What are 2-AG and anandamide?

2-AG (2-Arachidonoylglycerol) and anandamide are compounds naturally produced by the human body. They are part of the endocannabinoid system (ECS) and interact with cannabinoid receptors to help support various biological processes. Known as endocannabinoids, these molecules are structurally similar to cannabinoids found in the cannabis plant, but are made internally.

In my recent years working with CBD and at Formula Swiss, I’ve spent a lot of time focusing on cannabinoids and how they relate to the body’s natural processes. Two that continue to catch my attention are 2-AG and anandamide—endocannabinoids made by the body itself.

As I’ve followed research and stayed close to developments in this field, I’ve seen how these compounds are linked to the body’s efforts to keep things in balance. The more I’ve learned about the endocannabinoid system (ECS), the more I’ve come to understand how it’s involved in many everyday functions.

Looking at how 2-AG and anandamide work has helped me appreciate just how complex and well-coordinated the body really is. By sharing some of what I’ve learned, I hope to give others a better understanding of how these endocannabinoids fit into that picture.

With both practical experience and ongoing research in mind, I believe we’re getting closer to a clearer view of how the body’s own compounds help keep things running as they should.

Key takeaways

• The endocannabinoid system was discovered in 1992 by Dr Lumir Hanus and Dr William Devane.
• CB1 receptors are primarily located in the brain, spinal cord and central nervous system, while CB2 receptors are found mainly in immune tissues.
• 2-AG and anandamide are endogenous lipids that interact with cannabinoid receptors in the body.
• The discovery of endogenous cannabinoids helped explain the natural function of cannabinoid receptors in humans.
• Both 2-AG and anandamide are synthesised on demand rather than stored in the body.

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The role of endocannabinoids in the ECS

I often consider how the discovery of the cannabis plant contributed to identifying and naming the endocannabinoid system (ECS). Compounds found in the plant share notable similarities with the body’s endocannabinoids. Research continues to investigate how the ECS may be associated with various natural processes.

What are cannabinoids?

Role of 2-arachidonoylglycerol (2-AG)

One molecule that captures my attention is 2-arachidonoylglycerol, commonly referred to as 2-AG.  A study from the Journal of Molecules found that it binds to both CB1 and CB2 receptors and acts as a receptor agonist, allowing it to send signals through the nervous system.

The Obesity Research & Clinical Practice journal has examined the presence of 2-AG in processes linked to appetite, blood pressure, and neural activity. 2-AG has also been identified in human breast milk, with studies examining its potential association with early physiological development.

Endocannabinoids and cognitive ageing research

The relationship between endocannabinoids and ageing remains a fascinating area of exploration. While there are still many unanswered questions, particularly around conditions that affect cognitive function, researchers continue to study how the ECS may influence normal ageing processes.

The intricate nature of the system indicates that endocannabinoids could play a role in influencing neural networks as time progresses, though additional studies are required to deepen understanding in this area.

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Communication between endocannabinoids and glial cells

Another point that stands out is the way endocannabinoids interact with glial cells. Unlike neurons, glial cells do not typically bind directly to CB1 receptors, which makes their communication mechanisms more complex.

A study by Bilkei-Gorzo et al. (2018) has shown that neurons may act as intermediaries, detecting disruptions and relaying information through CB1 receptors to influence glial cell responses. These findings offer valuable insights into how the ECS could be involved in maintaining a balanced internal environment within the nervous system.

Glial cells and 2-AG endocannabinoids

In mice, glial cells appear to detect disruptions such as bacterial infections and can alter their functioning in response.

During these changes, the body increases its production of endocannabinoids. Neurons respond by activating nearby CB1 receptors and relaying signals to other nerve cells while influencing immune responses. They also use proteins to send status updates back to the glial cells, helping to regulate inflammatory activity.

One of the key endocannabinoids produced and released by neurons during this process is 2-arachidonoylglycerol (2-AG).

What happens when the brain slows down endocannabinoid production?

The natural decline in endocannabinoid production with ageing has been linked to changes in brain function. Reduced CB1 receptor stimulation may affect glial cell activity and disrupt communication between neurons, contributing to increased immune responses and nerve cell damage. 

In Alzheimer's disease, advanced stages are associated with the loss of nerve cell populations.

