How does cannabis get us high? When scientists started looking into it, their investigations led them to discover a previously unknown but fundamental biological system in our bodies.
Just like circulation, respiration or immune regulation, this system is so basic to life that it can be found in all animals except insects.
The endocannabinoid system, and how it was discovered, is just one of the incredible things featured in Science & Cannabis, a new documentary from The Nature of Things.
For millennia, humans have used cannabis as a medicine for all kinds of issues — even Queen Victoria relied on it to relieve menstrual cramps. Her physician, John Russell Reynolds, wrote in the Lancet: “When pure and administered carefully, [cannabis] is one of the most valuable medicines we possess.”
Cannabis is a complex plant with more than 100 active compounds, known as cannabinoids. The best-known cannabinoid is tetrahydrocannabinol (THC), which is responsible for the drug’s best-known effects. Feeling high? That’s THC at work. Many people have also heard of cannabidiol (CBD). CBD doesn’t get you high, but it may have a wide range of medical uses, including for reducing anxiety and inflammation.
Uncovering how we get high
Nobody knew the structure of THC until the 1960s when a young Israeli scientist, Raphael Mechoulam, wondered how exactly it got us high. He took the giant step of defining the chemical properties and structure of THC, setting the stage for the research that is having an enormous social, medical and economic impact today.
Still making important discoveries, Mechoulam, 92, is known as “the father of cannabis.”
In 1988, scientists learned that THC triggers specific receptors in the brain. They reasoned that these CB1 receptors must have evolved to be activated by something our bodies produced, and that THC hijacks the receptors when we use cannabis.
Then in 1992, Mechoulam’s lab discovered a new cannabinoid. But this one was produced in the brain, not the plant. Anandamide — whose name comes from the Sanskrit word ānanda, which translates to “joy” or “bliss” — is an endocannabinoid (“endo” meaning “inside”) involved in, among other things, the regulation of mood, pleasure and appetite.
When the THC from cannabis makes its way into the bloodstream, it eventually binds to the CB1 receptors, resulting in a high. What exactly does this high feel like? It can involve relaxation, euphoria and changes in appetite, but also sometimes confusion and an altered perception of space and time. THC’s impacts are varied: it can reduce anxiety, but in some cases it can instead increase it.
Our bodies are primed to respond to cannabis
Another receptor, CB2, was later found to be activated by a form of CBD produced by the body — a molecule with the much less sexy name of 2-arachidonoylglycerol (2-AG). 2-AG is involved in moderating appetite and mood, but may play a role in regulating inflammation and the immune system.
CB1 receptors are spread throughout the body, but they’re concentrated in the nervous system and the brain. CB2 receptors are mainly found in immune tissues in the spleen and thymus, but some studies have found them in brain neurons and other areas of the nervous system.
A person’s reaction to cannabis depends on their age, weight, metabolism and tolerance. And it also depends on the level of CBD in a product — CBD works against the psychiatric effects of THC, so a product with more CBD will provide less of a high than one with low CBD.
And the way you consume cannabis — whether it’s smoked, vaped or eaten — has a big impact too, as some methods can cause it to reach your bloodstream faster.
The discovery of a fundamental biological system
The discovery of the endocannabinoid system (ECS) changed much of what we thought we knew about how the human body works. It turns out the ECS plays a major role in regulating many basic biological and psychological systems, from cognition and memory to perception and pain.
Scientists have compared its function to a thermostat, which sends signals to change the temperature when needed: the ECS works to maintain balance in many of our body’s systems. For example, the ECS helps to regulate appetite by sending endocannabinoids that bind to cannabinoid receptors in the brain, resulting in hunger.
This system also plays a role in how we experience pain, releasing endocannabinoids that bind to cannabinoid receptors in the pain pathways of the brain and spinal cord. This system of endocannabinoids and receptors also modifies cognitive processes, mood, how we sleep, and even how we form new memories.
The discovery of the endocannabinoid system was huge. It has led to a greater understanding of almost all our physiological and cognitive processes. And in practical terms, it’s also opened up new avenues for the development of therapies for a wide range of health conditions.