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Diabetes Mellitus - Medical Marijuana Research Papers Worldwide - 2000- 2017

DIABETES MELLITUS - 15 MARIJUANA RESEARCH PAPERS

Diabetes Mellitus - Medical Marijuana Research Papers Worldwide - 2000- 2017

 

The results of clinical trials and research on medical marijuana is incredible, CBD found in Cannabis lowers blood sugar, marijuana users have a lower body-mass index, improved oxygen uptake.  

 

The challenge is to find the right strains with THC:CBD and other ingredients in the right amount, that works best for the individual.  Other lesser known cannabinoids like THCV hold particular promise in treating the core issues (insulin issues) in chronic cases of obesity and diabetes.

 

 

RESEARCH HIGHLIGHTS - MARIJUANA AND DIABETES

 

  • Remarkably, Cannabidiol - CBD attenuated (lowered) myocardial (muscular tissue of the heart) dysfunction, cardiac fibrosis, oxidative/nitrative stress, inflammation, cell death, and interrelated signaling pathways.

  • CBD also attenuated (lowered) the high glucose-created increased reactive oxygen species generation, nuclear factor-κB activation, and cell death in primary human cardiomyocytes.

  • We found that cannabis use was correlated with lower levels of fasting insulin and HOMA-IR, and smaller waist circumference.

  • The authors conclude that the prevalence of obesity is lower in cannabis users than in nonusers.

  • Cannabis users have smaller waists on average.

 

1 CBD INHIBITS OR DELAYS DIABETES IN RODENTS

1 Cannabidiol lowers the frequency of diabetes in nonobese diabetic rodents. Weiss et-al - year 2006. Autoimmunity 39: 143 to 151. I-bid

1 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.

1 We now report that Cannabidiol - CBD therapy significantly reduces the frequency of diabetes in Nonobese diabetic - NOD rodents from an frequency of 86 percent in non-treated control rodents to an frequency of 30 percent in CBD-treated rodents.

1 CBD therapy also resulted in the significant reduction of plasma (blood) levels of the pro-inflammatory cytokines, IFN-γ and TNF-α. Th1-correlated cytokine production of in vitro activated T-cells (killer cells) and peritoneal macrophages was also significantly decreased in CBD-treated rodents, whereas production of the Th2-correlated cytokines,  IL-4 (induces differentiation of naive helper T Cells) and  IL-10 (anti-inflammatory and inhibitor), was increased when compared to untreated control rodents.

1 Histological examination of the pancreatic islets of CBD-treated rodents revealed significantly decreased insulitis (inflammation of pancreas). Our results indicate that CBD can inhibit and delay destructive insulitis (inflammation of pancreas) and inflammatory Th1-correlated cytokine production in Non-obese diabetic - NOD rodents, resulting in a decreased frequency of diabetes possibly through an immunomodulatory mechanism shifting the immune response from Th1 to Th2 dominance.

 

 

2 CANNABIS PROTECTIVE OF CELLS IN DIABETICS?

2. Cannabis smoking & diabetes mellitus: Results from meta-analysis with eight independent replication samples. Alshaarway & Anthony. - year 2015 Epidemiology 26: 597 to 600.

2 Current evidence is too feeble for causal inference, but there now is a more stable evidence base for new lines of clinical translational research on a possible protective (or spurious) cannabis smoking-diabetes mellitus association suggested in prior research.

2 For each national survey participant, computer-assisted self-interviews assess cannabis smoking and physician-diagnosed diabetes mellitus; the National Health and Nutrition Examination Surveys provide additional biomarker values and a composite diabetes diagnosis. Regression analyses produce estimates of cannabis smoking-diabetes associations. Meta-analyses summarize the replication estimates.

 

3 ANOTHER KIND OF THC - THCV WITH CBD SHOWS GREAT THERAPEUTIC ACTIVITY IN DIABETES

3 The phytocannabinoid Δ9-tetrahydrocannabivarin (THCV (psychoactive, but different from regular THC)) ameliorates insulin sensitivity in two mouse models of obesity. Wargent et-al - year 2013. Nutrition & Diabetes

3 In summary, although THCV (psychoactive, but different from regular THC), which, like THC and AM251, has high affinity for Cannabinoid-CB-1 receptors and high brain penetration,  did produce some of the metabolically beneficial effects typical of Cannabinoid-CB-1 inverse agonists, its actions in obese rodents differed from those of a comparable dose of AM251, particularly as they were viewed in the absence of any effect on body weight. In this respect, THCV behaved in different manner also as compared with synthetic Cannabinoid-CB-1 neutral antagonists (dials down). The mechanism(s) through which THCV exerts these differential effects remains to be fully clarified.

