Cannabinoid System: Metabolism, Evolution & Energy Storage | Giovanni Marsicano | 245

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What is the core evolved function of the endocannabinoid system?

Episode Summary: Dr. Giovanni Marsicano is a neuroscientist based in Bordeaux, France, where he leads a research group at INSERM focusing on the endocannabinoid system.

About the guest: Giovanni Marsicano, PhD discusses the endocannabinoid system, starting with its core components like CB1 receptors and lipid-based molecules derived from omega-6 fatty acids; its cellular signaling, evolutionary role in energy storage for uncertain futures (exostasis vs. homeostasis); effects across tissues; motivation, appetite, pain relief, and anxiety regulation; biphasic effects of cannabinoids.

Discussion Points:

• The endocannabinoid system acts as an "exostatic" regulator, promoting energy accumulation for future needs by enhancing food palatability, nutrient absorption, and fat storage, unlike "endostatic" systems that address immediate hunger.
• CB1 receptors appear in vertebrates with adipose tissue, suggesting an evolutionary link to storing fat for survival in unstable environments.
• Endocannabinoids are lipids from omega-6 fats; high intake boosts their levels, potentially fueling obesity by creating a self-perpetuating cycle of overeating.
• Activation of CB1 can have biphasic effects due to receptors on different cell types like excitatory vs. inhibitory neurons.
• Pregnenolone, a steroid precursor, acts as a natural CB1 inhibitor to prevent excessive activation, blocking harmful effects like psychosis from high THC doses.
• The system influences motivation beyond food, including sex and even human activities like sports or storytelling, by rewarding actions for potential future benefits.
• In the brain, CB1 on mitochondria and astrocytes modulates energy use, olfaction, and social stress transmission, with implications for disorders like Alzheimer's.

Reference Paper:

• CB1 Receptor as the Cornerstone of Exostasis

Related episode:

• M&M 123: Endocan

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