IMS Magazine Winter 2019

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IMS MAGAZINE THINK. LEARN. DISCOVER.

WINTER 2019

ADDICTIONS

CAVEAT HEMP-TOR The Risk of Cannabis in Vulnerable Populations

THE OPIOID CRISIS Time for New Methods of Management

OVERCOMING ADDICTION

Is Admitting the First Step? IMS MAGAZINE FALL 2016 ISSUE THEME | 1


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IN THIS ISSUE Letter from the Editors............................... 4 Director’s Message.................................... 5 Raw Talk Podcast....................................... 6 IMSSA and IMS Events............................. 7 Infographic................................................. 8 Feature..................................................... 10 BMC Feature............................................ 22 Viewpoint................................................. 24 Faculty Spotlight...................................... 38 Student Spotlight..................................... 42 Future Directions...................................... 44 Travel Bites............................................... 45 Past Events............................................... 46

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FEATURE INFOGRAPHIC

MAGAZINE STAFF EDITORS-IN-CHIEF:

PHOTOGRAPHERS:

Chantel Kowalchuk Priscilla Chan

Dorsa Derakhshan Grace Jacobs Mikaeel Valli Krystal Jacques (DIRECTOR OF PHOTOGRAPHY) Nathan Chan

EXECUTIVE EDITORS:

Beatrice Ballarin Colin Faulkner Jonathon Chio Meital Yerushalmi Natalie Osborne

SOCIAL MEDIA TEAM:

Beatrice Ballarin (EXECUTIVE EDITOR) Louise Pei (DIRECTOR OF SOCIAL MEDIA) Maryam Bagherzadeh Riddhita De Sandy Che-Eun Serena Lee

DESIGN EDITORS:

Alex Young Colleen Tang Poy Julia Devorak Mona Li Shirley Long

SPONSORSHIP TEAM:

Carina Freitas

CONTENT COMMITTEE:

Aadil Ali Alexa Desimone Aravin Sukumar Ana Stosic Arpita Parmar Brenda Varriano Contessa Giontsis Cricia Rinchon Darby Lowe Diana Hamden Duncan Green Erika Opingari Frank Pang Gaayathiri Jegatheeswaran Gokce Ozdemir Jason Lau Jason Lo Jessie Lim

Krystal Jacques-Smith Melissa Galati Mikaeel Vali Mohammad-Masoud Zavvarian Muhtashim Mian Rehnuma Islam Riddihita De Parita Shah Parnian Pardis Samia Tasmin Sonja Elsaid Sumaya Dano Tamadher Alghamdi Valera Castanov Yena Lee Yousef Manialawy

By Julia Devorak MScBMC Candidate

Copyright © 2019 by Institute of Medical Science, University of Toronto. All rights reserved. Reproduction without permission is prohibited. The IMS Magazine is a student-run initiative. Any opinions expressed by the author(s) are in no way affiliated with the Institute of Medical Science or the University of Toronto.

Cover Art By Colleen Tang-Poy and Mona Li MSCBMC CANDIDATES

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LETTER FROM THE EDITORS Photo credits: IMS Photography team

Letter from the

W

EDITORS

hen we were brainstorming themes for this issue, no real creativity was required. With the recent legalization of marijuana and the devastating state of the opioid crisis, Addictions was the obvious choice for our Winter 2019 theme. In addition, many of our IMS community members are key leaders in addictions research. We have the unique opportunity to learn about the ground-breaking addictions research in our department which are influencing present-day policies and healthcare outcomes. With such as great group of individuals, our only challenge was to feature as many leaders as possible in our Winter 2019 issue. We speak with Dr. Tony George, the Chief of the Addictions Division at the Centre for Addiction and Mental Health, about the impact of marijuana legalization in the context of mental health. Dr. Andrea Furlan, gives us a pain specialist’s perspective on the opioid crisis and shares how she and her team are working to reduce this crisis with an educational app. Dr. Hance Clark touches on both the causes of opioid overuse and his excitement at the use of cannabis for pain management, from the perspective of an anesthesiologist. Dr. Isabelle Boileau discusses the use of brain imaging to understand the mechanism of addiction. Finally, Dr. Svetlana Popova touches on alcohol addiction and the importance of alcohol avoidance during pregnancy, while Dr. Jurgen Rehm discusses the epidemiology of drug use. We also have our Faculty Spotlight, where we feature non-addiction researchers Dr. Tom Waddell and Dr. Allan Kaplan, as well as our Student Spotlight where we catch up with former IMS student Dr. Kasey Hemington, a co-founder an e-newsletter featuring neuroscience, and former BMC student, Paul Kelly, a highly sought-after medical illustrator. Finally, we highlight recent events: the IMS Ori Rotstein lecture, and the Canadian Society of Nephrology conference. We have also put together a wide range of opinion pieces to spark your interests. What is addiction really? How prepared are we for the legalization of marijuana? What is the best method of rehabilitation? Should elder loneliness be a government priority? Is there a benefit to withholding patient diagnoses? We hope you find this issue fascinating, and that it provides new information and perspectives on addiction. As always, we welcome any feedback or comments you may have. Please feel free to email us at imsmagazine@gmail.com, visit our website at imsmagazine. com, or talk to us in person if you see us around campus.

Priscilla Chan

Chantel Kowalchuk

Priscilla is currently an MSc student engineering stem cells for traumatic spinal cord injury under the supervisor of Dr. Michael Fehlings at the Krembil Research Institute.

Chantel is currently a PhD student investigating the metabolic side-effects of drugs used to treat schizophrenia at the Centre for Addiction and Mental Health under the supervision of Drs. Margaret Hahn and Gary Remington.

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DIRECTOR’S MESSAGE

DIRECTOR’S Message

Photo credits: IMS Photography team

Dr. Mingyao Liu

Director, Institute of Medical Science Senior Scientist, Toronto General Research Institute, University Health Network

T

here is no better time to discuss Addictions than in this Winter 2019 edition of the IMS Magazine. While the recent legalization of marijuana and the ongoing opioid crisis have raised many questions and concerns surrounding drug use, they have also renewed our interest in understanding the fundamental concepts of addictions. This issue features the work of Drs. Tony George, Andrea Furlan, Hance Clark, Isabelle Boileau, Svetlana Popova, and Jurgen Rehm, and we are privileged to hear their perspectives on the achievements and challenges of addictions research. The IMS Magazine also speaks with Dr. Allan Kaplan, former Director of the IMS, and Dr. Tom Waddell, our Keynote Speaker for our 2018 Summer Undergraduate Research Program Research Day as part of the Faculty Spotlight. Past students Dr. Kasey Hemington and Paul Kelly reflect upon their time in the IMS and share how their graduate studies have contributed to their current success. During the fall, we also hosted the last of the IMS 50th Anniversary events: the 2018 Ori Rotstein Lecture in Translational Research, with Dr. Molly Schoichet, Ontario’s first Chief Scientific Officer, providing a riveting keynote presentation. I would like to thank everyone for attending this special event and I hope all our students went home feeling inspired and ready to take on the world of medical science. Lastly, I would like to extend my congratulations to the Editors-in-Chief, Priscilla Chan and Chantel Kowalchuk, and to the entire IMS Magazine team, for publishing this exciting issue. The IMS Magazine continues to demonstrate what makes our institute so special and I look forward to sharing this issue with my friends and colleagues. On behalf of everyone at the IMS, I would like to wish everyone a happy and successful new year! Sincerely, Dr. Mingyao Liu, MD, MSc Director, Institute of Medical Science

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RAW TALK PODCAST

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IMSSA & IMS EVENTS

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INFOGRAPHIC

ADDICTION Addiction is a primary, chronic disease of brain reward, motivation, memory and related circuitry. This is reflected in an individual pathologically pursuing reward and/or relief by substance use and other behaviors. Addiction is characterized by inability to consistently abstain, impairment in behavioral control, craving, diminished recognition of significant problems with one’s behaviors and interpersonal relationships, and a dysfunctional emotional response. Like other chronic diseases, addiction often involves cycles of relapse and remission. Without treatment or engagement in recovery activities, addiction is progressive and can result in disability or premature death11.

