Anandamide and 2-AG: Unlocking the Secrets of Endocannabinoids 

Anandamide and 2-AG are important and less-known lipid signaling molecules your body naturally produces. They both serve as endocannabinoids, meaning they interact with the cannabinoid receptors in your nervous system, influencing various physiological processes and behaviors. Although they may seem quite similar at first glance, anandamide and 2-AG have distinct differences in their affinities for specific receptors, their abundance in the body, and their particular roles in regulating brain function regulation.

You might be surprised to learn that 2-AG is the most prevalent endocannabinoid ligand in the brain. At the same time, anandamide tends to have a stronger affinity for CB1 receptors, one of the main types of cannabinoid receptors source. Additionally, it’s worth noting that 2-AG can be found at significantly higher levels than anandamide within most tissues throughout the body, indicating that their functions may vary considerably in different areas source.

As you delve deeper into the roles of anandamide and 2-AG within your body, we must recognize that our understanding of these endocannabinoids is still evolving. Scientists continue to explore their relative contributions to various bodily functions and behaviors, as well as how they might be harnessed to develop new therapeutic interventions for a range of conditions source.


Anandamide, also known as N-arachidonoylethanolamine (AEA), is one of the two major endocannabinoids and 2-arachidonoylglycerol (2-AG). These endocannabinoids are naturally produced in the body and function as ligands for cannabinoid receptors. They play crucial roles in maintaining homeostasis and regulating various physiological processes in the nervous system.


The discovery of anandamide dates back to the early 1990s, when it was first identified as an endogenous ligand for cannabinoid receptors. Its name is derived from the Sanskrit word “ananda,” meaning bliss, as it produces a sense of well-being and happiness when binding to CB1 receptors in the brain.

Structure and Properties

IUPAC NameN-(2-Hydroxyethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide
Other NamesAnandamide, AEA, N-arachidonoylethanolamine
CAS Number94421-68-8
Chemical FormulaC22H37NO2
Molar Mass347.53 g/mol
AppearanceColorless, viscous oil
Density0.979 g/mL
Melting Point48-50°C

Anandamide is a lipid mediator structurally similar to arachidonic acid. It is synthesized from membrane glycerophospholipids and is degraded by enzymes such as fatty acid amide hydrolase (FAAH).

Function and Benefits in the Body

Anandamide acts as a neurotransmitter in the central and peripheral nervous systems. Its functions are mediated mainly through CB1 and CB2 receptors:

  • CB1 receptors, primarily found in the brain, are responsible for the psychoactive effects of cannabis and modulate the release of other neurotransmitters.
  • CB2 receptors, primarily found in immune cells, help regulate inflammation and immune response.

Some health benefits of anandamide include:

Health BenefitExamples
NeuroprotectionSupports neuron health and may prevent neurodegenerative diseases
Pain ReliefNatural analgesic that helps manage pain and inflammation
Mood ImprovementEnhances mood by inducing euphoria and reducing stress
Appetite RegulationPromotes appetite and contributes to healthy feeding behavior
Cancer Cell InhibitionMay inhibit the growth and spread of certain types of cancer cells
Cardiovascular HealthMay lower blood pressure and provide anti-inflammatory benefits

Sources and Ways to Increase Levels

Although anandamide is produced naturally in your body, some factors may help increase its levels:

  • Exercise: Physical activity has been shown to increase anandamide levels, resulting in the “runner’s high” experienced by some athletes.
  • Diet: Consuming foods rich in essential fatty acids, such as omega-3s, can support anandamide production. Examples include fish, walnuts, and flaxseeds.
  • Retention: Inhibiting FAAH, the enzyme responsible for anandamide’s breakdown, can help maintain its levels. Certain compounds, such as those found in chocolate, are known to have this effect.

Maintaining a healthy lifestyle, engaging in regular physical activity, and consuming a balanced diet may contribute to increased and sustained levels of anandamide in your body, offering a range of potential health benefits.



2-Arachidonoylglycerol (2-AG), alongside anandamide, is one of the major endocannabinoids discovered in the 1990s. These endocannabinoids play a crucial role in the functioning of the endocannabinoid system, which regulates various physiological processes in the body, such as pain, mood, metabolism, and stress response.

Structure and Properties

2-AG is an ester of arachidonic acid and glycerol. It acts as a full agonist of both cannabinoid receptors, CB1 and CB2. The following table summarizes its physical and chemical features:

IUPAC namesn-Glycerol-1-(5Z,8Z,11Z,14Z-eicosatetraenoate)
Other names2-Arachidonoylglycerol
CAS Number53847-30-0
Chemical formulaC23H38O4
Molar mass378.55 g/mol
AppearanceColorless or pale yellow oil
Density0.979 g/cm³
Melting point-49 °C (-56.2 °F)

Function and Benefits in the Body

2-AG, like other endocannabinoids, plays a significant role in the body’s natural pain regulation, memory, mood, and appetite. The following table lists some of the key health benefits associated with 2-AG:

Pain relief2-AG activates cannabinoid receptors, which help in reducing inflammation and neuropathic pain.
Stress reliefIt modulates the release of stress hormones and neurotransmitters, promoting relaxation and stress reduction.
Appetite regulation2-AG stimulates appetite by activating CB1 receptors in the brain, which play a role in hunger and satiety signals.
NeuroprotectionBy reducing inflammation and oxidative stress, 2-AG can protect against neurodegeneration and help maintain brain health.

