Running head: MEDICINAL MARIJUANA DEBATE

Medicinal Marijuana Debate Katherine Hogan Northeastern University

MEDICINAL MARIJUANA DEBATE Abstract The use of marijuana as a medicine has recently become a topic of debate for medical

professionals across the United States. Eighteen states and the District of Colombia have passed laws that allow the use of marijuana for medicinal purposes. New studies are being published each year that reveal exactly how this plant affects the human body. Those that are proponents of this argument use this research to make a case that marijuana should be treated like any other drug that doctors prescribe their patients, keeping in mind the potential side effects and adverse reactions that can come about while also looking at how this drug could benefit the patient. Opponents to the use of marijuana as medicine state that this is an illegal drug that can cause more harm than good. Inhalation of smoke, addiction, and the pure fact that its illegal are some of the main arguments made against medicinal marijuana. What actually happens when marijuana is introduced into the body causes multiple chain reactions and involves more than one body system, the main one being the endocannabinoid system. Marijuana needs to be looked at as any other new medication being introduced, weighing in the pros and cons. Looking at it through this lens enables less bias and more focus on facts. Once one consolidates the surplus of information and compares the facts side by side from a purely medical point of view, the facts show that marijuana can be used safely as a medication.

MEDICINAL MARIJUANA DEBATE Medicinal Marijuana Debate Over the past few decades, marijuana (Cannabis sativa) has been a key point of discussion for politicians, health care workers, and the general population. Even more so in the past twenty years this topic has been of considerable debate over its legalization and use for medicinal purposes. Marijuana is the most widely used illicit drug in America (Fortney & Kindschi, 2013). It has been used for over 1,000 years for religious as well as recreational purposes all over the world. In 1937, it became a criminalized drug against the advice of the American Medical Association and the pharmaceutical industry (Fortney & Kindschi, 2013).

Today, marijuana is listed as a Schedule I drug; meaning the United States government deemed that it has no potential for medical use and it has a high potential for abuse both physically and psychologically (Williamson & Evans, 2000). Cannabis is in the same category of drugs as peyote, LSD, and heroin. Since this is the case, the government has made it difficult for scientists to get grants so that they can study the drug in a controlled way. Despite this roadblock, many studies have been produced that reveal how the chemicals in the plant produce an effect on the human body. These studies reveal the pure facts about marijuana. They show how it interacts with the body at a molecular level and the successive effects due to the activation of receptors. As a result of knowing how the drug works, scientists have been able to pinpoint specific illnesses that would benefit from cannabis and the potential side effects that this drug can trigger. There are challenges that the healthcare system would have to overcome and laws that would have to be changed, but patients should have the right to a drug that they can benefit from. How does it Work? The Endocannabinoid System

MEDICINAL MARIJUANA DEBATE The endocannabinoid system is responsible for the effects cannabis has on the human body (hence the name correlating to the plant that lead to its discovery). The goal of the endocannabinoid system is to maintain homeostasis through varying levels of neurons and

ligands. The discovery of the receptors was found in 1988 in rats and the human receptors were cloned in 1991 (Zogopoulos, Vasileiou, Patsouris, Theocharis, 2013). The two main ingredients in marijuana that are responsible for its effects are delta-9tetrahydrocannibinol (THC) and cannabidiol (CBD). Once THC is in the bloodstream it is available to the brain (because it can cross the blood-brain barrier) and to the central nervous system. The endocannabinoid system has receptors all over the body, which is why cannabis is able to have so many different effects. Two different receptors have been discovered thus far: CB1 and CB2. CB1 receptors are found in the brain and the peripheral nervous system, while CB2 receptors are found on immune cells and in related organs. They both work as G-protein coupled receptors (Pertwee, 2008). The CB1 and CB2 receptors can have various effects when a ligand binds to it. CB1 receptors usually mediate inhibition of ongoing release of a number of different excitatory and inhibitory transmitters that include acetylcholine, noradrenaline, dopamine, 5-hydroxytryptamine (5-HT), g-aminobutyric acid (GABA), glutamate, D-aspartate and cholecystokinin (Pertwee, 2008). This is saying that when a ligand binds to a CB1 receptor, it inactivates the release of other neurotransmitters. GABA and glutamate have been isolated as the main neurotransmitters associated with CB1 activation. These are responsible for the feelings of euphoria, increased appetite, an altered sense of time, and impaired memory (Zogopoulos et al., 2013). The analgesic properties of marijuana also arise from this mechanism of action because there are CB1 receptors in the gray matter in the midbrain and also in the dorsal root ganglion (these areas control pain

