CannabinoidsCannabisLifestyleLet’s talk about Cannabinoids Baby (Part 1)

June 13, 2019by John Cooper

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Let’s talk about…Cannabinoids, part 1

Cannabis produces a variety compounds, including cannabinoids, many of which have not been detected in any other plant. While some reports identify 100+ different cannabinoids, we only understand the pharmacology of a very small handful of cannabinoids. They are the active ingredients in cannabis and hemp-related products, such as tinctures, edibles, vapes/smokes, and topical creams, and are vital components to strain differentiation (as previously discussed in our blog post What is a Strain?). The potential effects of cannabis products depend on the presence and potencies of the various cannabinoids. Because they are critical to understanding the pharmacological effects of cannabis, this series on cannabinoids will focus on the six most well-understood compounds found in the cannabis plant: CBD, THC, THCv, CBN, THCa, and CBG. To kick off the series, we will discuss the different types of cannabinoids and their role in normal physiology. Cannabinoids are present endogenously in the body (called endocannabinoids) in addition to being derived from cannabis plants and laboratory synthesis.

Types of Cannabinoids

Endocannabinoids (endogenous neurotransmitters)

The endocannabinoid system (ECS) is comprised of endocannabinoids, which bind to cannabinoid receptors (CB1 and CB2) that are expressed throughout the nervous, cardiovascular, neuromuscular, immune, and gastrointestinal systems. The ECS mediates homeostasis, the balance of your body’s internal system, in response to your external environment and therefore regulates the immune system, gastrointestinal function, metabolism, appetite, pain, sleep, mood, learning and memory, cardiovascular function, and neural development1-4.

Examples: Palmitoylethanolamide (PEA), Anandamide (AEA), 2-Arachidonoylglycerol (2-AG)


Phytocannabinoids (Plant-derived cannabinoids)

The vital and ubiquitous presence of the ECS led to the realization of its therapeutic potential. Similar to endocannabinoids, phytocannabinoids can bind to the cannabinoid receptors and potentially other non-ECS receptors to exert physiological changes5-7.

Examples: Tetrahydrocannabinol (THC), Cannabidiol (CBD), Cannabinol (CBN), Cannabigerol (CBG)


Synthetic cannabinoids (cannabinoids synthetically derived in the laboratory)

While created to be an alternative to phytocannabinoids for therapeutic benefit, their effects can be felt with greater intensity. Synthetic cannabinoids bind and activate the cannabinoid receptors with 2-100 times the potency of endocannabinoids and phytocannabinoids and, as a result, their use can lead to adverse side-effects8,9. Synthetic cannabinoids have enabled researchers to study cannabinoid pharmacodynamics and potential therapeutic effects.

Examples: Arachidonyl-2′-chloroethylamide (ACEA), WIN 55,212-2


Phytocannabinoids appear to be the most convenient avenue to modulate our ECS for therapeutic benefit while avoiding adverse side effects from synthetic derivates. Appreciation for the pharmacological effects of phytocannabinoids dates back to 2700 B.C. as chronologized by Dr. Ethan Russo10. In addition to religious ceremonies, cannabis was used for its therapeutic value as a(n) appetite stimulant, mood modulator, anti-epileptic, and analgesic. It wasn’t until the 1970’s that the cannabinoids THC and CBD were being isolated to examine their pharmacological effects as therapeutics. Discovery of the CB1 cannabinoid receptor in 1988, followed by the CB2 receptor in 1993 led to understanding how cannabinoids regulate physiology. During this time, pharmaceutical companies, such as GW Pharmaceuticals, began developing cannabinoid therapies. In 2003, the first clinical trial for Sativex® (1:1 THC:CBD ratio) to treat multiple sclerosis symptoms was performed and its benefits continue to be discovered for its role as an analgesic for many clinical sources of pain. In more recent years, the pharmacological effects of other cannabinoids have been revealed such as THCv in appetite regulation or CBN as a sedative. Growing support and research surrounding cannabis will continue to unravel the pharmacology of cannabinoids. In the following posts that will be part of this series, we will dive deeper into what the current understanding is surrounding individual cannabinoids.

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  1. Lipina, C. & Hundal, H.S. Modulation of cellular redox homeostasis by the endocannabinoid system. Open Biol 6, 150276 (2016).
  2. Acharya, N. et al. Endocannabinoid system acts as a regulator of immune homeostasis in the gut. Proc Natl Acad Sci U S A 114, 5005-5010 (2017).
  3. Lau, B.K., Cota, D., Cristino, L. & Borgland, S.L. Endocannabinoid modulation of homeostatic and non-homeostatic feeding circuits. Neuropharmacology 124, 38-51 (2017).
  4. Biro, T., Toth, B.I., Hasko, G., Paus, R. & Pacher, P. The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities. Trends Pharmacol Sci 30, 411-20 (2009).
  5. Maroon, J. & Bost, J. Review of the neurological benefits of phytocannabinoids. Surg Neurol Int 9, 91 (2018).
  6. Horvath, B., Mukhopadhyay, P., Hasko, G. & Pacher, P. The endocannabinoid system and plant-derived cannabinoids in diabetes and diabetic complications. Am J Pathol 180, 432-42 (2012).
  7. Hill, A.J., Williams, C.M., Whalley, B.J. & Stephens, G.J. Phytocannabinoids as novel therapeutic agents in CNS disorders. Pharmacol Ther 133, 79-97 (2012).
  8. Castaneto, M.S. et al. Synthetic cannabinoids: epidemiology, pharmacodynamics, and clinical implications. Drug Alcohol Depend 144, 12-41 (2014).
  9. Cohen, K. & Weinstein, A.M. Synthetic and Non-synthetic Cannabinoid Drugs and Their Adverse Effects-A Review From Public Health Prospective. Front Public Health 6, 162 (2018).
  10. Russo, E. The pharmacological history of Cannabis, 747 (Oxford University Press, 2014).

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