Clinical Policy Title: Botanical marijuana for medical use

Clinical Policy Title: Botanical marijuana for medical use Clinical Policy Number: CCP.1132 Effective Date: January 1, 2015 Initial Review Date: August 20, 2014 Most Recent Review Date: October 2, 2018 Next Review Date: October 2019 Policy contains: Medical marijuana. Cannabis. Tetrahydrocannabinol. Hydrocannabinol. Related policies: None. ABOUT THIS POLICY: Select Health of South Carolina has developed clinical policies to assist with making coverage determinations. Select Health of South Carolina s clinical policies are based on guidelines from established industry sources, such as the Centers for Medicare & Medicaid Services (CMS), state regulatory agencies, the American Medical Association (AMA), medical specialty professional societies, and peerreviewed professional literature. These clinical policies along with other sources, such as plan benefits and state and federal laws and regulatory requirements, including any state- or plan-specific definition of medically necessary, and the specific facts of the particular situation are considered by Select Health of South Carolina when making coverage determinations. In the event of conflict between this clinical policy and plan benefits and/or state or federal laws and/or regulatory requirements, the plan benefits and/or state and federal laws and/or regulatory requirements shall control. Select Health of South Carolina s clinical policies are for informational purposes only and not intended as medical advice or to direct treatment. Physicians and other health care providers are solely responsible for the treatment decisions for their patients. Select Health of South Carolina s clinical policies are reflective of evidence-based medicine at the time of review. As medical science evolves, Select Health of South Carolina will update its clinical policies as necessary. Select Health of South Carolina s clinical policies are not guarantees of payment. Coverage policy Select Health of South Carolina considers the use of botanical marijuana not clinically proven and, therefore, not medically necessary (U.S. Food and Drug Administration, 2018; American College of Obstetricians and Gynecologists, 2017; National Academies of Sciences, Engineering, and Medicine, 2017; American Academy of Pediatrics, 2015). For the purpose of this policy, the term marijuana refers to the dried leaves and flowers of marijuana, and any mixture or preparation thereof, and does not include U.S. Food and Drug Administration-approved drugs that may contain active ingredients that are present in marijuana (e.g., dronabinol or nabilone). This policy applies to any method of absorption, including but not limited to smoking, vaporizing, nasal or oral sprays, and oral ingestion. Limitations: None. 1

Alternative covered services: U.S. Food and Drug Administration-approved drugs represented in evidence-based practice standards. Background Cannabis, also known as marijuana, is the dried leaves and flowering tops of the cannabis plant, most commonly, cannabis sativa. Cannabis produces terpenophenolic compounds called cannabinoids, which activate specific receptors found throughout the body, particularly in the central nervous system and the immune system, causing pharmacologic effects in the body. Tetrahydrocannabinol is the main cannabinoid found in cannabis and largely responsible for its psychoactive effects (National Cancer Institute, 2018). Cannabis may be taken by mouth or inhaled. When taken by mouth (in baked products or as an herbal tea), tetrahydrocannabinol is processed by the liver, making an additional psychoactive chemical. When cannabis is smoked and inhaled, cannabinoids quickly enter the bloodstream. The additional psychoactive chemical is produced in smaller amounts than when taken by mouth (National Cancer Institute, 2018). Medical marijuana refers to the use of cannabis and its constituents as a physician-recommended form of medicine or herbal therapy. Marijuana or marijuana-derived products are being used for a number of medical conditions, including AIDS wasting, epilepsy, neuropathic pain, treatment of spasticity associated with multiple sclerosis, and cancer- and chemotherapy-induced nausea and vomiting (U.S. Food and Drug Administration, 2018). The risks and benefits of its medicinal use are unclear (National Cancer Institute, 2018). The most rigorous studies have reported adverse events associated with its recreational use, but extrapolating results of recreational cannabis use cannot be expected to occur with medical marijuana use. The amounts used, the existence of comorbidities, and the methods of drug delivery may differ between the two populations. Therefore, there is a strong scientific rationale for evaluating medical marijuana separately (Wang, 2008). Regulation: In the United States, marijuana is a Schedule I controlled substance requiring special licensing for its use; it has no recognized medical use, carries a high risk of dependency, and is illegal to use and distribute (21 U.S.C. 801). The U.S. Food and Drug Administration (2017) is responsible for the approval and marketing of drugs for medical use, including controlled substances. Several states have either passed laws that remove state restrictions on the medical use of marijuana and its derivatives, or are considering doing so. To date, the U.S. Food and Drug Administration has not approved a marketing application for a drug product containing or derived from botanical marijuana, and has not found any such product to be safe and effective for any indication. 2

The U.S. Food and Drug Administration has approved two drugs that have synthetic tetrahydrocannabinol as an active ingredient. Dronabinol, marketed as Marinol (AbbVie Inc., North Chicago, Illinois) and Syndros (Insys Therapeutics, Inc., Chandler, Arizona), is approved for anorexia associated with weight loss in patients with AIDS and for nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments. Nabilone is marketed as Cesamet (Valeant Pharmaceuticals, Aliso Viejo, California), which has a chemical structure similar to tetrahydrocannabinol and is approved for chemotherapy-induced nausea and vomiting in patients who have failed to respond adequately to conventional antiemetic treatments. Dronabinol and nabilone are administered orally in capsule form (U.S. Food and Drug Administration, 2018). In April 2014, the U.S. Food and Drug Administration granted Fast-Track designation to the investigational drug product Sativex (GW Pharmaceuticals, United Kingdom) (U.S. Food and Drug Administration, 2016). Sativex is composed primarily of cannabidiol and tetrahydrocannabinol; it is administered as a metered dose oromucosal spray for the treatment of pain in patients with advanced cancer, who experience inadequate analgesia during optimized chronic opioid therapy. Sativex is currently in Phase III clinical trials for this indication. On June 6, 2014, the U.S. Food and Drug Administration granted Fast-Track designation to Epidiolex (GW Pharmaceuticals, United Kingdom), for treatment of Dravet syndrome, a rare and catastrophic treatment-resistant form of childhood epilepsy. Fast-Track designation provides for more frequent meetings and communications with the U.S. Food and Drug Administration to discuss the drug s development plan and ensures collection of appropriate data needed to support drug approval, including the design of the proposed clinical trials and use of biomarkers (U.S. Food and Drug Administration, 2016). Medical uses of smoked, inhaled, ingested, or sprayed botanical marijuana are the focus of this clinical policy. This policy excludes Marinol, Cesamet, Sativex, or Epidiolex for clinical use, and marijuana for recreational use. Searches Select Health of South Carolina searched PubMed and the databases of: UK National Health Services Centre for Reviews and Dissemination. Agency for Healthcare Research and Quality s National Guideline Clearinghouse and other evidence-based practice centers. The Centers for Medicare & Medicaid Services. We conducted searches on August 13, 2018. Search terms were: Cannabis (MeSH) and Medical Marijuana (MeSH). 3

We included: Systematic reviews, which pool results from multiple studies to achieve larger sample sizes and greater precision of effect estimation than in smaller primary studies. Systematic reviews use predetermined transparent methods to minimize bias, effectively treating the review as a scientific endeavor, and are thus rated highest in evidence-grading hierarchies. Guidelines based on systematic reviews. Economic analyses, such as cost-effectiveness, and benefit or utility studies (but not simple cost studies), reporting both costs and outcomes sometimes referred to as efficiency studies which also rank near the top of evidence hierarchies. Findings We identified 10 systematic reviews for this policy. The systematic reviews examined the safety and effectiveness of cannabis and cannabinoids for several medical uses. These uses include wasting and cachexia in patients with human immunodeficiency virus/autoimmune deficiency syndrome, pain and spasticity in patients with amyotrophic lateral sclerosis/motor neuron disease, antiemesis for chemotherapy-induced nausea and vomiting, ataxia associated with multiple sclerosis, dyskinesia in Parkinson s disease, intraocular pressure in glaucoma, and symptoms of asthma. We found no economic analyses or evidence-based guidelines for this policy. The evidence is insufficient to support the use of botanical (smoked) marijuana for medical use. Most of the available evidence from randomized controlled trials with placebo controls was intended to assess the safety and efficacy of oral delta-9-tetrahydrocannabinol in patients who had failed conventional therapies. Relatively few have evaluated the safety and efficacy of smoked marijuana for medical use. All of the studies involved small numbers of patients and were of short duration, lasting from several days to weeks, depending on the condition being treated. Studies carried out in the 1970s and 1980s compared medical marijuana to outdated standards of care and lacked measurement of benefits and harms associated with long-term inhaled marijuana use. The paucity and poor quality of the evidence make it difficult to compare botanical marijuana with current pharmaceuticals that have received regulatory approval under more rigorous experimental conditions. Marijuana contains a variable mixture of poorly defined biologically active compounds and the level of tetrahydrocannabinol fluctuates significantly between samples, making it impossible to quantify by inspection. The concept of a predictable, quantifiable "dose" is a fundamental principle of medical therapy, but few (if any) of the prescribing criteria of medical pharmacology can be met in the case of smoked or ingested botanical marijuana (Fisher, 2002). Our searches and a report by the Canadian Agency for Drugs and Technologies in Health (2013) found no evidence-based guidelines supporting the use of medical marijuana for specific medical conditions. Practitioners recognized that marijuana might have treatment potential for certain medical symptoms. However, they are not uniform in their support for, or opposition to, medical marijuana. Several major 4

