New approaches and challenges to targeting the endocannabinoid system

Area of Science:

• Pharmacology
• Neuroscience
• Microbiology

Background:

• The endocannabinoid system (ECS) was identified via Cannabis sativa compounds targeting its receptors.
• Endocannabinoids play roles in numerous physiological and pathological conditions.
• Related mediators and gut microbiome signaling complicate ECS drug development.

Purpose of the Study:

• To review current drug development targeting the ECS.
• To discuss future pharmacological manipulation strategies for the ECS.
• To highlight challenges and rewards in targeting the ECS for therapeutics.

Main Methods:

• Literature review of current research on endocannabinoid signaling.
• Analysis of challenges in developing enzyme inhibitors and multi-target drugs.
• Discussion of botanical and synthetic cannabinoid drugs' clinical status.

Main Results:

• Botanical cannabinoid drugs are clinically advanced.
• High-affinity synthetic agonists for cannabinoid receptor 1 pose societal risks.
• The gut microbiome communicates partly via the ECS.

Conclusions:

• Developing ECS-targeting therapeutics is complex due to numerous mediators and pathways.
• Multi-target drug design is a rational approach.
• Future pharmacological strategies for the ECS require careful consideration of its multifaceted roles.