1 Having the “Medical Marijuana” ConversationIDAA CME Snowbird, UT August 3, 2017 Mark A. Weiner, MD, DFASAM Section Head, Addiction Medicine and Medical Director of Substance Use Disorders – St. Joseph Mercy Hospital, Ann Arbor Medical Director, IHA Pain Management

2 Relevant Financial Relationships Content of Activity: ASAM Disclosure of Relevant Financial Relationships Content of Activity: Pain and Addiction Common Threads XV Name Commercial Interests Relevant Financial Relationships: What Was Received Relevant Financial Relationships: For What Role No Relevant Financial Relationships with Any Commercial Interests None

3 Objectives To walk out of this talk and not be afraid to have a good long discussion with your patient about marijuana. Develop some strategies to address the common questions that arise when discussing “medical marijuana”

4 Who are you?

5 How to prepare yourself for this talkImagine you are in the exam room and the topic of cannabis has come up At some points, imagine you are the patient with chronic pain

6 Disclaimer This talk is largely based on my clinical experience with chronic pain patients, addicted patients and consulting work I do with primary care doctors. There is a strong selection bias for the chronic patients I see: they have often failed everything. I like "shocking" patients by being unexpectedly open and understanding.

7 What conversation are we talking about?The patient who asks, “Doc, do you think I should try this medical marijuana everyone is talking about?” “Doc, I’ve been using marijuana for my pain. What do you think about that?” “What do you mean my drug screen says I’m smoking marijuana?”

8 CASE: D.D. DD is a 48 yo man with a history of chronic neck and back pain for 19 years subsequent to a traumatic MVA and failed back surgery syndrome. When I met him 5 years ago he was failing conventional pain medication that had included (at times) extended release morphine and oxycodone and methadone as well as multiple sedatives and "muscle relaxers". He was usually wheel chair bound. Labs at the time showed only mild vitamin D deficiency, urine toxicology was negative.

9 CASE: D.D. He was medically transitioned to buprenorphine and phenobarbital. His pain improved dramatically. After 6 months he would come to the office only using a cane. He was maintained on buprenorphine 12 – 16 mg/day, less in summer more in winter, over the next 3 years. He was able to interact with his son more which was very gratifying. In mid 2012, his pain began to worsen. No cause was identified. Imaging was unchanged.

10 CASE: D.D. Initially, I suggested increasing buprenorphine to 20 mg/ day but this resulted in no improvement. At the next visit, I recommended increasing to 24 mg/day. Again, no effect. Screening labs were updated. Urine toxicology was positive for THC >1000. Upon investigation, he clarified that he has been using marijuana to assist in pain relief for 3 months. We discussed a trial of discontinuation of marijuana to help clarify its impact. He agreed.

11 CASE: D.D. At the next visit, he reported continued poor pain control and a decrease in his quality of life. Urine toxicology again indicated THC> On further investigation, he reported that he did not stop using cannabis and was a certified “patient” and “caregiver/grower for six people” in The Michigan Medical Marijuana Program.

12 Stop: Why is this conversation difficult?Lots of emotion (fear): doctor and patient Expectations: doctor and patient Creates conflict: Patient advocacy vs ideals What does it mean to be a doctor?

13 Start off on the right footDo not get overly emotional However, it’s OK to talk honestly about your feelings or have the patient discuss their feelings

14 Why ARE we having this conversation?

15 Chronic Pain Patients are FrustratedConventional meds not effective, or not meeting expectations Meds too expensive (NB: regular use of cannabis is not cheap!) Lots of exposure to information on cannabis Apparent acceptance of cannabis by some medical professionals Weak science in both directions

16 Our responsibility to our chronic pain patientsSince many of these patients are frustrated with conventional medicines, we should enter into compassionate discussions about their pain and what they might be using to treat it (e.g. yoga, tai chi, supplements or marijuana) I think it is a disservice to act in a dismissive, dictatorial, pedantic or prejudiced manner (this may take some effort on our part)

17 Switch places for a momentFrustrated with conventional medical therapy Has family and friends (who really care) Sees advertisements/blogs/internet Is exposed to the media coverage May have used marijuana in the past May not know what you know

18 Why are WE having this conversation?

19 Remember someone called it “Medical” marijuanaPart of “voter approved” (medical) marijuana programs Need to certify or endorse use Potential efficacy of cannabinoids Thank goodness – we get an opportunity to intervene and educate!

