What Nurses Need to know about Cannabis

Hello and welcome. This is a four-part series that will introduce you to the world of medical cannabis. In the series, we’ll cover the endogenous cannabinoid system, the science behind medical cannabis, the plant’s chemical composition including main components THC and CBD, different varieties and what they’re used for, delivery methods, dosing, interactions, and finally, cannabis advocacy and where we are in the fight to legalize medical cannabis in the United States. We are grateful to the support of Advance for Nurses for getting the word out.

This series is written by:

Eileen Konieczny, RN, is the President of the American Cannabis Nurses Association, co-founder, lead strategist and Director of patient services for Valley Agriceuticals (a NY-based company); and founder of Olive’s Branch, an educational consulting firm bridging the information gap between the medical cannabis and healthcare industries.

Eloise Theisen MSN, RN, AGPCNP-BC has a Post Masters certification as an adult-Geratric nurse practitioner from University of Mass, Boston; an MSN in Nursing Administration from California State University; and a Bachelor of Science in Nursing from San Francisco State University. In 2014, she started Green Health Consultants (GHC), a clinic dedicated to ensuring patients receive the qualified counseling on cannabis therapeutics.

What Nurses Need to Know About Cannabis by Eileen Konieczny, RN

As nurses, we are in a unique position. Not only do we advocate for our patients, we are active participants in each patient’s experience of health and illness. As nurses, we share relevant information with patients—about their medical conditions, treatment options and ways of coping with both.

Whether you work in one of the 25 states that allows the use of medical cannabis, work in one of the 17 states that has passed CBD-only laws, or work in a state that has no legislation at all, you need to understand the science behind the plant Cannabis sativa. Your patients deserve a nurse who is educated about the endogenous cannabinoid system (endocannabinoid system, or ECS) and how cannabis interacts with that system.

A Personal Interest

I have specialized in oncology my entire nursing career. I was already an experienced nurse when I began looking into alternative treatments for my sister’s spreading breast cancer. Upon hearing that cannabis had medicinal properties, I began researching its use and discovered the science of the ECS, a physiologic regulatory system that is responsible for maintaining balance within our body, especially with respect to how we eat, sleep, protect, forget and relax.1

Since that time, after seeing firsthand how the medicine eases pain and suffering, I have become a passionate advocate for medical cannabis.

A 3,000-Year History

Many people are surprised to learn that only during the past 76 years has cannabis not been a medicine in the United States. Humans have used cannabis to ease pain and suffering for more than 3,000 years. By the 19th century, cannabis showed up in many “tonics” and was considered to be something of a “cure-all” drug. Unfortunately, the potency of medicinal preparations was variable, and individual responses seemed unpredictable (or even erratic at times).(2) While people understood that cannabis had healing properties, they didn’t understand how it worked.

In 1964, Israeli scientist Raphael Mechoulam and his colleagues isolated and synthesized delta-9-tetrahydrocannabinol (THC), a component of cannabis.5 During the subsequent two decades,scientists learned much about the clinical effects of cannabis, but no one understood how itworked on a molecular level to alter perception and achieve palliative results, such as relievingpain and nausea, increasing appetite, and suppressing seizures. It took until the early 1990sbefore researchers began to uncover the ECS and the brain receptors (CB1) and body receptors(CB2) that responded to cannabinoids.

The Endocannabinoid System

The ECS is a sophisticated network of neuromodulators (called endogenous cannabinoids), their receptors (CB1 & CB2), and the signaling pathways that help maintain homeostasis in the human body. The ECS, which is believed to be the largest receptor system in the human body, is found in the brain, organs, connective tissue, bones, adipose tissue, and nervous and immune systems.(2)

The ECS regulates internal processes such as movement, mood, memory, appetite and pain. Since it plays an important regulator function in the body, the ECS also plays a role in managing a variety of symptoms or underlying disease states. Clearly, a well-functioning endocannabinoid system is essential to our health and well-being. (6)

Patients experience the effects of cannabis because its compounds bind to and activate tiny molecular receptors encoded by our genes.(3) These cannabinoid-capturing receptors, known as cannabinoid receptors, are proteins that are expressed on the surface of cells.(3) Receptors may be thought of as locks, to which a corresponding chemical (natural or synthetic) will conform like a key, if it has the proper structure to conform to it.3

There are many different cells and tissue types in our bodies that express these cannabinoid receptors and are responsible for the diversity of cannabis’ effects.2

