Why THC Users Eat More but Don't Gain Weight | Nephi Stella | 305

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The biology of endogenous cannabinoids & history of cannabinoid-based therapeutics

TOPICS DISCUSSED:

• Anandamide vs 2-AG: The two major endocannabinoids with a shared arachidonic acid backbone but distinct head groups biological roles.
• On-demand production: Calcium-dependent enzymes release cannabinoids from membranes in response to neuronal activity patterns.
• Trafficking: Fatty acid binding proteins and extracellular microvesicles traffic endocannabinoids within and between cells.
• Adolescent THC: Global receptor activation during circuit wiring may contribute to cannabis use disorder and psychosis vulnerability in susceptible individuals.
• Enzyme inhibitors: Early FAAH clinical trial halted by off-target toxicity; MAGL inhibitors advancing in phase 2 for anxiety and addiction.
• Peripheral CB1: Liver receptors regulate metabolism; restricted antagonists aim to reduce weight without central psychiatric risks of the weight loss drug rimonabant.

ABOUT THE GUEST: Nephi Stella, PhD is a professor at the University of Washington School of Medicine. He has studied endocannabinoid signaling for more than 25 years, focusing on therapeutic strategies that separate beneficial effects from side effects of cannabinoid-system modulation.

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