Research by Bilkei-Gorzo (2012) highlights alterations in the endocannabinoid system during neurodegenerative conditions. Scientific interest has explored how phytocannabinoids such as THC and CBD interact with biological systems, including those involved in oxidative balance and inflammation.

What is THC (Tetrahydrocannabinol)?

Andandamide

I have found that anandamide, also known as arachidonylethanolamide, is one of the most studied endocannabinoids after 2-AG. It is derived from the unsaturated fatty acid arachidonic acid, which is found in significant amounts within the central nervous system.

Anandamide was first identified in 1992 by pharmacologist William Anthony Devane and analytical chemist Lumír Ondřej Hanuš. Its name is taken from the Sanskrit word "Ananda", meaning joy, delight, or bliss, a fitting reference to its role within the body.

Interaction with the endocannabinoid system

From what I have observed, anandamide interacts with CB1 and CB2 receptors, similar to plant-derived cannabinoids. At higher concentrations, it can even inhibit the effects of compounds such as THC within the endocannabinoid system. Although both anandamide and THC are highly fat-soluble, their molecular structures are quite different.

Production and stability

Anandamide is synthesised in tissues and cell membranes. In my review of the literature, I have noted two main pathways for its production: the combination of arachidonic acid with ethanolamine and the involvement of phosphodiesterase enzymes in tissue processes.

Despite its significance, anandamide’s strong fat solubility means it has a relatively short half-life within the body.

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Other receptor targets

Anandamide does not only interact with cannabinoid receptors. It also binds to other targets, including the TRPV1 receptor, sometimes referred to as the vanilloid receptor, according to a study by Zygmunt et al. (1999).

This receptor, present in sensory nerve cells throughout the central and peripheral nervous system, is associated with the detection of painful stimuli, heat, and sharp tastes.

Other endogenous ligands (endogenous ligands) in the endocannabinoid system are:

Anorexia and cachexia

I have seen how serious illnesses can severely affect a patient's eating patterns. Anorexia (loss of appetite or an increased craving for food) and cachexia (extreme weight loss combined with weakness and anaemia) are non-specific symptoms often seen in cases of autoimmune diseases, serious infections, and tumours.

In some situations, individuals dependent on psychoactive substances may also experience these symptoms. When not addressed over time, these conditions can lead to serious physical complications, sometimes requiring artificial nutritional support for recovery.

Which cannabinoids produce a psychoactive effect?

Impact on muscle mass and nutrient deficiency

Cachexia is associated with notable reductions in muscle mass and general declines in physical strength. Many individuals living with the condition may report feelings of fatigue, diminished physical capacity, and reduced overall well-being. Symptoms such as nausea, anxiety, and low mood are often observed alongside these physical changes.

Based on observations from scientific research, disruptions in the body's energy balance have been linked to potential deficiencies in key nutrients such as calcium, vitamin D, and phosphate. These imbalances may contribute to broader complications affecting bone and dental health.

Cognitive function and immune response can also be affected, although individual experiences vary. Continued research suggests that improvements in overall immune health may be possible following appropriate management and recovery strategies.

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Role of the endocannabinoid system

I have observed that the endocannabinoid system (ECS) is an area of interest in scientific studies related to hunger and physiological balance. One receptor, known as GPR55, has attracted attention for its involvement in regulating intracellular calcium levels in cells and neurons through cannabinoid interactions.

Researchers are investigating how this mechanism may relate to changes in the body's energy demands during illness. Anandamide, one of the body's endocannabinoids, has been studied for its interactions with CB1 receptors, with some research exploring possible associations with appetite signalling.

I have also seen studies suggesting a potential connection between the endocannabinoid system and energy metabolism, although further research is needed to clarify these findings.

The Endocannabinoid System (ECS)

Personal perspective

Over the past several years working with CBD, I’ve spent a lot of time following how research into the human endocannabinoid system has progressed—especially when it comes to 2-AG and anandamide. These two compounds are well known for how they naturally interact with CB1 and CB2 receptors as part of the body’s internal regulation.

From what I’ve seen, there’s a growing awareness among both professionals and everyday consumers about the importance of the body’s own cannabinoid production. It’s encouraging to see this shift in focus, as it leads to a more complete understanding of how the endocannabinoid system works—not just in relation to cannabinoids from external sources, but as a core part of how the body maintains balance.

How are new cannabinoids being discovered and classified?