Cannabis’ “Power Couple”

At the present time, we know the most about the cannabinoids tetrahydrocannabinol (THC) and cannabidiol (CBD), which are sometimes called “the power couple” of cannabis. Among cannabis’ many cannabinoids—there are more than 100— THC produces the well-known psychoactive effects of cannabis and is equally responsible for the majority of other pharmacological impacts, acting on both CB1 and CB2 receptors.(4) Activating the CB1 receptors in the brain induces a sensation of “being high,” which is often described as a feeling of intoxication, relaxation, giddiness, introspective dreaminess, sleepiness, and time distortion.(4) Activating CB2 receptors is known to relieve inflammation and allergic reactions.4

CBD is non-euphoric and does not appear to bind to either CB1 or CB2 receptors.(6) Cannabidiol shows great promise in treating many conditions, most notably seizure control in pediatric epilepsy patients. In addition, CBD offers anti-inflammatory, analgesic, anxiolytic, antipsychotic and anti-carcinogenic effects.

Effective use of medical cannabis often requires finding a balance between the “power couple’s” desired therapeutic effects and mitigating unwanted psychoactive effects. The extensive therapeutic action of THC is a very important component and should not be discounted.

Still a Schedule 1 Drug

At present, although legal in 25 states, the U.S. Drug Enforcement Administration (DEA) still lists cannabis and its cannabinoids as Schedule I controlled substances. This means that, despite the scientific evidence to the contrary, they are deemed to have no medical value and cannot legally be prescribed, possessed, or sold under federal law. So under federal law, physicians currently write “recommendations” for its use (rather than prescriptions), and patients need to visit a state licensed dispensary instead of a local pharmacy in order to obtain the medicine.

Public opinion on the topic is shifting, however. In 2015, Senator Elizabeth Warren (D-MA), along with some of her other Democratic colleagues in the Senate, wrote to multiple food and drug officials and asked them to reclassify cannabis in order to facilitate research into the plant’s medical benefits. The DEA stated that it would respond to Warren’s request by mid-2016.

It is our ethical and professional obligation as a trusted member of the healthcare profession to be educated about medical cannabis. I hope you will join me next month, when I will discuss the differences between herbal cannabis and its varieties and other cannabinoid-based medicines.

Cannabinoid Medicines by Eileen Konieczny, RN

Cannabis has a complex chemical profile containing more than 100 known compounds. Factors that can define a plant’s properties can be attributed to the cannabis variety’s lineage, the soil and climate conditions during cultivation. Each plant is made up of a unique chemical profile that includes cannabinoids, mono and sesqui-terpenes, sugars, hydrocarbons, steroids, flavonoids, nitrogenous compounds and others. Each of these chemically-distinct elements contain unique properties that works alone and in tandem to affect different parts of the brain and body. In other words, change the variety or chemical “recipe” and you change the therapeutic effect.

Cannabis Varieties

Although there are a plethora of cannabis varieties, they fall into just three categories: indica, sativa, and hybrid. In general, the medicating effect of an indica is predominantly physical. It is characterized as relaxing, sedating, heavy, lethargic, and pain reducing. Sativa produces an effect often characterized as cerebral, uplifting, thoughtful and energetic. It is characterized as having a strong psychological component giving feelings of well-being, focus and creativity.

Strain crosses, or hybrids, are the result of cross-pollination of cannabis varieties. The characteristics of the variety are not equal, so the effects of one variety will be stronger than the other. For example, indica-dominant crosses are good for pain relief, with the sativa component

helping with appetite stimulation. Sativa-dominant crosses are good for stimulating appetite, with the indica component helping with relaxation and reduced stress.

With the many combinations and complex pairings of modern hybrids, it is impossible to generalize about the qualities of effects. It is suggested that patients keep a record of their own experience with medicating; tracking variety, dose, method of delivery, time of day and experience.

Whole Plant Cannabis

In the recent past, most patients medicated with whole plant cannabis, typically smoking dried cannabis flower. All that is changing, however, in an effort to create acceptable legislation and regulation around a Schedule I substance, some states (CT, MN, NY & PA) have enacted rigid regulations that require creating standardized dosages of pharmaceutical or medical grade products. While standardized medicines make sense, many people believe that dismissing the value of the cannabis flower in its natural, safest and most economical form is misguided. That said, these requirements have led to the development of reliable, standardized cannabis products made from extracts and concentrates, which has precedent in the pharmaceutical industry. In fact, many of our common medicines come from natural substances; these products include morphine (which is derived from opium poppies), penicillin (derived from a fungus) and aspirin (derived from willow bark).

