Activating the Endocannabinoid System without Cannabis
Updated: Oct 12
In recent years Cannabis has gained traction as a medicinal herb for the treatment of chronic pain, sleep, epilepsy and mood disruption (particularly social anxiety). While this powerful plant and it’s primary psychoactive compound tetrahydrocannabinol (THC) has stolen the show - mostly because it’s the ‘fun’ one - it’s actually cannabis’ complex activity on the endocannabinoid system (eCS) via cannabidiol (CBD) and other CBD-like compounds that we can attribute its therapeutic effects.
In this article, I demystify the endocannabinoid system, and how to harness it’s therapeutic effects without the use of cannabis products. I will first explain how the eCS works, how its receptors interact with inflammation, and how herbal medicines like Kava and Echinacea activate this system to reduce pain and treat mental health. I'll also detail some easily overlooked lifestyle advice that help you release your own endocannabinoids without needing to smoke pot or get high to feel like a million dollars.
What is the endocannabinoid system?
The eCS serves as a regulatory network that is present throughout the central and peripheral nervous system, and is closely linked with pain signalling pathways. This is largely due to the influence of the eCS on the immune system, and any subsequent inflammatory cascades.
There are two main receptors that endocannabinoids activate:
CB1 - found primarily in the brain and central nervous system (CNS) and therefore are associated with behavioural changes, mood, memory, emotion and pain transmission.
CB1 receptors are also found throughout the reproductive system, cardiovascular system and all throughout the gut.
CB2 - found mostly within organs of the immune system (lymph, tonsils, spleen etc) where they exert immunomodulatory effects.
Endocannabinoids, the compounds that activate these receptors, are cannabis-like compounds that the body produces naturally. The most notable of which is anandamide (some people refer to it a the “bliss molecule”) and 2-arachidonyle glycerol. Both of these are derived from arachidonic acid, an omega-6 polyunsaturated fatty acid that forms the bases of our cell membranes, and serves as a regulator for two important inflammatory pathways; the cyclooxygenase (COX) and lipoxygenase (LOX) pathways.
How does this system interact with pain signalling?
These CB1 & CB2 receptors are located in several key areas that are involved in pain transmission along the neural highway that is our brain and spinal cord (the better known as the CNS)
It’s worth highlighting that pain does not actually exist, rather it is a warning signal that our CNS uses to convey that something is wrong within the body. Pain signals serve their purpose by triggering guarding (avoiding movement patterns that cause pain) and other behavioural changes (opting not to eat foods that cause digestive distress) to allow inflammation to resolve and for healing to occur.
CB1 receptors regulate the release of two key neurotransmitters; glutamate (excitatory) and GABA (inhibitory), which influence how pain signals are registered within the CNS.
CB2 receptors, on the other hand, downregulate inflammation pathways to reduce swelling and minimise the release of aggravating pro-inflammatory mediators.
The eCS also interacts with our endogenous opioid system; the natural analgesic mechanism that conventional painkillers like morphine and codine act upon. This effect confers to a natural reduction in pain, as well as cannabinoid-like compounds ability to serve as a relaxant. This pain reduction is also attributed to the interaction between the eCS and substance P; a compound I like to think of as “substance pain”, as substance P is a neuropeptide that enhances the perception of pain.
Conditions that can be eased by CB1 & CB2 antagonism
This list is not exhaustive:
Treatment resistant-epilepsy
Chemotherapy-adjunct treatment for nausea, pain and mood
Endometriosis, adenomyosis, pelvic pain
Chronic pain of musculoskeletal origin - neuropathic, fibromyalgia etc
Parkinson’s disease-related tremor and muscle spasticity
Insomnia and sleep disturbance
Headaches and migraines
Anxiety, depression, low-self esteem
But what if I were to tell you that you can activate the healing benefits of this system without the use of cannabis products?
There are alternate ways to light up the relaxing and pain relieving benefits, the simplest of which is spending time with people you can truly be yourself around.
Loved Ones & Social Connection
Cannabinoid receptors fire up when we experience distinct feelings of belonging on a social and interpersonal level. This experience can come from opting for a career in an aligned workplace that brings with it a deep sense of meaning and a shared effort toward a common goal. Moreover, spending time with friends that leave you feeling energised - the ones who fill up your cup rather than draining you - also light up this neurochemical pathway as fostering strong community connections created a sense of ease, calm and security associated with increased GABAergic activity. It goes without saying that the same is true for having a safe and secure home life that is reliable.
It stands to reason that protecting your sanctuary - that is your home and all of the people who live in it - serves as a basis for a relaxed, easy-going state of being that can also come with recreational and medicinal cannabis use. However, I argue that having a solid, secure home life is the very foundation of better health and a more aligned way of life. You can live a life filled with ease and laugher without the need to rely on cannabis consumption to get there.
Kava - Piper methysticum
You might be aware of Kava as it has gained popularity over the last few years as an alcohol alternative. It’s ability to deepen social connections and ease worries about the self lends itself to that, plus it has a pleasant psychoactive and body-high type of effect.
