Medical :

What nurses need to know Nurses can help patients make smart decisions by educating themselves.

By Eloise Theisen, MSN, AGPCNP-BC, and Eileen Konieczny, RN, BCPA

CNE CANNABIS has a long history as a 1.62 contact by synthetic . Ligands medicine, in spiritual use, and for hours act as chemical messengers to get recreational use. Currently, 33 states, cannabinoids to interact at the re- LEARNING O BJECTIVES the District of Columbia, Guam, ceptor site, while enzymes break and Puerto Rico allow medical 1. Describe effects of cannabinoids. down cannabinoids after they’ve cannabis use under specific qualify- 2. Compare cannabis preparations. completed their function. ing conditions, and 11 states (and 3. Discuss cannabis administration. the District of Columbia) allow receptors adult recreational use. The planners of this CNE activity have disclosed CB1 and CB2 are G-protein-coupled Nurses frequently care for patients no relevant financial relationships with any com- receptors. CB receptors are pre- mercial companies pertaining to this activity. 1 who use or are considering using Eileen Konieczny owns stock in and receives a dominantly found in the central and . In 2018, the Na- salary from Gloucester Street Capital, which over- peripheral nervous systems, in the tional Council of State Boards of sees the operations of a medical li- heart, lungs, adrenal glands, kidneys, cense in New York. Eloise Theisen owns stock in Il- Nursing (NCSBN) released guidelines lumeSense, a cannabis telehealth platform, and is pancreas, testes, ovaries, liver, colon, for nurses who care for patients who a consultant for Entire Health, which makes me- and prostate. When activated, CB1 use medical cannabis, stating, “Nurs- dicinal cannabis. This article underwent peer re- receptors can help mitigate anxiety view and no bias was found. See the last page of es need practical information to care the article to learn how to earn CNE credit. and stress, pain and inflammation, for the increasing number of patients depression, post-traumatic stress, Expiration: 11/1/22 who utilize cannabis…who self-ad- symptoms related to multiple sclero- minister cannabis as a treatment for sis, and neurodegenerative disorders. various symptomatology or for recre- about cannabis health claims. Finding Very few CB1 receptors are found in ational purposes. Individuals are us- and validating information can be the brainstem or the cardiorespirato- ing cannabis and nurses will care for challenging—proper and timely re- ry centers, making a lethal dose of these patients.” (See Cannabis: 6 es- search, however, can inform clinical cannabis impossible. sential principles.) practice for nurses. CB2 receptors also are found in Because cannabis science isn’t the brain and peripheral nervous taught in most nursing schools (ex- The systems, but they’re concentrated in cept in the context of misuse), nurses The main function of the endo- the peripheral immune cells. In ad- must find information about cannabis cannabinoid system (ECS) is to main- dition, CB2 receptors are located in on their own. And because health- tain homeostasis, which makes it a the lungs, uterus, brainstem neurons, care professionals typically possess unique target for medical applica- and microglia. When acti vated, they little knowledge about cannabis ther- tions. This molecular signaling sys- mitigate inflammation, mental health apeutics, patients frequently seek tem consists of cannabinoid re- disorders (including depression, information from other patients, ceptors (CB1 and CB2 are the most bipolar, schizophrenia, and eating workers, and the common and well studied), ligands, disorders), and neurologic diseases internet. However, a recent article and enzymes that regulate sleep, such as Alzheimer’s, Parkinson’s, by Boatwright and Sperry found that pain perception, memory, mood, Huntington’s, and multiple sclerosis. 90% of the information on the top 10 and appetite. The receptors can be cannabis websites was based on low- stimulated by our own endogenous Cannabinoids quality studies and only one website cannabinoids, by plant-derived can- Cannabinoids are chemical com- used a medical professional to write nabinoids (phytocannabinoids), and pounds that can influence the can-

