As you may already know, the unique chemical structure of the cannabis plant makes it one of the most interesting plants to research. There is always something new to discover – not only about the components that make it so unique, but also about the way it affects the human body.
That said, the psychoactive effects of cannabis are well-known and loved in the weed community. People have been using marijuana for recreational and medical purposes for ages, but only in recent decades have we been discovering the mystery behind its method of action.
Upon identifying its most important compounds – the phytocannabinoids THC (delta-9-tetrahydrocannabinol) and CBD (cannabidiol), it was also established that they interact with the human body in a very specific way.
THC is the main psychoactive compound that produces the well-known euphoric high. We know that THC binds to certain receptors in the body, but have you ever wondered about how exactly it does that?
In today’s article, we cover all the background on the workings of the endocannabinoid system and the way THC works with it.
What Is the Endocannabinoid System and What Is Its Role in the Body?
The endogenous cannabinoid system, or endocannabinoid system (ECS), is a large and organized neurotransmitter network located throughout the entire body. It regulates a wide range of biological functions, such as mood, appetite, sleep, stress response, memory, reproductive, immune, motor function, and thermoregulation.
The main role of the endocannabinoid system is to maintain homeostasis in the body, meaning to keep the physiological functions in balance regardless of the changes that happen in the external environment. Therefore, the ECS keeps the internal environment in the body stable and steady in response to outside stressors.
The Primary Components of the ECS
The endocannabinoid system is a complex system that consists of three important components that communicate with each other:
The endogenous cannabinoids or endocannabinoids are chemical compounds naturally produced by the body. They function as neurotransmitters, meaning, they deliver chemical signals that lead to a modulation of different bodily functions.
So far, scientists have discovered two major endocannabinoids – anandamide (AEA) and 2-arachidonoylglycerol (2-AG). The body produces endocannabinoids according to the needs of a specific function so they can help to keep the system running as it should.
The endocannabinoid receptors are a class of cell membrane receptors or neurotransmitters that belong to the G-protein-coupled receptor (GPCR) group. The endocannabinoids bind to them whenever a certain bodily function is disrupted and it signals that the ECS needs to get activated (and take action).
The endocannabinoid receptors work with three types of cannabinoids:
- Endocannabinoids – the cannabinoids produced by your own body;
- Phytocannabinoids – the cannabinoids produced by the cannabis plant;
- Synthetic cannabinoids – lab-produced cannabinoids used for pharmacological purposes.
The two major types of receptors that have been identified so far are the cannabinoid CB1 and CB2 receptors and they are located in different regions of the body (which means they help to regulate different functions).
The CB1 receptors are primarily located in the central nervous system (CNS). They were first detected in the brain, but it was later discovered that they can also be found in other organs and connective tissues.
The majority of CB1 receptors, however, are located in the hippocampus, basal ganglia, amygdala, cerebellum, and cerebral cortex. These parts of the brain are associated with cognitive performance (memory, learning, emotional reactions, decision making, etc.), mood (dopamine and serotonin secretion), sensory perception (taste, smell, touch, etc.), spatial orientation and coordination, appetite, and body temperature.
The CB2 receptors, on the other hand, are predominantly found in the peripheral nervous system, especially in the immune cells, and also in many organs such as the gut, spleen, liver, kidneys, endocrine glands, and reproductive organs. The CB2 receptors play a role in the anti-inflammatory and immune system response of the body.
The endocannabinoid 2-AG fully binds to both CB1 and CB2 (full agonist), meaning it triggers a more powerful response, while anandamide only binds to both receptors partially (partial agonist), and doesn’t trigger such a powerful response.
The enzymes break down the endocannabinoids once they have completed their action. There are two types of enzymes, one for each type of endocannabinoid. The enzyme fatty acid amide hydrolase (FAAH) breaks down anandamide, while monoacylglycerol acid lipase breaks down 2-AG.
How the ECS Works
Simply put, endocannabinoids are designed to fit with the cannabinoid receptors and activate them in order to initiate a certain course of action in the body.
When there is an internal function that needs to be balanced out, the body produces endocannabinoids from lipid cells. They travel through the bloodstream searching for receptors they can attach to and activate. The activation happens when the endocannabinoids attach themselves to the binding sites of the receptors which puts them into an immediate action. When their work is complete and the bodily process is back to normal, the ECS releases the enzymes to break down to endocannabinoids.
But, Here’s the Catch
The endocannabinoids and their receptors communicate a little differently than other systems in the body.
Typically, the neurons communicate with each other by exchanging intracellular chemical signals which tell the body what to do next. The neurons that send the signals are called presynaptic neurons, while the receiving neurons are called postsynaptic neurons. The chemical messages travel through a narrow space between the two, called a synapse, and once they reach their destination, they trigger a response that spurs the receptors into action.
The ECS, though, works backward. This means that the process actually starts from the postsynaptic neurons. When they get activated, the body starts producing endocannabinoids that travel “backward” through the synapse and into the presynaptic neurons where they bind to their chosen cannabinoid receptor.
This unique method of action allows the endocannabinoids to have control over what happens after a neuron is activated, which affects how chemical messages are sent, received, and processed.
How Does THC Interact With the Endocannabinoid System?
The phytocannabinoids present in the cannabis plant mimic the endocannabinoids that are naturally produced in the body. When you consume weed in its many forms, the cannabinoids travel through the bloodstream and find receptors they can bind to and modulate their function.
THC can bind to both the CB1 and CB2 receptors which makes it a full agonist to these receptors. However, the CB1 receptor is thought to be its main target. This is why the effects of THC can range from relieving pain to enhancing your senses and mood to causing side effects like anxiety and paranoia.
When you consume marijuana, THC takes over and it overwhelms the endocannabinoid system by interfering with the work of the natural cannabinoids in the body. This way, THC temporarily alters the function of some bodily processes, also known as “the high.”
Typically, the euphoria that comes with being high is a result of an increased production of dopamine, while the impaired sense of movement and coordination is a result of THC modulating different parts of the brain where CB1 receptors are located.
Does CBD Bind to the Same Receptors?
CBD does interact with the ECS, but in a different way than THC. In fact, it doesn’t bind to the receptors in the same manner, but it interacts with them indirectly. This means that CBD sits imperfectly within the receptors – it doesn’t activate them, but it limits the attachment of other cannabinoids. That said, CBD acts as an inhibitor to THC and prevents it from fully taking over and causing more pronounced side effects.
The endocannabinoid system is a smart and complex network within the body that regulates many processes. The cannabinoids present in the cannabis plant mimic the endocannabinoids produced by the body and modulate the function of the ECS.
THC, in particular, binds to both CB1 and CB2 receptors, with a focus on CB1. Through a unique interaction with the endocannabinoid receptors, THC can cause a variety of effects. CBD, on the other hand, interacts with the receptors indirectly – it causes an inhibition to the way other cannabinoids attach to the receptors.
NIDA. 2020, April 8. How does marijuana produce its effects?. Retrieved from https://www.drugabuse.gov/publications/research-reports/marijuana/how-does-marijuana-produce-its-effects on 2021, February 22
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