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What is the Endocannabinoid System
CBD

What is the Endocannabinoid System?

As many cannabis aficionados know, our beloved plant affects our endocannabinoid system [1] (also referred to as ECS). Put simply, endocannabinoids are molecules produced by humans and other mammals as part of our ECS, which is a fascinating, intricate network that affects multiple physiological processes, such as influencing our moods, central nervous system (CNS), and regulating pain.

In this article, we’ll look at our endocannabinoid system, its function in the human body, and how CBD and THC react with it.

The Endocannabinoid System: A Brief History

Although there was early evidence of cannabis use some 12,000 years ago, it wasn’t until 1964 that Israeli scientists Mechoulam and Gaoni determined the structure [2] of THC (delta-9-tetrahydrocannabinol), the primary psychoactive compound responsible for the effects of cannabis.

Decades later, two members of the G-protein receptor family, CB1 and CB2 [3], were found to react to cannabis when the endocannabinoids bind to them.

Endocannabinoid System Components

Our ECS comprises several parts, all working with impressive complexity to influence our physical and emotional feelings.

Endocannabinoids

The first endocannabinoid to be discovered by William Devane in 1992, anandamide (AEA) [4], was isolated from a pig brain. It is a fatty acid neurotransmitter found in the tissue of many mammals, including humans.

The second endocannabinoid to be identified is 2-Arachidonoylglycerol (2-AG) [5]. This activates the CB1 receptor, which affects a wide range of physiological functions such as pain, inflammation, balance, and emotion.

Receptors

The two receptors that bind to endocannabinoids are CB1 and CB2. CB1 is known [6] to bind to Cannabis sativa and controls the levels of neurotransmitter activity.

The CB2 receptor regulates inflammation [7], pain, and immune responses.

Enzymes

Enzymes are remarkable catalysts that play a crucial role in biochemical reactions within living organisms. These specialized proteins act as biological catalysts, speeding up cell chemical reactions by lowering the activation energy required.

Two enzymes metabolizing the receptors [8] are the fatty acid amide hydrolase (FAAH) and the monoacylglycerol lipase (MAGL). It has been researched that inhibitors of these two enzymes have shown effects on pain, anxiety, inflammation, and the spread of cancer cells in animals.

Endocannabinoid System Functions

Our complex ECS affects our bodies in intricate ways and is vital to keeping us in homeostasis, a state of balance crucial for good healthcare.

Some physiological functions that our ECS is responsible for include:

  • Regulating mood
  • Regulating emotions
  • Supporting brain health
  • Pain perception and management
  • Controlling appetite and satiety, the feeling of fullness
  • Regulating sleep
  • Immune system function
  • Reproductive function, including fertility and regulating hormones
  • Controlling inflammation

How Cannabinoids Interact with the Endocannabinoid System

Cannabinoids interact with the endocannabinoid system (ECS) through complex mechanisms, ultimately influencing its functioning and physiological responses. The ECS consists of three main components: endocannabinoids (cannabinoids produced naturally in the body), receptors, and enzymes.

Binding to Cannabinoid Receptors – Cannabinoids can bind to the CB1 and CB2 receptors throughout the body. CB1 receptors are primarily located in the central nervous system [9], while CB2 receptors are more abundant in the peripheral tissues and immune cells. Binding to these receptors can trigger various cellular responses and influence various physiological functions.

Modulating Neurotransmitter Release – Cannabinoids can modulate the release of neurotransmitters in the brain by interacting with CB1 receptors. This interaction can affect the release of neurotransmitters such as dopamine [10], serotonin, and GABA, leading to changes in neuronal activity and neurotransmission.

Enhancing Endocannabinoid Signaling – Cannabinoids can enhance the signaling of endocannabinoids, such as anandamide and 2-arachidonoylglycerol (2-AG), by inhibiting their breakdown enzymes. This results in increased levels of endocannabinoids [11], prolonging their effects and potentially influencing ECS-related functions.

Interacting with Non-Cannabinoid Receptors – Some cannabinoids, like cannabidiol (CBD), can interact with non-cannabinoid receptors such as serotonin, vanilloid, and nuclear receptors [12]. These interactions contribute to the broad range of effects exhibited by cannabinoids.

Influencing Enzyme Activity – Cannabinoids can affect the activity of enzymes involved in the synthesis and breakdown of endocannabinoids. For example, THC can inhibit the enzyme fatty acid amide hydrolase (FAAH), which breaks down anandamide and increases its levels in the body.

Endocannabinoid Deficiency

Clinical endocannabinoid deficiency (CED) suggests that certain people have an imbalance or inadequate endocannabinoid levels.

Dr. Ethan Russo, a renowned neurologist, and researcher, first researched CED. He suggested that CED could lead to certain medical conditions such as chronic migraines, irritable bowel syndrome (IBS), fibromyalgia, and other pain disorders [13].

It is now thought that CBD, THC, and other cannabinoids could enhance the endocannabinoid system and help alleviate symptoms of such disorders, although more research is needed.

Therapeutic Potential of Cannabinoids

Although research on the relationship between the endocannabinoid system and cannabinoids is limited, a few scientific studies have proven a few health benefits.

Pain Management – Cannabinoids have been widely studied for their analgesic properties, including their applicability in alleviating acute, chronic, and neuropathic pain [14].

Anti-inflammatory Effects – Cannabinoids possess anti-inflammatory properties, making them potentially useful in conditions characterized by inflammation, such as arthritis, inflammatory bowel disease (IBD), and multiple sclerosis (MS) [15].

