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Anandamide: How Cannabis Makes You Happy
7 min

Anandamide: How Cannabis Makes You Happy

7 min
Effects News

Anandamide, or AEA, is an endocannabinoid with a reputation for being a "bliss molecule". But, what exactly does this mean, and what is anandamide's relationship with cannabinoids like THC and CBD? Read on to uncover the mystery behind how cannabis makes you happy.

The cannabis plant has long enchanted scientists with a seemingly never-ending host of discoveries waiting to be unlocked—each more exciting than the last. But, perhaps most intriguingly, cannabis has helped us learn more about how our own bodies work. You see, in addition to plant-derived cannabinoids, there is another class of cannabinoids—those produced by the human body. So, what’s the secret behind anandamide, one of the two primary endocannabinoids holding the spotlight?

Below, we dig into the details on this "bliss molecule", including its action in the body, its relationship with THC and CBD, and just how cannabis is capable of making us feel happy.

What Is Anandamide?

What Is Anandamide?

Although THC, CBD, and other plant-derived cannabinoids—“phyto”-cannabinoids—are the ones we hear about most frequently, humans are another valuable source of these molecules. Endogenous cannabinoids—endocannabinoids—such as anandamide display unique actions of their own, and sustain significant interactions with plant-derived cannabinoids.

How Did Anandamide Get Its Name?

To begin any discussion on anandamide—aka AEA—it helps to explain the origin of its name. “Ananda”—sanskrit for “joy, bliss, and delight”—immediately hints at some of the key functions of this endogenous cannabinoid. “Amide” simply refers to the molecule’s chemical formula.

How Was Anandamide Discovered?

Interestingly, anandamide, and the other primary endocannabinoid 2-arachidonoylglycerol (2-AG), was discovered long after the discovery of phytocannabinoids like THC and CBD. In the early 1990s, upon determining phytocannabinoids were capable of binding with receptors in the human body, a research team led by Dr Raphael Mechoulam managed to isolate the first endocannabinoid in the human brain in 1992—anandamide.

How Does the Body Produce Anandamide?

Anandamide’s biosynthesis stems from the production of its membrane precursor[1] N-arachidonoyl phosphatidylethanolamine (NAPE). This reaction takes place via numerous enzymes and molecular pathways, with neurons creating the substance as necessary. Natural levels of anandamide in the body are typically low, and the cannabinoid has a short half-life, meaning it leaves the body relatively quickly.

Why Is Anandamide Important?

Why Is Anandamide Important?

So, if anandamide naturally exists in low concentrations in the body, why are researchers so interested in it? This is where we can begin to enter a discussion on the endocannabinoid system.

Composed mainly of two cannabinoid receptor types—CB1 and CB2—the endocannabinoid system plays a homeostatic role in which it oversees a wide variety of bodily processes. When Mechoulam’s team (made up of Lumír Hanuš and William Devane) discovered that phytocannabinoids were capable of binding to these receptors, they were determined to get to the bottom of this relationship. As a result, they discovered that anandamide has a very similar binding affinity for cannabinoid receptors as one of the most abundant cannabinoids found in cannabis—THC.

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As partial agonists of CB1 and CB2, AEA and THC are both able to exert effects on the central nervous system and immune system, among others. Yet, despite the innate relationship between anandamide and CB1, THC’s relationship with the receptor is even stronger, catalysing much more significant chemical changes for a longer period of time. Anandamide is more fragile, and thus isn’t capable of causing a “high” like that of THC.

What Is Anandamide Responsible For?

As mentioned above, the word “anandamide” itself begins to describe one of its primary functions in the body. Indeed, the compound is found[2] in areas of the brain linked to pleasure, reward, and motivation. However, it is also found in areas relevant to learning and memory, feeding, and movement. Researchers have even found preliminary evidence of anadamide’s ability to make[3] or break short-term neural connections, potentially leading to benefits in learning and memory.

Generally, anandamide plays a homeostatic role. It is released by the brain as needed to help the endocannabinoid system run smoothly.

What Does the FAAH Enzyme Do?

Understanding the relationship between cannabis, anandamide, and the endocannabinoid system becomes clearer when we reveal how anandamide is processed. As mentioned, anandamide has a short half-life, and is quickly broken down into arachidonic acid and ethanolamine by an enzyme known as fatty acid amide hydrolase (FAAH).

As such, FAAH inhibitors are capable of elevating levels of anandamide in the body, which researchers are eager to exploit for potential therapeutic purposes. In fact, some people are born with a genetic mutation that significantly dampens natural levels of FAAH, leading to much higher concentrations of AEA in the body. The result? Potential improvements in mood[4], nociception, response to stressful events, and more.

