Cobbers on the Brain

Marijuana has been gaining a foothold in the United States. A drug that was once illegal is now legal for recreational use in some states. In 1996, California became the first state to legalize its medical use. Now, in 2018, it is used recreationally in 10 states, and used medically in 23 states. It seems inevitable that this once prohibited plant will be legal in some shape or form in all 50 states within our lifetime. This warrants a closer look into this leafy substance.

The Endogenous Cannabinoid System (ECS) exists within our body. The ECS is made up of G-protein coupled receptors that are activated by cannabinoid-like molecules. Our body has a series of its own cannabinoid molecules called endocannabinoids. There are also exogenous cannabinoids, like marijuana, that can be used to stimulate this system.

Marijuana has numerous effects on the body. Therefore, the drug can be used medically to treat people. According to an article from webmd, doctors may prescribe medical marijuana to treat:

• Alzheimer’s disease

  

• Appetite loss
• Cancer
• Crohn’s disease
• Eating disorders such as anorexia
• Epilepsy
• Glaucoma
• Mental health conditions like schizophrenia and PTSD
• Multiple sclerosis
• Muscle spasms
• Nausea
• Pain
• Wasting syndrome (cachexia)

As you can see, marijuana can be used in a positive way. However, when it is used recreationally, marijuana could become addictive contrary to popular belief. Marijuana reaches the same pleasure centers in the brain that are targeted by heroin, cocaine and alcohol. While it is widely thought that marijuana is not addictive, about 30 percent users may have some degree of marijuana use disorder, according to NIDA.

Long-term marijuana users who try to quit experience cravings, irritability, sleeplessness, decreased appetite and anxiety — some of the same physical symptoms of those trying to quit other types of drugs or alcohol. A 2016 study found a link between certain genetic markers and symptoms of marijuana addiction, suggesting that some people may have a genetic predisposition to marijuana addiction. According to research from the Potency Monitoring Project, the average THC content of marijuana has soared from less than 1 percent in 1972, to 3 to 4 percent in the 1990s, to nearly 13 percent in 2010. Today, some retail marijuana has 30 percent THC or more. The increased potency makes it difficult to determine the short- and long-term effects of marijuana.

Therefore, I understand the positive impacts of medical marijuana, but marijuana for  recreational purposes warrants more research. As this leafy green substance gains popularity in the U.S., more research needs to be published that encompasses the overall picture of the drug. Is it really okay to smoke a little pot? The “blunt” truth is, marijuana may be more harmful than people think if it is used recreationally.

https://www.webmd.com/a-to-z-guides/medical-marijuana-faq#1-3

https://onlinelibrary.wiley.com/doi/full/10.1111/j.1556-4029.2010.01441.x

https://www.drugabuse.gov/publications/research-reports/marijuana/marijuana-addictive

https://www.livescience.com/24558-marijuana-effects.html

One would bet that every single person knows someone in their life that could potentially benefit from a pure medicinal marijuana or even the cannabidiols. Know anyone with cancer? Multiple sclerosis? Epilepsy? Pain? Could this illegal drug help our community? Should it?

Cannabis, marijuana, pot, etc is not something one would expect as a medically prescribed treatment plan, especially considering its prevalent recreational use. However, in the last 10 years endocannabinoids have slowly moved into the medical field. In the US its legalization for medicinal purposes has been spreading. We’ve heard it all over the news as certain states legalize it while others commit to keeping it illegal regardless of potential medicinal uses. Yet, as the medicinal is slowly becoming legalized, as a whole it is still illegal and categorized as a schedule 1 drug. Out of the five schedules it is in the highest along with heroin, LSD, ecstasy, methaqualone, and peyote. This means it is very difficult to legally obtain samples for research, and therefore it is not entirely understood. There is irony of this scheduling as it pertains to research, due to it being very ‘easy’ to get on the streets. From street knowledge and experience one would not have to look to hard to find it if they truly wanted. It’s in schools, found at parties, and has become a very generalized thing in the minds of the younger public, with a mindset that “everyone is doing it.” 

Cannabis has been prescribed more and more as the beneficial effects of certain compounds arise. These cannabinoids have been FDA approved within pill form, as cannabidiols (CBD), but so far the marijuana plant has not been approved as medicine by the FDA. This is because there has yet to be enough of the large extensive studies and clinical trials that need to be done prior to approval.

What are cannabinoids?

 Cannabinoids are a class of chemical compounds that act upon the cannabinoid receptors found within the brain that alter neurotransmitter signaling. This can now be broken into three different categories, endocannabinoids, phytocannabinoids, and synthetic cannabinoids.

Endocannabinoids are naturally produced within the bodies of animals. These endocannabinoids are retrograde signaling molecules made from phospholipid membranes found within the central nervous system (CNS). They bind to specific G-protein coupled receptors to inhibit the release of certain neurotransmitters for a specified time acting as a neuronal regulator.

  Phytocannabinoids are naturally occuring compounds within the certain plants such as cannabis sativa (marijuana). The most popular and well known of these is tetrahydrocannabinol, better known as THC or the psychotropic effect drug of marijuana. 

