For centuries Cannabis (aka marijuana) had been used as a medicine and misused as a psychedelic drug. In 1906, the US government first tried to regulate the use of the plant with the Pure Food and Drug Act. From there, more laws were enacted till the drug was effectively banned. However, as new information comes to light about the uses of medical marijuana, it becomes apparent that the decision needs to be revisited. Cannabinoids THC and CBD, chemicals derived from the Cannabis plant, affect the body by acting on the Endocannabinoid System. Research shows how understanding their functions could lead to the development of medication with fewer side effects when treating mental disorders like PTSD and anxiety disorder, chronic pain, neuropathic pain, symptoms of cancer treatment, etc. With this in mind, states are easing restrictions on marijuana, but more research needs to be done before it can be safely distributed and consumed.
Spoorthy Reddy, Grade 12, Lenape High School
#Cannabis #marijuana #CBD #THC #recreationalmarijuana #medicalmarijuana #CBDOil #hemp #endocannabinoidsystem #SpoorthyReddy
Cannabis for Medical Use: Benefits of CBD and THC
By Spoorthy Reddy
Mentors: Dr. Rajagoal Appavu and Jothsna Kethar
Abstract
For centuries Cannabis (aka marijuana) had been used as a medicine and misused as a psychedelic drug. In 1906, the US government first tried to regulate the use of the plant with the Pure Food and Drug Act. From there, more laws were enacted till the drug was effectively banned. However, as new information comes to light about the uses of medical marijuana, it becomes apparent that the decision needs to be revisited. Cannabinoids THC and CBD, chemicals derived from the Cannabis plant, affect the body by acting on the Endocannabinoid System. Research shows how understanding their functions could lead to the development of medication with fewer side effects when treating mental disorders like PTSD and anxiety disorder, chronic pain, neuropathic pain, symptoms of cancer treatment, etc. With this in mind, states are easing restrictions on marijuana, but more research needs to be done before it can be safely distributed and consumed.
Introduction
In recent years, the use of marijuana (aka Cannabis) for medical situations has been a topic of controversy. First banned in the US in 1937, Cannabis contains cannabinoids such as tetrahydrocannabinol (THC) and cannabidiol (CBD). Endocannabinoids, Cannabis-like substances, are also produced within the body and interact with the endocannabinoid system. The endocannabinoid system is crucial for homeostasis. It influences critical functions like appetite, digestion, immune function, inflammation, mood, sleep, reproduction/fertility, motor control, temperature regulation, memory, and pain. Since cannabinoids can cause changes in these systems, being able to understand their function and use them medically will be a breakthrough in medicine. However, one can not disregard the centuries-long history of marijuana abuse. The cannabinoids have to be evaluated on a case-by-case basis. Some cannabinoids, like CBD, are perfectly legal while other cannabinoids are banned. This includes THC, which has many medical benefits such as alleviating pain and inflammation (especially chronic forms), increasing appetite to prevent the extreme weight loss of AIDS, improving muscle control, controlling epileptic seizures, treating mental illnesses, and treating addiction. However, it is also the material in marijuana that makes people high. This controversy has led to a federal ban in the US, but some states still allow its use. This study hopes to compile the current information about marijuana and investigate the controversial effects of cannabinoids. To determine the effectiveness of Cannabis and its level of risk, CBD oil has also been compared to three common over-the-counter pain medications (Aspirin, Ibuprofen, and Tylenol).
What is Marijuana?
Marijuana is a mixture created from the flowers of the Cannabis sativa plant. Also going by the names of weed, pot, bud, and ganja, the Cannabis plant is often abused as a drug. It can be smoked, made into tea, and even mixed into food such as cookies and brownies. It can be consumed through a vaporizer or through a resin that is made using the active ingredients of marijuana.
Cannabis is composed of more than 500 different chemicals. Of them, over 100 have been identified as cannabinoids, notably THC and CBD. THC or tetrahydrocannabinol is the main chemical in marijuana that gives people the intoxicating feeling of a high. CBD or Cannabidiol, on the other hand, lacks these adverse effects and has been found to be harmless. This difference can be attributed to the role they both play in the Endocannabinoid System.