ADDICTION BY NUMBERS 19.1%

J

Q

K

A

10

16.2% 3%

13.4%

6.8%

Smoking

Cannabis

Source: Statistics Canada 20171

Source: Statistics Canada 20123

Gambling Source: Pedram et al. 20134

7%

$1K Avg. annual household spending on gambling5

1.7% Ontarians reporting difficulty limiting time and money spent gambling6

18.1% Alcohol

Source: Statistics Canada 2012

3

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5%

Food

Source: Azmier et al. 20055

3%


INFOGRAPHIC

OPIOID CRISIS Apparent opioid-related deaths in Canada8

3,005

2016

16

3,996

2017

1,036

2018

Jan-Mar

opioid overdose hospitalizations daily8

and counting

HARM REDUCTION Low-risk alcohol consumption 4,600 alcohol-related deaths per year

Recommended consumption

Projection based on adoption of Canada’s Low-Risk Alcohol Drinking Guidelines

2 3 Daily

3 10

E-cigarettes number of toxic chemicals present level of toxic chemicals present While likely less harmful than traditional tobacco cigarettes, e-cigarettes may still cause some negative effects on health. Their efficacy as a smoking cessation aid requires further study.

1 in 5

Source: National Academies of Science, Engineering, and Medicine (2018)9

former daily smokers now identify as non-smokers1

4 15 Weekly

Special occasions

Source: Stockwell et al. (2012)2

1. Smoking. Statistics Canada, Catalogue no.82-625-X • Health Fact Sheets, September 2017 2. Stockwell, T., Beirness, D., Butt, P., Gliksman, L., & Paradis, C. (2012). Canada’s lowrisk drinking guidelines. Canadian Medical Association Journal, 184(1), 75–75. 3. Statistics Canada, Canadian Community Health Survey – Mental Health, 2012. 4. Pedram P, Wadden D, Amini P, Gulliver W, Randell E, Cahill F, Vasdev S, Goodridge A, Carter JC, Zhai G, Ji Y. Food addiction: its prevalence and significant association with obesity in the general population. PloS one. 2013 Sep 4;8(9):e74832. 5. (Azmier, 2005) 6. CAMH Monitor eReport 2015: Substance Use, Mental Health and Well-Being Among Ontario Adults. CAMH Research Document Series No. 45 7. Levy A, Marshall P, Zhou Y, Kreek MJ, Kent K, Daniels S, Shore A, Downs T, Fernandes MF, Mutch DM, Leri F. Fructose: glucose ratios—a study of sugar self-administration and associated neural and physiological responses in the rat. Nutrients. 2015 May 22;7(5):3869-90. 8. Special Advisory Committee on the Epidemic of Opioid Overdoses. National report: Apparent opioid-related deaths in Canada (January 2016 to March 2018) Webbased Report. Ottawa: Public Health Agency of Canada; September 2018. 9. National Academies of Sciences, Engineering, and Medicine. 2018. Public Health Consequences of E-Cigarettes. Washington, DC: The National Academies Press. https://doi.org/10.17226/24952. 10. Ng J, Sutherland C, Kolber MR. Does evidence support supervised injection sites?. Canadian Family Physician. 2017 Nov 1;63(11):866. 11. American Society of Addiction Medicine Public Policy Statement: Definition of Addiction, April 12, 2011.

Safe injection sites

overdose deaths overdose-related emergency calls HIV infections

Source: Ng, Sutherland, & Kolber (2017)10

If you are concerned about addiction or substance abuse disorder, you can get help at: www.canada.ca/en/health-canada/ services/substance-use/get-help/ get-help-with-drug-abuse.html

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FEATURE

E R A W E B R E Y U B E R A W E B R E Y U B E R A W E B R E Y U B E R A W E B ER BUYER BEW

E R A W E B R E Y U B E R A EW B R E Y U B E R A W E B R E Y U B E R A RBBEEWWARE BUYER

Canadian Cannabis

BEWARE BU YEReat r” BEWA“Hem Cav RE BUp-to YER BEWARE BUYER BEWA RE BUYE R BEWARE BUYER BEWARE BUYER BE WARE BUYER

BEWARE BUYER BEWARE

By: Mikaeel Valli

O

ctober 17th, 2018 marked a new beginning for Canada—the legalization of cannabis for recreational use. From Southern Ontario to the Far North, from St. John’s to Vancouver, Canadians had mixed responses to this historic legislation. Many celebrated this monumental decision, while others stood in lines protesting and pushing for more regulations. Many argue that the legalization of cannabis is a great thing for Canada for several reasons. It will shift the burden of minor crimes of trafficking and possession away from law enforcement and the judicial system towards more serious crime. This would reduce tax dollars spent on incarceration. A shrinking “black” market share for illegal cannabis products will lead to billions of dollars in tax revenues for the government. A regulated market would ensure cannabis is safely produced and contains safe levels of THC—the component which is responsible for the “high” feeling that marijuana is commonly associated with. On the social level, easier access to cannabis would reduce the stigma associated with marijuana possession and use.

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However, one critical question is the mental health implications associated with drug use. The IMS Magazine had the pleasure of interviewing Dr. Tony George, a psychiatrist with a subspecialty in addictions, and a clinician-scientist at the Centre for Addiction and Mental Health (CAMH) in Toronto. Despite the advantages, Dr. George remains skeptical about this legal move. “Canada has the highest rate of cannabis use in the Western world. Among youths aged between 15 and 19, our rate is 28.5% while in the US in Washington, it is at 22%” Dr. George said with dismay. He is worried that the legalization will lead to greater increase in cannabis use in vulnerable subgroups— particularly for youth and those that are mentally ill. He expressed further that he does not truly know what to expect, “It is going to be interesting. We are heading into the largest cannabis-use prospective study in the world. Put your seatbelt on and hold on for the ride.” Cannabis is the most commonly used illicit drug in people with severe mental disorders. Dr. George recalled back to 1994 during his second year in residency

training in Psychiatry at Yale University School of Medicine, where his interest in the intersection of addiction and mental illnesses was sparked, “I had a chance to be on a unit that deals with schizophrenia and bipolar disorders… what I realized was that just about every one of those patients had an addiction problem.” He elaborated that most times, these patients are brought to the hospital as a result of their relapse to cocaine, alcohol, or other illicit drug use. Dr. George added that clinically, cases of addiction often get overlooked or are viewed as a non-primary issue—which is a challenge that needs to be addressed. In those with schizophrenia, about 25% have cannabis use disorder. Similarly, a high percentage (10-15%) of individuals with major depression and bipolar disorder also have a maladaptive use of cannabis. Compare this to the general population where it is only 3%. The use of cannabis “is like an accelerant to fire” for these vulnerable populations as it significantly worsens their mental illness, Dr. George warned. Cannabis use leads to longer psychotic and mood episodes, resulting in more relapses and re-hospitalizations, thereby increasing treatment needs. Dr. George’s advice to the


