Medical Research News

Other Plants That Affect Our Endocannabinoid Systems

Written by Christina Major

Like cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), other plants and foods affect the endocannabinoid system (ECS). The ECS performs several homeostatic (balancing) functions throughout the body, including in the brain and nervous system, skin, digestive tract, liver, cardiovascular system, genitourinary function, and immune system.

The ECS includes:

  • Cannabinoid receptors CB1, CB2, and the ionotropic cannabinoid receptor, and the transient receptor potential vanilloid 1 (TRPV1)
  • Endogenous cannabinoids (endocannabinoids): anandamide (AEA), and 2-arachidonoylglycerol (2-AG)
  • Regulatory metabolic and catabolic enzymes such as fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), and others

The combination and interaction of all these components create the effects we know. For example, CBD and THC directly interact with the ECS; however, we are discovering a wide range of other effects brought on by foods and herbs.


How Other Plants Affect the ECS Without Having CBD or THC


Plants Affecting CB1 Receptors

CB1 exerts a major homeostatic influence in the central nervous system. THC is the phytocannabinoid that most affects this receptor, however, scientists are discovering that molecules in Salvia divinorum (specific molecule thought to be salvinorin A but this is not fully understood), carrot (falcarinol), kava kava (yangonin), and liverwort (perrottetinene and perrottetinenic acid in Japanese and New Zealand varieties) also activate the receptor.  The effect is low, and these molecules do not produce the intoxicating effects of THC. A 2021 review paper by Dr Ethan Russo provides an excellent summary of these plants and the work done to date. [1]


Molecules that Interact with TRPV1 Receptors

TRPV1 affects pain sensitivity and the ECS response. CBD can stimulate the TRPV1 receptors, relieving pain. This is the same receptor chili peppers and their capsaicin affect, as well as piperine in black pepper. Although capsaicin and piperine can cause pain when applied to our skin, continued application effectively desensitizes the receptor, thus decreasing the painful effect. In Dr. Ethan Russo’s paper about these molecules, he reports that CBD and molecules that engage receptors in similar ways could provide treatment options for “neuropathic pain (causalgia, complex regional pain syndrome, migraine), burns, irritable bladder, interstitial cystitis, prostatitis, chronic pelvic pain, fibromyalgia, inflammatory bowel disease, irritable bowel syndrome, pancreatic pain, and various dermatological pruritic conditions.”


CB2 Agents and Antagonists

The active ingredients in Echinacea (alkylamides) resemble the endocannabinoids AEA and AG-2. It readily binds to the CB2 receptors, possibly aiding the immunomodulatory effect. CB2 receptors affect the peripheral nervous system and help control inflammation and pain. Beta-caryophyllene found in plants including black pepper, cloves, hops, and cannabis binds to CB2 receptors.


Inhibitors of Fatty Acid Amide Hydrolase

Breaking down FAAH can prolong the effect of the endocannabinoids on the ECS. Chocolate, maca, as well as apples and blackberries, all contain phytochemicals like kaempferol or N-oleoyl-ethanolamine that inhibit FAAH. Reducing and inhibiting FAAH can help reduce pain and anxiety. Russo reports that, “[c]ontrary to popular belief, there are no endocannabinoids in chocolate…”


CB2 Antagonist Inhibitors

Probiotics and prebiotics both demonstrate the ability to reduce CB2 antagonist inhibitors in the gut, which can help reduce inflammation. Probiotics come from fermented food or supplements. Prebiotics come from food rich in fructooligosaccharides, like garlic and onions, and the roots of sunchokes, chicory, burdock, and dandelion.


Thus, there are many other plants, herbs, and spices that engage with our ECS. Although it took a long time to discover the ECS, scientific study around cannabis forged the foundation of this monumental physiological system. Dr. Russo concludes that “[a]long with other lifestyle factors, such as aerobic exercise, dietary adaptations and supplementation may form important strategies to what has been aptly called ‘the care and feeding of the endocannabinoid system’ [2].”



[1] Russo EB. Beyond cannabis: Plants and the endocannabinoid system. Trends Pharmacol Sci. 2016;37(7):594-605. [journal impact factor = 11.6; times cited = 81]


[2] McPartland JM, Guy GW, Di Marzo V. Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system. PLoS One. 2014;9(3):e89566. [journal impact factor = 3.24; times cited = 111]


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Christina Major

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