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Rehashing endocannabinoid antagonists: can we selectively target the periphery to safely treat obesity and type 2
1Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02215, USA. mary.elizabeth.patti@joslin.harvard.edu
Abstract:
A growing body of evidence supports an important role for the endocannabinoid system as a regulator of appetite, body weight, and systemic metabolism, which is overactive in obesity and type 2 diabetes. While initial attempts to target this system using the cannabinoid receptor inverse agonist rimonabant were successful in producing modest weight loss and improving obesity-related metabolic complications in humans, adverse central nervous system side effects precluded introduction of this drug into clinical practice. However, new data, presented by Tam and colleagues in this issue of the JCI, demonstrate that selective blockade of peripheral cannabinoid receptors may be a novel successful therapeutic approach.
Insights
Blocking peripheral cannabinoid receptors may offer a new therapeutic strategy for obesity and type 2 diabetes. This approach avoids the adverse side effects associated with targeting the central nervous system, unlike previous treatments.
Area of Science:
- Metabolic research
- Endocrinology
- Pharmacology
Background:
- The endocannabinoid system regulates appetite, body weight, and metabolism.
- This system is often overactive in obesity and type 2 diabetes.
- Previous attempts to target this system with rimonabant caused adverse central nervous system effects.
Purpose of the Study:
- To investigate the potential of selectively blocking peripheral cannabinoid receptors as a therapeutic strategy.
- To evaluate a novel approach for managing obesity and related metabolic complications.
Main Methods:
- Selective blockade of peripheral cannabinoid receptors.
- Evaluation of therapeutic efficacy in preclinical or clinical models (details not provided in abstract).
Main Results:
- Selective blockade of peripheral cannabinoid receptors shows promise.
- This approach may overcome the limitations of earlier treatments targeting the central nervous system.
Conclusions:
- Targeting peripheral cannabinoid receptors represents a potential novel therapeutic avenue.
- This strategy may offer a safer alternative for treating metabolic disorders like obesity and type 2 diabetes.
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