Terpenes and Extraction

Terpenes are organic compounds found in a variety of plants, and contribute to their scent. These substances are the building blocks for essential oils and plant resins. Each variety of cannabis contains its own distinct collection of terpenes. Alpha-pinene (pine), Myrcene (musk), Limonene (lemon), Linalool (lavender), and Beta-caryophyllene (pepper) are examples of the aromatic compounds that figure prominently in cannabis strains. According to a September 2011 report by Dr. Ethan Russo in the British Journal of Pharmacology, terpenes have specific medicinal attributes, which combine to create a holistic “entourage effect,” so that the therapeutic impact of the whole plant is greater than the sum of its parts. Dr. Russo reports that cannabinoid-terpenoid interactions “could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal, and bacterial infections.”

While standardized, concentrated medicines are valuable, the production process often removes valuable terpenes from the medicine. Why does this matter if the power couple —THC and CBD—are still present? While extracted pharmaceutical grade cannabinoid medicines are certainly efficacious, they could be more effective if terpenes were not sacrificed in the production process. As the industry matures, improved extraction processes will hopefully be able to preserve terpenes and the “entourage effect” of whole plant cannabis.

Why Standardization is Important

While it may be comforting for patients to rely on cannabis varieties reputed to provide relief for a particular symptom or illness, relying on an exact chemical profile may prove to be just as effective and then some. Firstly, an exact chemical profile will allow physicians and patients to consistently access the same medicines, every time they need it. This is very important when patients find products that are effective. Secondly, once cannabis is removed from Schedule I and standardized cannabis medicines are available, insurance companies will begin to track the documented effects of its use, which may encourage insurance coverage thus making cannabis more affordable for vast numbers of patients.

Standardized Natural and Synthetic Cannabis Medicines

While U.S. physicians practicing in states with medical cannabis laws are allowed to “recommend” medical cannabis products found in local dispensaries, all U.S. physicians are able to prescribe two of the four medications listed below. In time, it is ACNA’s hope that all U.S. doctors will be able to prescribe all natural and synthetic cannabinoid medications, including the four currently in production:

Marinol®: dronabinol9 – A synthetic derivative of Delta-9 THC formulated in sesame oil. Round, soft gelatin capsules contain 2.5 mg, 5 mg, or 10 mg. Suggested medical uses are to treat nausea and vomiting for patients in cancer treatment; stimulate appetite in AIDS patients; and as an analgesic to ease neuropathic pain in multiple sclerosis patients. Approved in the United States as a Schedule II drug for appetite stimulation (1992) and for nausea (1985); moved to Schedule III effective July 2, 1999.

Cesamet®: nabilone10 – A synthetic analogue of THC. Capsules are available in 1mg & 1.5mg doses. Suggested medical use is to treat nausea and vomiting caused by cancer chemotherapy. Made available in U.S. pharmacies on Aug. 17, 2006.

Sativex®: nabiximols8 – A standardized dose of 1:1 THC:CBD whole cannabis extract that comes as a peppermint-flavored mouth spray. The first pharmaceutical drug of its kind, Sativex can be prescribed for patients with multiple sclerosis in countries such as Canada, Australia, the United Kingdom, and Spain. In early 2014, Sativex was granted Fast Track designation by the FDA in order to accelerate the drug’s approval. Its suggested method of use is for treatment of neuropathic pain and spasticity in patients with Multiple Sclerosis.

Epidiolex©11 – An investigational drug that has not been approved for use by the FDA or any other national regulatory agency. Epidiolex is a purified, 99% oil-based extract of CBD that is standardized to produce consistent amounts in each dose. The drug led to an average reduction in seizure frequency of 50% among a group of 27 children and young adults with treatment-

resistant epilepsy. “The initial open-label study with Epidiolex has provided encouraging results,” said Orrin Devinsky, MD, director at the NYU Comprehensive Epilepsy Center and one of the drug’s lead investigators. “Some children have had marked reductions in their seizures and overall, the medication has been well tolerated.”

