• Shaina Painter

The Endocannabinoid System & CBD



Cannabis has been a controversial topic for many years due to propagated negative stigma and criminalization of a natural plant that warrants medicinal benefits. When writing this post, my intention is to deliver a scientifically sound outline of the benefits this plant exhibits.


Despite the controversy, I am a proponent of conscious cannabis use, meaning, if you chose to smoke, ingest or intake cannabis, THC or CBD, rather than having a glass of wine or a beer at the end of your day - enjoy! Conscious use means following the laws of your state and ensuring you are engaging in safe & mindful behavior with your use. Although you cannot technically overdose on CBD or THC, it is important to ensure you are regulating your use to curating dependence, like any tool relieving stress or modulating physiological function, which can become either healthy or unhealthy based on our choices.


A little history about marijuana: the cannabis plant was first noted by the ancient Chinese in 2737 B.C.E, (1), in addition to dating back to areas of Eastern Europe by anthropologists. Furthermore, marijuana played a role in many religious ceremonies across different multicultural groups for ages.


In 1937, the U.S. criminalized the use of marijuana, a notion moving against the advice provided by the American Medical Association, (1). Becoming a Schedule I substance under the Controlled Substance Act in 1970, marijuana remains illegal in many states and under federal law today. Recently, certain states have moved forth with legalization for recreational purposes, recognizing the economic and medical benefits of legalization. The classification of marijuana as a Schedule I placed a restriction on the use of clinical trials on the effects medicinally. Other drugs under Schedule I include heroin, mescaline, psilocybin, and LSD, further elucidating the notion marijuana elicits a highly addictive property leading to further abuse and false stereotypes thus fueling negative propaganda and increasing the stigma among cannabis-using society.


Cannabis is complex, constructed of over 100 different cannabinoids with the ability to benefit those suffering from pain through neuromodulation, eliciting neuroprotective effects, anti-cancer effects, increasing muscle tone, improving overall mood, appetite, and contributing to the reduction of inflammation in varying conditions, (1).


 

What is the Endocannabinoid System (ECS)?


The endocannabinoid system is a modular series of receptors maintained by mammalian cells responding to various cannabinoids, (2). The system was originally discovered in 1992, uncovering receptors known as CB-1 and CB-2, and in 1995, the first cannabinoid-like chemical called arachidonylethanolamide or Anandamide was discovered, (2). Anandamide is a fatty acid neurotransmitter derived from eicosatetraenoic acid, an essential omega-6 PUFA, acting on both receptors, and particularly modulating the immune system of the peripheral nervous system in conjunction with its co-partner lipid-derived ligand 2-arachidonyl glycerol (2-AG), (2).


CB-1 receptors fall under the family of GPCR, G-protein-coupled receptors, otherwise known as the largest group of receptors in eukaryotes, (4). The most abundant amount of CB-1 receptors lie within the central nervous system and the brain, many among the fore- and midbrain (4). In particular, these areas of the brain modulate motor function, memory, nociception, and cognition. THC has an affinity to bind to CB-1 receptors, in addition to the agonistic substance anandamide, creating either an excitatory or inhibitory effect on the receptor, (4). CB-1 plays both an inhibitory and excitatory role in neurotransmitter release, further maximizing its effects in pain modulation and mood regulation, (4).


CB-2 receptors also belongs to the G-protein family and are selectively activated, (5,6,7). In healthy individuals, CB-2 receptors are an abundant form of a macrophage cell found in immune and peripheral nervous system cells, (5,6,7). Specifically, CBD has an affinity to bind with CB-2 receptors which have been shown to be agonists in therapies combatting neuroinflammatory conditions and neuropathic, such as atherosclerosis, chronic pain, IBS, Alzheimer's, Parkinson's, MS, etc, (5,6,7). In both in vitro and in vivo analysis of CB-2 activation, a decrease of inflammation was recognized and in cases of deletion of these cells, inflammation was exacerbated, (5,6,7).


