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  1. Medical Marijuana and Clinical Oncology in 2022 "The Good the Bad and the Potentially Ugly" 1
  3. Some disclaimers No financial or other intellectual conflicts of interest to report Slides/materials have been derived from the internet and various other educational resources-special thanks to Dr Kerba University of Calgary To paraphrase our current prime minister “Some may have smoked but of course they never inhaled!” 3
  4. What we hope to exploretoday • History • Biology, pharmacology, and neuropharmacology of cannabinoids • Individual products and their mechanism of effect • Some of the current evidence for use • Potential concerns : drug interactions, college and provincial recommendations, other possible issues • Some Considerations: If you do take the endorsement plunge 4
  5. A Brief History 5
  6. History of cannabisasamedicine for cancer • First reported medical use>3000 yearsago • Siberian Ice Maiden: 5th century BC • Traditional Indian medicine • Analgesic, sedative, anxiolytic, appetite- Introduced into UKby O’Shaughnessyin 1842 • British physician working inIndia • Analgesic,anti-convulsant • Fell out of favour in1930s • Plant material too variable • Shelf-life short andunpredictable • Replacedby pure opiates and morereliable synthetic drugs • Removedfrom UK/USPharmacopeia1932 & ’41 • Prohibition 1930s related to bad publicity and “Reefer Madness” • Until recently-illegal in Canada since the 1970’s 6
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  8. Some Terminology • Cannabis-is the botanical term for the plants Cannabis sativa or Cannabis indica • Marijuana -is a cultural term for the cannabis plant - refers to the dried leaves, flowers, stems, and seeds • Medical marijuana/cannabis-marijuana that is recommended/ endorsed by a medical professional for the treatment of a variety of medical conditions 8
  9. Plant Biology and Forms 9
  10. Cannabismaybeendogenous, synthetic or derived fromplants • Phytocannabinoids • derived from plants: Cannabissativa • dried leaves and flowering heads(marijuana) • also resin of upper leaves & flowering beds (hashish) • Synthetic cannabinoids • synthetic THC:dronabinol,nabilone • many other forms (someillicit) • Endogenous:Endocannabinoids - anandamide • alter intracellular signaling • ?function is to modulate painresponse and a variety of other physiological functions 10
  11. Cannabissativa Marijuana (dried leaves/ flowering heads) Isolated purecompounds Non-cannabinoids Cannabinoids Psychoactive Δ9- THC Δ8-THC cannabinol (CBN)(weak) Active, not psychoactive Cannabidiol (CBD) Inactive >60 compounds >400 chemical compounds >70 types of cannabinoids Most potent psychoactive ingredient Phytocannabinoids Kalant H. PainResManage2001;6:80-91 Dr Marc KerbaTBCCJune12th 2019 11
  12. Forms of phytocannabanoids (plant-derived cannabis) • Inhaled leaf (smoked or vaporized) • rapid onsetbut short duration(2-4 hrs) • Buccalspray: Nabiximols (Sativex) • 1:1 THC:CBD,TGAregistered forMS • Ingested forms • cannabisoil • oral drops • oral capsule(liposomalformulation) • onset30-90 mins, duration 4-12hrs • Concentration of THC,CBD,other constituents vary widely but customizable with commercial preparations ie THC/CBD ratio 12
  13. The synthetic products maybe less than ideal 13
  14. Who Currently Uses Marijuana/Cannabinoids 14
  15. Marijuana/Cannabinoids are commonly used In North America, marijuana/cannabinoids are the 3rd most commonly used substances after alcohol and tobacco: Probably 22 Million Users in the last 30 days (8% of people 12 years and older) 2014 National Survey of Drug Use and Health 15
  16. Some homegrown Canadian statistics- pun intentional • More than 200 types of medical cannabis are available from Canadian licensed producers • The highest % of THC studied is 9.4%, but many current products around 15%. • 43 % of adults reported prior lifetime usage- 12% within the past year. • Average user consumed cannabis 2 -3 x week - 40% actually consuming >14 grams / week. 16
  17. Why Do North Americans Use Marijuana/Cannabinoids? Among North Americans who used marijuana in the past year: 17 SOURCE: Pew Charitable Trust, 2013 (reference list). 47% 30% 23% For Fun For Medical Reasons For Fun and for Medical Reasons
  18. Why do North Americans Use Medical Marijuana/Cannabinoids? DISORDER THAT REQUIRES TREATMENT % CITING AS REASON FOR MJ USE Chronic Pain 58.2% Mental Health Disorders 22.9% Sleep Disorders 21.3% Neurological Disorders 16.6% HIV 1.6% Cancer 1.5% Glaucoma 1.3% 18 SOURCE: Reinarman et al., 2011 (reference list).
  19. Who Uses Marijuana/Cannabinoids-1 ? • Joe (23 years old) • First used at a party age 15, continued using through college • Now uses when he goes out or is playing video games with friends • Also uses when stressed out • On average, uses about 4-5 times/week 19
  20. Who Uses Marijuana/Cannabinoids-2 ? • Maria & Terry (46 & 48 years old) • Used in college; stopped when she got pregnant • Now smoke socially and when they go to concerts • Maria uses when work stresses her out • Terry uses for pain stemming from chronic neuropathy 20
  21. Who Uses Marijuana/Cannabinoids-3 ? • Elise (78 years old) • Never used marijuana until she turned 63 • First used to improve appetite during chemotherapy for breast cancer • Cancer has now metastasized to her spine. • Conventional painkillers don’t work well; now uses several times a day for pain relief 21
  22. Meanwhile in Colorado, Oregon , California and more northern climes 22
  23. Colorado – The impact- of some early aspects of legalization was actually studied 23
  24. Colorado – Some Initial Impacts (2014) • Traffic fatalities involving operators testing positive for marijuana increased 100% from 2007 to 2012 • Increase in youth current marijuana users in 2012, to 10.47% of youth from 7.55% -nationally. Colorado, now ranked 4th in the nation, 39% higher than the national average • School drug related suspensions/expulsions increased 32% from school years 2008/2009 through 2012/2013 • A 57% increase in marijuana-related emergency room visits from 2011 through 2013 • Hospitalizations related to marijuana increased 82% from 2008 to 2013 24
  25. Did US legalization produce increased compassionate care danda use of cannabinoids/marijuana? <5% ■ Less than 5% of users had cancer, HIV/AIDS, or life-threatening diseases ■ 90% are registered for ailments such as general pain or headaches 25
  26. US legalization-Increased compassionate care use versussimply increased access to marijuana? >80% ■ Most card holders in CA and CO are white men between the ages of 17 -35 ■ No true history of chronic illness ■Often history of Alcohol and Drug Use 26
  27. • Wearenow in alegalizedenvironment • Bill C45the “CannabisAct” receivedRoyalAssent June21st2018 (Thank-you Wilson-Raybould...) • Legalto purchase cannabis from retailors authorizedby provinces – Oils – Dry or freshleaves – Seeds – Plants – Edibles -pending • Legal to purchase from any federally licensed producer And What about Canada-1? Regulation-BillC-45 Dr Marc Kerba TBCCJune 12th 2019 27
  28. AndWhatAboutCanada-2?USE2018National CannabisSurvey Dr Marc Kerba TBCCJune 12th 2019 28
  29. Canadian veterans' affairs-it was a marijuana growth powerhouse before funding was cut 29
  30. Cannabinoid Neurobiology 30
  31. Phylogenetically the endocannabinoids system evolved long before the actual plants appeared • The endocannabinoid system appears to help regulate numerous aspects of normal physiologic function, including cognition, coordination, memory, appetite, pain perception, heart rate, gastrointestinal mobility, intraocular pressure and immune function 31
  32. CB1 and CB2 receptors • CB1 receptors are the most widely expressed, located mainly in the central and peripheral nervous systems, plus a few other locations including cardiovascular, visual and gastrointestinal systems. • CB2 receptors have a more limited distribution, being located primarily in the immune system, including lymphatic tissue, spleen, macrophages and the immune cells of the CNS • Psychotropic effects are largely due to activation of the CB1 receptors, while the CB2 receptors in the periphery affect immune cells and play a role in inflammation and the immune response 32
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  34. Where THC acts in the brain 34
  35. WARNING if you are under age 25: Possible mis-wiring of the early brain: THC disrupts cortex development in fetus (Tortoriello et al., The EMBO J 2014) • THC reorganizes wires in the developing and adult nervous systems (Kano et al, 2009, Keimpema et al, 2010) • THC disrupts development and maintenance of connections critical for highly ordered executive and cognitive functions (Kittler et al, 2000). 35
  36. ? Explains the documented effects of cannabinoids on the brain of adolescents • The cerebellum plays a role in balance, psychomotor speed, language generation, rhythm production, inhibition, attention, and memory 36
  37. Adolescent Marijuana Users Have Enlarged Brain Cerebellum: Association with Poor Executive Function Source: Medina KL, Nagel BJ, Taper SF. Abnormal cerebellar morphometry in abstinent adolescent marijuana users. Psychiatry Research: Neuroimaging 182: 152-159, 2010. Following one month of abstinence, adolescent MJ users had significantly larger posterior cerebellar vermis volumes than non-using controls. These greater volumes are associated with poorer executive and cognitive functioning. . Chronic adolescent MJ users have shown significantly poorer sustained attention, cognitive inhibition, and abstract reasoning 37
  38. Howcannabinoidswork:postulated non-psychotropiceffects
  39. Cannabinoid Pharmacology 39
  40. Some cannabinoid pharmacology •THC identified in 1964 •Smoking: o1 cigarette contains 0.5 to 1g of cannabis o20% absorbed by lungs oOnset 15 minutes, duration 3 to 4 hours Oral consumption: oProlonged but poor absorption-average 10-15% oOnset 3-4 hours, duration 6 to 8 hours •Converted to metabolites o11-hydroxy-THC o11-nor-carboxy-THC • Accumulates in fat stores oT1/2 = 20-30 hours • Removal from body: o1/3 excreted as urine o2/3 eliminated in feces 40
  41. Vaporization of medical cannabis • Cannabinoids vaporize at a temp lower than combustion • Increasingly popular • Lower % of noxious chemicals • Volcano unit costs around $450 Accessed 08/31/2012 41
  42. A reversal of potency problems- “It’s not your dad’s ‘pot’ anymore” • Marijuana growers have worked hard to make the drug as potent as possible. • In 1960s-70s average THC concentrations were 1-2%. Today, they are as high as 20% 42
  43. Cannabinoid Physiology and Psychological Effects 43
  44. Potential effects of cannabis • Low-dose • mild euphoria, relaxation, sociability, reduced anxiety • temporal slowing • High-dose • agitation, anxiety, depersonalisation • dry mouth and eyes • tachycardia • psychomotor function impairment • paranoia, hallucinations, psychosis • Long-term • possible impaired verbal reasoning, memory, attention • addictive potential (< opioids), mild withdrawal syndrome Longo NEJM 2014 44
  45. However adverse events in cancer patients appear tolerable and possibly transient for most patients 45 Practical Considerations in Medical Cannabis Administration And Dosing MacCalluma et al, European Journal of Internal Medicine 49 (2018) 12–19
  46. Cannabis and psychosis • There is reasonable evidence that heavy cannabis use, and perhaps acute use in sensitive individuals, can induce an acute psychosis (Paranoia) • Scientific literature documents that heavy marijuana use can precipitate schizophrenic episodes but it is unknown if usge can cause the underlying psychotic disorder • At a population level, assuming a causal relationship, elimination of cannabis might reduce the incidence of schizophrenia by approximately 8%, 46
  47. Marijuana and abuse/dependence • SUD falls on a continuum of alcohol and drug use 47 PROBLEMATIC SUBSTANCE USE Risky Substance Use Substance Abuse Substance Dependence SUBSTANCE USE DISORDERS (SUD)
  48. Marijuana abuse/dependence • Most individuals use marijuana without developing SUD. • However, because usage is so widespread, more people end up using marijuana problematically than other drugs. • In LA County, marijuana use accounted for more substance use disorders treatment admissions (23.3%) than any other drug, including alcohol (22%). SOURCES: Los Angeles County DPH, 2011; NIDA, 2012a (reference list). 48
  49. Cannabis use disorder-How might the addictive risk compare? DRUG LIFETIME RISK OF DEPENDENCE Nicotine 32% Heroin 23% Cocaine 17% Alcohol 15% Marijuana 9% 49 SOURCE: Bostwick, 2012 (reference list).
