Eight Ways to Stimulate and Enhance Your Endocannabinoid System

Mar 3, 2023 | Written by Scott Sherr, MD | Reviewed by Marion Hall

Eight Ways to Stimulate and Enhance Your Endocannabinoid System

The endogenous cannabinoid (endocannabinoid) system is named after the cannabis plant (Cannabis sativa, or marijuana) that led to its discovery, and represents a major physiological system for the maintenance of human health [1,2].

Endocannabinoids and their receptors are found throughout the body, its tissues, and organs, effectively forming a link between body and mind that offers substantial promise for enhancing physical health and warding off disease [1,3,4]. 

The biological effects of cannabinoids are made possible by cannabinoid receptors 1 (CB1R) and 2 (CB2R). The former is prominent in the central nervous system whereas the latter links to the peripheral nervous system, with both receptors activated by the presence of endocannabinoids [2]. There are exogenous ("outside the body") cannabinoids (such as THC) but also endogenous cannabinoids such as 2-arachidonoyl glycerol and anandamide [5]. 

This article looks to examine eight possible ways to stimulate and enhance your endocannabinoid system for the promotion of health and wellness, according to the latest available research. 

Exposure to Cold 

Obesity and metabolic disease are major health challenges, and brown adipose tissue (BAT) has emerged as a potential therapeutic avenue. BAT is a type of body fat that keeps us warm when we get cold by breaking down blood sugar (glucose) and fat molecules to generate heat and maintain body temperature [6].

In obesity, the endocannabinoid system is upregulated, and blocking CB1R has been shown to cause weight loss and decrease risk factors for cardiometabolic disease. Human and rodent research has demonstrated that CB1R and endocannabinoids are stimulated in BAT following exposure to cold temperatures, but this response was blunted in overweight subjects [3,7]. Therefore, maintaining a healthy weight and body composition when undergoing exposure to cold temperatures might be the best way to stimulate the endocannabinoid system. 

Physical Exercise 

Regular physical activity is important for so many aspects of health. Increased levels of circulating endocannabinoids in the blood tend to be associated with aerobic exercise, such as jogging, and these bring about the so-called "runner’s high" that makes us feel good after a long bout of training [8].

In a systematic review and meta-analysis of research evidence, acute exercise (whether it be running or cycling) was found to increase the endocannabinoids anandamide and 2-arachidonoylglycerol across species (human or rodent) and in those with and without pre-existing health conditions [9]. This might be a potential mechanism for the role of the endocannabinoid system in modulating the effects of exercise on mental health [10].

Flaxseed Oil 

Overactivation of the endocannabinoid system, when paired with inflammatory processes, can serve as a risk factor for coronary artery disease. Research in humans has shown that dietary fat, flaxseed oil in particular, can help to blunt this overactivation. Supplementation with flaxseed oil containing 2.5 g alpha linoleic acid for 10 weeks increased the gene expression of CB2R [11]. This demonstrates the potential cardioprotective properties of flaxseed oil through its action on the endocannabinoid system.

Managing Stress 

Stress affects a vast swathe of physiological systems and brings about a shift in many neurobehavioral processes [12]. The endocannabinoid system is a central regulator of the stress response. Research has shown that stress increases 2-arachidonoyl glycerol levels whilst reducing anandamide levels [12]. In addition, studies on the brain have shown that in virtually all regions, chronic stress exposure results in the downregulation or loss of CB1R receptors. The decline in anandamide also contributes to the stress response by activating the hypothalamic-pituitary-adrenal axis and increases anxiety behavior [12,13].

Individuals that do not release 2-arachidonoyl glycerol in response to stress exposure seem to exhibit dramatically higher levels of cortisol [14], a well-known marker of physiological stress and a catabolic hormone.

As discussed above, physical exercise is a key strategy to help ward off stress and offers a wealth of benefits for overall health and wellness.

