Cobbers on the Brain

The use of marijuana as a prescription has been becoming increasingly popular since 1996 when California became the first state to legalize its medical use. Now, 22 years later, over half of the United States has legalized medical marijuana. In addition to its medicinal use, 10 states to date have legalized the recreational use of marijuana. With over 12% of the population of the United States over the age of 12 admitting to using marijuana in the past year, and with over 2.1 million individuals meeting the criteria of being dependent on marijuana, one begins to wonder if the drug is really as “harmless” as everyone believes.

So how does marijuana work in the body?

Within the body exists a special system known as the Endogenous Cannabinoid System (ECS). This system is made up of a series of special G-protein coupled receptors that are capable of being activated by cannabinoid-like molecules produced inside the body, termed endocannabinoids, or by outside cannabis-derived drugs, such as marijuana.  There are two specific families of these receptors in the body:

• CB1 receptors are found in the central nervous system. Because these receptors are found in regions of the brain such as the hippocampus, cerebral cortex, and cerebellum, the binding of cannabis-derived molecules has the ability to effect one’s ability to learn, form memories, and even move!
• CB2 receptors on the other hand are found on cells that are a part of our bodies immune system, such as natural killer cells and B-lymphocytes. Because of this, the binding of endogenous or exogenous cannabinoids can also effect how this system functions.

No matter the type of cannabinoid that binds to these receptors, a multitude of physiological responses are activated. Some of these responses can be beneficial to the body, while others may lead to deleterious effects.

So is marijuana truly harmless?

Although more research is needed to truly understand the mechanism by which marijuana works in the body, numerous studies have concluded that the drug is just as responsible for doing some “bad” in the body as it is for doing some “good”.

The Good:

• A treatment for:
  • Cancer:
    • Endocannabinoids are able to distinguish between cancerous cells and healthy ones. When endocannabinoids bind to cancerous cells, they initiate cell death. This cell death can stop the growth of tumors and the spread of cancer throughout the body.
      • Cancerous cells also have more CB1 receptors on their surface than healthy ones and are therefore more likely to have endocannabinoids bind to them.
  • Anxiety:
    • One of the main active ingredients in cannabis, THC, is capable of inducing relaxing and calming effects when it binds to CB1 receptors, however, THC only treats anxiety if it is used at an optimal concentration. Too much THC has been shown to actually worsen anxiety levels.

The bad:

• Altered Brain Development
  • The brain remains malleable until around the age of 21. With that being said, it is more vulnerable to changes during this time.
    • Research has found that individuals who smoked marijuana before their brains were fully developed have damaged neuronal connections in brain regions responsible for proper memory, learning, and self-awareness.
      • The earlier an individual starts smoking marijuana, the more likely they are to experience these adverse effects for the rest of their lives:

        

• Cognitive Impairment
  • Long-term use of cannabis has been shown to impact cerebral blood flow, specifically, it has been shown to decrease the flow of blood to and within the brain
    • This may lead to neuronal cell death.
  • Research has also shown that individuals that use cannabis are more likely to experience symptoms of psychosis, problems in executive function and spatial processing, and a difficulty forming and recalling memories when compared with those that have never used cannabis

The ugly:

The sad truth about marijuana is this:
Although a growing body of research has been done on the many different effects that marijuana has on the body, much about the drug is still unknown. Therefore, more research is needed to determine if marijuana, and other cannabinoid derivatives, are actually “okay” to be selling over the counter.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827335/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3221171/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691841/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366283/pdf/nihms-373922.pdf

https://www.ncbi.nlm.nih.gov/pubmed/23474290

What is Medical Marijuana?

Medical marijuana is the use of cannabis to treatment various diseases although the U.S. Drug and Administration (FDA) has not approved the plant a use of medication. There are two major components of marijuana, cannabinoids (CBD) and tetrahydrocannabinol (THC). THC is the major psychoactive chemical, that gives individuals the feeling of “high” while CBD is the derivative of cannabis that is typically used to treat the disease. In addition. there are over 100 different known types of CBD contained within marijuana that bind to different receptors throughout the entire body. The human body also produces chemicals that bind to these same receptors, called endocannabinoids.

Image 1: This image shows the differences between the two majors components in marijuana, CBD and THC
Source: https://www.pinterest.com/pin/448319337891247374/

Since marijuana is considered a schedule one drug, which means that is is considered to have no medical uses, although there appears to be some evidence to the contrary. Some large clinical trials have shown that the benefits of marijuana and the diseases that it treats outweigh the negative effects. This classification makes it difficult for researchers to find new medications or treatments. Despite this, there are two FDA approved medications that contain CBD, but no THC, that are used to increase appetite and reduce nausea.

What is Medical Marijuana used to treat?

