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Re-visiting the Endocannabinoid System and Its Therapeutic Potential in Obesity and Associated Diseases

Abstract

Purpose of review

The purpose of the review was to revisit the possibility of the endocannabinoid system being a therapeutic target for the treatment of obesity by focusing on the peripheral roles in regulating appetite and energy metabolism.

Recent findings

Previous studies with the global cannabinoid receptor blocker rimonabant, which has both central and peripheral properties, showed that this drug has beneficial effects on cardiometabolic function but severe adverse psychiatric side effects. Consequently, focus has shifted to peripherally restricted cannabinoid 1 (CB1) receptor blockers as possible therapeutic agents that mitigate or eliminate the untoward effects in the central nervous system.

Summary

Targeting the endocannabinoid system using novel peripheral CB1 receptor blockers with negligible penetrance across the blood-brain barrier may prove to be effective therapy for obesity and its co-morbidities. Perhaps the future of blockers targeting CB1 receptors will be tissue-specific neutral antagonists (e.g., skeletal muscle specific to treat peripheral insulin resistance, adipocyte-specific to treat fat excess, liver-specific to treat fatty liver and hepatic insulin resistance).

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Correspondence to Joyce M. Richey.

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Joyce M. Richey and Orison Woolcott declare that they have no conflict of interest.

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This article is part of the Topical Collection on Pathogenesis of Type 2 Diabetes and Insulin Resistance

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Richey, J.M., Woolcott, O. Re-visiting the Endocannabinoid System and Its Therapeutic Potential in Obesity and Associated Diseases. Curr Diab Rep 17, 99 (2017). https://doi.org/10.1007/s11892-017-0924-x

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Keywords

  • Adipose tissue
  • Endocannabinoid system
  • Cannabinoid 1 (CB1) receptor
  • Metabolism
  • Obesity
  • Peripheral cannabinoid blocker