Echinacea Root Extract 

The indigenous peoples of the North American prairies are known to have addressed many painful ailments using Echinacea. The pharmacological basis for this is grounded in the endocannabinoid system [15]. Rodent studies of inflammatory pain have shown that Echinacea has dose-dependent analgesic effects [16]. These effects were partially reversed when cannabinoid receptor antagonists were provided at the same time. Echinacea could therefore offer benefits for inflammatory pain such as burns and arthritis, supporting its use by indigenous peoples all those years ago.


The endocannabinoid system regulates the health and integrity of the intestinal barrier in the gut. It allows communication between the gut microbiota and the host organism [17]. Issues with the intestinal barrier can lead to inflammatory bowel disorder, obesity, and major depressive disorder. The health of the host is influenced by the endocannabinoid system, the gut microbiota, and the integrity of the intestinal barrier [17].

Supplementing with probiotics (live bacteria that have health benefits) that target the endocannabinoid system can be a potent strategy for the improvement of gut health. Probiotics can enhance the endocannabinoid system, bolstering the integrity of the intestinal barrier, and lower the inflammatory response. In rodents, administration of the probiotic Lactobacillus acidophilus brought about enhanced expression of CB1R in the colon, suggesting activation of the endocannabinoid system [18].

Omega-3 Fatty Acids

Endocannabinoids are built within the body from omega-3 and omega-6 polyunsaturated fatty acids – these are the building blocks and can be obtained from the diet [19,20]. Deficiency in omega-3 fatty acid intake leads to reduction in CB1R in mood-controlling structures and is associated with impaired emotional behavior [21]. A study from 2019 also showed that endocannabinoids built from omega-3 fatty acids possess higher anti-inflammatory and anti-proliferative potential [22]. A diet high in omega-3 fatty acids might also augment the neurological aspects of the endocannabinoid system [21].


That cherished caffeinated beverage we all love (and some would say need!) could also help the activation of CB1R due to the augmenting effects of caffeine on the endocannabinoid system [23]. Chronic caffeine consumption enhances the sensitivity of striatal GABAergic synapses to the stimulation of CB1R, and might offer potential benefits in the treatment of stress-associated neuropsychiatric conditions [24-26].


This article has discussed several ways to leverage the endocannabinoid system to benefit health and wellness from the perspectives of nutrition, exercise, and mental health. By using these strategies, you can make use of this important physiological system to enhance your overall awesomeness (i.e., well-being). 

What's your favorite strategy to enhance your ECS among those listed above? Or do you have any of your own? Of course, here at Troscriptions we love to use Tro Calm to enhance our ECS. Let us know your favorites in the comments below!



[1]        B.E. Alger, Getting high on the endocannabinoid system, Cerebrum. 2013 (2013) 14. 

[2]        S. Zou, U. Kumar, Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System, Int J Mol Sci. 19 (2018) 833. https://doi.org/10.3390/ijms19030833

[3]        M. Lahesmaa, O. Eriksson, T. Gnad, V. Oikonen, M. Bucci, J. Hirvonen, K. Koskensalo, J. Teuho, T. Niemi, M. Taittonen, S. Lahdenpohja, M. U Din, M. Haaparanta-Solin, A. Pfeifer, K.A. Virtanen, P. Nuutila, Cannabinoid Type 1 Receptors Are Upregulated During Acute Activation of Brown Adipose Tissue, Diabetes. 67 (2018) 1226–1236. https://doi.org/10.2337/db17-1366

[4]        M.P. Dimmito, A. Stefanucci, A. Della Valle, G. Scioli, A. Cichelli, A. Mollica, An overview on plants cannabinoids endorsed with cardiovascular effects, Biomedicine & Pharmacotherapy. 142 (2021) 111963. https://doi.org/10.1016/j.biopha.2021.111963

[5]        H.-C. Lu, K. Mackie, An Introduction to the Endogenous Cannabinoid System, Biol Psychiatry. 79 (2016) 516–525. https://doi.org/10.1016/j.biopsych.2015.07.028