Synthetic cannabinoids are THC derivatives made in a lab. They’re commonly mislabeled as “synthetic marijuana,” “fake weed,” “natural herbs,” “herbal incense,” and “herbal smoking blends.” These mislabels come from spraying the synthetic on dried, shredded plant material without divulging the spraying. Presently they’re considered new psychoavive substances (NPS), or unregulated mind-altering substances with intent to produce similar effects to illegal drugs. These however are quite dangerous as they are more powerful than marijuana and as most are designed based on THC they bind to the same receptors but stronger. The stronger the binding the more interaction and therefore the longer the neurological effects. These are also deadly and highly addictive according to the CDC. 

How can this be used medicinally or therapeutically?

Cannabis’ properties of increased appetite and food consumption has lead researchers to study the effects of the cannabinoid 1 receptor (CB1) on appetite. It has been found to have a “role in central appetite control, peripheral metabolism, and body weight regulation.”1 This has lead to Rimonabant, a weight loss drug, for those really obese. On the other side it lead to Dronabinol, a treatment for nausea and vomiting in cancer and AIDs patients that is also associated with increased appetite. These effects also allow it to be used as a treatment for anorexia and those with diseases in which people tend to ‘waste away.’ 

Another use of cannabis is for pain-relief. This is done by the inhibition of the neuronal transmission in pain pathways. Some of these treatments include THC, CBS, and CBD-dimethyl heptyl (DMH) which actively block neurotransmitter release. These pain-relieving effects are used for many different disorders and diseases. 

On top of this it has been shown or thought to help with multiple sclerosis (MS), Parkinson’s disease (PD), Huntington’s disease, Tourette’s syndrome, Alzheimer’s disease (AD), epilepsy, amyotrophic lateral sclerosis (ALS); bipolar disorder, schizophrenia, post-traumatic stress disorder (PTSD), depression, anxiety, insomnia; asthma, cardiovascular disorders, and glaucoma. 

If you would like to read more about how it works in these diseases, I recommend this paper.

The Endocannabinoid System

The endocannabinoid system consists of three parts:

1. Endocannabinoids
2. Enzymes that synthesize and break down endocannabinoids
3. Receptors that bind endocannabinoids

There are two endocannabinoids that are most prevalent to the system, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG). These molecules are cleaved from bigger lipids that are a part of cell membranes until being released to formendocannabinoids. This “on demand” synthesis is done by enzymes that cleave sections of the lipids that go on to signal through the endocannabinoid receptors. The synthesis only takes place when there is an increase in calcium in the cell, membrane depolarization, or receptor activation. With that, endocannabinoid signaling is highly regulated and stabilizes signaling throughout the body.

Video: Endocannabinoid signaling and the components of the endocannabinoid system

There are two types of receptors most often used in the endocannabinoid system, CB1 and CB2. Both are G-protein coupled receptors that inhibit cyclic-AMP. CB1 receptorsare most often found in the brain and nervous tissue, while CB2 are found in immune tissues. Inhibition of cyclic-AMP leads to a decrease in excitability and signaling, preventing action potentials from spreading between neurons. The endocannabinoid system is a component in many diseases, and can be targeted for many therapeutic benefits. One of these benefits is reducing the signaling associated with pain.

Pain and the Endocannabinoid System

The endocannabinoid system can be used to target the pain nociception pathway. Endocannabinoids function to inhibit signaling that uses the excitatory neurotransmitter glutamate by inhibiting cyclic-AMP. In CB1 receptors, this inhibition extends to the pain pathway, and can inhibit signaling in areas of the brain like the amygdala, periaqueductal grey matter, rostral ventromedial medulla, and superficial dorsal horn. CB2 receptors can also play a role in anti-pain signaling, as they are expressed in several cells with inflammatory and immune-competent nature. The inhibition of these cells therefore causes relief from pain caused by inflammation.

References:

• https://www.cbdschool.com/the-endocannabinoid-system-explained
• https://metacangroup.com/endocannabinoid-system
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4120766/https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2826.2008.01671.x
• http://www.guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=13
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834283/#!po=9.77011
• http://jaoa.org/article.aspx?articleid=2093607
• https://www.youtube.com/watch?v=jznQfMj9RWM
• http://communitybasedispensary.org/pain/x

1. The benefits to marijuana outweigh the dangers
Marijuana is an endocannabinoid, which means the drug stimulates the endocannabinoid receptors in the body. There are two types of endocannabinoid receptors in the body, CB1 and CB2. CB2 receptors are typically found in the immune system. CB1 are found in the brain and spinal cord. Therefore, this drug can be used to target that area if it is the cause of the problem.

But how does marijuana help? Well, remember that CB1 receptor. Scientists believe that the CB1 is linked to several pathways in the body. The CB1 receptor is classified as a G-protein coupled receptor, acting as a second messenger, sending different signals throughout the body. Once activated, the CB1 receptor inhibits Ca2+ influx and increases K+ influx. This prevents the calcium from coming into the cell and stimulating a reaction by releasing certain neurotransmitters. For someone who has too much stimulation, such as those suffering from seizures, Parkinson’s Disease, or MS, this could be an option to decrease the symptoms. Another way that an activated CB1 receptor helps these patients is that when the CB1 receptor is turned “on,” then the sphingomyelin (SM) protein gets broken down by the protein, sphingomyelinase (SMase). This results in the release of ceramide, which is known to build up the lipid barrier and further prevents the Ca2+ from coming into the cell.
The danger of marijuana comes from when too much prevention leads to cell death. However, not many studies have been done on the drug, since it is still illegal on a national level.

To summarize, the chemicals in marijuana tell the body to “shut down” for a little bit. This helps those suffering from chronic pain and illness to experience some relief.

2. The contents within the marijuana can be regulated
Another danger of marijuana is when the drug is purchased off of the streets. No one truly knows what is in the pot. Frequently, police have picked up marijuana that was laced with either heroin or fentanyl. Combining marijuana with other very dangerous drugs can lead to death. If marijuana was legal on a national scale, the product would need to be under FDA regulations and the number of deaths from synthetic marijuana or pot laced with fentanyl (often referred to by cops as “pink death”) to decrease significantly.

3. Marijuana can be taxed
Remember that pothole that you hit on the way to work? That hole could be repaired with pot. Right now, the marijuana market is a trade that goes untaxed. Even in medical marijuana shops where is it legal in the state, they typically only accept cash payment. If the drug became legal, it would help fund a lot of projects that we currently don’t have the money for at this moment.

4. Eliminate the amount of non-violent criminals in the prison system
Several men and women are in jail for possession or distribution of marijuana. From 2001 to 2010, there have been 8.2 million arrests for marijuana. Out of those arrests, 88% were taken into custody for only possession of marijuana https://www.aclu.org/gallery/marijuana-arrests-numbers. The inmates were not being violent and bad; they were smoking or had pot. And, as it turns out, a great number of those arrested, are people of color. ‘“Criminalizing drug use has devastated families across the US, particularly in communities of color, and for no good reason,” said Maria McFarland Sánchez Moreno, executive director of the Drug Policy Alliance, in a statement.’ (https://www.washingtonpost.com/news/wonk/wp/2017/09/26/more-people-were-arrested-last-year-over-pot-than-for-murder-rape-aggravated-assault-and-robbery-combined/?noredirect=on&utm_term=.eed0c725a2de) If we legalize marijuana, we can decrease the number of arrests on non-violent offenders and overall, save money in the legal system.

Pharmaceutical companies are rushing to develop and start distributing cannabinoids, which are the active ingredient in CBD oil. With increasing amounts of research backing CBD oil for a treatment of autism, depression, anxiety, brain cancer, pain relief, and many more diseases, it’s not hard to see why CBD oil is one of the hottest therapies on the market.

No THC

 CBD oil differs from marijuana in that it is just the cannabinoids and not the THC. With no THC present, the user won’t experience the high one would from smoking or ingesting marijuana. THC creates a “high” by binding to specific CB1 and CB2 receptors in the brain. CBD doesn’t bind to these receptors, so it is safe to use at any time of the day, and the user will receive all of the benefits with no CNS side-effects. In fact, CBD oil is legal in all 50 states.

Digestive Benefits

 A normal appetite is vital to helping the body heal from illness, allowing the body to take in the nutrients it needs to repair itself. Some sicknesses and diseases decrease the appetite enough that it impairs the body’s ability to heal itself.

CBD helps with loss of appetite in diseases such as cancer by binding to cannabinoid receptors in the body that stimulate hunger. Scientific studies have shown that cannabinoid receptors are linked to the feeling of hunger.

Additionally, CBD helps to relieve nausea and vomiting, which are experienced by most patients going through chemotherapy.

Anxiety Alleviation

 CBD has also been shown to help with anxiety, including social anxiety. This is especially important because many THC users complain of social anxiety or a paranoid feeling after using the drug.

A scientific study in 2011 tested a group of people with social anxiety disorder who had never received treatment. One group took CBD daily while the control group received a placebo. All participants participated in a simulated public speaking test while their blood pressure, heart rate, and other markers for stress were measured.

The control group experienced higher anxiety compared to the CBD group, proving the benefits CBD oil has combating anxiety.

Pain Relief

 CBD binds to CB1 receptors throughout the body to relieve pain. It has also been shown to create an anti-inflammatory effect and reduce swelling.

 Importance of High Quality Product

 There have been numerous studies that point to a whole marijuana plant extract being far more effective than lab-synthesized, fully purified CBD. The best plants contain a very high CBD to THC ratio, with less than one percent THC concentration. Users should also take precaution to purchase CBD oil that is free of additives and third party tested.

Is CBD Oil Right For You?

 CBD has scientifically proven benefits for almost any health condition imaginable. From acne to Alzheimer’s, or from motion sickness to diabetes, CBD oil can be useful in anyone’s health regimen. Even if you feel that you are completely healthy, CBD oil can still be useful if you’re feeling stressed out, or simply if you want to relax after a long day of work.