Accurate Education – Marijuana (Cannabis): The Endocannabinoid System

Marijuana (Cannabis)

The Endocannabinoid System (ECS)

The endocannabinoid system (ECS) is a naturally occurring neuroendocrine communication network that is present throughout the brain, nervous system and the rest of the body and plays a role in many physiological processes. The ECS regulates many physiologic functions including gastrointestinal (GI) function, appetite and metabolism, pain, memory, movement, immunity, and inflammation.

See:

Marijuana – Legislative Update for Louisiana

Marijuana – Medical Use Overview

Medical Marijuana” – Getting Started

Marijuana vs Hemp

 

Cannabis-Based Medications:

Over-the-Counter Cannabinoid Medications:

Marijuana – Cannabidiol (CBD)

 

Prescription Cannabis-Based Medications:

FDA-Approved Prescription Cannabis-Based Medications

Louisiana Prescription Cannabis-Based Products – “Medical Marijuana”

Clinical Applications of Cannabis:

Cannabis – Anxiety (coming soon)

Cannabis – Fibromyalgia

Cannabis – Headaches (coming soon)

Cannabis – Inflammatory Bowel Disease (coming soon)

Cannabis – Neuroinflammation (coming soon)

Cannabis – Pain (coming soon)

Cannabis – Sleep (coming soon)

 

The Medical Science of Cannabis:

The Endocannabinoid System

Marijuana – Botanical

Marijuana – Pharmacokinetics

Marijuana – Inhaled (Smoked and Vaporized)

Marijuana – Cannabinoids and Opioids

Cannabinoids and Terpenes:

Cannabinoids & Terpenes – An Overview (coming soon)

Cannabinoids:

Marijuana – Cannabidiol (CBD)

Terpenes:

Terpenes – An Overview (coming soon)

   

See also:

Marijuana – Discontinuing Use

Marijuana Addiction – Cannabis Use Disorder (CUD)

 

 

 

Key to Links:

Grey text – handout

Red text – another page on this website

Blue text – Journal publication

cannabis-caduceus 

This section remains incomplete and is still being edited for accuracy and completeness.

The Endocannabinoid System

Cannabinoids: Endocannabinoids and Phytocannabinoids

There are a number of physiologically active constituents of the cannabis (marijuana) plant, some of which have shown therapeutic benefits in a broad range of conditions. One group of compounds found to be uniquely abundant in cannabis is the “cannabinoids.”  Originally thought to be unique to cannabis, naturally occuring cannabinoids (endocannabinoids) were subsequently discovered in humans and animals (all vertebrates). An entire endocannabinoid system consisting of multiple types of endocannabinoids and cannabinoid receptors is distributed throughout the body.

 

Cannabinoid receptors are distributed in the central nervous system and many peripheral tissues including spleen, white blood cells (leukocytes), reproductive, urinary and gastrointestinal tracts; endocrine glands, arteries and heart. These receptors respond to the presence of cannabinoids in many differenst ways, whether the cannabinoid is plant-based (phytocannabinoids), naturally occuring in the body (endocannabinoids), or synthetically manufactured. The entire field of cannabinoid pharmacology remains in its infancy but is now offering many potential clinical applications, although at this stage it is providing more questions and possibilities than answers or confirmed benefits.

 

The endocannabinoid system of naturally occuring endocannabinoids and receptors is similar to the opioid system of naturally occuring opioids (endorphins) and receptors in the body. The endocannabinoid system (ECS) regulates many physiologic functions ranging from the immune system to the nervous system and affects sleep, appetite, mood, pain and other functions. For this reason, marijuana has attracted a great deal of attention from a pharmacotherapy perspective for its potential to affect many physiologic functions with possible benefit.

 

The ECS is comprised of two G-protein-coupled receptors (GPCRs): cannabinoid receptors 1 (CB1) and 2 (CB2). CB1 receptors are predominantly found in the central nervous system (CNS) where they have  psychoactive effects as well as being found in the central nervous system (CNS), Gastrointestinal (GI) system, adipocytes (fat cells), liver tissue, and skeletal muscle.

