cannabidiol and Diabetes-Mellitus--Type-1

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Autoimmune Diseases; Cannabidiol; Cannabinoids; Cannabis; Cartilage Diseases; Cytokines; Diabetes Mellitus, Type 1; Dronabinol; Humans; Immunomodulation; Lupus Erythematosus, Systemic; Mice; Multiple Sclerosis; Th17 Cells

Cannabis (delta-9-tetrahydrocannabinol), a nonselective cannabinoid-receptor agonist, relieves nausea and pain. Cannabidiol (CBD), a cannabinoid receptor 2 inverse agonist with central effects, also reduces gut sensation and inflammation. We compared the effects of 4 weeks of treatment with pharmaceutical CBD vs placebo in patients with idiopathic or diabetic (diabetes mellitus) gastroparesis.. We performed a randomized, double-blinded, placebo-controlled study of CBD twice daily (Epidiolex escalated to 20 mg/kg/d; Jazz Pharmaceuticals, Dublin, Ireland) in patients with nonsurgical gastroparesis with delayed gastric emptying of solids (GES). Symptoms were assessed by the Gastroparesis Cardinal Symptom Index Daily Diary. After 4 weeks of treatment, we measured GES, gastric volumes, and Ensure (Abbott Laboratories, Abbott Park, IL) satiation test (1 kcal/mL, 30 mL/min) to assess volume to comfortable fullness and maximum tolerance. Patients underwent specific FAAH and CNR1 genotyping. Statistical analysis compared 2 treatments using analysis of variance including baseline measurements and body mass index as covariates.. Among 44 patients (32 idiopathic, 6 diabetes mellitus type 1, and 6 diabetes mellitus type 2), 5 patients did not tolerate full-dose escalation; 3 withdrew before completing 4 weeks of treatment (2 placebo, 1 CBD); 95% completed 4 weeks of treatment and diaries. Compared with placebo, CBD reduced the total Gastroparesis Cardinal Symptom Index score (P = .008), inability to finish a normal-sized meal (P = .029), number of vomiting episodes/24 hours (P = .006), and overall symptom severity (P = .034). Patients treated with CBD had a higher volume to comfortable fullness and maximum tolerance and slower GES. FAAH rs34420 genotype significantly impacted nutrient drink ingestion. The most common adverse events reported were diarrhea (14 patients), fatigue (8 patients), headache (8 patients), and nausea (7 patients).. CBD provides symptom relief in patients with gastroparesis and improves the tolerance of liquid nutrient intake, despite slowing of GES.. gov NCT #03941288.

Topics: Cannabidiol; Diabetes Mellitus, Type 1; Drug Inverse Agonism; Gastric Emptying; Gastroparesis; Humans; Nausea

Destruction of the insulin-producing beta cells in type 1 diabetes (T1D) is induced by invasion of immune cells causing pancreatic inflammation. Cannabidiol (CBD), a phytocannabinoid, derived from the plant, Cannabis sativa, was shown to lower the incidence of diabetes in non-obese diabetic (NOD) mice, an animal model of spontaneous T1D development.. The goal of this study was to investigate the impact of experimental CBD treatment on early pancreatic inflammation in T1D by intravital microscopy (IVM) in NOD mice.. Seven-week-old female NOD mice were prophylactically administered daily 5 mg/kg CBD or control vehicle i.p. five times weekly for ten weeks. Animals underwent IVM following confirmation of T1D diagnosis by blood glucose testing. Leukocyte activation and functional capillary density (FCD) were quantified via IVM.. CBD-treated NOD mice developed T1D later and showed significantly reduced leukocyte activation and increased FCD in the pancreatic microcirculation.. Experimental CBD treatment reduced markers of inflammation in the microcirculation of the pancreas studied by intravital microscopy.

Topics: Animals; Cannabidiol; Diabetes Mellitus, Type 1; Disease Models, Animal; Female; Intravital Microscopy; Mice; Mice, Inbred NOD; Pancreatitis

Cannabidiol (CBD), a phytocannabinoid compound, presents antidepressant and anxiolytic-like effects in the type-1 diabetes mellitus(DM1) animal model. Although the underlying mechanism remains unknown, the type-1A serotonin receptor (5-HT1A) and cannabinoids type-1 (CB1) and type-2 (CB2) receptors seem to play a central role in mediating the beneficial effects on emotional responses. We aimed to study the involvement of these receptors on an antidepressant- and anxiolytic-like effects of CBD and on some parameters of the diabetic condition itself. After 2 weeks of the DM1 induction in male Wistar rats by streptozotocin (60 mg/kg; i.p.), animals were treated continuously for 2-weeks with the 5-HT1A receptor antagonist WAY100635 (0.1 mg/kg, i.p.), CB1 antagonist AM251 (1 mg/kg i.p.) or CB2 antagonist AM630 (1 mg/kg i.p.) before the injection of CBD (30 mg/kg, i.p.) or vehicle (VEH, i.p.) and then, they were submitted to the elevated plus-maze and forced swimming tests. Our findings show the continuous treatment with CBD improved all parameters evaluated in these diabetic animals. The previous treatment with the antagonists - 5-HT1A, CB1, or CB2 - blocked the CBD-induced antidepressant-like effect whereas only the blockade of 5-HT1A or CB1 receptors was able to inhibit the CBD-induced anxiolytic-like effect. Regarding glycemic control, only the blockade of CB2 was able to inhibit the beneficial effect of CBD in reducing the glycemia of diabetic animals. These findings indicated a therapeutic potential for CBD in the treatment of depression/anxiety associated with diabetes pointing out a complex intrinsic mechanism in which 5-HT1A, CB1, and/or CB2 receptors are differently recruited.

Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Cannabidiol; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Male; Maze Learning; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Receptor, Serotonin, 5-HT1A

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.

Topics: Animals; Cannabidiol; Cytokines; Diabetes Mellitus, Type 1; Disease Models, Animal; Female; Gene Expression Regulation; Lymphocytes; Macrophages; Mice; Mice, Inbred NOD; Statistics, Nonparametric

Cannabidinoids 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 cannabidinoid 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.

Topics: Animals; Cannabidiol; Cytokines; Diabetes Mellitus, Type 1; Female; Immunosuppressive Agents; Interferon-gamma; Islets of Langerhans; Macrophages, Peritoneal; Mice; Mice, Inbred NOD; Th1 Cells; Th2 Cells; Tumor Necrosis Factor-alpha