medical organizations in the United States have not endorsed the use of medical marijuana, but most have called for expedited clinical research to discern its safety, dosage, and effectiveness, particularly of cannabinoids rather than smoked marijuana (American Academy of Pediatrics, 2015; American Academy of Child and Adolescent Psychiatry, 2012; American College of Physicians, 2008). Policy updates: In 2015, we identified one new systematic review for this update (Koppel, 2014). The results of the review do not change the previous conclusions. Therefore, no changes to the policy are warranted. In 2016, we identified two new evidence-based guidelines, four systematic review and meta-analyses, and one large epidemiologic study for this policy. Guidelines by the American Congress of Obstetricians and Gynecologists (2015) and the American Academy of Neurology (Yadav, 2014) cite the limited evidence supporting the safety and efficacy of medical cannabis use in pregnant women and persons with multiple sclerosis, respectively. Both guidelines highlight concerns for known adverse effects and knowledge gaps in standardized administration of cannabis, long-term effects, and interactions with other drug treatments. Results of three new systematic reviews and meta-analyses suggest botanical cannabis offers short-term relief of chronic neuropathic pain with non-serious side effects when used in conjunction with traditional analgesics, but comparisons to treatment alternatives are lacking, as are long-term safety and effectiveness data (Andreae, 2015; Deshpande, 2015; Whiting, 2015). In addition, Whiting (2015) found low-to-moderate quality evidence that botanical cannabis improved chemotherapy-induced nausea and vomiting, weight gain in HIV infection, sleep disorders, and Tourette syndrome, but also increased the risk of adverse effects, including some serious ones such as psychosis. Gurney (2015) found low-quality evidence supporting an association between cannabis use and increased risk of developing nonseminoma testicular germ cell cancer, particularly among current users, at least weekly users and chronic users (> 10 years), compared to those who never used cannabis. Finally, a large epidemiologic survey of 34,653 adults aged 18 years in the United States found cannabis use was significantly associated with an increased risk for several substance use disorders (Blanco, 2016). Based on the new evidence, the benefits of botanical cannabis for medical use do not outweigh the risks of adverse events for any indication. According to the U.S. Food and Drug Administration (2016), additional research of its safety and effectiveness should be registered by the Drug Enforcement Administration and conducted under an U.S. Food and Drug Administration investigational new drug application and research protocol using medical grade cannabis supplied by the National Institute on Drug Abuse. In 2017, we added one evidence-based guideline by the American Society of Clinical Oncology that addressed medical marijuana use for treating chronic cancer pain in adults (Paice, 2016), and one comprehensive systematic review of the health effects of cannabis and cannabinoid use for multiple indications (National Academies of Sciences, Engineering, and Medicine, 2017). The National Academies 5