 

In contrast, CB2 receptors are more limited in their distribution where they are primarily found on immune cells located in the tonsils, thymus, spleen, and bone marrow, as well as in the enteric nervous system within the GI tract. Activation of these receptors is dependent on endogenous endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG).

 

The medicinal properties of cannabis are attributed primarily to the phytocannabinoids ∆9-THC (THC) and cannabidiol (CBD). THC and CBD, the most pharmacologically active phytocannabinoids, mimic AEA and 2-AG, respectively. THC binds to the CB1 receptor in the nervous system and CBD binds strongly to the CB2 receptor where it exerts effects on the immune system and together  they impact pain, especially neuropathic pain.

 

Many preclinical animal and labatory-based studies have shown that modifying the activity of the ECS affects many medical conditions including: mood, anxiety disorders, movement disorders, neuropathic (nerve) pain, epilepsy, multiple sclerosis, spinal cord injury, cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, insomnia, drug addiction, Alzheimer’s disease, and osteoporosis.  However, there is a lack of good quality human-based research to confirm the specifics of what these preclinical studies suggest.  It is been believed that some conditions including migraine headaches, fibromyalgia, and Irritable Bowel Syndrome (IBS) may be the result of an underlying endocannabinoid deficiency, indicating they may be effectively treated with cannabinoid medications.

 

Pain

The analgesic effect of cannabinoids as a result of binding of cannabinoids to cannabinoid receptors has been confirmed, and the role of the endocannabinoid system in pain relief has been verified in various types of pain: somatic, visceral and neuropathy. Classical analgesics, nonsteroidal anti-inflammatory drugs,  opioids, and antidepressants increase the activity of the endocannabinoid system.

  

Resources:

National Academy of Sciences

The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research

 

www.Healer.com

This website appears to be good resource for exploring medical marijuana.

 

References:  

 

Endocannabinoid System (ECS) – Basic Science

  1. The Discovery of the Endocannabinoid System – 2012
  2. Endocannabinoid signaling at the periphery – 50 years after THC – 2015
  3. A Personal Retrospective – Elevating Anandamide (AEA) by Targeting Fatty Acid Amide Hydrolase (FAAH) and the Fatty Acid Binding Proteins (FABPs) – 2016
  4. Are cannabidiol and Δ9-tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review – 2015
  5. Cannabinoid Receptors – Nomenclature and Pharmacological Principles – 2013
  6. CB1 & CB2 Receptor Pharmacology – 2017
  7. GPR3 and GPR6, novel molecular targets for cannabidiol. – PubMed – NCBI – 2017
  8. The Endocannabinoid System Modulating Levels of Consciousness, Emotions and Likely Dream Contents. – PubMed – NCBI – 2017
  9. Pharmacokinetics and pharmacodynamics of cannabinoids. – PubMed – NCBI
  10. Clinical Pharmacodynamics of Cannabinoids – 2004
  11. Affinity and Efficacy Studies of Tetrahydrocannabinolic Acid A at Cannabinoid Receptor Types One and Two. – 2017
  12. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. – PubMed – NCBI
  13. Pharmacology of Cannabinoids
  14. Cannabinoid receptor 2 – Potential role in immunomodulation and neuroinflammation Review – 2013
  15. Cannabinoid Receptors and the Endocannabinoid System – Signaling and Function in the Central Nervous System – 2018
  16. Crystal Structure of the Human Cannabinoid Receptor CB1 – 2017
  17. The_Endogenous_Cannabinoid_System_A_Budding_Source
  18. Does Cannabis Composition Matter? Differential Effects of Delta-9-tetrahydrocannabinol and Cannabidiol on Human Cognition – 2017
  19. Evidence for THC versus CBD in cannabinoids – 2018

 

 

