A new review argues that higher linoleic acid exposure may be beneficial. But dietary intake, circulating LA and tissue fatty-acid composition are not the same biological exposure. This article explains why that distinction matters for arachidonic acid, membrane biology and the endocannabinoid system.
Tag: 2-AG
Endocannabinoid System (ECS)
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When Metabolic Dysfunction Acts on Both Sides of CB1 Signalling
A new Diabetologia study shows that insulin-resistant visceral adipose tissue overproduces 2-AG and anandamide, while recent work suggests insulin can also increase CB1 receptor stability. Together, these findings raise a testable question: can metabolic dysfunction amplify CB1 signalling by increasing both endogenous ligand production and receptor abundance?
Fatty Acid Research
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Your ECS Runs on What Your Metabolism Does With What You Eat
New human tracer data show that the same dietary fatty-acid exposure can produce very different biological outcomes depending on metabolic state. For the endocannabinoid system, this strengthens the case for measuring achieved DBS/RBC fatty-acid profiles rather than assuming intake equals substrate availability.
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.
Commentary
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The missing membrane layer in a new marathon endocannabinoid study
A new BMC Medicine study shows that marathon running triggers distinct temporal changes in anandamide, 2-AG and arachidonic acid. The missing piece may be the runners’ membrane fatty-acid state before exercise.
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…
Endocannabinoid System (ECS)
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2025 in ECS Research: The Year the Substrate-Driven ECS Model Came of Age
Endocannabinoid system substrate—specifically membrane fatty acid composition—is the primary determinant of CB1 receptor function, not genetics or receptor density. For years, I’ve been making the case that endocannabinoid system function is not primarily about receptor density or genetic variants, it’s about substrate availability. The composition of fatty acids in cell…
Endocannabinoid System (ECS)
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Paracetamol Confirmed as a Direct Analgesic DAGL Inhibitor: New Preprint Evidence
Important Note: This blog post discusses findings from a recent scientific preprint, meaning the research has not yet been formally peer-reviewed. Preprints allow for rapid dissemination of findings, but results should be interpreted cautiously until confirmed by peer-reviewed publication. Recently, we reported on a surprising new way that paracetamol (also known…
Pharmacology
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Acetaminophen (APAP) & the ECS: A Surprising New Twist in How Tylenol Really Works
New research upends our understanding of how acetaminophen (paracetamol) provides pain relief via the endocannabinoid system. Discover how it directly inhibits DAGLα, reducing 2-AG levels – a surprising twist on conventional ECS wisdom. Explore the implications for future drug development.
Commentary
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Seeing is Believing: New Tech Reveals How The Endocannabinoid System Works in Real-Time
A paradigm-shifting review in Neuron (Malhotra et al., 2025) highlights how new technologies allow scientists to visualize endocannabinoid (ECS) dynamics in real-time in behaving animals. This post breaks down the key breakthroughs, including the central role of 2-AG in rapid signaling, its precision, its function in memory and seizures, and the implications for healthcare professionals and medical cannabis.