20 Ideals collide As a physician who practices Addiction Medicine I have serious concerns about the use of cannabis, a proven addictive substance As a physician who manages pain in patients who have failed all conventional therapy, I am open to any therapy that improves the patients quality of life Some patients are using cannabis and feel it is improving their quality of life

21 Overstate the obvious If we truly take inventory on this subject, the use of “medical marijuana” is potentially frustrating for us. Pro-marijuana advocacy groups are attempting to use “compassion” as a manipulation. If we let that frustration take over, we will lose an important opportunity to help. We can turn potential difficulty into a “golden moment” for you and the patient.

22 Is “medical marijuana” really medical?Should have: Consensus of medical professionals on efficacy and safety (not a referendum) Have an ongoing doctor-patient relationship Have a definable and objective diagnosis Would involve a prescription by a licensed physician (not just a recommendation or endorsement)

23 General Guidelines Take a deep breath (room air) Do not panic!Let the patient talk (and listen carefully) Do not be judgmental Do not be dismissive Do not roll your eyes (even though you might want to)

24 What are you listening for?Changes in function Changes in pain Sleep changes Mood changes Effect on nausea Appetite/weight changes Motivational changes Changes in memory Social interaction Many more…

25 Conversational Tips Patients generally do not like being told or “treated as” they are: Idiots Criminals Deviants Childish Addicts Many patients respond well to being treated with respect and compassion

26 Set the stage for the conversationClarify that your discussion will be based on your medical opinion and experience Clarify you will not be discussing the legal, moral, political or spiritual aspects of marijuana. “I am not a lawyer, a policeman, a politician, a priest, a rabbi or your spiritual leader. You are paying me to be your medical consultant and I will give you my medical opinion.”

27 You now need a medical opinion about marijuanaHow do you get one? Ask the experts….

28 Who Are The Experts?

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31 Why Talk about Marijuana?We are part of the system (like it or not) 28 states have allowed medicinal use of marijuana The market for “legal marijuana” in the U.S. stood at $11.9 B in 2016 (legal plus medical) For comparison, all Harry Potter films total take, $2.4 B; Eli Lilly 2015 sales, $19.9 B

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33 So lets learn about…..

34 History 2737 BC. Chinese Emperor Shen Neng used marijuana tea for the treatment of gout, rheumatism, malaria. 1000 BC Hindu description of cannabis use for pain of childbirth, insomnia, headaches 500 Heroditus described the Scythians burning hemp for intoxication and religious trance 200 AD Cannabis described in Chinese Pharmacopoeia

35 Conversational Tip AlertIt is very important to understand the following terms: Cannabis (marijuana) Cannabinoid (there are 85 known in cannabis) Endocannabinoid Endocannabinoid pain system Lack of understanding these terms can lead to confusion about the medicinal nature of cannabis Educate your patient!

36 Cannabinoid Research Sir William B. O’Shaughnessay , MD , FRS . Published methodical assessment of cannabis potential in medicine. Evidence that he successfully treated pain of rheumatism 1899 – Wood et al. isolate cannabinol from cannabis resin 1932 – Cahn identifies structure of cannabinol 1960 – Rapheal Mechoulam identifies THC as principle psychoactive component to cannabis 1986 – Gardner proves THC is addictive and activates brain reward center 1988 – Howlett identifies THC binding sites in the brain

37 General Medical Opinion about CannabinoidsThe general opinion of the modern medicine is encouraging and sympathetic toward the research and development of cannabinoid based medicines. This has been true for over 40 years. White papers from medical societies, including ASAM, support this.

38 Medical Opinion about CannabisThe Therapeutic Potential of Marijuana, Cohen and Stillman, 1976: “It should not be expected, nor is it anticipated that some cannabinoid will be available commercially in the near future. The nature of the approval process is such that years elapse Between initial testing, however promising, and final approval for marketing. This is particularly true for a completely new chemical entity, and even more so for one with a checkered reputation. Cannabis, itself, will never be adopted for medical indications. It contains dozens of constituents, some of which have undesirable effects. Delta-9- tetrahydrocannabinol is a possible candidate, but it is more likely that a synthetic analogue, tailored to intensify the desired action and to avoid the undesired ones, will be preferred.”