Patient Reactions

A survey performed in 2013 by the International Association for Cannabinoid Medicines12 asked patients who used cannabis or cannabinoids about their experiences with different methods of intake. The survey was the largest international survey to date, completed by 953 participants from 31 countries. The results showed that in general, patients preferred and received better results from herbal, non-pharmaceutical cannabinoid medicines rather than pharmaceutical products. The survey’s authors did report, however, that while the number of patients who reported experience with pharmaceutical products was low, the data might be useful for developing new, safe and effective cannabinoid-based medications.

It’s an exciting time for medical cannabis. Ongoing and future scientific studies will help us better understand this complex plant, which will allow us to better serve qualifying patients across our nation and around the world.

Cannabis Dosing and Administration by Eloise Theisen, RN, MSN, AGPCNP-BC

Patients have different delivery methods for medicinal cannabis.

In the last two articles, readers were introduced to different terms such as endogenous cannabinoid system, cannabinoids and terpenes. This article will build on those different terms while focusing on the clinical applications of cannabis as a medicine. There are some things worth mentioning around dosing and administration of cannabis first. Cannabis has biphasic effects. In small doses, it can be helpful for things like nausea, appetite, pain, sleep, mood and anxiety. However, in larger doses, cannabis can have the opposite effect leading to an increase in anxiety, pain and/or depression (19).

The bidirectional effects of cannabis make it is essential that patients start low and go slow to avoid experiencing any adverse reactions. The most common side effects of Delta-9 tetrahydrocannabinol (THC) are dizziness, dry eyes and mouth, euphoria, increased heart rate, decreased blood pressure, fatigue and increased appetite. Cannabidiol (CBD) can cause psycho-activity, dizziness, jitteriness, diarrhea, palpitations and even decreased appetite with prolonged use (15). With proper guidance, patients can utilize medical cannabis with optimal results and minimal adverse reactions.

Delivery Methods

Today we have many different delivery methods for cannabis. Long gone are the days where the only option was smoking. Now patients can choose from vaporizing, edibles, tinctures, suppositories, topicals and even transdermal patches. There are pros and cons to each delivery method.

Inhalation

The most well-known and popular delivery method is smoking. Smoking cannabis flowers provides relief of symptoms within 5-15 minutes. For many patients with chronic pain, anxiety or acute nausea and vomiting, this delivery method is ideal. The number one concern with smoking cannabis is potential lung damage and/or cancer. Tashkin looked at the possible long term effects on the lungs in chronic cannabis smokers. Tashkin found that there was no link to an increased risk of lung cancer or chronic obstructive lung disease. In fact, they found that cannabis may have some protective effects in those who smoke cannabis. 13

When patients smoke cannabis in a joint or pipe, they are heating the medicine at a high temperature close to 600 degrees. At that temperature, burning cannabis is more likely to produce carcinogens and tars. While smoking has not been correlated with any increased risk of lung damage or cancer, it can lead to chronic bronchitis and/or chronic cough (16).

An alternative to smoking is vaporization. There are many different products available for vaping. Some patients vaporize the flowers or buds of the cannabis plant while others prefer to vaporize concentrated cannabis. Some other names of concentrated forms of cannabis are oils, dabs, waxes, shatter, nail hits and rosin. Concentrated forms of cannabis are often extracted with chemical solvents such as butane. Testing for residual solvents is a must to avoid inhaling high levels of residual solvent chemicals. Also, some concentrated forms of cannabis oil have been mixed with propylene glycol to ease inhalation administration. Inhalation of propylene glycol has been linked to respiratory and immune disorders (18). The concentrated forms are higher potency ranging from 50-90% THC. There is much debate about whether high potency cannabis is truly medicinal or just an attempt for people to get extremely intoxicated. For many patients with neuropathic or cancer related pain, high concentrated cannabis is most effective at relieving their pain.

Inhalation is a quick and easy way to medicate. Contrary to popular belief, inhalation is low dose and easiest to control. Patients can titrate up slowly. While the onset of relief is fast, the length of relief is around 2-3 hours. Inhalation requires more frequent administration and may not be ideal for long lasting relief.

Ingestibles

Ingestibles can include anything from cookies, brownies, candies, capsules, tinctures, sprays, tea, and oils. The advantage of ingesting cannabis is that it will provide much longer relief than inhalation. In general, patients can experience a reduction in their symptoms for 6-8 hours or more. Most ingestibles in the form of edibles (cookies, brownies, candies, sodas) come in dosages that far exceed the necessary amount to obtain relief.

