Cannabinoid receptors: key to understanding the effects of cannabis

What are cannabinoid receptors?

Cannabinoid receptors are components of the cell wall that interact with cannabinoids. These receptors are involved in signal transmission and play a crucial role in the effects and therapeutic properties of cannabinoids, including cannabidiol or CBD and tetrahydrocannabinol or THC. By binding to cannabinoid receptors, cannabinoids can modulate various physiological and biochemical functions in the human body.

These receptors are part of the endocannabinoid system along with cannabinoids and cannabinoid enzymes.

You may never have heard of cell receptors or they may vaguely ring a bell from high school biology classes. However, understanding cannabinoid receptors is fundamental to understanding certain news about hemp and cannabis pharmacology. Below, we will explain what they are, how they work and what effects the different types of cannabinoid receptors have.

Definition of cannabinoid receptors

Cannabinoid receptors are cell membrane proteins to which cannabinoids are bound. Its function is to activate the endocannabinoid system and produce all its effects.

Without cannabinoid receptors, neither CBD, THC, nor any other cannabinoid would have any effect on the body. Therefore, they are an essential part of the endocannabinoid system.

This system plays an essential role in numerous physiological processes, such as modulation of neurotransmitter release, regulation of pain perception and cardiovascular function. Cannabinoid receptors are essential for the functioning of this system.

Functions of cannabinoid receptors

Cannabinoid receptors have a specific structure that allows them to bind to cannabinoids. You can imagine them as locks on cell membranes, which can only be opened by the right “keys”, which are the endocannabinoids produced by the body.

Cannabinoids in cannabis have also been found to act as keys, activating these cannabinoid receptors. When the cannabinoid receptors are activated, various changes occur in our body that give rise to the multiple effects of cannabinoids.

Importance of cannabinoid receptors

Cannabinoid receptors are of great importance in the investigation of the effects of cannabinoids. Depending on the type of receptor that is activated, cannabinoids will have different effects. This makes the difference between a cannabinoid like THC and one like CBD. Although both are psychoactive and affect the central nervous system, only THC has significant psychoactive effects, while CBD does not.

In addition, more and more substances are becoming known that modify the effects of cannabinoids by acting on cannabinoid receptors. These substances can potentiate or block the effects of cannabinoids. For example, there is talk of synergies between terpenes and cannabinoids in the full-spectrum CBD oil . Another interesting example is how CBD reduces the toxicity of THC.

In other words, cannabinoids do not act alone: their effects are the result of a complex interaction between cannabinoid receptors, enzymes and the cannabinoids themselves. Cannabinoid receptors, both CB1 and CB2, play an important role in the body and are responsible for the different effects of cannabinoids. Here is the exciting world of cannabinoid receptors and all that it implies about the endocannabinoid system!

Types of cannabinoid receptors

There are two main types of cannabinoid receptors: CB1 and CB2. The complexity of the subject of cannabinoid receptors lies in the fact that each type of receptor is distributed in the organism in different ways, and each one is responsible for different functions(1).

CB1 cannabinoid receptors

CB1 cannabinoid receptors are found primarily in the brain and are closely related to the psychoactive effects of THC. psychoactive effects of THC .

CB1-type cannabinoid receptors are distributed mainly in the brain, but also in many other parts of the body.

They are distributed in various brain regions (such as the hippocampus, basal ganglia, cortex, cerebellum and other regions of both the telencephalon and diencephalon), and are also found in other organs and tissues of the body such as adipocytes (fat cells), liver, lungs, smooth muscle tissue of the digestive tract, pancreatic beta cells (responsible for insulin release and blood glucose regulation), vascular endothelium (the lining of our arteries and veins), as well as the reproductive organs, in the immune system and in peripheral sensory nerves and sympathetic nerves in other parts of the body.

CB1 cannabinoid receptors appear to be involved in biological activities related to the cardiovascular system, gastrointestinal system and liver. Specifically, in the liver, it influences de novo lipogenesis (3). In addition, they seem to have an important role on pain sensation, olfactory memory and stress response (4, 5, 6, 7). These receptors are also responsible for the euphoriant and anticonvulsant effects of cannabis.

The presence of CB1 cannabinoid receptors in the cardiovascular system would explain one of the most well-known side effects produced by THC: lipotimia. Lipotimia is a brief loss of consciousness that occurs when the blood supply to the brain decreases, and can be caused by heavy marijuana smoking, as THC exerts a sedative effect on the walls of blood vessels (with many CB1 receptors).

The digestive system contains CB1 and CB2 cannabinoid receptors, which would explain the use of medical cannabis in cases of anorexia.

Moreover, the presence of CB1 and CB2 cannabinoid receptors in the digestive organs, which regulate nutrient absorption and energy balance, explain some of the therapeutic effects of cannabinoids. THC is widely recognized in medicine for inducing increased hunger and is therefore used in treatments for anorexia and debilitating diseases such as HIV and cancer.

CB2 cannabinoid receptors

On the other hand, CB2 cannabinoid receptors are located mainly in the immune system and in peripheral tissues, including the endocannabinoid system of the skin. These receptors are associated with anti-inflammatory properties and may play a role in pain relief and modulation of the immune response.