39 Medical Opinion about CannabisNIDA Research Monograph, Pederson (Ed.) , 1977: ““If consistently useful medical applications for marihuana are found, it is quite likely that the product or products resulting will be chemically related but not identical to the natural material’s constituents. Cannabis, which was used therapeutically earlier in Western medicine for a variety of reasons, was eventually abandoned because of such problems as variable potency -- it often ranged from being inert to being much more powerful than the prescriber intended -- and undependable shelf life.”

40 “In regard to what we know about the endocannabinoid system and pain, anyone who chooses to smoke the raw product, cannabis, is performing and extraordinary experiment in polypharmacy.” Eliot L. Gardner, Ph.D “Common Threads XI” San Francisco, CA April 15, 2010

41 Structure of Cannabinoids

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43 Endocannabinoid Research1990 – Matsuda et al., clone CB1 recepter Mechoulam’s group and Pertwee’s group simultaneously indentify first endocannabinoid, anandamide 1993 – Munro clones CB2 receptor 1994 – CB1 receptor anatagonist developed, SR141716A, Rimonabant 1995 – second endocannabinoid identified, 2-AG

44 CB1 and CB2 Receptors

45 Morrone W: Endocannabinoid History, Cannabis Dependence & Medical Marijuana, 2009

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48 CB1 Receptors Inhibits nerve function (i.e. firing)Expressed very densely in: Hippocampus: memory Cortex: reasoning Basal ganglia: motor control and motivation Proven to activate the VTA and Nucleus accumbens, the reward center responsible for addiction Likely do many different things based on location Wide distribution = very important to “mother nature”

49 Cannabinoid receptorsCB2 Spleen, Lymphatics, Tonsils Modulates immune function,inflammation. CB1 CNS, Testis, Uterus Modulates pain movement emesis emotion seizures

50 Cannabinoids and Pain Endocannabinoid receptors in:nerve endings: Stander, et al. J of Dermat. Science, 2005 Dorsal root ganglia: Bridges et al, Neuroscience119:3, 2003 Spinal Cord: Farquar-Smith et al Mol Cell Neuroscience 2000 Thalamus: Tsou et al., Neuroscience 1997 Endocannabinoids have anti-nocioceptive (anti-pain) effects - Guindon et al 2006 CB1 and CB2 antagonists can block anti-nocioceptive effects of anadamide - Guindon et al 2006 “Unimpeachable evidence” of cannabinoids aiding in pain relief

51 Ware, et al. CMAJ, 2010 23 patients with neuropathic painLow number, but excellent methods Patient given precisely 25mg aliquot of cannabis in 4 different strengths Titanium pipe Specific instruction on how to inhale

52 Ware, et al. CMAJ, 2010

53 Ware, et al. CMAJ, 2010

54 Conversation Point It is probable that the “sweet spot” for cannabis benefits occurs at a level before intoxication If one gets “high” they may have overshot the mark

55 Cannabis and Palliative CareDronabinol® indicated for chemotherapy induced nausea (CINV) Due to lack of compelling evidence, cannabis is no longer recommended for CINV (Todaro, 2010) Poll of Hospice in Washtenaw County: 4 requests for MMMP card of about 1200 patients

56 Cannabis and the heart Cannabis predictably increases heart rate up to 25 bpm or up to 35% over controls The effect persists for many hours From a physiologic standpoint, this leads to a significant increase in myocardial oxygen demand In a patient with abnormal coronary arteries, this could lead to a mismatch of oxygen supply vs demand and possible ischemia

57 Cannabis and the heart

58 Conversation Point “Cannabis is known to increase heart rate which could be problematic with your history of heart disease.”

