Anandamide: the path to a happy life
The cannabis plant has long intrigued scientists with a seemingly endless number of discoveries waiting to be unlocked - each more exciting than the last. But perhaps most interestingly, cannabis has helped us learn more about how our own bodies work. You'll see that in addition to plant cannabinoids, there is another class of cannabinoids - those produced by the human body. So what is the secret behind anandamide, one of the two primary endocannabinoids that attract attention?
In this text, we'll look at the details of this "bliss molecule," including its action in the body, its relationship with THC and CBD, and how cannabis is able to make us feel happy.
What is anandamide?
Although THC, CBD and other cannabinoids found in plants - phytocannabinoids - are the ones we hear about most often, another valuable source of these molecules is humans. Endogenous cannabinoids - endocannabinoids - such as anandamide, carry their own unique properties and have significant interactions with plant-derived cannabinoids.
How did the name anandamide come about?
To start any discussion about anandamide (or AEA), it helps to explain the origin of its name. "Ananda"-the Sanskrit term for "joy, bliss and pleasure"-immediately suggests some key functions of this endogenous cannabinoid. "Amide" simply refers to the chemical formula of the molecule.
How was anandamide discovered?
Interestingly, anandamide and another primary endocannabinoid, 2-arachidonoylglycerol (2-AG), were discovered long after the discovery of phytocannabinoids such as THC and CBD. In the early 1990s, while identifying phytocannabinoids that are able to bind to receptors in the human body, a research team led by Dr. Raphael Mechoulam, of which the Czech scientist Lumír Ondřej Hanuš was an essential part, succeeded in isolating the first endocannabinoid in the human brain - anandamide - in 1992.
(from left) Lumír Ondřej Hanuš, William Devan
How does the body produce anandamide?
The biosynthesis of anandamide is based on the production of its membrane precursor [1] N-arachidonoylphosphatidylethanolamine (NAPE). This reaction proceeds through a number of enzymes and molecular pathways, with neurons producing the substance as required. Natural levels of anandamide in the body are usually low and the cannabinoid has a short half-life, meaning it leaves the body relatively quickly.
Why is anandamide important?
So if anandamide exists naturally in the body at low concentrations, why are scientists so interested in it? Here we need to talk about the endocannabinoid system.
The endocannabinoid system is composed mainly of two types of cannabinoid receptors - CB1 and CB2 - and plays a homeostatic role in which it oversees a wide range of bodily processes. When Mechoulam's team (consisting of Lumir Hanush and William Devan) discovered that phytocannabinoids were able to bind to these receptors, they were determined to get to the bottom of this relationship. As a result, they found that anandamide has a very similar binding affinity to cannabinoid receptors as one of the most abundant cannabinoids in cannabis - THC.
What is the endocannabinoid system?
As partial agonists of CB1 and CB2, AEA and THC are capable of acting on the central nervous system and the immune system, among others. Despite the innate relationship between anandamide and CB1, THC's relationship with the receptor is even stronger and catalyses much more significant chemical changes over a longer period of time. Anandamide is more fragile and therefore unable to produce a psychoactive effect like THC.
What is anandamide responsible for?
Anandamide generally plays a homeostatic role. It is released by the brain as needed to help the endocannabinoid system (ECS) function smoothly.
As mentioned above, the word "anandamide" itself describes one of its main functions in the body. The compound is actually found in areas of the brain associated with pleasure, reward, and motivation. However, it is also found in areas related to learning and memory, food intake and movement. Researchers have even found preliminary evidence of anadamide's ability to make or break short-term neural connections, which could mean benefits in learning and for memory.
What does the FAAH enzyme do?
Understanding the relationship between cannabis, anandamide and the endocannabinoid system will become clearer as we uncover how anandamide is processed. As already mentioned, anandamide has a short half-life and is rapidly broken down into arachidonic acid and ethanolamine by an enzyme known as fatty acid amidohydrolase (FAAH).
As such, FAAH inhibitors are able to increase the levels of anandamide in the body, which scientists want to exploit for potential therapeutic purposes. In fact, some people are born with a genetic mutation that significantly suppresses natural FAAH levels, leading to much higher concentrations of AEA in the body. The result? Potential improvements in mood, nociception, response to stressful events, and more.
While natural AEA levels are mostly low, what if we increased the concentration? And how would we do that?
How does cannabis affect anandamide?
Cannabis has a multifaceted relationship with anandamide because the individual cannabinoids have dramatically different effects on the molecule. Let's take a look at how the two main cannabinoids - THC and CBD - affect AEA.
How does THC affect anandamide?
THC and anandamide have similar chemical structures and are both partial agonists of the CB1 receptor, but when THC is consumed, it "hijacks" these receptors. In addition, THC is able to elicit a much more dramatic response from CB1, manifesting a characteristic psychoactivity.
More specifically, THC alters the functioning of the hippocampus, orbitofrontal cortex, cerebellum and basal ganglia, causing changes in short-term memory and coordination, among other things. It also stimulates the release of dopamine - much more than is produced naturally - a chemical involved in pleasure, reward, food intake, sex and more.
How does CBD affect anandamide?
CBD, the other primary cannabinoid in cannabis, has a much more direct effect on anandamide than THC, although it has a generally indirect relationship with cannabinoid receptors. It all has to do with FAAH, which, as mentioned, is responsible for breaking down AEA and is the reason anandamide doesn't stay in the system very long.