  50. Cannabis withdrawal syndrome • A true clinical entity noted in heavy users • 3 (or more) of the following signs and symptoms develop within approximately 1 week: • Irritability, anger, or aggression. • Nervousness or anxiety. • Sleep difficulty (e.g., insomnia, disturbing dreams). • Decreased appetite or weight loss. • Restlessness. • Depressed mood. • At least 1 of the following physical symptoms causing significant discomfort: abdominal pain, shakiness/tremors, sweating, fever, chills, or headache. 50
  51. Cannabinoid hyperemesis syndrome Impressyourcolleagueswithyourdiagnosticacumen • First described in 2004 • Associated with chronic, heavy use of cannabis -presumably recreational or medical • Patient presents to emerg →complaint-recurrent episodes of severe nausea, retching and cyclical vomiting in the absence of other pathology • Pathgnomic history→temporary relief from hot showers/baths triggers compulsive showering! • Symptoms stop after cannabinoid cessation but may recur within weeks of resuming Schreck B., et al. Cannabinoid hyperemesis syndrome: review of the literature DrugAlcohol Depend. (2017) 182 27–32.
  52. Potential Indications Including Oncology 52
  53. Resurgencein interest in cannabisas treatmentforcancerover last 20 years • Non-legal use in community: anecdotes • Researchsince 1980s (esp. Israel) • Identified endogenous cannabinoids with influenceon neurologic, immune, gastro-intestinal systems • Synthetic THCdeveloped • FDAapproved: nauseaand vomiting due to chemotherapy • Dronabinol 1986 ,Nabilone2010) • Subsequently approved in various jurisdictions • Clinical trials launched in a variety of countries • Medical prescribing permitted in a number of countries including Europe, Canada, Australia, Israel etc 53
  54. Medline-indexedpublicationson cannabisor cannabinoids AND cancerhave increased dramatically since the 1970‘s 160 140 120 100 80 60 40 20 0 Number of papers Y ear 54
  55. Alberta’a own contributions-What’s That, Bud? Dr Marc Kerba TBCCJune 12th2019 55
  56. Dr Marc Kerba TBCCJune12th2019 Malignancy All respondents (n=1987) Anylifetime use (n=834) Usein last 6 months(n=356) Breast 428 166 (39%) 65 (15%) Lung 171 78 (46%) 43 (25%) Genitourinary 286 107 (37%) 43 (15%) Brain/H&N 240 105 (44%) 42 (18%) Gastrointestinal 345 152 (44%) 70 (20%) Hematologic 290 135 (47%) 55 (19%) Skin 28 13 (46%) 3 (11%) Gynecologic 129 52 (40%) 24 (19%) Other 70 26 (37%) 11(16%) Cannabis/Cannabinoidsusebycancerpatientsbytumorsite 56
  57. No. of activeusers n=356(%) Reasonfor Use Anycancersymptom (combined) 70 Cancerrelated pain 46 Cancerrelated nausea 34 Other cancersymptoms 31 Anynon-cancerreason (combined) 56 ReasonsforCannabis/Cannabinoidsusebycancerpatientswithinthelast6months Dr Marc Kerba TBCCJune12th2019 57
  58. So what might we really know about usefulness in cancer patients?-Two large well conducted trials –Netherlands-Israel 58
  59. Important aspects of this comprehensive study involving> 1700 cancer patients • >60% achieved satisfactory pain reduction with cannabinoid therapy • In relation to opioids • 50% continued to take same dose • 10% decreased dosing • 36% ceased taking completely • Other Improvements in: insomnia, restlessness, anxiety, depression, pruritus and headache. • 30% of patients experienced one side effect, • Commonest side effects were, dizziness, dry mouth, hyperphagia, sleepiness,psychoactive effect. Conclusion: cannabis represents a safe well-tolerated palliation for the majority of cancer patients 59
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  61. Somepossibleclinicalrecommendations/concernsinCancerPatients EVIDENCE FOR EFFCTS in CANCER PATIENTS Cannabis can be a useful adjunct in treating cancer pain. Cannabis is effective for nausea and vomiting. Cannabis may be useful in some patients for stimulating appetite. Cannabis may help treat anxiety, depression and insomnia. There is moderate evidence that cannabinoids are effective for seizures/spasticity. There is no concrete evidence that cannabis cures cancer or significantly alters tumor growth There are a number of theoretical concerns regarding potential interactions between cannabis/cannabinoids and various cancer therapies or individual oncology drugs 61
  62. Lets look at some study evidence 62
  63. A systematic review identified 28 studies (27 placebo-controlled, 1 treatment- controlled) of cannabis in a total of 2454 participants with chronic pain. 12 studies of neuropathic pain 6 trials of other types of pain 3 for cancer pain Chronic Pain 3 for diabetic neuropathy 2 for fibromyalgia 2 for HIV-associated sensory neuropathy Preparations tested included nabiximols, nabilone, inhaled cannabis, THC (oral or oromucosal), and dronabinol. Studies generally showed improvements in pain measures with cannabis and cannabinoids. 63
