What is the endocannabinoid system?
The endocannabinoid system is a nerve signaling system throughout the human body that helps maintain physiological, emotional and cognitive stability.
The endocannabinoid system (ECS) is a complex nerve cell signaling system that modulates the central nervous system’s function and helps maintain homeostasis. Homeostasis is the state of equilibrium in the body in which all the organs function optimally, maintaining physiological, cognitive and emotional balance.
The endocannabinoid system is made up of three key components:
- Endocannabinoids: Chemical compounds that carry signals between nerve cells (neurotransmitters). The two main identified endocannabinoids are:
- Anandamide (AEA)
- 2-Arachidonoylglycerol (2-AG)
- Endocannabinoid receptors: Proteins embedded on the cell membrane which bind to the endocannabinoids and react, initiating neural activity. The two main identified endocannabinoid receptors are:
- CB1-R
- CB2-R
- Endocannabinoid recycling: Enzymes in the nerve cells break down the endocannabinoids back into their components for reuse when the next neurotransmission is required. The two principle enzymes found in the endocannabinoid system are:
- Fatty acid amide hydrolase (FAAH) that breaks down AEA
- Monoacylglycerol lipase (MAGL) that breaks down 2-AG
What are endocannabinoids?
“Endocannabinoid” derives its name from phytocannabinoids — “phyto” meaning “plant-based” — a class of psychoactive substances first discovered in Cannabis sativa (marijuana) plants. Endocannabinoids are cannabis-like compounds naturally produced by the body in the nerve cells.
Two endocannabinoids, AEA and 2-AG and their functions have been studied to a great extent. Several more endocannabinoids have been discovered, though their functions and roles in the endocannabinoid system are yet to be determined.
How are endocannabinoids released?
Unlike other neurotransmitters, endocannabinoids are not stored in the nerve cells. Endocannabinoid precursors are present in the fat molecules in the cell membrane and are released upon demand, when the endocannabinoid receptors are activated.
What is the function of endocannabinoids?
Endocannabinoid receptors are concentrated in the brain, but are also present in nerve tissues all over the body. When a condition such as injury, fever or infection disrupts the body’s homeostasis, the endocannabinoid system helps restore the body’s homeostasis.
The endocannabinoid system plays a significant role in the normal functioning of the body’s systems that include:
- Central nervous system
- Cardiovascular system
- Gastrointestinal system
- Reproductive system
- Skeletal system
- Immune system
- Metabolic processes
The endocannabinoid system is an important mediator in regulating:
- Memory and learning
- Appetite
- Stress response
- Pain sensation
- Mood
- Sleep
- Inflammation
- Drug addiction
The functions of the endocannabinoid system are not fully understood. Some studies suggest endocannabinoid deficiency and a disturbed homeostasis may be the cause for certain diseases such as migraine, fibromyalgia and irritable bowel syndrome. Research continues on the gamut of roles endocannabinoids play, and their potential therapeutic uses.
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What are the therapeutic uses of cannabinoids?
The Cannabis sativa plant contains hundreds of compounds. Two of them, tetrahydrocannabinol (THC) and cannabidiol (CBD), bind to the human endocannabinoid receptors CB1-R and CB2-R. Both THC and CBD have medical benefits, but only THC produces euphoric effects.
The cannabis plant contains other minor cannabinoids that interact with the human endocannabinoid system, but their effects are far weaker and they are present in lower concentrations.
Medications can target the ECS therapeutically in two ways:
- Cannabinoid receptor agonists: These drugs bind to the CB1-R and CB2-R and stimulate their activity (for example, CBD).
- Cannabinoid receptor antagonists: These drugs are used to suppress cannabinoid receptor activity (for example, rimonabant).
The potential therapeutic uses for cannabinoids include:
- Pain management
- Anti-nausea
- Cough
- Glaucoma
- Neurologic diseases such as:
- Parkinson’s disease
- Huntington disease
- Amyotrophic lateral sclerosis
- Multiple sclerosis
- Alcohol induced neurodegeneration/neuroinflammation
- Traumatic brain injury
- Stroke
- Seizures
- Autoimmune diseases such as:
- Autoimmune uveitis
- Systemic sclerosis
- Inflammatory bowel disease
- HIV-1 brain infection
- Psychiatric disorders such as:
- Anxiety disorders
- Bipolar disorder
- Personality disorders
- Attention deficit and hyperactivity disorder
- Substance abuse and addictions
- Anorexia nervosa
- Atherosclerosis (plaque buildup in the artery walls)
- Gastrointestinal conditions such as:
- Alcoholic and chronic liver diseases
- Gut motility disorder
- Inflammatory bowel syndrome
- Diabetic nephropathy (diabetes-related kidney disease)
- Osteoporosis
- Cancers
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What are the FDA-approved cannabinoid drugs?
Currently, medical use of cannabis is legal in 29 states. Three cannabinoid receptor agonist drugs are approved by FDA.
Dronabinol (Miranol)
Approved for use as
- Antiemetic (anti-nausea and vomiting) for chemotherapy
- Appetite stimulant for people with acquired immunodeficiency syndrome (AIDS)
Side effects include:
- Dizziness
- Drowsiness
- Confusion
- Feeling high
- Lightheadedness
- Nausea and vomiting
- Abdominal pain
- Central nervous system toxicity
Nabilone (Cesamet)
Antiemetic for chemotherapy when other therapies are unsuccessful
Side effects include:
- Dizziness
- Drowsiness
- Dry mouth
- Feeling high
- Lightheadedness
- Headache
- Trouble sleeping
- Memory problems
Epidiolex (Cannabidiol)
The FDA in 2018 approved this first-ever CBD-based drug for childhood seizure disorders like Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) in patients 2 years of age and older.
Side effects include: