Non-Hemp Alternatives to Harness the Power of the Endocannabinoid System

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When we think of cannabinoids and the body’s endocannabinoid system (ECS), hemp and CBD automatically come to mind. However, the ECS is not exclusively responsive to hemp—there are various non-hemp botanicals (other phyto-cannabinoids) and natural compounds like terpenes that interact with this intricate system, offering different therapeutic benefits and promoting homeostatic regulation within the body. Terpenes are aromatic oils produced in a variety of plants, including cannabis, and are responsible for their unique odors and flavors.

Terpenes play important roles in nature, including attracting pollinators, repelling predators, and acting as chemical defenses, but they also have potential interactions with the body’s ECS through different mechanisms. One way is by modulating the activity of cannabinoid receptors, namely CB1 and CB2 receptors. Some terpenes can bind to these receptors and either enhance or reduce their activity, influencing the overall effect of cannabinoids.

Terpenes can also affect the ECS indirectly by influencing the metabolism of endocannabinoids. Enzymes such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) are responsible for breaking down endocannabinoids. Certain terpenes have been found to inhibit these enzymes, leading to increased levels of endocannabinoids and prolonged effects.

The ECS is a complex network of cannabinoid receptors, endocannabinoids (produced by the body), and enzymes that regulate their synthesis and breakdown. It plays a crucial role in maintaining balance and modulating various physiological processes, including mood, pain perception, immune response, and more.

In this blog, we will explore some non-hemp alternatives and their interactions with the ECS, particularly with the cannabinoid receptors (CB1 and CB2), key ECS enzymes, as well as other signaling pathways that contribute to physiological processes.

Non-Hemp Alternatives and Their Interaction with the ECS

Let’s examine several specific ECS agents and their remarkable potential in harnessing the power of the ECS.

1. Plants such as black pepper, cloves, hops, and oregano are known to be high in beta-caryophyllene which is one of the most common terpenes found in nature. Beta-caryophyllene selectively binds to CB2 receptors and acts as a full agonist, and it is readily bioavailable[1]. – E Russo] Orally administered beta-caryophyllene has been shown to increase enzymes involved in anti-inflammatory pathways and to exert potentially analgesic effects [2]. It may contribute to balancing immune response.

2. Lemon Balm (Melissa officinalis) contains compounds like rosmarinic acid and terpenes, including citral, which may interact with CB1 receptors and enhance GABAergic activity [3]. These interactions contribute to relaxation, mood improvement, and potential sleep benefits.

3. Ginger (Zingiber officinale) interacts with the ECS indirectly by inhibiting the enzyme FAAH (fatty acid amide hydrolase), responsible for breaking down endocannabinoids [4]. By slowing down FAAH activity, ginger supports higher levels of anandamide, an endocannabinoid neurotransmitter associated with mood regulation.

4. Rosemary (Rosmarinus officinalis) contains terpenes such as alpha-pinene and beta-pinene, which may influence the ECS indirectly through various mechanisms. These terpenes have shown potential anti-inflammatory effects [5] and may support cognitive function.

5. Lavender (Lavandula angustifolia) exerts its effects on the ECS through its aromatic compounds, such as the terpene linalool. Linalool may interact with the ECS indirectly, by inhibiting enzymes that degrade the endocannabinoids anandamide and 2-AG [6], contributing to relaxation, stress reduction, and potential anti-anxiety properties.

6. Echinacea contains alkamides and fatty acids, including palmitic acid and linoleic acid. Alkamides interact with CB2 receptors, modulating immune response [7], while fatty acids may influence the ECS indirectly through their effects on endocannabinoid metabolism and inflammation. Alkamides are bioactive compounds that show structural similarity with anandamide, an endogenous ligand of cannabinoid receptors [7,8]. Anandamide is a neurotransmitter that binds to cannabinoid receptors in the brain and body, stimulating a sense of happiness and mental balance.

