A science backed op-ed on health and CBD.

Health is defined as the condition of being sound in body, mind, and spirit by Merriam-Webster. So, we have the health of our physical bodies, our mental health, and the health of our “drive” as I would call it. As humans, we have a lot of ways that we try to understand health. Some may say that being “skinny” is healthy and being over-weight is “unhealthy”. Is a professional lineman in the NFL unhealthy? I would assume not and yet we have these ideas of what health is driven into us by what? Or whom?

As a child, I dealt with weight issues a lot, but in reflection, I never really dealt with health issues. I was athletic, able-bodied, and energetic, and yet I was harassed at school by my peers for being big. This made me question a lot about myself and how I fit in with society. It also gave me the drive to be better than I was. But, it’s interesting to me that it was my “peers” who told me I was “unhealthy”. It’s also interesting to me that I listened to this feedback, as many of us do, regardless of whether it’s accurate information or not.

I don’t think many things change from middle school to “adult life”. The way we as people interact with each other on a personal and professional level. There is usually a person in a situation who “controls” the tempo and direction of a conversation. That person has a lot of responsibility to steer the conversation on the right course whether they know it or not. As for everyone else, they all have to have the ability and composure to decipher truth from fiction. Science was what I found when looking for truth in college. I graduated with a BS in Forestry and a minor in Wildlife Conservation in 2008 from Unity College in Maine and it was at this time where I learned to appreciate the scientific method and how it can teach us how to learn.

13 years later and I’m still learning every day. I read clinical trials and scientific articles because I want to know everything about how my products work. This process never really stops for me, but I thought it was time to tell you all what I’ve discovered. Please understand though. I am not a doctor, just a guy trying to understand a plant and to better appreciate what that plant gives us. What I mean is that please do not take this as medical advice. Use this instead as inspiration to go out and read clinical trials on your own so that you can also better understand what science is trying to tell us and decipher your truths from fiction.

Into the nitty-gritty

CBD research is still in its infancy in many ways. This is partly due to the complex relationship CBD has within our body as it has many possible functions depending on what is needed at the time. When CBD interacts with receptors it can fulfill a few different roles including; acting as a modulator, a partial agonist, and an antagonist. These are terms used by researchers that may take some time to get used to but after a few additional open tabs on your browser, you’ll get familiar with them. I’ll also do my best to explain. Other terms to identify are the difference between a phytocannabinoid and an endocannabinoid. Remember, phyto means plant so a phytocannabinoid comes from cannabis and an endocannabinoid is produced by your body. The other cause of the lack of CBD research is that the work hasn’t received positive attention in the past because of the common misperception that cannabis is “unhealthy.” Even though Cannabis as a whole has been used for pain treatment for longer than written history (3).

CBD is moved by the blood after absorption by the stomach (your stomach has many endocannabinoid receptors FYI). It is then filtered by the liver which can lead to some enzymatic changes to some of the CBD molecules. There are other ways CBD can get into your body and interact as well, like sublingual administration if rested in your mouth for 60 seconds or inhalation if it is smoked as flower, but let’s focus on ingestion.

Before and after the liver has processed CBD, it can function as a “modulator”, an “antagonists” and other times as a “partial agonists.” In these ways CBD is more “indirect” in its functionality than a “full agonist” (6). It’s important to know that an antagonist is a molecule that does not initiate a response when attached to a receptor while an agonist aka “full-agonist” does initiate a response (6). CBD interactions take place at receptor sites between presynaptic and postsynaptic neuron sites and the area of space between called the “synaptic cleft” where molecules float around available for the opportunity to attach to a permitting receptor (9). Not all keys “fit” into a particular “lock” and while some interactions are very straight forward, others are a little more ambiguous and complex like CBD.

Full-agonists, or a chemical that initiates a physical response to a receptor are easily understood. For example, THC is an agonist to the CB1 receptor which initiates the physical response of euphoria mixed with a little mindfulness (aka psychoactive). It is this distinction that makes CBD so difficult to understand. Since there is no direct path of functionality, we have to look at the “soup” from a little further back to see how it fully interacts. This is really where the rubber meets the road too in that technically CBD is psychoactive in that it does have an effect on the mind and our behavior. If it didn’t, then why can I feel it when I take it? Why do I “relax” or fall asleep faster? Especially if I take a little more than I typically do.