When cannabinoids are ingested they are processed through the liver. The liver converts delta-9 tetrahydrocannabinol (THC) into 11-hyrdroxy-THC (11-OH-THC) which is a much more potent form of THC. The bio-availability of ingested cannabis ranges from 4-20% (20). Cannabis is fat soluble, delaying full onset of action from 1-3 hours. These factors make it difficult to dose a majority of THC rich-edibles. The high variability of ingested cannabis coupled with the delayed onset of effectiveness can lead to potential overmedicating. Often while a patient is waiting for relief, they will consume more than they need, thinking that they didn’t take enough originally. Unfortunately, this leads to side effects that can be unpleasant and uncomfortable. In higher dosages of 10 mg or more, patients can experience anxiety, paranoia and/or hallucinations.

Also worth noting is the potential for drug-drug interactions with cannabis. There hasn’t been standards of administration or safety established with CBD and other medications. We know that CBD can either be an inducer or inhibitor of the P450 pathway. More specifically, CBD is metabolized by the CYP3A4, CYP2C9 and CYP2C19. As a result, CBD can either decrease or increase the serum levels of other medications metabolized through these enzymes. THC is also metabolized by CYP3A4 and CYP2C9 (14). Levels of THC can be affected by other medications metabolized through these enzymes. More often than not, cannabinoids will increase the effectiveness/toxicity of other medications. Patients must be observed for potential increase in side effects from medications such as blood thinners, anti-depressants and anti-epileptics.

Edibles

Edibles, such as baked goods, lozenges and capsules can be difficult to part out in equal amounts. For example, if a brownie has 100 mg of cannabinoids per package it can be challenging to break that brownie into several small pieces and expect each piece to be evenly distributed. In a cannabis naïve patient, a recommended starting dose is generally between 2.5-10 mgs of cannabinoid. The more potent the product, the higher chance a patient has of over medicating.

Tinctures, Sprays and Oils

Liquid forms of cannabinoids can be a great way to start low and slow. As long as the products are clearly labeled with dosing, patients can start with as little as one drop or one spray. By definition, a tincture is in an alcohol or glycerin base. Among many cannabis products, tinctures

are now being developed in an oil base such as olive oil, coconut oil or medium chain triglycerides (MCT) oil.

Sprays can also be a great way to start low and slow. Many cannabis sprays deliver a metered doses allowing patients to self-titrate.

Topicals and Transdermals

Topical cannabis products can be beneficial for localized issues. Pain, muscle spasms, eczema, psoriasis, bug bites and/or burns can be treated with topical cannabis. The advantage is that the cannabinoids will act locally and not regionally thereby decreasing the potential for systemic side effects. Animal studies have shown that THC topically is two times stronger than hydrocortisone. Topical THC can be effective at reducing itching and inflammation on the surface of the skin. CBD has also been shown to decrease inflammation, muscle tightness and itching. As a topical, CBD absorbs into the skin 10x better than THC (17). When using a topical, patients can expect to experience relief within 20 minutes that can last for several hours.

Transdermal products can come in patches and/or topical gel pens. The transdermal products have been designed to penetrate the skin and reach the blood stream for more system relief. Patches can provide relief within 20 minutes and last for 12 hours. Additionally, if a patch is removed, the adverse reaction will dissipate within 20-30 minutes. It can be a great way to introduce cannabis into a patient who is concerned about negative side effects and allow them some control over dosing and administration.

Special Considerations

As with all cannabis products, patients should be looking for medicines free of pesticides, solvents, molds, fungus and bacteria. Without standards in place, pesticide use in growing cannabis is unregulated. Solvents, such as butane, hexane and isopropyl alcohol are used to extract concentrated forms of cannabis. Testing the final cannabis product for pesticides, mycotoxins, residual solvents and potency would help ensure the safety of the medicine being consumed.

Finally, cannabis is best when it is individualized to the patient. Dosing is not a one size fits all model and it is not a sliver bullet. Cannabis medicine works best when patients have someone there to guide them and empower them. Nurses are the perfect ones to fill that role.

