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The Three Components Of The ECS

This scientific illustration visually highlights the essential parts of the ECS, with the title 'Three Key Components of the Endocannabinoid System.' Set against a microscopic cellular backdrop, it identifies an 'ENDOCANNABINOID,' illustrated as a purple sphere; a 'CANNABINOID RECEPTOR,' shown as a socket on the blue cell wall; and 'METABOLIC ENZYMES,' depicted as orange and yellow clusters engaging with the endocannabinoid. All key parts are prominently displayed, indicating the importance of these three components in the functioning of the ECS. This vivid visualization removes any confusion and is great for educational purposes.

The three lesser-known guardians of internal balance tirelessly toil in the shadows of our biology. These are the key parts of the Endocannabinoid System (ECS): ENDOCANNABINOIDS (messengers), CANNABINOID RECEPTORS (message receivers/deliverers), and METABOLIC ENZYMES (cannabinoid clean up crew).

The harmonious interplay of these three components give us profound insights into human health and homeostasis.

Table of Contents

EST. READING TIME: 6 Minutes
EST. READING TIME: 6 Minutes

POP QUIZ!

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Today, you’ll learn about the three main components of the Endocannabinoid System; covering the following four points for each:

  1. The scientific definition
  2. A detailed and more comprehensive explanation
  3. The roles andamp; responsibilities
  4. The main types

Backed by tremendous research for every discussion point, you will find a supporting research study for verification.

#1. Endocannabinoids:

  • Scientific definition: Endocannabinoids are endogenous lipid-based retrograde neurotransmitters that bind to cannabinoid receptors [1].
  • Comprehensive Explanation: Endocannabinoids are naturally occurring molecules produced by the body that activate the same receptors as the active components in cannabis (cannabinoids). They are part of a complex cell-signaling system known as the endocannabinoid system, which helps regulate various physiological processes [2].
An illustrative digital rendering portrays the interaction between an endocannabinoid and a receptor. In the foreground, a detailed cellular structure with a blue and white cell wall is depicted. A labeled arrow points to the wall indicating "cannabinoid receptor type 1, also known as cb1. " above this, a spherical entity with a lavender glow represents the endocannabinoid n-arachidonoylethanolamine, labeled "endocannabinoid, also known as anandamide (aea). " the deep space-like background with scattered light particles adds a cosmic feel to the image, emphasizing the significance of this microscopic interaction. A disclaimer at the bottom notes, "for illustration purposes not actual representations," reminding viewers of the artistic interpretation of the scientific concept. A cannabis leaf icon is subtly included, associating the image with cannabis research and science.

Roles and responsibilities:

  • Modulating neurotransmitter release [3]
  • Regulating pain, inflammation, and immune responses [4]
  • Influencing appetite, mood, and memory [5]
  • Maintaining homeostasis in the body [6]

Two Main Endocannabinoids In The ECS

The two main endocannabinoids are:

  1. anandamide (AEA)
  2. 2-arachidonoylglycerol (2-AG) [7].

#2 Cannabinoid Receptors:

  • Scientific definition: Cannabinoid receptors are G protein-coupled receptors that are activated by endocannabinoids and exogenous cannabinoids [8].
  • Comprehensive Explanation: Cannabinoid receptors are cell membrane receptors that bind to endocannabinoids and cannabinoids, triggering various cellular responses. They are found throughout the body, particularly in the central and peripheral nervous systems, as well as in immune cells [9].
This is a digital visualization depicting a segment of a neuron with a detailed focus on cannabinoid receptors. The image showcases the neuron in a vibrant blue tone with highlighted receptor sites that glow in a vivid orange, labeled as "cannabinoid receptors". The background is artistically blurred, featuring contrasting red and blue hues that create a dynamic and moody atmosphere.

Roles and responsibilities:

  • Mediating the effects of endocannabinoids and cannabinoids [10]
  • Regulating neurotransmission and synaptic plasticity [11]
  • Modulating pain perception, inflammation, and immune function [12]
  • Influencing appetite, mood, and memory [13]

Two Main Cannabinoid Receptors In The ECS

The two main types of cannabinoid receptors are CB1 and CB2 receptors [14].