6 American Nurse Today Volume 14, Number 11 AmericanNurseToday.com Cannabis: 6 essential principles

The National Council of State Boards of Nursing has identified six principles of nabinoid receptors and promote essential knowledge about cannabis for nurses, advance practice nurses, and the release of neurotransmitters. nursing students. They include phytocannabinoids, 1 The nurse shall have a working knowledge of the current state of legalization endocan nab inoids, and synthetic of medical and recreational cannabis use. can na bin oids. 2 The nurse shall have a working knowledge of the jurisdiction’s medical mari- Phytocannabinoids produced juana program. by cannabis plants can activate re- 3 The nurse shall have an understanding of the endocannabinoid system, ceptors and are responsible for cannabinoid receptors, cannabinoids, and the interactions between them. the medicinal and therapeutic ef- 4 The nurse shall have an understanding of cannabis pharmacology and the fects of cannabis. Cannabis plants research associated with the medical use of cannabis. contain 100+ cannabinoids, but 5 The nurse shall be able to identify the safety considerations for patient use of the most abundant and well stud- cannabis. ied are delta-9-tetrahydrocannabi- 6 The nurse shall approach the patient without judgment regarding the patient’s nol (THC) and (CBD). choice of treatment or preferences in managing pain and other distressing Researchers hypothesize that phy- symptoms. tocannabinoids work better to- gether than in isolated forms of cannabinoids. For example, CBD being available by prescription for olex, an oral solution of plant-de- can enhance the medicinal bene- decades, synthetic cannabinoid prep - rived CBD. It’s approved for treat- fits of THC while also reducing arations have not led to any black ing seizures in Lennox-Gastaut and THC’s unwanted adverse effects. market or addiction treatment issues. Dravet syndromes in patients 2 (See THC vs. CBD.) years old and older. Dosages start Endocannabinoids (endogenous Epidiolex at 2.5 mg/kg twice daily and can cannabinoids) are molecules pro- In 2018, the FDA approved Epidi- be titrated up to 20 mg/kg/day. duced naturally and on demand by our own bodies. The two most re- searched and understood are anan- damide and 2-arachidonoylglycerol. are cre- ated in the laboratory and are sin- gle, isolated molecules that contain no other components of the canna- bis plant.

Cannabis options Cannabis products sold through THC vs. CBD state-licensed dispensaries can’t be The most commonly studied phytocannabinoids are delta-9-tetrahydrocannab inol prescribed in the United States. De- (THC) and cannabidiol (CBD). The two have important differences and similarities. spite widespread use around the THC is the most abundant cannabinoid in the cannabis plant and produces eu- world, cannabis was effectively taxed phoric, psychoactive effects that influence mood, consciousness, and behavior. into prohibition by the Marihuana Research shows that THC is effective for treating conditions that cause pain, nau- Tax Act of 1937 and was prohibited sea, appetite loss, insomnia, inflammation, and post-traumatic stress. Side effects under federal law in 1970, when it are dose dependent and can include hypotension, hallucinations, tachycardia, was placed in the Controlled Sub- central nervous system depression, euphoria, dizziness, drowsiness, somnolence, stances Act Schedule I category, the confusion, new or worsening nausea and vomiting, and seizures. THC also can most restrictive of five categories. By lead to substance use disorder. CBD is the second-most abundant cannabinoid found in the cannabis plant. definition, all Schedule I drugs have Both THC and CBD are mood-altering substances, which makes them psychoac- no medicinal value and are highly tive, but THC’s psychoactivity is more likely to cause impairment. CBD has been addictive. All cannabinoids found in shown to improve mood by decreasing anxiety and depression and is effective THC-rich cannabis plants remain in for treating nausea and vomiting; seizure, inflammatory, and neurodegenerative Schedule I. However, the Food and disorders; and pain. CBD also has been shown to cause apoptosis in various can- Drug Administration (FDA) has ap- cer cell lines. Side effects associated with CBD are dose dependent and can in- proved three synthetic cannabinoids. clude dizziness, anxiety, diarrhea, jitteriness, decreased appetite, hepatocellular (See FDA-approved synthetic canna- injury, somnolence and sedation, and suicidal ideation. binoid pharmaceuticals.) Despite

AmericanNurseToday.com November 2019 American Nurse Today 7 FDA-approved synthetic cannabinoid pharmaceuticals The U.S. Food and Drug Administration (FDA) has approved the following synthetic delta-9- (THC) formu - lations for medical use.

