The Endocannabinoid System

Overview of the Endocannabinoid System

The endocannabinoid system is the main system in our bodies that cannabinoids, endocannabinoids (from our bodies) and phytocannabinoids (from the cannabis plant), interact with. All animals except for insects are proposed to have endocannabinoid systems, which is why cannabis products often work similarly in dogs, cats, and other animals as they do in humans (that does not mean that cannabis products are safe for all animals). For the purpose of this article, we will only be discussing the human endocannabinoid system.
The endocannabinoid system functions as a regulatory system, meaning that it regulates different aspects of the body including but not limited to:
·      Temperature
·      Thirst and Hunger
·      Mood
·      Sleep
·      Memory
·      Reproduction
Your body is constantly working to maintain homeostasis or a balance within itself. This means that when there is too much of something in your body, let’s say cortisol (a stress hormone), your body has to act to lower the levels of cortisol back to normal levels. Or when you are too hot so you start sweating, that is partly because of your endocannabinoid system. When something is not functioning properly or needs to be regulated, the endocannabinoid system kicks in to regulate it.

The endocannabinoid system is comprised of three components:

 ·     Endocannabinoids
·      Receptors
·      Enzymes

Endocannabinoids

Endocannabinoids, also called endogenous cannabinoids, are cannabinoids that the body produces on its own. There are two main endocannabinoids.

·Anandamide (AEA)

  • Known to produce a relaxing and calming effect as well as a host of other effects when it binds to receptors
  • Sometimes called the “bliss molecule,” anandamide comes from the Sanskrit word “Ananda,” which means joy, happiness, or sensual pleasure


2-Arachidonyl Glycerol (2-AG)

  • Plays a role in regulating the immune system, pain perception, mood, appetite, sleep, and more.


These endocannabinoids are created by the endocannabinoid system when they are needed to regulate something in our bodies. They work by binding to endocannabinoid receptors to elicit a variety of effects. Although endocannabinoids can cause a variety of effects, our bodies naturally work to only do what is necessary. If there is pain or inflammation that needs to be reduced, our endocannabinoids will work only to lessen that pain and inflammation, even though they are able to do a lot more.

infographic
receptors

Receptors

Endocannabinoid receptors are G-protein coupled receptors or GPCR’s (for more info see the “Cannabinoid Receptors” article under the ‘Resources’ page). They sit in the cell membranes (the outermost part of the cell) and when activated, signal the cells in ways that produce specific physiological effects. The receptors tell the cells what to do. The most common cannabinoid receptors are the CB1 and CB2 receptors.

           CB1 receptors are located mainly along the central nervous system, specifically your brain. CB1 receptors are also located in other parts of your body such as your cardiovascular, reproductive, immune, gastrointestinal, peripheral nervous systems, and more. Though, they are most concentrated in the brain. It is thought that CB1 receptors outnumber any other type of receptor in our brain, partially explaining why cannabinoids like THC can have such a profound variety of effects. Some compounds like THC that bind to CB1 receptors are capable of producing psychoactive effects (making you high/intoxicated). CB1 receptors are involved in a variety of functions such as:
·      Regulating learning and memory
·      Neuronal development & synaptic plasticity
·      Regulating reward and addiction
·      Reducing pain
·      Reducing neuroinflammation and degeneration
·      Regulating metabolism & food intake
·      Regulating bone mass
·      Cardiovascular effects

           CB2 receptors are located mainly in the immune system, in your gut, and in the peripheral nervous system. CB2 receptors play a large role in the regulation of inflammation and specifically inflammatory immune responses. People with conditions such as IBS, Chron’s, and Colitis may benefit from drugs and cannabinoids that target CB2 receptors. No psychoactive effects will occur from CB2 activation. The CB2 receptor was discovered more recently than the CB1 and as such is less studied. Using mice with the genetically-deleted receptor, many functions of CB2 have been deduced. Mice lacking CB2 receptors had more severe conditions in a variety of disease models:
·      Allergic and autoimmune inflammatory diseases
·      Osteoporosis (loss of bone mass)
·      Neurodegenerative diseases
·      Ischemic injury from stroke or heart attack
·      Chronic pain
·      Hepatic (liver) injury and disease
·      Alcohol and nicotine addiction
·      Weight gain
·      Stress responses
Since these are animal studies, we cannot definitively say that all of these instances will be true for humans, however there is additional clinical and nonclinical evidence to suggest that CB2 receptors play a role in most of those aspects and more in humans. It is clear that CB2 receptors have an effect on inflammation and specifically inflammatory immune responses.

Enzymes

Once the endocannabinoids and receptors have done their work to restore homeostasis, enzymes in the endocannabinoid system break down and recycle endocannabinoids. The enzymes also break down phyto-cannabinoids (cannabinoids from plants like cannabis i.e. THC, CBD, CBG, etc…). Without these enzymes, there would be nothing to stop the endocannabinoids from going overboard or doing too much and causing symptoms like exhaustion, lack of motivation, and all the negative effects that typically come with long-term taxation of the endocannabinoid receptors (I’m talking about using THC too much). Your endocannabinoid system is responsible for restoring balance and promoting homeostasis, but over-activation of cannabinoid receptors can be a bad thing. The main enzymes in the endocannabinoid system are Fatty Acid Amide Hydrolase (FAAH) and monoacylglycerol lipase (MAGL).

           FAAH typically breaks down Anandamide whereas MAGL typically breaks down 2-AG.

CBD inhibits FAAH, which leads to higher levels of anandamide in our bodies. This is one of the ways that CBD produces a relaxing feeling, relieves pain and inflammation, and can be neuroprotective. Other cannabinoids have a similar effect on FAAH and anandamide.

Overview of theendocannabinoid
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