When people hear the word “cannabinoid,” they usually think of compounds found in the hemp plant, such as CBD or THC. Yet cannabinoids are not exclusively associated with plants. The human body produces its own cannabinoid-like signalling molecules, which participate in an extensive biological communication network known as the endocannabinoid system (ECS). Understanding this system provides a fascinating perspective on how our bodies regulate everyday physiological processes. 

 The discovery of the ECS began with research into THC, the principal intoxicating compound in cannabis. In 1988, scientists identified specific binding sites for THC in the brain, later characterised as cannabinoid receptors. This raised an intriguing question: why would the human body possess receptors capable of recognising a plant-derived molecule? The answer emerged when researchers discovered that our bodies produce their own substances capable of activating these receptors. 

 Two of the best-characterised endocannabinoids are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Both are lipid-derived signalling molecules, meaning they originate from fatty acid-containing components of cell membranes. Anandamide was discovered in 1992. Its name comes from the Sanskrit word ananda, meaning bliss, although describing it simply as a “bliss molecule” considerably oversimplifies its biological functions. Anandamide participates in signalling pathways associated with mood, memory, pain processing and other physiological activities. 

 The second major endocannabinoid, 2-AG, was identified in 1995. It is generally present at substantially higher concentrations than anandamide in the brain and acts as an important signalling molecule throughout the nervous system and elsewhere in the body. Unlike many classical neurotransmitters, which are stored in vesicles until needed, endocannabinoids are typically produced on demand from membrane-associated lipid precursors. This allows cells to generate signals in response to changing physiological conditions. 

 The ECS includes two extensively studied cannabinoid receptors: CB1 and CB2. Both belong to the G protein-coupled receptor family, a large group of proteins that translate extracellular signals into changes in cellular activity. CB1 receptors are particularly abundant in the central nervous system, including regions involved in memory, movement, appetite and pain processing. They also occur in peripheral tissues. CB2 receptors are strongly associated with immune cells and immune-related signalling, although they are also found in other tissues. Their activation can influence cellular responses involved in inflammation and immune regulation. These distributions are not absolute. CB1 receptors are not exclusive to the brain, and CB2 receptors are not exclusive to the immune system. Their functions depend on the tissue, cell type and physiological circumstances. 

 One particularly interesting feature of endocannabinoid signalling is that it can operate in reverse. In conventional neuronal communication, a presynaptic neuron releases neurotransmitters that act on a postsynaptic neuron. Endocannabinoids can travel in the opposite direction, from the postsynaptic neuron back towards the presynaptic terminal. This process, called retrograde signalling, allows the receiving neuron to influence how much neurotransmitter is subsequently released. It provides an important mechanism for adjusting communication between nerve cells. 

 Endocannabinoid signalling is also tightly controlled by enzymes. Anandamide is commonly synthesised through pathways involving N-acyl phosphatidylethanolamine-specific phospholipase D (NAPE-PLD), although alternative pathways exist. It is primarily broken down by fatty acid amide hydrolase (FAAH). For 2-AG, diacylglycerol lipase enzymes (DAGL) play a central role in production, while monoacylglycerol lipase (MAGL) is responsible for much of its degradation. These enzymes help determine when signals appear, how strongly they act and how quickly their activity ends. 

 The ECS participates in numerous physiological processes, including appetite regulation, stress responses, sleep, memory, immune signalling and pain modulation. However, describing it as a universal system that simply “restores balance” can be misleading. Biological regulation is considerably more sophisticated. Endocannabinoid activity varies between tissues, changes over time and interacts with many other signalling networks. Increasing cannabinoid receptor activity is not automatically beneficial, just as reducing it is not automatically harmful. 

 The relationship between CBD and the ECS is equally complex. Unlike THC, CBD has relatively low affinity for the classical cannabinoid receptor binding sites. Its biological effects involve multiple molecular targets and signalling pathways, some of which interact indirectly with endocannabinoid function. Many proposed mechanisms remain under investigation. 

The discovery of the ECS transformed cannabinoid research from the study of plant compounds into a much broader investigation of human physiology. For anyone interested in hemp and cannabinoids, the essential lesson is that the ECS already exists and functions independently of cannabinoid consumption. Plant-derived cannabinoids enter an established and highly regulated biological signalling environment. Understanding anandamide, 2-AG, CB1, CB2 and their associated enzymes provides a far stronger scientific foundation than simply claiming that CBD “balances the body.” The real fascination lies not in a miraculous biological switch, but in the remarkable precision with which our cells communicate, adapt and regulate their activities every day. 

Dr. Peter Verdegem, Ph.D., MBA