Endocannabinoid Deficiency and Cannabis Use Disorder

an opinion piece written by staff writer Alexandra Arnett @calyx.alex

It is my opinion that psychiatrists and psychologists may be misdiagnosing some people who use cannabis with Cannabis Use Disorder (CUD). Now, my argument is not that people cannot misuse cannabis or cannot be addicted to it. Instead, I want to focus on how some symptoms of endocannabinoid deficiency can fit in with the diagnostic profile of Cannabis Use Disorder. It wasn’t until recently that cannabis education for medical and mental health professionals became more common, and maybe even more desirable to those professionals. Let’s start with some basics. Cannabis Use Disorder is defined as having 2 or more of the following symptoms; 

  1. Cannabis is often taken in larger amounts over a longer period than was intended.
  2. There is a persistent desire or insignificant effort to cut down or control cannabis use.
  3. A great deal of time is spent in activities necessary to obtain cannabis, use cannabis or recover from its effects.
  4. Craving or a strong desire or urge to use cannabis.
  5. Recurrent cannabis use resulting in failure to fulfill major role obligations at work, school or home.
  6. Continued cannabis use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of cannabis.
  7. Important social, occupational or recreational activities are given up or reduced because of cannabis use.
  8. Recurrent cannabis use in situations which is physically hazardous.
  9. Cannabis use is continued despite knowledge of having persistent or recurrent physical or psychological problems that are unlikely to have been caused or exacerbated by cannabis.
  10. Tolerance, as defined by either:
    1. A need for markedly increased amounts of cannabis to achieve intoxication and desired effect, or
    2. A markedly diminished effect with continued use of the same amount of cannabis.
  11. Withdrawal, as manifested by either:
    1. The characteristic withdrawal symptoms for cannabis, or
    2. A closer related substance is taken to relieve or avoid withdrawal symptoms.

Again, I am not saying that cannabis is not addicting or that people don’t misuse it. It is very understandable for criteria such as failing to fulfill major obligations due to your use of cannabis to be cause for a CUD diagnosis. I generally agree with criteria 2, 3, 5, 6, 7 and 9. The reasons I didn’t include 1, 4, and 8 are because I think that they can be easily misinterpreted in sessions, however, they do have standing when paired with other criteria and situations. For criteria 10 and 11, this is where I think endocannabinoid deficiency can provide a different explanation.

Cannabis tolerance is still a new research topic. It is very dependent on one’s own endocannabinoid system, for example, some people have developed a high tolerance in order to function on their dosage of medication. Some doctors may misinterpret this high dosage use of cannabis to indicate the cannabis tolerance is negative. One withdrawal symptom of cannabis is stated to be a lack of appetite, but what if that is the reason you choose to medicate with cannabis? Other withdrawal symptoms include anxiety, insomnia, depression and irritability, several of the many reasons why people choose to medicate with cannabis in the first place. Therefore, it would make sense that these symptoms would occur when cannabis use is stopped. However, therapists and other mental health professionals often stigmatized the use of cannabis and may misdiagnose their patients, creating a problem that does not exist.

Humans have two major endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Research has found that the endocannabinoid system in humans plays a large role in several bodily processes and functions, including ones that occur in the above-mentioned conditions. The purpose of the endocannabinoid system is to maintain homeostasis. When someone is deficient in certain endocannabinoids, this can cause dysregulation of that homeostasis, which in turn may be the possible cause of several conditions and symptoms. Endocannabinoid deficiency has been suggested to be the cause of several types of disorders that before have not been found to have a specific cause. Conditions such as fibromyalgia, irritable bowel syndrome, migraines, glaucoma, bipolar disorder, and more have all been suggested to be linked to endocannabinoid deficiency. 

As an example, let us take a brief look at migraines and the endocannabinoid system. From 1843 to 1943 when cannabis was put on Schedule I, cannabis was one of the main treatments for someone suffering from a migraine. While there are limited human clinical trials, the case studies and survey research that have been conducted have shown that cannabis use may help to treat migraines. From the research that has been done, individuals who suffer migraines show decreased anandamide and 2-AG levels. CBD acts via the TRPV1, a specific cannabinoid receptor, and also limits the production of the enzyme fatty acid amidohydrolase (FAAH) which is responsible for the breakdown of anandamide. THC on the other hand activates the CB1 receptors which may help treat migraines by potentially inhibiting the trigeminovascular system which plays a huge role in migraines and headaches. Supplementing with cannabis, THC and CBD can help bring the endocannabinoid system back into homeostasis. 

In addition to phytocannabinoids, there are things that an individual can do to naturally boost the body’s endocannabinoid system. We call these “cannabimimetic agents” and they include activities such as exercising, eating foods, or taking supplements high in Omega-3 fatty acids. 