WA

ER

E

FEATURE vulnerable Canadians that are interested in buying cannabis is: “caveat hemp-tor—let the buyer beware of the risks of cannabis.” Given the high prevalence of addiction in mental disorders and how misuse of drugs significantly impacts their day-to-day function, Dr. George leads the Biobehavioural Addictions and Concurrent Disorders Research Laboratory (BACDRL) at CAMH to devise novel treatment methods to combat addiction in patients with schizophrenia, bipolar disorder, and depression. One of the main projects funded by the US National Institutes of Health is a double-blind, randomized control study examining the effects of repetitive transcranial magnetic stimulation (rTMS) on cannabis use and cognitive outcomes in schizophrenia (abbreviated as “CANSTIM”). This trial is led by Karolina Kozak, an IMS PhD student. In the treatment arm, patients with cannabis use disorder receive brain stimulation at the dorsolateral prefrontal cortex—a region responsible for cognition

including working memory and executive functioning. In the control arm, patients with cannabis use disorder receive a sham rTMS, which mimics the look, sound, and feel of rTMS without receiving actual stimulation to the brain. Kozak explained that this trial is under way, “and we hope that this approach with rTMS will be effective in the management and treatment of cannabis use disorder in schizophrenia patients and improve their cognitive and functional impairment.” Another study that is an extension of the CANSTIM project is aimed at predicting cannabis abstinence using cognitive and clinical factors. Dr. George and his IMS Master’s student, Darby Lowe, are using baseline clinical, neuropsychological, and neurophysiological data from the CANSTIM project and examining its association with cannabis use reductions and abstinence during the CANSTIM trial. Lowe expressed that that they hope to “determine the clinical and cognitive markers for the ability and inability to

abstain from cannabis. This will help highlight potential therapeutic targets, therefore aiding with addiction and abstinence in schizophrenia.” In addition to examining the schizophrenia population, the BACDRL also looks at patients with mood disorders. In particular, Aliya Lucatch—an IMS Master’s student—is exploring the effects of extended cannabis abstinence on symptoms and cognition in patients with major depressive disorder. This is a longitudinal study with eight study visits involving a variety of clinical assessments relating to depression, anxiety, and mood, as well as cognitive assessments to evaluate memory and attention. These patients are also provided behavioral coaching to provide motivational support to help with their cannabis addiction. As an incentive, a $300 cash bonus is provided at the end of the 28 days if successful cannabis abstinence is achieved. Lucatch added that this study “will provide new insights about the impact of heavy cannabis use on major depression. Given that cannabis was recently legalized, it is important to have a good understanding of the potential risks which might impact policies and public perception.” When asked about the challenges associated with his lab research, Dr. George quickly replied, “funding!” Dr. George expressed that the funding agencies need better awareness of the importance of mental health and its impact on daily functioning as there is still stigma of mental health that is persistent in our society. “The best way to combat this stigma is through dissemination of knowledge” Dr. George expounded. However, on the flipside to the legalization of cannabis is the increase in tax revenues from cannabis sales, and Dr. George hopes that the revenue will be used towards funding mental health research and combatting addictions in these vulnerable populations.

Photo By: Mikaeel Valli

DR. TONY GEORGE, MD, FRCPC Clinician-Scientist, Campbell Family Mental Health Research Institute, CAMH Chief, Addictions Division, CAMH Professor, Department of Psychiatry, University of Toronto

Through his research and clinical practice, Dr. George hopes to leave the legacy of “approaching complex problems in mental disorders in a rational way. If we ask the right questions, and we follow through with it, we would learn more about it—and thereby be able to help a lot more patients improve their lives.” IMS MAGAZINE WINTER 2019 ADDICTIONS | 11


FEATURE

A Hard Look at Addiction in Society An Interview with Dr. Jürgen Rehm

By: Yousef Manialawy

A

n addiction is not something that is easily overcome. Many challenges lie in effectively counteracting the biochemical changes in the brain observed in countless studies of people with addictions. But just as difficult is identifying the aspects of our society that put people at risk of addictive behaviours and coming to terms with the changes needed to address them. As a leading expert on addictions and health risk management, Dr. Jürgen Rehm is tasked with ensuring that public health policy remains well-informed when making decisions that affect the lives of people in Canada and beyond. Dr. Rehm has spent a long and illustrious career influencing public health policy through quantitative social research. He obtained his PhD in Philosophy of Science and Statistics in his native Germany before joining the nation’s Federal Health Office. He quickly rose up through the ranks to become Director for Risk Evaluation, where he was responsible for evaluating the significance of various health risks within the population, chief among them alcohol and tobacco use. After a few years working in Germany, he was recruited to the University of Toronto in 1994 as an executive member of the Addiction Research Foundation (which eventually was one of the hospitals merged into the

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Centre for Addiction and Mental Health). In 2010, he was made Senior Director of the Institute for Mental Health Policy Research. In addition to being an Associate Member of IMS since 1998, he also holds appointments within the Department of Psychiatry and Dalla Lana School of Public Health. Despite his role as a leading expert on addiction, he confesses that it wasn’t an interest in addictions per se that originally got him into the field, but rather the psychology of risk. “There are a number of very interesting questions around why our society accepts certain risks in some behaviours, but not in others. If the state is producing a risk like radon in your house, you will shout and go to the street even if the risk of lifetime death is one in a million” Dr. Rehm explains. “If you inflict much higher health risks on yourself such as binge drinking with a risk of lifetime death of lower than one in a hundred, you do not care. We tend to underestimate any self-inflicted risk and overestimate any risk others do to us.” Perhaps one of Dr. Rehm’s most significant research contributions to date is his work clarifying the link between alcohol and dementia risk. In 2016, the high-profile journal The Lancet published a study describing the six biggest risk factors for dementia. To Dr. Rehm’s surprise, the

article did not so much as mention alcohol as a risk factor, despite his group’s certainty of the existence of a relationship. “It made us so mad because we knew there was a risk, it just couldn’t be easily quantified” he explains. “So, we teamed up with a group of French researchers and studied the hospital data of 42 million French patients over four years1. We found that the dementia risk associated with alcohol was actually higher than for any of the other risk factors in the original Lancet publication.” How could such a major risk factor have been overlooked in The Lancet study? Dr. Rehm believes it reflects a major issue with the hyper-specialization of science today. “Science is compartmentalized, and people unfortunately don’t always look over the borders of their own field.” As an expert in risk management, Dr. Rehm is often called on by government bodies such as the Ministry of Health to help them make informed decisions on policies regarding Canadian health. More so than in other scientific fields, his line of work often forces him to address socioeconomic realities of addiction and illness that may not always be easy to acknowledge. A major topic that has gradually emerged within public discourse is the stigmatization of people with mental illness and addictions, to which Dr. Rehm offers some personal insight. “I’m seeing with addiction this self-righteous categorization into


I’m seeing with addiction this self-righteous categorization into ‘us and them’, between people who use and people who become addicted… it’s not a line, it’s a continuum

‘us and them,’ between people who use and people who become addicted… it’s not a line, it’s a continuum.” Despite these challenges, Dr. Rehm believes that public perception on addictions has the potential to change the way it has for depression. “Depression 25 years ago was to just say ‘Oh, all they have to do is think a little and be happy, but now it’s much less common to hear that. There is more education and better realization, but it’s a slow process; it took about 15, 20 years but it was an achievement for depression.” Unfortunately, however, he doesn’t believe that society is progressing quickly enough in their negative perceptions of addictions, such as alcohol abuse. “It’s still not there for alcohol, and the surveys don’t say [that perception is changing]. I think we have to treat it like hypertension, without big judgments [about lifestyle].” One of the most pressing topics surrounding substance abuse comes in the wake of Canada’s legalization of cannabis in October 2018, with many Canadians wondering if and how this will change Canadian society and their daily lives. Dr. Rehm believes legalization to be a step in the right direction, but argues that it depends on how we choose to proceed with it. He explains that optimally, cannabis should be sold in locations where they check I.D., with clear, plain packaging that properly displays the THC and CBD content with an explanation. “But unfortunately, in some politics–including in this province–they basically say, ‘the goal of cannabis legalization is to make the biggest profit for companies and make our companies the strongest in the world’,” says Dr. Rehm. “Cannabis is not, say, as dangerous as alcohol; however, if we treat cannabis like an ordinary commodity (i.e., unrestricted marketing and advertisements, no enforcement of minimal age, no control of THC content) there may be problems of risky use patterns and use disorders.”

