A smart person once told me that what we call psychology is only the biochemistry we did not fully understand yet. So today we will look at one small part of the biochemistry of happiness we do understand (at least in parts) : The Endocannabinoid System.
I should really call this article “Part 1 of a long series of articles about BLISS : The Biochemistry of Happiness”. This first part will be about one of the most important biochemical underpinnings of happiness, and at the same time one of the most underappreciated. We will check out how serotonine, dopamine, the sexual hormones, oxytocin, the endorphins and other substances influence happiness in later parts of this series.
When I wrote the book „Eishockey Performance“ I had two chapters dedicated to the natural production of two powerful drugs. Dopamine and Testosterone. Both are prohibited substances under WADA regulations if you substitute them externally, but what most readers did not realise at that time was that not only does our body produce these drugs in relevant quantities, but our bodies production of these powerful drugs varies a lot depending our environment and how we act. So we can basically dope naturally when we modify our behaviour to maximise natural synthesis of these drugs.
Testosterone and Dopamine are by far not the only powerful drugs our body produces. Some other heavy duty drugs that are part of our own biochemistry are melatonin (the most powerful anti-oxidant), adrenaline (a potent stimulant), cortisol (strong anti-inflammatory and immune modulator), and DMT (the most potent psychedelic drug), which is produced by our pineal gland and possibly plays a large role in dream formation.
Cannabis is not produced by our bodies. With its two primary cannabinoid substances Tetrahydrocannabinol (THC) and Cannabidiol (CBD), it is currently widely discussed for its effects on a wide variety of physiological processes including hunger modulation, anti-depressive effects, anti-epileptic effects, anti-inflammation, immune modulating effects and…happiness. But we do have something that is VERY similar to THC/CBD and in some aspects a lot more valuable and effective.
THE HUMAN ENDOCANNABINOID SYSTEM
THC and CBD from the Cannabis plant interact with Cannabinoid Receptors in our body (mostly found in our brain and immune system). These receptors have been discovered in the 1980’s by Allyn Howlett. Because the only substance we knew of (at that time) that interacted with these receptors was from cannabis, we called them cannabinoid receptors.
Now this is really weird. One of the most abundant receptor types in our brain is for a plant substance??? Of course this sparks a lot of mystical discussion about the relationships of mammals and plants or even the development of a joint consciousness (pun intended) between plants and humans, but it turns out there is a much simpler explanation.
In 1993 it was discovered what these cannabinoid receptors were really for. The Israelian researcher Raphael Mechoulam discovered the substance that is being produced by the human body and interacts with these receptors. This substance was later called Anandamide. So what we call cannabinoid receptors are actually anandamide receptors that also interact with THC or CBD from the cannabis plant.
This receptor system is way older than the cannabis plant. It first evolved around 600 million years ago and governs many physiological processes of all mammals, including humans. It is responsible for the normal formation of bones, blood sugar, appetite and mood regulation, memory formation, and most other homeostatic processes.
If we are able to understand and modulate this underlying system we might actually be able to induce some of the same health benefits that cannabis can have without actually having to ingest cannabis.
ANANDAMIDE : THE BLISS MOLECULE
Ananda is the Sanskrit word for „Bliss“ or „Happiness“. Anandamide plays a central role in the human experience of „Bliss“. It activates mainly the CB1 receptor in the brain and this has many effects :
CB1 and Mood
Depression is related to low levels of anandamide. The levels of anandamide in the brain seem to have a large genetic component. This is mainly because the levels of the enzyme that breaks down anandamide are strongly genetically determined. This enzyme is called fatty acid amid hydrolase (FAAH) and the lower the levels of this enzyme, the fewer anandamide is being broken down, leading to higher anandamide levels in the brain. Interestingly it has been found out that the people in the world with the highest perceived happiness show exactly this genetic mutation, which leads to low levels of FAAH and therefore high levels of anandamide.
The nations in this world which rated themselves as „most happy“ include Ghana, Nigeria, Mexico and Colombia. People from these nations are also most likely to possess the genetic mutation in the gene variant rs324420 that leads to higher anandamide concentrations. Vice versa the people from nations that rated themselves as „least happy“ do not have this genetic mutation and therefore a lot less anandamide. These nations include China, Thailand, Taiwan, Iraq and Jordan.
Aside from anandamide sparking a feeling of bliss it acts by another path as well. Anandamide plays a role in being happy DESPITE of bad circumstances. People with higher anandamide levels produce less cortisol in response to stressful events. This means anandamide improves resilience.
Does this mean that people with the genetic variant that leads to low anandamide levels are doomed to a life of misery, depression and low resilience? No it does not. There are two main concepts by which the effects of anandamide can be increased independently of genetic predisposition.
