The ECS was only discovered in the late 1980s and we’re still learning about it, but we do know that it promotes homeostasis of the body and is involved in sleep, inflammation, mood, and many other critical functions.² The body makes cannabinoids, known as endocannabinoids, which are messaging molecules that regulate the ECS. The ECS in turn plays a role in regulating many of the critical functions of our bodies, especially those associated with our nervous and immune systems. Many plants contain phytocannabinoids, which are naturally occurring, plant-derived cannabinoids. Just like endocannabinoids, the cannabinoids that come from plants, also act as messaging molecules that can help regulate the ECS. CBD is one of many phytocannabinoids found in the Cannabis sativa plant. Hemp is the highest known source of cannabinoids and most CBD supplements are extracted from it.

CBD creams, salves, lotions, and bath products

CBD creams, salves, lotions, and bath products can be used instead of CBD supplements. There is evidence from animal models and in vitro research that, when applied to the skin, CBD makes its way into the blood stream.¹ Topical CBD products are an especially good option if you’re looking to modulate inflammation or need relief for occasional muscle or joint discomfort in a specific spot. There are elements of the ECS throughout the skin. Furthermore, CBD has skin-specific benefits too, such as scavenging free radicals and modulating inflammation.³

While CBD supplements are probably the most well-known compounds that can regulate the ECS, there are many other natural compounds that also act on the ECS and can offer similar benefits to those of CBD.

PEA (palmitoylethanolamide)

PEA (palmitoylethanolamide) is a naturally occurring compound produced throughout the body that helps to maintain many important physiological functions and is available as a supplement derived from safflower oil. PEA indirectly supports the ECS by decreasing the breakdown of anandamide, one of our endocannabinoids. Anandamide is considered one of the most important endocannabinoids the body makes and has been dubbed the bliss molecule because it binds to endocannabinoid receptors in the brain and body, stimulating a sense of happiness and mental wellness. PEA, by decreasing its breakdown, enhances the effects of anandamide. PEA also indirectly supports the ECS by increasing the expression of endocannabinoid receptors.⁴ Because PEA influences the ECS, it has many health supportive benefits including supporting a balanced inflammatory response in the body and brain as well as supporting restful sleep and a healthy mood. Its ability to modulate inflammation goes beyond PEA’s interaction with the ECS, as it also modulates some of the enzymes responsible for driving inflammation.⁴ Human clinical trials have successfully used PEA to support a balanced pain response in a variety of populations.^{4 5 6 7 8}

Kava (Piper methysticum)

Kava (Piper methysticum) is an herb long revered for its ability to promote mental wellbeing, and scientists now believe that one of the ways it does this is through its interaction with the endocannabinoid system. The kavalactone yangonin has been discovered to have a weak affinity for one of the endocannabinoid receptors.⁹ Although its effects are not as strong as cannabinoids themselves, kava has an excellent reputation for modulating our stress response, promoting calm, and supporting healthy sleep.¹⁰

Echinacea (Echinacea angustifolia, Echinacea purpurea)

Echinacea (Echinacea angustifolia, Echinacea purpurea) is well known to support the healthy function of the immune system, but Native Americans also used it for occasional aches and pains. We now know that compounds called alkamides that are abundant in echinacea are structurally similar to one of our own endocannabinoids and also appear to have an affinity for our endocannabinoid receptors.¹¹ In one study, researchers found that echinacea administered to rats modulated inflammation through the ECS, in part by supporting endocannabinoid receptor sensitivity, but also by maintaining healthy levels of endocannabinoids.¹²

EPA and DHA

EPA and DHA from fish oil (or algae for a vegetarian and vegan version) are necessary for the proper signaling of the ECS.¹³ They appear to work as homeostatic regulators of the system, helping it to work better.  

Like every other system in our bodies, the ECS also benefits from a good diet, stress management practices, and appropriate exercise. For instance, flavonoids found in brightly colored fruits and vegetables and green tea, as well as many different spices, have direct positive effects on the ECS, while pesticides negatively alter its normal function.¹³ In animals, chronic stress impairs the ECS, including desensitizing cannabinoid receptors to exogenous cannabinoids (e.g., phytocannabinoids), while stress-reducing activities such as massage maintain their function.¹³ Exercise supports healthy levels of endocannabinoids; the “runner’s high” may actually be induced by the ECS, not by endorphins.¹³ To get the full benefits of whatever supplement you may take to support your ECS, it’s best to keep it optimally functioning with diet and lifestyle interventions too

What about CBD alternatives for my pet?

