Cannabinoids And The Endocannabinoid System: How Do They Work?

by greenrush

Cannabinoids and the effects of medical marijuana is a hot topic.

It seems that not a day goes by without a new study revering cannabis as a miracle cure for an age-old disease.

But how exactly does marijuana work? What is it about this age-old plant that gives it the ability to curb pain and seizures and possibly even halt the growth of tumors?

Well, it all boils down to cannabinoids, unique chemical compounds found in the cannabis plant, and the way they interact with our bodies on a cellular level.

In this article, we take an in-depth look at cannabinoids, the endocannabinoid system, and show you how the two interact to create the unique effects of marijuana.

Cannabinoids, What Are They?

Cannabinoids are a unique group of chemical compounds that interact with specific receptors found in cells throughout the brain and body.

Cannabinoids can be divided into 2 main groups:
Endocannabinoids: These are compounds produced naturally within our body.
Phytocannabinoids: These are plant-derived compounds found in plants like cannabis.

Cannabinoids were first discovered in the mid-1960s when Dr. Raphael Mechoulam, a chemist, and professor at the Hebrew University of Jerusalem in Israel, first identified and isolated THC (or tetrahydrocannabinol).

THC is the main psychoactive compound found in cannabis and is responsible for producing the iconic “high” we feel when we consume marijuana.

This discovery marked the beginning of when modern science began to scratch the surface of how cannabis interacts with our bodies.

In the 1980s, US researchers finally found a receptor for THC located in the brain and central nervous system. This receptor was adequately named CB1.

The discovery of this receptor sparked a very interesting question; why was there a receptor located in our brains specifically designed to process THC?

In 1992, we got an answer to this question when Dr. Raphael Mechoulam, together with William Devane and Dr. Lumir Hanus discovered the first endocannabinoid, known as anandamide.

Anandamide is a neurotransmitter often referred to as the “bliss compound” because it stimulates feelings of joy, happiness, and euphoria.

In fact, despite having a different chemical structure to THC, anandamide also activates the CB1 receptor and, in doing so, produces very similar effects to THC yet to a much milder degree.

In 1993, researchers at Cambridge University discovered CB2, a second cannabinoid receptor. Unlike CB1, however, CB2 was found in higher concentrations throughout the body rather than the brain.

CB2 was mainly found in immune cells and peripheral nerve terminals and began to shine a light on how THC and other cannabinoids may affect our immune system.

Later, Dr Mechoulam, together with Dr. Lumir Hanus and Dr. Shimon Ben-Shabat, discovered 2-AG, or 2-arachidonoylglycerol, the second endocannabinoid found to date.

2-AG is believed to produce similar effects to CBD, or cannabidiol, a major non-psychoactive phytocannabinoid found in the cannabis plant.

Today, cannabis is believed to contain over 100 different cannabinoids. The two most iconic cannabinoids are THC and CBD, but there are plenty of others out there, including cannabigerol (CBG), cannabidivarin (CBDV), and cannabinol (CBN).

The concentration of these cannabinoids varies from one cannabis plant to the other. However, THC and CBD tend to be found in the highest concentrations while others are found in lower, even minute amounts.

What Is The Endocannabinoid System?

The discovery of cannabinoids and their receptors eventually lead to the discovery of the endocannabinoid system (or ECS).

The ECS consists mainly of CB1 and CB2 receptors, although new research shows that there may be a third CB receptor out there and that a wide variety of other receptors might also contribute to this system.

The system is involved in managing many physiological processes, including appetite, mood, memory, and the sensation and regulation of pain. It is also responsible for mediating the effects of cannabis produced by the interaction between phytocannabinoids and CB receptors in the body.

Given the scope of current research, the ECS is believed to be made up of 3 main parts:

  • Endocannabinoids like anandamide and 2-AG,
  • Enzymes responsible for breaking down these cannabinoids, such as fatty acid amide hydrolase or monoacylglycerol lipase, and
  • Cannabinoid receptors CB1 and CB2.

When we consume cannabinoids like THC and CBD or when our bodies produce cannabinoids like anandamide and 2-AG, they bind to either CB1 or CB2 receptors.