MEDICINAL MARIJUANA DEBATE transmission) (Fortney & Kindschi, 2013). On the other hand, CB2 receptors can modulate

immune cell migration and cytokine release both outside and within the brain (Pertwee, 2008). If the CB2 receptor is activated, it can signal the body to release more cytokines, which in turn signal to produce more immune cells. This is helpful if the body is sick (as with cancer or HIV/AIDS) and the body needs to be producing more of these cells. The CBD component of marijuana is the non-psychoactive chemical that has inhibitory effects on the limbic system. THC and CBD have anti-inflammatory effects as well as neuroprotective effects (Fortney & Kindschi, 2013). Two endocannabinoids that are endogenous to the human body, anandamide and 2arachidonoyl glycerol (2-AG), have also been discovered as part of this system. When the cannabis is ingested, the THC and CBD act as one of these endogenous ligands and therefore have subsequent effects. There are also two receptors that can terminate the response of these ligands. These are known as fatty acid amide hydrolase and monoacylglycerol lipase (Zajicek & Apostu, 2011). The effect of this is that if the body suspects that the endocanabinoid system is controlling too many bodily processes, it will send out these two substances to counteract the effects. Its the bodys own way of balancing itself out and not letting one system take over. As a result of this, it is highly unlikely that one can ingest too much of this drug because the human body will send out these ligands to block the receptors so that no more THC can bind to them (Zajicek & Apostu, 2011). The endocannabinoid system can have systemic effects, which can benefit patients with debilitating illnesses. The activation of the CB1 and CB2 receptors maintains homeostasis by inactivating the release of neurotransmitters. The result of this is that many different symptoms

MEDICINAL MARIJUANA DEBATE that can interfere with a patients life can be minimized by one drug. Pain, nausea, and anxiety can all be reduced and/or eliminated through the endocannabinoid system. Pharmacokinetics How a drug interacts with the body in terms of absorption, metabolism, and excretion

dictate how often the drug should be ingested and the correct dose of it. Cannabis has two main forms of absorption; it can either be inhaled or ingested. The fastest method of delivery of its main ingredient, THC, is by inhalation showing maximum plasma concentration after 15-30 minutes with a duration of three to four hours. In this delivery method, the THC goes into the lungs and diffuses from the alveoli into the bloodstream rather than having to go through the digestive system and be metabolized by the liver. If ingested orally, the maximum plasma concentration is achieved 30-90 minutes after ingestion and has the potential to last up to 12 hours (Fortney & Kindschi, 2013). These numbers are of great importance when discussing medications. The time that a drug takes to have the desired effect can mean the difference between waiting an over an hour for pain to be reduced or just 15 minutes. Ingesting the drug has effects that can last up to 12 hours meaning that a patient wouldnt have to remember to take their pills every four hours and could be symptom free for the entire day. This drug has the potential for allowing patients to stay on top of their symptoms and make it less stressful to manage. Medicinal Uses When a new drug hits the market, it can be approved for use in multiple different diseases and/or illnesses. As mentioned previously, the CB1 receptors have an influence over multiple different neurotransmitters and these neurotransmitters are responsible for a lot of the effects that

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marijuana has on the body. In an article published in Addiction Biology in 2008, the author noted the following: Proven targets for CB1 and/or CB2 receptor agonists are postoperative pain or chronic neuropathic pain experienced by patients with disorders such as multiple sclerosis, spinal cord injury, brachial plexus injury or cancer, tremor, spasms, spasticity and certain other symptoms experienced by patients with multiple sclerosis or spinal cord injury, nausea and vomiting induced by cancer chemotherapy, and loss of appetite in patients with cancer or AIDS. (Pertwee, 2008) As of when this source was published, these were the only proven diseases. It is not the first line treatment, but the option is available. Others that have potential CB1/CB2 agonist properties include diagnoses such as Alzheimers disease, anxiety problems, tics and other behavioral problems in people with Tourette syndrome, tardive dyskinesia induced by neuroleptic drugs in psychiatric patients, gastrointestinal disorders such as Chrons disease, hypertension, glaucoma, artherosclerosis, hemorrhage and carcinogenic shock (Pertwee, 2008). This list is not inclusive and there have been studies to show the positive effects that marijuana has on these disorders, however there is not enough clinical evidence to definitively say that marijuana can be a prescription to help people with these issues at this time. Marijuana also has synergistic effects with other medications. Cannabis can potentiate the effects of narcotics when used in combination, which can lead to a lower dose of opiods needed for the same effect (Capriotti, 2013). Cannabinoids have a synergistic effect on the hypothalamus and the amygdala that may dampen the strength of fear and emotionally traumatic memories through regulation of neuroendocrine and behavioral responses to stress (Williamson & Evans,