Cannabinoids and the Endocannabinoid System
First discovered in marijuana, cannabinoids are chemically similar to endocannabinoids. The “endo” in endocannabinoid is short for endogenous, showing that the chemicals are naturally produced by the body. The endocannabinoid system (ESC) consists of 3 main parts: endocannabinoids, receptors, and enzymes. The CB1 receptors are located in the central nervous system (which is the brain and spinal cord) while CB2 receptors are in the peripheral nervous system (being scattered throughout the body). Both receptors bond with both endocannabinoids and cannabinoids due to their similar chemical structure. After the receptor is activated and a change occurs in the body, enzymes are released. These enzymes break down the endocannabinoids and cannabinoids and effectively reset the system for when another round of endocannabinoids is released.
The endocannabinoid system plays a key role in maintaining homeostasis. Homeostasis refers to the body’s need to maintain a stable internal environment so that all parts of the body are in the optimal state to function. This can mean regulating temperature, pH, or even heart rate. When something is outside of the normal range, the ECS is activated to correct it. For instance, the ECS makes the body sweat to get rid of excess heat. It plays a critical part in regulating a number of functions such as sleep, mood, motor control, temperature, memory, pain, appetite, immune function, inflammation (including neuroinflammation), and a sense of pleasure/reward. By learning how cannabinoids work, one can influence these functions. Due to the effects that cannabinoids have on these systems, they could serve a critical role in medicine. Of course, before that one would need to figure out how the different cannabinoids work and if they are safe for use.
CBD and THC in the Endocannabinoid System
While both THC and CBD influence the CB1 receptors, they create very different effects. To explain this, let’s consider endocannabinoid anandamide. The chemical structure of anandamide is similar to that of THC and they bind to the same receptor, inducing the same calming effect. In the brain, cannabinoids, and endocannabinoids function as neurotransmitters that transmit info between cells. When an endocannabinoid is sent out, it attaches to the receptor of a nearby cell, prompting it into action before being broken down by enzymes. If it does not get broken down, it can continue to bind to the receptor. This is what happens with THC. While anandamide is broken down by the FAAH enzyme, the enzyme can’t break down THC. Due to this, the chemical stays in the body for longer and has a greater effect, eventually inducing a feeling of euphoria.
CBD, on the other hand, functions differently from both chemicals. Instead of bonding to the receptor itself, one of its known functions is that it bonds to the FAAH enzyme and induces a change such that it can no longer break down anandamide. This way anandamide can have a larger calming effect, making CBD a good way to treat anxiety-related disorders. This process might sound similar to what happens with THC, but it does not cause a feeling of euphoria. Though some FAAH enzymes will be inhibited by CBD, not all of them will be. So they will eventually break down the anandamide molecules. THC can not be broken down at all, causing its effects to be more pronounced.
While this process happens in the hippocampus, CBD also impacts other parts of the brain, working to reduce anxiety. In a study done on mice, CBD acted on the dPAG and the BNST to provide an anxiolytic effect. The dPAG refers to the dorsal part of the periaqueductal gray or PAG. The PAG is a part of the brain that deals with the recognition and categorization of pain as well as the development of defensive behaviors. This means that it can control how the brain perceives pain and induces panic attacks and anxiety. CBD works on this part of the brain to reduce anxiety though there is evidence that it affects defensive behaviors as well. In the mice, the CBD decreased “defensive behaviors evoked by predator exposure,” hinting that it could help reduce panic attacks or PTSD. (Campos et al., 2012). On another note, it is said that marijuana does not reduce pain and instead makes it seem less bothersome. The effect of CBD on the PAG, which controls one’s perception of pain, could justify this claim.
To continue, the BNST, or the bed nucleus of the stria terminalis, is a structure that is found in many mammals including humans. It plays a part in “both anxiety and addiction through connections with other brain regions, including the amygdala and nucleus accumbens.” (Avery et al., 2014). Though the effect of CBD on the BNST was observed in mice, it could impact humans in the same way. In a study where volunteers were injected with CBD, it was noted that “CBD can also reduce anxiety in healthy volunteers during a neuroimaging study or after a simulated public-speaking procedure after stressful simulated public-speaking procedure.” (Campos et al., 2012). Another study conducted in 2015 concluded the same: “current evidence indicates CBD has considerable potential as a treatment for multiple anxiety disorders.” (Blessing et al., 2015). The influence of cannabinoids on this part of the brain could also explain why taking marijuana helps with opioid addiction. Due to similar studies being conducted and the uses of CBD being discovered, it has been implemented in many medications, most notably CBD Oil.
