CBD Uses, Pharmacology and Legality

CBD Essay: Introduction
In recent years, Cannabidiol (CBD) has risen in popularity and is known as a holistic miracle for a variety of ailments. Cannabidiol (CBD) can be used to help with certain skin conditions, disease states, and mental disorders. CBD is related to cannabis plant, but is used more for its medicinal properties. As the legalization of marijuana becomes more prevalent in our society, the United States and other countries are slowly starting to legalize and pass laws regarding cannabidiol use. In the pharmaceutical industry, medications containing cannabidiol have been approved and patented by the Food and Drug Administration (FDA) to treat specific epileptic disorders. Because of the cannabidiol explosion, more research and information is now becoming available.

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What Is CBD
Cannabidiol (CBD) is derived from the Cannabis sativa hemp plant which contains many unique compounds such delta-9 tetrahydrocannabinol, also known as THC. Because CBD and THC share the same molecular formula, C21H3O2, their chemical structure is nearly identical. The only significant difference in their chemical structure is that CBD contains a hydroxyl group and THC contains a cyclic ring.
Cannabidiol does not have a psychoactive effect on the brain, which essentially means it does not cause a feeling of being ‘high’. The level of THC in CBD can be high or low, or none, depending on how cannabidiol is extracted from the cannabis plant. Once the medicinal properties of CBD are extracted from the plant, by methods of dilution, CO2, ethanol, or through oils (like olive oil or coconut oil), it is made into oil that can be used in a wide variety of products such as oils, tinctures, pills, balms, or edible forms. Many researchers focus on THC or a combination of THC and cannabidiol and not enough recognition and research is solely committed to understanding cannabidiol on its own.
Brief CBD History
The cannabidiol molecule was first discovered in 1940 by Dr. Roger Adams and his team at the University of Illinois. This molecular was not fully understood until 1946, when Dr. Walter S. Loewe was the first to conduct a study on lab animals and cannabidiol. The research showed that cannabidiol did not cause the same altered state of mind that was found with THC. In 1963, Mechoulam and Shvo first termed the chemical structure of cannabidiol. This eventually led Mechoulam to have another cannabidiol breakthrough in 1980, when he conducted a study that showed cannabidiol as a possible treatment for epilepsy.
Pharmacokinetics
Pharmacokinetics describes the actions, the time of onset and the duration of effects of a particular drug or supplement. The route of administration for CBD can determine the absorption, distribution, and elimination process of the products therapeutic effect. The amount needed and the time it takes for the absorbed CBD to travel through the bloodstream to the specific target sites is called the bioavailability.
CBD can be administered orally, rectally, topically, through injection, or inhalation. First pass metabolism can affect the low oral bioavailability of CBD. First pass metabolism is caused by the actions of enzymes of the gastrointestinal lumen, gut wall enzymes, bacterial enzymes, and hepatic enzymes before reaching the circulatory system. The specific enzymes are the CYP2C19 and CYP3A4 enzymes, and UGT1A7, UGT1A9, and UGT2B7 isoforms.
The most effective way to take CBD would be sublingually, because it would bypass the first pass metabolism, or as an inhalant, which did have a study done with having a bioavailability of 11% – 45% (Scuderi, 2009). The half-life of cannabidiol was determined to be18–32 hours (Devinsky et al. 2014).
Pharmacodynamics
Cannabidiol (CBD) has been found to interact with a variety of different biological targets, including cannabinoid receptors (Pisanti et al.,2017) and other neurotransmitter receptors (Laun et al.,2018). Research has shown that when CBD and THC are consumed at the same time, CBD is an indirect antagonist towards cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2). CBD will bind with CB1 and turn off the receptor because of its biochemical shape. CBD also decreases the ‘high’ from the THC because THC is unable to bind to the CB1 receptor (Mechoulam et al., 2007; Pertwee, 2008). These receptors are what protect the central nervous system and immune system from stressful influences and provide cellar homeostasis from becoming over active in the body (Laprarie, et. al., 2015). The CB2 receptor is usually found in organs that impact the immune system. It has been studied to act as an antagonist of GPR55, a G protein-coupled receptor and putative cannabinoid receptor that is expressed in the caudate nucleus and putamen in the brain. (Ryberg et al., 2007)
It has also been found to act as an inverse agonist of GPR3, GPR6, and GPR12. (Laun et al., 2018)  Although currently classified as orphan receptors, these receptors are most closely related phylogenetically to the cannabinoid receptors.[12] In addition to orphan receptors, CBD has been shown to alter serotonin signals and act as a serotonin 5-HT1A receptor partial agonist (Russo et al., 2005) boosting signals through the through serotonin receptors to block reabsorption of serotonin in the brain. Can increase the availability of serotonin in synaptic space, helping brain cells transmit more serotonin signals to reduce anxiety and boost mood. Research suggests that CBD regulates the production and function of the endocannabinoid system, increasing the levels of endocannabinoids, such as anandamide, produced by the body. (Campos et al., 2002)  The endocannabinoid system aids in regulating mood, appetite, memory, and pain sensation (Hampson AJ, et. al, 1998). 
Uses for CBD
Cannabidiol has been shown to suppress inflammation which is one of the primary causes of chronic pain (Russo, 2008), neuropathic pain (Xiang, 2012), Parkinson’s disease (Chagas et al., 2014), Lennox-Gastaut syndrome (Devinsky et. al, 2017; Devinsky et al., 2018a) and Dravet syndrome (Devinsky et. al., 2018b) and schizophrenia (Leweke et al., 2012). In 2015, an analysis of previous studies concluded that CBD oil is a promising treatment for numerous forms of anxiety, including social anxiety disorder, panic disorder, obsessive-compulsive disorder, generalized anxiety disorder, and post-traumatic stress disorder (Blessing et al., 2015). This has potentially had results of reducing hyperalgesia which is the sensitivity to pain as a result of having an enhanced pain response. Based on multiple studies done in the late 1990s, this could have been a result from a previous body injury or from opioid pain killers. Opioid use has been known to induce hyperalgesia. Research specifically on cannabidiol, however, has found few or no negative side effects. This means CBD oil may be a good option for people who do not tolerate the side effects of other medications or are afraid of becoming dependent on an abusive drug.
Pharmaceuticals
On June 2018, the U.S. Food and Drug Administration (FDA) approved Epidiolex, an oral administered cannabidiol solution, as a medical treatment for two rare forms of pediatric epilepsy: Lennox-Gastaut syndrome and Dravet syndrome. Lennox-Gastaut syndrome (LGS) is a severe form of epilepsy that has multiple types of seizures that usually take effect during infancy or between the ages of 3 to 5 years old. Dravet syndrome (DS) is a rare and complex childhood epilepsy disorder that is associated with drug-resistant seizures and a high mortality rate which takes during infancy.
The medication is only indicated for those clinically diagnosed with LGS or DS. Its availability to be dispensed is by the five specialty pharmacies that are currently in the limited distribution network and not by other retail pharmacies. It is controlled as a Schedule V of the Controlled Substances Act because it has a low potential for abuse.
Drug testing
On June 2018, Quest Diagnostics released post in regard to the rise of CBD use and the likelihood for false positive drug tests for marijuana. They stated that if CBD or other hemp oil products could test positive on a drug test, an individual would need to use or consume about 1000-2000 mg, or more, of the cannabidiol product. Because of the availability of cannabidiol, some oils could have a THC concentration that could trigger a positive test result depending on usage patterns. These tests are detecting other cannabinoids, including cannabidiol, not selectively seeking for just THC.
Legalization
Cannabidiol has been deemed as a Schedule 1 substance and remains illegal at the Federal level. While there are some states that permit the sale and purchase of CBD within their state lines, products have a strict limit as to how much THC can be allowed in the product itself.  An example is in Texas, CBD products may have THC in it but it must be at or below 0.3%.
Conclusion
There is a present interest in understanding the benefit of CBD’s holistic approach through supplements and other forms. Testing and research have become more prevalent within the few years as governments look to approve laws and regulations for cannabis. Because CBD oil is not regulated as a medical treatment, it is unclear what dosage a person should use or how frequently they should use it. A person should consult a doctor or healthcare professional that has experience with CBD oil to determine the right dosage for their needs. It could be safe to say that next year will be the most successful year for cannabis and cannabidiol industry to date.
References