While most people's natural levels of AEA are generally low, what if we were to boost the concentration? And, how would we go about doing so?

How Does Cannabis Affect Anandamide?

How Does Cannabis Affect Anandamide?

Cannabis has a multifaceted relationship with anandamide, as individual cannabinoids sustain dramatically different effects on the molecule. Let's examine how the two main cannabinoids—THC and CBD—impact AEA.

How Does THC Affect Anandamide?

THC and anandamide have a similar chemical structure, and both are partial agonists of the CB1 receptor; but when THC is consumed, it “hijacks” these receptors. Moreover, THC is capable of eliciting a much more dramatic response from CB1, manifesting in the characteristic “high” experienced by cannabis consumers.

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More specifically, THC alters functioning of the hippocampus, orbitofrontal cortex, cerebellum, and basal ganglia, causing changes in short-term memory and coordination, among others. It also stimulates the release of dopamine—much more than is produced naturally—a brain chemical involved in pleasure, reward, feeding, 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, despite having an indirect relationship with cannabinoid receptors in general. It all has to do with FAAH, which, as mentioned, is responsible for breaking down AEA—and the reason why anandamide doesn’t stay in the system very long.

Compellingly, CBD inhibits the breakdown of FAAH, causing anandamide to last longer in the synaptic cleft. This doesn’t cause a high like THC would, as anandamide’s binding affinity for CB1 doesn’t change, but it is able to exert its effects longer and with potentially more significant results.

Can Marijuana Make You Happy in the Long Term?

Can Marijuana Make You Happy in the Long Term?

The question of whether marijuana can make you happy in the long term is one rife with variables. Given THC’s similarity to anandamide, as well as the potential soothing properties of other cannabinoids like CBD, it stands to reason that cannabis use can help you nurture a better, more open outlook on life. Though THC’s release of dopamine is believed to be partially behind this effect, its similarities to AEA are arguably more crucial regarding potential long-term improvements in mood.

A qualitative study[5] on cannabis use in a Swiss male prison from 2009–10, published in 2013, alludes to this with its findings. Both the detainees and the staff reported positive effects associated with cannabis, including its ability to ease the prison experience, relieve tension, prevent violence, and act as a “social pacifier”. Access to marijuana was also believed to limit the use of harder drugs in the respondents. Negative effects of cannabis use included sleepiness, social isolation, and, under restriction, the use and trafficking of harder drugs.

Other anecdotal and preclinical studies suggest a potential spirit-lifting effect of cannabis that could help regulate mood in certain users. However, overuse of THC is believed to downregulate endocannabinoid activation—specifically, CB1 receptors in the central nervous system—making it more difficult to achieve the same feeling of pleasure over time at the same dose.

For this reason, it’s often recommended to enjoy strains with THC levels below 20%, and, if possible, with a good helping of CBD. This way, not only will you experience the benefits of THC, but you'll also raise natural levels of anandamide in the body thanks to CBD's inhibition of FAAH. Being “happy” is a lot more complicated than just a discussion surrounding anandamide and cannabis, but it ultimately leads to the conclusion that responsible weed use could help one look on the bright side.

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Other Ways to Increase AEA in the Body

Other Ways to Increase AEA in the Body

Aside from smoking or vaping THC-rich cannabis, augmenting anandamide levels in the body can be done with certain foods, activities, and even other cannabinoids. Some of these substances contain anandamide itself and/or inhibit FAAH, leading to naturally elevated AEA levels in the body.

1. CBD Extract

Yes, CBD extract, like that found in CBD oils, CBD capsules, and supplements, is one of the best ways to raise AEA levels in the body. As mentioned, this is down to CBD’s inhibition of FAAH, resulting in a slower breakdown of anandamide. In addition to this process, CBD engages with the endocannabinoid system in other ways, promoting overall homeostasis in the body.

It’s recommended to take CBD in extract form, as opposed to smoking or vaping, as dosing is made far easier, and it’s possible to consume larger amounts for a more significant impact.

2. Eat Certain Foods

Other Ways to Increase AEA in the Body: Eat Certain Foods

Various foodstuffs contain a wealth of unique compounds that can also impact AEA levels in the body.

  • Black Truffles

Black truffles are intriguing life forms independent of their effect on AEA, but here too they display something fascinating. Despite not containing any cannabinoid receptors themselves, winter black truffles[6] contain AEA and many of the metabolic enzymes involved in the ECS. Researchers believe this could be in an effort for the truffles to attract hungry animals to spread their spores.

