What peer‑reviewed clinical trials exist testing CBD (cannabidiol) for insulin resistance or glycemic control?
Executive summary
Two small human clinical trials and a scattering of phase‑level and case reports have tested cannabidiol (CBD) for insulin resistance or glycemic control, but the evidence is limited, mixed, and far from definitive: a 2016 randomized, double‑blind, placebo‑controlled pilot tested CBD (often paired with THCV) and found biomarker changes versus baseline but not versus placebo (Diabetes Care), while a more recent phase I randomized trial of a CBD/Δ9‑THC sublingual spray reported improved glycemic measures over eight weeks but requires cautious interpretation pending broader peer review and replication [1] [2] [3] [4].
1. The clinical‑trial landscape: only a handful of small trials and pilots
Peer‑reviewed clinical trials specifically testing CBD for insulin resistance or glycemic control are scarce: the landmark randomized pilot in Diabetes Care enrolled 62 non–insulin‑treated type 2 diabetes patients to CBD, THCV, combinations, or placebo for 13 weeks and remains the most cited controlled trial [1], while other human trials noted in reviews and press accounts include a phase I sublingual CBD/THC study and small open reports—none approach the size or rigor needed to settle efficacy questions [3] [5].
2. Jadoon et al. (Diabetes Care, 2016): what it actually showed
The Diabetes Care randomized, double‑blind, placebo‑controlled pilot randomized 62 subjects across five arms (CBD 100 mg twice daily, THCV 5 mg twice daily, two combination ratios, or placebo) for 13 weeks; the trial reported that CBD decreased resistin and increased glucose‑dependent insulinotropic peptide compared with baseline but did not demonstrate statistically significant improvements in primary glycemic or lipid endpoints compared with placebo—THCV, not CBD, showed the more promising glycemic signal in that dataset [1] [2] [6].
3. The 2021–2023 phase I sublingual CBD/THC trial: promising but preliminary and not widely vetted
A randomized, double‑blind, placebo‑controlled phase I trial from Tehran tested a sublingual spray combining CBD and Δ9‑THC (10:1) over eight weeks and reported statistically significant declines in fasting glucose, HbA1c, insulin secretion, and lipids in the treated group [3]; coverage by advocacy outlets (NORML) and inclusion in later reviews has amplified interest, but the study’s phase I status, small scale, single‑center conduct, and the need for independent replication mean it cannot be taken as conclusive proof of CBD’s glycemic efficacy [4] [3].
4. Supporting preclinical and review literature: mechanisms and caveats
Animal studies and mechanistic reviews suggest CBD influences pathways relevant to insulin resistance—endocannabinoid signaling, PPAR‑γ, gut hormones, and inflammation—and some preclinical models show improved insulin sensitivity and glucose handling, but authors and systematic reviews emphasize that clinical data remain limited and inconsistent, and safety/interaction profiles with standard antidiabetic drugs require careful study [5] [7] [8].
5. What the evidence does not show and why caution is warranted
No large, phase II/III randomized controlled trials definitively demonstrate that isolated CBD monotherapy lowers A1c or reliably improves insulin resistance in people with diabetes; the Diabetes Care pilot failed to show CBD benefit versus placebo on primary endpoints, and the positive signals reported in smaller or mixed CBD/THC trials require replication and independent peer review—some popular or industry sources overstate results or conflate CBD with mixed‑cannabinoid regimens, which introduce THC and alter pharmacology [1] [2] [4] [9].
6. Bottom line for clinicians, patients, and researchers
Current peer‑reviewed clinical evidence consists chiefly of the 2016 randomized Diabetes Care pilot and a later phase I sublingual CBD/THC trial; these studies generate hypotheses—biomarker shifts, possible insulin‑sensitizing signals—but do not justify clinical adoption of CBD as a glucose‑lowering therapy without larger, rigorous trials that isolate CBD effects, define doses/formulations, and evaluate long‑term safety and drug interactions [1] [3] [5].