FEATURE

DR. JÜRGEN REHM, PhD Senior Director, Institute of Mental Health Policy Research, CAMH Professor and Inaugural Chair of Addiction Policy, Dalla Lana School of Public Health Professor, Department of Psychiatry Associate Member, Institute of Medical Science With much to learn about cannabis following legalization, Dr. Rehm also stresses the importance of effectively assessing the benefits and drawbacks without jumping to conclusions. One example is a study that his team recently published identifying a decreased likelihood of developing diabetes among both long-term and 12-month cannabis users relative to non-users2. “Research would indicate that there is a chance [that cannabis use decreases diabetes risk] but this is still just a correlation. So, we cannot establish causality, but I think it’s an interesting proposition and it has to be tested more rigorously.” With addiction and mental health research more pertinent than ever, the field is quickly evolving to adapt to a rapidly changing society. “Currently life expectancy is declining for the first time since 1945 in the US. If you look more closely you see that the life expectancy of the welloff is still increasing, but it’s actually the life expectancy of the poor that’s decreasing because of greater inequality between socioeconomic classes.” So how can this issue be effectively addressed? Dr. Rehm believes outside-thebox thinking is the solution. “I’m all for an experimental society where we explore certain things like a minimum income,” he explains. This is pertinent considering the recently scrapped Ontario Basic Income Pilot program3, which was set to explore providing a minimal income to eligible couples or individuals, regardless of employment status. For example, someone

Courtesy of CAMH

who was working but earning below the basic income level would receive monthly payments for up to a 3-year period, and impacts on education, housing, health, and employment would be assessed. “Do we know what comes out of it? No, but how could we know without trying?” asks Dr. Rehm. “It makes no sense [for the Ontario government] to have stopped the universal basic income pilot…even if it was wrong it doesn’t matter, we needed to have learned from it.” How society chooses to address these socioeconomic issues going forward ultimately rests in the hands of aspiring public health researchers, to whom Dr. Rehm offers some encouraging advice. “Currently we have more funding in our field than ever before…and the overall chance of being able to establish research has never been better. People should be passionate about what they’re doing and try to do it because this is an up and coming field. We believe that people are now more willing to admit to having mental health issues… and it allows us to do something about those numbers.” 1. Schwarzinger M, Pollock BG, Hasan OSM, Dufouil C, Rehm J, QalyDays Study Group. Contribution of alcohol use disorders to the burden of dementia in France 2008-13: a nationwide retrospective cohort study. Lancet Public Health. 2018 Mar;3(3):e124–32. 2. Imtiaz S, Rehm J. The relationship between cannabis use and diabetes: Results from the National Epidemiologic Survey on Alcohol and Related Conditions III. Drug Alcohol Rev. 2018;37(7):897–902. 3. Ontario government defends move to cancel basic income pilot project | Globalnews.ca [Internet]. 2018. Available from: https:// globalnews.ca/news/4365399/ontario-cancels-basic-income-pilot-project/

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FEATURE

An Interview with Dr. Isabelle Boileau By: Gökçe Özdemir Have you ever felt like you just can’t get enough of something? Think of a chocolate bar that you opened for just one piece but ended consuming the entire thing, or being next to someone you love and are inseparable from because of how happy they make you. It’s a funny thing the brain. It has a constant hunger for whatever it wants, and it is not easy to say no to. But what brain characteristics determine whether an individual will become addicted to a certain substance? How do addictions to drugs of abuse develop, and importantly, what factors contribute to relapse? Dr. Isabelle Boileau, Head of the Addiction Imaging Research Group at the Centre for Addiction and Mental Health (CAMH), is using neuroimaging to investigate how drugs of abuse affect the brain. Currently an Associate Professor of Psychiatry and an Associate Member of the Institute of Medical Science at the University of Toronto, Dr. Boileau began her training studying the neural mechanisms behind addiction at McGill University. Here, she completed a PhD 14 | IMS MAGAZINE WINTER 2019 ADDICTIONS

studying the increase in levels of dopamine that occur upon acute drug administration (alcohol and amphetamines in particular) using positron emission tomography (PET). PET is an imaging technique that uses radioactive tracers to measure metabolic activity, levels of receptors and enzyme in the body, including in the brain. She then went on to New York City to complete her post-doctoral fellowship at Columbia University and then returned to continue her science career in Toronto. Dr. Boileau’s research investigates the neural pathways involved in pathological gambling, as well as compares the dopamine systems of patients with Parkinson’s disease (caused by lack of dopamine producing cells) to people with amphetamine addiction. Dr. Boileau is currently looking at factors that may contribute to the chronic nature of addiction in the dopamine and endocannabinoid systems, as well as investigating glial cell markers as indications of whether chronic drug use causes brain damage. Regarding the dopamine system, a recent study from Dr. Boileau’s laboratory used a radiotracer ([11C]-(+)-PHNO) that is

specific to dopamine D3 receptors to show that these receptors are expressed at higher levels in the brain of people who chronically use drugs than in healthy controls, and are related to “wanting” more drugs. Conversely, D2 receptor density and dopamine levels are down regulated in drug users. Low D2 receptor expression and low synaptic dopamine have been suggested as factors that make an individual more vulnerable to addiction, whereas other studies suggest that high D2 receptor density protects against addiction.1 The finding of higher D3 receptor density in addicted individuals suggests that any therapeutic effort to increase “deficient” activity at the D2 receptor may increase an individual’s motivation to use drugs –clinical trials targeting the dopamine system need to consider the contradictory effects of stimulating D2 versus D3 receptors. Although no research has been able to prove whether different levels of D2 or D3 receptors are causes of addiction or consequences of drug use, Dr. Boileau believes that it’s likely both. For example, a recent study suggests that individuals with high familial risk for addiction have differences in the dopamine system which


