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Endocannabinoid System

The Human Body's Endocannabinoid System

The endocannabinoid system is the term used to refer to the endogenous cannabinoids produced by the human body as well as the receptors that they bind to in order to exert their effects on the body. These are the same receptors that cannabinoids derived from plants (such as the ones from the Cannabis genus of plants) bind to, which has accelerated research into this system in recent years.

It is important to understand that this is a complex system with many “moving parts”. We have provided a summary of the endocannabinoid system, but it is just a brief summary. Physiological systems which involve multiple receptors, body systems, and active compounds can become very complex, and research is still actively being pursued in this area.

Locations of Key Receptors in the Endocannabinoid System

The endocannabinoids produced by the body were first identified as neurotransmitters in the brain. It took a while to identify them as such because they do not act like classical neurotransmitters. Instead of being stored in neurons waiting on a release signal, the endocannabinoids are believed to be synthesized as needed (“on demand”) by neurons. Also unlike traditional neurotransmitters, endocannabinoids send retrograde signals – signals sent backwards to the preceding neuron that was bringing the original message. This retrograde signaling plays an important role in the ability of the brain to alter its own signals – a key process called synaptic plasticity. This means that the endocannabinoid system is a key player in the brain’s ability to learn and form memories.

It is now well understood that the endocannabinoid system now includes more than just the brain. As discussed in more detail below, endocannabinoid receptors have been identified throughout the body, including in the cardiovascular system, the gastrointestinal tract, the immune system, the kidneys, bones, muscles, skin, and the reproductive systems. To provide one specific example, the endocannabinoid system regulates skin cell growth and differentiation and plays a key role in the regulation of sebum production in the skin.

The first receptors identified were given the name “cannabinoid receptors” and are now referred to as CB1 and CB2 receptors. However, in recent years other receptors which bind to cannabinoids have been identified and studied. Cannabinoid receptors are found throughout the entire body (they are estimated to have a 10-to-1 majority over opioid receptors in human) and they are found on the surface of the cell as well as inside the cell on various organelles. We will briefly explain the difference between the most well-known endocannabinoid receptors.

What Does Anandamide Do?

Anandamide (also known as arachidonyl ethanolamide) was one of the first discovered endogenous cannabinoids (endocannabinoid). Anandamide has been the studied in the most detail in the central nervous system, particularly the brain. Anandamide plays a large role in the process of learning and memory (it can actually impair memory formation) and it exerts neuroprotection to protect the brain from injury. Anandamide also seems to play a role in eating and sleeping patterns and pain relief. Anandamide’s roles in other areas of the body besides the brain are drawing a lot of attention these days as well. While research is undergoing, there are hints that anandamide may help inhibit cancer cell proliferation, help with the implantation of embryos in the uterus, and positively activate the immune system, just to name a few of the findings.

The CB1 receptor is found in abundance in the brain. It is expressed in many different areas of the brain and affects many different neurotransmitters, both excitatory and inhibitory ones. In the brain, CB1 receptors play a role in synaptic plasticity, mood and emotions, anxiety, pain, reward, and appetite. But CB1 receptors can also be found in the periphery where they can affect intestinal motility, fertility, the protective response to cardiovascular damage, and obesity-related metabolic pathway.

The CB2 receptor was initially identified in the immune system. It is now known to play a key role in immune function and immune tissues. The identification of CB2 receptors in the brain is a relatively new finding, and the role of CB2 receptors in the brain is much less understood than that of the CB1 receptors. It has been hypothesized that CB2 receptors can also play a role in synaptic plasticity within the brain.

Endocannabinoids send signals back to the preceding neuron

Other cannabinoid receptors are garnering attention in the scientific community. TRPV1 receptors are particularly noteworthy because of the role they play in pain signaling. Widely expressed in the body, the TRPV1 receptors are thought to underlie the pain relieving effects of cannabinoids.

GPR55 receptors are another type of cannabinoid receptor getting attention. These receptors (along with their cousins GPR18 and GPR119) are found in many of the tissues that are known to respond to cannabinoids.

CBD can also bind to peroxisome proliferator-activated receptors (also known as PPARs). These receptors are found in the nucleus of cell and help to change the expression of specific target genes. All cannabinoids seem to be able to bind to the PPAR-alpha subtype receptor, but CBD is one of the few to bind to the PPAR-gamma subtype receptor.

Body System Effects of Endocannabinoids
Central Nervous System
  • Brain Development
  • Aging
  • Hunger/Satiety (Food Intake Regulation)
  • Reward
  • Memory
  • Pain Perception
Gastrointestinal System
(including fat cells)
  • Digestion
  • Hunger/Satiety (Food Intake Regulation)
  • Nutrient Absorption
  • Energy Processing
  • Insulin Function
  • Energy Storage and Utilization
Immune System
  • Production of White Blood Cells
  • Balance between Antibody-Mediated and Cellular-Mediated Immune Responses
Musculoskeletal System
  • Bone Structure and Strength
  • Nutrient Processing By Muscles
  • Muscle Fiber Thickness
Reproductive System
  • Control of Sex Cell Development
  • Regulation of Embryo Implantation
Cardiovascular System
  • Decreased Heart Rate
  • Decreased Blood Pressure
  • Control of Skin Barrier

Table 1: Summary of System-Wide Endocannabinoid System

CBD (cannabidiol) is a plant-based cannabinoid that binds to many of the receptors considered to be part of the endocannabinoid system as well as others. CBD can actually block activity at the CB1 and CB2 receptors, which allows it to neutralize some of the negative effects of THC. CBD’s actions at other receptors underlies many of its beneficial properties. For example, binding at TRPV1 receptors allows it to provide pain relief, and binding at the serotonin receptors allows it to decrease depression and anxiety. You can order purified CBD from Wai Natural to begin experiencing these positive effects yourself!

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