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2000). The result of this is that patients with post traumatic stress disorder (PTSD) will feel less anxious, depressed, and be able to sleep more soundly. There is a wide range of disorders that cannabis can help. It is not a cure for any disease, but it helps dampen the symptoms associated with certain illnesses. This drug minimizes pain, nausea, and spasms that other drugs on the market are not able to help. Patients with cancer might be on an anti-emetic, analgesic, and an appetite stimulant. This same patient could take one medication, marijuana, and minimize all those symptoms at once. Marijuana Paradox Surprisingly, cannabis can cause the opposite effect than what one might normally expect. For example, its main method of delivery (smoking) can cause damage to the cardiopulmonary system. However, based on the location and the known facts about the receptors (being located in vessel walls), the activation of the endocannabinoid system can help play a role in preventing atherosclerosis. This is not something one would normally expect because smoking is known to cause atherosclerosis (Fortney & Kindschi, 2013). Along these same lines, it has been reported at the American Association of Cancer Research in 2013 that a study done involving more than 4,000 participants showed that those who smoke marijuana on a daily basis were no more likely to develop lung cancer than those who didnt, whether or not they also smoked cigarettes (Fortney & Kindschi, 2013). This finding shows that in some cases, the benefits of the drug may outweigh the potential side effects. Another study that was done showed the paradoxical effects its metabolic pathways. Typically users of marijuana have an increase in appetite, but it was just recently discovered that obesity was much lower among cannabis users than non-users (Fortney & Kindschi, 2013).

MEDICINAL MARIJUANA DEBATE These effects are not the case for everyone who uses this drug but it shows how diverse the drug is. It can cause one problem in some, but also fix that same problem in others. Those who prescribe marijuana need to be aware that these effects are possible and educate their patients about them. Synthetic Ligands Since scientists know that these receptors exist and that THC has an affinity for these receptors, cant scientists make a synthetic form of THC rather than having a patient use

marijuana? Simply put, scientists have tried this. First, there was nabilone (Cesamet), which was licensed for use in 1981 as an anti-emetic in chemotherapy patients. Then came Marinol (dronabinol) in 1985 and Sativex in 2005. Marinol was also used as an anti-emetic, but doctors started to see how it could be useful in other ways and later started prescribing it as an appetite stimulant for patients with AIDS who were wasting away from the disease. Sativex started to be used as an adjunctive pain relief medication for patients with advanced cancer (Pertwee, 2008). These advancements have been scientific breakthroughs but they are not yet completely understood. There may be other effects of the analogs that have not yet been discovered and there are also more benefits that can accompany using the marijuana plant itself. Herbal cannabis preparations contain up to 70 cannabinoid constituents beside 9-THC (Pertwee, 2008). Therefore differences are to be expected between controlled studies using analogs and the studies done using marijuana due to the other cannabinoids in the plant. Side Effects Every drug on the market has side effects and can affect one person differently than another. The known side effects of marijuana are mainly due to the fact that people inhale smoke to get the desired effect. Studies have shown that marijuana can have up to as many as three

MEDICINAL MARIJUANA DEBATE times the amount of carcinogens as a cigarette. This leads to the effects of smoking marijuana similar to that of chronic obstructive pulmonary disease (COPD) (Capriotti, 2013). In other

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studies done on cannabis, it has been noted that participants held the marijuana smoke in their lungs longer and deeper than if they smoked a placebo cigarette (Capriotti, 2013). This also contributes to the pulmonary effects. Patients who smoke the plant are running the risk of getting respiratory infections, asthma, frequent cough, and reduced lung density (Williamson & Evans, 2000). Other side effects of marijuana include hypotension, sedation, dizziness, decreased reaction time, reduced motor skills, diminished cognitive ability, and impaired memory (Capriotti, 2013). These side effects are not always present and do not occur in everybody. They are merely effects that have the potential of happening. There is the possibility for side effects to occur with every drug that is introduced to the body. Depending on age, weight, other medications, and gender the side effects could range from mild to severe. This is a risk with every medicine. The effects of marijuana, however, are reported to be more tolerable for some patients than those of other medications they might be prescribed. These effects, such as increased appetite and some short-term memory loss, are good trade offs for being able to lead a relatively normal life. Isnt Marijuana Addictive? The debate over addiction to a drug that a doctor prescribes can be used for every single drug on the market today. Many patients in hospitals are afraid to take Dilaudid or Oxycontin out of fear that they will become addicted, and yet doctors prescribe these medications on a daily basis. Cannabis use is in the Diagnostic and Statistical Manual of Mental Disorders, Fifth edition (DSM-V). The DSM-V classifies that addiction happens due to the reward system the body has. It recognizes that some people are more prone to addiction than others, but overall the reason

MEDICINAL MARIJUANA DEBATE addiction comes about is because the body likes the sense of euphoria that a substance can induce. If the substance isnt there, then the euphoria doesnt occur, and the body craves the substance. The DSM-IV had two different categories (abuse and dependence), but the new