Sources and Ways to Increase Levels

Your body synthesizes 2-AG endogenously from the metabolism of arachidonic acid. However, certain lifestyle changes and dietary choices can help enhance the synthesis and efficacy of 2-AG:

  • Increase your intake of omega-3 and omega-6 fatty acids, precursors for endocannabinoid synthesis, through foods like fish, nuts, and seeds.
  • Exercise regularly, as physical activity has been shown to increase the production of endocannabinoids, including 2-AG.
  • Manage stress levels – chronic stress can impair the endocannabinoid system, so finding ways to reduce stress, like practicing yoga or meditation, may be beneficial.
  • Consider CBD (cannabidiol) supplements, which have been reported to boost the endocannabinoid system, including 2-AG levels.

Similarities and Differences between Anandamide and 2-AG

Comparison of Their Effects on the Body

Both anandamide and 2-arachidonoylglycerol (2-AG) are endocannabinoids that play essential roles in your body’s functions. They both interact with cannabinoid receptors, specifically CB1 and CB2 receptors, which are found throughout your body and play a part in pain, inflammation, appetite, and mood regulation, among other processes. While 2-AG is a full agonist at CB1 and CB2 receptors, anandamide is a partial agonist. This means that 2-AG has a stronger effect on cannabinoid receptors than anandamide (source).

Differences in How They Are Produced and Metabolized

Even though anandamide and 2-AG share similar functions in your body, there are differences between these two endocannabinoids in terms of their production and metabolism. They are both synthesized on demand, meaning they are not stored in the cell but are generated as needed.

Anandamide’s production usually relies on the cleavage of a precursor molecule known as N-arachidonoyl-phosphatidylethanolamine (NAPE), while 2-AG’s synthesis starts with diacylglycerol (DAG) (source).

After fulfilling their roles, both endocannabinoids are broken down by enzymes. Anandamide is metabolized by the enzyme fatty acid amide hydrolase (FAAH). At the same time, 2-AG is mainly broken down by monoacylglycerol lipase (MAGL) and, to a lesser extent, by alpha/beta-hydrolase domain-containing 6 (ABHD6) (source).

In addition to these differences in production and metabolism, anandamide also acts as an agonist for the transient receptor potential vanilloid 1 (TRPV1) receptors, while 2-AG does not have this function (source).

The Endocannabinoid System

The endocannabinoid system (ECS) is a complex cell-signaling system that plays a crucial role in regulating various physiological processes in your body. This system comprises several components: receptors, enzymes, and endogenous cannabinoids like anandamide and 2-AG.

Explanation of the Endocannabinoid System

Your endocannabinoid system (ECS) is primarily composed of three elements:

  • Endocannabinoids: These are endogenous lipid-based neurotransmitters, such as anandamide and 2-AG.
  • Receptors: The two main types of receptors in the ECS are CB1 receptors, predominantly found in the central nervous system (CNS), and CB2 receptors, predominantly found in your immune system.
  • Enzymes are responsible for breaking down endocannabinoids after they’ve fulfilled their purpose. Examples include fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL).

These components work together to maintain homeostasis, ensuring your body’s internal environment remains stable and balanced.

Role of Anandamide and 2-AG in the System

Anandamide and 2-AG are the two primary endocannabinoids involved in the ECS. Both molecules interact with CB1 and CB2 receptors to produce various physiological effects.

Anandamide is a neurotransmitter that acts on CB1 receptors in your brain and CB2 receptors in your peripheral organs (source). It plays a role in regulating mood, appetite, and pain sensation, among other functions. Anandamide has a similar structure to THC, the psychoactive component of cannabis, and can produce comparable effects.

2-AG is also an endogenous cannabinoid that interacts with CB1 and CB2 receptors. It has a higher concentration in your nervous tissue and may have a more significant role in analgesia and antinociception than anandamide (source). The levels of 2-AG can be influenced by exposure to substances like THC, ethanol, and opioids (source).

In addition to their interactions with CB1 and CB2 receptors, both anandamide and 2-AG can also interact with other receptors, such as vanilloid receptors, which are involved in pain perception.

The delicate balance of endocannabinoids, receptors, and enzymes within the ECS significantly impacts your overall health and well-being. Understanding the roles of anandamide and 2-AG in this complex system can help inform future therapeutic applications for ECS modulation.


Summary of the Importance of Anandamide and 2-AG

Throughout this article, we’ve explored the significance of anandamide (AEA) and 2-arachidonoylglycerol (2-AG), two of the primary endocannabinoids in the human body. While different in some aspects, these molecules share various pharmacological properties and play a crucial role in maintaining physiological balance.

Anandamide is known to be highly attracted to CB1 receptors, while 2-AG has a lesser affinity for the same receptors. On the other hand, 2-AG is more abundant than anandamide in most body tissues, making it an essential player in the endocannabinoid system. Both of these compounds contribute to mood regulation, inflammation control, and overall homeostasis in the body.

Final Thoughts on Their Role in the Body

As we wrap up, it’s essential to remember that research on the endocannabinoid system and its components, such as anandamide and 2-AG, is ongoing. Although considerable knowledge has been gained, areas still need further investigation, such as their precise mechanisms of action and potential therapeutic applications.

In conclusion, understanding and appreciating the roles of anandamide and 2-AG within your body helps you better comprehend your endocannabinoid system’s complex interactions and functions. Doing so can give you deeper insight into maintaining a healthy physiological balance and how these endocannabinoids contribute to overall well-being.