Activities such as these help to boost your body’s endocannabinoid system without using any part of the cannabis plant. While you may be able to boost your endocannabinoid system without cannabis, there are still many unknowns when it comes to treating things like migraines, fibromyalgia, bipolar disorder, irritable bowel syndrome, and more. If using cannabis helps mediate symptoms than your standard pharmaceuticals, then the concern needs to be focused on researching why cannabis is working to treat that disorder instead of stigmatizing and misdiagnosing patients.

References

Russo E. B. (2016). Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes. Cannabis and cannabinoid research, 1(1), 154–165. https://doi.org/10.1089/can.2016.0009 

Cannabis, COVID-19, and our Lungs

Written By Alexandra Arnett, photographed by Danny Avina

Shortly before the world was hit with the COVID-19 pandemic, the US was suffering another lung crisis. Vape pens were all over the news in 2019 for reports of illnesses and deaths related to smoking them. The most recent update by the CDC was on February 18th, 2020. It showed that there have been 2,807 cases of illnesses related to nicotine or cannabis vapes, with 68 deaths. Among these patients, 2,022 of them reported which substance was being vaped, with 82% reported using THC containing products, while 33% reporting the use of exclusive THC containing products. Of the affected, 50% reported where their product was sourced, with 16% having obtained them from retail businesses and 78% obtaining them from friends, online, or other dealers. Overall, since the last article in February, there has not been a large rise in cases. However, it’s possible that the pandemic took front row for CDC priorities and it simply was not viable to keep reporting vaping illnesses, especially with what we know about the virus.

As a recap from the last Cannabis & The Lungs piece, we know that cannabis, specifically the terpene pinene and the cannabinoid THC, are both bronchodilators. As a bronchodilator, they help open up the airways to the lungs and may even help with conditions such as Chronic Obstructive Pulmonary Disease (COPD) and asthma. However, there are several ingredients that companies have been found to use in vape cartridges that have not shown to be safe for vaping—or have not been tested for inhalation safety at all. These ingredients include MCT oil, natural and artificial flavorings and non-cannabis derived terpenes.

So far, the vaping crisis seems to have been subdued and the focus has been shifted. Other than Colorado, no other states pursued permanent bans on anything other than Vitamin E acetate. Currently, in Oregon, the OLCC is in the process of putting together a cannabis vape-additive ban which would ban all additives other than natural cannabis-derived terpenes. This means no more natural and artificial flavoring, no non-cannabis-derived terpenes, and no MCT oil or other additives. California has similar pending legislation but it would allow for botanically derived terpenes and other natural flavors. 

More recently, COVID-19 and cannabis have been in the news as researchers have been scrambling to find some sort of medicine that can help ease symptoms and/or treat the effects of the virus. As mentioned in the paragraphs above, we know that THC and pinene are bronchodilators. Currently, researchers have been analyzing CBD and specific terpene formulations for potential to help fight against the virus. 

CBD has been found to be an ACE2 inhibitor and it reduces inflammatory cytokine production. The inhibition of ACE2 expression plays an important role in how COVID-19 enters host cells. When ACE2 expression is inhibited, the virus has a more difficult time entering a host cell. In relation to cytokine production, COVID-19 creates what is called a “cytokine storm.” This cytokine storm is the release of so many cytokines that they become harmful to the host cells. Researchers in Israel are currently looking at CBD in combination with a terpene formulation. This terpene formulation is a blend of 30 various terpenes that have shown to have anti-inflammatory properties. While the research has not gone through any clinical trials, the results the research has produced is promising information. 

Neither the author nor Green Eugene endorses anything in this article as medical advice for treating or curing COVID-19. If you are having symptoms please get tested and speak with your doctor. Remember to wear a mask, practice social distancing out in public spaces, and avoid large crowds.

CBD for Dummies

written by Alexandra Arnett, photographed by Nina Compeau

There has been a lot of buzz surrounding cannabidiol, or CBD, and while the FDA still restricts its use in food and beauty products, hundreds of new products have begun popping up since the enactment of the Hemp Farming Act of 2018.  So with all these products filling the shelves, what is the deal and what exactly is legal? How can one tell a quality hemp CBD product from an inferior hemp CBD product? 

As of August 2019, the DEA has retracted the status of CBD derived from cannabis from the Schedule 1 list, which means many new (and old) companies are hopping on the CBD bandwagon. At the end of October, the United States Department of Agriculture sent out interim rules for hemp production and testing. Currently, farmers can be issued a license for hemp production under their state or tribes’ own hemp regulation program or through the USDA. Individual states still have the right to make the production of hemp and hemp products illegal. Even though some states still have hemp production bans in place, the USDA reassured producers in legal states that interstate transfers of hemp may not be seized in states where hemp production is illegal.