Before Kava became a modern Westernized alternative to alcohol, it has been a cherished ceremonial plant by communities across the Asia Pacific.
Kava is believed to foster connections between spirits and the mortal realm, and it’s a deeply communal experience. Traditionally the root is masticated - literally chewed on - by multiple members of the community before being brewed into a tea. Human saliva acts as a solvent, drawing out the psychoactive component of Kava responsible for the mood-altering and body high-inducing effects - the Kavalactones. There are 6 primary kavalactones that confer calming, relaxing and pain-relieving effects, and some varietals will be more sedating (or “heavier”) than others, depending on the ratios of these kavalactones.
In my opinion, Kava as a beverage is best shared with friends for a night of storytelling, or in a respectful private manner in order to cultivate a deeper connection to the spiritual realm or to fully sink into creative endeavours. Moreover, while Kava is arguably a healthier alternative to alcohol, it can itself gift a toxic hangover-like experience for some. This is particularly the case for those with a specific genetic polymorphism that makes it hard for some people to break down and eliminate flavokavain B. Like all psychoactive plants, kava deserves to be respected and used only in moderation, with the appropriate set and setting to get the most out of the experience.
Kava as a herbal medicine is a different thing all together; it’s a potent anti-anxiety herbal ally that eases muscle tension, boosts social batteries and allows us to be fully present in the moment. This effect is due in large part to a constituent called yangonin, which binds to CB1 receptors. I find Kava useful for highly strung, tense people that struggle to ease into social situations, or for people that are too up in their head about things to really live in the moment. It’s a useful tool for muscular aches and pains, as it actus upon endocannabinoid receptors to relax overly tensed holding patterns resulting in uncomfortable muscle stiffness.
It can have paradoxical effects in some - just like how cannabis can activate some and completely zonk others. However generally, low doses to act like a gentle Dutch-courage-type of herbal medicine, and larger doses are generally quite sedating. In fact it improves sleep latency, and the quality of sleep architecture without any morning grogginess.
On a personal level, Kava is a part of my “Party Potion” - a herbal tincture I take when attending parties and festivals. It helps me get out of my own way, to settle into a dancefloor upon arrival, and it actually does help me drink less alcohol on a night out because I feel calm, relaxed, and ready to connect with the music and the people around me.
Echinacea - Echinacea angustifolia & Echinacea purpurea
Echinacea is one of our primary immune system herbs. She helps improve immune surveillance, promotes lymphatic flow and expedites the process of eliminating the toxic by-products that arise as collateral damage from the healing process. This is due to one of it’s primary active phytochemicals; alkylamides. Alkylamides are also potent selective cannabinomimetics, binding strongly to CB2 receptors and mildly to CB1 receptors. This then potentiates beneficial cytokine production (such as TNF-a), helping to balance immune surveillance without overstimulating immune tissues.
Magnolia - Magnolia officinalis
Magnolia is a superb herb for stress, tension and anxiety, with it’s main active constituents, magnolol & honokiol, exerting strong anti-depressant potential. Naturally, its these two bioactive compounds that bind with CB1 & CB2 receptors, while also affecting other neurochemical pathways that lift mood and ease worried minds. It also modulates GABA receptors, and acts as a 5-HTP6 receptor agonist, thereby altering levels of GABA and serotonin in the central nervous system. Magnolia also downregulates sympathetic fight-or-flight hyperactivation, allowing a sense of ease to wash over the body and reducing the impact of late-night surges of cortisol in the wired-and-tired individual who struggles with sleep. This makes Magnolia a wonderful alternative for patients who struggle with sleep problems, without being an outright sedating plant.
Zone 2 Cardio, Hiking & the “Runner’s High”
Many of us have heard about, or perhaps even experiences a so-called “runner’s high” - when the endorphins kick in on a long run that help make the otherwise arduous form of exercise tolerable, or even enjoyable. For many years, this endorphin release was merely a theory backed up by mountains of anecdotal and empirical evidence, however in recent years the data has confirmed the phenomena to be true. Researchers determines that steady-state exercise increased plasma levels of endocannabinoids in as little as 45-minutes. That's good news for hikers, people having a boogie on a dancefloor, and runners alike.
The interesting thing about this is that while you can also get a hefty dose of endocannabinoids from short bursts of high intensity exercise like sprints and HIIT, this type of longer, more relaxed form of physical activity has stronger mood regulating effect, without needing to obliterate yourself with hill sprints. Moreover, this kind of sustained exercise typically takes place outdoors, and perhaps with friends or family or a beloved pet. This layers in key mood and connection neurochemical releases from sunshine, fresh air and socialisation. This triggers the simultaneous release of serotonin, dopamine, oxytocin and endocannabinoids, giving our central nervous system a wonderful feel-good neurochemical bubble bath.