[6]        T. Yoneshiro, Q. Wang, K. Tajima, M. Matsushita, H. Maki, K. Igarashi, Z. Dai, P.J. White, R.W. McGarrah, O.R. Ilkayeva, Y. Deleye, Y. Oguri, M. Kuroda, K. Ikeda, H. Li, A. Ueno, M. Ohishi, T. Ishikawa, K. Kim, Y. Chen, C.H. Sponton, R.N. Pradhan, H. Majd, V.J. Greiner, M. Yoneshiro, Z. Brown, M. Chondronikola, H. Takahashi, T. Goto, T. Kawada, L. Sidossis, F.C. Szoka, M.T. McManus, M. Saito, T. Soga, S. Kajimura, BCAA catabolism in brown fat controls energy homeostasis through SLC25A44, Nature. 572 (2019) 614–619. https://doi.org/10.1038/s41586-019-1503-x

[7]        L.M. Krott, F. Piscitelli, M. Heine, S. Borrino, L. Scheja, C. Silvestri, J. Heeren, V. Di Marzo, Endocannabinoid regulation in white and brown adipose tissue following thermogenic activation, Journal of Lipid Research. 57 (2016) 464–473. https://doi.org/10.1194/jlr.M065227

[8]        V. Bristot, G. Poletto, D.M.R. Pereira, M. Hauck, I.J.C. Schneider, A.S. Aguiar, The effects of exercise on circulating endocannabinoid levels—a protocol for a systematic review and meta-analysis, Syst Rev. 11 (2022) 98. https://doi.org/10.1186/s13643-022-01980-x

[9]        S. Desai, B. Borg, C. Cuttler, K.M. Crombie, C.A. Rabinak, M.N. Hill, H.A. Marusak, A Systematic Review and Meta-Analysis on the Effects of Exercise on the Endocannabinoid System, Cannabis and Cannabinoid Research. 7 (2022) 388–408. https://doi.org/10.1089/can.2021.0113

[10]      S. Amatriain-Fernández, H. Budde, T. Gronwald, C. Quiroga, C. Carreón, G. Viana-Torre, T. Yamamoto, C. Imperatori, S. Machado, E. Murillo-Rodríguez, The Endocannabinoid System as Modulator of Exercise Benefits in Mental Health, Curr Neuropharmacol. 19 (2021) 1304–1322. https://doi.org/10.2174/1570159X19666201218112748

[11]      S. Saleh-Ghadimi, M. Alizadeh, H. Jafari-Vayghan, M. Darabi, A. Golmohammadi, S. Kheirouri, Effect of flaxseed oil supplementation on the erythrocyte membrane fatty acid composition and endocannabinoid system modulation in patients with coronary artery disease: a double-blind randomized controlled trial, Genes Nutr. 15 (2020) 9. https://doi.org/10.1186/s12263-020-00665-1

[12]      M. Morena, S. Patel, J.S. Bains, M.N. Hill, Neurobiological Interactions Between Stress and the Endocannabinoid System, Neuropsychopharmacol. 41 (2016) 80–102. https://doi.org/10.1038/npp.2015.166

[13]      C.J. Hillard, M. Beatka, J. Sarvaideo, Endocannabinoid Signaling and the Hypothalamic-Pituitary-Adrenal Axis, Compr Physiol. 7 (2016) 1–15. https://doi.org/10.1002/cphy.c160005

[14]      M.N. Hill, S. Patel, Translational evidence for the involvement of the endocannabinoid system in stress-related psychiatric illnesses, Biol Mood Anxiety Disord. 3 (2013) 19. https://doi.org/10.1186/2045-5380-3-19

[15]      K. Woelkart, W. Xu, Y. Pei, A. Makriyannis, R.P. Picone, R. Bauer, The endocannabinoid system as a target for alkamides from Echinacea angustifolia roots, Planta Med. 71 (2005) 701–705. https://doi.org/10.1055/s-2005-871290

[16]      R. Liu, N.L. Caram-Salas, W. Li, L. Wang, J.T. Arnason, C.S. Harris, Interactions of Echinacea spp. Root Extracts and Alkylamides With the Endocannabinoid System and Peripheral Inflammatory Pain, Front. Pharmacol. 12 (2021) 651292. https://doi.org/10.3389/fphar.2021.651292

[17]      J. Jansma, F. Brinkman, S. van Hemert, S. El Aidy, Targeting the endocannabinoid system with microbial interventions to improve gut integrity, Progress in Neuro-Psychopharmacology and Biological Psychiatry. 106 (2021) 110169. https://doi.org/10.1016/j.pnpbp.2020.110169

[18]      C. Rousseaux, X. Thuru, A. Gelot, N. Barnich, C. Neut, L. Dubuquoy, C. Dubuquoy, E. Merour, K. Geboes, M. Chamaillard, A. Ouwehand, G. Leyer, D. Carcano, J.-F. Colombel, D. Ardid, P. Desreumaux, Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors, Nat Med. 13 (2007) 35–37. https://doi.org/10.1038/nm1521

[19]      J.E. Watson, J.S. Kim, A. Das, Emerging class of omega-3 fatty acid endocannabinoids & their derivatives, Prostaglandins Other Lipid Mediat. 143 (2019) 106337. https://doi.org/10.1016/j.prostaglandins.2019.106337

[20]      S. Komarnytsky, T. Rathinasabapathy, C. Wagner, B. Metzger, C. Carlisle, C. Panda, S. Le Brun-Blashka, J.P. Troup, S. Varadharaj, Endocannabinoid System and Its Regulation by Polyunsaturated Fatty Acids and Full Spectrum Hemp Oils, Int J Mol Sci. 22 (2021) 5479. https://doi.org/10.3390/ijms22115479

[21]      M. Lafourcade, T. Larrieu, S. Mato, A. Duffaud, M. Sepers, I. Matias, V. De Smedt-Peyrusse, V.F. Labrousse, L. Bretillon, C. Matute, R. Rodríguez-Puertas, S. Layé, O.J. Manzoni, Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions, Nat Neurosci. 14 (2011) 345–350. https://doi.org/10.1038/nn.2736

[22]      I. de Bus, R. Witkamp, H. Zuilhof, B. Albada, M. Balvers, The role of n-3 PUFA-derived fatty acid derivatives and their oxygenated metabolites in the modulation of inflammation, Prostaglandins Other Lipid Mediat. 144 (2019) 106351. https://doi.org/10.1016/j.prostaglandins.2019.106351

[23]      S. Rossi, V. De Chiara, A. Musella, G. Mataluni, L. Sacchetti, A. Siracusano, G. Bernardi, A. Usiello, D. Centonze, Caffeine drinking potentiates cannabinoid transmission in the striatum: Interaction with stress effects, Neuropharmacology. 56 (2009) 590–597. https://doi.org/10.1016/j.neuropharm.2008.10.013

[24]      S. Rossi, V. De Chiara, A. Musella, G. Mataluni, L. Sacchetti, A. Siracusano, G. Bernardi, A. Usiello, D. Centonze, Effects of caffeine on striatal neurotransmission: Focus on cannabinoid CB1 receptors, Mol. Nutr. Food Res. 54 (2010) 525–531. https://doi.org/10.1002/mnfr.200900237

[25]      D.T. Leffa, S.G. Ferreira, N.J. Machado, C.M. Souza, F. da Rosa, C. de Carvalho, G.C. Kincheski, R.N. Takahashi, L.O. Porciúncula, D.O. Souza, R.A. Cunha, P. Pandolfo, Caffeine and cannabinoid receptors modulate impulsive behavior in an animal model of attentional deficit and hyperactivity disorder, Eur J Neurosci. 49 (2019) 1673–1683. https://doi.org/10.1111/ejn.14348

[26]      D. Navarro, A. Gasparyan, F. Navarrete, A.B. Torregrosa, G. Rubio, M. Marín-Mayor, G.B. Acosta, M.S. Garcia-Gutiérrez, J. Manzanares, Molecular Alterations of the Endocannabinoid System in Psychiatric Disorders, IJMS. 23 (2022) 4764. https://doi.org/10.3390/ijms23094764

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