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 Oct;39(10):1777-86. doi: 10.2337/dc16-0650. Epub 2016 Aug 29.

Abstract

Objective: Cannabidiol (CBD) and Δ(9)-tetrahydrocannabivarin (THCV) are nonpsychoactive phytocannabinoids affecting lipid and glucose metabolism in animal models. This study set out to examine the effects of these compounds in patients with type 2 diabetes.

Research design and methods: In this randomized, double-blind, placebo-controlled study, 62 subjects with noninsulin-treated type 2 diabetes 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 HDL-cholesterol concentrations from baseline. Secondary/tertiary 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. Safety and tolerability end points were also evaluated.

Results: Compared with placebo, THCV significantly decreased fasting plasma glucose (estimated treatment difference [ETD] = -1.2 mmol/L; P < 0.05) and improved pancreatic β-cell function (HOMA2 β-cell function [ETD = -44.51 points; P < 0.01]), adiponectin (ETD = -5.9 × 10(6) pg/mL; P < 0.01), and apolipoprotein A (ETD = -6.02 μmol/L; P < 0.05), although plasma HDL was unaffected. Compared with baseline (but not placebo), CBD decreased resistin (-898 pg/ml; P < 0.05) and increased glucose-dependent insulinotropic peptide (21.9 pg/ml; P < 0.05). None of the combination treatments had a significant impact on end points. CBD and THCV were well tolerated.

Conclusions: THCV could represent a new therapeutic agent in glycemic control in subjects with type 2 diabetes.

Trial registration: ClinicalTrials.gov NCT01217112.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Blood Glucose / metabolism
  • Body Mass Index
  • Body Weight
  • Cannabidiol / therapeutic use*
  • Cholesterol / blood
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Dronabinol / analogs & derivatives*
  • Dronabinol / therapeutic use
  • Endpoint Determination
  • Female
  • Gastric Inhibitory Polypeptide / blood
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Triglycerides / blood

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Triglycerides
  • Cannabidiol
  • tetrahydrocannabivarin 9
  • Gastric Inhibitory Polypeptide
  • Dronabinol
  • Cholesterol

Associated data

  • ClinicalTrials.gov/NCT01217112