To illustrate again how complex these systems are, certain terpenes also play a role in inflammation and even pain reduction as beta-caryophyllene selectively attaches to the CB2 receptor (acting as an agonist) allowing it to serve as a “phytocannabinoid” (6). Myrcene displays opiate-type analgesic (pain relief) effects along with anti-inflammation properties too (6). The ECS has also been found to interact with the endogenous opioid system. This interaction is also non-direct in its functionality, but it has been proposed that CBD may be able to help “wean” people off opioid dependency as well as lessen the strength of opiates one needs to take to reach the desired effect, lowering the chance of developing dependency in the first place. (7)

As stated before, CBD is partially considered a “modulator” and of the roles it plays this seems to be the most often referenced and possibly its most important “function”. Modulation to me is a system of checks and balances. Where, when one type of presynaptic neuron within our body gets out of balance or overly stimulated and needs something to control it (an agonist) there is a release of a molecule from the presynaptic cell that attaches to a specific receptor or enzyme on the postsynaptic cell side which in turn releases another molecule (not CBD, but the endocannabinoid anandamide) to interact with the original neuron needing attention. CBD if available at the right time can facilitate the release of anandamide and thus prevent the initial neuron “excitement”. The signal to release a molecule from the presynaptic side is kind of like the fuel light in your car turning on before you run out of gas. That way you know to go to the gas station and refill the tank so you can get back on the road. It’s not overly complicated, there are just a lot of steps. The difference though is that there are an estimated 30 trillion cells in an individual’s body and CBD is just one type of molecule looking to interact with particular receptors. It’s a literal metropolis. 

These extremely complicated series of highly variable interactions have led some to believe that the effects observed from CBD might be “state-dependent”. (8) As CBD can sometimes be a partial agonist, it is known that these types of agonists are dependent on receptor expression, density, and tonic activity of the system, meaning that it may vary under different tissues and different conditions. (8) This is one of the more profound ideas I came across in my research and it resonated with me deeply. This idea that our bodies are in a constant state of change seeking equilibrium, stability and that there is this molecule that seems to be able to effectively strengthen the “balance” of this system. Unfortunately, it also makes understanding this concept a little harder to understand. Essentially though, CBD is able to indirectly control or “guide” our bodies systems to a more stable position. Aka a “healthier” state of being.

Sometimes, someone in the scientific community will write a paper looking at multiple studies to better understand a more general outlook of what is happening. In 2017 a paper was published by Mary Ann Liebert, Inc in the cannabis and cannabinoid Research Journal titled “An Update on Safety and Side Effects of Cannabidiol: A review of Data and Relevant Animal Studies”. The article reviewed previously published clinical studies revolving around CBD and looked to better understand potential interactions with other drugs and to look at the safety of CBD as a whole. This paper gives a lot of insight into the preliminary work that needs to be done to begin to understand the chain reactions that occur when a substance like CBD is taken. The paper looked at clinical studies written by their professional peers ranging from patients with Parkinson’s disease, Huntington’s disease, cancer and how it may affect the immune system. It included patients suffering from leukemia, malfunctioning endocrine systems, seizures, epilepsy, schizophrenia, bipolar disorder, anxiety, cell migration of cancer, Alzheimer’s, and addiction to name a few.

If you’re like me and saying to yourself, “I don’t have any of those conditions?” other than some anxiety maybe? I get it, and I understand your confusion. But hang in there. Here’s what they found.

CBD didn’t always have a positive correlation or outcome in terms of treating these serious ailments, but it never was reported to have any serious negative side effects either. It specifically states, “In conclusion, CBD safety profile is already established in a plethora of ways”(1). What the paper does say though is that CBD did have several beneficial pharmacological effects. For instance, it is anxiolytic (lessens anxiety), antiemetic (good for nausea), and an antipsychotic. Physiological effects were observed as well including anti-oxidative, anti-inflammatory, and neuroprotective effects which help promote and maintain health (1).

Back to that word health again.

So, science couldn’t completely put its finger on what ailments CBD could be used to treat clinically, not including its current use in treating rare pediatric seizures. But they could tell us that it won’t hurt you and that there are in-fact many positive attributes that CBD has. This is where we need to think about what we want to get out of CBD when we take it. For example, as a 36-year-old young man, I find myself not feeling the same as I did when I was 26. Spending a day out skiing is a little harder on the body, inflammation lasts a little longer and is more systemic than in my youth. I get more severe gastrointestinal issues than ever before too and yet I have never been more conscientious of health and how I want to feel. I eat well, I drink less and I still exercise and practice yoga 2-3 times a week… I guess what I am saying is that while I’m taking steps to better my health, I am fighting an uphill battle with time, as many of us are. And, while I don’t have any major health problems that need specific medical attention, I do have small health issues that CBD can help with. Inflammation? Yes. Headaches? Yes. Stress? Yes (I started a business during a pandemic). Anxiety? Yes. Troubles going to sleep, not so much actually. I go out fast, fortunately. But, “winding down” after a long day, oh yes. Every one of these things positively contributes to my mental and physical health when they are managed correctly, I feel healthier. And, if I choose CBD some nights over having 2-3 beers? That’s where I really feel the difference.

