ON THE COVER

12 | MINNESOTA MEDICINE SPECIAL REPORT | JUNE 2016 ON THE COVER

The Intractable conundrum

Medical cannabis will soon be available for a new set of patients—those with intractable pain. A look at the controversial decision to expand eligibility for the state’s program and what it could mean.

BY HOWARD BELL

ast December, Minnesota Commissioner of Health Edward Ehlinger, MD, MSPH, added intractable pain to the list of qualifying conditions for Minnesota’s program. Starting July 1, physicians, physician assistants and advanced prac- Ltice nurses can certify patients with “pain whose cause cannot be removed, and according to generally accepted medical practice, the full range of pain management modalities appropri-

JUNE 2016 | MINNESOTA MEDICINE SPECIAL REPORT | 13 ON THE COVER ate for this patient has been used without adequate result or with intolerable side effects.” Those patients will be able to pur- chase medical cannabis starting August 1. Certifying pain patients Adding intractable pain is expected to increase the number of patients enrolled Minnesota’s medical cannabis program will work the same way for intractable pain as it in Minnesota’s medical cannabis program, does for other eligible conditions. Physicians, physician assistants and advanced practice although no one knows by how much. In nurses can create an Office of Medical Cannabis (OMC) account at any time and certify other states in which medical cannabis is patients for intractable pain starting July 1. Creating an account takes just a few minutes; legal, chronic pain is often the most com- certifying a patient for intractable pain will take another five minutes, according to Tom mon reason for its use. Arneson, MD, MPH, the OMC’s research director. Certifying patients for intractable pain, as opposed to other conditions, requires three Unified uncertainty additional steps: The decision to add intractable pain as a 1. Stating that the patient has intractable pain. qualifying condition came after lengthy study and debate. The Minnesota Depart- 2. Identifying the primary medical condition causing the pain (chosen from a drop-down ment of Health’s Office of Medical Canna- menu of 30-plus conditions). bis (OMC) held 13 public meetings around 3. Providing the date and score of the most recent pain severity assessment so that the the state last fall and solicited comments effect of the cannabis on the patient’s pain can be tracked over time. (Practitioners can online. It heard from about 500 Minneso- select from six commonly-used pain scales or specify one that isn’t listed.) tans, more than 90 percent of whom sup- The OMC recommends using the PEG pain scale, which uses a score of zero to 10 to ported the addition of intractable pain. measure Pain on average over the past week, how much pain interfered with one’s The OMC also asked for input from Enjoyment of life, and how much it interfered with the patient’s General activity. an eight-member advisory panel of phy- The certifying clinician gives the patient a list of their clinical problems and their current sicians, physician assistants, pain psy- medications. The patient then takes those to the dispensing pharmacist at the medical chologists, nurses and pharmacists. The cannabis distribution center. The pharmacist reviews the patient’s health history and uses panel, which met four times, reviewed that information to suggest a dosage and formulation. The pharmacist also is responsible a large number of published papers and for educating the patient about the medication, monitoring its effects and reporting heard expert opinion on the safety and adverse reactions. effectiveness of cannabis for pain, risk for addiction and other adverse effects. Pharmacists must give patients a hard copy summary of information about the drug They analyzed the research and clinical product and dose. Patients are encouraged to share this with their clinician. evidence with help from the University of Certifying clinicians can see this summary any time by logging into their OMC account, Minnesota’s Evidence-Based Practice Cen- where they also can see which cannabis medicine the patient purchased and when. (This ter. Initially, a majority of the eight panel feature became available last fall.) Arneson says the OMC encourages clinicians to call members supported adding intractable pharmacists at the distribution centers with any questions or concerns. pain. But after the panel’s fourth meet- Minnesota’s medical cannabis law requires that the certifying clinician continue treating ing, sentiment changed, and the majority the patient’s intractable pain and report outcomes and side effects to the OMC as long as recommended not adding it. The primary the patient is taking cannabis for intractable pain. reason cited: the lack of good studies. Six months after a patient’s first cannabis purchase, the certifying clinician must submit Advisory panel member Erin Krebs, to the OMC a brief survey (they must re-submit the survey every six months thereafter). MD, MPH, an associate professor of medi- The survey is the same as the one used to document benefits and harms for other eligible cine at the University of Minnesota who conditions. However, these two questions have been added for patients with intractable studies chronic pain management, says pain: there just wasn’t strong enough evidence to support it. “Most of what’s out there is 1. Over the past six months has this patient’s use of medical cannabis assisted in reducing so weak,” she says. “Studies are too small, dosage or eliminating other medications used for pain? If yes, specify the change(s) in too short and we found lots of reporting medication(s). bias where results showing no benefit were 2. What is the pain rating scale, score and date of the most recent assessment?—H.B. left out and only results showing benefits were reported.” (The panel found there was “low-strength” evidence that cannabis

