting the endocannabinoid system and certain plant-derived cannabinoids, such as cannabidiol and Δ9-tetrahydrocannabivarin, which are devoid of psychotropic effects and possess potent anti-inflammatory and/or antioxidant properties, in diabetes and diabetic complications is also discussed.
(Horvath B 2012)

The Impact of Marijuana Use on Glucose, Insulin, and Insulin Resistance among US Adults  
There are limited data regarding the relationship between cannabinoids and metabolic processes. Epidemiologic studies have found lower prevalence rates of obesity and diabetes mellitus in marijuana users compared with people who have never used marijuana, suggesting a relationship between cannabinoids and peripheral metabolic processes. To date, no study has investigated the relationship between marijuana use and fasting insulin, glucose, and insulin resistance.
We included 4657 adult men and women from the National Health and Nutrition Examination Survey from 2005 to 2010. Marijuana use was assessed by self-report in a private room. Fasting insulin and glucose were measured via blood samples after a 9-hour fast, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated to evaluate insulin resistance. Associations were estimated using multiple linear regression, accounting for survey design and adjusting for potential confounders.
Of the participants in our study sample, 579 were current marijuana users and 1975 were past users. In multivariable adjusted models, current marijuana use was associated with 16% lower fasting insulin levels (95% confidence interval [CI], −26, −6) and 17% lower HOMA-IR (95% CI, −27, −6). We found significant associations between marijuana use and smaller waist circumferences. Among current users, we found no significant dose-response.
We found that marijuana use was associated with lower levels of fasting insulin and HOMA-IR, and smaller waist circumference.
(Elizabeth A. Penner 2013)

Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, and inflammatory and cell death signaling pathways in diabetic cardiomyopathy.
In this study, we have investigated the effects of cannabidiol (CBD) on myocardial dysfunction, inflammation, oxidative/nitrative stress, cell death, and interrelated signaling pathways, using a mouse model of type I diabetic cardiomyopathy and primary human cardiomyocytes exposed to high glucose.
Cannabidiol, the most abundant nonpsychoactive constituent of Cannabis sativa (marijuana) plant, exerts anti-inflammatory effects in various disease models and alleviates pain and spasticity associated with multiple sclerosis in humans.
Diabetic cardiomyopathy was characterized by declined diastolic and systolic myocardial performance associated with increased oxidative-nitrative stress, nuclear factor-κB and mitogen-activated protein kinase (c-Jun N-terminal kinase, p-38, p38α) activation, enhanced expression of adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1), tumor necrosis factor-α, markers of fibrosis (transforming growth factor-β, connective tissue growth factor, fibronectin, collagen-1, matrix metalloproteinase-2 and -9), enhanced cell death (caspase 3/7 and poly[adenosine diphosphate-ribose] polymerase activity, chromatin fragmentation, and terminal deoxynucleotidyl transferase dUTP nick end labeling), and diminished Akt phosphorylation. Remarkably, CBD attenuated myocardial dysfunction, cardiac fibrosis, oxidative/nitrative stress, inflammation, cell death, and interrelated signaling pathways. Furthermore, CBD also attenuated the high glucose-induced increased reactive oxygen species generation, nuclear factor-κB activation, and cell death in primary human cardiomyocytes.
Collectively, these results coupled with the excellent safety and tolerability profile of CBD in humans, strongly suggest that it may have great therapeutic potential in the treatment of diabetic complications, and perhaps other cardiovascular disorders, by attenuating oxidative/nitrative stress, inflammation, cell death and fibrosis.