ECS – In Disease

  1. Role of the endocannabinoid system in diabetes and diabetic complications – 2016
  2. Cannabinoid receptor-specific mechanisms to alleviate pain in sickle cell anemia via inhibition of mast cell activation and neurogenic inflammation – 2016
  3. The Role of Endocannabinoids System in Fatty Liver Disease and Therapeutic Potentials – 2013
  4. The endocannabinoid system in pain and inflammation – Its relevance to rheumatic disease – 2017
  5. The endocannabinoid system in pain and inflammation – Its relevance to rheumatic disease – 2018
  6. Endocannabinoid System: A Multi-Facet Therapeutic Target. – PubMed – NCBI
  7. Enhanced endocannabinoid tone as a potential target of pharmacotherapy. – PubMed – NCBI
  8. Targeting cannabinoid receptor CB2 in cardiovascular disorders- promises and controversies – 2012
  9. Targeting Cannabinoid Signaling in the Immune System – “High”-ly Exciting Questions, Possibilities, and Challenges – 2017

 

 

ECS – Pain

  1. Cannabinoid receptor-specific mechanisms to alleviate pain in sickle cell anemia via inhibition of mast cell activation and neurogenic inflammation – 2016
  2. Dissociation between morphine-induced spinal gliosis and analgesic tolerance by ultra-low-dose α2-adrenergic and cannabinoid CB1-receptor antagonists – 2018
  3. Impact of Efficacy at the m -Opioid Receptor on Antinociceptive Effects of Combinations of m -Opioid Receptor Agonists and Cannabinoid Receptor Agonists – 2015
  4. Targeting CB2 receptors and the endocannabinoid system for the treatment of pain – 2009
  5. The Endocannabinoid System and Pain – 2009
  6. The endocannabinoid system in pain and inflammation – Its relevance to rheumatic disease – 2017
  7. The endocannabinoid system in pain and inflammation – Its relevance to rheumatic disease – 2018
  8. The Endocannabinoid System, Cannabinoids, and Pain – 2013

 

ECS – Entourage Effect (Synergy)

  1. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. – PubMed – NCBI
  2. Cannabis and cannabis extracts – greater than the sum of their parts? – 2001
  3. Clinical and Preclinical Evidence for Functional Interactions of Cannabidiol and Δ9-Tetrahydrocannabinol. – PubMed – NCBI – 2018
  4. Does Cannabis Composition Matter? Differential Effects of Delta-9-tetrahydrocannabinol and Cannabidiol on Human Cognition – 2017
  5. Evidence for THC versus CBD in cannabinoids – 2018

 

ECS – Related

  1. Cannabis-conclusions – 2017 National Academy of Sciences
  2. Cannabis-chapter-highlights – 2017 National Academy of Sciences
  3. Cannabis-report-highlights – 2017 National Academy of Sciences
  4. Clinical Endocannabinoid Deficiency (CECD): Can this Concept Explain Therapeutic Benefits of Cannabis in Migraine, Fibromyalgia, Irritable Bowel Syndrome and other Treatment-Resistant Conditions?-2004
  5. Cannabimimetic phytochemicals in the diet – an evolutionary link to food selection and metabolic stress adaptation? – 2016
  6. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. – PubMed – NCBI
  7. Cannabinoids and Cytochrome P450 Interactions. – PubMed – NCBI Pharmacogenetics of Cannabinoids – 2018
  8. Adverse effects of medical cannabinoids – a systematic review – 2008
  9. Cannabimimetic effects modulated by cholinergic compounds. – PubMed – NCBI
  10. Antagonism of marihuana effects by indomethacin in humans. – PubMed – NCBI
  11. Pharmacokinetics and pharmacodynamics of cannabinoids. – PubMed – NCBI
  12. Clinical Pharmacodynamics of Cannabinoids – 2004
  13. Affinity and Efficacy Studies of Tetrahydrocannabinolic Acid A at Cannabinoid Receptor Types One and Two. – 2017
  14. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. – PubMed – NCBI
  15. Pharmacology of Cannabinoids
  16. Current-status-and-future-of-cannabis-research-Clin-Researcher-2015

Emphasis on Education

 

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