Nutrition and neuroscience: Foods that feed your endocannabinoid system

Medical cannabis is showing the world that it has the power to help people get their lives back after a period of illness or due to a lifelong diagnosis. When we look at why medical cannabis has such a profound effect on so many people, we start to find there might be other ways to take advantage of the natural health-governing endocannabinoid system. 

You will notice similarities between some of these different chemical properties and structures as you read this article. That's because many of them contain similar building blocks, giving us clues about where we can further investigate to discover why they have the results they do.  

Can diet influence your endocannabinoid system?

The influence of diet on your health is unquestionable. If you're not putting the right stuff in, your body may encounter problems somewhere down the line. When you think of it, the human body is like one big organic walking chemistry lab. We are about to explore the effect of diet on the healthy functioning of your endocannabinoid system and learn why certain foods are so good for us. 

The endocannabinoid system was only discovered in 1989. Since then, scientists have begun to learn that many plants we eat regularly contain molecules that interact with the endocannabinoid system. We aptly call these dietary cannabinoids. 

So, is it the case that you can eat these foods, and they will give you the benefits of cannabis? No, not quite, and it shouldn't be misinterpreted as that. They definitely won't give you any psychoactive properties or even a jogger's high. However, there are clear health benefits that can be yielded from foods that stimulate your CB1 and CB2 receptors with beneficial results. 

THC and CBD are powerful phytocannabinoids that interact with the same receptors that endocannabinoids Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) have been shown to activate. Dietary cannabinoids not otherwise found in the body have a much lower affinity than endocannabinoids and phytocannabinoids. However, they still produce positive health effects when researched. 

Why don't many people know about the endocannabinoid system?

Education for doctors on the endocannabinoid system during their training is limited and brief. This is because restrictive cannabis laws prevented scientists from fully researching it for over 50 years. Talk about making up for lost time! 

Now that medical cannabis is legal and cannabis is a Schedule 2 drug, it opens up the floor for conversations around once-controversial and taboo topics. Doctors who want to learn about the endocannabinoid system and how cannabis medicine works generally have to take it upon themselves to fill in the gaps in their education, and there are increasingly more resources online to aid this. 

Once trusted members of the medical field openly talk about the endocannabinoid system on daytime TV, the public will finally know and understand how responsible it is for so many essential bodily functions and health reasons. When is it likely to happen? When there are more conclusive studies published providing the right information. Until then, it's left for people who know to disseminate the information to those we think will find it helpful. 

What are dietary cannabinoids?

Dietary cannabinoids are naturally occurring cannabinoids and receptor-binding molecules found in edible foods. Are they enough to produce cannabis-like effects? The Journal of Nature said no back in 1998. Though few people know about their positive dietary benefits, many have probably eaten them before without knowing it. You may even start to wonder if that's why you like certain foods so much. 

Anandamide (AEA)

Believe it or not, Anandamide is an endocannabinoid found in humans and all animals; it evolved before vertebrates and has been passed on to every living species. It plays a fundamental role in every major system in our body. Its natural abundance is not strictly limited to animals; it's also found in edible plants and fungi! 

When scientists first started looking at the endocannabinoid system in more detail, the first endocannabinoid they discovered was Anandamide. Endocannabinoids are lipid messengers telling your body to perform certain functions when needed, such as to control pain, inflammation and even appetite. Endocannabinoids have been discovered to play a governing role in most of the body's major functioning systems, including respiratory and significant reproductive functions. 

Anandamide is named after the Sanskrit word for bliss or joy - "ananda" coined with "amide". It is named this way because of the feeling anandamide creates in the brain. It sounds kind of fun!

A hidden gem in nature

So where can you find it? A world-famous delicacy, truffles are the fruiting body of an underground fungi species (tubor melansporum), and scientists have discovered they contain Anandamide. Interestingly, truffles do not contain an endocannabinoid system, and researchers have hypothesised that this is probably because Anandamide and other cannabinoids evolved before endocannabinoid receptors. 

Other theories suggest Anandamide influences the smell of truffles, which attracts the animals with endocannabinoid binding receptors that hunt them out, enabling them to continue spreading and reproducing through being disturbed and passed as waste. Pigs are famously used to hunt for truffles, and they just so happened to be the first animal that Anandamide was isolated in the brain of. Lastly, it is believed truffles might use Anandamide to help them mature. 

Fun fact: Truffles also contain around 15% melanin. Anandamide is responsible for melanin synthesis in human epidermal melanocytes. However, eating melanin-rich foods has no impact on your skin's pigmentation. It just indicates how many functions cannabinoids play a part in governing our bodies. 

You can also find Anandamide in tiny traces in cacao beans, which increases after fermentation due to metabolic processes. 

2-Arachidonoylglycerol (2-AG)

This one might take you by surprise to find in your food. Another abundant endocannabinoid, 2-AG, is found in relatively high levels within the human nervous system. It is an ester formed from the omega-6 fatty acid, arachidonic acid and glycerol. It activates the CB1 receptor and illicit (path)psychological functions, like cognition, emotion, energy, balance, pain sensation, neuroinflammation and retrograde signalling . 

Sadly, scientists did not give 2-AG an interesting name like its counterpart. However, that doesn't change the level of importance that it plays within our everyday functioning. 2-AG is significantly more potent than Anandamide and is a full-efficacy agonist. 

Scientists consider it a very important endocannabinoid. Not simply because of its role in synthesis but also because it has been discovered to be abundant in human breast milk, bovine, goat, and other mammal milk. How much 2-AG did they find? Small amounts but enough to count, 0.11ug/ml. A 150ml glass of milk would contain 16.5ug of 2-AG. 

It's interesting to think one of the first foods many of us eat contains cannabinoids vital for our essential functioning. 

Oleamide

Oleamide is not an endocannabinoid specifically; it is very similar, a fatty acid amide system activator. It is found alongside 2-AG and Anandamide in mammalian milk and is active at the CB1 receptor. Oleamide has a similar structure to Anandamide but has different functions and is known as a sleep-inducing agent. 

While oleamide has similarities to Anandamide, it can benefit it when it is present because it is also a fatty acid amide hydrolase inhibitor (FAAH). This means it prevents fatty acid amides from being broken down as quickly, allowing them to be pharmacologically active in the system for longer periods, increasing the chances of hitting a receptor. 

If you didn't think that 16ug of 2-AG in milk was significant, when it is in the presence of oleamide, it is longer-lasting, allowing it a greater chance to interact with the receptor. So, in essence, oleamide improves the effectiveness of Anandamide, 2-AG and other cannabinoids.

Eating to feed your endocannabinoid system

Cannabis oil may be hailed as a great discovery in health wellness and medicine in recent years. The CBD market has boomed, and medical cannabis is available on prescription. Everyone in the UK now has access to some form of cannabis oil product. Hemp seed oil has even tagged along on the journey because it contains high levels of essential fatty acids (EFA). EFA are precursor chemicals to arachidonic acid, a precursor to Anandamide and 2-AG. Other oils show similar properties to endocannabinoids and interact with CB2 receptors linked to the immune system.

Olive Oil 

Olive oil is known for its far-reaching health benefits. It is good for your heart, lowers inflammation, is an antioxidant, and lowers the risk of stroke in older people. It is a glycemic regulator, helping stabilise blood sugar, improving insulin sensitivity, and reducing overall calorie intake by improving satiety. It can lead to better bone density in old people by improving calcification and bone mineralisation, reducing osteoporosis. This may be why people live longer in Mediterranean countries. It's definitely food for thought. 

So why is it so good for us? Our good friends in the science lab have discovered that olive oil is full of olivetol and olivetolic acid, a building block for phytocannabinoids. Studies also show it activates the CB2 receptor, which plays a role in the immune system. It has opened up many pathways of exploration as to why it has so many health benefits, and the similar shape of the molecules to cannabinoids might play a part.

For people suffering from or at risk of obesity, which is a contributing factor to type 2 diabetes, oleic acid supplementation increased the endocannabinoid oleylethanolamide, which was associated with feeling satisfied and fuller sooner. Studies looking into obesity in mice have shown that feeding a diet enriched with olive oil significantly induced CB2 receptor expression and was able to control inflammatory and proliferative activity. It showed that olive oil was a key ingredient in a healthy eating plan. 

Abundant in nature

Olivetol and olivetolic acid are not just found in olive oil. It can also be found in the cannabis plant! The reported benefits of olive oil seemingly don't stop coming, almost like the endless flow of new studies into cannabinoids' potential health and wellness benefits. 