- Increasing the synthesis of anandamide
- Increasing the density of CB1 receptors
Increasing the synthesis of Anandamide
The most straightforward way to increase anandamide is just increasing its synthesis. To improve the synthesis of ANY molecule in the body we have to make sure to have enough of its precursor, the stuff that its made of. When we want an omelette, we first need eggs, when we want Joghurt we first need milk and when we want Anandamide we first need fats. More specifically we need arachidonic acid. The chemical term for anandamide is arachidonoyl ethanolamide, because it is synthesised from arachidonic acid. Arachidonic acid is a type of omega-6 fatty acid. It is heavily involved in muscle growth and neurological development and can mostly be found in eggs, fish, chicken and beef.
Another fatty acid found in eggs, fish, chicken and beef has anandamide-like qualities. The omega-3 fatty acid docosahexaenoic acid can morph into a substance that functions very similar to anandamide. Fats are important for many functions in the body. They serve as substrate for most important hormones like testosterone and estrogen, they regulate inflammatory process and they are -at least in parts- also the substrate for BLISS.
Aside from increasing its precursor there are two other habits that increase anandamide levels. When we go really hard in training and run on our last pipe we experience a feeling of „bliss“ we usually call „runners high“. It was long speculated that this feeling is induced by endorphins, but in 2015 a research team from Germany found that that can’t possible be true, because endorphins are too large to pass the blood-brain barrier. This same research team also found out that „runners high“ was created in large by anandamide. This runners high leads to a feeling of fulfilment, reduces anxiety and reduces sensitivity to pain. All because of anandamide.
The second habit that increases anandamide levels is cold exposure like a cold shower in the morning. Animal studies suggest it not only increases anandamide levels, but it also increases the density of CB1 receptors if used regularly.
Increasing the density of CB1 receptors
All of the previously mentioned strategies (Exercise, Cold Exposure, High Fat diets) also increase the density of CB1 receptors. With an increased density of receptors we need less anandamide to achieve the same effect of bliss. With a higher density our body becomes more sensitive to anandamide. This means we have a lower „bliss threshold“ and can more readily experience it.
It has been found that sunlight, especially UV-A rays will increase the density of CB1 receptors in some areas of the brain. This is an interesting mechanism of how sunlight improves mood I did not know of before researching for this article. We know of the effects of Vitamin D on mood, and how UV-B rays stimulate Vitamin D synthesis in the body, but this sunlight->CB1 mechanism highlights once more that it is a lot better to step into the sun than simply substituting Vitamin D.
Another interesting mechanism how CB1 density is increased is via Butyrate. Butyrate is a key nutrient for colon cells. Without butyrate they will inflame and die. Without butyrate they are also at a higher risk of cancerous modification. Simply speaking : Without butyrate our colon runs the risk of being inflamed (ulcerative colitis) and/or developing colon cancer.
Butyrate is naturally being produced by bacteria in our colon. These bacteria feed on dietary fibre, which is undigestible plant matter. Optimizing butyrate and the bacterial flora that produces it is a highly complex topic. I just attended a 3-day conference almost solely on that topic. The benefits of an optimised bioflora/butyrate system are enormous and have wide ranging effects on gut health, brain health, and in the treatment/prevention of autoimmune disease. The single best habit one can have in this context is eating plenty of plants. I prefer parsley and cruciferous vegetables like brokkoli, cauliflower and brussel sprouts. I love just munching on whole bundles of parsley. I also enjoy eating raw brokkoli for that purpose.
There are also some things to avoid, because they can decrease the density of CB1 receptors. The first and most important thing that reduces CB1 receptors is excessive cannabis use. And it makes sense. When we trigger our CB1 receptors with outside substances our body tries to balance the effect by reducing the amount of receptors for that outside substance. A similar thing happens when we eat too much sugar and our body down regulates insulin receptors to prevent our cells from being full of sugar all the time.
Other substances that reduce the density of CB1 receptors include Ibuprofen, Prozac, and Sugar. Its kind of ironic that substances that give us short-term relief (happiness in case of sugar and prozac and pain reduction in the case of Ibuprofen) actually reduce our chance of long-term relief by way of reducing CB1 receptor density.
Outlook on Happiness and the Endocannabinoid System
I will be interested to find out more about the connections of social relationships, sense of meaning, and gratitude with the endocannabinoid system, as we know these are huge factors in TRUE BLISS. But I am sure we will find that these „psychological“ concepts of relationships, meaning and gratitude will have biochemical representation in the endocannabinoid system as well. After all psychology is only biochemistry we do not fully understand yet.
Medical Considerations in THC treatments
Wouldn’t it be very smart to improve the internal efficiency of our endocannabinoid system via maximisation of CB1 receptors before we start treatment with external cannabinoids? With all the knowledge about the endocannabinoid system I feel it is the responsibility of every medical practitioner to educate the patient on habits that influence the efficiency of the endocannabinoid system. Treatment with cannabinoids can in my opinion only prove successful in the long run when the efficiency of the endocannabinoid system is not sacrificed at the same time.
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Gerrit Keferstein is a Medical Doctor specialised in Performance & Functional Medicine. He is most known for his work on the optimisation of recovery and adaptation in elite athletes.
