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Faculty/Presenter Disclosure Faculty: Philippe Lucas Relationships with commercial interests: Philippe Lucas is a Research Affilliate with the Centre for Addictions Research of BC, as well as VP, Patient Research & Access at Tilray, the sponsor of the patient survey that is the focus of the following presentation. Philippe is also Interim Executive Director of the Canadian Medical Cannabis Council, an industry association representing Licensed Producers and patients.

Disclosure of Commercial Support This program has received financial support from Tilray in the form of travel funds. Potential for conflict(s) of interest: Philippe Lucas is a Research Affiliate with the Centre for Addictions Research of BC, as well as VP, Patient Research & Access at Tilray, the sponsor of the patient survey that is the focus of the following presentation.

Mitigating Potential Bias The Patient Survey has gone through ethics approval at the University of Victoria as well as Institutional Review Board Services, and data analysis of the patient survey results was conducted by academic colleagues with no direct affiliation with Tilray.

Medical Cannabis in the Treatment of Pain & Mental Health Philippe Lucas MA, PhD(c) Graduate Scholar, Centre for Addictions Research of BC Social Dimensions of Health, University of Victoria VP, Patient Research & Access, Tilray plucas@uvic.ca/philippe@tilray.ca

Medical Cannabis in Canada Canada was one of the first nations in the world to establish a federal medical cannabis program. R. v. Parker (2000) - constitutional right to choose cannabis as medicine without fear of criminal sanction. In response to court decisions, Health Canada launched the Marihuana Medical Access Regulations (MMAR). To date, approximately 200,000 Canadians have obtained an authorization to possess cannabis for medical purposes. 1 million Canadians used cannabis for self-defined medical conditions. (Adlaf, Begin & Sawka, 2005; Belle-Isle & Hathaway, 2007)

Canadian Medical Marihuana System MMAR ENDED March 31, 2014 MMPR LAUNCHED April 1st, 2014 ACMPR LAUNCHED August 24, 2016 Health Canada Santé Canada

The MMPR & ACMPR The Marihuana For Medical Purposes Regulations (MMPR) & Access to Cannabis for Medical Purposes Regulation (ACMPR) The most significant change in medical cannabis access since 2001, the MMPR regulations were implemented by Health Canada in December 2012, and went into full effect on April 1 st 2014. The new ACMPR took effect on August 24th, 2016. Simplified/decentralized application process NPs can prescribe (ON) Multiple Licensed Producers Increased quality control Increased strain/symptom awareness Re-instatement of personal production (ACMPR) No community-based storefront access Significant limitations on products

The Endocannabinoid System This system is complex and is responsible for extensive physiological and pathophysiological activity. Inflammation Appetite Metabolism Cardiovascular function Bone density Synaptic plasticity Pain Memory Sleep Reward/addiction Stress regulation Mood Reproduction Digestion

THC & CBD, Rationale for Use The pharmacodynamic effects of CBD include: The pharmacodynamic effects of THC include: Analgesic Muscle Relaxant Anxiolytic Neuroprotective Anti-oxidant Anti-psychotic activity Anti-seizure (more than THC) Analgesic (more than CBD) Muscle relaxant (more than CBD) Anti-emetic Appetite stimulating Immunomodulant Anti-seizure Psychoactive effects

Tilray Research Program; Current Studies Phase 2 placebo-controlled clinical trial agreement with the University of British Columbia to examine the therapeutic potential of medical cannabis on the symptoms of PTSD. 42 participants; military and police veterans and other survivors of physical violence. Study will compare vaporized cannabis of varying cannabinoid concentrations to placebo. Launched Sept. 2016. Pilot studies of Tilray cannabis-based extracts and preparations Pediatric Epilepsy (Hospital for Sick Children, Toronto, Canada) COPD (McGill University, Montreal, Canada) Nausea/vomiting in oncological treatment (New South Wales, Australia) Patient patterns of use and cannabis substitution research Tilray Observational Patient Survey (TOPS) 20+ sites, >1000 patients

Tilray Patient Survey 2017 - Methodology 239 question French and English survey launched at 9am on January 9th 2017 via email to 16,675 patients. Response rate of 3405 (3390 English and 15 French), 2032 of which provided a verifiable patient number and were therefore included in the final analysis. Mean Age: 40 yrs old Gender: Male: 1271 (62.5%) Female: 758 (37.3%) Other (non-binary, transmasculine): 3 (0.01%)

Primary Condition AIDS/HIV Arthritis Brain Injury Cancer/Leukemia Chronic Pain Chron s Disease Diabetes Eating Disorder Epilepsy Gastrointestinal Glaucoma Headache Hepatitis Insomnia Mental Health Movement Disorder MS Osteoporosis 0 300 600 900 1,200 Mental Health & Pain conditions account for 77.5% of patients (n=1574) Mental Health (insomnia, mental health, PTSD; n=813) = 40%. Pain (arthritis, chronic pain, headache; n=761) = 37.5%. PTSD Seizure Disorder Skin Condition Wasting Syndrome Other (please specify)

Primary Symptoms Anxiety Appetite Loss Chronic Pain Depression Gastrointestinal Headache Insomnia Infraocular Eye Disease Memory Loss Nausea Seizures Spasms Stress Other (please specify) 0 300 600 900 1,200 1. 56.8 (n=1154). 2. 48.8 (n=991) 3. 45.8 (n=930) 4. 45.7 (n=929) =767) 6. Headache: 24.3% (n=494) 7. Appetite Loss: 18.2% (n=369) 8. Nausea: 16.7% (n=340) 9. Spasms: 11.8% (n=240) 10. GI Disorders: 11.7% (n=238)

CANNABIS USE

Cannabis Use: Days Per Week & Grams Per Day 1 0.25 grams or less 2 0.50 grams 3 0.75 grams 4 1 gram 5 2 grams 6 3 grams 7 4 grams or more 01 400 800 1,200,600 7.6 (n=1515). 05 125 250 375 00 78.5% use <3 gms/day (n=1595).