14 | MINNESOTA MEDICINE SPECIAL REPORT | JUNE 2016 ON THE COVER relieves MS-related pain and peripheral neuropathic pain.) “We could find only 10 or 12 legitimate studies, so instead of saying approve it, we said study it,” says panel member Daniel More eligible Truax, PA-C, who treats chronic pain at the Center for Pain Management in conditions possible Sartell. After reviewing the panel’s discus- More medical conditions may be added to the list of those eligible for medical cannabis sions and recommendations, the public use. During June and July, groups and individuals can petition for the addition of other testimony and the literature, however, the conditions by completing a form on the Office of Medical Cannabis website. A new commissioner chose advisory panel will be appointed to shape arguments for or against adding each condition. to add intractable The Commissioner of Health will review those arguments and announce his decision by pain to the list of December 1, 2016. Tom Arneson, MD, MPH, research director for the OMC, says they have qualifying condi- already received calls from patients wanting other conditions to be added. These include tions. His reasoning: PTSD, ulcerative colitis and . Patients with a newly eligible condition the strong public would be certified for medical cannabis starting July 1, 2017, and could begin purchasing support for doing medicine starting August 1, 2017. so, a clear need for Erin Krebs, MD, MPH more chronic pain treatments, and the smoked. The manufacturing facilities and oid abuse in Minnesota. That possibility significant anecdotal distribution centers are physician-run. has led some to take a more open view. and limited scien- Standardized testing by manufacturers and Hennepin County Medical Cen- tific evidence that outside labs goes far beyond what most ter addiction medicine expert Charles medical cannabis states do to assure consistent purity and Reznikoff, MD, who served on the De- helps some people dose. A “black box” warning sheet is given partment of Health’s medical cannabis ad- with some types of to all patients, cautioning them against visory committee in 2014, says he’s heard Daniel Truax, PA-C chronic pain. “Clini- using medical cannabis if they have a fam- hopeful stories from colleagues. “An on- cal trials show a ily history of psychosis or are pregnant cologist who wasn’t a believer told me he’s thread of effective- or breast-feeding, or allowing its use by becoming a believer because some of his ness,” says OMC children or adolescents. In addition, the patients taking cannabis have less pain, are Research Director OMC’s data collection and analysis of ef- more engaged with life and have lowered Tom Arneson, MD, fectiveness and adverse effects may be the their use.” MPH. most rigorous in the country. A study published in the October 2014 The commis- Although he voted against adding in- JAMA Internal Medicine found that states sioner also cited the tractable pain as a qualifying condition, with medical cannabis laws had a 25 per- Tom Arneson, MD, MPH Minnesota medical advisory panel member Arthur Wineman, cent lower annual opioid overdose death cannabis program’s MD, says he’s comfortable with the com- rate, on average, compared with states rigor and conserva- missioner’s decision. Wineman chairs that haven’t legalized medical cannabis. tive approach as HealthPartners family medicine depart- Another study published in the February other reasons for ap- ment and is regional medical director for 2016 Clinical Journal of Pain showed that proving the addition HealthPartners Medical Group, where among 274 chronic pain patients, medical of intractable pain. he helps design protocols for managing cannabis lowered pain severity scores by Minnesota has one chronic pain. “It was a decision based less 10 percent and raised ability to function Arthur Wineman, MD of the most restric- on scientific evidence and more on com- scores by 18 percent. Opioid consump- tive programs in the passion, acknowledging that medical can- tion at follow-up decreased by 44 percent. country. Its medical nabis may help some people,” he says, “We’re guardedly hopeful that medical cannabis products cannabis will decrease opioid use in Min- are available only in Less need for ? nesota,” Arneson says. “We’re hearing pill, liquid and vapor One hope is that allowing medical can- from more clinicians who tell us cannabis forms—no edibles or nabis to be used for intractable pain may has helped them get patients off of opioids whole-plant medi- help curb the problem of prescription opi- or reduce their use.” Brian Erickson, MD cines that can be

