5 Easy Ways to Enhance Your Endocannabinoid Tone

Did you know that because of cannabis, getting high on your own supply has never been easier? It's all because of our body's endocannabinoid system (ECS), a major regulatory system, which was discovered because people love their cannabis... and have for almost 5000 years.

Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most known active compounds in the cannabis plant. Over the last several decades, these cannabinoids were discovered to modulate the ECS.

To dig deeper into the ECS's inner workings, we first need to define some basic biology. Briefly, we will describe what elements comprise the nervous system, its internal communication process, and how the neurons talk to each other. 

After that, we'll discuss 5 easy ways to enhance your ECS. Ready? As always at Tro Nation, #buccalup! 

Nervous system 101

We are perfectly wired with an internal electrical transmission system: the nervous system, formed by the brain, retina, spinal cord, and thousands of interconnected nerves. The nerves spread throughout our body, connecting different organs (this is known as the peripheral nervous system or PNS) and transmitting signals to and from the central nervous system (CNS). The basic elements are the neurons, highly specialized cells with the ability to generate an electrical current (the “action potential”) and chemically communicate via unique molecules called “neurotransmitters."

Neurons are not the typical round-shaped cell. They have a cell body, usually with protrusions or dendrites, and an axon, a long projection transmitting signals away from the cell body. Input signals typically arrive at the dendrites from axons of neighbor neurons and are prolonged across the axon to the terminal section, generating network activity. A single neuron can be connected to as many as 100,000 others, creating an impressive network, and each confluence between two of them comprises a synapse [1]. This space between the axon (i.e., the presynaptic location) and the dendrite of the next neuron (i.e., the postsynaptic location) is filled with moving vesicles stuffed with neurotransmitters. Think of them as a message to action. Several molecules, ranging from tiny gases (e.g., nitric oxide) to large peptides (e.g., endorphins), can act as neurotransmitters.

When a specific neurotransmitter is received by a neuron, it unravels the activation of cell signaling pathways, regulating the cell’s gene expression profile and prolonging the action potential. It does this by binding to specific receptors in the neuron´s cell membrane in a super-fast and accurately regulated manner.

Neural communication takes only a fraction of a millisecond. This process enables us to feel, think, react, and basically every other body function. The specificity of the action (what our body wants or needs) is determined by whichever neurotransmitter is involved.

The Basic ECS elements

The identification of the ECS didn’t arrive until the late 90s, three decades after THC and CDB were first identified.

ECS emerged as a neuromodulatory system. It is built with an impressive number of receptors, related endocannabinoids, and enzymes responsible for their production and eventual degradation.

Endocannabinoids are lipid neurotransmitters synthesized by specific enzymes in lipid metabolism. In fact, their precursors (polyunsaturated fatty acids or PUFA) are part of the intrinsic lipid cell membrane. Quantities of endocannabinoids may vary depending on demand. They are liberated after a few swift enzymatic steps and released into the synaptic space. This mechanism is different from other neurotransmitters that are synthesized in advance and stored in synaptic vesicles [3].

Anandin (आनन्दिन्) means blissful in Sanskrit. The name of the first discovered endocannabinoid, anandamide (AEA), comes from this term. AEA and 2-arachidonoylglyerol (2-AG) are the most studied endogenous cannabinoids produced by our body to stimulate specific cannabinoid (CB) receptors.

These CB receptors are embedded in the neuron's cell membrane and belong to the well-known family of G-protein-coupled receptors (GPCRs) [4]. GPCRs convert extracellular signals into intracellular responses, a sort of environmental sensing and response. Because of this, they comprise the best targets for drugs. More than half of all modern drugs are targeted at these receptors, and only a few have been commercialized, still leaving considerable space for potential drug development [5].

Two CB receptors have been studied in detail: CB1 and CB2. CB1 is abundant in the CNS and specific brain regions (cortex, basal ganglia, hippocampus, and cerebellum) [6]. CB2 is mainly detected in immune tissue, supporting cells in the CNS (microglia), and blood vessel components. Even though CB2 is underrepresented in the CNS compared to CB1 [7], CB2 has raised interest in the development of new drugs since they don’t provoke the unwanted psychoactive effects related to cannabis after stimulation (AKA feeling high).

Now that we understand the essential components, how does ECS work?

ECS is responsible for homeostasis in our body, balancing mood, emotion, memory, and learning. So, BIG ROLE, right? It has also been directly related to our immune system, appetite, perception of pain, new neuron formation, neuroprotection, and fertility [3]. It's practically everywhere!

