A new study published in the American Journal of Physiology-Endocrinology and Metabolism by researchers from the National Institute on Aging at the National Institutes of Health found that the cannabinoid-related drug nabilone increased insulin sensitivity in a small group of healthy men, while a higher dose of a CB1 receptor blocker had the opposite effect.

The study involved 21 healthy men who took part in four separate visits, each spaced at least six weeks apart. During those visits, participants were given either 2 milligrams of nabilone, a low dose of the CB1 receptor antagonist CP-945,598, a high dose of the same antagonist, or a placebo. Researchers then used a series of glucose clamp procedures after an overnight fast to measure insulin secretion, insulin sensitivity, glucose disposal and related metabolic changes.

According to the findings, neither nabilone nor the CB1 blocker changed insulin secretion during the hyperglycemic portion of testing when compared to placebo. But the results were different when researchers looked at insulin sensitivity. Nabilone significantly increased insulin sensitivity during the euglycemic-hyperinsulinemic clamp, while the higher 45-milligram dose of CP-945,598 significantly decreased it.

Researchers also found that non-esterified fatty acids and several circulating N-acylethanolamines, including the endocannabinoid anandamide, were reduced in an insulin-dependent manner during the clamp procedures.

The findings add to the growing body of evidence showing that the endocannabinoid system plays a direct role in metabolic regulation. In this case, the results indicate that short-term activation of cannabinoid signaling may improve how the body responds to insulin under tightly controlled laboratory conditions, while blocking CB1 receptors at a higher dose may impair that response.

Because the study was small and limited to healthy men in a clinical setting, the findings do not show that cannabinoid-based medications would improve metabolism more broadly or in people with diabetes. Even so, the research provides another look at how the body’s cannabinoid system may influence insulin action and glucose control.