Anandamide (AEA) is an important neurotransmitter in the endocannabinoid system, which helps regulate the flow of other neurochemical systems to keep your body and mind functioning smoothly — one medical expert called anandamide and the rest of the endocannabinoid system “the traffic cop” of neurological function.

This 3-dimensional schematic shows the endogenous cannabinoid neurotransmitter anandamide (AEA). AEA is made of hydrogen (white), carbon (gray), nitrogen (blue) and oxygen (red). This shape acts like a key in the lock of the cannabinoid receptors. Image courtesy of PubChem.

The endocannabinoid system, like any other chemo-electric system in your central nervous system, comprises molecules called neurotransmitters, which fit into molecular slots on the outer membranes of nerve cells called receptors. Anandamide is the most-studied endocannabinoid system neurotransmitter, and it interacts mainly with the neuroreceptor creatively named “cannabinoid receptor 1” or CB1– The CB1 receptors coded by the CNR1 gene.

CB1 receptors are embedded within the membranes of cells, allowing for extracellular and intracellular (i.e. outside and inside the cell) communication. The unique shape of the receptor allows it to successfully capture anandamide (an endocannabinoid) and other phytocannabinoids (like THC and THCv).

The endocannabinoid system (ECS) is named after cannabis because it was discovered as a result of studying the effects of marijuana on the brain and body. Researchers discovered anandamide is similar in structure to the main psychoactive component in pot, Delta-9 tetrahydrocannabinol (THC). Because THC is made by a plant outside the body, it’s called a phytocannabinoid, as opposed to AEA, which is an endocannabinoid.

Endocannabinoids come from the inside (endo)

Phytocannabinoids come from plants (phyto)

Because it’s chemical structure is similar to AEA, THC displaces anandamide in the CB1 receptors. Because the structure is slightly different than anandamide and because ingesting marijuana floods the system with THC, the phytocannabinoid fits into the CB1 receptor and activates it only partially (a “partial agonist”). This leads to the shift in perception and mood that most know as the marijuana high; this high is theoretically similar to what it would feel like if your body endogenously produced an overload of anandamide and/or its sister endocannabinoid 2-AG

anandamide neurotransmitters
A “synaptic gap” between two neurons (brain cells). Neurotransmitters like Anandamide are released into the synaptic gap by one neuron, where they bind to the receptors like CB1 on the other neuron and trigger intracellular reactions.

How do we know about anandamide?

Researchers discovered CB1 and CB2 receptors in the 1980s and confirmed their existence by research in the early 1990s. This led to a race to identify the ligand neurotransmitters which fit into the receptor. In a series of complex experiments using mouse testicles and pig brains, researchers in Jerusalem isolated and identified anandamide and published their initial findings in the late 1990s.

Anandamide is so named from the Sanskrit word ananda, which means bliss. This is because of the euphoric feeling described as the marijuana high by many users and also because of anandamide’s function in the nervous system.

The NAPEPLD gene is responsible for producing anandamide. It produces the catalyst your body uses to manufacture anandamide. The FADS1 gene also codes for precursors to arachidonic acid, according to Arachidonic acid is the base molecule for both anandamide and 2-AG (2-arachidonoyl glycerol), the other major endocannabinoid.

ananda means bliss in sanskrit
Ananda is the sanskrit word for bliss— a goal of meditation.

Anandamide and the broader ECS is one system that helps govern and temper emotional regulation. From things like the response to chronic stress, the development of post-traumatic stress disorder, or the emotional response to pain, sleep, appetite, mood… anandamide has a hand in most important human physiological functions. The ECS is also crucial for maintaining homeostasis — that is, maintaining an even, baseline body functioning. A perfect example of how anandamide and the ECS maintain homeostasis is the fact that unless something is wrong, your body temperature remains at about 98.6-degrees Fahrenheit. The endocannabinoid system has a hand in the feedback loop that governs your temperature regulation, partially through its interaction through TRPV1 receptors, scientists theorize.

How is AEA different than other neurotransmitters?

There are a few odd things about the endocannabinoid neurotransmitters. 

First, as mentioned earlier, they are fats. Most other neurotransmitter chemicals medical researchers have isolated and studied are made of amino acids or some other water-soluble base. Before the discovery of endocannabinoids and other lipid (fat) signalers, medical researchers didn’t think the brain could work right with loose fat molecules floating around. Cell membranes are made of fat, so fat molecules can pass in and out at any point, which scientists figured would screw up the works on a chemical level.

Weirder still: Anandamide and 2-AG run backward compared with other neurotransmitters. In nerve fibers — whether in the brain, spinal cord, or elsewhere — neurons are lined up end-to-end so the electrochemical impulse can travel along. 

The receiving end of the cell is called the dendrite and transmitting end is the axon. The space in between is called the synapse or synaptic gap. In a typical nerve impulse, the dendrite of the neuron receives neurotransmitters from the axon of the previous cell in the chain, which initiates an electrical impulse along the body (soma) of the neuron, which then releases neurotransmitters from the axon of that cell through the synapse to the dendrite of the next cell in the chain and so on.

a typical illustration of neuronal communication
In typical neuronal communications, a neuron (brain cell) will send an electrical impulse down to the Axon, which releases neurotransmitters to a synapse, where it can be picked up by receptors on the dendrites of other neurons and cause an electrical impulse in that neuron, starting the whole process over again.

Endocannabinoids Anandamide and 2-AG, however, are released from the dendrite and go back toward the axon — the opposite direction of the nerve signal — where they lock into CB receptors to help regulate the flow of other neurotransmitters.

An article in the journal Cerebrum described Anandamide and 2-AG as the “traffic cops” for other neurotransmitters. They maintain balance by regulating the supply of neurotransmitters exiting neurons.

If there is already enough of a particular neurotransmitter in the receiving neuron, the endocannabinoids can jam the transmitting neuron so it doesn’t sent more.

The same goes in the other direction; if a crucial neurotransmitter is missing from the post-synaptic neuron, the endocannabinoids can signal to the pre-synaptic neuron to squirt more into the synaptic gap to fill in the missing components.

This balancing act is why the endocannabinoid system is so regularly associated with homeostasis, and may even be the key to maintaining it.

Throwing this balancing act out of whack with phytocannabinoids can have significant impacts, given how pervasive the ECS is. That’s why cannabis has been proclaimed the closest thing to a panacea known to humans. It’s also why overuse or use among people at risk for schizophrenia, for instance, can have serious consequences.

Also, because AEA and 2-AG can’t be stored the same way other neurotransmitters (typically made of amino acids) are stored, they are thought to be created on-demand from components floating around in the cell membrane. Because of this, their effects, though powerful and crucial for nerve function, don’t last very long. Once they lock into the CB receptors, they get digested pretty fast. This concept plays a role in why cannabis-induced highs last only a couple hours as compared to other drugs like LSD, which produces highs that last up to 14 hours.

Anandamide is transported around with the help of fatty acid binding proteins (FABPs) in between cells. FABPs also delivered anandamide to the enzyme FAAH, which breaks down used AEA into smaller molecules for reuse or disposal.

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