2 of 3 Endocannabinoids

Jamie Hadfield

The term endocannabinoid may seem complex, but all it really means is ‘internal cannabis’. That’s the literal definition, at least, and also the most helpful when trying to conceptualize the biological role that endocannabinoids (eCB’s) play.

While many people now use CBD oil, and even more people have heard terms like ‘CBD’ and ‘cannabis’, few are aware that their bodies produce internal equivalents. Further, these endocannabinoids don’t just exist for their own sake. They play a critical role in regulating a system designed specifically for them. In other words, you might think of eCB’s as a gift that our physiology purposefully - intentionally - gives itself.

But what are Endocannabinoids, exactly?

For starters, they’re large, fat-soluble molecules. Their size and high molar mass means they stay relegated to the small areas in which they’re created. eCB’s are transient in nature: they bond to endocannabinoid receptors, send their message, and then dissolve back down into simpler components.  They’re also produced in nearly all parts of the body, nearly all the time. Wherever there is an endocannabinoid receptor, an endocannabinoid is also active, ready to fulfill its demands.

Perhaps the most important thing to remember about endocannabinoids is that they travel backwards. More precisely, they travel backwards across the synapses that exist between cells. In doing so, a positive feedback loop is created. This unique process is called retrograde signalling, and it’s integral to the smooth flow of other neurotransmitters. So integral, in fact, that Dr. Bob Melamede calls endocannabinoids “the oil of life”.

Endocannabinoids come from healthy fats - that means fats are their precursors, or building blocks. If you look at the endocannabinoid Anandamide, for example, you’ll see that its full name is Arachidonoyl Ethanolamide. The prefix refers to arachidonic acid, an essential omega six fat. Some leading researchers theorize that one of the reasons essential fatty acids are, well, so essential, is because they are needed to form our body’s preferred form of inner cannabis!

There are two main endocannabinoids that circulate within the body: 2-AG and Anandamide. Several other minor eCB’s also exist, but we’ll focus on the major ones for now.  


2-arachidonoyl-glycerol is the endocannabinoid of CB2 receptors. While that’s a simplification, it is accurate to say that both 2-AG and CBD ‘unlock’ CB2 and therefore possess some of the same health benefits.

2-AG has a ‘gentler’ affinity for ECS receptors than anandamide, but its higher concentrations within the brain, gut, and periphery mean it’s still very important.

Dr. Raphael Mechoulam, the godfather of cannabis research, found that 2-AG is involved in the initial stages of immune response and likely prevents chronic disease. 2-AG is also broadly anti-inflammatory, and has anti-cancer effects, too. Overall, think of 2-AG as the calming, adapting endocannabinoid.

Anandamide: The Bliss Molecule

Of the two main eCB’s, Anandamide was discovered first. A clinical-sounding term that gets its name from a humorous combination of the Sanskrit word “bliss” and the scientific suffix “amide”, Anandamide is produced and processed primarily in the brain. Its interactions with CB1 receptors there mean it’s responsible for a number of positive psychological functions.

Anandamide helps make a person sleep better after a long day; it helps someone relax when they’re subject to stress; it even helps one process difficult memories and selectively categorize information.

Anandamide’s delicate structure means it’s easy for the body to process.

Anandamide is also responsible for the phenomena known as ‘runner’s high’. Once thought to be caused by endorphin release, scientists now realize that eCB’s like anandamide are mostly to thank for post-exercise euphoria. As early as 2003, it was found that an intense workout can double circulating endocannabinoid levels. And when anandamide is high, mood and mental clarity usually are too.

Courtesy of the Journal of Cognitive Neuroscience and Neuropsychology


More than anything else, though, endocannabinoids exist to help deal with and overcome stress. Why else would anandamide be secreted after a tough workout? Could it be that endocannabinoids provide us motivation to endure positive stressors so that we can adapt and grow stronger?

Probably so. Endocannabinoids, by selectively becoming more active at the right times, allow us to respond to the harms of a stressful environment in the very moment they happen.

Following this principle to its logical end, eCB’s help our bodies appropriate stress correctly so that we grow stronger in the face of it - instead of getting sick and rundown. This concept is called hormesis.

Another example: you may have heard of free radicals. Also called reactive oxygen species (ROS) because they’re a byproduct of normal oxidative metabolism, free radicals are conditionally harmful. A little bit of them is good, while too many of them are detrimental and need to be counteracted with antioxidants like vitamin C. Excess free radical production, if left unchecked, leads to inflammation, chronic disease, and accelerated aging.

Endocannabinoids, as it turns out, actively ‘quench’ the metabolic dangers of free radicals. They do this largely by boosting the production of yet another helpful endogenous molecule, a ‘master antioxidant’ called glutathione. eCB’s are among the most effective ways to boost glutathione - even more potent than vitamin C!

The US government agrees, too, having stated that Cannabinoids have been found to have antioxidant properties...useful in the treatment and prophylaxis of wide variety of oxidation associated diseases…” when they applied for a research patent on the subject in 1999.

Keep in mind that the field of endocannabinoid research is still young. The ECS itself was only discovered in the early 90’s, and even today’s research studies continue to yield surprising new information. While the full number and role of endocannabinoids is unclear, we can be assured of one thing: that endocannabinoids fulfill a subtle but hugely important role in keeping every facet of our bodies in homeostasis.