Primary Method of Use Oral (Edibles suc.. Joint Pipe Waterpipe/bong Vaporizer/nail/vape pen Topical (lotions/salves) Juicing 27.8% (n=557) Oral/edibles 16.0% (n=320) Joint 30.2% (n=605) Pipe 11.0% (n=221) Waterpipe/bong 10.4% (n=209) 3.5% (n=271) Topical (on the skin; e.g. lotions/salves, etc. ) 0.3% (n=6) Juicing 0.2% (n=4) Other (please specify) 0.6% (n=12) ; n=628 47.3% primarily use non-smoked methods of ingestion (vaporization + oral ingestion; n=948). Other (please specify) 08 200 400 600 00

Favorite Type of Flower Cannabis 17. 5% Counts/frequency: 7.1% 7.4% 24.9% Indica (500, 24.9%), Sativa (436, 21.7%), Hybrid (427, 21.3%), 1:1 CBD (142, 7.1%), 3:1 CBD (149, 7.4%), I don t have a favorite (351,17.5%) 21.3% 21.7% High THC cannabis accounts for 68% of patient favorites, while higher CBD cannabis accounts for 32%.

Oral Extract Products; Use and Strain Types (oral) : (n=769

Extract Products Did you also use dried cannabis flower on the days that you used this product? 67% of patients who use extracts also report using flower product on the same day.

SUBSTITUTION EFFECT

Cannabis Substitution Have you ever substituted cannabis for: Prescription drugs: 69% of previous/current regular users Alcohol: 44% of previous/current regular users Tobacco: 31% 5 f previous/current regular users Illicit Substances: 26% of previous/current regular users

Cannabis Substitution, Prescription Drugs Fraction of all drug substitutions in each drug class (n=1,730 total substitutions) 3.4% Stimulant No Match Found Number of drug substitutions per drug class 700 600 Opioid 35.3% 5.5% Muscle Relaxer/Sleep Aid 8.1% Antiseisure 8.6% Number of patients 500 400 300 200 100 0 Antiemetic 1.4% Antipsychotic 3.01% Benzodiazepine 4.3% Non-opioid Pain Reliever 30.9% 21.4% Antidepressant Opioids account for 35.3% of all prescription drugs reported. followed by antidepressants (21.4%) and non-opioid pain medications (10.9%). opioid (n=610) antidepressant (n=371) non-opioid pain reliever (n=189) antiseisure (n=149) muscle relaxer/sleep aid (n=140) benzodiazepine (n= 75) stimulant (n= 59) antiemetic (n= 24) antipsychotic (n= 18)

Cannabis Substitution, Prescription Opioids 400 350 300 p s (1 1 250 200 150 100 50 0 Use (p<.01) Oral extracts, Primary Oral extracts, days/wk Opioid Subbers Other 1.71 1.46 11.64 9.81 21% 15% 4.3 3.6

Cannabis Substitution, Prescription Opioids Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999-2010 States with medical cannabis laws had a 24.8% lower mean annual opioid overdose mortality rate (95%CI, 37.5%to 9.5%; P=.003) compared with states without medical cannabis laws. Bachhuber et al. JAMA, 2014 Medical Marijuana Laws Reduce Prescription Medication Use in Medicare Part D In medical cannabis states, the number of Medicare prescriptions to seniors dropped for drugs that treat pain, depression, anxiety, nausea, psychoses, seizures and sleep disorders. For pain, the annual number of annual doses prescribed per physician fell by 1826 doses. Bradford & Bradford, Health Affairs, 2016 According to Veterans Affairs Canada, significant increase in the use of medical cannabis by patients is paralleled by a nearly 30% decrease in the use of benzodiazapines and a 16% decrease in the use of opioids. Mike Hager, Globe & Mail, June 6th, 2016

Cannabis Substitution, Alcohol 200 150 r s 100 50 th a further r at least r 0 Patients who report mental health symptoms were more likely to sub for alcohol (n=834; p=.0005). Patients who report pain symptoms less likely to sub for alcohol (n=761; p=.002).

Cannabis Substitution, Tobacco 250 200 150 100 u 1 report r r 50 0 (n=60) (n=206) as their primary mode of use (p<.0001) Tobacco subbers, smoked ingestion = 66% (n=406) All other patients, smoked ingestion = 48% (n=1626)

Cannabis Substitution, Illicit Drugs ents report substituting cannabis. illicit Cocaine: 79.1% (n=76) Psychedelics: 68.2% (n=58) Opioids: 71.8% (n=23) Stimulants: 86.6% (n=13) Depressants: 55.5% (n=5) Of those who sub for illicits, an average of 72.2% say they gave them up completely (n=332).

Conclusions Medical cannabis is primarily used in the treatment of chronic pain and mental health, both of which may be issues in palliative care. Medical cannabis patients commonly self-report substitution of pharmaceuticals, alcohol, tobacco and illicit substances, often leading to complete abstinence of the substances identified. Cannabis may be playing a harm reduction role in the lives of many patients, particularly in regards to the high morbidity and mortality associated with opioids, alcohol, tobacco, and some illicit substances. Longitudinal research and clinical trials examining cannabis substitution effect are warranted to better understand the circumstances and mechanisms leading to substitution, and to maximize its potential personal and public health benefits.

Thank You...Questions? Philippe Lucas, MA, PhD(c) Graduate Researcher, Centre for Addictions Research of BC Social Dimensions of Health, University of Victoria VP, Patient Research & Access, Tilray plucas@uvic.ca/philippe@tilray.ca