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What are endocannabinoids?

Understanding Endocannabinoids: The Body’s Signalling Molecules

Endocannabinoids are signalling molecules made by the body that play a crucial role in modulating the endocannabinoid system (ECS). The term “endocannabinoid” is derived from the ancient Greek word ‘ἔνδον’ (éndon), meaning “within”, and “cannabinoid” refers to molecules capable of binding to cannabinoid receptors. These molecules share a similar structure with cannabinoids found in nature, such as THC and CBD, which are present in cannabis and other herbs.

The Key Endocannabinoids

Researchers have identified two key endocannabinoids: Anandamide (AEA) and 2-arachidonoylglycerol (2-AG). These molecules influence various factors like mood, sleep, appetite, memory, and learning by binding to cannabinoid receptors. AEA is a low-efficacy agonist of both the CB1 and CB2 receptor, while studies have shown 2-AG to be a full agonist of both receptors, resulting in increased receptor activation.

Mechanism of Action

Endocannabinoids function as retrograde signalling messengers, acting in the opposite direction of typical nervous system transmission. Synthesised in postsynaptic neurons, they are released into the synaptic cleft to bind to target sites on presynaptic neurons, inhibiting the release of neurotransmitters. This mechanism helps the body maintain physiological balance, contributing to homeostasis.

Production of Endocannabinoids

Endocannabinoids like AEA and 2-AG are produced on-demand in the membranes of postsynaptic neurons. They originate from fat-based molecules and are quickly broken down by specific enzymes after binding to receptor sites. AEA is catabolised by enzymes like fatty acid amino hydrolase (FAAH) and COX-2, while 2-AG is broken down by MGL, α/β domain hydrolases, and COX-2.


Endocannabinoids play essential roles within the ECS and the human body, controlling neurotransmitter release and maintaining homeostasis. These molecules are involved in various physiological processes, from appetite and mood to sleep. Ongoing research continues to uncover the extensive functions of endocannabinoids in human physiology.


[1] Lu, H., & Mackie, K. (2017). An introduction to the endogenous cannabinoid system. NCBI. [Source]

[2] Ohno-Shosaku, T. (2009). Retrograde Messenger. Encyclopedia of Neuroscience, 3529-3533. [Source]

[3] Fenwick, A. J., Fowler, D. K., Wu, S. W., Shaffer, F. J., Lindberg, J. E. M., Kinch, D. C., & Peters, J. H. (2017). Direct Anandamide Activation of TRPV1 Produces Divergent Calcium and Current Responses. Frontiers in Molecular Neuroscience, 10. [Source]