The ECS has displayed within research to be a system important for modulating vital physiological functions within mammalian species. The main end goal from the endocannabinoid system is homeostasis, (3). The ECS modulates ALL body systems by regulating intercellular communication, modulating metabolism processes, and coordinating tissues, organs, and body systems, (3).


Noteworthy, the ECS influences aspects of metabolism pertaining to the peripheral and central mechanisms of food intake but additionally, lipid synthesis, and glucose metabolism, (8). Thus leading to a reduction in adipose tissue, improvements in HDL, a decrease in LDL, leptin, and C-reactive protein (a pro-inflammatory marker playing a role in cardiovascular disease), (8). A deficient ECS system could propagate conditions such as IBS, migraine headaches, fibromyalgia, PCOS, and other conditions displaying symptoms closely relating to a deficiency in this system, (9).


Ultimately, we are all dependent upon a functional ECS system. The more these receptors are activated, the more abundant they become within our bodies.


Below, I have included a diagram of the areas in which the body maintains ECS receptors:


 

What is CBD?


Of the many different cannabinoids found in the marijuana plant, the only psychoactive cannabinoid is THC, or delta-9-tetrahydrocannabinol, (2), therefore, the extreme conditions under which this plant has been placed under is quite fascinating. The experienced THC psychoactive effects include relaxation, an altered sense of sight, smell, and hearing, fatigue, hunger, and reduced aggression or irritation. CBD on the other hand does not assert these effects and exclusively provides various benefits for conditions such as Alzheimer's, Parkinson's, Chronic pain, ALS, Rheumatoid Arthritis, MS, Autism, any predominantly inflammatory conditions, various autoimmune diseases, anxiety, ADHD, Schizophrenia, cardiovascular diseases, and some gastrointestinal disorders.


CBD is not to be confused with hemp, the anti-psychoactive marijuana plant containing less CBD and terpenes (if any) but still upholds its own benefits. CBD can be extracted from hemp plants, which most of the CBD oils on the market are sourced from. Checking out testing facts, extraction methods and processing are very important when utilizing a hemp-based source. However, both marijuana and hemp plants come from the same species - cannabis Sativa, cannabis Indica, or cannabis ruderalis.


Cannabidiol, or CBD, is highly anti-inflammatory and induces upregulation activity of regulatory T-cells to fight off harmful pathogens, (10). CBD enhances IL-2 production, an interleukin regulating white blood cell activity, when T-cell stimulation is inherently low, (11). It is possible the anti-inflammatory effect of CBD is attributed to the dysregulation of inflammatory cytokines, specifically relevant and important in those with autoimmunity, (10).


Warranting immune supportive and anti-inflammatory effects, CBD and THC exhibit a neuroprotective effect. Glutamate, an excitatory neurotransmitter can become toxic under relative conditions, (12). CBD and THC have shown a neuroprotective response and exhibited potent antioxidant-like characteristics during conditions of glutamate toxicity, (12).



Most importantly, CBD has been shown to elicit anti-cancer effects. A study by Marcu et al., (2010) uncovered CBD with THC acted synergistically to interact with glioblastoma cells, the most aggressive form of brain cancer, modulating cell life, inducing apoptosis, and modulating extracellular signal-regulated kinase (ERK), (13). The study specifically noted these effects were not witnessed individually, therefore, the compound elucidates the need for a full-spectrum CBD supplement (maintaining a small % of THC) to experience the full medicinal benefits of the marijuana plant.


CBD has also been studied on forms of invasive aggressive breast cancer. A study conducted by McAllister et al., (2007), uncovered CBD inhibits expression of Id-1, in which the primary role of expression is to induce cancer cell growth and promote cell survival, (16). This study revealed CBD is the first form of an exogenous agent to down-regulate tumor aggressiveness, particularly in aggressive breast cancer, (16). Lastly, anandamide has been also shown to inhibit the growth of colorectal carcinoma (CRC) cells by inducing cell death, (18).


Of the 100+ cannabinoids involved in marijuana plants, CBD & THC are most predominant, however, there are other types of cannabinoids that may play significant roles within the endocannabinoid system in our physiology. There is a very small subset of scientific evidence on these, so more research is needed to make definitive associations.