  64. Cannabis-Opioid Interactions A study of 21patients with chronic pain treated with sustained-release morphine or oxycodone found that adding inhaled cannabis for 5 days  Significantly decreased pain by 27% (95% CI 9-46)  Had no significant effect on plasma opioid levels. OPIOID Co-administration of cannabis or cannabinoids withopioids is safe and may allow for use of lower doses of opioids. CANNABIS
  65. A systematic review identified 28 RCTs (8 placebo-controlled, 20 treatment-controlled) with 1772 participants that examined the effects of cannabinoids on CINV. 14studies tested nabilone (which mimics THC) 9 studies tested dronabinol (THC) 4 studies tested levonantradol (no longer used inmedicine) 1study tested nabiximols (THC and CBD) Studies generally showed a benefit of cannabinoids for CINV. Chemotherapy-Induced Nausea and Vomiting (CINV) 65
  66. (Machado Rocha2008) 6 6 Summary:Chemotherapy-Induced Nausea and Vomiting (CINV)
  67. An RCT of 243 patients with CACS found no superiority of cannabis extract or THC over placebo for affecting appetite or quality of life. A double-blind, RCT of 469 patients with CACS found that megestrol acetate was more effective than dronabinol for stimulating appetite and increasing weight gain.  Combined treatment was no more effective than megestrol acetate alone. The effect of dronabinol on appetite and weight gain are small; megestrol acetate is superior. Summary:Appetite/Weight Cancer-related Anorexia Cachexia Syndrome (CACS)
  68. A randomized treatment-controlled crossover trial in 29 fibromyalgia patients with chronic insomnia found that nabilone 0.5-1 mg/kg before bedtime was superior to amitriptyline for improving sleep. 19 other studies that assessed sleep as a secondary outcome measure found that cannabinoids (primarily nabiximols) improved sleep quality. A randomized controlled trial of 10 patients with generalized Social Anxiety Disorder found that 4 0 0 mg CBD significantly decreased anxiety. Cannabinoids may help with some measures of sleep quality/anxiety. Sleep Disorders/Anxiety
  69. What about cancer cure or changes in tumor growth/progression 69
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  71. Current evidence – anti-tumour effects NIH summary of laboratory/animal/preclinical studies • Theoretically Cannabinoids mightcauseanti-tumour effects by variousmechanisms • induction of cell death and inhibition of cell growth • inhibition of tumour angiogenesis, invasion and metastasis • Someevidenceof potential anti-tumour effects in cellcultures/xenografts • glioma, hepatocellular carcinoma,non-small cell lung cancer and breast cancer • CBDmayalso enhance uptake of cytotoxic drugs into certain malignantcells • Thus far, shown in mouse models ofglioma • Only 1 human study (Spanish,n=9) • patients with glioblastoma multiforme(GBM)-non randomiseddesign • THCdirectly infused into tumour daily by subcutaneouscatheter • established safety but no conclusions reefficacy • Guzmán et al, Br JCancer2006 71
  72. Cannabis and Immunosuppression • Possibly Good news: THC was found to induce cell death in different types of cancer cells that have cannabinoid receptors. • Possibly Bad news: it can lead to enhanced growth of tumors that express low to undetectable levels of cannabinoid receptors by specifically suppressing the antitumor immune response. All these studies have been done in vitro and therefore little is known about the immune effects of chronic low- dose exposure to cannabis. 72
  73. Possible drug Interactions and other safety concerns in oncology 73
  74. 74 The cytochrome system and drug metabolism
  75. What potential interactions need we be mindful of? Cannabis Pharmacokinetics • Most of the potential cannabinoid cytochrome interactions concern inhibition, rather than stimulation of transport or metabolism • THC is metabolized by CYP3A4 and CYP2C9 • CBD is metabolized by CYP3A4 and 2CY2C19 • Both THC and CBD competitively inhibit CYP3A4, with CBD being far more potent in this regard • A number of anticancer medications are also metabolized by cytochromes CYP3A4 and CYP2D6 Brigden and England Oncology Exchange 17, 3, 2018 75
  76. Pharmacokinetic Interactions AndCannabis Drugsthat maytheoretically increase/decrease cannabis/cannabinoidblood levels 1.CYP2C9 inhibitors may increase serum concentration of THC Strong inhibitors: capecitabine, 5-fluorouracil Moderate inhibitors: abiraone, sorafenib, omeprazole, Septra 2.CYP3A4 inhibitors may increase serum concentration of THC & CBD Strong inhibitors: ketoconazole, clarithromycin, antiretrovirals, idelalasib moderate: aprepitant, diltiazem, imatinib, nilotinib, fluconazole, grapefruit 3.CYP3A4 inducers may reduce serum levels of THC and CBD Strong inducers: carbamazepine, phenytoin, enzalutamide 76 Brigden and England Oncology Exchange 17, 3, 2018
