Evidence based conversations about cannabis for pain

Transcription

1 Evidence based conversations about cannabis for pain Lori Montgomery, MD CCFP Medical Director, Chronic Pain Centre Clinical Lecturer, Depts of Family Medicine and Anesthesia, Perioperative and Pain Medicine University of Calgary 1

2 Faculty: Dr. Lori Montgomery Relationships with commercial interests: Grants/Research Support: [none] Speakers Bureau/Honoraria: [none] Consulting Fees: [none] Others: [none] 2

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6 The patient experience 6

7 Objectives 1. Articulate the evidence supporting and refuting the use of medical cannabis. 2. Identify patients at risk of adverse events from marijuana and patients who may be appropriate for medical marijuana 3. Understand the emerging trend of converting opioid use in patients with chronic, non-cancer pain to cannabis. 4. Implement safe practice in prescribing medical cannabis. 5. Report the potential impact of the legalization of cannabis. 7

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11 More than 400 chemical compounds hundreds of compounds Cannabis Sativa Marijuana (dried leaves and flowering heads) Isolated pure compounds Non-cannabinoids Cannabinoids (>100) Psychoactive Δ 9 -THC Δ 8 -THC cannabinol (weak) Active but?not psychoactive cannabidiol Inactive more than 60 compounds Kalant

12 Cannabinoids brain PAG RVM brainstem Location of CB receptors 1 dorsal root ganglion spinal cord Lynch M. Pain Management & Research, Volume 10 Suppl A, Autumn 2005 primary afferent receptor 12

13 Endocannabinoids Anandamide (AEA), 2-arachidonoylglycerol (2-AG), and others Decrease formation of cyclic AMP Decrease activity of protein kinase A Inhibits release of stored neurotransmitters Effects on pain, mood, cognition, wake/sleep cycles, immune function, inflammation, metabolism and energy homeostasis, bone development and bone density among many other things 13

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16 Therapeutic 16

17 Therapeutic Predictable effects in the body 17

18 Therapeutic Predictable effects in the body Safety issues are understood 18

19 Therapeutic 19

20 Clearly proven risks and benefits for pain patients Bostwick JM, Blurred boundaries: the therapeutics and politics of medical marijuana, Mayo Clinic Proceedings 87.2 (Feb. 2012): p172. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research, Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda, Board on Population Health and Public Health Practice, Health and Medicine Division, National Academies of Sciences, Engineering and Medicine, Washington DC January

21 Neuropathic pain Fibromyalgia Back pain HIV neuropathy MS pain Muscle spasm Myofascial pain Pelvic pain Migraine Tension headache 21

22 CFPC guidance There is no evidence to support use of marijuana for fibromyalgia, back pain, OA Should be considered only for neuropathic pain that has failed to respond to standard treatments, including pharmaceutical cannabinoids Should not be used for sleep or anxiety 22

23 Evidence to date Abrams, D. I., Jay, C. A., Shade, S. B., Vizoso, H. and others. (2007). Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology. 68: Wilsey, B., Marcotte, T., Tsodikov, A., Millman, J. and others. (2008). A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J.Pain. 9: Ellis RJ, Toperoff W, Valda F, van den Brande G and others. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology. 34(3): (2009) Ware MA, Wang T, Shapiro S, Robinson A, Ducruet T, Huynh T, Gamsa A, Bennett GJ, Collet JP, Smoked cannabis for chronic neuropathic pain: a randomized controlled trial, CMAJ 182(14): E (2010) Wilsey, B., Marcotte, T., Deutsch, R., Gouaux, B. et al. Low-Dose Vaporized Cannabis Significantly Improves Neuropathic Pain. J.Pain. 14: (2012) Wallace MS, Marcotte TD, Umlauf A, Gouaux B, and Atkinson JH, Efficacy of Inhaled Cannabis on Painful Diabetic Neuropathy, The Journal of Pain, Vol 16(7): (2015) 23

24 Evidence to date Average N=30 Duration of studies 5 days All previous smokers of marijuana Amounts ranging 25mg-900mg THC 9.4% Smoking or vapourizing Reduction in pain ranging from 0.7 to 3 points on the NRS 24

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26 Therapeutic Predictable effects in the body 26

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29 Edibles Making at home can result in unpredictable distribution of active ingredients in the product Highly lipophilic Delayed but prolonged effects Users can inadvertently take too much Adverse effects observed in Colorado, Washington 29

30 National Academies Scientific data indicate the potential therapeutic value of cannabinoid drugs, primarily tetrahydrocannabinol (THC) smoked marijuana, however, is a crude THC delivery system that also delivers harmful substances. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research, Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda, Board on Population Health and Public Health Practice, Health and Medicine Division, National Academies of Sciences, Engineering and Medicine, Washington DC January

31 National Academies Clinical trials of cannabinoid drugs for symptom management should be conducted with the goal of developing rapid-onset, reliable, and safe delivery systems. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research, Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda, Board on Population Health and Public Health Practice, Health and Medicine Division, National Academies of Sciences, Engineering and Medicine, Washington DC January

32 Therapeutic Predictable effects in the body Safety issues are understood 32

33 Neurocognitive effects Psychotic disorders Memory impairment Driving Natania A. Crane & Randi Melissa Schuster & Paolo Fusar-Poli & Raul Gonzalez, Effects of Cannabis on Neuroacognitive Functioning: Recent Advances, Neurodevelopmental Influences, and Sex Differences, Neuropsychol Rev (2013) 23:

34 Pulmonary effects (Tashkin 1988 vs 2006) 34

35 Cardiac effects m.medindia.net Raises heart rate Decreases HR variability Lowers blood pressure? Increased risk of MI if at risk Natania A. Crane & Randi Melissa Schuster & Paolo Fusar-Poli & Raul Gonzalez, Effects of Cannabis on Neuroacognitive Functioning: Recent Advances, Neurodevelopmental Influences, and Sex Differences, Neuropsychol Rev (2013) 23:

36 Mood Happy, relaxed, sleepy Anxious, agitated, depressed, hallucinations Ste-Marie PA, Fitzcharles MA, Gamsa A, Ware MA, Shir Y, Association of Herbal Cannabis Use With Negative Psychosocial Parameters in Patients With Fibromyalgia, Arthritis Care & Research, Vol. 64, No. 8, August 2012, pp

37 Takes time and frequent use 5-9% prevalence Unclear with medical use Tongtong Wang MSc, Jean-Paul Collet PhD MD, Stan Shapiro PhD, Mark A. Ware MBBS MSc, Adverse effects of medical cannabinoids: a systematic review, CMAJ June 17, (13) 37

38 Diversion Need similar controls to opioids Difficult with current regulations deathandtaxes.mag.com Thurstone C, Lieberman SA, Schmiege SJ, Medical marijuana diversion and associated problems in adolescent substance treatment, Drug Alcohol Depend November 1; 118(2-3):

39 Evidence of risks Ware MA, Wang T, Shapiro S, Collet JP for the COMPASS study team, Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS), Journal of Pain (2015) Cohort study; n=215 who chose to use cannabis and 216 who didn t; 12.5% THC x one year; median dose 2.5g Serious and non-serious adverse events, pulmonary and neurocognitive function, pain, mood, QoL 39

40 Evidence of risks Cannabis group younger, more alcohol and tobacco 67 cannabis patients and 34 controls stopped the study and were lost to follow-up (cannabis naïve and ex-users more likely to withdraw than current users) No difference in SAE; 818 AEs in cannabis group, 581 in non-cannabis Headache, nasopharyngitis, nausea, somnolence and dizziness most common 40

41 Evidence of risks Neurocognitive function improved in both groups FEV1 declined by 50ml in cannabis group 41

42 Evidence of risks Cannabis Use Disorder Mood Cognitive impairment Driving Pregnancy Children and adolescents COPD Cardiovascular/hepatic Hyperemesis 42

43 Benefit assessment Better sleep Improved Pain Less pain-related distress Quality of life (not at all clear) 43

44 Benefit assessment Taper opioids??? 44

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46 CFPC guidance Physicians seeking a second opinion on the potential clinical use of cannabis for their patient should only refer to facilities that meet standards for quality of care typically applied to specialized pain clinics It is essential that the authorizing physician, if not the patient s most responsible health care provider, communicate regularly with the family physician providing ongoing comprehensive care for the patient 46

47 CPSA Standard Evaluate the patient on a regular basis to determine the benefits and risks of cannabis as a treatment for the condition in question At minimum see the patient every three months following stabilization Provide ongoing care for the patient for the condition for which cannabis is the treatment, including a process to identify abuse or misuse 47

48 Weighing risks and benefits Cannabis Use Disorder Mood, psychosis Cognitive impairment Driving COPD/cancer Cardiovascular/hepatic Hyperemesis Severe (neuropathic) pain Impaired function despite evidence-based therapies No relevant risk factors No current substance abuse Third party issues considered Not pregnant/breastfeeding >24 48

49 Third Parties (consent) Unknown implications Rules are evolving surrounding insurance, disability programs, employer responsibilities Smoking certainly can have an impact on coverage Legal cases in progress 49

50 CFPC guidance Don t drive: Four hours after inhalation Six hours after oral ingestion Eight hours after inhalation or oral ingestion if the patient experiences euphoria Note that Health Canada warns of impairment up to 24h later 50

51 Lay the groundwork Document consent discussion and patient education Document risk assessment, UDT and cannabis treatment agreement Document concrete, measurable functional goals Agree that treatment will be stopped if function does not improve 51

52 The Medical Document Patient s name, DOB Daily quantity of cannabis Period of use Health care practitioner s name, business address etc Signature, date 52

53 Google: Health Canada marihuana licensed producers May 22, producers 53

54 Mark Ware, 2014 used with permission 54

55 WHO says that 1g = 2 cannabis cigarettes Image from leafly.com 55

56 CFPC guidance Start with lowest possible THC concentration Start with one inhalation once daily, at a time when the patient doesn t need to be alert and ideally will be supervised Increase slowly to no more than 3g daily of 9.4% THC Likely better to vaporize than smoke or consume orally Consider at this point unsafe to drive or combine with ETOH 56

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58 Like scraping ice from the car windows on a cold winter morning, we believe that we can now see enough to move forward. - Ann McLellan and Mark Ware, task force co-chairs 58

59 Goals - implement appropriate restrictions, in order to minimize the harms associated with cannabis use, and - provide adult access to a regulated supply of cannabis while reducing the scope and scale of the illicit market and its social harms. 59

60 Recommendations Minimum age 18 (or older) Similar labelling, advertising restrictions to Tobacco Act Standardized single servings for edibles, with a maximum THC amount Price/tax to discourage high potency products Public education on problematic use Tax revenue to benefit education/research/enforcement Address SDOH that drive substance use disorder 60

61 Safe supply chain Federal regulation of producers Provincial regulation of distribution, collaborating with municipalities Dedicated storefronts or mail order NOT colocated with alcohol or tobacco Away from schools, parks, community centres Personal cultivation max 4 plants per residence 61

62 Driving invest in research to determine a safe THC limit Public education to emphasize that cannabis is impairing and the best policy is not to use before/while driving 62

63 Medical use Maintain a separate framework for medical use Maintain affordability, availability, access Eliminate designated person Same tax system for medical and non medical use Support research and medical education Reassess in 5 years 63

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