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Brian Erickson, MD, has seen firsthand how it can help alleviate pain and reduce the need for opioids. The psychiatrist and medical director for HealthEast’s pain clinic in St. Paul treated more than 70 pain patients with medical cannabis when he practiced at the University of Vermont’s pain clinic. Vermont has used cannabis tinctures that can be vaporized or placed under the tongue for pain since 2011. “It was very helpful for patients with peripheral neu- ropathy, back pain and headaches, who weren’t responding to other treatments,” New protocol for he says. “About 75 percent of my patients were able to reduce their opioid use and about 25 percent were able to get off of replacing opioids with them entirely. I had a patient who was on 80 mg a day of oxycodone and another who was on 100 mg a day of medical cannabis who got off opioids entirely.” That’s a “no brainer” benefit of using Vireo Health of Minnesota, the parent company of Minnesota Medical Solutions, one cannabis for intractable or chronic pain, of the state’s two medical cannabis manufacturers, has created a protocol to help says Kyle Kingsley, MD, founder and CEO patients replace opioids with medical cannabis. The protocol called Flexible Reduction of Otsego-based Minnesota Medical So- and Expedited Discontinuation of Opioid Medications (FREDOM) includes guidance for lutions, one of Minnesota’s two medical clinicians on medical cannabis dosing and formulation, “gentle tapering” from opioids, cannabis manufacturers. (Eagan-based and monitoring for side-effects and scoring patients’ pain. LeafLine Labs is the other.) FREDOM uses a “slowed-down” version of the opiate discontinuation methods used by the In April, Minnesota Medical Solutions’ Department of Veterans Affairs. parent company, Vireo Health, released “The FREDOM protocol is for patients who, along with their health care team, have a protocol for physicians wishing to help decided that opioid reduction would increase their quality of life,” says Kyle Kingsley, patients replace opioids with medical can- MD, founder and CEO of Vireo Health and Minnesota Medical Solutions. “We’re providing nabis. “Opioids kill 16,000 people in the a framework for physicians to interact with patients to decrease opioid use while using U.S. each year, more than motor vehicle medical cannabis to support pain management.” A March 2016 study in the Journal of accidents. Cannabis doesn’t do that,” Pain showed that chronic pain patients receiving medical cannabis from state-approved Kingsley says. dispensaries were able to reduce their total opioid use by 64 percent. Nor is cannabis as addictive, according Despite this promising finding, addiction experts remain skeptical. Charles Reznikoff, to Reznikoff. “Most marijuana addiction is MD, an addiction medicine specialist with Hennepin County Medical Center, says he’s relatively harmless and remits on its own,” concerned a protocol for weaning patients from opioids would be mistaken for treatment he says. “Opioids are far more addictive, of addiction. “Medical cannabis substitution for opioid addicts would likely expose those far more harmful, and the addiction does patients to serious risk. Opioid addicts should be referred to evidence-based treatment not remit on its own.” That said, Reznikoff programs.” cautions not to think of cannabis as a fix Some patients who have pain caused by cancer or other eligible conditions are already for the opioid crisis. “It’s a false choice,” he using the protocol. No outcomes data are available yet. Kingsley expects a significant says. “If you change from opioids to can- increase in use of the protocol when intractable pain patients can begin purchasing nabis, you’re just changing to a new, still medical cannabis. unproven therapeutic for a complex prob- lem.” Patients could end up using both The FREDOM protocol is available at http://vireohealth.com/research. It is considered a working draft, and Kingsley wants feedback from participating clinicians. Clinicians interested in the protocol can contact Vireo Health at 612-999-1606 or provider@ vireohealth.com.—H.B.