FEATURE

Courtesy of CAMH

DR. ISABELLE BOILEAU, PhD (centre) Head of the Addiction Imaging Research Group, CAMH Associate Professor, Department of Psychiatry, UofT Associate Professor, Institute of Medical Science, UofT predate drug use, suggesting an inherent vulnerability.2 However, studies (including the work of Dr Boileau) have linked drug use severity with the magnitude of the D2 receptor deficit, and longitudinal studies also exist where people detoxifying from drugs show a normalization of dopamine neurons and transporters. This indicates that abnormal dopamine receptor density represents both a “state” associated with chronic drug use and a predisposing “trait”. More research is needed to understand how genetics and natural brain chemistry might predispose (or protect) us from developing addictions. Another project that Dr. Boileau’s team is working on is related to fatty acid amide hydrolase (FAAH), an enzyme that metabolizes endocannabinoids. Using a probe that attaches itself to FAAH, they have discovered that in response to early withdrawal from cannabis or alcohol, FAAH is downregulated. “Our gut interpretation is that this might be a compensatory response to acute exposure: FAAH downregulates in an effort to increase anandamide (an endocannabinoid neurotransmitter, the body’s own version of cannabis) in the brain, and this might be

a reason why the withdrawal signs are not present early on in cannabis use disorder”, says Dr. Boileau. Despite the relatively low risk of addiction and less intense withdrawal symptoms with cannabis, she highlighted that exposure to cannabis during development may change one’s ability to learn, and warns younger users to be responsible and avoid using cannabis in school. When asked what the most rewarding part of her job is, Dr. Boileau said: “This is. I think sharing knowledge is very fun, especially with students, because working with motivated and curious students brings me back to science and to the questions, and away from the paperwork!” As to where the future of addiction research is headed, because PET scans can confirm where in the brain medications are acting and rate at which they are metabolized, Dr. Boileau hopes that PET findings will contribute to the development of evidence-based therapeutics: “Often we go in blind; we try medications in different populations and hope for the best. With more resources invested in PET, we can know better whether there are valid

reasons to use a certain medication or not, and it’ll help us approach the right target”. She also added some advice for graduate students: “Zoom out from time to time from your work to understand the relevance of it all, and where you want to go with it. It’s a very fun career but one in which you have to keep reinventing yourself. It’s relentless, and you always have to keep going, so it’s important to think about every new step you’re taking and why you’re doing it rather than just following the path blindly.” While there are still many unanswered questions about how a “high” brain is different or how addiction can be alleviated, Dr. Boileau is optimistic about the potential role PET imaging can play in developing better medications and better outcomes for those dealing with addiction. 1. Thanos PK, Volkiw ND, Freimuth P, et al. Overexpression of dopamine D2 receptors reduces alcohol self-administration. J Neurochem. 2001 Sep;78(5):1094-103. 2. Casey KF, Benkelfat C, Cherkasova M, et al. Reduced dopamine response to amphetamine in subjects at ultra-high risk for addiction. Biol Psychiatry. 2014 Jul;76(1):23-30.

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FEATURE

P OS T- S U RG I CA L PA I N AT THE BOUNDARIES OF PAIN & ADDICTION By: Alexa Desimone

M

ore than 230 million people worldwide undergo a surgical procedure each year.1 Commonly, patients experience moderate to severe acute post-surgical pain, which dissipates within three to six months. However, as many as half of patients

can develop chronic post-surgical pain (CPSP). Due to the persistent and debilitating nature of this pain, these patients are at a greater risk of persistent opioid use one year after surgery.2 Though fraught with side effects and addictive potential, opioids are still the most effective medication for acute pain, making them useful for patients after surgery. Unfortunately,

Photo by Krystal Jacques

DR. HANCE CLARKE, MD, PhD Anesthesiologist, Assistant Professor, Director of Pain Services, Director of Transitional Pain Service, Medical Director of Pain Research Unit, Medical Director of Ehlers-Danlos Syndrome Program Department of Anesthesia, University of Toronto

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an increasing number of CPSP patients remain on long-term, high-dose prescription opioids with limited knowledge and assistance on how and when to taper off. In Ontario, about half of surgical patients are discharged with an opioid prescription.3 When patients suffering from chronic pain after surgery stringently take their required dose of an opiate to mitigate their symptoms, their bodies eventually develop a tolerance to the drug. Inevitably, they express to their physicians that their pain is still impeding daily-living, and their dose increases, starting a repeating cycle. Thankfully, this is a relatively rare occurrence, seen in about 15% of CPSP patients (which is only a small subset of the 50% of patients who go on to develop CPSP).3 Furthermore, patients who are opioid-naĂŻve, meaning they have never taken an opiate in the past, have less than a 3% risk of persistent opioid use six months after surgery, and less than 1% after one year.4 Nevertheless, the subset of the population that do continue to rely on opioids can be very challenging to treat and can experience significant decreases in their quality of life if their pain is not appropriately managed. In the past, pain scientists looked at pain and addiction as separate entities. The pain that leads to the opiate consumption is all but forgotten when pain and addiction are separated. However, Dr. Hance Clarke, Director of Pain Services and Medical Director of the Pain Research Unit at Toronto General Hospital (TGH), was one of the key opinion leaders in Canada to challenge that ideology. He believes pain and addiction do coexist in some patients. People may develop an opioid use disorder even though the medication was intended


FEATURE for their pain—and both the pain and addiction need to be treated in tandem. Dr. Clarke completed his PhD through the Royal College Clinical Investigator Program at the Institute of Medical Science, and is currently an assistant professor in the Department of Anesthesia at the University of Toronto. As an anesthesiologist, Dr. Clarke appreciates the ability to take a more interventional approach with patients. Indeed, pain management incorporates a number of specialists including neurologists, family physicians, rheumatologists, physiatrists, and more. Thus, during the time of his PhD, Dr. Clarke had opportunities to connect and network with people from many different fields. This allowed him to appreciate the value and expertise that different fields bring to pain management.

admitted to the program, patients are seen every two weeks. Their opioid or other analgesic medications are adjusted with the goal of optimizing their daily function. Additionally, these patients receive psychological treatments (e.g. Acceptance and Commitment Therapy), alternative medicine treatments (e.g. acupuncture), and physiotherapy to assist in restoring function and to help them better cope with their pain.5 Overall, the TPS aims to break the cycle of chronic pain treatment that can lead to chronic opioid misuse and addiction. For Dr. Clarke, it is the individual victories that keep him going. When patients on high dose opioids start to understand that they also have a misuse issue, the ability to introduce other coping strategies and even change the course of their lives becomes

This is an industry that has yet to be medically driven...it is time that science starts to lead the Canadian population

In 2014, a multidisciplinary pain program called the Transitional Pain Service (TPS) was developed at TGH to identify patients at risk of CPSP and provide a holistic approach to pain management.1 As the current director of the TPS program, Dr. Clarke understands the need to incorporate various interventions, including psychological, medical, pharmacological, and physical therapies, in order to prevent and treat factors that increase the risk of CSPS and opioid misuse. The TPS targets high risk patients, such as patients with a history of chronic pain, drug or opioid misuse, as well as those with significant psychological comorbidities. When

possible. This potential is what motivates Dr. Clarke. “We’re all just human beings and the moments in your life which enable you to change an individuals’ trajectory in a meaningful way, well, that’s what keeps me going,” said Dr. Clarke. Working in the midst of the current opioid crisis, Dr. Clarke is keenly aware of the importance of the work that he is doing. “[We] really have an opportunity to help direct change, but we need to make sure we direct change with good science and evidence,” explained Dr. Clarke. He certainly is not someone who wants to stop the use of opioids. He explains that