3 For instance, it has been reported that Cannabinoid-CB-1 receptor blockade promotes mitochondrial biogenesis through endothelial nitric oxide synthase expression in white adipocytes, and it would be interesting to investigate if THCV is capable of similar effects in vitro, as such effects were suggested to underlie Rimonabant-created lipid diversion from storage towards utilization and its reduction of fat mass.

3 On the other hand, the counteraction of chronic insulin- and palmitic acid-created impairment of insulin receptor signalling in hepatocytes, reported here for THCV, suggests that the effect of this compound on glucose tolerance in obese rodents might be partly due to antagonism of Cannabinoid-CB-1-created impairment of insulin inhibition of hepatic glycogenolysis. Yet, it remains to be seen whether chronic Cannabinoid-CB-1 antagonism in insulin-resistant peripheral organs is the main mechanism of action for THCV, or whether there are other additional molecular targets contributing to its therapeutic benefits.

3 For example, this compound was reported to antagonize or activate Cannabinoid-CB-2 receptors depending on its concentrations. Furthermore, THCV is also known to activate TRPV1 channels, which were recently implicated in the restoration of insulin sensitivity in DIO rodents by capsaicin (active component of chili peppers,).

3 In conclusion, THCV produces therapeutic metabolic effects in two different mouse models of obesity. In particular, its strongest effects are exerted on plasma (blood) glucose and insulin levels, especially following an OGTT in DIO rodents and on liver triglycerides in ob/ob rodents. Based on these data, it can be suggested that THCV may be useful for the therapy of the metabolic syndrome and/or type 2 diabetes, either alone or in combination with existing treatments. Given the reported benefits of another non-THC phytocannabinoid, CBD in type 1 diabetes,  a CBD/THCV combination may be beneficial for different types of diabetes mellitus.

 

4 CBD IS BENEFICIAL TO DIABETICS IN MANY WAYS

4 Neuroprotective & blood-retinal barrier preserving effects of cannabidiol in experimental diabetes. El-Remessy et-al - year 2006. American Journal of Pathology 168: 235 to 244.

4 Cannabinoids produce their biological effects by acting through at least three receptors. The cannabinoid receptor CB-1 is responsible for psychoactivity and is expressed predominantly in the brain and retinal neurons. Receptor CB-2 is expressed predominantly in immune cells, cerebral microglial cells, and in the retina.The third receptor, abnormal-cannabidiol-sensitive receptor, is not cloned, but is pharmacologically defined in the cerebral microglial cells and endothelial cells in rodents lacking receptors Cannabinoid-CB-1 and Cannabinoid-CB-2. CBD has very low affinity to either Cannabinoid-CB-1 or Cannabinoid-CB-2, but is a partial agonist of abn-CBD-sensitive receptor.

4 The anti-inflammatory effects of CBD may be attributable to its activity on the abn-CBD-sensitive receptor. The neuroprotective effect of CBD may depend on its antioxidant ability directly to scavenge ROS or indirectly to inhibit reuptake/degradation of endogenous phyto-cannabinoids, including arachidonoyl-ethanolamide and 2-arachidonoyl glycerol. These endogenous cannabinoids act presynaptically to activate CB-1, which inhibits N-type calcium channels and so further reduces calcium influx and glutamate release.

4 CBD has been shown to inhibit the reuptake and degradation of arachidonoyl-ethanolamide in vitro and is a candidate for an anti-ischemia drug. Because the release of arachidonoyl-ethanolamide or 2-arachidonoyl glycerol occurs only in damaged regions and does not produce psychotropic effects, compounds that inhibit their transport/degradation may be of therapeutic utility without producing psychotropic effects.

4 Current efforts are in progress to study the role of Cannabinoid-CB-1 receptor by following the effects of CBD in Cannabinoid-CB-1 receptor knockout rodents. The nonpsychotropic CBD is a promising candidate for anti-inflammatory and neuroprotective therapeutics.

 

 

5 SYNTHETIC CANNABIS (AND CANNABIS) MIGHT BE EFFECTIVE PAINKILLERS IN DIABETES

5 Phyto-cannabinoids block tactile allodynia in diabetic rodents without attenuation of its antinociceptive (decreased sensitivity to pain) effect. Dogrul et-al - year 2004. Neuroscience Letters 368: 82 to 86.

5 Diabetic neuropathic pain is one of the most commonly encountered neuropathic pain syndromes. However, the therapy of diabetic neuropathic pain is challenging because of the partial effectiveness of currently available pain relievers. It is well known that diabetic animals are less sensitive to the analgesic (pain killing) effect of morphine, and opioids are found to be ineffective in the therapy of diabetic neuropathic pain.

