Cannabinoids and terpenes for diabetes mellitus and its complications: from mechanisms to new therapies

Trends Endocrinol Metab. 2022 Dec;33(12):828-849. doi: 10.1016/j.tem.2022.08.003. Epub 2022 Oct 21.


The number of people diagnosed with diabetes mellitus and its complications is markedly increasing worldwide, leading to a worldwide epidemic across all age groups, from children to older adults. Diabetes is associated with premature aging. In recent years, it has been found that peripheral overactivation of the endocannabinoid system (ECS), and in particular cannabinoid receptor 1 (CB1R) signaling, plays a crucial role in the progression of insulin resistance, diabetes (especially type 2), and its aging-related comorbidities such as atherosclerosis, nephropathy, neuropathy, and retinopathy. Therefore, it is suggested that peripheral blockade of CB1R may ameliorate diabetes and diabetes-related comorbidities. The use of synthetic CB1R antagonists such as rimonabant has been prohibited because of their psychiatric side effects. In contrast, phytocannabinoids such as cannabidiol (CBD) and tetrahydrocannabivarin (THCV), produced by cannabis, exhibit antagonistic activity on CB1R signaling and do not show any adverse side effects such as psychoactive effects, depression, or anxiety, thereby serving as potential candidates for the treatment of diabetes and its complications. In addition to these phytocannabinoids, cannabis also produces a substantial number of other phytocannabinoids, terpenes, and flavonoids with therapeutic potential against insulin resistance, diabetes, and its complications. In this review, the pathogenesis of diabetes, its complications, and the potential to use cannabinoids, terpenes, and flavonoids for its treatment are discussed.

Keywords: cannabinoid receptors; cannabinoids; diabetes mellitus; inflammation; terpenes; the endocannabinoid system.

Publication types

  • Review

MeSH terms

  • Aged
  • Cannabinoid Receptor Agonists / pharmacology
  • Cannabinoids* / therapeutic use
  • Cannabis*
  • Child
  • Diabetes Mellitus* / drug therapy
  • Flavonoids
  • Humans
  • Insulin Resistance*
  • Terpenes / therapeutic use


  • Cannabinoids
  • Terpenes
  • Cannabinoid Receptor Agonists
  • Flavonoids