59 Cannabis Hyperemesis SyndromeIntractable nausea vomiting and abdominal pain Similar, but distinct from, Cyclic Vomiting Syndrome Usually occurs after prolonged use of cannabis Refractory to all treatments except abstinence Usually have multiple ER admission over years Simonetto, 2012; Nicolson, 2012; Freeman-Keller, 2012

60 Cannabis Hyperemesis SyndromeUnusual association with taking long hot baths to relieve symptoms Toxic buildup of cannabinoids in gut tissue leads to potent down-regulation motility 86% cure rate from abstinence Simonetto, 2012; Nicolson, 2012; Freeman-Keller, 2012; Darmani, 2010

61 Conversation Points Cannabis is no longer a generally accepted treatment for chemotherapy induced nausea Prolonged cannabis use has been associated with debilitating, intractable nausea and vomiting

62 Cannabis and Driving Cannabis, even at low doses, affects cognitive and psychomotor abilities required for driving Combining cannabis with alcohol eliminates compensation strategies and results in impairment (often unrecognized by the patient) This occurs even at doses which would be insignificant if either drug were taken alone Raes, 2008; Stewell, 2009

63 Conversation Point “Although this is still being studied and there is not complete agreement, for patients using marijuana, I suggest you do not drive for your own safety and those who might be injured if you were an impaired driver.” “Low levels of alcohol and THC can combine to lead to significant but unappreciated impairment that may injure you or innocent people.”

64 Cannabis and Memory THC reduces hippocampal neuron activation, below the level needed to trigger memory formation With chronic THC exposure neuron connections involved in memory are gradually lost due to continual suppression Brain imaging studies show regular THC users have a smaller hippocampus by volume and have poor memory. Sources: Iversen L. Howell cannabis works in the brain. Marijuana and Madness. Ed. Castle and Murray, 2004 Oxford University Press. Got Marijuana? R. Corey Waller MD, MS, FACEP, ABAM ASAM Annual Fall Meeting, 2013

65 Marijuana and Cognitive ImpairmentUse of 4 joints or more per week resulted in a decrement in mental test performance, subjects who smoked regularly for a decade or more did the worst . Long-term marijuana users were impaired 70% of the time on a decision making tests, compared to 55% for short-term users and 8% for non-users Sources: Messinis et al. Neurology 2006;66:737 Got Marijuana? R. Corey Waller MD, MS, FACEP, ABAM ASAM Annual Fall Meeting, 2013

66 Conversation Point If you are concerned about your memory or decision making ability, you may want to reconsider marijuana.

67 So who should NOT use MJ History of substance use disorderHistory of psychiatric disorder History of cardiovascular disease History of dementia or other cognitive disorder (e.g. TBI) Anyone worried about maintaining good brain function Anyone who drives or operates machinery

68 How Addiction Medicine Can Help“"My hope about the medical marijuana controversy is that we [ASAM] are able to inform the discussion … and provide some leadership that respects the science and the potential for therapeutic uses of cannabinoids and also protects the public health from what I consider a reckless exposure to an abused drug.” Robert Dupont, MD – 2011

69 CASE: D.D. I explained to D that I was very pleased he had the courage to openly discuss with me his marijuana use. I also clarified that I was concerned that his use of marijuana was interfering with my ability to manage his pain with buprenorphine. I further explained that I was uncomfortable continuing to prescribe buprenorphine if he was going to continue to use cannabis based on what I have seen. After some discussion he decided to be withdrawn from buprenorphine. I assisted him in this regard.

70 CASE: D.D. We gradually reduced the buprenorphine over the next three months. After the taper, he missed his next appointment and did not return for three months. Upon his return he shared with me his lack of improvement and wished to discontinue cannabis restart buprenorphine. His pain significantly improved again and the quality of his life has improved as well. He is been cannabis free for almost one year.

71 “I will prescribe regimens for the good of my patients according to my ability and my judgment and never do harm to anyone.”

72 Appropriate Ends: a doctor is to do what is best for the patient, rather than what is best for the physician.

73 Summary Conversations with your patients about cannabis should be expected Conversations with your patients about cannabis should be encouraged Relax and use these conversations to learn about your patient’s particular frustrations, expectations, fears, dreams, etc.

74 Summary Take time to educate Take time to be compassionateAlthough patients will bring their own agenda to the visit, treat them all with respect, understanding and dignity.

75 Thank you for listeningHow to reach me: Mark A. Weiner, MD, DFASAM Office: Google Voice: