Cannabis Research Series: The Endocannabinoid System

By Oscar Ortiz | April 08, 2016

Part 1: Cannabinoids

Endocannabinoid System: You don’t need to be a scientist to appreciate the grandeur and significance of the endocannabinoid system. You may have come across this term as debates around cannabis’ legalization have entered the mainstream media. But what does it mean, and why is it such an exciting discovery?

Some Basic Biology…

Before we get into the endocannabinoid system specifically, let’s cover some basic groundwork.

Neurotransmission is the process whereby our brains send and receive all the chemical messages that govern our physical and mental functioning. Neurons are specialized cells that carry these messages throughout the brain and body, and there are different types of neurons for different tasks – for example, motor neurons that control our muscle movements.

Neurons aren’t long strings that run continuously through the body; instead, they are like links in a chain with tiny gaps between each link, known as synapses. Neurotransmission occurs when electrical signals run along the neuron, and are then transferred across the synaptic gaps by chemical compounds called neurotransmitters. These chemical messengers come in a variety of ‘shapes’ depending on their molecular structure, and they act on specific receptor sites: think of it like a lock and key system, where only certain keys can open and close certain locks. When the right neurotransmitter meets the right receptor, the electrical impulse is carried on through the chain of neurons, and the body responds. Endorphins, for instance, are the ‘feel good’ chemicals released when we feel fear or pain, when we exercise, and even when we eat chocolate – and they’re actually the body’s ‘natural opiates’.

The Endocannabinoid System

Knowledge of how cannabis acts on the brain was fairly crude until recently. While researchers had begun discovering cannabinoids as early as the 1940s, it wasn’t until 1964 that THC was isolated and synthesized by Raphael Mechoulam and Yechiel Gaoni.

In 1973, scientists uncovered opiate receptors in the brain, and assumed that similar receptors for cannabis would be identified shortly after. But cannabinoids don’t act on our systems as opioids do, and it wasn’t until the late 80s and early 90s that cannabinoid receptors were finally mapped in the brain. And, surprisingly, “cannabinoid receptors turned out to be far more abundant in the brain than any other type of neurotransmitter.”[1]

In 1992, Mechoulam and William Davene discovered that the body produces its own cannabinoids; hence the term endocannabinoid (‘endo’ meaning ‘internal’). They named the first endocannabinoid ‘anandamide’, after the Sanskrit word for ‘bliss’ – as it turned out, this neurotransmitter worked on “the same pathways that offer feelings of security, comfort, or happiness that cause humans to seek social interaction, cozy homes, and sex.”[2] A second endocannabinoid was discovered – 2-arachidonylglycerol, or 2-AG – and the network of receptors and neurotransmitters was dubbed the endocannabinoid system (ECS).

But why was this such a groundbreaking discovery?

Firstly, we’re not the only ones with an ECS. In fact, it’s present in every animal except insects, and “this ancient, internal signal system started evolving over 600 million years ago (long before cannabis appeared) when the most complex life form was sponges.”[3] Contemplate that incredible fact next time you toke.

Secondly, the ECS is a neurotransmission system that operates in every part of the body, modulates our moods and appetite, and has the potential to impact a variety of health conditions – like arthritis, obesity, cancer, asthma, and Alzheimer’s, to name a few. Endocannabinoids are our bodies’ natural way of keeping us stable and healthy, and can be produced and released on demand, as we need them. Phytocannabinoids (cannabinoids derived from the cannabis plant), then, act on these same receptors, offer an array of therapeutic effects, and are more effective than synthetic cannabinoids like Marinol.

How Does the ECS Work?

Remember the lock-and-key metaphor? The ECS operates in the same way, where cannabinoids ‘open’ and ‘close’ specific receptors and cause specific effects. This system has many receptors, but two of the most studied receptors are the CB1 and CB2 receptors.

CB1 receptors are found mostly in the central nervous system (CNS) – which includes the brain and spinal cord – as well as in our connective tissues, glands, organs and gonads (testes and ovaries). CB1 receptors are stimulated by THC, the psychoactive phytocannabinoid, which is why we feel ‘high’ when we ingest cannabis. However, CB1 receptors also affect our moods, sleep, appetite, and pain reception. Targeting these CB1 receptors with cannabinoids can help us to control pain signaling, and researchers are investigating how cannabinoids can be used to treat metabolic syndrome and obesity. Studies have also shown that stimulating CB1 receptors enhanced mice’s taste response to a sugar solution, which may also contribute to an increased appetite (and why we get the munchies).

CB2 receptors are found mostly in the immune system, which controls our body’s defenses against diseases, so they are of obvious importance in the world of medicine. CB2 receptors are also found in the hematopoietic system, which include blood-making organs such as the spleen, lymph nodes, thymus, and bone marrow.  Although these receptors also respond to THC, they aren’t responsible for your high. Instead, their interactions with other phyto- and endocannabinoids impact the aforementioned systems, and research is being done into how we can treat inflammation, rheumatoid arthritis, various cancers, and even HIV/AIDS by manipulating CB2 receptors.

Interestingly enough, research also shows that one of the effects of cannabidiol (CBD) is to slow down the degradation of anandamide. This means that CBD actually keeps anandamide active in the body for longer, enhancing the natural protective benefits of the ECS.

The Future of Cannabinoids

The discovery of the endocannabinoid system has opened up new avenues of research in medical science, and we’re only just getting started. Beyond understanding how cannabis acts as a drug, we’re discovering more about how the body maintains a healthy balance, and how cannabinoids can combat hundreds of diseases. The complexity and beauty of our neurochemistry is just waiting to be unraveled, and we have the humble cannabis plant to thank for this burgeoning field of research.

[1] Martin A Lee, “The Discovery of the Endocannabinoid System,” The Prop 215 Era. 2010. PDF available at

[2] Alyson Martin and Nushin Rashidian, A New Leaf: The End of Cannabis Prohibition (New York: The New Press, 2014), 19.

[3] Lee, np.

Oscar Ortiz

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