not all deaths from overdose start with the prescription pad. As with many public health officials, he is deeply concerned about the supply of illicit fentanyl, an opioid 100 times stronger than morphine, being mixed in with street drugs. In the pain world, he knows that if we are going to start cutting down on opioid use, we must embrace other methods of pain control-a goal which his TPS clinic is striving towards. In the future, Dr. Clarke is most excited to begin looking at the effects of cannabis on pain. With the new legalization of cannabis in Canada, we have greater ability to investigate its potential therapeutic effects. Dr. Clarke’s current projects surrounding cannabis aim to investigate publicly available products and test what active ingredients are in those products. He has observed 10-90% variability between these products, yet individuals are paying the same amount of money for two completely different products leading to differing effects. “This is an industry that has yet to be medically driven and has been lead by a venture capitalist industry, it is time that science starts to lead the Canadian population” Dr. Clarke remarks. However, he believes that in 5-10 years, a rigorous medical cannabis industry will evolve and patients will have products available with good science and randomized control trials to ensure the public’s confidence in the effects the product is reported to have. There are still many unanswered questions regarding pain and opioid use disorder, however, Dr. Clarke is eager to pursue his research into medical cannabis and pain. At the same time, he and the TPS team are busy working to tackle addiction from a novel angle-hopefully before it even develops. 1. Katz, J., Weinrib, A., Fashler, S. R., et al. (2015). The Toronto General Hospital Transitional Pain Service: development and implementation of a multidisciplinary program to prevent chronic postsurgical pain. Journal of Pain Research, 8, 695-702. 2. Clarke, H. (2016). Transitional Pain Medicine: novel pharmacological treatments for the management of moderate to severe postsurgical pain. Expert Review of Clinical Pharmacology, 9(3), 345-349. 3. Huang, A., Azam, A., Segal, S., et al. (2016). Chronic post-surgical pain and persistent opioid use following surgery: the need for a transitional pain service. Pain Management, 6(5), 435-443. 4. Clarke, H., Soneji, N., Ko, D. T., et al. (2014). Rates and risk factors for prolonged opioid use after major surgery: population based cohort study. British Medical Journal, 348. 5. Weinrib, A. Z., Azam, M. A., Birnie, K. A., et al. (2017). The psychology of chronic post-surgical pain: new frontiers in risk factor identification, prevention and management. British Journal of Pain, 11(4), 169-177.

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FEATURE

Rx

Canadian Opioid Guidelines Development and Implications for Pain Management By: Parnian Pardis

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ver-prescription of opioids is common, especially among North Americans. As a nation, we consume over 80% of the opioids produced in the world. Opioids may be essential to treat chronic pain, a debilitating symptom of many diseases. However, opioids are misused among 21% to 29% of patients who receive a prescription and addiction occurs in 8% to 12% of users.1

Dr. Andrea Furlan is a Staff Physician and Senior Scientist at the Toronto Rehabilitation Institute (TRI), and Scientist at the Institute for Work and Health. Within the Faculty of Medicine at the University of Toronto, she is also an Associate Member of the Institute of Medical Sciences and Associate Professor in the Division of Physical Medicine and Rehabilitation. As a pain specialist, she suggests four reasons why our nation has become so liberal when prescribing opioids. “It starts with a desire to help. Why should you suffer when I have the power to give you something that’s not expensive?” says Dr. Furlan. Physicians may assume that addiction is a myth, or at least very rare, given the multitude of advertisements suggesting the benefits of opioid use. To complicate matters further, opioids are covered by every formulary, from private insurance to OHIP. In comparison, the same coverage may not be offered for services such as physiotherapy, acupuncture, or massage. In fast-paced healthcare environments (emergency care, walk-in clinics), it may also be easier to prescribe a pain medication than it is to examine the patient and teach them appropriate exercises. Dr. Furlan suggests this is a common problem when healthcare professionals are paid by the volume of patients seen, rather than the quality of care provided. 18 | IMS MAGAZINE WINTER 2019 ADDICTIONS

Ultimately, we perpetuate a system that leads to opioid overdose, which can cause death or irreversible brain damage. Dr. Furlan suggests that approximately one third to a half of individuals who overdose were prescribed opioids for a health condition at some point in their lives. They may inadvertently consume a dose to which they are intolerant, take a higher dose because they perceive no initial effect, or mix the drug with alcohol or sleeping pills–all of which have detrimental consequences. Patients who become addicted, but are then refused further opioids prescriptions, may resort to illicit or street sources, such as fentanyl. While Dr. Furlan is a “believer that opioids are essential for us to treat pain,” she recognizes that only a minority of people with chronic pain actually benefit from them. During her doctoral studies in Clinical Epidemiology at the University of Toronto, Dr. Furlan published a meta-analysis in collaboration with the Cochrane Database on the use of opioids for chronic pain. This 2005 publication piqued the interest of the College of Physicians and Surgeons of Canada, and they invited her to lead the development of the Canadian Opioid Guideline. Additionally, the College established the National Opioid Use Guideline Group (NOUGG), co-chaired by Rhoda Reardon and Clarence Weppler and comprised of 49 experts nominated from across the Canadian provinces. In 2008, with the support of NOUGG, Dr. Furlan conducted a systematic review of the available literature on opioid use at the Institute of Work and Health. She then compiled evidence and drafted recommendations together with a small team of local experts. Following three rounds of appraisals by the NOUGG, Dr. Furlan and her team finalized a list of 24 recommendations and published the guidelines in 2010. The guideline covered topics such

as selecting the appropriate patients with chronic pain to take opioids, appropriate dose and course of treatment, identification of risk factors for developing opioid use disorder and overdose, how to monitor patients on opioids, and best practices for tapering and stopping opioids. Initially, these guidelines were in the form of a 200-page document. Even Dr. Furlan had a difficult time remembering all of its contents, so she created a quick and easy cheat sheet to rely on. When others expressed interest in this cheat sheet, she applied for and received funding from the Toronto Rehabilitation Institute for the creation of Opioid ManagerTM, a point-of-care tool for use by healthcare providers. Opioid ManagerTM started as a two-page brochure. It has since been adapted to be compatible with common Electronic Medical Records and turned into both an iOS App and a Youtube video. Finally, My Opioid Manager was created; a book and mobile app written in lay language by Dr. Furlan and Amy Robidas (RN) to explain opioid use to patients with chronic pain. These avenues of knowledge translation were imperative to Dr. Furlan, as they facilitate evidence-based practice and informed decision-making in the clinical setting. Prior to the development of the Canadian Opioid Guideline, Dr. Furlan recalls learning in medical school that “the sky was the limit for opioids: you increase the dose, you increase the effect.” When Dr. Furlan coined the term “watchful dose” in the guideline, however, she initiated a fundamental shift in thinking. For the first time, many physicians in Canada were introduced to the idea that there was a ceiling recommended opioid dose. If physicians prescribe over this dose, they are now responsible for justifying their decision and are warned to exercise added caution.


FEATURE

Photo by Krystal Jacques

DR. ANDREA FURLAN, MD, PhD Staff Physician and Senior Scientist at Toronto Rehabilitation Institute Scientist at Institute for Work and Health; Associate Member of Institute of Medical Science, Faculty of Medicine, UofT Associate Professor in Division of Physical Medicine and Rehabilitation, Faculty of Medicine, UofT

Dr. Furlan notes that the impact of this guideline has yet to be determined. However, while presenting a series of lectures across Canada, one of her colleagues found that one in two physicians attending the lectures were aware this guideline exists. As a reflection of physicians becoming more careful, it is more common now for Dr. Furlan to receive referrals of patients on 100’s rather than 1000’s of milligrams of morphine equivalents. Dr. Furlan’s current focus at TRI with her team of a nurse, pharmacist, and nurse practitioner, includes helping patients taper their opioid use. Of course, this is no small task given the physiological changes that occur with opioid use and the resulting dependence the body develops. Patients experience severe withdrawal symptoms, and Dr. Furlan “suffers with those patients because when they describe how they feel, it’s really, really horrible.” Consequently, she finds her work especially rewarding when patients report

feeling much better after they are weaned off the drug. In addition to her clinical responsibilities, Dr. Furlan co-chairs the Extension of Community Healthcare Outcomes (ECHO) Ontario Chronic Pain/Opioid Stewardship. Launched in 2014 as the first ECHO in Canada, its success during a two-year pilot project led to permanent funding by the Ministry of Health and Long Term Care. This telemedicine network connects primary care providers from all over Ontario with Dr. Furlan and her team. During two-hour sessions every week, a short didactic lecture is followed by one to two anonymized cases presented by healthcare professionals from their community. “We tell them how we would treat that patient, using the opioid guidelines, but also guidelines for lower back pain, fibromyalgia, and so on. We apply all the evidence to each case,” says Dr. Furlan.