I've seen this wheel float around the internet a bit, although, I am unable to locate a scientifically-based source - it places into perspective the many manifestations cannabis can take on within our system.








 

Okay, so what's the deal with THC?


Delta-9-tetrahydrocannabinol or THC obviously is psychoactive but it elucidates benefits when in combination with a high CBD product. Although THC has not been shown to affect adult neurogenesis, it has been shown to affect teenage neurogenesis and learning capabilities, (14,15). In comparison, a study uncovered CBD improved adult neurogenesis, thus working antagonistically with THC, (14).


Within adolescent early-onset users (16 or younger), this study observed a decline in white matter in addition to fractional anisotropy (FA) or connections within the brain, in comparison to a non-smoking control group, (15). Even later onset, age 16~25, resulted in a significant reduction of FA leading to a greater probability of impulsive behaviors, (15).


Taking this information into consideration, age, frequency of use, dose, and quantity of intake are all important factors to understand when ingesting this information.


 

How to Utilize


Cannabis can be utilized in many different forms: smoking, vaporizing, topically, ingestion, and sublingually.


Smoking cannabis, whether it be CBD or THC dominant, can lead to exposure of harmful by-products such as tar, pesticides, heavy metals, and other biological contaminants such as bacteria or fungus, (17). Vaporizing, however, does not reach the point of combustion thus resulting in a reduced risk of damaging the respiratory tract, (17). When smoked or vaporized, the effects can be felt within minutes, lasting a duration of 2-3 hours on average, (17).


Oral ingestion can include edibles or sublingual ingestion. Edibles can take the form of cookies, candy, brownies, drinks, butter, or any other edible product. These products take anywhere from 30-90 minutes to onset and last roughly 4-12 hours, (17). Edibles are more variable due to the need for metabolism by the GI tract and liver.


Sublingual products can take the form of an oil or spray. This form of administration is fairly rapid, experiencing onset within 10-15 minutes, lasting for roughly 2-4 hours, (17). Ingestion through this method results in direct contact with the mucosal membrane, entering into the systemic circulation, and lastly, passing through the liver, (17).


Based on individuals who reside in states where marijuana is deemed illegal, or prefer not to experience the psychotropic effects, a CBD isolates derived from hemp oil may be a suitable form of intake. Please be sure to read testing information (aka sending an email and asking for their testing papers), ensure it is good sourcing and processing before purchasing.

 

My Experience with CBD


I started supplementing with CBD roughly 2 years ago. My anxiety became wicked and I needed some support. I have previously used THC but it never truly subsided my anxiety quite like CBD.


CBD has been a powerful supplement in my life, struggling with a thyroid condition for 11 years has resulted in a roller-coaster of symptoms, emotions, and experiences. I've spoken to my thyroid condition before and the difficulty I've faced managing a normal function since being diagnosed. I can truly say after nixing food sensitivities and incorporating anti-inflammatories. like CBD, has resulted in close to the normalization of my off the chart antibodies.


The brand I use right now is Select CBD, a hemp-derived CBD isolates paired with herbs such as lavender, chamomile, & passionflower, peppermint, ashwagandha, & Rhodiola, and lemon, ginger & turmeric.


I typically purchase a 1000mg CBD blend of peppermint, ashwagandha, and Rhodiola. Both are labeled as adaptogens and assist in adaptations to stress & anxiety. Since Rhodiola can have contraindications with thyroid replacement hormones, I typically ingest my serving of CBD before bed. I LOVE the pepperminty detail on both my Ritual vitamin & CBD - it really puts you in a restful mood, ya know? I used to vaporize but I've found a greater effect utilizing it sublingually.


Anyways, CBD has become a large part of my supplement ritual and I am so excited to share this wealth of knowledge with you. I have always been very open to ideas others are against because there is no one size fits all. EVER. There will and is always two sides to every story. This poor beautiful, magical plant has been criminalized so badly - people have learned to abuse and misuse it's powers.


If you learn anything from this post, other than the details of how our body is designed to ingest the marijuana plant, I hope it is to not judge a book by its cover.