Let’s take THC as an example:

When you smoke marijuana, the THC present in the smoke enters your bloodstream via the lungs and is quickly transported to your brain.

Once in the brain, THC binds to its relative receptors and begins to affect the way that neurons in your brain communicate.

This can ultimately produce feelings of euphoria, relaxation, altered pain sensations, and an altered perception of time (all classic signs that you’re “high”).

How Can Cannabinoids Be Used As Medicine?

It’s important to remember that cannabinoids can do much more than just leave you giggly and rummaging through the fridge.

Recent research has found that cannabinoids like THC and CBD can produce a wide variety of medicinal benefits.

THC, for example, is known to be a very effective painkiller. When it binds to cannabis receptors in the brain, THC alters the communication between neurons that form part of the traditional pain pathways in the brain.

In effect, THC temporarily blocks these pain signals from reaching the brain as they would normally, ultimately relieving those painful symptoms for some time.

There are many studies that have looked at the efficiency of THC and other cannabinoids in relieving pain, and there is a strong general consensus among the medical community that cannabis is effective in pain treatment.

In 2016, for example, a study published in the Clinical Journal of Pain showed that cannabis effectively helped to reduce pain severity and the extent to which it interfered with the lives of over 270 patients.

The study also found that cannabis helped these patients become more functional and helped drive down the use of opiate-based painkillers by over 40%.

In 2010, Canadian researchers found similar results:

The researchers were working with adult patients with postsurgical neuropathic pain and required the patients to consume a single inhalation of a joint with cannabis (which contained roughly 10% THC) 3 times per day.

Even in such small doses, the study found that cannabis helped reduce pain intensity, improved sleep, and was generally well-tolerated.

Another cannabinoid that is highly regarded for its medical potential is CBD, which has been shown to reduce seizures in patients with epilepsy.

In 2015, researchers published an extensive study in The Lancet medical journal examining the effects of CBD on patients with refractory types of epilepsy such as Dravet and Lennox-Gastaut syndrome.

The study involved 214 patients who were treated with a 99% CBD extract (similar to the iconic Charlotte’s Web extract) and monitored for 12 weeks.

It found that the CBD extract reduced motor seizures by 36.5%, while 2% of patients became completely seizure free. However, it also noted that 79% of the patients experienced some side effects due to the treatment.

However, the medicinal properties of cannabinoids like THC, CBD and others aren’t just limited to treating pain and seizures. In fact, new research suggests that these compounds may help in treating a wide variety of physical and mental conditions, including PTSD; anxiety; nausea, vomiting, and wasting (common side effects of chemo and radio therapy); glaucoma and more.

In fact, the signaling of CB receptors has been noted to modulate a whole variety of physiological happenings, including analgesia, inflammation, appetite, gastrointestinal motility, and sleep cycles.

It is also known to affect the production and efficiency of immune cells as well as neurotransmitters such as serotonin and dopamine. New studies also suggest that certain cannabinoids have neuroprotective properties, which could be beneficial in treating neurodegenerative conditions like Alzheimer’s.

Cannabinoids are also believed to play a key role in homeostasis, a complex principal best described as the balancing of all of the body’s various functions to maintain stable conditions for survival.

This can include something as simple as maintaining body pressure, but can also go much deeper.

Imagine you come down with a fever: your body’s immune system suddenly goes into overdrive to fight the virus or bacteria causing your symptoms. Once the fever has passed, your immune system kicks back into regular gear and normality is restored to your body.

Endocannabinoids are believed to play a key role in turning down the heat on the immune system and slowly restoring a balance to your body (known as homeostasis).

The Future of Cannabis Research

When reading through the content of this article, it seems like we’re well on the way to understanding cannabis and the unique ways it interacts with our bodies.

However, the truth is we are just beginning to scratch the surface.

Most of the research we’ve discussed above has taken place within less than a century, and while some of the discoveries we’ve mentioned above are nothing short of groundbreaking, we still don’t fully understand cannabis, how it works, how it affects us, and how we can manipulate it as a medicine.

Luckily, new legislation and changing perceptions around cannabis are starting to change that, making it easier for researchers to investigate this plant and come to more concrete conclusions about how it can help potentially millions of patients across the globe.

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