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Blessing, E., Steenkamp, M., Manzanares, J., & Marmar, C. (2015). Cannabidiol as a Potential Treatment for Anxiety Disorders. Neurotherapeutics, 12(4), 825-836.
Campos, A., Moreira, F., Gomes, F., Del Bel, E., & Guimaraes, F. (2012). Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders. Philosophical Transactions Of The Royal Society B: Biological Sciences, 367(1607), 3364-3378.
Devinsky, O., Cilio, M., Cross, H., Fernandez-Ruiz, J., French, J., & Hill, C. et al. (2014). Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia, 55(6), 791-802.
Devinsky, O., Cross, H., Laux, L., Marsh, E., Miller, I., & Nabbout, R. et al. (2017). Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. New England Journal Of Medicine, 376(21), 2011-2020.
Devinsky, O., Patel, A., Cross, H., Villanueva, V., Wirrell, E., & Privitera, M. et al. (2018). Effect of Cannabidiol on Drop Seizures in the Lennox–Gastaut Syndrome. New England Journal Of Medicine, 378(20), 1888-1897.
Devinsky, O., Patel, A. D., Thiele, E. A., Wong, M. H., Appleton, R., Harden, C. L., et al. (2018b). Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome. Neurology 90, e1204–e1211.
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Demystifying Medical Marijuana and CBD

Medical Marijuana Essay
As additional states continue to pass laws that allow for the use of medical and recreational marijuana, it is important for us as providers to be able to answer basic questions that patients will inevitably have. Being blindsided by inquiries about potential benefits of medical marijuana and CBD related products can be thwarted with fundamental fact-based information. As the CBD market is projected to reach $20 billion in sales over the next 5 years (BDS Analytics), we would seemingly have our heads in the sand if we think that the absence of these products on a patient profile list tells a complete story. Our patients are using these products, and it is our responsibility to know how these products work and influence our patient’s health and wellbeing.

