All of the therapeutic effects of Cannabis are caused by its interaction with a unique system in the brain and body: The Endocannabinoid System (ECS). The ECS is one of the most important regulatory systems in all mammals and plays an important role in many basic functions, such as appetite, metabolism, memory, mood, sensitivity, sleep, pain, inflammation, and the immune system.

There is a large body of evidence that suggests the ECS can be altered to help people with an array of disorders: physical, mental, and metabolic. 

But before going into exactly how this system interacts with Cannabis, first I need to cover a little pre-requisite pharmacology and define some scientific terms. Bear with me – it’ll come back to Cannabis after the next section!

A drug is something you put into your body for a specifically desired effect. Drugs come in all different shapes and sizes; we’ve come to a point now where there’s almost a drug for everything. Interestingly, almost every drug shares the same interactions with the body and brain at a molecular level, no matter how different they may seem.

Simplified, it comes down to this: every human is run by billions and billions of microscopic machines and drugs can control specific machines at a molecular level to cause the desired effects in the human. Ready for the slightly less simple version?

Zoomed in all the way down to the cellular level (think about 1,000 times smaller than a penny) – drugs aren’t pills or liquids anymore, they are individual molecules. A molecule is any combination of atoms. A ten-miligram pill can contain over 12 Quintillion (a thousand millions) drug molecules! Some examples of drug molecules are shown below.

These drugs are designed so that they fit a certain target and the molecules float around your body until they find that target. Historically this has been called a “lock and key” fit, with the drugs as keys and their targets as locks. Except when a drug molecule finds its target, both drug and target change their shape slightly to fit together perfectly (think of a lock and key made of play doh, then smushing them together so there’s no air in between). Changing the shape of the “lock” is what eventually causes all the effects of the drug!

This is possible because almost all the “locks” in the human body are proteins. At the molecular level, proteins aren’t meat or even nutrition, but tiny machines that each have a specific “job” to carry out. Drugs can alter how well a machine is doing its job. The two main jobs are to receive/transmit signals and to carry out chemical reactions. We call the proteins that receive/transmit signals receptors; the proteins that carry out chemical reactions are called enzymes. 

Receptors and enzymes that work together regularly can be grouped into systems. The dopamine system, serotonin system, endocrine system, and endocannabinoid system are all examples!

Still with me? All right, time to get endogenous.

In the 1960’s when THC was first purified, we didn’t know what its target was. It wasn’t until 1990 that the first receptor target in the system was cloned, Cannabinoid Receptor 1 (or CB1). Shortly after, a naturally-occurring signaling molecule in the human body and brain was discovered that activated CB1 – the first endocannabinoid, anandamide (named after the sanskrit word for bliss).

Since then the system has been expanded to include other receptors, enzymes,and  another endocannabinoid, called 2-arachidonoyl glycerol (or 2AG). This entire system exists in every mammal and is extremely important in our everyday functions. Interestingly, anandamide has been found in chocolate, which means the evolutionary origin of the system could be from before plants and animals split!

Anandamide and 2AG are structurally very similar (shown below). They share a large fatty tail, called arachidonic acid. This fatty tail is the main difference between the endocannabinoid system and most of the other systems in the brain and body: instead of fat, others have salty, watery pieces attached to them.

 

This fatty tail means the entire system is located close to the membrane of cells (the outside skin, like the shell of an egg). It’s also likely one of the reasons the endocannabinoids move from one location to another by their own unique system called retrograde signalling.

Congratulations you made it to the mechanism – here’s where things start to get super interesting! In the brain, the ECS is the only major system that functions through retrograde signaling. This means that the endocannabinoids are synthesized at the postsynaptic cell and are transported to the presynaptic cell where they bind to the receptors and cause changes.

So everyone’s ECS is functioning at its own specific level, which is called “Endocannabinoid tone.” This is why different strains and different potencies will affect each and every one of us in a slightly unique manner. 

Glossary of Terms

(in order of appearance)

The ECS: The Endocannabinoid System is a system in the human brain and body that plays a key role in maintaining the balance of other hormones, neurotransmitters, and inflammatory cytokines.

Protein: On a molecular level, proteins are tiny “machines” that are very good at one specific “job.” When these machines do their jobs correctly, the human body functions normally.

Receptor: A protein