Dietary Factors
Dietarily, increasing intake of foods rich in the fatty acid arachidonic acid (ARA) such as animal foods, particularly fatty fish like salmon & sardines, egg yolk, full-fat dairy, the dark meat of chicken and turkey and red meat can also light up the endocannabinoid receptor pathways. These kinds of foods bring with them rich sources of essential amino acids, minerals and a complement of B vitamins that promote healthy neurotransmitter synthesis. Think about it from an evolutionary standpoint; we are biologically wired to seek out animal protein, so we have evolved to require the very kind of nutrition they make available to us.
I know I may have lost a few of you there, but that’s okay. ARA is a semi-essential polyunsaturated fatty acid (PUFA) that is a part of the inflammatory mediating pathways of omega-3 and omega-6s. Luckily for our plant-based friends, supplementing with Evening Primrose Oil capsules or increasing dietary intake of hemp-, sunflower-, sesame- and pumpkin- seeds and oils will provide plentiful Linoleic acid (LA), arachidonic acids precursor.
The Bottom Line
While it is a modern marvel that we have access to medicinal cannabis here in Australia, I do feel conflicted about it. Cannabis is a potent psychoactive plant that has a way of transforming lives for better AND worse, sometimes simultaneously. Innervating the endocannabinoid system has powerful mood stabilizing, inflammation-dampening and analgesic powers, but in the wrong hands it can result in debilitating addictive tendencies, anxiety and panic disorders.
This area of medicine is ever evolving, and while I believe medicinal cannabis products can be truly life-changing for some, I don’t believe it is the right medicine for every body, nor is it a decision to take lightly.
Something I’m passionate about as a herbalist and naturopath is helping people achieve a more balanced, and soul nourishing way of being. As a woman who spent many years smoking cannabis who swore it wasn’t a problem (spoiler alert: it was), I have lived experience about how to move away from leaning on cannabis in order to feel more relaxed and at ease with life. If you do smoke, and you love it, by all means you do you - this post is not meant to detract from the medicinal and psychosocial benefits it confers for some. But if you are curious about maybe giving up the wacky tobacc-y, herbs like Kava and Magnolia can ease this transition, while Echinacea can help clean up the mess of withdrawal.
There’s also many other tools in my naturopathic toolbelt for those interested in quitting cannabis, and I would be honoured to be a part of your journey to a clearer mind and a more vibrant life. Get in touch, or book in for a Discovery Call to see if my services align with your next steps forward in a judgement free, inclusive space.
References
Burlou-Nagy, C., Bănică, F., Jurca, T., Vicaș, L. G., Marian, E., Muresan, M. E., Bácskay, I., Kiss, R., Fehér, P., & Pallag, A. (2022). Echinacea purpurea (L.) Moench: Biological and pharmacological properties. A review. Plants, 11(9), 1244. https://doi.org/10.3390/plants11091244
Chevallier, A. (2016). Encyclopedia of herbal medicine: 550 herbs and remedies for common ailments. National Geographic Books.
Chow, L., Lin, P., Chen, Y., Chen, Y., & Huang, E. Y. (2024). Yangonin, one of the kavalactones isolated from piper methysticum G. Forst, acts through cannabinoid 1 (CB1) receptors to induce an intrathecal anti-hyperalgesia. Journal of Ethnopharmacology, 333, 118394. https://doi.org/10.1016/j.jep.2024.118394
Fuchs, A., Rempel, V., & Müller, C. E. (2013). The natural product Magnolol as a lead structure for the development of potent cannabinoid receptor agonists. PLoS ONE, 8(10), e77739. https://doi.org/10.1371/journal.pone.0077739
Joseph E. Pizzorno, J., & Murray, M. T. (2012). Textbook of natural medicine. Elsevier Health Sciences.
Krehl, J., Mamallapalli, J. N., Xing, C., & Grundmann, O. (2026). Kava (Piper methysticum G. Forst) for substance use disorders: A review of mechanism, pharmacology, clinical evidence, and therapeutic potential. Nutrients, 18(17), 2747. https://doi.org/10.3390/nu18172747
Matei, D., Trofin, D., Iordan, D. A., Onu, I., Condurache, I., Ionite, C., & Buculei, I. (2023). The endocannabinoid system and physical exercise. International Journal of Molecular Science, 24(3), 1989. https://doi.org/10.3390/ijms24031989
Rempel, V., Fuchs, A., Hinz, S., Karcz, T., Lehr, M., Koetter, U., & Muller, C. E. (2012, November 14). Magnolia extract, Magnolol, and metabolites: Activation of cannabinoid CB2 receptors and blockade of the related GPR55. PubMed. https://doi.org/10.1021/ml300235q
Romm, A. (2018). Botanical medicine for women's health: Botanical medicine for women's health. Elsevier Health Sciences.
Sarris, J., & Wardle, J. (2019). Clinical naturopathy: An evidence-based guide to practice. Elsevier Health Sciences.
Thorpe, R. (2007). Happy high herbs. Possibilty Publishing.
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