CB2 receptors are found in peripheral tissues, particularly in the immune system, and have been shown to have a strong ability to modulate the response of defensive cells.

Specifically, CB2 receptors are present in bone marrow cells, thymus, spleen, tonsils, T and B lymphocytes, monocytes, NK cells, PMNs and mast cells, all of which are key parts of the immune system. Stimulation of CB2 receptors has been associated mainly with pain relief and anti-inflammatory effects.

71% of CB2 cannabinoid receptors have been localized in lymph nodes.

Unlike CB1, CB2 receptors are almost absent in the central nervous system (CNS). Although CB2 has been detected in glial cells and astrocytes in the brain, its presence in neurons is unclear. Recent research suggests that the cannabinoid CB2 receptor may modulate emotions and be related to schizophrenia, anxiety, depression and memory.

CBD and cannabinoid receptors

As for CBD, although it does not bind directly to CB1 or CB2 cannabinoid receptors, it has been found that it can modulate the activity of these receptors and other related receptors(10, 11, 12). This partly explains why CBD can have diverse therapeutic effects and how it can influence the body’s response to cannabinoids.

How substances can interact with cannabinoid receptors

There are different substances that act on cannabinoid receptors. These interactions can be of different types:

  • Natural agonists: Endocannabinoids endocannabinoids are the natural agonist ligands of the cannabinoid receptors, because they are the physiological or endogenous substances (produced by our body) for which the cellular receptor is “designed”.
  • Agonists: Cannabinoids from cannabis and artificial cannabinoids are agonist ligands of cannabinoid receptors. An agonist is a substance capable of binding to a cellular receptor and eliciting a specific action in the cell, generally similar to that produced by a physiological substance. Although phytocannabinoids are structurally very different from endocannabinoids, they can bind to their same receptors. This union can be total or partial.
  • Allosteric modulators: Some cannabinoids (and other substances, such as terpenes) can partially bind to a receptor, modifying the shape of the receptor and its binding to cannabinoids. These are called allosteric modulators. Modulators can be positive (they increase the affinity of cannabinoids for the receptor and potentiate its effects) or negative (they decrease the affinity of cannabinoids for the receptor and diminish its effects).

CBD is an example of a negative allosteric modulator of the CB1 receptor. This means that their binding does not activate the receptor, but rather decreases its activity. Thus, CBD reduces the psychoactive effects of THC.

cb1 and cb2 receptors
Types of interactions between substances and CB1 and CB2 cannabinoid receptors. Adapted from source.
  • Antagonists: Finally, there are cannabinoid receptor antagonist ligands, which are molecules that block the receptor, preventing cannabinoids from binding. It is a natural self-regulation system of the cells, to limit the excess activation of these receptors, but it can also be used pharmacologically to mitigate the effects of cannabinoids. Antagonists can be competitive (competing with cannabinoids to bind to receptors) or non-competitive. They can also be reversible or not…

So far the main interactions with cannabinoid receptors. Similar interactions also occur with cannabinoids, and with the enzymes that degrade them. At this point, the reader will be able to imagine the complexity of research on new cannabinoid substances…

In conclusion…

Cannabinoid receptors are key components in the endocannabinoid system and play a crucial role in modulating physiological and biochemical functions in the human body. Their distribution and specific functions, both in the brain and in the immune system and other tissues, are fundamental to understanding the effects of cannabinoids and their therapeutic potential.

Cannabinoid Receptor Frequently Asked Questions (FAQ)

What is the difference between CB1 and CB2 cannabinoid receptors?

The difference between CB1 and CB2 cannabinoid receptors lies in their different distribution in the body and functions. In general, CB1 cannabinoid receptors are found primarily in the central nervous system and play an important role in brain and nerve functions, while CB2 cannabinoid receptors are found primarily in the immune system and are associated with the regulation of immune response and inflammation.

What drugs affect cannabinoid receptors?

Cannabinoid receptors open up a new pharmacotherapeutic approach. Several drugs have been developed to affect cannabinoid receptors, such as Sativex and Epidiolex, which contain natural cannabinoids and are used to treat spasticity and rare forms of epilepsy respectively. Other medications such as Marinol and Cesamet contain synthetic cannabinoid and are used to treat nausea, vomiting and stimulate appetite. Another example was Rimonabant, a drug that acted as a cannabinoid CB1 receptor antagonist and was used for the treatment of obesity and metabolic syndrome. However, due to its side effects related to depression and an increased risk of suicide, it was withdrawn from the market. The use of this class of drugs is challenging due to the complexity of the regulation of these receptors in the body.

Are there other cannabinoid receptors besides CB1 and CB2?

In addition to the cannabinoid receptors CB1 and CB2, other types of cannabinoid receptors have been suggested to exist in the human body, such as the GPR55, GPR18 and GPR119 receptors. These receptors are being investigated in relation to functions such as pain regulation, inflammatory response and metabolic processes. However, their precise classification and interaction with cannabinoids is still under debate, and more research is needed for a complete understanding of how cannabinoids interact with the body and their therapeutic potential. This discovery suggests that the endocannabinoid system is more complex than initially thought and could have implications for the development of new therapies.

Laura Salas
R&D Cannactiva | Cannabis Cosmetologist. Expert in cannabis and natural cosmetics with CBD

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