Cannabinoid Compounds for Type 2 Diabetes

Two non-psychoactive derivatives of cannabis may have positive effects on glycemic and lipid parameters in patients with type 2 diabetes mellitus (T2DM), according to a new study.

Medical cannabis is often used to ease pain or nausea, and there are claims that cannabis and its derivative compounds have medicinal use for diabetes. The evidence of the effects of cannabis on diabetes ranges from anecdotal reports of benefits and harms to experimental research on cannabinoids. The endocannabinoid system appears to have a role in the regulation of body weight and food intake, and the development of hyperglycemia, insulin resistance, and dyslipidemia.

Unlike tetrahydrocannabinol (THC), the most well-known constituent in cannabis, cannabidiol (CBD) and tetrahydrocannabivarin (THCV) are non-psychoactive phytocannabinoids that do not activate CB₁ receptors in the brain and have been shown to affect lipid and glucose metabolism in animal models, state the researchers, led by Khalid A. Jadoon, of the University of Nottingham, Derby, United Kingdom.

Jadoon and colleagues conducted a randomized, double-blind, placebo-controlled trial of 62 patients with noninsulin-treated T2DM. The patients were randomized to five treatment arms: CBD (100 mg twice daily), THCV (5 mg twice daily), 1:1 ratio of CBD and THCV (5 mg/5 mg, twice daily), 20:1 ratio of CBD and THCV (100 mg/5 mg, twice daily), or matched placebo for 13 weeks.

The primary end point was a change in high-density lipoprotein (HDL) cholesterol concentrations from baseline. Other end points included changes in glycemic control, lipid profile, insulin sensitivity, body weight, liver triglyceride content, adipose tissue distribution, appetite, markers of inflammation, markers of vascular function, gut hormones, circulating endocannabinoids, and adipokine concentrations.

The results show that THCV had no effect on HDL cholesterol from baseline, or on low-density lipoprotein cholesterol levels, but did significantly increase apolipoprotein A concentrations from baseline. CBD alone and in combination with THCV did not affect any of the lipid parameters, but did induce desirable changes in some adipokines and gut hormones.

“Compared with placebo, THCV significantly decreased fasting plasma glucose and improved pancreatic β-cell function (HOMA2 β-cell function), adiponectin, and apolipoprotein A, although plasma HDL was unaffected. Compared with baseline (but not placebo), CBD decreased resistin and increased glucose-dependent insulinotropic peptide,” they stated.

Neither compound appeared to influence cardiovascular parameters, plasma markers of vascular function, plasma markers of inflammation (C-reactive protein, tumor necrosis factor-alpha, and interleukin-6), or anthropomorphic parameters (body weight, waist circumference, waist-to-hip ratio, or skinfold thickness), visceral adiposity, or appetite.

Adverse events were similar between the groups and no new safety concerns arose. Reduced appetite was common with the cannabinoids, reported in up to one-third of the treatment groups as compared to none in the placebo group. Two people reported diarrhea with THCV while there was none in the other groups. There were no deaths or treatment-related serious adverse events.

“These findings suggest that THCV may represent a new therapeutic agent for glycemic control in subjects with type 2 diabetes,” the researchers stated. “THCV improved glycemic control and therefore warrants further investigation in this therapeutic area.”

Reference: Jadoon KA, et al. Efficacy and safety of cannabidiol and tetrahydrocannabivarin on glycemic and lipid parameters in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel group pilot study. Diabetes Care. 2016 Aug 29.