Indications Dosage Side effects

Dronabinol • Anorexia in patients with AIDS 2.5 mg to 10 mg, three • Hypotension (Schedule III) • Nausea and vomiting associated to four times daily • Tachycardia with chemotherapy in patients • Central nervous system depression for whom conventional • Euphoria treatment has failed • Dizziness • Drowsiness • Somnolence • Confusion • New or worsening nausea and vomiting • Seizures and seizurelike activity • Substance misuse

Dronabinol oral • Same as dronabinol 2.1 mg to 4.2 mg, Same as for above dronabinol solution (Schedule II) four to six times daily

Nabilone (Schedule II) • Nausea and vomiting associated 1 mg to 2 mg, two to • Tachycardia with chemotherapy in patients three times daily (no • Orthostatic hypotension for whom conventional treatment more than 6 mg per day) • Dizziness has failed • Drowsiness • Hallucinations • Ataxia • Substance misuse

Epidiolex is approved as a Sched- removed from restrictions un- tection and allowing product manu- ule V drug (the least restricted of der the Controlled Substances Act. facturers complete autonomy when the five categories and includes Many hemp-derived CBD products marketing their products. Consumer drugs with low potential for mis- are available for purchase on the in- health and safety are at risk until use). Side effects include hepatocel- ternet; in health food stores, pet food these products are subject to a com- lular injury, somnolence, sedation, stores, and gas stations; and at many pliance pathway. and suicidal ideation. other retail locations. Conflicting fed- eral laws have led to debate about Cannabis administration Nabiximols the legality of these products; how- Cannabis products can be adminis- Nabiximols, a cannabis plant-de- ever, hemp-derived products in the tered via various routes, including rived oral mucosal spray, is a delta- United States remain unregulated. topical, transdermal, inhalation, 9-THC and CBD 1:1 formulation Without oversight, the products may sublingual, and ingestion. Under- (each spray is 2.7 mg THC and 2.5 contain toxins or be mislabeled. The standing the onset and duration of mg CBD). Nabiximols isn’t available Journal of the American Medical As- action can help patients determine in the United States, but it’s been sociation released a study by Bonn- which route will effectively treat approved in 25 countries for mul- Miller in 2017 that found 70% of CBD their symptoms. Unfortunately, the tiple sclerosis spasticity. Dosages products were mislabeled. The study products available to patients de- range from two sprays up to 12 included vaporizer cartridges and pend on their state’s cannabis laws, sprays daily. Side effects include tinctures and found that 42% con- and many state cannabis programs tachycardia; transient alterations in tained more CBD than advertised severely limit the product and for- blood pressure; dizziness; mood, and 26% contained less than adver- mulary options. memory, and coordination changes; tised. Consumers should purchase and it has the potential for misuse. only products with a certificate of Topical analysis from a third-party testing Topical administration can provide Hemp facility. (See Buyer beware.) quick, localized relief with little to In December 2018, the Agricultural The U.S. Department of Agricul- no side effects. Unless the skin is Improvement Act (“Farm Bill”) legal- ture doesn’t anticipate providing broken, topicals typically don’t reach ized hemp and defined it as any part the regulations that oversee the the bloodstream. When activated, of the L. plant, in- Farm Bill until 2020, leaving pa- CB1 receptors on the skin can help cluding cannabinoids. These changes tients and consumers with little pro- reduce redness and inflammation as-