In synthesising phytocannabinoid CBGA, the precursor cannabinoid to THCA, there is an enzymatic reaction from the alkylation of olivetolic acid and geranyl pyrophosphate.

A study looking at the anticonvulsant effects of CBGA methyl ester and olivetolic acid in hypothermia-induced seizures in mice found that CBGA had greater brain penetration (13%) with low anticonvulsant effects compared to olivetolic acid, which only penetrated the brain at 1% but showed greater anticonvulsant effects similar to that of cannabidiol. 

This should not be translated into drinking a bottle of olive oil, sitting in a freezer, and not having seizures when you finally get hypothermia. It does help scientists learn about the neuroprotective and anticonvulsant effect cannabinoids and their building blocks may have. 

A deep-rooted history

Olive comes from the Greek word oil, indicating that it was the oil of the time. The oil tree. Archaeological evidence shows how long humans have been involved with olive oil and its purposeful production, with digs uncovering vast landfills full of broken and some still intact ceramic oil vessels from thousands of years ago. 

Because oil goes rancid within a season (especially in warm climates) and can harm health, pots couldn't be reused because they spoiled new oil that went into them. This means that people consume relatively fresh supplies of olive oil frequently, and fresh and extra virgin olive oils contain higher levels of the active compounds. 

Hemp Seeds & Omegas

Omega essential fatty acids have been discovered to play a vital role in human health. They can be found in seeds or nuts and their oils, fish, soybeans, avocado and Brussels sprouts. 

Hemp seeds are obviously very related to the cannabis plant, being as if you germinate them, that's what you end up with (if you have a licence or live in a part of the world that allows you to grow). Even if you can't grow it, you can probably buy hemp seeds from your local health food store or supermarket. 

Hemp seeds are considered one of the planet's healthiest superfoods, packed full of essential fatty acids, omegas 3 and 6, with macro and micronutrients. 

There's a reason we call them essential oils

Omegas are essential because your body cannot make them, so you must gain them from an external source. They are necessary for their role in heart and brain health, metabolism, joints, and inflammatory response, and an imbalance of them has been linked to serious chronic disease. 

Omegas 3 and 6 are fatty acids involved in the synthesis of endocannabinoids. Anandamide and 2-AG are synthesised from omega-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA). So, they are essential because they are the building blocks for some of the most important neurotransmitters in your body. 

There is something quite beautiful about the cyclical nature of hemp seeds from a plant that produces phytocannabinoids, which have the ingredients you need to produce your own endocannabinoids. 

Terpenes and flavonoids in your food

The flavour and scent compounds found in medical cannabis are also found in foods. Many have antioxidants, and others have been shown to have potent medical effects in interactions with the endocannabinoid system.

Kaempferol

Kaempferol is not an endocannabinoid but rather a dietary flavonoid. In multiple studies, Kaempferol has been shown to reduce the risk of chronic diseases such as Alzheimer's disease, Parkinson's, ischemic stroke, epilepsy, major depressive disorder, anxiety disorders, and neuropathic pain. 

Another naturally occurring FAAH inhibitor that slows down the breakdown of Anandamide, 2-AG and THC, this time one that vegans can happily gain access to! It is a polyphenol antioxidant in fruits and vegetables such as apples, blackberries, kale, beans, black tea and broccoli, just to name a few. Oh yes, it's also found in…you named it cannabis.

As a flavonoid, you may wonder what Kaempferol tastes like. It's bitter and is what gives rapeseed oil its bitter taste.

A powerful natural agent

It helps reverse increased levels of oxidative stress markers and inflammatory mediators in the prefrontal cortex, which can cause anxiety and depressive symptoms in people with major depressive disorder. 

It is a potent chemopreventive agent for cancer and modulates cellular signalling pathways linked to apoptosis, angiogenesis, inflammation, and metastasis. While taking care of the dirty work, Kaempferol also appears to play a role in preserving the vitality of normal cells, with evidence that it can have a protective effect. 

Apoptosis is the programmed cell death that all cells go through in their life cycle, but malignant cells have forgotten. Significant attention is being paid to this aspect in combination with Kaempferol's cell protective qualities because it offers a solution to the problem of chemotherapy treatments that damage normal cells during treatment. 

