How the Body Makes and Breaks Down Its Own Cannabinoids | Research

The takeaway

A comprehensive review detailed the synthesis and degradation pathways of anandamide and 2-AG, the two primary endocannabinoids, including their oxidative metabolism by enzymes beyond FAAH and MAGL.

Readers wanting to understand the basic biochemistry of the endocannabinoid system.

Two main endocannabinoids, three degradation pathways (hydrolysis, COX-2, lipoxygenase)

What the researchers found

This review provided a detailed account of how the body produces and breaks down its two main endocannabinoids: anandamide (AEA) and 2-arachidonoylglycerol (2-AG).

Both are synthesized from phospholipids in cell membranes. Anandamide is formed from N-arachidonoyl phosphatidylethanolamine through multiple enzymatic pathways. 2-AG is produced primarily through DAGL-mediated hydrolysis of phosphatidylinositol.

The primary role of endocannabinoids is activating cannabinoid receptors, with 2-AG having stronger affinity than anandamide. Unbound endocannabinoids are degraded: anandamide mainly by FAAH, 2-AG mainly by MAGL. Beyond hydrolysis, both can be oxidized by cyclooxygenase-2, lipoxygenases, and cytochrome P450 enzymes, producing metabolites that also have biological significance.

Why it matters

Understanding how the body makes and breaks down its own cannabinoids is fundamental to understanding both the effects of external cannabinoids (like THC) and the development of drugs that target the endocannabinoid system for therapeutic purposes.

The numbers in context

Two main endocannabinoids: anandamide and 2-AG. Both are primarily CB1 agonists, with weaker CB2 and TRPV1 activity. 2-AG has stronger receptor affinity. Primary degradation enzymes: FAAH (anandamide) and MAGL (2-AG). Additional oxidative metabolism by COX-2, lipoxygenases, and cytochrome P450.

How the study worked

This was a comprehensive review of endocannabinoid biochemistry published in a Polish journal of hygiene and experimental medicine, synthesizing the current understanding of endocannabinoid synthesis, receptor interactions, and degradation pathways.

What this study cannot tell us

This was a review of known biochemistry rather than new research. The complexity of endocannabinoid metabolism means many details and regulatory mechanisms remain to be fully characterized. The biological significance of oxidative endocannabinoid metabolites is still being explored.

How to read the evidence

This is a comprehensive biochemistry review synthesizing well-established metabolic pathways with emerging findings on oxidative metabolism.

When this study was published

Published in 2016. The fundamental metabolic pathways described remain accurate, though new details and regulatory mechanisms continue to be discovered.

The bigger picture

The endocannabinoid system is involved in virtually every physiological process, from mood and pain to appetite and immune function. This biochemical foundation is essential for understanding why cannabis produces its effects and how therapeutic interventions targeting this system might work.

Questions still open

How do the oxidative metabolites of endocannabinoids contribute to health and disease? Could targeting specific metabolic pathways offer more selective therapeutic effects than broadly activating cannabinoid receptors?

Common questions

What are endocannabinoids?

Endocannabinoids are molecules the body naturally produces that activate the same receptors as THC and other cannabis compounds. The two main ones are anandamide and 2-AG. They are made from fatty acids in cell membranes and broken down by specific enzymes after they have done their job.

Why does the body have its own cannabinoid system?

The endocannabinoid system evolved to regulate many physiological processes including pain perception, mood, appetite, immune function, and memory. Cannabis compounds happen to activate the same receptors, which is why they produce such wide-ranging effects.

Read the original research

Metabolism of endocannabinoids.

Postepy higieny i medycyny doswiadczalnej (Online), 70(0), 830-43

View on PubMed ↗

Citation

Biernacki, Michał; Skrzydlewska, Elżbieta. (2016). Metabolism of endocannabinoids.. Postepy higieny i medycyny doswiadczalnej (Online), 70(0), 830-43.