Evaluations of Project ECHO determined that its participants are indeed modifying patient treatment. The prescribing habits of participants have improved, and post-questionnaires indicated greater knowledge and self-efficacy related to chronic pain. “The primary care providers are teachable and want to do the very best for their patients,” says Dr. Furlan. There are still many unanswered questions, both with regards to the development of newer and better opioids and to the understanding of the pain system. With the dual perspective of a clinician and a scientist, Dr. Furlan brings clinical questions to the research field to find answers. Dr. Furlan’s contributions to the field ensure that “we’re using [opioids] with the right people… otherwise, we are going to penalize those who need it.” 1. Vowles KE, McEntee ML, Julnes PS, et al. Rates of opioid misuse, abuse, and addiction in chronic pain: a systematic review and data synthesis. Pain. 2015;156(4):569-76.

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FEATURE

Dr. Svetlana Popova Defining, Understanding, and Preventing Fetal Alcohol Spectrum Disorder By: Ana Stosic

H

Courtesy of Dr. Svetlana Popova

ealth myths readily propagate through society: “We only use 10% of our brains, bubble gum remains in your stomach for seven years, eggs are bad for your heart.” While common, we often pay little attention to these statements if we’re aware of their invalidity. Yet, when faced with indisputable evidence-based medical recommendations: “do not consume alcohol during pregnancy”, we seem to fail. In 2017, a study published in The Lancet Global Health estimated that globally, on average, one in 10 women consume alcohol during pregnancy and 20% of these women binge drink, meaning they consume four or more alcoholic drinks on a single occasion.2 These findings are alarming because 50% of the pregnancies in developed countries and over 80% in developing countries are known to be unplanned. That means that many women do not realise they are pregnant during the early stages and continue drinking when pregnant. 20 | IMS MAGAZINE WINTER 2019 ADDICTIONS

DR. SVETLANA POPOVA, MD, PhD, MPH Senior Scientist, Institute for Mental Health Policy Research, CAMH World Health Organization/Pan-American Health Organization Collaborating CAMH Associate Professor, Epidemiology Division, Dalla Lana School of Public Health, UofT Associate Professor, Factor-Inwentash Faculty of Social Work, UofT Graduate Faculty Associate Member, Institute of Medical Science, UofT


FEATURE Alcohol is a teratogen and thus, poisonous to the developing fetus throughout all nine months of gestation. When a mother-to-be consumes alcohol, it goes directly to the fetus through her blood stream. These children may be born with Fetal Alcohol Spectrum Disorder (FASD), which is an umbrella term that covers several alcohol-related diagnoses. This includes Fetal Alcohol Syndrome (FAS), which is the most severe and visibly identifiable form of FASD. Dr. Svetlana Popova is one of the leading scientists at the frontier of advocacy for FASD intervention and prevention. She is a Senior Scientist in the Institute for Mental Health Policy Research at the Centre for Addiction and Mental Health. Amongst her numerous accolades, she holds two faculty appointments at the University of Toronto: Associate Professor at the Dalla Lana School of Public Health, Epidemiology Division, and the Factor Inwentash Faculty of Social work, and a Graduate Faculty Associate Member position with the Institute of Medical Sciences. Dr. Popova is currently the principal investigator of an international initiative aimed to estimate the global prevalence of FASD, guided by the World Health Organization (WHO) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA). The ultimate goal of these studies is to prevent future cases and implement adequate policy and program responses for people diagnosed with FASD. She served previously as the principal investigator of a study supported by the Public Health Agency of Canada aiming to assay the burden and economic cost associated with FASD in Canada. FASD is a serious, incurable, and disabling condition, which is associated with a wide range of physical and central nervous system disabilities. These can include behavioural and learning problems, growth impairments, facial abnormalities, and developmental delays. In a recent comprehensive literature review and meta-analysis published in The Lancet, Dr. Popova and her team identified more than 400 conditions that co-occur in people with FASD.3 Unfortunately, FASD is highly unreported and unrecognized by health care providers globally. As such, many people suffering from FASD go

undiagnosed or misdiagnosed, and experience a barrier to receiving proper health care and other interventions. Recently, the group led by Dr. Popova completed and published the results of the Canadian Component of the WHO International Study on the Prevalence of FASD. Prior to this study, the prevalence of FASD amongst the general Canadian population was unknown. Their study design focused on screening children between the ages of seven and nine years from elementary schools in the Greater Toronto Area (GTA). This study was the first of its kind to provide a population-based estimate for the prevalence of FASD among elementary school children, citing a prevalence of 2-3%.1 This estimate suggests that the prevalence of FASD is higher than the prevalence of some more commonly known birth defects in Canada, such as anencephaly, Down syndrome, spina bifida, as well as autism spectrum disorder. It is important that preventative measures targeting maternal alcohol consumption be taken, as FASD is preventable. However, it is equally important that individuals with FASD are properly diagnosed, as FASD is a complex and chronic condition, for which lifelong assistance and interventions are required. Dr. Popova’s work is not limited to epidemiology and economic analyses of maternal alcohol consumption and FASD. Dr. Popova is responsible for an impressive history of prevention and intervention strategies, as well as education initiatives. In collaboration with the Pan American Health Organization (PAHO)/WHO and other colleagues, Dr. Popova undertook several workshops on FASD diagnostics for countries in Africa, Latin America, and Eastern and Central Europe. The most recent workshop was conducted in the Dominican Republic in October 2018 in order to “teach their pediatricians, psychologists, psychiatrists, and other health professionals how to diagnose children with FASD” explains Dr. Popova. “During this workshop we diagnosed the first child in the country with FAS! It’s very important because the first child that was diagnosed with FAS in the world was in the United States in 1973.”

With the first diagnosis being a mere 40 years ago, many countries are still unaware of the detrimental consequences of alcohol consumption during pregnancy, including FASD. However, educational interventions by Dr. Popova and her colleagues have made great strides in bridging this gap. Dr. Popova notes that, “in some countries, like the Dominican Republic, the population was unaware of this problem. It was eye-opening for them; now, they plan to implement their own research and their own policies, and even include diagnostic of FASD in medical schools’ curricula.” The utilization of platforms catering to the future of health care is critical. Dr. Popova’s work targets education, prevention, and intervention, all with a specific aim: “One of my goals is to educate our public about the health risks of prenatal alcohol exposure and the young IMS population is a great resource, as they are the future of healthcare.” “Ultimately, I want to communicate one crystal-clear message, because messages from the media are quite often mixed and confusing for the public.” She explains. “There is no safe amount, there is no safe type, and there is no safe time to drink alcohol during pregnancy or when planning to become pregnant. Therefore, women should completely abstain from alcohol during the entire nine months of pregnancy and up to three months when they are trying to get pregnant.” While health myths propagate through society, Dr. Popova’s research has indisputably shown that alcohol consumption during pregnancy should be recognized globally as a serious public health problem. More effective prevention strategies targeting alcohol use before and during pregnancy are needed worldwide. 1. Popova, S., Lange, S., Chudley, A.E., Reynolds, J.N., & Rehm, J. in collaboration with May, P.A. and Riley, E.P. (2018). World Health Organization International Study on the Prevalence of Fetal Alcohol Spectrum Disorder (FASD): Canadian Component. Toronto, ON: Centre for Addiction and Mental Health. 2. Popova, S., Lange, S., Probst, C., Gmel, G., & Rehm, J. (2017). Estimation of national, regional, and global prevalence of alcohol use during pregnancy and fetal alcohol syndrome: a systematic review and meta-analysis. The Lancet Global Health, 5(3), e290–e299. 3. Popova, S., Lange, S., Shield, K., Mihic, A., Chudley, A. E., Mukherjee, R. A. S., Bekmuradov, D., & Rehm, J. (2016). Co-morbidity of Fetal Alcohol Spectrum Disorder: A systematic literature review and meta-analysis. The Lancet, 387, 978-8. DOI: http://dx.doi. org/10.1016/S0140-6736(15)01345-8.