The primary benefits of having Kaempferol as part of a healthy diet are that it has protective properties, and maintaining a healthy system is the first line of defence against medical irregularities in the body. Researchers looking into using it to target already established cancers require a little more assistance to make it the effective treatment it can potentially be. Kaempferol has relatively poor bioavailability, but new developments in nanotechnology look like a promising pairing with this natural cancer-fighting agent.

Many cancers are lifestyle-related, with only 5-10% of cancers being caused by genetics. A healthy diet with preventative foods sounds like it could be a step in the right direction for sustained wellness. 

Beta-caryophyllene (BCP)

Beta-caryophyllene is a sesquiterpene found in the flowers and leaves of the cannabis plant and is reported as a dietary cannabinoid. BCP isn't confined to life just inside cannabis, though. It is contained in many other plants, such as cloves and black pepper, giving it its peppery taste. Hops, rosemary, cinnamon, and sage also have relatively high levels of BCP. 

Caryophyllene is among the most abundant terpenes in certain medical cannabis varieties.

BCP binds to the CB2 cannabinoid receptor in the body, and by doing so, it helps maintain a healthy inflammatory response. It promotes the health of the digestive system, skin, and liver. It is being looked at as a novel therapeutic tool in modern medicine. Still, anyone can include it in a healthy, balanced diet. 

A multifunctioning health food

Despite being a sesquiterpene and not directly a cannabinoid, beta-caryophyllene does bind to the CB2 receptor, reducing pro-inflammatory mediators (TNF-a, IL1β, IL-6 AND NF-Kb). That means it reduces metabolic oxidative stress and neurological diseases to lower inflammation. Scientists are seeing BCP showing benefits for obesity, nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH), liver diseases, cardiovascular diseases, diabetes, pain and other nervous system disorders. 

Diabetes is an issue affecting one in ten people over 40 in the UK, according to 2019 data. That's 3.8 million people with a diagnosis, 90% of those with type 2, a further 1 million people who are living without a diagnosis and a further 2.4 million at risk. Type 2 diabetes can be more easily controlled by maintaining a healthy diet and level of exercise. 

Beta-caryophyllene has been looked into as a potential treatment option for diabetes. 

Diabetes studies in mice and rats have shown this same CB2 receptor activation can have positive results in alleviating diabetic cardiomyopathy and supplementing BCP, decreasing blood glucose significantly and improving serum insulin levels. It also reduced the rise in inflammatory cytokines in the pancreas and plasma as well as an ability to alleviate hyperglycemia and protect β-cells by increasing insulin release.

The obscure and interesting

More research into plants and what happens when we eat them is bringing endocannabinoid interactions to the surface. Many of these interesting compounds have multiple functions, allowing scientists to explore how they can be adapted for more targeted uses. Health food companies have been quick to market some of their proposed effects, but do their claims hold up? 

Diindolylmethane (DIM)

We produce a compound in our bodies called di-indolylethane or DIM when we eat cruciferous vegetables. These include brassicas such as cauliflower, cabbage, broccoli and Brussels sprouts. Again, it isn't considered a cannabinoid, but it has shown cannabinoid receptor activity.

Two human prostate cancer models showed that DIM is both a CB1 and CB2 agonist, and it has a potential anti-proliferative effect on androgen-independent/androgen receptor-negative prostate cancer cell lines PC3 and LNCaP.

DIM is formed when stomach acids break down indole-3-carbinol found in the vegetables. It's become a popular health-food supplement due to its supposed immune-boosting properties and the fact that if you want to get the quantities you're looking for, you'd need to eat multiple large portions of vegetables throughout the day. 

Benefits for everyone

In women, it has also been studied, looking into its effects on oestrogen, where it was found to help maintain balance and even stimulate a beneficial form called 2-hydroxyestrone. It may also reduce the effects of another form, 16 alpha-hydroxyestrone, linked to weight gain and breast and uterine cancers. DIM inhibits the enzyme aromatase, which plays a role in converting testosterone to oestrogen. 

In men, DIM plays a role in prostate health, as proven by double-blind studies. It helps to protect it from enlargement and prostate cancer.  

In young people, it may help with acne. A Korean acne diet study looked into the frequency of vegetable intake and found it was significantly associated with the acne-free control group than the acne group consuming more hyperglycemic carbohydrates, processed meat and dairy products. Researchers believe it could be due to them containing multiple precursors of DIM. 