  • Chocolate

In addition to containing caffeine, sugar, and theobromine, chocolate contains small amounts of anandamide alongside two compounds that inhibit its breakdown. This combination is thought to be partly responsible for the cravings[7] associated with chocolate.

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  • Maca Root & Galangal

Maca root, or Peruvian ginseng, contains macamides, which are FAAH inhibitors with a similar chemical structure to anandamide. Maca root is commonly used as a supplement, with a range of traditional and modern uses.

Galangal, which is closely related to ginger and turmeric, is commonly used in East and Southeast Asian cooking, and has several traditional applications of its own. It too is a FAAH inhibitor capable of raising AEA levels.

  • Kaempferol

Kaempferol[8] is one of the most potent FAAH-inhibiting flavonoids. Found in common fruits and vegetables such as apples, blackberries, grapes, peaches, raspberries, broccoli, Brussels sprouts, cucumbers, endive, green beans, lettuce, potatoes, spinach, squash, tomatoes, and green tea, it’s possible to raise anandamide levels just by maintaining a healthy, diverse diet.

  • Black Pepper and Long Pepper

Black pepper and long pepper both contain the alkaloid guineensine, which inhibits cellular reuptake[9] of both AEA and 2-AG. The compound is also believed to offer potential soothing properties via cannabinoid receptors. Interestingly, black pepper also contains the dietary cannabinoid/terpene caryophyllene, which binds to the CB2 receptor[10], producing positive effects of its own.

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3. Exercise

Other Ways to Increase AEA in the Body: Exercise

Exercise—specifically endurance exercise—has been shown to dramatically raise levels[11] of anandamide in blood plasma. This mechanism is believed to be partially behind the “runner’s high” phenomenon, which long posited dopamine as the sole chemical responsible for the euphoria and analgesia often experienced following activity. So, if you want to release more anandamide, alongside other endorphins, long-distance running, biking, and other endurance activities are a great bet.

4. Increase Oxytocin Levels

Oxytocin, dubbed the “love hormone”, may stimulate the release of anandamide in the nucleus accumbens, as demonstrated by a 2015 animal study[12] out of the University of California, Irvine. Oxytocin is naturally released by the pituitary gland during childbirth, intimacy (hugging, orgasm), social bonding, and in other instances. This means, activities like cuddling, or even yoga, may naturally increase levels of the sensual hormone.

Anandamide — The Bottom Line

Our knowledge of anandamide has come a long way since the endocannabinoid was first discovered, but there’s still a long way to go in learning how exactly we can use cannabis to help us feel happy in the long term. That said, by enjoying THC-rich cannabis in moderation, taking CBD oil, exercising, and enjoying a well-balanced diet, you can naturally boost your AEA levels!

Zamnesia

Written by: Zamnesia
Zamnesia has spent years honing its products, ranges, and knowledge of all things psychedelic. Driven by the spirit of Zammi, Zamnesia strives to bring you accurate, factual, and informative content.

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Disclaimer:
We are not making medical claims. This article has been written for informational purposes only, and is based on research published by other externals sources.

External Resources:
  1. A biosynthetic pathway for anandamide | PNAS - https://www.pnas.org
  2. General Chemistry Online: The Bliss Molecule - https://antoine.frostburg.edu
  3. The Endocannabinoid System, Our Universal Regulator - https://pdfs.semanticscholar.org
  4. Microdeletion in a FAAH pseudogene identified in a patient with high anandamide concentrations and pain insensitivity - https://bjanaesthesia.org
  5. Cannabis use in a Swiss male prison: Qualitative study exploring detainees’ and staffs’ perspectives - ScienceDirect - https://www.sciencedirect.com
  6. Truffles contain endocannabinoid metabolic enzymes and anandamide - ScienceDirect - https://www.sciencedirect.com
  7. Brain cannabinoids in chocolate. - https://escholarship.org
  8. Inhibition of fatty acid amide hydrolase by kaempferol and related naturally occurring flavonoids - https://www.ncbi.nlm.nih.gov
  9. An Endocannabinoid Uptake Inhibitor from Black Pepper Exerts Pronounced Anti-Inflammatory Effects in Mice - PubMed - https://pubmed.ncbi.nlm.nih.gov
  10. Frontiers | A Neglected Link Between the Psychoactive Effects of Dietary Ingredients and Consciousness-Altering Drugs | Psychiatry - https://www.frontiersin.org
  11. Endocannabinoids and exercise - https://bjsm.bmj.com
  12. ‘Love hormone’ helps produce ‘bliss molecules’ to boost pleasure of social interactions | UCI News | UCI - https://news.uci.edu

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