#3. Metabolic Enzymes:

  • Scientific definition: Metabolic enzymes are proteins that catalyze the synthesis, transport, and degradation of endocannabinoids [15].
  • Comprehensive definition: Metabolic enzymes are responsible for the production, movement, and breakdown of endocannabinoids within the endocannabinoid system. They help maintain the balance of endocannabinoids in the body and ensure that they are available when needed and removed when their function is complete [16].
An illustrative digital rendering portrays metabolic enzymes interacting with endocannabinoids within the body. The composition is set against a dark backdrop that is reminiscent of the interior of a biological environment, highlighted with faint glimmers resembling cellular activity. Foregrounded are vibrant orange and yellow enzyme clusters with bulbous outgrowths, symbolizing their active sites as they latch onto spherical endocannabinoid molecules. Textual cues narrate the biochemical drama: "metabolic enzymes attach to an endocannabinoid to begin the metabolizing it," and a follow-up "further along the process; enzymes have covered the endocannabinoid and will soon completely eliminate it in order to restore balance. " the note at the bottom, "for illustration purposes not actual representations," serves as a reminder that this is an artistic conceptualization of a microscopic process.

Roles and responsibilities:

  • Synthesizing endocannabinoids from precursor molecules [17]
  • Transporting endocannabinoids to target receptors [18]
  • Degrading endocannabinoids to terminate their signaling [19]
  • Regulating the overall activity of the endocannabinoid system [20]

Four Main Metabolic Enzymes In The ECS

The main metabolic enzymes involved in the ECS are:

  • Fatty acid amide hydrolase (FAAH): Degrades anandamide [21]
  • Monoacylglycerol lipase (MAGL): Degrades 2-AG [22]
  • N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD): Synthesizes anandamide [23]
  • Diacylglycerol lipase (DAGL): Synthesizes 2-AG [24]

Summary andamp; Final Thoughts

These three components work together to form the endocannabinoid system, which plays a crucial role in maintaining homeostasis and regulating various physiological processes in the body [25].