Lactobacillus 

Bacteria are having their time in the spotlight at the moment, and their full potential probably hasn't even been realised. Lactobacillus has become a bit of a hot-shot, with millions of supplements containing different strains and different strengths in different bottles of pills. 

The gut microbiome is being analysed, and scientists are exploring the properties and effects of the multitudes of bacteria present in the digestive system.

But did you know some lactobacillus strains increase endocannabinoid receptors in the intestines? Taking specific Lactobacillus strains orally induced the expression of mu-opioid and cannabinoid receptors in intestinal cells and mediated analgesic functions in the gut, similar to the effects of morphine. Researchers believe it poses a new approach to treating abdominal pain and irritable bowel syndrome (IBS). 

Partnering with nature

The endocannabinoid system regulates gut motility, permeability, and inflammatory responses. It is hypothesised that the gut-brain axis affects mental health by influencing stress-induced changes and crosstalk between the microbiota and intestinal endocannabinoid system.

It's good to point out that lactobacillus is found naturally in healthy soil and on the surface of grown plants. So, it is interesting that they are found alongside other naturally occurring compounds that are potentiated in some way by the presence of lactobacillus. 

Furthermore, in gardening and agriculture, lactobacillus is used to clean soil and help fermentation to increase organic bioavailable nutrients. It is a biostimulant boosting plants' immune systems and increasing flavour compounds such as flavonoids and terpenes; it is believed to modulate cannabinoid receptor activity, influencing the range of effects felt from different medical cannabis varieties. 

Alkylamides

You've most probably heard that Echinacea is good for when you've got a cold. It has a broad spectrum of uses in indigenous medicine, including pain and inflammation-reducing properties. The leaves and the roots have been used in indigenous North American medicine for thousands of years. It was not until 2006 that major discoveries were made into what the active compounds were and how and why they worked. 

It turns out they are extremely active with endocannabinoid receptors CB1 and CB2. 

Like cannabinoids, there are multiple pharmaceutically active alkylamides. The predominant ones studied are A1 (dodeca-2E,4E,8Z,10Z-tetraenoic acid isobutylamide), and A2 (dodeca-2E,4E-dienoic acid isobutylamide). They both bind specifically at the CB1 and CB2 receptors. A1 and A2 also bind to the CB2 receptor more strongly than the endogenous cannabinoids 2-AG and Anandamide. 

Interesting action on immunity

The CB2 receptor is heavily involved in the regulation of the immune system. It regulates cytokine synthesis to support immune function, so this could be why alkylamides found in Echinacea might be so helpful when you're feeling under the weather - although the science is still unsure if Echinacea actually prevents your cold from getting worse (as some over the counter products might suggest). 

More high-quality research is needed to discover how to harness the effects of alkylamides. In a review of nearly 2,500 people, alkylamides decreased recurrent respiratory tract infections and complications like pneumonia and tonsillitis, reducing the risk of ear infections.

Alkylamides are not only found in Echinacea. The wall herb pellitory, the Sichuan pepper, Gold Root, Paracress (the toothache plant), black pepper, maca and Cat's claw all have alkylamides and are all used in traditional medicine. However, it's important to remember that you cannot simply reapply the scientific data on isolated alkylamides and apply them to using plants that contain them. 

Food for thought

It's fascinating that so many plants and foods we've benefited from have an effect on the endocannabinoid system. And  we're only really starting to understand how they play their part in keeping us healthy in many different ways. 

Cannabinoids are more abundant in nature than we might think, and the endocannabinoid system isn't strictly limited to working with just endo or phytocannabinoids. If anything, the endocannabinoid system creates the illusion of excitement that other compounds so effectively work with it as a receptor system when it's just the language we have assigned to them. 

We also have a vanilloid receptor system, but we haven't seen the same kind of medical vanilla clinics or as a health food supplement for all things vanilla as we do for all things CBD. 

Dietary cannabinoids and their building block components are another part of maintaining a healthy diet. They should not be considered the answer to any or all of your health or medical problems. Seek medical advice if you are experiencing medical symptoms or prolonged health problems. The information in this article is not intended to replace or encourage you to try these foods instead of getting the attention you need.