Cannabidiol lowers incidence of diabetes in non-obese diabetic mice.
Cannabinoids are components of the Cannabis sativa (marijuana) plant that have been shown capable of suppressing inflammation and various aspects of cell-mediated immunity. Cannabidiol (CBD), a non-psychoactive cannabinoid has been previously shown by us to suppress cell-mediated autoimmune joint destruction in an animal model of rheumatoid arthritis. We now report that CBD treatment significantly reduces the incidence of diabetes in NOD mice from an incidence of 86% in non-treated control mice to an incidence of 30% in CBD-treated mice. CBD treatment also resulted in the significant reduction of plasma levels of the pro-inflammatory cytokines, IFN-gamma and TNF-alpha. Th1-associated cytokine production of in vitro activated T-cells and peritoneal macrophages was also significantly reduced in CBD-treated mice, whereas production of the Th2-associated cytokines, IL-4 and IL-10, was increased when compared to untreated control mice. Histological examination of the pancreatic islets of CBD-treated mice revealed significantly reduced insulitis. Our results indicate that CBD can inhibit and delay destructive insulitis and inflammatory Th1-associated cytokine production in NOD mice resulting in a decreased incidence of diabetes possibly through an immunomodulatory mechanism shifting the immune response from Th1 to Th2 dominance.
(Weiss L. 2006)

Neuroprotective and blood-retinal barrier-preserving effects of cannabidiol in experimental diabetes.
Diabetic retinopathy is characterized by blood-retinal barrier (BRB) breakdown and neurotoxicity. These pathologies have been associated with oxidative stress and proinflammatory cytokines, which may operate by activating their downstream target p38 MAP kinase. In the present study, the protective effects of a nonpsychotropic cannabinoid, cannabidiol (CBD), were examined in streptozotocin-induced diabetic rats after 1, 2, or 4 weeks. Retinal cell death was determined by terminal dUTP nick-end labeling assay; BRB function by quantifying extravasation of bovine serum albumin-fluorescein; and oxidative stress by assays for lipid peroxidation, dichlorofluorescein fluorescence, and tyrosine nitration. Experimental diabetes induced significant increases in oxidative stress, retinal neuronal cell death, and vascular permeability. These effects were associated with increased levels of tumor necrosis factor-alpha, vascular endothelial growth factor, and intercellular adhesion molecule-1 and activation of p38 MAP kinase, as assessed by enzyme-linked immunosorbent assay, immunohistochemistry, and/or Western blot. CBD treatment significantly reduced oxidative stress; decreased the levels of tumor necrosis factor-alpha, vascular endothelial growth factor, and intercellular adhesion molecule-1; and prevented retinal cell death and vascular hyperpermeability in the diabetic retina. Consistent with these effects, CBD treatment also significantly inhibited p38 MAP kinase in the diabetic retina. These results demonstrate that CBD treatment reduces neurotoxicity, inflammation, and BRB breakdown in diabetic animals through activities that may involve inhibition of p38 MAP kinase.
(El-Remessy AB 2006)

Cannabidiol arrests onset of autoimmune diabetes in NOD mice.
We have previously reported that cannabidiol (CBD) lowers the incidence of diabetes in young non-obese diabetes-prone (NOD) female mice. In the present study we show that administration of CBD to 11-14 week old female NOD mice, which are either in a latent diabetes stage or with initial symptoms of diabetes, ameliorates the manifestations of the disease. Diabetes was diagnosed in only 32% of the mice in the CBD-treated group, compared to 86% and 100% in the emulsifier-treated and untreated groups, respectively. In addition, the level of the proinflammatory cytokine IL-12 produced by splenocytes was significantly reduced, whereas the level of the anti-inflammatory IL-10 was significantly elevated following CBD-treatment. Histological examination of the pancreata of CBD-treated mice revealed more intact islets than in the controls. Our data strengthen our previous assumption that CBD, known to be safe in man, can possibly be used as a therapeutic agent for treatment of type 1 diabetes.
(Weiss L. 2008)


