The endocannabinoid system (eCs) is a very complex regulatory system, broad in its function and found within all complex animals. It is perhaps the most important physiological system involved in establishing and maintaining human health.  

The main function of the eCs is to regulate our bodily functions and to maintain its balanced state of homeostasis (the body’s stable state). It performs many different functions and can be very specific to each area of the body. The regulatory functions can affect: memory, digestion, motor function, immune response, inflammation, appetite, pain, blood pressure, bone growth, protection of neural tissues, internal and external injuries, etc. In each tissue, the eCs performs different tasks but the goal is always the same. Homeostasis; the maintenance of a stable internal environment despite fluctuations in the external environment.  

All vertebrate species share the endocannabinoid system as an essential part of life and adaptation to environmental changes. By comparing the genetics of cannabinoid receptors in different species, scientists estimate that the endocannabinoid system evolved in primitive animals over 600 million years ago.  

The eCs comprises three principal elements: Endocannabinoid receptors, Endocannabinoids and Enzymes.

Endocannabinoid receptors

  1. CB1 & CB2 receptors are distributed throughout the nervous and immune systems
  2. Within many tissues (including the brain)
  3. Gastrointestinal system
  4. Reproductive and urinary tracts
  5. Spleen
  6. Endocrine system (hormones)
  7. Heart
  8. Circulatory system

Cannabinoid interactions extend beyond the CB1 and CB2 receptors and interact with other CB-type and related receptors and ion channels, for example TRPVI receptor, also known as capsaicin receptor.  

Endocannabinoids and their enzymes  

The discovery of the receptors leads to the discovery of the endocannabinoids themselves. Endocannabinoids are the substances our bodies naturally make to stimulate these receptors. The two most well understood of these molecules are called anandamide and 2-arachidonoylglycerol (2-AG).  After isolating the endocannabinoids, enzymes that degrade endocannabinoids were also isolated: monoglyceride lipase (MAGL) which is responsible for degrading 2-AG and fatty acid amide hydrolase (FAAH) which degrades anandamide.  

All endocannabinoids are derivatives of polyunsaturated fatty acids, closely related to omega-3 fatty acids. Since they are fatty acids, they are not water soluble and have difficulty moving around the body. They are biosynthesized on demand and are intended to work locally.  

Endocannabinoids effectively modulate the flow of neurotransmitters keeping our nervous system running smoothly and are directly linked to the mechanisms underlying memory and learning. The direct link between endocannabinoids and homeostasis can help redress specific imbalances presented by disease or injury.  

Endocannabinoid levels may be responsible for the baseline of pain throughout the body, which is why cannabinoid based medicines may be useful in treating conditions like:  

  • Fibromyalgia (a condition marked by heightened background pain levels)
  • Muscle tightness (or spasticity) in MS  
  • Neuropathic pain
  • Inflammation
  • Baseline appetite

Endocannabinoid activity  

CB1 receptor is expressed throughout the brain, where endocannabinoids and CB1 combine to form a “circuit breaker” which modulates the release of both inhibitory and excitatory neurotransmitters across the synapse. It is the activation of the CB1 receptor that is responsible for the psychoactive effects of cannabis, since THC (a phytocannabinoid) is mimicking an endocannabinoid binding to this receptor.  

Body functions affected by the eCs

In the brain:

  • Decision-making
  • Cognition
  • Emotions
  • Learning
  • Memory

One brain region that does not express many CB1 receptors is the brain stem. Responsible for respiration and circulation, which is a primary reason why cannabis overdoses do not cause respiratory depression and death, both of which are very possible with opioid overdoses.  As well as regulating:

  • Body-movement
  • Anxiety
  • Stress
  • Fear
  • Pain
  • Body temperature
  • Appetite
  • Sense of reinforcement
  • Blood-brain permeability
  • Motor control

CB2 expression has been identified in key regions of the brain, including the hippocampus. CB2 has been shown to modulate midbrain reward circuitry, such as the self-administration of cocaine. In the hippocampus, CB2 receptors appear to modulate self-activity and information flow between brain network, potentially assisting in the selection of inputs that may guide complex behaviors.

CB2 receptors are mainly found in white blood cells, in the tonsils and in the spleen. The immune cells also express CB1, although there are fewer of them than CB2. In the immune system, one important functions of the cannabinoid receptors is the regulation of cytokine release (which are small proteins that are important in cell signaling).  

Michael Backes, Cannabis Pharmacy: The Practical Guide to Medical Marijuana.