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Delving deeper into anandamide – the human THC

There’s a compound made by the human body that has a striking resemblance to the primary psychoactive compound in cannabis: THC. This endocannabinoid is known as anandamide, or the ‘bliss molecule’, with its name coming from the Sanskrit for bliss, which is ‘ananda’.

This compound is changing what we thought about humans’ history with cannabis, and it’s possible that our bodies were made to work with this plant. Anandamide can increase our appetite, make us happy, tired and contribute to several other feelings that we take for granted. In this post, we’ll showcase what scientists have found out about this intriguing compound.

Understanding anandamide (AEA)

Anandamide – a compound with many names. The “bliss molecule” moniker came from Dr William Devane, who found it when working with legendary Israeli cannabis researcher Raphael Mechoulam, who had earlier identified tetrahydrocannabinol (THC).

Anandamide (scientific name: N-arachidonoylethanolamine) is one of the two key endocannabinoids that operate in the endocannabinoid system (ECS) – the other being 2-AG (2-Arachidonoylglycerol). Endocannabinoids are the name given for chemicals produced endogenously that are similar to cannabinoids produced by marijuana.

There are more than 100 cannabinoids, or phytocannabinoids, in weed, and we know that the most important cannabinoids bind with receptors in the huge and critically important ECS.

A huge regulatory network of neurotransmitters and receptors, the ECS has great power over several physical and psychological functions. These include appetite, sleep pattern, cognition, fear, mood, memory, immune system response, the reproductive cycle – that just scratches the surface!

The endocannabinoid system is so critical, it’s amazing that we never found it before the 1990s. This network influences nearly all the body’s organs, which we can tell from the presence of cannabinoids virtually everywhere. The ECS helps keep the body and brain in tune, facilitated by endocannabinoids such as anandamide – it’s possible that endocannabinoid deficiency could be a factor in fibromyalgia, migraines and more.

Anandamide is the most famous endocannabinoid, but it is far from the most abundant in the endocannabinoid system – that honour goes to 2-Arachnidonoylglycerol (2-AG), which is nearly 200 times as concentrated as anandamide in the brain. But it appears that anandamide does its most useful work in the body’s central and peripheral nervous systems.

Scientists have an incomplete knowledge of what anandamide does, but researchers have identified a few key properties of this crucial endocannabinoid over the past few years. In the next section, we’ll five of those: memory, mental health, post-workout relief, pain relief and appetite.

1) Memory

At first glance, a chemical that makes you forget doesn’t sound like a very helpful one. But bear with us. Renowned author Michael Pollan queried Israeli cannabis researcher Dr Raphael Mechoulam about the true purpose of anandamide in a documentary.

Mechoulam was also of the initial view that a “drug for forgetting” is hardly an “adaptive” quality. We know the memory to help us survive – for example, we remember that fire is hot and not to touch it again if we burn ourselves. Therefore, how could forgetting be adaptive? Because we remember a lot of useless information and a lot of negative information – forgetting allows us to let go.

2) Mental health

The bliss molecule potentially helping with mental health sort of makes sense, but there’s now scientific research to back it up. Namely, a 2016 study which was featured in the European Neuropsychopharmacology journal. Researchers sought to examine the depressive behaviour of diabetic male rats by treating them with anandamide. When anandamide was block, the rats became more depressed.

Translational Psychiatry published a study in 2014 on rodents, which showed that stress-induced anxiety could be eased, and mood could be boosted by stopping anandamide breakdown. Tests on mice found that stress and anxiety worsened among those with low levels of anandamide.

3) Post-workout relief

Runners often report a “runner’s high” after a certain amount of running – perhaps this isn’t dissimilar to the high we get from using marijuana. Initially, endorphins were thought to be behind the mood boost of a “runner’s high,” but German research in 2015 revealed that endorphins can’t reach the brain as the molecules are too big, so get blocked by the blood-brain barrier. However, anandamide can navigate through this.

PNAS published the German study which revealed that cannabinoid receptors not only facilitate but are “crucial” for a runner’s high. Post-exercise, anandamide levels increase in the blood and can pass through the blood-brain barrier. Early evidence suggests anandamide lifts mood and reduces post-workout pain.

4) Pain relief

Anandamide also helps with pain relief. In 2013, a review was published amalgamating existing research on the endocannabinoid and how it influences pain and inflammation through two key receptors. The CB1 receptor is part of the ECS and reduces pain perception, whereas the TRPV1 receptor that anandamide also interacts with enables the body to feel heat-related pain and general pain.