Diabetic retinopathy: Role of inflammation and potential therapies for anti-inflammation.
Diabetic retinopathy is a leading cause of blindness among working-age adults. Despite many years of research, treatment options for diabetic retinopathy remain limited and with adverse effects. Discovery of new molecular entities with adequate clinical activity for diabetic retinopathy remains one of the key research priorities in ophthalmology. This review is focused on the therapeutic effects of cannabidiol (CBD), a non-psychoactive native cannabinoid, as an emerging and novel therapeutic modality in ophthalmology based on systematic studies in animal models of inflammatory retinal diseases including diabetic retinopathy - a retinal disease associated with vascular-neuroinflammation. Special emphasis is placed on novel mechanisms which may shed light on the pharmacological activity associated with CBD preclinically. These include a self-defense system against inflammation and neurodegeneration mediated by inhibition of equilibrative nucleoside transporter and activation of adenosine receptor by treatment with CBD.
Cannabinoids alter endothelial function in the Zucker rat model of type 2 diabetes.
Circulating levels of anandamide are increased in diabetes, and cannabidiol ameliorates a number of pathologies associated with diabetes. The aim of the present study was to examine how exposure to anandamide or cannabidiol might affect endothelial dysfunction associated with Zucker Diabetic Fatty rats. Age-matched Zucker Diabetic Fatty and Zucker lean rats were killed by cervical dislocation and their arteries mounted on a myograph at 37 °C. Arteries were incubated for 2h with anandamide, cannabidiol or vehicle, contracted, and cumulative concentration-response curves to acetylcholine were constructed. Anandamide (10 µM, 2h) significantly improved the vasorelaxant responses to acetylcholine in aortae and femoral arteries from Zucker Diabetic Fatty rats but not Zucker lean rats. By contrast, anandamide (1 µM, 2h) significantly blunted acetylcholine-induced vasorelaxation in third-order mesenteric arteries (G3) from Zucker Diabetic Fatty rats. Cannabidiol incubation (10 µM, 2h) improved acetylcholine responses in the arteries of Zucker Diabetic Fatty rats (aorta and femoral) and Zucker lean (aorta, femoral and G3 mesenteric), and this effect was greater in the Zucker Diabetic Fatty rat. These studies suggest that increased circulating endocannabinoids may alter vascular function both positively and negatively in type 2 diabetes, and that part of the beneficial effect of cannabidiol in diabetes may be due to improved endothelium-dependent vasorelaxation.


The endocannabinoid system in obesity and type 2 diabetes.
Endocannabinoids (ECs) are defined as endogenous agonists of cannabinoid receptors type 1 and 2 (CB1 and CB2). ECs, EC anabolic and catabolic enzymes and cannabinoid receptors constitute the EC signalling system. This system participates in the control of lipid and glucose metabolism at several levels, with the possible endpoint of the accumulation of energy as fat. Following unbalanced energy intake, however, the EC system becomes dysregulated, and in most cases overactive, in several organs participating in energy homeostasis, particularly, in intra-abdominal adipose tissue. This dysregulation might contribute to excessive visceral fat accumulation and reduced adiponectin release from this tissue, and to the onset of several cardiometabolic risk factors that are associated with obesity and type 2 diabetes. This phenomenon might form the basis of the mechanism of action of CB1 antagonists/inverse agonists, recently developed by several pharmaceutical companies as adjuvants to lifestyle modification for weight reduction, glycaemic control and dyslipidaemia in obese and type 2 diabetes patients. It also helps to explain why some of the beneficial actions of these new therapeutics appear to be partly independent from weight loss.
Cannabinoids and endocannabinoids in metabolic disorders with focus on diabetes.
The cannabinoid receptors for Δ(9)-THC, and particularly, the CB(1) receptor, as well as its endogenous ligands, the endocannabinoids anandamide and 2-arachidonoylglycerol, are deeply involved in all aspects of the control of energy balance in mammals. While initially it was believed that this endocannabinoid signaling system would only facilitate energy intake, we now know that perhaps even more important functions of endocannabinoids and CB(1) receptors in this context are to enhance energy storage into the adipose tissue and reduce energy expenditure by influencing both lipid and glucose metabolism. Although normally well controlled by hormones and neuropeptides, both central and peripheral aspects of endocannabinoid regulation of energy balance can become dysregulated and contribute to obesity, dyslipidemia, and type 2 diabetes, thus raising the possibility that CB(1) antagonists might be used for the treatment of these metabolic disorders. On the other hand, evidence is emerging that some nonpsychotropic plant cannabinoids, such as cannabidiol, can be employed to retard β-cell damage in type 1 diabetes. These novel aspects of endocannabinoid research are reviewed in this chapter, with emphasis on the biological effects of plant cannabinoids and endocannabinoid receptor antagonists in diabetes.



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