Appetite Stimulation – Cannabis has often demonstrated the ability to stimulate appetite [16], making it useful in conditions associated with appetite loss and cachexia, such as cancer and HIV/AIDS [17].

Sleep Disorders – Certain cannabinoids, including THC and CBD, may have a role in managing sleep disorders like insomnia and sleep apnea [18].

Skin Conditions – Topical applications of cannabinoids have been explored for their potential benefits in managing various skin conditions, including acne, psoriasis, eczema, and dermatitis [19].

Neurological Disorders – Certain cannabinoids, particularly CBD, have shown promise in treating neurological disorders such as epilepsy, Parkinson’s disease, Alzheimer’s disease, and Tourette syndrome [20].

Mental Health Conditions – Cannabinoids have been investigated for their potential benefits in managing mental health conditions like anxiety disorders, depression, post-traumatic stress disorder (PTSD), and schizophrenia [21].

Nausea and Vomiting – THC has been widely utilized to alleviate nausea and vomiting associated with chemotherapy and other medical treatments [22].

* It is important to note that the medical benefits of cannabinoids have not been conclusively proven, and the NHS has not made any guarantees about the efficacy of such products.

Final Thoughts

CBD products are legal and found nationwide, but you can shop from the comfort of your home at Blessed CBD! Bring balance to your body and improve your holistic health with CBD oils, gummies, or topical CBD cream

CBD products are legal and found nationwide, but you can shop from the comfort of your home at Blessed CBD! Bring balance to your body and improve your holistic health with CBD oils, gummies, or topical CBD cream.

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Sources:

CBD products are legal and found nationwide, but you can shop from the comfort of your home at Blessed CBD! Bring balance to your body and improve your holistic health with CBD oils, gummies, or topical CBD cream.

[1] Grinspoon, Peter. “The endocannabinoid system: Essential and mysterious” https://www.health.harvard.edu/blog/the-endocannabinoid-system-essential-and-mysterious-202108112569

[2] Crocq, Marc-Antoine. “History of cannabis and the endocannabinoid system” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605027/

[3] Zou, Shenglon and Ujendra Kumar. “Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877694/

[4] Scherma, Maria and Paolo Masia, Valentina Satta, Walter Fratta, Paola Fadda, and Gianluigi Tanda. “Brain activity of anandamide: a rewarding bliss?” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460372/

[5] Justinová, Zuzana, Sevil Yasar, Godfrey H. Redhi, and Steven R. Goldberg. “The Endogenous Cannabinoid 2-Arachidonoylglycerol Is Intravenously Self-Administered by Squirrel Monkeys” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123903/

[6] Kendall, Debra A., and Guillermo A. Yudowski. “Cannabinoid Receptors in the Central Nervous System: Their Signaling and Roles in Disease” https://www.frontiersin.org/articles/10.3389/fncel.2016.00294/full

[7] Turcotte, Caroline and Marie-Renée Blanchet, Michel Laviolette, and Nicolas Flamand. “The CB2 receptor and its role as a regulator of inflammation” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075023/

[8] Petrosino, Stefania and Vincenzo Di Marzo. “FAAH and MAGL inhibitors: therapeutic opportunities from regulating endocannabinoid levels” https://pubmed.ncbi.nlm.nih.gov/20047159/

[9] Almogi-Hazan, Osnat and Reuven Or. “Cannabis, the Endocannabinoid System and Immunity—the Journey from the Bedside to the Bench and Back” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352399/

[10] Spanagel, Rainer. “Cannabinoids and the endocannabinoid system in reward processing and addiction: from mechanisms to interventions” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605022/

[11] Mangieri, Regina A. and Daniele Piomelli. “Enhancement of endocannabinoid signaling and the pharmacotherapy of depression” https://www.sciencedirect.com/science/article/abs/pii/S1043661807001624

[12] Capodice, Jillian L. and Steven A. Kaplan. “The endocannabinoid system, cannabis, and cannabidiol: Implications in urology and men’s health” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221009/

[13] Russo, Ethan B. “Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects” https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/j.1476-5381.2011.01238.x

[14] Mallick-Searle, Theresa and Barbara St. Marie. “Cannabinoids in Pain Treatment: An Overview” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036282/

[15] Nagarkatti, Prakash and Rupal Pandey, Sadiye Amcaoglu Rieder, Venkatesh L Hegde, and Mitzi Nagarkatti. “Cannabinoids as novel anti-inflammatory drugs” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828614/

[16] Kirkham, Tim C. “Cannabinoids and appetite: food craving and food pleasure” https://pubmed.ncbi.nlm.nih.gov/19367510/

[17] Pinto, Joaquim S. and Fátima Martel. “Effects of Cannabidiol on Appetite and Body Weight: A Systematic Review” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9525229/

[18] Kaul, Malvika and Phyllis C. Zee, and Ashima S. Sahni. “Effects of Cannabinoids on Sleep and their Therapeutic Potential for Sleep Disorders” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116407/

[19] Martins, Ana M. and Ana L. Gomes, Inês Vilas Boas, Joana Marto, and Helena M. Ribeiro. “Cannabis-Based Products for the Treatment of Skin Inflammatory Diseases: A Timely Review” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8878527/

[20] Chayasirisobhon, Sirichai. “The Role of Cannabidiol in Neurological Disorders” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8817911/

[21] Scherma, Maria and Anna Lisa Muntoni, Gernot Riedel, Walter Fratta, and Paola Fadda. “Cannabinoids and their therapeutic applications in mental disorders” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605020/

[22] Parker,  Linda A and Erin M Rock, and Cheryl L Limebeer. “Regulation of nausea and vomiting by cannabinoids” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165951/

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