The ECS patrols the activity of most neurotransmitters by regulating their levels in systems that need adjustment. It’s not coincidental that most CB receptors in the CNS are located in the presynaptic space. This fact indicates that endocannabinoids travel backward to the common synaptic neurotransmitter. They are released from the postsynaptic cell and act on the presynaptic cell as a sort of override or inhibitory signal [8]. This is also known as retrograde signaling. In addition, it has been shown that endocannabinoid production (specifically 2-AG) increases after postsynaptic activity [9].

Whenever you are feeling anxious or depressed, endocannabinoids help you mitigate that heavy feeling. Researchers have confirmed that endocannabinoid levels in depression and stress conditions are reduced [10]. On the contrary, studies have shown that fasting increased endocannabinoids in the brain, and administration of 2-AG stimulates feeding behavior in animal models [9]. And these are just two simple examples of how vast the ECS spectrum of action is and its flexibility to respond to different conditions.

5 Ways to Enhance Your ECS

The ECS has a central role in our body and multiple implications for physical and mental health. Here, we discuss some ways to boost and strengthen its action.

Stimulating the ECS may lead to the following health benefits:

• Less stress, anxiety, and impulsivity
• Better mood and optimism
• Increased levels of neuron regeneration and plasticity
• Better sleep
• Reduced inflammation
• Faster learning and memory strengthening

Take a gander at these positive interventions and try to implement some of them in your daily routine!

Exercise

Keep moving! Whether you enjoy running, swimming, or practicing Tai chi, no matter your choice of discipline, active exercise enhances the ECS, resulting in increased AEA blood level increments and promoting general well-being [11]. Also, according to recent studies, the ECS may be involved in the rewarding feeling after exercising and the “runner’s high” effect. Besides promoting the liberation of endorphins (the happiness hormone), exercise produces a rise in endocannabinoids that can easily pass through the blood-brain barrier and evoke this deeply euphoric state after intense exercise [12]. Always remember to not overstress your body, however, as this would actually decrease CB1-signaling, leading to the dissipation of this blissful feeling.

Flavonoids

Did your mom always make sure you would have at least 1 piece of fruit for dessert? Mine did and I was not a fan, but I must admit she was right in pushing us to incorporate them as raw as possible. Flavonoids are a group of compounds found in several fruits and vegetables. Usually the brighter the color of the fruit, the better the supply of flavonoids. Genistein, kaempferol, 7-hydroxyflavone, and 3,7-dihydroxyflavone are known flavonoids that inhibit the enzyme responsible for breaking down AEA in the CNS, the fatty acid amide hydrolase (FAAH) [13, 14]. Increased AEA levels could lead to an internal adjustment and stabilization of various neurotransmitters for longer. FAAH inhibition has also been related to the extinction of fear and anxiety in rodents and humans [15]. Because of this, targeting FAAH has raised interest in drug development for anxiety, depression, PTSD, autism, and several other associated conditions.

Cold Exposure

Are you a fan of the Wim Hof method? Do you or would you love to be one those brave and crazy people jumping into frozen lakes during the winter [16]? Exposure to cold increases endocannabinoid levels in fatty cells [17] as part of the override signal typical of ECS for temperature regulation. ECS then induces the production of heat (thermogenesis) by energy burn.

PUFA-Rich Diet

Low levels of omega-3 PUFAs have been linked to neuropsychiatric diseases and poor endocannabinoid function [19]. Remember that PUFAs are the endocannabinoid precursors in the cell. Omega-3 PUFAs can be found in cold water fish (salmon, black cod, sablefish, sardines, herring, etc.). Since they can’t be produced by our bodies, it’s essential to incorporate them into some of our meals or include a supplement such as krill oil in our diet.

As a slight (high) side note, appetite stimulation is one of the most remarkable effects of cannabis in humans. If you've ever had the munchies and just had to stop at your local taco shop at 2 am, you know what we're talking about! Several studies have demonstrated that the ECS regulates the trigger to eat (feeding behavior) via CB1 activation [18]. CB1 is also present in adipose tissue and the gastrointestinal tract, both of which are essential for energy metabolism [18].

CBD

CBD is just one of the more than 500 compounds found in cannabis and hemp plants. It fascinates researchers since it lacks the feel of a high, as opposed to THC. Studies have shown that CBD boosts the expression of CB1 in the brain and prevents the degradation of 2-AG [20]. CBD has many possible medical applications, some only recently available to the public. It is proposed as an anticonvulsant, anti-inflammatory, antioxidant, antipsychotic, and to ease pain, anxiety, and depression, among others. Although not all potential side effects have been explored, CBD has shown low toxicity and no effects indicative of any abuse or dependence potential, as stated by the World Health Organization [21].

CBD can be acquired in multiple formats, but we recommend trying Tro Calm to melt away the stress in your day and get in your Zen zone!

If you decide to try CBD, no matter the form, don’t forget to discuss it with your doctor to ensure it doesn’t interfere with your regular medication and/or supplements.