Medical marijuana can be used to treat, not cure, many different illnesses and disorders including:

• Multiple Sclerosis — a disease that affects both the brain and spinal cord due to the death of myelin sheaths in the CNS often has medical marijuana prescribed to lower the severity of relapses and pain associated with the disease.
• Cancer — while cannabis is not a cure for cancer, it is often used for those who are undergoing chemo treatment by acting as an appetite stimulant and fighting nausea.
• HIV/AIDS — medical marijuana works to improve the quality of life for those diagnosed with HIV/AIDS, much like the way that cannabis acts as a treatment for cancer through appetite stimulation and reducing pain.
• Epilepsy — cannabis products, especially those having higher CBD concentrations, are shown to lower the frequency of seizures as well as the severity.
• Many more (see Image 1 for more examples)

Where is Medical Marijuana Legal?

Image 2: As of Nov. 14th 2018, these are the states that have legalized medical and recreational marijuana.
Source: https://www.vox.com/identities/2018/8/20/17938366/medical-marijuana-legalization-states-map

The image above shows the states that have legalized both medical and recreational marijuana usage. As mentioned earlier, the federal government still considers marijuana as a class one drug which means that is either subject to change or the dozens of states that now have laws that allow marijuana in one form or another will have marijuana become illegal again. However, it appears that more and more states are not only legalizing medical marijuana but recreational as well. This trend may lead to the eventual nationwide legalization and decriminalization of marijuana.

Guidelines that Doctors often follow

Although there is variation between doctors and how they prescribe medical marijuana in different situations there does appear to be some strategy that is followed by some. In 2017 the Medical Board of California as well as governor Jerry Brown created a pamphlet for doctors to follow when prescribing medical marijuana. Included in the pamphlet is the flowchart that is seen below.

Image 3: A flow chart that some doctors may follow when deciding to prescribe marijuana.
Source: http://www.blog.greatzs.com/2017/11/how-to-prescribe-medical-marijuana.html

Also, because of the classification of marijuana there is no direct way for doctors to “prescribe” it as they would any other drug. Instead they become certified and recommend patients that qualify. Usually before recommending a patient for medical marijuana, the doctor forms a relationship with them in an effort to not just become what is often known as a “marijuana mill” and just give the recommendation to all who come through. Other information that must be taken into consideration when recommending medical marijuana such as

• The patient’s history with other drugs.
• How long will the patient being taking the medication.
• Does the patient know the risks of being under the influence while driving and other possible risks?
• Knowing the CBD and THC content (if any THC content) and where and how they are going to obtain it.
• Any possible side effects, if combined with other drugs the patient is taking.

It inevitably boils down to the individual’s situation and the doctor who is prescribing the medication. There are many guidelines and different standards that people may follow.

Sources:

10 Most Common Conditions Medical Cannabis Is Prescribed For

https://www.drugabuse.gov/publications/drugfacts/marijuana-medicine

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1071601/

https://www.mdlinx.com/internal-medicine/article/2548

Over half of the states in the United States have legalized marijuana for medical uses, however so far, the FDA has only approved the treatment by medical marijuana for two specific types of epilepsy and some effects of chemotherapy. There is a lack of research on the effects of marijuana for medical uses as the FDA classifies marijuana as an abusive drug, therefore making it extremely dangerous to be a prescribed drug. This causes researchers to go through extensive testing and licensing just to be given permission to research medical marijuana and its effects.

The endocannabinoid system produces chemicals called cannabinoids and is a system that works to maintain homeostasis in the nervous system. Endocannabinoids are inhibitory and are made when needed to reduce a reaction and counteract overstimulation. The endocannabinoid system is responsible for maintaining:

• reproduction and fertility
• digestion and appetite
• sleep
• motor control
• pain
• pleasure
• immune function
• memory
• mood
• temperature 

The two most common cannabinoids are THC and cannabidiol. Both bind to the endocannabinoid receptors, which are CB1 and CB2. These receptors are moderated by GPCRs and when activated, are responsible for the symptoms caused by cannabinoids. The receptors were created for the endocannabinoid system, but they can also be activated by the chemicals in cannabis. 

CB1:

• located in brain and nervous system, as well as some other specific organs
• bind with THC and endocannabinoids
• aid in pain relief

CB2: 

• located in immune system
• bind CBD and specific endocannabinoids, such as 2-AG
• aid with appetite, inflammation, and immunity

The two most common endocannabinoids are anandamide and 2-AG. Endocannabinoids act like the body’s natural THC, with a much shorter and less extreme effect. THC is the psychoactive component of marijuana and is known for causing many changes in the brain, including:

• Increased blood flow in areas of cognition, emotion, and awareness
• Decreased blood flow in areas of sensory
• Altered brain activity in areas of reward, emotion, coordination, and speech

THC is responsible for the “high” feeling of marijuana. Cannabidiol, or CBD, is legal in all states and is naturally occurring. It is used to relieve symptoms of many diseases, including pain, inflammation, anxiety, depression, epilepsy, and chronic conditions. 