While people often confuse hemp and cannabis, they are the same species of plant. Hemp has served as a legal definition for cannabis with less than 0.3% THC for the better part of its cultivation in the United States. Both cannabis and “hemp” varieties have the ability to produce high amounts of CBD. Hemp can also be grown for seed and fiber, which produce oils for beauty and food products and material for cloth. CBD products can come in many different forms, some of the most popular being edibles, tinctures and topicals, such as lotions and salves. CBD has also been seen in hair care products, beauty products, beverages and even clothing. To note, products using hemp seed oil will not always contain CBD. If the product has only hemp seed oil, then there will be little to no chance of CBD being present in the formulation. If the product uses hemp seed oil as a carrier for the CBD oil, then there will be CBD (and potentially other cannabinoids) present.

So what exactly is it that makes a CBD product worthwhile? CBD products can be made using three different CBD infusions: full-spectrum, broad-spectrum and isolate. Full-spectrum CBD is made using whole-plant extract and will contain at least the legal limit of total THC, 0.3%, and may contain other amounts of cannabinoids. Broad-spectrum CBD is similar to full-spectrum CBD, but with an extra step of extraction to pull out any THC that may be present. Isolated CBD is made from an extract that has had all other cannabinoids pulled from the oil and is typically at 99% purity. The number one thing consumers should look for in a CBD brand is those who have both full and broad-spectrum CBD products. While full-spectrum is highly recommended for help with pain, loss of appetite and nausea, it can also cause anxiety in some, as well as a positive drug test. If you are worried about a drug test, look for either broad-spectrum or isolate based products. Quality products include brands that source their flower from a trusted farm. Farms in California, Colorado, Oregon and Washington all have rigorous testing standards for their hemp and many of the “craft” hemp farms are located in these states. In addition to this, companies that can supply you with a verifiable lab report from an ISO 17025 certified lab are at the top of the list for having a higher quality product.

Now, how exactly do these CBD products work? 

First, let us start by saying that there are two types of cannabinoid receptors present throughout the body, CB1 and CB2. CB1 receptors are found all throughout the body and are mainly located in the brain. CB2 receptors are mainly found in the peripheral nervous system, gut and immune cells. CBD has a weak binding affinity for both the CB1 and CB2 receptors and instead plays a more indirect role in regulating cannabinoid receptors. 

CBD is also known to mediate the intoxication affects many people feel with THC. This happens because CBD blocks THC molecules from binding to more receptors by attaching to what is called an allosteric binding site. Think of it as if you were trying to put a key into a keyhole that a substance like gum had been stuffed into.

Indirect pathways in which CBD interacts with include those involved in anxiety, depression, pain, cancer cell growth and even heart health. For anxiety, CBD has various mechanisms of action by which it may contribute to combating the symptoms. CBD can mediate the 5-HT1A receptor, which is one that serotonin interacts with. Serotonin is involved in a variety of actions such as anxiety, addiction, nausea, sleep, pain perception and vomiting. 

In addition, CBD can inhibit the reuptake of adenosine through the GPR55 receptor, which helps contribute anti-inflammatory effects, as well as the anti-anxiety effects. This inhibition increases the amount of adenosine within the synapse of a neurotransmitter, allowing for more transmission of adenosine through your system. Because of this, CBD can also help regulate coronary blood flow and oxygen flow throughout the heart muscles. Referencing back to the GPR55 receptor, when it is activated, it promotes the growth of cancerous cells. CBD is able to help fight the growth of cancerous cells by blocking the activation of the GRP55 receptor. Activation of the GPR55 can also be thought of as like a key fitting into a keyhole while blocking it can be thought of as the gum that blocks keys from fitting.

Overall, CBD is a wildly new research topic with human clinical trials just beginning to pop up in various countries. There is so much that we don’t know about the cannabis plant and scientists are itching at the possibilities for treatments of epilepsy, anxiety, psychotic disorders, cancer and pain. Everyone has their own unique endocannabinoid system, so it is important to remember that cannabis products are not a one size fits all deal. It may take some trial and error to find that perfect product, so don’t be afraid to try various quality brands. Now, this doesn’t mean that the products that didn’t work for you aren’t quality products, maybe there was just too much of a certain terpene or cannabinoid that your body doesn’t like, or maybe it was grown with outdoor flower and was contaminated with an allergen your body is sensitive to. Consumer safety is very important, and thus education is key. Brands that I personally recommend include; Sun God Medicinals, Angel Hemp (Angel Industries), Empower, grön and Wyld.