CBD Oil
Cannabidiol (CBD) oils are low-tetrahydrocannabinol products. The “tetrahydrocannabinol” part refers to THC. The “low” shows that they are less psychotropic, having less of an effect on the brain than THC. CBD oils (aka hemp oils) are derived from the flowers and leaves of a hemp plant. Hemp plants are Cannabis plants with THC levels that are less than 0.3% while marijuana plants contain much more THC. They are generally considered less dangerous since the THC levels are often too low to induce euphoria. CBD oils are mainly made out of CBD, BCP (β-caryophyllene, another cannabinoid), and other low tetrahydrocannabinol. As they are made using hemp, they also contain less than .3% THC.
They should not be confused with Cannabis oils or Hemp Seed oils. Cannabis oils contain more THC and less CBD as they mainly serve to harness the medical properties of THC. It is created from the flowers and leaves of the marijuana plant. Hemp Seed oils, on the other hand, don’t contain any THC and little to no CBD. They mainly consist of Omega-6 and omega-3 fatty acids, γ-linolenic acid, and nutritious antioxidants, making them good for use as nutritional supplements.
These distinctions were made fairly recently provided that hemp and marijuana were not distinguished until the 2014 Agricultural Act. The law also allowed for hemp to be used for research purposes. However, even now there are laws against the use of CBD. 38 states in the US allow for CBD to be used for medical purposes with each state limiting the amount of CBD that can be consumed to different degrees. The other states either allow for the use of CBD only for the treatment of seizure disorders or have completely banned CBD. Additionally, it is illegal to sell any product containing CBD across states. Many people go around this limitation by imposing the product from Europe before distributing it in the US. To continue, the federal government and the DEA have labeled CBD and hemp oils as schedule I substances, causing them to still face scrutiny. Many Cannabis products are not allowed to be prescribed by doctors. States, if they deem that marijuana should be used medically, allow physicians to “recommend” the use of a certain product. Luckily, CBD/hemp oils don’t need a prediction to be purchased as they have low levels of THC.
However, other issues come up when buying this product. For instance, the oils are sometimes marketed as being synonymous with synthetic cannabinoids, such as spice, the consumption of which can be dangerous and lead to hospitalization. Even if CBD Oil is the object being advertised, the medication can be mislabeled. In fact, “a 2017 survey reported that of 84 online CBD and hemp oil products examined, only 26 were accurately labeled for CBD and THC content, with CBD often being over labeled and THC under labeled, consistent with the statements made by the FDA.” (VanDolah et al., 2019). Both of these things can easily lead one to believe that CBD Oils are more dangerous than they seem.
Are CBD Oils truly dangerous? While there is little to no evidence for the long terms safety of CBD with it being such a new medication, its short-term safety is supported by much evidence. Doses up to “300 mg/d have been used safely for up to 6 months” while doses of 1200 to 1500 mg/d” have been used safely “for up to 4 weeks.” (VanDolah et al., 2019). While there have been reports of liver damage and gastrointestinal problems, these complications only appear to occur in particular situations. For instance, “concomitant use of CBD and other medications such as leflunomide, lomitapide, mipomersen, pexidartinib, teriflunomide, and valproate can increase the risk of liver damage.” (Meissner & Cascella, 2022). This is not uncommon as other medications also produce advertise effects if taken together. Common doses for CBD are only 20-40mg/d, and assuming the product is not mislabeled or taken with another medication, it is safe to consume.
Of course, there are cases where large doses of CBD must be taken to have an effect. This is the case when CBD is used to treat epileptic patients. Though about a third of the patients experienced symptoms of drowsiness, decreased appetite, and diarrhea, “these adverse effects were less severe and less frequent when compared with the usual adverse effects of clobazam treatment.” (VanDolah et al., 2019). This demonstrates that CBD can be used to replace more dangerous treatments and provide even better results. Though more research is necessary, CBD can not be simply brushed off as dangerous.
CBD Oil and OTC Medications
If manufactured properly CBD Oil could be sitting right alongside common OTC medications. Even when compared with Ibuprofen, Aspirin, and Tylenol, medications that are considered safe by many, CBD Oil has much to offer. While all four help with pain, CBD Oil has the additional benefit of reducing anxiety and seizures and positively impacting mental diseases. Despite doing so much more, there is little evidence that points to any side effects for lower doses. Furthermore, CBD oil can have a greater length of effect of up to 8 hours (depending on the dosage) while the other drugs can only last 4 or 6 hours. I found that CBD Oil provides more benefits than the other medications and with fewer side effects attached.
