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

Jadoon, Khalid A.; Ratcliffe, Stuart H.; Barrett, David A.; Thomas, E. Louise; Stott, Colin; Bell, Jimmy D.; O'Sullivan, Saoirse; Tan, Garry D.

Abstract

OBJECTIVE Cannabidiol (CBD) and Δ9-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 × 106 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.

Citation

Jadoon, K. A., Ratcliffe, S. H., Barrett, D. A., Thomas, E. L., Stott, C., Bell, J. D., …Tan, G. D. (2016). 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, 39(10), 1777-1786. https://doi.org/10.2337/dc16-0650

• Journal Article Type: Article
• Acceptance Date: Jul 21, 2016
• Online Publication Date: Aug 29, 2016
• Publication Date: 2016-10
• Deposit Date: Oct 21, 2016
• Publicly Available Date: Oct 21, 2016
• Journal: Diabetes Care
• Print ISSN: 0149-5992
• Electronic ISSN: 1935-5548
• Publisher: American Diabetes Association
• Peer Reviewed: Peer Reviewed
• Volume: 39
• Issue: 10
• Pages: 1777-1786
• DOI: https://doi.org/10.2337/dc16-0650
• Public URL: https://nottingham-repository.worktribe.com/output/974684
• Publisher URL: http://care.diabetesjournals.org/content/39/10/1777
• Additional Information: This is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes Care. The American Diabetes Care Association (ADA), publisher of Diabetes Care, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version is available in print and online at http://care.diabetesjournals.org/content/39/10/1777
• Contract Date: Oct 21, 2016