Anandamide

Anandamide, also called N-arachidonoylethanolamine (AEA), is a lipid neurotransmitter that interacts with particular receptors in the body’s central nervous system. It is named for the Sanskrit word ananda, meaning “bliss,” which is why it is sometimes known as “the bliss molecule.”

What is anandamide?

THC (delta-9-tetrahydrocannabinol) is the most well-known compound, or cannabinoid, in cannabis, responsible for the plant’s psychoactive effects. It was first isolated in 1964 by Dr. Raphael Mechoulam and his team at the Hebrew University of Jerusalem. Once researchers discovered THC, they sought to investigate how the compound interacted with the body.

 

Decades later, the CB1 receptor was discovered. This receptor, part of the body’s central nervous system, directly interacted with THC, which indicated that there must be an endogenous or natural molecule in the body that also acted on the receptor.

 

 

In 1992, researchers William Devane and Lumir Hanus discovered anandamide, the first endocannabinoid to be found in the body. The discovery essentially meant that humans had a naturally-produced chemical similar to THC, which eventually led to the characterization of the endocannabinoid system.

 

The human body naturally produces several endocannabinoids, the most abundant being anandamide and 2-arachidonoylglycerol (2-AG).

How does anandamide work?

Anandamide acts as a part of the body’s endocannabinoid system, a complex system of lipids, enzymes, and cannabinoid receptors that play a role in maintaining homeostasis in many of the body’s automatic functions such as sleep, energy balance, and reproduction. The endocannabinoid system is one of the oldest biological systems in nature: it is known to have emerged before the evolution of vertebrates and exists across many species.

 

The ECS plays an active, dynamic role in keeping our cells and bodily systems functioning at their best. Unlike other kinds of neurotransmitter molecules, which sit in large pools waiting to be released, anandamide and 2-AG are produced on demand. Once a biological need stimulates their production, the endocannabinoids seek out their targets, namely the CB1 and CB2 cannabinoid receptors. CB1 receptors play a role in cognitive, sensory, and motor functions and are found mostly in the central nervous system where they are acted upon by anandamide and other cannabinoids like THC. The CB2 receptor is thought to play a more important role in neuroprotection and inflammation, and is mostly expressed in the cells involved with immune function.

 

Anandamide acts most prominently at CB1 receptors, the most abundant receptor of its kind in the brain. According to a 2019 human brain imaging study published in Neuroscience, CB1 receptors are clustered in the human frontal cortex, hippocampus, cerebellum, and basal ganglia. This evidence supports what has been seen previously in animals, confirming the roles of anandamide and the CB1 receptor in thinking, memory, sensory processing, movement, and more. Anandamide helps to regulate feeding behavior by creating a neural reward of pleasure whenever we eat, motivating us to do so again. Anandamide also plays a role in mood regulation, boosting happiness, reducing pain, managing stress, and regulating sleep, among many other bodily functions affected by the endocannabinoid system.

 

Anandamide has also been shown to bind to other targets in the brain including the CB2, TRPV1, GPR55, and PPAR receptors, according to a scientific review of anandamide’s functions published in Acta Pharmacologica Sinica and another review of anandamide’s potential target receptors published in Vitamins and Hormones. Per the studies, these receptors are all considered to be important components of the endogenous cannabinoid system. By acting at these targets, anandamide contributes to several functions such as anti-inflammation and neuroprotection, as shown in two animal studies published in Neural Plasticity and The Journal of Pain, respectively.

What happens when there is too little anandamide?

When the body has too little anandamide in its system, the condition is diagnosed as a clinical endocannabinoid deficiency. A review published in Cannabis and Cannabinoid Research linked many diseases to a deficiency of endocannabinoids, including migraines, fibromyalgia, and irritable bowel syndrome. Another in vivo study published in Molecular Autism found that children with autism spectrum disorder showed lower plasma anandamide levels on average.

What increases anandamide?

Some individuals naturally have more anandamide present in their systems than others. One large genetic study published in Springer’s Journal of Happiness Studies showed that some nations are happier than others, and that many residents of these “happier” nations share a mutation in the gene that makes the FAAH enzyme (the one that is responsible for breaking down anandamide). Because of this mutation, researchers think that the citizens of “happier” nations may have higher levels of anandamide because their bodies don’t degrade this molecule as quickly. This genetic study supports the notion of anandamide as the “bliss molecule.” 

 

Here are some ways to naturally boost levels of anandamide, according to research.

Exercise regularly

Many people are aware of the runner’s high or endorphin rush experienced after a particularly good workout, but the so-called rush of endorphins (our bodies’ natural opioid molecules) is only part of the story. 

runner's high
Endogenous cannabinoids acting at the CB1 receptor are crucial components of the runner’s high. (Photo by: Gina Coleman/Weedmaps)

A 2015 study in mice published in the Proceedings of the National Academy of Sciences found that endogenous cannabinoids acting at the CB1 receptor are crucial components of the runner’s high. The researchers found that after 30 minutes of continuous exercise, anandamide levels were increased in rodents and that elevated endocannabinoids were associated with anxiety relief and pain relief. This suggests that anandamide plays an important role in the brain’s reward circuitry and “glow” a person feels after working out.

Try some CBD

CBD is the second most abundant cannabinoid in recreational varieties of cannabis, and the primary ingredient found in hemp varieties of cannabis. One in vitro study published in the British Journal of Pharmacology showed evidence that CBD inhibits the activity of the FAAH enzyme (which breaks down anandamide), thus increasing anandamide levels in the brain. Another study published in Translational Psychiatry demonstrated that CBD enhanced anandamide signaling in humans with psychiatric disorders and improved their symptoms.

CBD tincture
CBD is the second most abundant cannabinoid in recreational varieties of cannabis, and the primary ingredient found in hemp varieties of cannabis. (Photo by: Gina Coleman/Weedmaps)

Eat a piece of dark chocolate

Research indicates that cacao stimulates the endocannabinoid system in two possible ways. An in vitro study published in Scientific Correspondence showed that chocolate stimulates cannabinoid receptors due to the presence of N-acylethanolamines that mimic cannabinoids. In this study, cacao also blocked the degradation of anandamide, potentially increasing its levels in the body. However, it appears that the cannabinoid-mimicking chemicals are only present in high-quality dark chocolate.

Find some black truffles

A 2015 study published in Phytochemistry discovered that black truffles carry both anandamide and endocannabinoid metabolic enzymes. However, as a fungus, black truffles don’t have a developed endocannabinoid system. The study authors conclude that anandamide’s presence plays a role in the truffles’ interaction with its environment, perhaps tempting animals with cannabinoid receptors to eat them, thus releasing their spores.

Eat fruits and vegetables

Kaempferol is a flavonoid found in fresh fruits and vegetables including grapes, apples, tomatoes, and broccoli. One study published in the British Journal of Pharmacology demonstrated that Kaempferol and other related flavonoids inhibited the production of FAAH, which breaks down anandamide. While the study concludes the levels of inhibition aren’t enough to have a significant impact on humans via dietary changes, it’s certainly another reason to eat healthy fruits and veggies.

Get Acupuncture

Although acupuncture medicine has been practiced for centuries, the mechanisms by which it relieves pain and other symptoms are not well known. Recent animal studies, including one published in the Journal of Pain, have shown that acupuncture stimulates the release of anandamide, which reduces pain by acting at the CB2 receptor. Much more research is needed, but the endocannabinoid system appears to play an important role in the medical benefits of acupuncture.