Other Uses for Cannabis
Though CBD has many uses, there are other effects that Cannabis induces that can be attributed to other cannabinoids.
Management of chronic pain:
Chronic pain can be defined as lasting for more than 3 months and is independent of the original cause of the pain such that treating the underlying illness will have no effect on the pain. A study in 2018 was conducted with 984 participants who were all diagnosed with some form of chronic pain, including back/neck pain, neuropathic pain, post-surgical pain, and abdominal pain. The patients had a variety of physical conditions such as arthritis, cancer, and diabetes. When marijuana was given to the patients, more than 70% of them found the medication to be effective. It was more than 75% effective in patients with cancer, abdominal, and menstrual pain. This study clearly demonstrates the effects that marijuana can have on chronic pain and the impact it can have on the lives of many people.
Appetite control:
Though marijuana research indicates that the drug causes an increased appetite, the results of many experiments suggest that the probability of this happening is variable. In a 1994 study, the effects of marijuana on both fed and fasted participants (who were instructed to skip breakfast), were recorded. When the relationship between pre and post-food intake was observed, there was only a significant increase if the subject has previously fasted. The total intake in both cases was the same. Not to mention that “the difference in self-selected energy intake on the fed and fasted days is not attributable to differences in drug levels or degree of induced ‘high.’” (Mattes et al., 1994). This indicated that THC does not have too much of an effect on appetite. However, a 2001 study later concluded that THC “can induce a degree of overeating that matches that produced by other hyperphagic pharmacological manipulations” and that “these effects are due to interaction with central, endocannabinoid systems.” (Kirkham & Williams, 2001). The observed effects of THC on appetite do not appear to be consistent, however, it can be concluded that it does have some effects on appetite.
Opioid abuse control:
Opioid abuse is a prevailing issue in the US and, though marijuana is also misused, there are indications that Cannabis use can reduce opioid abuse. A 2016 study focused on opioid use in chronic pain patients. It found that “Cannabis use was associated with 64% lower opioid use,” a “better quality of life,” and “fewer medication side effects and medications used.” (Boehnke et al., 2016). Other studies suggest a more indirect impact. One published 2021 analyzed the mortality rates in 23 states that allowed the legal distribution of Cannabis. It found a relationship between “increased prevalence of medical and recreational Cannabis dispensaries and reduced opioid related mortality rates. ” (Hsu & Kovács, 2021). In either case, Cannabis shows promise for reducing dependency on other painkillers due to its effectiveness.
Conclusion
Though marijuana has a history of abuse, its benefits should not be disregarded. CBD in particular, if investigated further, has the potential to be used to save many lives. For instance, Epidiolex, which contains a purified form of CBD is used for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex (TSC). The drug was approved by the FDA and was classified as a Schedule V drug. This means that it has a much smaller chance of being misused compared to the cannabinoids that are still categorized as Schedule I drugs. If more research is done into CBD, then similar medications could be created. Its ability to impact mental health is especially something that needs to be considered when pursuing this goal.
Furthermore, THC should not be disregarded just because of its high potential for misuse. Marinol and Syndros are both medications that contain dronabinol, a synthetic THC. Both drugs are used to treat nausea and vomiting caused by cancer chemotherapy as well as a loss of appetite and weight loss in people with HIV/AIDS. Another drug created with the influence of THC is Cesamet. It contains nabilone, a synthetic drug similar to THC that can also help with nausea and vomiting caused by cancer treatment. Since they are based on THC, all three drugs can cause people to experience a high. That is not to say that they are not useful at all. They can still act as a last resort and are used in extreme situations where other drugs have no effect. Though THC is harmful, it can be used in a medical setting if carefully regulated. Further research can also be done to synthesize a chemical that does not have the demerits of THC but can still help cancer patients. Medicine should not be halted due to bias against Cannabis or the reputation that marijuana has made for itself over years of misuse; CBD and even THC show promise for furthering the advancement of medical drugs.
Limitations
There is little to no research regarding long-term medical cannabis use. As such, any conclusions reached do not take into account any long-term side effects.
Acknowledgments
I want to give my thanks to Dr. Rajagoal Appavu for guiding me through my research and writing this paper as well as Jothsna Kethar for facilitating this mentorship. I also want to give thanks to my loved ones for supporting me through the whole process and for giving me encouragement. I could not have done this without you.
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