8 American Nurse Today Volume 14, Number 11 AmericanNurseToday.com minutes. Patients suffering from con- ditions that vary in intensity can ben- efit from this route because it pro- vides nearly immediate relief, is the most predictable of administrations, and is the easiest to control. It also is preferable for patients who can’t ingest other forms of medications. You must assess the patient to determine if the risks of inhalation outweigh the benefits, but an ex- Buyer beware tensive review of the medical litera- ture by the National Academies of Cannabis plants (including hemp) are bioaccumulators that absorb contami- nants and pollutants from the soil and environment. Heavy metals, pesticides, Sciences, Engineering, and Medi- and other toxins may be present in the plant and when extracted or concentrat- cine determined that smoking can- ed can be detected in the final product. Cannabis requirements nabis doesn’t lead to increases in vary from state to state, so check with your state’s cannabis regulatory agency to lung, head, or neck cancers. understand specific testing requirements.

Sublingual Patient education Explain to patients that because the hemp industry isn’t regulated, they should Sublingual applications can be an review the certificate of analysis (COA) for any over-the-counter cannabidiol prod- option for patients who can’t inhale. ucts they purchase. The COA must include testing for: They take effect within 15 minutes • potency and last 2 to 3 hours. However, • pesticides many sublingual products are oil- based and might not absorb quickly • molds into the mucosa, thereby following • residual solvents • the pattern of ingestion and delaying heavy metals onset by 1 to 2 hours. With oil-based • mycotoxins. sublingual products, patients should Also explain that any vape products they use should be free of flavoring agents be advised to wait a full 2 hours be- or other petroleum-derived additives (such as propylene glycol). These additives fore repeating the dose to avoid any haven’t been studied for inhalation. Remind patients that more research is need- potential adverse effects that can oc- ed to better understand vaping as a delivery method because there have been cur with over-ingesting cannabis. multiple reports associated with lung injury. Check the Centers for Disease Con- trol and Prevention website for updated information. Ingestion Ingesting cannabis can provide longer-lasting relief than other ad- sociated with condi tions like atopic calized relief; they might be less ministration methods and is ideal and contact dermatitis and psoria- beneficial to patients who have for patients who suffer from chron- sis. Topical cannabis also has been more generalized conditions. ic pain, inflammation, nausea, and shown to reduce pain and inflam- insomnia. A major disadvantage to mation associated with arthritis. A Transdermal ingestion is the variability in onset study by Stinchcomb and colleagues Transdermal cannabis products of action. Depending on the pa- reported that CBD can penetrate the (typically patches) take effect with- tient’s metabolism, genetics, gender, skin 10 times more effectively than in 1 hour and can provide between and food intake, the onset of action THC because it’s slightly more water 8 and 12 hours of relief while avoid- can range from 30 minutes to 2 soluble. ing first-pass metabolism. In pa- hours (and sometimes longer). The Patients have reported pain relief tients where drug interactions or effects, however, can last for 5 from topicals for muscle spasms medication adherence is a concern, hours or more. Because of this un- and tightness, pain, burns, transdermal products can be the predictability, patients can more itching, and peripheral neuropathy. best administration route. easily overconsume and experience Onset of action generally occurs adverse effects, such as tachycardia, within 10 minutes and can last 2 to Inhalation paranoia, hypotension, vomiting, 3 hours. Topical cannabis products Inhalation provides rapid relief, and even hallucinations. To avoid are ideal for patients who need lo- reaching the bloodstream within overconsumption, patients should