As it turns out, our furry friends also utilize the endocannabinoid system to regulate the same critical functions we do.⁴ Studies have found palmitoylethanolamide (PEA) helps support a healthy inflammation response in the digestive tract, skin, and joints of dogs and cats.¹⁵ The studies found PEA could be safely used for dogs in doses up to 30 milligrams/kilogram (13.6 milligrams/pound) of body weight, and up to 15 milligrams/kilogram of body weight in cats.¹⁶ Omega-3 fatty acids EPA and DHA are also essential in regulating ECS function in animals and have a long history of safe use. Doses up to a maximum of 310 milligrams/kilogram of EPA/DHA per day have been shown to be safe.¹⁷

For more information on CBD please see the articles CBD and CBD—FAQs.

References

1. Information for Health Care Professionals: Cannabis (marihuana, marijuana) and the cannabinoids (2018). Retrieved June 13, 2023, from https://www.canada.ca/content/dam/hc-sc/documents/services/drugs-medication/cannabis/information-medical-practitioners/information-health-care-professionals-cannabis-cannabinoids-eng.pdf
2. Pertwee, R.G. (2006). Cannabinoid pharmacology: the first 66 years. Br J Pharmacol, 147(Suppl 1), S163-S171. doi: 10.1038/sj.bjp.0706406
3. Baswan, S.M., Klosner, A.E., Glynn, K., Rajgopal, A., Malik, K., Yim, S., Stern, N. (2020). Therapeutic potential of cannabidiol (CBD) for skin health and disorders. Clin Cosmet Investig Dermatol, 13, 927-942. doi: 10.2147/CCID.S286411
4. Artukoglu, B. B., Beyer, C., Zuloff-Shani, A., Brener, E., & Bloch, M. H. (2017). Efficacy of Palmitoylethanolamide for Pain: A Meta-Analysis. Pain physician, 20(5), 353–362.
5. Steels, E., Venkatesh, R., Steels, E., Vitetta, G., & Vitetta, L. (2019). A double-blind randomized placebo controlled study assessing safety, tolerability and efficacy of palmitoylethanolamide for symptoms of knee osteoarthritis. Inflammopharmacology, 27(3), 475–485. https://doi.org/10.1007/s10787-019-00582-9
6. Marini, I., Bartolucci, M. L., Bortolotti, F., Gatto, M. R., & Bonetti, G. A. (2012). Palmitoylethanolamide versus a nonsteroidal anti-inflammatory drug in the treatment of temporomandibular joint inflammatory pain. Journal of orofacial pain, 26(2), 99–104.
7. Calignano, A., La Rana, G., Giuffrida, A., Piomelli, D. (1998). Control of pain initiation by endogenous cannabinoids. Nature, 394(6690), 277-281. https://doi.org/10.1038/28393
8. Paladini, A., Fusco, M., Cenacchi, T., Schievano, C., Piroli, A., & Varrassi, G. (2016). Palmitoylethanolamide, a Special Food for Medical Purposes, in the Treatment of Chronic Pain: A Pooled Data Meta-analysis. Pain physician, 19(2), 11–24.
9. Ligresti, A., Villano, R., Allarà, M., Ujváry, I., Di Marzo, V. (2012). Kavalactones and the endocannabinoid system: the plant-derived yangonin is a novel CB1 receptor ligand. Pharmacological Research. 66(2), 163-169. https://doi.org/10.1016/j.phrs.2012.04.003
10. Blumenthal, M. (2003). The ABC Clinical Guide to Herbs. American Botanical Counsel.
11. Woelkart, K., Xu, W., Pei, Y., Makriyannis, A., Picone, R. P., & Bauer, R. (2005). The endocannabinoid system as a target for alkamides from Echinacea angustifolia roots. Planta medica, 71(8), 701–705. https://doi.org/10.1055/s-2005-871290
12. Liu, R., Caram-Salas, N. L., Li, W., Wang, L., Arnason, J. T., & Harris, C. S. (2021). Interactions of Echinacea spp. Root Extracts and Alkylamides With the Endocannabinoid System and Peripheral Inflammatory Pain. Frontiers in pharmacology, 12, 651292.
    https://doi.org/10.3389/fphar.2021.651292
13. McPartland, J.M., Guy, G.W., Di Marzo, V. (2014). Care and feeding of the endocannabinoid system: a systematic review of the potential clinical interventions that upregulate the endocannabinoid system. PLoS One, 9(3), e89566. doi: 10.1371/journal.pone.0089566