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addition just has one category (substance use disorder). There is a spectrum from mild to severe depending on how many of the criteria a patient would meet (Highlights of Changes). Only about 10% of users become psychologically addicted and the use of marijuana leads to occupational and interpersonal problems (Fortney & Kindschi, 2013). Doctors everywhere recognize that drugs have potential for abuse. This potential needs to be balanced out with the benefits the drug can provide. If cannabis can give someone less side effects than other medications while still providing adequate relief of their symptoms, then it should be able to be an option for that patient. Legal Issues National laws for receiving a prescription and obtaining the drug need to be abided by ahead of the state laws. Before a patient can even receive a prescription they need to get a state issued identification card and be evaluated by a health-care provider. A public health board will then review their application and discuss the patients eligibility for medicinal marijuana. If the patient gets approved, they can get the marijuana from a state approved dispensary. It is still illegal to grow, sell, produce or distribute marijuana (Capriotti, 2013). This makes it difficult for patients to procure the drug because in some states one may need to go to a dealer to get it. Each state has different laws regarding how to obtain a state issued identification card and how much a patient can purchase at once. The legal issues surrounding this come about because it is still a Schedule I drug. In order for America to produce more scientific evidence the first step would be to move cannabis from a

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Schedule I drug to a Schedule II drug. Once that is done, America will have legally recognized that there is some medical benefit to marijuana. This will make it seem less scary of a drug to patients who can actually benefit from it and more clinical trials can be followed (Zajicek & Apostu, 2011). Moving Forward: Challenges Making marijuana available for medical use across America will not happen quickly. Once more clinical trials are completed, the medical field will have more insight as to what dose, what plant strain, and what route of administration is best for each type of disease (Capriotti, 2013). The lack of consistency in the amount of THC in the marijuana that dispensaries sell makes it hard for physicians to know what dose to prescribe. If this becomes consistent, it will be easier to monitor. Lastly, there are also concerns about patients going through this process who arent really ill, but just want to smoke marijuana legally (Capriotti, 2013). Each drug that is on the market has potential for abuse outside of its therapeutic uses. This may just be a case where those in charge make the decision that the benefits of medicinal marijuana for patients outweigh the chance of abuse. Overall, there have been medical advancements in clinical trials that show marijuana has medical uses and this warrants a closer look by all healthcare professionals. There are diseases that have already benefited from the use of cannabis in which the patients illness became easier to manage. It can cover a multitude of symptoms so the patient would only need to use this one medication rather than multiple different pills. These proven benefits should be not only be for those in critical condition for which no other option is available, but should be readily available if the doctor deems it acceptable. Taking in all this information, it is clear that marijuana should be approved for use as medicine across the United States.

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Note: I dont think I will use this in my portfolio because it is such a controversial topic with so many different areas to explore and I only touched on a few key points. I feel like I did a good job analyzing and using resources to my advantage though.

MEDICINAL MARIJUANA DEBATE Resources

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Capriotti, Teri. "What you should know about medicinal marijuana." Clinical Advisor for Nurse Practicioners 20 (2013): 92-96. Clinical Advisor. Web. 12 Mar. 2014. Fortney, Luke, and Jason Kindschi. "Medical marijuana: navigating the controversy." EBSCOhost. Integrative Medicine Alert, 1 June 2013. Web. 12 Mar. 2014. <http://eds.b.ebscohost.com.ezproxy.neu.edu/ehost/pdfviewer/pdfviewer?vid=6&sid=52e 1577b-e8ba-4654-99e8-c825ac92c304%40sessionmgr113&hid=105>. "Highlights of Changes from DSM-IV-TM to DSM-V." American Psychiatric Associstion. N.p., n.d. Web. 21 Mar. 2014. <http://www.dsm5.org/Documents/changes%20from%20dsmiv-tr%20to%20dsm-5.pdf>. Pertwee, Roger. "Ligands that target cannabinoid receptors in the brain: from THC to anandamide and beyond." Addiction Biology 13 (2008): 147-159. EBSCOhost. Web. 11 Mar. 2014. Williamson, Elizabeth, and Fred Evans. "Cannabinoids in clinical practice." Drugs 17 (2000): 1303-1314. EBSCOhost. Web. 12 Mar. 2014. Zajicek, John, and Vicentiu Apostu. "The role of cannabis in multiple sclerosis." CNS Drugs 25 (2011): 187-201. EBSCOhost. Web. 11 Mar. 2014. Zogopoulos, Panagiotis, Ioanna Vasileiou, Efstratios Patsouris, and Stamatios Theocharis. "The role of endocannabinoids in pain modulation." Fundamental and Clinical Pharmacology 27 (2013): 64-80. Web. 11 Mar 2014.