Cannabis: From a plant that modulates feeding behaviors toward developing selective inhibitors of the peripheral endocannabinoid system for the treatment of obesity and metabolic syndrome

Shira Hirsch, Joseph Tam*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

23 Scopus citations

Abstract

In this review, we discuss the role of the endocannabinoid (eCB) system in regulating energy and metabolic homeostasis. Endocannabinoids, via activating the cannabinoid type-1 receptor (CB1R), are commonly known as mediators of the thrifty phenotype hypothesis due to their activity in the central nervous system, which in turn regulates food intake and underlies the development of metabolic syndrome. Indeed, these findings led to the clinical testing of globally acting CB1R blockers for obesity and various metabolic complications. However, their therapeutic potential was halted due to centrally mediated adverse effects. Recent observations that highlighted the key role of the peripheral eCB system in metabolic regulation led to the preclinical development of various novel compounds that block CB1R only in peripheral organs with very limited brain penetration and without causing behavioral side effects. These unique molecules, which effectively ameliorate obesity, type II diabetes, fatty liver, insulin resistance, and chronic kidney disease in several animal models, are likely to be further developed in the clinic and may revive the therapeutic potential of blocking CB1R once again.

Original languageAmerican English
Article number275
JournalToxins
Volume11
Issue number5
DOIs
StatePublished - May 2019

Bibliographical note

Funding Information:
Funding: This review article was made possible by the financial support provided by the ERC-2015-StG grant (#676841) to J.T.

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • CB1 receptor
  • Cannabis
  • Central CB1 receptor blockade
  • Marijuana
  • Peripheral CB1 receptor blockade

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