Anandamide: Nootropic Compound That Makes You High

Definition

Anandamide also known as N-arachidonoylethanolamine (AEA), is a naturally occurring endocannabinoid compound that plays a significant role in the endocannabinoid system. It was first discovered in the early 1990s and has since been the subject of extensive research. Here is some information about anandamide’s formula, structure, and usage:

Formula

The chemical formula of anandamide is C22H37NO2. It consists of 22 carbon atoms, 37 hydrogen atoms, one nitrogen atom, and two oxygen atoms.

Structure

Anandamide belongs to the class of fatty acid amides. It is derived from arachidonic acid, an essential omega-6 fatty acid. Structurally, anandamide consists of a long hydrocarbon chain with a carboxamide group at one end. The hydrocarbon chain contains 20 carbon atoms and is known as arachidonoyl, derived from arachidonic acid.

Endocannabinoid System

Anandamide is one of the key endocannabinoids produced naturally in the body. It acts as a lipid signaling molecule and binds to cannabinoid receptors in the central nervous system and peripheral tissues. The endocannabinoid system, including anandamide and its receptors, is involved in various physiological processes such as pain regulation, mood, appetite, sleep, and immune function.

Probably everyone who has run more than 5 miles or who is professionally involved in athletics or skiing has at least once felt incredible, akin to euphoria, emotions towards the end of the distance and, especially, at the finish line. Along with general fatigue and a desire to fall apart on a nearby lawn or in a snowdrift, you are overwhelmed by an incredible feeling of either joy, or pride in yourself, or love for the whole world. This feeling is due to anandamide which is an endogenous cannabinoid.

What is it?

This cute molecule is actively produced in the body during a long run, and its name (or rather, the word “ananda” – is taken from Sanskrit and translates as “bliss” or “ideal happiness” (Skt. आनंद). “Runner’s Euphoria” – at least and an exclusively subjective concept, is by no means jargon of athletes, but a scientific term that describes the state of long-distance runners as an unexpected and pleasant feeling of joy and euphoria, relaxation, anxiety and pain relief.
Since all our emotions and sensations are nothing but the result of various biochemical processes in the body, this state also has a well-defined biochemical “underpinning”. Let’s try to figure this out.

For decades, it was believed that this condition was mediated by endogenous (formed within the body) endorphins produced during running, although all the associated neurobiological mechanisms were not fully understood. Endorphins are often referred to as “happiness hormones”. This is not entirely true, since formally they are still not hormones, but neuromodulators. A large amount of endorphins can put a person in a state of euphoria, hence the name.
In terms of action, endorphins are similar to opiates – narcotic derivatives of opium and opioids – drugs that have an effect similar to opium on the body. It is very interesting that endorphins can also be produced by unicellular organisms (for example, the ciliate Tetrahymena pyriformis and the amoeba Amoeba proteus). And what, the amoeba also has the right to be happy!
The production of endorphins is carried out in response to stress (long running is also a kind of stress) as a natural protective reaction of the body, causing an analgesic effect when bound to opioid receptors – the very ones that are affected by morphine-like drugs.

Euphoria: yay or nay?

Over time, the “endorphin hypothesis”, as the only one responsible for the runner’s euphoria, has been seriously criticized by researchers due to a number of inconsistencies. So, for example, the results, enzyme-linked immunosorbent assay determining the concentration of endorphin, were questioned. Since the structure of endorphin is very similar to some other neuromolecules, such as adrenocorticotropic hormone (which also rises during stress), antibodies for analysis could find and bind to the wrong antigens and substances that are needed.

Yes, and from a physiological point of view, it was not all smooth sailing. β-endorphins bind best to the μ-opioid receptors of the endogenous opioid system, which mediates those very sensations of euphoria and analgesia. At the same time, slight activation of the same endogenous opioid system also leads to respiratory failure, suppression of gastrointestinal motility, and some other effects that were clearly not observed in happy runners.

Gradually, researchers came to the conclusion that during prolonged exercise, the endocannabinoid system is also activated. In particular, not so long ago, a group of German scientists led by Peter Gass showed that during running, the level of both β-endorphin (an opioid) and anandamide (an endocannabinoid) increases in the blood.

Anandamide

Cannabinoids are found naturally in plants of the hemp family and are the active ingredients of hashish and marijuana. These cannabinoids are called phytocannabinoids. At the same time, our body is able to synthesize a number of substances that are very similar to them both in structure and in function. They are called endogenous cannabinoids or endocannabinoids and act as neurotransmitters, regulating a large number of vital biochemical processes in the central nervous system.

What does the mouse race tells us?


To support their hypothesis of cannabinoid happiness, the scientists did not stress the runners after the race, but conducted studies on their favorite subjects – laboratory mice. Overall, the mice in the test group ran almost 7 km on the wheel for several days, after which they were subjected to a series of biochemical and behavioral tests.

The runner mice also felt less pain and were less stressed, and also became lazier on the following days and ran much less than their control relatives, which indicated relaxation – one of the characteristic features of the runner’s euphoria. The only thing that remains beyond the control of the researchers is to understand whether the mouse is happy after running or not.

With regard to biochemical tests, indeed, the levels of a number of endogenous cannabinoids (anandamide, 2-arachidonoglycerol, palmitylethanolamide, oleylethanolamide, and arachidonic acid) in the blood plasma of runner mice significantly increased compared to control groups.

At the same time, if we “block” the action of the receptors that endocannabinoids bind to, preventing them from exercising their biological effect, then the sensitivity of animals to stress and pain became the same as before exercise, that is, it was cannabinoid receptors that mediated the withdrawal of anxiety and pain after a long running.

Are you addicted to running?


The questions why it happened so evolutionarily and a person enjoys running can probably be answered as follows: at the dawn of human development, the more actively an individual behaved, the more chances he had for survival, and running euphoria seemed to be an exceptionally useful evolutionary skill. Indeed, it has been proven that mice deficient in CB-1 receptors (cannabinoid receptors of the first type) on GABAergic neurons show much less running activity and are more passive, probably because they do not enjoy running and quickly lose interest in it. . And such behavior is unlikely to be the key to success when a bunch of predators are running around for whom you are food, and even when you yourself have to run for food.

So what happens: if cannabinoids, which can be called “internal drugs”, are actively produced in the body during running, then does regular exercise become addictive?

Research and Potential Therapeutic Applications

The study of anandamide and the endocannabinoid system has gained significant attention due to their potential therapeutic applications. Researchers are investigating the role of anandamide in various health conditions, including pain management, mood disorders, neurodegenerative diseases, and inflammation.

Understanding the mechanisms of anandamide action may lead to the development of novel therapeutic strategies targeting the endocannabinoid system. However, it is important to note that research in this field is ongoing, and further studies are needed to fully elucidate the therapeutic potential of anandamide

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