CBD inhibits the breakdown of FAAH, resulting in anandamide lasting longer in the synaptic cleft. This does not cause psychoactive effects, as is the case with THC, because the binding affinity of anandamide to CB1 is not altered, but it is able to exert its effects for longer and with potentially more significant results.
Can cannabis bring a sense of happiness in the long term?
The question of whether cannabis can bring a sense of happiness in the long term is fraught with variables. Given the similarity of THC to anandamide and the potential calming properties of other cannabinoids such as CBD, it stands to reason that cannabis use may help cultivate a better and more open outlook on life. Although THC's dopamine release is thought to be partly behind this effect, its similarities to AEA are arguably more important in terms of potential long-term mood improvement.
A qualitative study on cannabis use in a Swiss men's prison from 2009-10, published in 2013, mentions this in its findings. Detainees and staff reported positive effects associated with cannabis, including its ability to ease the prison experience, relieve tension, prevent violence and act as a "social calmer". Access to cannabis also appeared to reduce respondents' use of harder drugs. Negative effects of cannabis use included drowsiness, social isolation, and under-restricted use and dealing of harder drugs.
Other anecdotal and pre-clinical studies suggest a potential effect of cannabis to boost spirits, which could help regulate mood in certain users. However, it is believed that overuse of THC impairs the activation of endocannabinoids - specifically CB1 receptors in the central nervous system - making it difficult to achieve the same feeling of pleasure over time at the same dose.
For this reason, it is often recommended to use varieties with sufficient levels of CBD. In this way, the user will increase the body's natural levels of anandamide by inhibiting the FAAH of CBD. Being "happy" is more complicated than a simple discussion of anandamide and cannabis can encompass, but ultimately leads to the conclusion that responsible cannabis use could help one look on the bright side of the world.
Other ways to increase AEA levels in the body
In addition to smoking or vaporizing cannabis, certain foods, activities, and even other cannabinoids can be used to increase anandamide levels in the body. Some of these substances contain anandamide itself and/or inhibit FAAH, leading to naturally elevated levels of AEA in the body.
1. CBD extract
Yes, CBD extract, like that found in CBD oils, CBD capsules, and other supplements, is one of the best ways to increase AEA levels in the body. As mentioned, it is the inhibition of FAAH by CBD that leads to a slower breakdown of anandamide. In addition to this process, CBD acts on the endocannabinoid system in other ways and promotes overall homeostasis in the body.
It is recommended to take CBD in extract form, as opposed to smoking or vaping, as the dosage is much simpler and larger amounts can be consumed for a more pronounced effect.
2. Eating certain foods
Various foods contain a large amount of unique compounds that can also affect the levels of AEA in the body.
Black truffles
Black truffles are an interesting life form with no direct effect on AEA, but they show something fascinating here as well. Although they contain no cannabinoids
themselves, winter black truffles contain AEA and many metabolic enzymes involved in the endocannabinoid system (ECS). Scientists believe this could be due to the truffles' efforts to attract hungry animals to spread spores.
Chocolate
In addition to caffeine, sugar and theobromine, chocolate contains small amounts of anandamide along with two compounds that inhibit its breakdown. This combination is thought to be partly responsible for the cravings associated with chocolate.
Maca root and Galangal
Maca root, or Peruvian ginseng, contains macamides, which are FAAH inhibitors with a similar chemical structure to that of maanandamide. Maca root is commonly used as a supplement with a variety of traditional and modern uses.
Maca Root
Galangal, which is closely related to ginger and turmeric, is commonly used in East and Southeast Asia and has several traditional applications. It is also a FAAH inhibitor capable of increasing AEA levels.
Kaempferol is one of the most potent flavonoids inhibiting FAAH. It is found in common fruits and vegetables such as apples, blackberries, grapes, peaches, raspberries, broccoli, Brussels sprouts, cucumbers, chicory, green beans, lettuce, potatoes, spinach, squash, tomatoes and green tea. Thus, anandamide levels can be increased simply by eating a healthy and varied diet.
Black pepper and long pepper
Black pepper and long pepper contain the alkaloid guineesine, which inhibits the cellular reuptake of both AEA and 2-AG. The compound is thought to offer potential calming properties via cannabinoid receptors. Interestingly, black pepper also contains the dietary cannabinoid/terpene caryophyllene, which binds to the CB2 receptor and has its own positive effects.
3. Exercise
Exercise - specifically endurance exercise - has been shown to dramatically increase blood plasma levels of anandamide. This mechanism is thought to be partly behind the phenomenon of the "runner's high," in which dopamine has long been assumed to be the sole chemical responsible for the euphoria and analgesia that often come after activity. So if you want to release more anandamide along with other endorphins, long-distance running, cycling, and other endurance activities are great options.
4. Increasing oxytocin levels
Oxytocin, called the "love hormone," can stimulate the release of anandamide in the nucleus accumbens, as a 2015 animal study from the University of California, Irvine, showed. Oxytocin is naturally released by the pituitary gland during childbirth, intimate situations (hugging, orgasm), social bonding, and in other instances. This means that activities such as cuddling or even yoga can naturally increase levels of the sensual hormone.
Anandamide - Summary
Our knowledge of anandamide has come a long way since the endocannabinoid was first discovered, but much remains to be discovered about exactly how cannabis can help us feel happy in the long term. That said, by using cannabis, taking CBD oil, exercising, and eating a balanced diet, you can naturally increase your AEA levels!
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