5 Phyto-cannabinoids are promising drugs and they share a similar pharmacological properties with opioids. It has been reported that cannabinoid analgesia remained intact and to be effective in some models of nerve injury. Thus, we investigated antinociceptive (decreased sensitivity to pain) efficacy and the effects of phyto-cannabinoids on behavioral signs of diabetic neuropathic pain in diabetic rodents by using WIN 55212-2, a cannabinoid receptor agonist.

5 Diabetes was created by streptozotocin (STZ) (200 mg/kg) and animals were tested between 45 and 60 days after onset of diabetes. Antinociception was assessed using the radiant tail-flick test. Mechanical and thermal sensitivities were measured by Von Frey filaments and hot-plate test, respectively.

5 Tactile allodynia, but not thermal hyperalgesia (increased sensitivity to pain) developed in diabetic rodents. Systemic WIN 55212-2 (1, 5 and 10mg/kg) produced a dose-dependent antinociception both in diabetic and control rodents. WIN 55212-2-created antinociception were found to be similar in diabetic rodents when compared to controls, suggesting efficacy of cannabinoid antinociception was not diminished in diabetic rodents. WIN 55212-2 also produced a dose-dependent antiallodynic effect in diabetic rodents. This study suggests that phyto-cannabinoids have a potential beneficial effect on experimental diabetic neuropathic pain.

 

 

6 SYNTHETIC CANNABIS - PROMISING IN TREATING PAIN ASSOCIATED WITH DIABETES

6 The effect of WIN 55212-2 (synthetic cannabinoid) , a cannabinoid agonist, on tactile allodynia in diabetic rats.Ulugol et-al - year 2004. Neuroscience Letters 71: 167 to 170.

6 The antinociceptive (decreased sensitivity to pain) action of cannabinoids in acute and inflammatory pain states have been well-documented. There is also accumulating evidence suggesting that cannabinoids are effective analgesic (pain killer) in chronic pain conditions. WIN 55212-2 (synthetic cannabinoid) , a mixed Cannabinoid-CB-1 and Cannabinoid-CB-2 cannabinoid receptor agonist, has been shown to be effective against hyperalgesia (increased sensitivity to pain) and allodynia in painful peripheral mononeuropathy. Recently, in addition to their spinal and supraspinal antinociceptive (decreased sensitivity to pain) action, cannabinoids have also reported to exert local analgesic (pain killing) effects.

6 The aim of this study is to view the effect of a high affinity cannabinoid, WIN 55212-2 (synthetic cannabinoid) , on tactile allodynia and thermal hyperalgesia (increased sensitivity to pain) in diabetic rats. Diabetes was produced with the injection of a single dose of streptozotocin (50 mg/kg,ip) and this procedure resulted in neuropathic pain behaviors in the hindlimbs.

6 Mechanical allodynia was detected by application of von Frey filaments to the plantar surface of the foot, and thermal hyperalgesia (increased sensitivity to pain) was studied using the Hargreaves' method; however, thermal hyperalgesia did not develop in diabetic rats. With its higher doses, both systemic (3 and 10 mg/kg,ip) and peripheral (30 microg,ipl.) injections of WIN 55212-2 (synthetic cannabinoid)  decreased mechanical allodynia. These results suggest that WIN 55212-2 (synthetic cannabinoid)  has an antiallodynic effect in streptozotocin-created diabetic rats and may be a promising approach in the therapy of diabetic neuropathy.

 

7 CBD EFFECTIVE IN MANY ISSUES OF DIABETES - CARDIO, INFLAMMATION, PAIN..

7 Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, & inflammatory cell death signaling pathways in diabetic cardiomyopathy. Rajesh et-al - year 2010. Journal of the American College of Cardiology 56: 2115 to 2125.

7 In this study, we have investigated the effects of cannabidiol (CBD) on myocardial (muscular tissue of the heart) 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.

7 Results... Diabetic cardiomyopathy was characterized by declined diastolic and systolic myocardial (muscular tissue of the heart) performance correlated with greater oxidative-nitrative stress, nuclear factor-κB and mitogen-activated protein kinase activation, enhanced expression of adhesion molecules, 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 polymerase activity, chromatin fragmentation, and terminal deoxynucleotidyl transferase dUTP nick end labeling), and diminished Akt phosphorylation.
 