of Sciences, Engineering, and Medicine review included the systematic reviews identified previously in this policy. While fairly high quality evidence from controlled studies supports the effectiveness of medical cannabis for treating chronic pain of various etiologies, most of the studies were carried out in other countries (National Academies of Sciences, Engineering, and Medicine, 2017). Very little is known about the efficacy, dose, routes of administration, or side effects of commonly used and commercially available cannabis products in the United States. Moreover, many of the cannabis products sold in stateregulated markets do not resemble the products available for research at the federal level in the United States. There is insufficient evidence upon which to base conclusions about therapeutic risks and benefits for other medical indications. The new information does not change previous policy findings, and no policy changes are warranted. In 2018, we added one updated guideline from the American College of Obstetricians and Gynecologists (2017, updates 2015) and three systematic reviews (Mucke, 2018; O Neil, 2017; Wong, 2017). The new results continue to question the clinical effectiveness of medical marijuana in light of concerns for its uncertain safety profile in adult and pediatric populations. The medical necessity of medical marijuana remains inconclusive, and no policy changes are warranted. Policy ID changed from CP# 00.02.10 to CCP.1132. Summary of clinical evidence: Citation Mucke (2018) Content, Methods, Recommendations Cochrane review Cannabis-based medicines for chronic neuropathic pain in adults Systematic review of 16 randomized controlled trials (n = 1,750 participants) of the efficacy, tolerability, and safety of cannabis-based medicines (herbal, plant-derived, synthetic) compared to placebo (15 studies) or an analgesic (dihydrocodeine) (one study). Length of studies ranged two to 26 weeks: oromucosal spray with tetrahydrocannabinol and cannabidiol (10 studies); nabilone (two studies); inhaled herbal cannabis (two studies); and dronabinol (two studies). Overall quality: very low to moderate. Moderate-quality evidence suggests cannabis-based medicines: May increase the number of people achieving pain relief of 30% versus placebo. Were associated with a greater number of study withdrawals due to adverse events than with placebo (10% vs. 5%, respectively). Low-quality evidence suggests Oromucosal spray with tetrahydrocannabinol and cannabidiol may increase the number of people achieving 50% pain relief versus placebo. Cannabis-based medicines may increase nervous system adverse events versus placebo. 6

Citation American Congress of Obstetricians and Gynecologists Committee Opinion (2017) Marijuana use during pregnancy and lactation O'Neil (2017) for the Veterans Health Administration Benefits and harms of plant-based cannabis for posttraumatic stress disorder Wong (2017) Medical cannabinoids in children and adolescents National Academies of Sciences, Engineering, and Medicine (2017) Health effects of cannabis and cannabinoids: the Content, Methods, Recommendations Psychiatric disorders were higher cannabis users than placebo (17% versus 5%, respectively). Very low quality evidence suggests cannabis improves the Patient Global Impression of Change measure, and herbal cannabis and placebo have comparable tolerability. Inconclusive or an absence of evidence for assessing: the frequency of serious events with cannabis-based medicines versus placebo; the long-term risks in the studies analyzed, and whether herbal cannabis reduces mean pain intensity (very low-quality evidence). Because of concerns regarding impaired neurodevelopment, as well as maternal and fetal exposure to the adverse effects of smoking, women who are pregnant or contemplating pregnancy should be encouraged to discontinue marijuana use. Obstetrician gynecologists should be discouraged from prescribing or suggesting the use of marijuana for medicinal purposes during preconception, pregnancy, and lactation. Pregnant women or women contemplating pregnancy should be encouraged to discontinue use of marijuana for medicinal purposes in favor of an alternative therapy for which there are better pregnancy-specific safety data. There are insufficient data to evaluate the effects of marijuana use on infants during lactation and breastfeeding, and in the absence of such data, marijuana use is discouraged. Systematic review include two systematic reviews and three observational studies. Studies had medium to high risk of bias, and overall evidence was judged insufficient. Two randomized trials and six other studies examining outcomes of cannabis use in patients with posttraumatic stress disorder are ongoing and are expected to be completed within three years. Systematic review of five randomized controlled trials, five retrospective chart reviews, five case reports, four open-label trials, two parent surveys, and one case series (n = 795 participants). Overall quality: low with high risk of bias, uncontrolled, underpowered, short follow up. Evidence for benefit was strongest for chemotherapy-induced nausea and vomiting, with increasing evidence of benefit for epilepsy. Insufficient evidence to support use for spasticity, neuropathic pain, posttraumatic stress disorder, and Tourette syndrome. Systematic review of selected fair-to-good quality systematic reviews (published since 2011) and subsequent high-quality primary research for multiple medical conditions. Evidence of treatment effectiveness of cannabis: 7