References

  1. Mechoulam, R., andamp; Parker, L. A. (2013). The endocannabinoid system and the brain. Annual review of psychology, 64, 21-47. https://doi.org/10.1146/annurev-psych-113011-143739
  2. Lu, H. C., andamp; Mackie, K. (2016). An introduction to the endogenous cannabinoid system. Biological psychiatry, 79(7), 516-525. https://doi.org/10.1016/j.biopsych.2015.07.028
  3. Kano, M., Ohno-Shosaku, T., Hashimotodani, Y., Uchigashima, M., andamp; Watanabe, M. (2009). Endocannabinoid-mediated control of synaptic transmission. Physiological reviews, 89(1), 309-380. https://doi.org/10.1152/physrev.00019.2008
  4. Witkamp, R. (2018). The endocannabinoid system and inflammation: potential for therapeutic intervention. Current Pharmaceutical Design, 24(21), 2413-2421. https://doi.org/10.2174/1381612824666180703161325
  5. Mechoulam, R., andamp; Parker, L. A. (2013). The endocannabinoid system and the brain. Annual review of psychology, 64, 21-47. https://doi.org/10.1146/annurev-psych-113011-143739
  6. Di Marzo, V. (2018). New approaches and challenges to targeting the endocannabinoid system. Nature reviews Drug discovery, 17(9), 623-639. https://doi.org/10.1038/nrd.2018.115
  7. Marzo, V. D., Bifulco, M., andamp; Petrocellis, L. D. (2004). The endocannabinoid system and its therapeutic exploitation. Nature reviews Drug discovery, 3(9), 771-784. https://doi.org/10.1038/nrd1495
  8. Pertwee, R. G. (2008). The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9‐tetrahydrocannabinol, cannabidiol and Δ9‐tetrahydrocannabivarin. British journal of pharmacology, 153(2), 199-215. https://doi.org/10.1038/sj.bjp.0707442
  9. Mackie, K. (2008). Cannabinoid receptors: where they are and what they do. Journal of neuroendocrinology, 20(s1), 10-14. https://doi.org/10.1111/j.1365-2826.2008.01671.x
  10. Howlett, A. C., Barth, F., Bonner, T. I., Cabral, G., Casellas, P., Devane, W. A., … andamp; Pertwee, R. G. (2002). International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacological reviews, 54(2), 161-202. https://doi.org/10.1124/pr.54.2.161
  11. Castillo, P. E., Younts, T. J., Chávez, A. E., andamp; Hashimotodani, Y. (2012). Endocannabinoid signaling and synaptic function. Neuron, 76(1), 70-81. https://doi.org/10.1016/j.neuron.2012.09.020
  12. Pertwee, R. G. (2001). Cannabinoid receptors and pain. Progress in neurobiology, 63(5), 569-611. https://doi.org/10.1016/S0301-0082(00)00063-5
  13. Zanettini, C., Panlilio, L. V., Alicki, M., Goldberg, S. R., Haller, J., andamp; Yasar, S. (2011). Effects of endocannabinoid system modulation on cognitive and emotional behavior. Frontiers in behavioral neuroscience, 5, 57. https://doi.org/10.3389/fnbeh.2011.00057
  14. Pertwee, R. G. (2006). The pharmacology of cannabinoid receptors and their ligands: an overview. International journal of obesity, 30(1), S13-S18. https://doi.org/10.1038/sj.ijo.0803272
  15. Ahn, K., McKinney, M. K., andamp; Cravatt, B. F. (2008). Enzymatic pathways that regulate endocannabinoid signaling in the nervous system. Chemical reviews, 108(5), 1687-1707. https://doi.org/10.1021/cr0782067
  16. Fezza, F., Bari, M., Florio, R., Talamonti, E., Feole, M., andamp; Maccarrone, M. (2014). Endocannabinoids, related compounds and their metabolic routes. Molecules, 19(11), 17078-17106. https://doi.org/10.3390/molecules191117078
  17. Tsuboi, K., Uyama, T., Okamoto, Y., andamp; Ueda, N. (2018). Endocannabinoids and related N-acylethanolamines: biological activities and metabolism. Inflammation and regeneration, 38(1), 1-10. https://doi.org/10.1186/s41232-018-0086-5
  18. Chicca, A., Marazzi, J., Nicolussi, S., andamp; Gertsch, J. (2012). Evidence for bidirectional endocannabinoid transport across cell membranes. Journal of Biological Chemistry, 287(41), 34660-34682. https://doi.org/10.1074/jbc.M112.374124
  19. Lodola, A., Castelli, R., Mor, M., andamp; Rivara, S. (2015). Fatty acid amide hydrolase inhibitors: a patent review (2009-2014). Expert opinion on therapeutic patents, 25(11), 1247-1266. https://doi.org/10.1517/13543776.2015.1067683
  20. Savinainen, J. R., Saario, S. M., andamp; Laitinen, J. T. (2012). The serine hydrolases MAGL, ABHD6 and ABHD12 as guardians of 2‐arachidonoylglycerol signalling through cannabinoid receptors. Acta physiologica, 204(2), 267-276. https://doi.org/10.1111/j.1748-1716.2011.02280.x
  21. Cravatt, B. F., Giang, D. K., Mayfield, S. P., Boger, D. L., Lerner, R. A., andamp; Gilula, N. B. (1996). Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature, 384(6604), 83-87. https://doi.org/10.1038/384083a0
  22. Dinh, T. P., Carpenter, D., Leslie, F. M., Freund, T. F., Katona, I., Sensi, S. L., … andamp; Piomelli, D. (2002). Brain monoglyceride lipase participating in endocannabinoid inactivation.Proceedings of the National Academy of Sciences, 99(16), 10819-10824. https://doi.org/10.1073/pnas.152334899
  23. Okamoto, Y., Morishita, J., Tsuboi, K., Tonai, T., and Ueda, N. (2004). Molecular characterization of a phospholipase D generating anandamide and its congeners. Journal of Biological Chemistry, 279(7), 5298-5305.andnbsp;https://doi.org/10.1074/jbc.M306642200
  24. Bisogno, T., Howell, F., Williams, G., Minassi, A., Cascio, M. G., Ligresti, A., … and Doherty, P. (2003). Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain. The Journal of cell biology, 163(3), 463-468.andnbsp;https://doi.org/10.1083/jcb.200305129
  25. Lu, H. C., and Mackie, K. (2016). An introduction to the endogenous cannabinoid system. Biological psychiatry, 79(7), 516-525.andnbsp;https://doi.org/10.1016/j.biopsych.2015.07.028
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