7 Remarkably, CBD attenuated (lowered) myocardial (muscular tissue of the heart) dysfunction, cardiac fibrosis, oxidative/nitrative stress, inflammation, cell death, and interrelated signaling pathways. Furthermore, CBD also attenuated (lowered) the high glucose-created increased reactive oxygen species generation, nuclear factor-κB activation, and cell death in primary human cardiomyocytes.

7 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 therapy  of diabetic complications, and perhaps other cardiovascular disorders, by attenuating oxidative/nitrative stress, inflammation, cell death and fibrosis.

 

8 TRIAL RESULT - CANNABIS KILLS PAIN IN DIABETICS

8 Efficacy of inhaled cannabis in painful diabetic neuropathy. Wallace et-al - year 2015. The Journal of Pain 16: 616 to 627.

8 This small, short-term, placebo-controlled trial of inhaled cannabis demonstrated a dose-dependent reduction in diabetic peripheral neuropathy pain in patients with treatment-refractory pain. This adds preliminary evidence to support further research on the efficacy of the phyto-cannabinoids in neuropathic pain.

8 A randomized, double-blinded, placebo controlled crossover study was conducted in 16 patients with painful diabetic peripheral neuropathy to assess the short-term efficacy and tolerability of inhaled cannabis. In a crossover design, each participant was exposed to 4 single dosing sessions of placebo or to low, medium (4 percent THC), or high (7 percent THC) doses of cannabis.

8 Baseline spontaneous pain, evoked pain, and cognitive testing was performed. Subjects were then administered aerosolized cannabis or placebo and the pain intensity and subjective "highness" score was measured at 5, 15, 30, 45, and 60 minutes and then every 30 minutes for an additional 3 hours. Cognitive testing was performed at 5 and 30 minutes and then every 30 minutes for an additional 3 hours.

8 The primary analysis compared differences in spontaneous pain over time, between doses using linear mixed effects models. There was a significant difference in spontaneous pain scores between doses . Specific significant comparisons were placebo versus low, medium, and high doses and high versus low and medium doses . There was a significant effect of the high dose on foam brush and von Frey evoked pain . There was a significant negative effect of the high dose on 2 of the 3 neuropsychological tests

 

9 MARIJUANA USERS SUFFER FROM DIABETES LESS FREQUENTLY

9 Decreased prevalence of diabetes in cannabis users. Rajavashisth et-al - year 2012. BMJ Open 2

9 Marijuana users had a lower age-adjusted prevalence of DM compared to non-cannabis users. The prevalence of elevated C reactive protein was significantly higher among non-cannabis users (18.9 percent) than among past (12.7 percent) or current light (15.8 percent) or heavy (9.2 percent) users. In a robust multivariate model controlling for socio-demographic factors, laboratory values and comorbidity, the lower odds of DM among cannabis users was significant .

9 Marijuana use was independently correlated with a lower prevalence of DM. Further studies are needed to show a direct effect of cannabis on DM.

 

10 CANNABIS USERS HAVE SMALLER WAISTS

10 Marijuana use on glucose, insulin, and insulin resistance among US adults. Penner et-al - year 2013.American Journal of Medicine 126: 583 to 589.

10 We included 4657 adult men and women from the National Health and Nutrition Examination Survey from  year 2005 to 2010. Cannabis 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 was calculated to evaluate insulin resistance. Associations were estimated using multiple linear regression, accounting for survey design and adjusting for potential confounders.

10 Of the participants in our study sample, 579 were current cannabis users and 1975 were past users. In multivariable adjusted models, current cannabis use was correlated with 16 percent lower fasting insulin levels and 17 percent lower HOMA-IR. We found significant associations between cannabis use and smaller waist circumferences. Among current users, we found no significant dose-response.

10 We found that cannabis use was correlated with lower levels of fasting insulin and HOMA-IR, and smaller waist circumference.

 

 

11 POT SMOKERS GET DIABETES LESS FREQUENTLY

11 American Journal of Epidemiology Strat & Foll. - year 2011. 174: 929 to 933.

11 The role of cannabis and endocannabinoids (body's own) in appetite regulation has been extensively studied, but the association of cannabis use with weight in the general population is not known. The authors used data from 2 representative epidemiologic studies of US adults aged 18 years or older, the National Epidemiologic Survey on Alcohol and Related Conditions and the National Comorbidity Survey–Replication, to estimate the prevalence of obesity as a function of cannabis use.