Some final thoughts

For 5000 years, humans have loved cannabis and with the help of modern science, we now know why... because its myriad effects on the ECS, our system of hemostasis and of bliss + relaxation. 

You can, of course, use cannabis to stimulate this system, but in addition, there are many other natural ways to activate and balance the ECS as well. And you don't even have to get high if you don't want to (but you can)!

References

[1] US Department of Health and Human Services. 2018. What are the parts of the nervous system? Retrieved from: https://www.nichd.nih.gov/health/topics/neuro/conditioninfo/parts

[2] Lu HC, Mackie K. An Introduction to the Endogenous Cannabinoid System. Biol Psychiatry. 2016 Apr 1;79(7):516-25. doi: 10.1016/j.biopsych.2015.07.028.

[3] Zou S, Kumar U. Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. Int J Mol Sci. 2018 Mar 13;19(3):833. doi: 10.3390/ijms19030833.

[4] Gambi F, De Berardis D, Sepede G, et al. Cannabinoid receptors and their relationships with neuropsychiatric disorders. Int J Immunopathol Pharmacol. 2005 Jan-Mar;18(1):15-9. doi: 10.1177/039463200501800103.

[5] Hopkins AL, Groom CR. The druggable genome. Nat Rev Drug Discov. 2002 Sep;1(9):727-30. doi: 10.1038/nrd892.

[6] Mackie K. Distribution of cannabinoid receptors in the central and peripheral nervous system. Handb Exp Pharmacol. 2005;(168):299-325. doi: 10.1007/3-540-26573-2_10.

[8] Lu HC, Mackie K. An Introduction to the Endogenous Cannabinoid System. Biol Psychiatry. 2016;79(7):516-525. doi:10.1016/j.biopsych.2015.07.028

[9] Kano M, Ohno-Shosaku T, Hashimotodani Y, et al. Endocannabinoid-mediated control of synaptic transmission. Physiol Rev. 2009 Jan;89(1):309-80. doi: 10.1152/physrev.00019.2008.

[10] Amatriain-Fernández S, Budde H, Gronwald T, et al. The Endocannabinoid System as Modulator of Exercise Benefits in Mental Health. Curr Neuropharmacol. 2021;19(8):1304-1322. doi:10.2174/1570159X19666201218112748

[11] Watkins BA. Endocannabinoids, exercise, pain, and a path to health with aging. Mol Aspects Med. 2018 Dec;64:68-78. doi: 10.1016/j.mam.2018.10.001.

[12] Dietrich A, McDaniel WF. Endocannabinoids and exercise. Br J Sports Med. 2004 Oct;38(5):536-41. doi: 10.1136/bjsm.2004.011718.

[13] Russo EB. Beyond Cannabis: Plants and the Endocannabinoid System. Trends Pharmacol Sci. 2016 Jul;37(7):594-605. doi: 10.1016/j.tips.2016.04.005.

[14] Gertsch J, Pertwee RG, Di Marzo V. Phytocannabinoids beyond the Cannabis plant - do they exist?. Br J Pharmacol. 2010;160(3):523-529. doi:10.1111/j.1476-5381.2010.00745.x

[15] Mayo LM, Asratian A, Lindé J, et al. Elevated Anandamide, Enhanced Recall of Fear Extinction, and Attenuated Stress Responses Following Inhibition of Fatty Acid Amide Hydrolase: A Randomized, Controlled Experimental Medicine Trial. Biol Psychiatry. 2020 Mar 15;87(6):538-547. doi: 10.1016/j.biopsych.2019.07.034.

[16] Wim Hof Method. 2015. Cold Therapy. Retrieved from: https://www.wimhofmethod.com/cold-therapy

[17] Krott LM, Piscitelli F, Heine M, Borrino S, et al. Endocannabinoid regulation in white and brown adipose tissue following thermogenic activation. J Lipid Res. 2016 Mar;57(3):464-73. doi: 10.1194/jlr.M065227.

[18] Arias Horcajadas, F. Cannabinoids in Eating Disorders and Obesity. Mol Neurobiol 36, 113–128 (2007). https://doi.org/10.1007/s12035-007-0018-x

[19] Lafourcade M, Larrieu T, Mato S, et al. Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions. Nat Neurosci. 2011 Mar;14(3):345-50. doi: 10.1038/nn.2736.

[20] McPartland JM, Duncan M, Di Marzo V, et al. Are cannabidiol and Δ(9) -tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review. Br J Pharmacol. 2015 Feb;172(3):737-53. doi: 10.1111/bph.12944.

[21] World Health Organization. 2017. Drugs (psychoactive): Cannabidiol (compound of cannabis). Retrieved from: https://www.who.int/news-room/questions-and-answers/item/cannabidiol-(compound-of-cannabis)