 



 

References:


1. Aggarwal et al. (2009). Medicinal use of cannabis in the United States: historical perspectives, current trends, and future directions. Journal of Opioid Management, 5, 153–168.

https://www.ncbi.nlm.nih.gov/pubmed/19662925


2. Pacher, P., Bataki, S., & Kunos, G. (2006). The Endocannabinoid System as an Emerging Topic of Pharmacotherapy. Pharmacol Rev. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2241751/pdf/nihms38123.pdf


3. Melamede, R. (2005). Harm reduction-the cannabis paradox. Harm Reduction Journal.

https://harmreductionjournal.biomedcentral.com/articles/10.1186/1477-7517-2-17


4. Mackie, K. (2006). Mechanisms of CB1 receptor signaling: endocannabinoid modulation of synaptic strength. International Journal of Obesity.

https://www.nature.com/articles/0803273


5. Dhopeshwarkar, A., & Mackie, K. (2014). CB2 Cannabinoid Receptors as a Therapeutic Target - What Does the Future Hold? Molecular Pharmacology.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164977/pdf/mol.114.094649.pdf


6. Turcotte, C., Blanchet, M., Laviolette, M., & Flamand, N. (2016). The CB2 receptor and its role as a regulator of inflammation. Cell. Mol. Life Sci.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075023/pdf/18_2016_Article_2300.pdf


7. Cassano, T., Calcagnini, S., Pace, L., De Marco, F., Romano, A., & Gaetani, S. (2017). Cannabinoid Receptor 2 Signaling in Neurodegenerative Disorders: From Pathogenesis to a Promising Therapeutic Target. Frontiers in Neuroscience.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288380/pdf/fnins-11-00030.pdf


8. Komorowski, J., & Stepien, H. (2007). The role of the endocannabinoid system in the regulation of endocrine function and in the control of energy balance in humans. Postepy Hig Med Dosw.

https://www.ncbi.nlm.nih.gov/pubmed/17369778


9. Russo, E. (2008). Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuro Endocrinol Lett.

https://www.ncbi.nlm.nih.gov/pubmed/18404144


10. Nagarkatti, P., et al,. (2009). Cannabinoids novel anti-inflammatory drugs. Future Med. Chem.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828614/pdf/nihms155268.pdf


11. Dhital et al. (2017). Cannabidiol (CBD) induces functional Tregs in response to low-level T cell activation. Cellular Immunology.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5327652/pdf/nihms-830656.pdf


12. Hampson, A., Grimaldi, M., Axelrod, J., & Wink, D. (1998). Cannabidiol and (-)Delta9-tetrahydrocannabinol are neuroprotective antioxidants. Proc. Nat Acad Sci U.S.A

https://www.ncbi.nlm.nih.gov/pubmed/9653176


13. Marcu, et al., (2010). Cannabidiol enhances the inhibitory effects of Δ9- tetrahydrocannabinol on human glioblastoma cell proliferation and survival. Mol Cancer Ther.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806496/pdf/nihms162015.pdf


14. Wolf, S., et al. (2010). Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis. Cell Commun Signal.

https://www.ncbi.nlm.nih.gov/pubmed/20565726


15. Gruber, S., Dahlgren, M., Sagar, K., Gonenc, A., & Lukas, S. (2014). Worth the wait: effects of age of onset of marijuana use on white matter and impulsivity. Psychopharmacology.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967072/pdf/213_2013_Article_3326.pdf


16. McAllister, S., et al., (2007). Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells. Molecular Cancer Therapies.

http://mct.aacrjournals.org/content/6/11/2921.long


17. Ciccone, C. (2017). Medical Marijuana: Just the Beginning of a Long, Strange Trip? Physical Therapy

https://academic.oup.com/ptj/article/97/2/239/2937746


18. Patso, H., et al., (2005). The endogenous cannabinoid, anandamide, induces cell death in colorectal carcinoma cells: a possible role for cyclooxygenase 2. Gut.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1774787/pdf/gut05401741.pdf

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