7. Omega-3/6 fatty acids, particularly found in fish oil, play a crucial role in maintaining the health and balance of the ECS. They are necessary for the production of endocannabinoids like anandamide and 2-arachidonoylglycerol (2-AG), which bind to cannabinoid receptors and act as signaling molecules within the ECS [9]. The omega-3 fatty acid DHA helps to maintain the sensitivity and responsiveness of the CB1 cannabinoid receptors, allowing for effective communication within the ECS. Additionally, Omega-3 fatty acids promote anti-inflammatory effects [10].

The compounds discussed in this blog provide a glimpse of the growing list of natural agents that interact with the endocannabinoid system and hold the potential for therapeutic benefits. The study of the ECS and its interaction with botanical compounds is an area of ongoing research, revealing new insights into the vast array of plants that can influence this important system. We can anticipate the discovery of additional natural compounds with ECS-modulating properties, along with an expanded understanding of their potential contributions to our health.

Learn More

View Beyond Cannabis: Plants and the Endocannabinoid System by prominent medical researcher and neurologist, Ethan B. Russo, MD.

References

  1. Gertsch, Jürg, et al. “Beta-Caryophyllene Is a Dietary Cannabinoid.” Proceedings of the National Academy of Sciences, vol. 105, no. 26, 1 July 2008, pp. 9099–9104, https://doi.org/10.1073/pnas.0803601105.
  2. Fidyt, Klaudyna, et al. “β-Caryophyllene and β-Caryophyllene Oxide-Natural Compounds of Anticancer and Analgesic Properties.” Cancer Medicine, vol. 5, no. 10, 2016, pp. 3007–3017, https://doi.org/10.1002/cam4.816.
  3. Wang CC, Hsieh PW, Kuo JR, Wang SJ. Rosmarinic Acid, a Bioactive Phenolic Compound, Inhibits Glutamate Release from Rat Cerebrocortical Synaptosomes through GABAA Receptor Activation. Biomolecules. 2021 Jul 15;11(7):1029. doi: 10.3390/biom11071029. PMID: 34356653; PMCID: PMC8301814.
  4. Petrangolini G, Donzelli F, Berlanda D, Allegrini P, Rossignoli A, Stucchi M, et al. (2020) Targeting Cannabinoid Receptors and Fatty Acid Amide Hydrolase: An Innovative Food-Grade Delivery System of Zingiber officinale and Acmella oleracea Extracts as Natural Adjuvant in Pain Management. J Nutr Food Sci 10:766. doi: 10.35248/2155-9600.20.10.766
  5. Benincá, Jucélia Pizzetti, et al. “Analysis of the Anti-Inflammatory Properties of Rosmarinus Officinalis L. in Mice.” Food Chemistry, vol. 124, no. 2, 2011, pp. 468–475, https://doi.org/10.1016/j.foodchem.2010.06.056.
  6. Johnson SA, Rodriguez D, Allred K. A Systematic Review of Essential Oils and the Endocannabinoid System: A Connection Worthy of Further Exploration. Evid Based Complement Alternat Med. 2020 May 15;2020:8035301. doi: 10.1155/2020/8035301. PMID: 32508955; PMCID: PMC7246407.
  7. Woelkart K, Xu W, Pei Y, Makriyannis A, Picone RP, Bauer R. The endocannabinoid system as a target for alkamides from Echinacea angustifolia roots. Planta Med. 2005 Aug;71(8):701-5. doi: 10.1055/s-2005-871290. PMID: 16142631.
  8. Gertsch, J. et al. (2004) Echinacea alkylamides modulate TNF-/ gene expression via cannabinoid receptor CB2 and multiple signal transduction pathways. FEBS Lett. 577, 563–569
  9. Watson JE, Kim JS, Das A. Emerging class of omega-3 fatty acid endocannabinoids & their derivatives. Prostaglandins Other Lipid Mediat. 2019 Aug;143:106337. doi: 10.1016/j.prostaglandins.2019.106337. Epub 2019 May 11. PMID: 31085370; PMCID: PMC6685292.
  10. Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr. 2002 Dec;21(6):495-505. doi: 10.1080/07315724.2002.10719248. PMID: 12480795.