16 | MINNESOTA MEDICINE SPECIAL REPORT | JUNE 2016 ON THE COVER cannabis and opioids, which Reznikoff scale will allow manufacturers to produce ments to try first and for how long, before says “would be the worst-case scenario.” it at a lower cost. resorting to cannabis,” he says. Regardless of cost, some clinicians are Clinician concerns, concerned that using cannabis for pain More education needed misconceptions will create another opioid-like epidemic of The OMC’s website (www.health.state. Many physicians admit they just aren’t addiction and abuse, despite evidence that mn.us/topics/cannabis) provides an abun- ready to participate in the this hasn’t happened in other dance of information and resources, and medical cannabis pro- states. “Clinicians are still reel- HealthPartners and other health systems gram—for intractable pain ing from the opioid crisis and are doing their own clinician education. or any other eligible condi- now they want us to provide Yet clearly, physicians have questions tion. Reznikoff surveyed access to a drug the federal about medical cannabis and Minnesota’s 262 physicians at four health government doesn’t even con- program. “Most clinicians get their edu- systems in October 2015 sider legal,” Truax says. That cation through CME, and CME is about and found 74 percent of said, he acknowledges that more mainstream elements of medicine,” those who responded said “cannabis is safer than opioids Reznikoff says. “None of the specialty they didn’t have the knowl- and probably helpful to some medical societies are jumping on board edge to discuss the risks patients.” to educate their members about medical and benefits of medical can- That’s because cannabinoids cannabis. There needs to be more effort to Charles Reznikoff, MD nabis with a patient seeking attach to a completely different inform doctors about this.” certification for a qualifying condition. set of receptors than opioids. There are Kingsley says he believes that in time Fifty-three percent said they didn’t think almost no cannabinoid receptors in the and as evidence mounts, many of the intractable pain should be a qualifying respiratory center of the brain, making concerns about medical cannabis will condition. Eighty-one percent said even medical cannabis far less likely than opi- fade. (The OMC is required by law to if they believed medical cannabis was ap- oids to cause respiratory suppression. study whether patients in the program are propriate for a patient, they wouldn’t have As for giving patients a drug that makes experiencing benefits or harms. See p. 18 the time or know-how to go about certify- them “high,” Kingsley points to read about their prelimi- ing patients and managing their response out that side effect is reduced nary findings.) “We realize to treatment. “The results show that or eliminated when THC that only a small number of some clinicians feel uncomfortable with is properly combined with clinicians will ever register the whole program,” Reznikoff says. “It another cannabinoid, canna- to certify patients, based on places an undesired burden on them and bidiol (CBD). “We don’t make numbers from other states forces them to practice medicine outside any pure THC products,” he that have had programs for of evidence-based norms and rely on un- says. Minnesota Medical Solu- longer,” he says. “And we conventional production, regulation and tions uses a variety of THC/ realize some Minnesota clini- dispensing of medication.” CBD ratios in its products. cians will never be comfort- Some of their reluctance stems from Kingsley says most patients able until medical cannabis misunderstandings about how the can- start at a 50/50 ratio. goes through the entire FDA nabis program works. For example, some Some clinicians fear an Kyle Kingsley, MD vetting process.” But in the still think whole-plant products are used. onslaught of patients demanding medi- meantime, a number of patients are al- Some think pain patients must get a sec- cal cannabis once those with intractable ready benefitting, and the number of clini- ond opinion from a pain specialist. “Certi- pain can become certified. They’re also cians and patients signing up for the state’s fication for pain doesn’t require a second, concerned about having to turn patients program grows every week. “In time,” concurring opinion,” Arneson says. away, if they feel a patient doesn’t qualify. Kingsley predicts, “medical cannabis will Those who have certified patients for Part of the reason for that concern is the be a standard option for intractable pain the program expressed concern over the difficulty of diagnosing pain. “It’s the only management.” MM high cost of medical cannabis, which has eligible condition that can’t be objectively Howard Bell is a medical writer and frequent prevented some eligible patients from diagnosed,” Reznikoff says. Yet Arneson contributor to Minnesota Medicine. buying it. Kingsley anticipates prices will points out clinicians face that same diag- go down with the addition of intractable nostic challenge when pain patients ask pain. “It may double the number of pa- about opioids. “We rely on a clinician’s tients certified to use medical cannabis,” professional judgement to decide whether he predicts, explaining that economies of a patient has intractable pain, what treat-

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