So, my body is in a different state now than it was when I was 26? Right. Your body is attempting to balance itself right now with all the tools that it has as well as the tools you have given it. Over time our bodies may need more “help” with controlling our internal bodily functions. Now, there are a lot of ways to go about re-balancing out your system as modern pharmacology has shown all of us, but if you’re like me than you’re probably trying to wean yourself from that indoctrination of prescription drug culture and looking for more natural alternatives. Now, is CBD going to help every single person in the world be “healthier”? It could, but not everyone is open-minded about cannabis and that’s okay. But for those of us who need or want a little plant-assisted relaxation/aid in our lives without the need for a prescription. Well, we have the solution.

What I know so far is this: If I don’t have anything seriously medically wrong with me but I want to continue to improve or maintain my health, CBD can help facilitate that. To me, that sounds like another tool in my toolbox. A tool I can use to improve my wellness or “health” naturally.

“The more I learn, the more I realize how much I don’t know.”

Albert Einstein

Resources:

1. Iffland K, Grotenhermen F. An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies. Cannabis Cannabinoid Res. 2017 Jun 1;2(1):139-154. doi: 10.1089/can.2016.0034. PMID: 28861514; PMCID: PMC5569602.

2. Fankhauser M. History of cannabis in Western medicine. In: Grotenhermen F, Russo EB, editors. Cannabis and cannabinoids: pharmacology, toxicology and therapeutic potential. Binghamton: Haworth Press; 2002. p. 37–51.

3. Russo EB. History of cannabis as medicine. In: Guy GW, Whittle BA, Robson P, editors. Medicinal uses of cannabis and cannabinoids. London: Pharmaceutical Press; 2004. p. 1–16.

 4. Russo EB. History of cannabis and its preparations in saga, science and sobriquet. Chem Biodivers. 2007;4(8):2624–48.

5. Mechoulam R. The pharmacohistory of Cannabis sativa . In: Mechoulam R, editor. Cannabinoids as therapeutic agents. Boca Raton: CRC Press; 1986. p. 1–19.

6. Fankhauser M. History of cannabis in Western medicine. In: Grotenhermen F, Russo EB, editors. Cannabis and cannabinoids: pharmacology, toxicology and therapeutic potential. Binghamton: Haworth Press; 2002. p. 37–51. 19. Russo EB. History of cannabis as medicine. In: Guy GW, Whittle BA, Robson P, editors. Medicinal uses of cannabis and cannabinoids. London: Pharmaceutical Press; 2004. p. 1–16. 20. Russo EB. History of cannabis and its preparations in saga, science and sobriquet. Chem Biodivers. 2007;4(8):2624–48. 21. Mechoulam R. The pharmacohistory of Cannabis sativa . In: Mechoulam R, editor. Cannabinoids as therapeutic agents. Boca Raton: CRC Press; 1986. p. 1–19.

7. Fankhauser M. History of cannabis in Western medicine. In: Grotenhermen F, Russo EB, editors. Cannabis and cannabinoids: pharmacology, toxicology and therapeutic potential. Binghamton: Haworth Press; 2002. p. 37–51. 19. Russo EB. History of cannabis as medicine. In: Guy GW, Whittle BA, Robson P, editors. Medicinal uses of cannabis and cannabinoids. London: Pharmaceutical Press; 2004. p. 1–16. 20. Russo EB. History of cannabis and its preparations in saga, science and sobriquet. Chem Biodivers. 2007;4(8):2624–48. 21. Mechoulam R. The pharmacohistory of Cannabis sativa . In: Mechoulam R, editor. Cannabinoids as therapeutic agents. Boca Raton: CRC Press; 1986. p. 1–19.

8. Cannabidiol for Pain Treatment: Focus on Pharmacology and Mechanism of Action Jakub Mlost † , Marta Bryk † and Katarzyna Starowicz * Department of Neurochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, 31-343 Krakow, Poland; mlost@if-pan.krakow.pl (J.M.); bryk@if-pan.krakow.pl (M.B.) * Correspondence: starow@if-pan.krakow.pl; Tel.: +48-12-66-23-206 † These authors contributed equally to this work. Received: 31 October 2020; Accepted: 20 November 2020; Published: 23 November 2020 P.12

9. Synaptic effects of cannabinoids

Complexity, behavioral effects, and potential clinical implications

Eduardo E. Benarroch

Neurology Nov 2014, 83 (21) 1958-1967; DOI: 10.1212/WNL.0000000000001013