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The 1970 Controlled Substances Act set the tone for marijuana and hemp. This lumped them in with heroin and LSD as Schedule 1 drugs that are characterized as having a “high potential for abuse” and are of no medical use or value. Despite the federal prohibition, individual states were emboldened by a Department of Justice memo in the 2009 that provided states with basic guidelines for legalizing medical marijuana and a later memo in 2013 outlined the same for recreational marijuana. These memos laid the foundation for states to set up marijuana regulatory structures.
The 2018 Farm Bill passed by President Trump officially removed hemp from the federal list of controlled substances making it an ordinary agricultural commodity. However, marijuana remained on the list and it remains there today. This has created confusion for many of us as individual states are left to wrestle with their own decisions about the use and legal status of marijuana. Our nation is faced with an entire spectrum of legality. Certain states like Alabama and South Carolina have deemed medical and recreational marijuana fully illegal while other states like California and Maine have made it fully legal.
Other states such as Arkansas and Oklahoma have made recreational use illegal but have approved the use of medical marijuana. To muddy the water even further, some states like Georgia have approved medical marijuana but only in the form of low THC oil. In total, 16 states have recreational marijuana laws and 38 have approved varying medical marijuana laws. Additionally, each state that has approved medical marijuana laws has laid out specific conditions that must be verified by a physician before a prescription is signed and treatment can begin. The amounts and places to obtain medical marijuana are also state specific.
As confusion exists among state laws, it is important there not be any when considering the differences between marijuana and hemp. The two primary classifications within the cannabis family are indica (marijuana) and sativa (hemp). The leaves are similar in appearance, and this likeness contributed to hemp’s inclusion with marijuana as a Schedule 1 drug under the 1970 Controlled Substances Act. Two naturally occurring compounds, tetrahydrocannabinol (THC) and cannabidiol (CBD), are found in cannabis but they have significant differences in the levels of THC and CBD. THC is the primary chemical compound in marijuana that gives the high sensation, and although natural potency can vary, the average strain of marijuana contains approximately 12% THC. This is an important distinction since marijuana is cannabis that includes more than 0.3% THC and hemp is cannabis that has less than 0.3% THC (by dry weight). This distinction is the basis for legal medical marijuana and CBD products derived from hemp versus illegal medical marijuana and CBD products derived from marijuana.
THC and CBD both interact with the Endocannabinoid System (ECS) found throughout the body. The THC and CBD from cannabis interact with the CB1 and CB2 cannabinoid receptors and induce particular effects that may or may not be beneficial to patients. Manipulation of this system opens the pharmaceutical door. This could be achieved synthetically from pharmaceutical companies or naturally from hemp or marijuana. There are four currently FDA-approved cannabinoid medicines available in the United States. These include Marinol, Syndros, Cesamet and Epidiolex. Since these medications’ costs range from $700 to $32K, it is not hard to see why patients would be willing to try natural cannabis alternatives.
THC binds to CB1 and CB2 receptors to induce the mind-altering euphoric effect. Additionally, antiemetic effects and influences on appetite occur with this binding. Conversely, CBD inhibits binding to the receptors. It also inhibits enzymes that break down endogenous cannabinoids. These combined actions are thought to elicit the desired effects that patients are seeking. These effects influence stress- response, inflammation, immunity, pain, mood, and more. Although CBD is tolerated well in large doses, the World Health Organization research shows any side effects tend to arise from drug to drug interactions with medications that might already be in the system.
Dosing and delivery methods vary, and the condition patients are looking to influence should direct the delivery method. When considering the immune system, mood and pain management, patients should use vaporizers and orals. Oral products like CBD oils, tinctures, edibles, capsules, and powder deliver a sustained and steady level of CBD throughout the day. If conditions are localized, topical products should be considered. Inhaled delivery methods such as dabs, smoking, or vaporizers provide immediate short-term relief, and it takes about 10 minutes to obtain the highest bloodstream levels using these methods. Added benefits have been shown when combining delivery methods.
There presently is not an FDA Recommended Daily Intake (RDI) or universal guide for CBD, so patients are often left to seek guidance on their own. CBD Origin authors recommend taking 1–6MG of CBD for every 10 pounds of body weight when consuming edibles such as gummies. Dosing with tinctures and oils requires some math, as the total CBD in the bottle must be divided by the number of milliliters in the bottle. As therapy begins, low dosing is recommended, and a general rule of thumb is to wait approximately 6 hours for oral delivery methods and 1 hour for vaporizers before repeating any dosage. An important note when using other medications in conjunction with CBD is that it inhibits cytochrome p450 which, like grapefruit, will interfere with the ability to process certain pharmaceutical drugs.
Clearly, CBD and medical marijuana are the trendy choices for many individuals that are seeking relief for their conditions, and research is ongoing. Often those choices are the last stop on the option train when they have not received the expected relief from other pharmaceuticals. Other times it is the first stop because of the “natural” appeal of CBD versus the manufactured synthetic options. Either way, having a basic knowledge of medical marijuana and CBD establishes trust with our patients, and this helps prepare us for the inevitable questions that will come sooner than later.