A new PNAS study identifies a previously underappreciated Gq/11–PLC–PKC–NEDD4L pathway that marks CB1 receptors for proteasomal degradation. The findings help explain how repeated THC exposure can reduce receptor availability and contribute to cannabinoid tolerance.
Tag: CB1 Receptor
Commentary
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The Endocannabinoid System Is No Longer the Limiting Factor? Almost.
A new review argues that policy and stigma, rather than lack of ECS science, are now the main barriers to cannabinoid medicine. I agree, but an important gap remains: medicine still lacks a practical clinical physiology of the endocannabinoid system.
Endocannabinoid System (ECS)
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Paracetamol, 2-AG and CB1: The ECS Story Just Got More Complicated
New mouse research reveals that paracetamol’s pain-relieving effects depend on CB1 receptors and the enzymes DAGL and MAGL, while reshaping prostaglandin and wider lipid signalling.
Endocannabinoid System (ECS)
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Tolerance changes the economics of medical cannabis
A New York study found that 49% of surveyed medical cannabis patients could not afford enough cannabis to manage their symptoms. This article examines a missing variable in the affordability debate: whether chronic high-THC exposure, tolerance and CB1 adaptation may increase the amount of cannabis required for sustained therapeutic effect.
Announcements
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Open letter to CB1 researchers
An open letter inviting researchers to investigate whether metabolic state influences CB1 receptor stability, trafficking and degradation across insulin-sensitive tissues, and whether this represents a broader principle of endocannabinoid system regulation.
Endocannabinoid System (ECS)
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How the Endocannabinoid System Helps the Brain Adapt and Learn
The Endocannabinoid System and the Biology of Learning: How Endocannabinoids Help the Brain Adapt Why one-shot learning matters for survival Imagine touching a hot surface for the first time. The experience lasts only a moment, but the lesson can last a lifetime. The brain does not need repeated exposure to…
Endocannabinoid System (ECS)
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ECS Literacy in Medicine: Why It Makes Better Doctors
What happens to clinical reasoning when a physician understands the endocannabinoid system? Seven conditions, two kinds of doctors, and the reasoning gap that a better curriculum could close.
Endocannabinoid System (ECS)
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How Poor Diet and Insulin Spikes Disrupt the Endocannabinoid System and Drive Fatty Liver
Scientists have identified a new mechanism linking everyday diet to endocannabinoid system (ECS) dysfunction: normal post‑meal insulin spikes can increase CB1 receptors in the liver by about 50% by slowing their lysosomal recycling. Together with an omega‑6‑heavy fat intake, this amplifies diet‑driven steatosis and helps explain how common foods drive fatty liver disease.
Critical analysis
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Low plasma linoleic acid is a marker of high FADS activity – not a license to drink seed oil
A new UK Biobank paper on omega‑6 and adiposity just landed, and if you only read the abstract, you’d think the story was simple: higher linoleic acid (LA) in plasma is “protective” against obesity and therefore we should be recommending more LA‑rich oils to everyone. Look one level deeper, and…
Critical analysis
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The Missing System: How a Major 2026 Review on Cardiometabolic Health Ignores the Endocannabinoid System
Last August, I wrote about a troubling pattern in inflammation research: brilliant scientists studying arachidonic acid metabolism while remaining “blissfully unaware that half the arachidonic acid story exists in a parallel research universe.” I documented how eicosanoid researchers and endocannabinoid scientists study the same substrate, same concentration ranges, same tissues—yet publish in…