Medical Marijuana in the United States by Eileen Konieczny, RN

“There was a time in the United States when extracts of cannabis were almost as commonly used for medicinal purposes as is aspirin today,” wrote Solomon Snyder in a 1971 book entitled Uses of Marijuana. In fact, the history of marijuana medical use predates the written word. Every

civilization since the dawn of man has employed the unique therapeutic properties of this plant. The Chinese were medically using cannabis twenty-eight centuries before the birth of Christ, recommending it for a variety of disorders including rheumatic pain and constipation. In cultures widely separated by geography and time there are consistent reports of marijuana’s medical benefits easing digestive upsets, enhancing appetites, relieving muscle spasms and reducing melancholia. (21)

Today, the United States boasts a patchwork of medical cannabis laws. States that have legalized the plant for medicinal purposes have unique rules and regulations, qualifying conditions and allowable medicines. Where a patient lives in the country impacts his or her ability to legally access cannabinoid therapies: If a patient experiencing debilitating chronic pain lives in Connecticut, Georgia, Maine, New Jersey, or New York, he or she cannot legally access medicinal cannabis. If that same patient lived in one of the other 20 states that legalized medical cannabis, he or she would be able to do so.

1996-2016: Twenty Years of Medical Cannabis in the US

Since 1996, twenty-five states and the District of Columbia have adopted laws that permit the cultivation, processing, distribution and possession of cannabis for medicinal purposes. Another seventeen states have adopted laws that permit the possession of cannabis extracts high in cannabidiol (CBD) and low in THC. Additionally, four states—Colorado, Washington, Oregon, Alaska—and the District of Columbia currently allow adults to consume cannabis for recreational purposes.

In the beginning, California, Oregon, and Washington passed laws to protect qualified patients from arrest and prosecution and allowed them to cultivate limited amounts of cannabis. Distribution models were non-profit, member-based collectives with members providing their excess cannabis to those in need. In 2010, Colorado was the first state to classify medical cannabis distribution as a “business” regulated under the state’s Department of Revenue, formally creating the medical cannabis industry. (22)

In the current medical cannabis industry, most state-sanctioned programs regulate production and distribution processes in order to protect patients. West Coast states give patients a broad array of medicines and delivery methods to choose from, from raw flower for vaporization to potent extracted oils. Depending on the nature of the political landscape, some state programs are barely functional. Too few dispensaries, limited qualifying conditions, restricted THC, capital requirements, and aggressive timelines harm patients who could greatly benefit from this medicine. Patients in Minnesota, New York, and Pennsylvania only have access to processed cannabis extracts in the form of tinctures, extracts for inhalation, oral mucosal sprays and capsules with limited ratios of cannabinoids. The prohibition of qualified patients from using the

actual plant unnecessarily eliminates the safest and most affordable route of administration and has had the unintended consequence of empowering a robust black market of unregulated cannabis with no quality control or quality assurance measures.

DEA and Drug Scheduling

Despite the fact that half of the states allow cannabis to be used for medical purposes and people across all 50 states are advocating for the federal government to legalize the plant, on Thursday August 11, 2016, the U.S. Drug Enforcement Agency (DEA) announced that it would uphold its current position that cannabis has no currently accepted medical use and a high potential for abuse. This decision leaves cannabis on Schedule 1 which is the same classification as heroin, lysergic acid diethylaminde (LSD), 3,4-methylenedioxymethamphetamine (ecstasy), methaqualone, and peyote. (23) The DEA’s decision was a big blow to advocates across the country who would like to see the federal government once again recognize the medicinal value of cannabis. This announcement did reveal, however, that the DEA would expand the number of sites that can cultivate cannabis for research so there is reason to believe the federal government may revisit this decision in the future.

Medical Cannabis and the November 2016 Election

On November 8, 2016, voters nationwide will cast their ballots. In four states—Arkansas, Florida, Missouri and Montana—voters will decide if medical marijuana should be legal. In five states—Arizona, California, Maine, Massachusetts and Nevada—voters will decide whether or not marijuana should be legal for recreational use. (24)

Despite the recent DEA decision and no matter the outcome of the November election, medical cannabis in the United States is here to stay. Regardless of where you live, cannabis is going to become part of the arsenal you will carry in order to provide patients with the best possible quality of life. Educate yourself about the laws in your states. Advocate on behalf of your patients, they deserve it!

References

1. Di Marzo, V, Melck, D, Bisogno, T & De Petrocellis, L. (1998). Endocannabinoids:endogenous cannabinoid receptor ligands with neruomodulatory action. Trends inNeuroscience. 21: 521-528.