Citation current state of evidence and recommendations for research (Results for smoking or inhaled cannabis only) Blanco (2016) Cannabis use and risk of psychiatric disorders Paice (2016) for the American Society of Clinical Oncology Guideline: management of chronic pain in survivors of adult cancer Whiting (2015) Content, Methods, Recommendations - Sufficient evidence for pain, but very little is known about the efficacy, dose, routes of administration, or side effects of commonly used and commercially available cannabis products in the United States. - Insufficient for chemotherapy-induced nausea and vomiting. - Limited for increasing appetite and decreasing weight loss associated with human immunodeficiency virus/autoimmune deficiency syndrome. - No or insufficient evidence for all other indications. Limited evidence of no association between smoking cannabis and risk for certain cancers (i.e., lung, head and neck) in adults. Limited evidence of an association between cannabis smoking and non-seminoma-type testicular germ cell tumors (current, frequent, or chronic cannabis smoking). No or insufficient evidence of association between cannabis use and incidence of esophageal cancer. A nationally representative sample of 34,653 U.S. adults aged 18 years interviewed three years apart in the National Epidemiologic Survey on Alcohol and Related Conditions (wave 1, 2001-2002; wave 2, 2004-2005) using multiple regression analysis and propensity score matching used to estimate association between cannabis use at wave 1 and incidence and prevalence of Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV psychiatric disorders at wave 2. Within the general population, cannabis use in wave 1 was significantly associated with an increased risk for several substance use disorders in wave 2 (odds ratio [95% confidence interval]): - Any substance use disorders: 6.2 (4.1-9.4). - Any alcohol use disorder: 2.7 (1.9-3.8). - Any cannabis use disorder: 9.5 (6.4-14.1). - Any other drug use disorder: 2.6 (1.6-4.4). - Nicotine dependence: 1.7 (1.2-2.4). - But not mood disorder (1.1, 0.8-1.4) or anxiety disorder (0.9, 0.7-1.1). Clinicians may follow specific state regulations that allow access to medical cannabis or cannabinoids for patients with chronic pain after a consideration of the potential benefits and risks of the available formulations. (Evidence-based; benefits outweigh harms; evidence quality: intermediate; strength of recommendation: moderate). Cannabinoids for medical use: chemotherapy-induced nausea and vomiting, appetite stimulation in human immunodeficiency virus/autoimmune Systematic review and meta-analysis of 79 randomized controlled trials (6,462 total participants). Overall quality: low to moderate. Only four judged at low risk of bias. Mostly placebocontrolled. Most trials showed non-statistically significant improvement in symptoms. Moderate-quality evidence supports cannabinoid use for treatment of chronic pain and spasticity. 8

Citation deficiency syndrome, chronic pain, spasticity due to multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, or Tourette syndrome Yadav (2014) for the American Academy of Neurology Evidence-based guideline: complementary and alternative medicine in multiple sclerosis Content, Methods, Recommendations Low-quality evidence suggests cannabinoid use improved chemotherapy-induced nausea and vomiting, weight gain in human immunodeficiency virus infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term adverse events, including serious adverse events. Common adverse events included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination. Guideline included two non-randomized controlled trials of inhaled cannabis use (57 total patients with mixed types of multiple sclerosis). Conflicting findings with respect to short-term reductions in spasticity, pain, measures of posture and balance and cognitive performance. Cannabinoids may cause adverse effects. Clinicians should exercise caution regarding standardized vs. non-standardized cannabis extracts and overall quality control/nonregulation. Interaction with multiple sclerosis disease-modifying therapies is unknown. Insufficient evidence to recommend for or against cannabis use. References Professional society guidelines/other: ACOG Committee Opinion No. 722: Marijuana use during pregnancy and lactation. Obstet Gynecol. 2017; 130(4): e205 e209. DOI: 10.1097/aog.0000000000002354. American Academy of Pediatrics. The impact of marijuana policies on youth: clinical, research, and legal update. Pediatrics. 2015; 135(3): 584. DOI: 10.1542/peds.digest1353. Medical marijuana policy statement. American Academy of Child and Adolescent Psychiatry website. http://www.aacap.org/aacap/policy_statements/2012/aacap_medical_marijuana_policy_statement.a spx. Accessed August 14, 2018. National Academies of Sciences, Engineering, and Medicine. The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research. Washington, DC: The National Academies Press; 2017. DOI: 10.17226/24625. Rapid response report: reference list. The use of medical marijuana: guidelines and recommendations. 15 January 2013. Canadian Agency for Drugs and Technologies in Health website. http://www.cadth.ca/media/pdf/htis/jan-2013/ra0611%20medical%20marijuana%20final.pdf. Accessed August 14, 2018. 9