11 The adjusted prevalences of obesity in the NESARC and the NCS-R were 22.0 percent and 25.3 percent, respectively, among participants reporting no use of cannabis in the past 12 months and 14.3 percent and 17.2 percent, respectively, among participants reporting the use of cannabis at least 3 days per week. These differences were not accounted for by tobacco smoking status. Additionally, after adjustment for sex and age, the use of cannabis was correlated with body mass index - BMI differences in both samples. The authors conclude that the prevalence of obesity is lower in cannabis users than in nonusers.

 

12 CANNABIS BALANCES BLOOD SUGAR

12 Cannabis users have better blood sugar control. Science Daily. May 15, - year 2013

12 "Previous epidemiologic studies have found lower prevalence rates of obesity and diabetes mellitus in cannabis users compared to people who have never used cannabis, suggesting a relationship between phyto-cannabinoids and peripheral metabolic processes, but ours is the first study to investigate the relationship between cannabis use and fasting insulin, glucose, and insulin resistance," says lead investigator Murray A. Mittleman, MD, Dr. Pharmacy, of the Cardiovascular Epidemiology Research Unit at the Beth Israel Deaconess Medical Center, Boston.

 

13 CANNABIS USERS HAVE A LOWER BMI - BODY MASS INDEX

13 Cannabis use in relation to obesity & insulin resistance in the i\Inuit population. Nguta et-al - year 2015. Obesity 23: 290 to 295.

13 Cannabis use was highly prevalent in the study population (57.4 percent) and was statistically correlated with lower body mass index, lower  percent fat mass, lower fasting insulin, and lower HOMA-IR , after adjusting for numerous confounding variables. Further adjustment for BMI rendered fasting insulin and HOMA-IR differences statistically nonsignificant between past-year cannabis users and nonusers. Mediation analysis showed that the effect of cannabis use on insulin resistance was indirect, through BMI. In multivariate analysis, past-year cannabis use was correlated with 0.56 lower likelihood of obesity..

13 Cannabis use was correlated with lower BMI, and such an association did not occur through the glucose metabolic process or related inflammatory markers. The association between cannabis use and insulin resistance was mediated through its influence on weight.

 

14 MARIJUANA IMPROVES APPETITE YET LOWERS BMI - BODY MASS INDEX

14 Estimating the Relationship between Cannabis Use & Body Mass Index. Beulaygue & French. - year 2016. The Journal of Mental Health Policy & Economics

14 Although cannabis use is commonly correlated with improved appetite and the likelihood of weight gain, research findings in this area are mixed. Most studies, however, report cross sectional associations and rarely control for such important predictors as physical activity, socioeconomic status, and alcohol and other drug use. Methods: Using data from Waves III and IV of the National Longitudinal Survey of Adolescent Health, we estimate fixed-effects models to more rigorously study, the relationships between cannabis use and body mass index - BMI over time.

14 Our analyses include numerous sensitivity tests using alternative estimation techniques and at Wave IV we investigate the relationship between cannabis use and an alternative measure of body size (waist circumference).  Results show that daily female cannabis users have a BMI that is approximately 3.1 percent lower than that of non-users, whereas daily male users have a BMI that is approximately 2.7 percent lower than that of non-users. Discussion:

14 The present study indicates a negative association between cannabis use and BMI. Uncovering a negative association between cannabis use and weight status is a valuable contribution to the literature, as this result contradicts those from some previous studies, which were unable to address time-invariant unviewed heterogeneity. Implications for Future Research: Future theory-based research is necessary to explore the metabolic and behavioral pathways underlying the negative associations between cannabis use and BMI. A broader understanding of such mechanisms along with causal estimates will be most helpful to both policymakers and clinicians.

 

15 OBESITY LOWER IN POT SMOKERS

15 Obesity & cannabis use: Results from 2 representative national surveys. Le Strat & Le Foll. - year 2011. American Journal of Epidemiology 174: 929 to 933

15 The role of cannabis and endocannabinoids (body's own) in appetite regulation has been extensively studied, but the association of cannabis use with weight in the general population is not known. The authors used data from 2 representative epidemiologic studies of US adults aged 18 years or older, the National Epidemiologic Survey on Alcohol and Related Conditions and the National Comorbidity Survey-Replication , to estimate the prevalence of obesity as a function of cannabis use.

 

15 The adjusted prevalences of obesity in the NESARC and the NCS-R were 22.0 percent and 25.3 percent, respectively, among participants reporting no use of cannabis in the past 12 months and 14.3 percent and 17.2 percent, respectively, among participants reporting the use of cannabis at least 3 days per week. These differences were not accounted for by tobacco smoking status. Additionally, after adjustment for sex and age, the use of cannabis was correlated with body mass index - BMI differences in both samples. The authors conclude that the prevalence of obesity is lower in marijuana users than in nonusers.


 

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