2. Gerdeman, Gregory L., PhD, and Jason B. Schechter, PhD. “The Endocannabinoid System.”The Pot Book: A Complete Guide to Cannabis: Its Role in Medicine, Politics, Science andCulture. By Julie Holland. Rochester, VT: Park Street, 2010 52-62 Print.

3. Grotenhermen F., Russo E (eds). Cannabis and Cannabinoids: Pharmacology, Toxicology,and Therapeutic Potential. New York, NY: Routledge; 2002: 123-142.

4. Grotenhermen, Franjo, Dr. Med. "Medical Effective Cannabis Compounds." Medical-cannabis-declaration.org. 29 Apr. 2016. Reading

5. Mechoulam R. The pharmacohistory of Cannabis sativa. In: Mechoulam R, ed.Cannabinoids as Therapeutic Agents. Boca Raton, Fla: CRC Press; 1986: 1-19.

6. Sulack, Dustin. “Preventative Medicine and Health Promotion with Cannabis.” PatientsOut of Time Tenth National Clinical Conference on Cannabis Therapeutics: Cannabis aBotanical Medicine. Maryland, Baltimore. Apr. 2016. Lecture.

7. Russo, Ethan M.D., “Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects,” British Journal of Pharmacology. 2011 Aug; 163(7): 1344–1364. Retrieved from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165946/

8. http://www.gwpharm.com/Sativex.aspx9. http://www.rxabbvie.com/pdf/marinol_PI.pdf10. https://www.cesamet.com/pdf/Cesamet_PI_50_count.pdf11. http://www.epilepsy.com/learn/treating-seizures-and-epilepsy/other-treatment-

approaches/medical-marijuana-and-epilepsy12. Arno Hazekamp Ph.D.af*, Mark A. Ware M.D.b, Kirsten R. Muller-Vahl M.D.c, Donald

Abrams M.D.d & Franjo Grotenhermen M.D. “The Medicinal Use of Cannabis andCannabinoids—An International Cross-Sectional Survey on Administration Forms,”Journal of Psychoactive Drugs, vol. 45, iss. 3, 2013, p. 199-210. Retrieved from:http://www.tandfonline.com/doi/full/10.1080/02791072.2013.805976

13. Tashkin, D.P. (2013). Effects of marijuana smoking on the lung. Annals of the AmericanThoracic Society, Vol. 10, No. 3 (2013), pp. 239-247.doi: 10.1513/AnnalsATS.201212-127FR

14. Devitt-Lee, A. (2015). CBD-Drug Interactions:Role of Cytochrome P450. Retrieved fromhttps://www.projectcbd.org/article/cbd-drug-interactions-role-cytochrome-p450

15. Lee, M. (2014). What is CBD? Retrieved from www.projectcbd.org16. Joshi,M, Joshi, A and Bartter, T. (2014) Marijuana and Lung Disease. Current Opinion

Pulmonary Medicine. doi: 10.1097/MCP.0000000000000026.17. Jorge, L.L., Feres, C.C., Teles, V.E. (2011). Topical preparations for pain relief: efficacy and

patient adherence. Journal of Pain Resolution. http://dx.doi.org/10.2147%2FJPR.S949218. Agency for Toxic Substances and Disease Registry. (2008). Addendum to the

toxicological profile of propylene glycol. Retrieved fromhttp://www.atsdr.cdc.gov/toxprofiles/propylene_glycol_addendum.pdf

19. National Cancer Institute. (2015). Cannabis and cannabinoids for professionals. Retrievedfrom ://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq#section/_3

20. WebMD. (n.d.) Cannabis Pharmacology. Retrieved fromhttp://www.webmd.com/cancer/tc/cannabis-and-cannabinoids-pdq-complementary-and-alternative-medicine---health-professional-information-nci-human--clinical-studies

21. Marijuana in America: Memoir of a Pioneer. Middletown: n.p., 2016. N. pag. Print.22. ASA. "Medical Marijuana Access in the US." Medical Marijuana Access in the US.

Americans for Safe Access, Jan. 2016. Web. 21 Aug. 2016.23. "DEA / Drug Scheduling." DEA / Drug Scheduling. United States Department of Justice,

n.d. Web. 22 Aug. 2016.24. Wallace, Alicia. "Definitive Guide to Marijuana on the 2016 Ballot: Recreational & Medical

Initiatives." The Cannabist. The Denver Post, 14 July 2016. Web. 22 Aug. 2016.