Supporting research into the therapeutic role of marijuana. A position paper of the American College of Physicians. American College of Physicians website. https://www.acponline.org/system/files/documents/advocacy/current_policy_papers/assets/medmarij uana.pdf. Accessed August 14, 2018. Yadav V, Bever C, Jr., Bowen J, et al. Summary of evidence-based guideline: complementary and alternative medicine in multiple sclerosis: report of the guideline development subcommittee of the American Academy of Neurology. Neurology. 2014; 82(12): 1083 1092. DOI: 10.1212/WNL.0000000000000250. Peer-reviewed references: 21 U.S.C. 801. Controlled Substances Act. Andreae MH, Carter GM, Shaparin N, et al. Inhaled cannabis for chronic neuropathic pain: a metaanalysis of individual patient data. J Pain. 2015; 16(12): 1221 1232. DOI: 10.1016/j.jpain.2015.07.009. Blanco C, Hasin DS, Wall MM, et al. Cannabis use and risk of psychiatric disorders: prospective evidence from a US national longitudinal study. JAMA Psychiatry. 2016; 73(4): 388 395. DOI: 10.1001/jamapsychiatry.2015.3229. Cannabis and Cannabinoids (PDQ ). Overview. Updated June 19, 2018. National Cancer Institute website. http://www.cancer.gov/cancertopics/pdq/cam/cannabis/healthprofessional. Accessed August 14, 2018. Deshpande A, Mailis-Gagnon A, Zoheiry N, Lakha SF. Efficacy and adverse effects of medical marijuana for chronic noncancer pain: Systematic review of randomized controlled trials. Can Fam Physician. 2015; 61(8): e372 e381. National Center for Biotechnology Information website. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4541447/. Accessed August 14, 2018. Fisher B, Johnston D, Leake P for the Medical Services Workers' Compensation Board Alberta. Marijuana for medicinal purposes: An evidence-based assessment. June, 2002. Workers' Compensation Board of British Columbia website: https://www.worksafebc.com/en/resources/health-careproviders/guides/marijuana-for-medicinal-purposes-an-evidence-based-assessment?lang=en. Accessed August 14, 2018. Gurney J, Shaw C, Stanley J, Signal V, Sarfati D. Cannabis exposure and risk of testicular cancer: a systematic review and meta-analysis. BMC Cancer. 2015; 15: 897. DOI: 10.1186/s12885-015-1905-6. Koppel BS, Brust JC, Fife T, et al. Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014; 82(17): 1556 1563. DOI: 10.1212/WNL.0000000000000363. 10

Lutge EE, Gray A, Siegfried N. The medical use of cannabis for reducing morbidity and mortality in patients with HIV/AIDS. Cochrane Database Syst Rev. 2013; 4: CD005175. DOI: 10.1002/14651858.CD005175.pub3 Mucke M, Phillips T, Radbruch L, Petzke F, Hauser W. Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2018; 3: Cd012182. DOI: 10.1002/14651858.CD012182.pub2. News & Events. FDA and Marijuana: Questions and Answers. Page last updated June 25, 2018. U.S. Food and Drug Administration website. http://www.fda.gov/newsevents/publichealthfocus/ucm421168.htm. Accessed August 14, 2018. News & Events. Researching the Potential Medical Benefits and Risks of Marijuana. July 13, 2016. U.S. Food and Drug Administration website. http://www.fda.gov/newsevents/testimony/ucm511057.htm. Accessed August 14, 2018. O'Neil ME, Nugent SM, Morasco BJ, et al. Benefits and harms of plant-based cannabis for posttraumatic stress disorder: a systematic review. Ann Intern Med. 2017; 167(5): 332 340. DOI: 10.7326/m17-0477. Wang T, Collet JP, Shapiro S, Ware MA. Adverse effects of medical cannabinoids: a systematic review. CMAJ: Canadian Medical Association Journal. 2008; 178(13): 1669 1678. National Center for Biotechnology Information website. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2413308/. Accessed August 14, 2018. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for medical use: A systematic review and metaanalysis. Jama. 2015; 313(24): 2456 2473. DOI: 10.1001/jama.2015.6358. Wong SS, Wilens TE. Medical cannabinoids in children and adolescents: a systematic review. Pediatrics. 2017; 140(5). DOI: 10.1542/peds.2017-1818. Centers for Medicare & Medicaid Services National Coverage Determinations: No National Coverage Determinations identified as of the writing of this policy. Local Coverage Determinations: No Local Coverage Determinations identified as of the writing of this policy. Commonly submitted codes 11

Below are the most commonly submitted codes for the service(s)/item(s) subject to this policy. This is not an exhaustive list of codes. Providers are expected to consult the appropriate coding manuals and bill accordingly. CPT Code Description Comment No codes ICD-10 Code Description Comment No codes HCPCS Level ll Code No codes Description Comment 12