  77. Purity concerns-few Canadian studies Despite legalization, quality control problems persist • American study-After analyzing > 600 samples from certified growers /sellers, a state licensed lab detected little THC/CBD and lots of contamination. • The average CBD amount: just 0.1 % • Several marijuana flowers were "crawling" with up to 1 million fungal spores. • Some grower spray crops with dangerous pesticides-residues may pass into cannabis smoke • Any extraction process may leave behind residual solvents • Standards for quality control and analytical testing need to be rigorously enforced 77
  78. Some Provincial and College Issues 78
  79. • Listing conditions for which marijuana can be obtained, including other conditions as determined in writing...” Why Canadian regulatorybodies wereappropriately leery of US style "Marijuana Pill Mills” 79
  80. CMA, Canadian Family Physician, CMPA, Individual Provincial College’s Positions • The Canadian Medical Association has consistently opposed Health Canada’s approach which places physicians in the role of gatekeeper in authorizing access to marijuana. • Current Canadian Family Physician guidelines do not enthusiastically endorse cannabinoids • CMPA publications detailed individual physician’s responsibility and informed decision-making- also emphasize no obligation on the part of reluctant physicians to participate in prescribing • All of the above-? Relevance after legalization 80
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  82. Some ethical and professional issues 82
  83. If an individual decides to take the endorsement plunge 83
  84. First-Somequestionstopose… Dr Marc Kerba TBCCJune 12th, 2019 84
  85. Next: Be sure to satisfy any legal and documentation concerns • Few absolute contraindications but if recommending should assess/council for psychosis, bipolar disorder, significant cardiac disorder, lactation and pregnancy, prior history of significant substance abuse, and documented cannabis allergies. • Should document education:driving not recommended for 4 hours after inhaled, 6 hours after oral, or 8 hours if any “high” or euphoria experienced , as well as other risks • Fortunately no longer necessary to arrange and document regular follow-ups as per earlier pre-legalization individual provincial requirements 85
  86. Some final considerations if one decides to recommend POTENTIAL AREAS OF CAUTION Cannabis is contraindicated with any history of psychosis; current or past substance use disorder, cardiovascular or respiratory disease; pregnancy. • Use caution in patients with active mood disorders, risk factors for cardiovascular disease, users of high doses of alcohol or benzodiazepines • Use caution in patients younger than 25. • Do not suggest smoking dried product- suggest oral intake or vaporization, which is likely safer in the long run. • Recommend products with a balanced THC/CBD ratio (for example, 5%: 6% or 9%:9%). • Once started and effects accessed , THC/CBD ratio can be further adjusted to meet symptom needs . “Start low, go slow” 86
  87. Trying to Summarize/Make Sense of a Very Complex Topic 87
  88. Some final conclusions-my take1 • "Love it or leave it"-medical marijuana/cannaboid use is now commonly encountered in clinical practice in Canada, so it is critical for all health care providers to understand both the scientific rationale and practical implications of possible usage. • Medical marijuana/cannabinoids are not a panacea- may have significant health risks as well as many potential medical benefits. • IF physicians decide to make recommendations/endorsement for medical cannabis based on an individual's medical history/situation, appropriate documentation and counselling are recommended 88
  89. Some final conclusions-my take 2 Specific to oncology • Marijuana/cannabinoids are particularly appealing for oncology patients offering the possibility of a single medication to encompass a variety of problems, such as pain, nausea, anorexia, sleep disorders , and anxiety • More research is clearly needed in relations to indications, efficacy, potential interactions with other oncology therapies, plus who is most likely to benefit 89
  90. As always-Potential therapeutic benefit and convenience But never without a little Risk!
  91. Some potential resources University of California's Center for Medicinal Cannabis Research The CanadianConsortium for the Investigation of Cannabinoids Patients Out of Time 9 1
  92. Additional potential resources 9 2