Some studies propose that stopping anandamide breakdown could be a key pain management tool, and a good target area for drug researchers. It’s no surprise that some cannabinoids can slow and prevent the breakdown of anandamide.

5) Appetite

It appears that anandamide has some level of control over our appetite, and that this connection may go back to our earliest years. Anandamide is present in breast milk, so we are essentially taking it in from birth. Animal studies have given scientists reason to suggest that anandamide teaches the act of suckling to newborns.

Studies on rodents and anandamide revealed that doses of the compound encouraged them to eat extra. Contrastingly, stopping the flow of anandamide by sealing off receptors led to a fall in food consumption. A synthetic cannabinoid to stop weight gain by doing exactly this has been developed, but the severe psychological side effects associated with Rimonabant led to it being taken off the market – yet another lesson for researchers who should stick to real cannabis.

What influence does marijuana have on anandamide?

Anandamide wasn’t labelled the ‘human THC for the sake of it. This endocannabinoid is what usually connects to CB1 receptors, unless THC is also present and links up first. Anandamide also interacts with CB2. It’s slightly more complex, but THC and anandamide bind pretty much to the same points in the ECS.

Some research has shown THC to agonise CB1 and CB2 receptors. Therefore, instead of forming strong bonds with cannabinoid receptors, the connections are somewhat clunky.

THC’s half life is much longer than anandamide’s, meaning it stays in the body for longer. While anandamide breaks down after about half an hour, you can expect to find evidence of THC in your urine for up to a week after a single, moderate dose.

THC has a hijacking effect on cannabinoid receptors where anandamide would otherwise bind, however other cannabinoids form different types of bonds with these landing sites. Research into cannabidiol (CBD) has found that the compound may stop anandamide breakdown, thereby boosting the overall concentration of the chemical in the ECS. Furthermore, CBD is non-psychoactive, so won’t send you on a mind-bending trip. Other studies on CBD have shown the molecule to have an inhibitory effect on the FAAH enzymes, which contributes to the prevention of anandamide breakdown. CBD oil may reduce anxiety by promoting anandamide in the ECS.

Clinical Endocannabinoid Deficiency and anandamide

Genetics could have some involvement in how the body makes use of anandamide. Some people may naturally have higher levels of anandamide in their system – those people are incredibly lucky. Dr Richard Friedman, a clinical psychiatry professor at Weill Cornell Medical College penned an editorial for the New York Times which shed some light on the possible connection between anandamide and genetics.

He said that scientists have shown that a “genetic variation in the brain” is responsible for making some people less anxious than others. Such people also find it easier to forget scary and unpleasant memories. This fortunate genetic mutation means that anandamide levels stay consistently higher, giving the brain a regular supply of “human cannabis”.

The genetic variation also stifles FAAH, further protecting anandamide from degradation. Scientists have theorised that this mutation promotes better circulation of anandamide. People with increased levels of anandamide are usually more relaxed and tend to experience fewer stressful episodes.

However, not all of us are so lucky to have a genetic mutation that boosts anandamide. JAMA Psychiatry journal recently published a genetic study that identified a correlation between severe depression and dependence on marijuana. Some depression patients opt to self-medicate with cannabis, but it doesn’t work for everyone. Perhaps genetics have an important influence on how responsive our body is to cannabis therapy.

Dr Ethan Russo, a cannabis researcher and neurologist presented the concept of Clinical Endocannabinoid Deficiency (CECD) in 2008. Russo proposed that deficiencies in vital endocannabinoids such as anandamide could be the root cause of obscure, debilitating conditions. Studies into the medical efficacy of cannabis products in treating fibromyalgia, irritable bowel syndrome and migraines suggests these ailments could be caused by CECD.

Russo produced an updated and more complete review recently, where he suggested that the endocannabinoid system could have much wider implications. He argued that ECS imbalance could be linked to conditions such as Parkinson’s, post-traumatic stress disorder (PTSD), autism, multiple sclerosis and more. It’s interesting how the endocannabinoid system seems to have influence across the entire spectrum of illness.

Final thoughts

In cannabis, we have a plant that is made up of unique and incredibly therapeutic compounds that happen to regulate a hugely important system in our bodies. THC, the main cannabinoid in the herb, works as a direct replacement for the critical endocannabinoid anandamide. CBD helps to make existing endocannabinoids more expressive, rather than latching onto receptors.

In time, we should know more about how other cannabinoids interact with the ECS. THCV, a potent psychoactive compound has been found to have appetite-suppressant effects, while non-psychoactive CBDV exhibits strong anti-nausea properties. Our understanding of cannabis is improving, but we still only have basic knowledge of this complex plant.

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