As medical marijuana contains both THC and CBD, there are varying effects that this treatment could have on an individual. In some cases, this could cause pain relief, a reduction in inflammation, or a feeling of relaxation and calmness. However, in other situations, it could cause panic, paranoia, or a worsening of symptoms. Similar to other prescription drugs, the reactions to the drug would have to be closely monitored. Some negative side effects of medical marijuana include:

• depression
• dizziness
• hallucinations
• low blood pressure
• judgement and coordination issues
• mental function deficits

However, the main conflict with the legalization of medical marijuana is the claim of it being a gateway drug. As the levels of THC increase, the addictive levels increase and cause an individual to become dependent on the drug for the symptom relief and “high” feeling. Another main issue is the regulation of medical marijuana and how it is administered to patients. As medical marijuana does not go through a pharmacy, it is argued that is could be easily abused and the marijuana will be different in every place it is received based on THC and CBD concentrations. 

Despite the negative effects and controversy behind medical marijuana, it could potentially have positive effects and aid in the treatment of many diseases. Some of these include:

• Alzheimer’s Disease
• appetite loss/eating disorders
• cancer
• chronic diseases
• epilepsy
• mental health disorders
• pain
• nausea
• muscle spasms
• glaucoma

The fight for the legalization of medical marijuana in all states and for many types of conditions will continue, however it seems that there may need to be more regulations and research done in order to truly understand the effects of medical marijuana, how to prescribe it and regulate its use, and in what ways medical marijuana can be beneficial for the population. 

https://www.greenrelief.ca/blog/cannabinoid-receptors/

https://www.webmd.com/a-to-z-guides/medical-marijuana-faq

“You look up and see stars. The sun shining down on you seems extra bright. You’re not really sure what is going on, so you look around for clues around you. You look at the scoreboard, ‘Okay I’m at school.’ You look down at your body and see your padded body, ‘Okay I was playing football.’ You look at the trainer, ‘What the heck just happened?’ She answers, ‘You got hit in the head pretty hard, you might have a concussion.’ That is the first thing that makes sense because your head feels like it is splitting in two.”

This is a real story from an individual who suffered a concussion during a football game. He told me about the confusion he felt, how dizzy he was, and how blinding the light was to look at right after. There are many stories that are just like this one told by many athletes around the world, but not only athletes suffer concussions. The Brain Injury Research Institute (BIRI) says that in the United States there are around 2-4 million concussions every year.

But what is a concussion?

A concussion is described as a biomechanical force to the brain. This causes a potassium efflux, and a sodium and calcium influx. This increase of calcium can lead to neurofilaments collapsing and axons losing their structural integrity leading to axonal dysfunction. There is also glutamate release at times when it is not meant to release, causing excitotoxicity inside of cells. With everything going wacky, ATP is required to bring everything back to normal. This calls for an increased consumption of glucose to provide ATP. This causes your energy stores of glucose to be low after a concussion and you can feel very exhausted from small activities.

Why Don’t We Eliminate Concussions?

http://a1.espncdn.com/combiner/i?img=%2Fphoto%2F2017%2F1026%2Fr280294_1296x729_16%2D9.jpg

Joe Flacco sustained a concussion on this hit from Kiko Alonso in a football game last year.

Since concussions are so prevalent and they can cause lasting and worsening effects of the brain and people’s lives, why don’t we just eliminate them? I believe that the main reason for this is: people care so much about their activities and the possibility of suffering a brain injury is worth it to participate in something they love doing. Just look at sports, according to BIRI 10% of all college football players and 20% of all high school players sustain brain injuries, 87% of professional boxers have sustained a brain injury, 5% of soccer players have sustained brain injuries, and an athlete who sustains a concussion is 4-6 times more likely to sustain a second concussion. In my personal opinion, we need to start looking at concussions more as a serious injury and I believe we have as a society. We need to get more information out there to those who are at risk for suffering concussions and for those who have already suffered concussions. We should be taught that the sport could end up costing you a normal life and that if you need to give it up, you should. Sometimes you need to sacrifice things you love for other things you love, whether that is not playing your sport after sustaining an injury; or a healthy brain. Sometimes love hurts.

Sources:

http://www.protectthebrain.org/Brain-Injury-Research/What-is-a-Concussion-.aspx

https://moodle.cord.edu/pluginfile.php/708078/mod_resource/content/3/2014%20The_New_Neurometabolic_Cascade_of_Concussion.3.pdf