AmericanNurseToday.com November 2019 American Nurse Today 9 Resources for nurses

Use these resources to learn more about medical cannabis and patient care: be advised to “start low and go • slow,” waiting at least 2 hours be- American Cannabis Nurses Association uses advocacy, collaboration, educa- fore repeating a dose. Also, patients tion, research, and policy development to support cannabis nursing practice. cannabisnurses.org must know how to read the labels and understand serving sizes of the • Americans for Safe Access is dedicated to ensuring safe and legal access to products they ingest. cannabis for therapeutic use and research. safeaccessnow.org Drug interactions • Healer is an online support community for patients using medical cannabis. Although drug interactions with healer.com cannabis are rarely dangerous, re- • Project CBD is a nonprofit in California dedicated to promoting and publiciz- view the patient’s medication and ing research into medical cannabidiol use. supplement list to ensure no con- projectcbd.org traindications exist before begin- • ning cannabis therapy. Most in- Society of Cannabis Clinicians provides continuing education, facilitates best teractions occur with ingested practices, and conducts research related to medical cannabis. cannabisclinicians.org can na binoids. When taken orally, cannabinoids For more resources, vsit americannursetoday.com/?p=58596. are metabolized by the CYP family of enzymes. THC is commonly me- tabolized by the CYP2C9, CYP2C19, Work collaboratively with the pa- to guide patients on where to start. and CYP3A4 enzymes, which con- tient to determine his or her goals Everyone is different, so responses vert THC into 11-hydroxy-THC (11- and encourage initially focusing on to cannabinoid dosages will vary OH-THC). CBD is commonly metab- a single condition (which can de- from person to person, medicine. olized by the CYP2C19 and CYP3A4 crease variables and improve ad- The more information the patient enzymes, which convert CBD into 7- herence). Your nursing care plan records (such as the route, dosage, hydroxy-cannabidiol (7-OH-CBD). should facilitate the patient’s goals time of administration, length of ac- Because most medications are me- while decreasing potential adverse tion, and effect), the more you can tabolized by the CYP3A4 enzyme, effects and maximizing outcomes. help him or her improve outcomes. CBD and THC can inhibit or induce Teaching patients how to read and Also, cannabis has biphasic proper- other medications metabolized understand product labels will help ties, producing one effect at a low through that same enzyme. Also, them better understand dosages and dose and an opposite effect at a high- some medications, such as warfarin, enable them to independently self- er dose. Adverse effects from canna - can inhibit or induce THC and CBD, titrate their medicine. The more in- bis frequently depend on dose, and increasing or decreasing cannabi- formation the patient records (such larger doses can exacerbate symp- noid plasma levels. as the route, dosage, time of ad- toms like anxiety, insomnia, and pain. Because cannabis can produce ministration, length of action, and sedative effects, it should be used effect), the more you can help him Learn more with caution with other central nerv- or her improve outcomes. As cannabis legalization continues ous system depressants, including A typical cannabinoid serviing to gain momentum, more patients alcohol. Monitor patients throughout size can range from 5 mg to 10 mg will want to explore it as a medi- cannabis therapy to ensure safety (10 mg might be too high for a cine. Nurses must learn about the and treatment adherence and to re- cannabis-naive patient), but the ECS, cannabinoids, routes of ad- duce potential interactions. general cannabis protocol of “start ministration, potential drug interac- low and go slow” is widely accept- tions, and clinical implications to Assessment and dosing ed. No established national dosage better serve patients. For patients using medical canna- protocols exist for specific condi- bis, perform a systems assessment tions. And because of federal Eloise Theisen is the chief executive officer at Radicle and thorough health history that in- cannabis laws, don’t recommend Health in Walnut Creek, California, and incoming cludes a review of past treatments, specific dosages to patients. president of the American Cannabis Nurses Associa- comorbidities, previous can nabis Cannabis dosing remains a chal- tion. Eileen Konieczny is past-president of the Ameri- can Cannabis Nurses Association and author of Heal- experience, medication and supple- lenge, but some providers have de- ing with CBD: How Cannabidiol Can Transform Your ment reconciliation, food and med- veloped best practices. For example, Health Without the High. ication allergies, physical assess- Dustin Sulak, DO, of Healer.com ment, and risk for substance use provides patient education materials Visit americannursetoday.com/?p=58596 to disorder and psychiatric disorders. on tincture and inhalation dosages view a list of selected references.

10 American Nurse Today Volume 14, Number 11 AmericanNurseToday.com CNE Medical cannabis: What nurses need to know POST-TEST • CNE: 1.62 contact hours Earn contact hour credit online at americannursetoday.com/article-type/continuing-education/

Provider accreditation opment’s accredited provider status refers only to CNE activities The American Nurses Association’s Center for Continuing Edu- and does not imply that there is real or implied endorsement of cation and Professional Development is accredited as a pro- any product, service, or company referred to in this activity nor vider of continuing nursing education by the American Nurses of any company subsidizing costs related to the activity. The Credentialing Center’s Commission on Accreditation. ANCC planners of this CNE activity have disclosed no relevant finan- Provider Number 0023. cial relationships with any commercial companies pertaining Contact hours: 1.62 to this activity. Eileen Konieczny owns stock in and receives a salary from Gloucester Street Capital, which oversees the opera- ANA’s Center for Continuing Education and Professional Devel- tions of a medical marijuana license in New York. Eloise Theisen opment is approved by the California Board of Registered Nurs- owns stock in IllumeSense, a cannabis telehealth platform, and ing, Provider Number CEP6178 for 1.95 contact hours. is a consultant for Entire Health, which makes medicinal canna-

bis. This article underwent peerreview and no bias was found.. Post-test passing score is 80%. Expiration: 11/1/22 See the banner at the top of this page to learn how to earn ANA Center for Continuing Education and Professional Devel- CNE credit.

Please mark the correct answer online. 5. Which statement about the classifica- 9. Which statement about hemp products tion of cannabis in the United States is cor- in the United States is correct? 1. Which of the following are chemical rect? a. Hemp-derived products are unregulat- messengers that cause cannabinoids to in- a. Cannabis products sold through state- ed. teract at a receptor site of the endo- licensed dispensaries can be prescribed. b. Hemp-derived products are well regu- cannabinoid system? b. The Food and Drug Administration lated. a. Ligands (FDA) has not approved any form of c. Only a small percentage of hemp prod- b. Enzymes cannabinoids. ucts are mislabeled. c. Proteins c. All cannabinoids found in cannabis d. Selling of hemp-derived products is il- d. Microglias plants are classified in the Schedule I legal. category. 2. Which of the following break down 10. The cannabis plant-derived oral mu- cannabinoids after they’ve completed d. Prescription of plant-based cannabis has been prohibited since 1910. cosal spray that has been approved in oth- their function? er countries (but not the United States) for a. Ligands 6. Which has been approved by the FDA multiple sclerosis spasticity is b. Enzymes for treating seizures in Lennox-Gastaut a. dronabinol. c. Proteins and Dravet syndromes in patients 2 years b. nabilone. d. Microglias old and older? c. Nabiximols. a. Nabiximols d. Epidiolex. 3. CB2 receptors are b. Epidiolex a. found in the liver, colon, and prostate. 11. Transdermal cannabis products typi- b. most prevalent in the brainstem. c. Hemp d. THC cally take effect within c. not found in the peripheral nervous a. 30 minutes. system. 7. The maximum dose of nabilone is no b. 1 hour. d. concentrated in the peripheral immune more than c. 90 minutes. cells. a. 2 mg per day. d. 2 hours. b. 4 mg per day. 4. Which statement about types of 12. Sublingual cannabis products usually cannabinoids is correct? c. 6 mg per day. d. 8 mg per day. last a. Synthetic cannabinoids are created in a. 30 to 45 minutes. the laboratory and are made up of 8. The FDA has approved which synthetic b. 2 to 3 hours. clusters of four molecules. delta-9-THC as a Schedule III agent? c. 6 to 8 hours. b. Phytocannabinoids are molecules pro- a. Epidiolex d. 8 to 10 hours. duced naturally and on demand by our b. Nabilone own bodies. c. Nabiximols c. The most common phytocannabinoids d. Dronabinol are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). d. The most researched synthetic cannabinoids are anandamide and 2- arachidonoylglycerol.

AmericanNurseToday.com November 2019 American Nurse Today 11