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BMC FEATURE

Master of Science in

BIOMEDICAL COMMUNICATIONS

Avesta Rastan 1T9 I believe the power of art lies in its ability to educate, influence, and inspire people. With this in mind, I aim to reveal the beauty of nature and inner-workings of the human body through beautiful, innovative, and highly accurate visuals. For my Master’s Research Project, I am developing an educational 3D animation for the Taylor Lab at the Hospital for Sick Children about their research on a newly uncovered pathway for the spread of medulloblastoma, a childhood brain cancer. In the future I hope to use animation, data visualization, and user interface design to enhance the educational experience for others.

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BMC FEATURE

Lesia Szyca, 2T0 I graduated from the Faculty of Science and Faculty of Education, at York University [First Class with Distinction, Hons. B. Sc., Maj/Min Biology & Visual Arts], and [B.Ed., Inter/Senior Biology and Visual Arts]. In my artistic practice my work deconstructs traditional images of death by taking them out of their intended context and exploring their components. In particular, I explore beauty in its ties to death and the macabre of preservation. This approach carries over into my medical illustration where I further explore themes of death and disease.

Jenny Chin, 1T9 I grew up drawing cartoons in Vaughan, Ontario and eventually moved into realism while completing my Bachelors of Science in Cell Biology & Immunology at the University of Toronto. In BMC, I am currently working on a Master's Research Project animation that aims to teach undergraduate students about how microscopic scale is (sometimes inaccurately) portrayed in visualizations. It is my goal to make engaging 3D cellular & molecular animations that help facilitate sciences learning.

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VIEWPOINT

Canada’s Opioid Crisis What are we doing wrong? By: Melissa Galati

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he “abuse” of opioids has resulted in a national public health crisis— one that appears to be worsening. The understanding that many Canadians have is that the cause of the crisis largely stems from the overprescribing of opioids for pain management. Subsequent addiction, sale of prescription drugs on the black market, or sharing of medication with family members and friends has led to substance abuse and a dramatic increase in opioid-related deaths. Indeed, Canada leads the world in per-capita pharmaceutical opioid consumption— second only to the United States1—and opioid-related deaths in Canada are at an all-time high—nearly 4000 reported in 2017, up from 3000 in 2016.2 But this is an over-simplified explanation for a complex issue—addressing this problem requires an understanding of history, community dialogue, and an overhaul of Canada’s current drug policy. Opioids—specifically opiates like heroin and morphine, derived from the flowering opium poppy plant—have been used recreationally and medically throughout history. In the mid-1900’s, chemists began synthesizing opioids in the lab, such as methadone and oxycodone, which have similar properties to opiates, without the need for plant-derived opium. Since then, various groups have produced synthetic opioids with specific, “desired” qualities— like slow-release formulations—ideal for treatment of chronic pain. The most infamous of these is OxyContin, produced by 24 | IMS MAGAZINE WINTER 2019 ADDICTIONS

Purdue Pharma and aggressively marketed to physicians as an effective painkiller without risk of side effects like addiction. As prescriptions for OxyContin increased, so did addiction and reported overdose deaths. In 2007, several of Purdue’s executives pled guilty to criminal charges of misleading regulators and the public about the harmful effects of OxyContin. OxyContin has since been removed from the market. Despite increased knowledge of the effects of these drugs and decreases in opioid prescriptions, the number of opioid-related hospitalisations, emergency room visits, and deaths continue to increase.3 This is largely fueled by the influx of illegal, black market opioids such as fentanyl and its analogues, which are extremely potent and can cause overdose in small quantities. The increasingly prevalent illicit fentanyl is often unknowingly combined with other controlled substances, most commonly heroin. This affects recreational drug users as well as individuals cut off from prescription opioids who look to the black market to avoid withdrawal. Indeed, a staggering increase in the rate of fentanyl-related deaths has been observed in provinces with the highest rate of opioid-related deaths (British Columbia and Alberta)— an “epidemic within an epidemic.”4 By the time the Government of Canada released its first national strategy to address the widespread problem of prescription drug abuse in March 2013, illicit fentanyl had pervaded the Canadian

landscape, particularly on the West Coast. The strategy focused on: prevention, treatment, and enforcement. It addressed prescription drugs like opioid pain relievers to “stem abuse of those substances”. The Prevention Action Plan included educational campaigns to remove unused prescriptions from circulation, the Treatment Action Plan increased the availability of healthcare services to at risk populations (e.g. First Nations), and the Enforcement Action Plan provided support and tools for better monitoring of controlled substances.5 While these initiatives work in theory, opioid-related deaths are still rising as none of the strategic plans addressed the fentanyl crisis. To develop solutions, it is necessary to obtain reliable information on overdose events in the community. This is challenging because of the stigma attached to opioid use. In a letter published in the Canadian Medical Association Journal (CMAJ), authors encouraged altering the language we use to discuss substance use. For example, the term “overdose” implies personal failure—that an individual knew the nature of a substance and took more than she or he could knowingly tolerate.6 This is not the case since “correct doses” do not exist for illicit formulations that are often laced with substances like fentanyl. The authors suggest using terms such as “poisoning” or “intoxication” as is the case with other substances, e.g. “alcohol poisoning.”6 Another challenge lies in the criminalisation associated with opioid use. If


VIEWPOINT

illicit fentanyl is fueling the crisis, then a tough-on-crime-approach essentially criminalises addiction. This drives people who use illegal drugs away from prevention services and treatment, and into unsafe environments with increased risk of injury and disease (e.g. HIV). A report by the Canadian Centre on Substance Use and Addiction (CCSA) addressing the use of naloxone (a drug used to counteract the effects of opioids during opioid poisoning) kits found that 30% to 65% of individuals who witnessed an apparent overdose situation did not call 9-1-1, citing concerns about police involvement and possible arrest.7 To combat this, the Good Samaritan Drug Overdose Act became law in Canada in May, 2017. The Act provides some legal protection for people who experience or witness an overdose and call emergency services. Despite this, a lack of formal training has left police officers ill-equipped to work with the Act, and charges continue to be laid often enough to discourage drug users from seeking help. To address these challenges, a fourth pillar was formally added to the Canadian Drugs and Substances Strategy: harm reduction. Part of Canada’s harm reduction approach has been to establish supervised consumption sites (SCS)—medically-supervised, clean spaces, where people can consume illegal substances. These, in addition to overdose prevention sites (OPS; like SCS but temporary and under provincial jurisdiction), are essential to preventing opioid-related deaths since harm reduction workers can intervene at the earliest stages and reverse poisoning with oxygen

and administration of naloxone. Despite assertions that SCSs/OPSs promote drug use, no evidence exists to support these claims. Moreover, these sites continue to succeed in reversing opioid poisonings without fatalities. Despite the importance of OPSs as an emergency response to communities in need, the new Ontario government has overhauled its current system for OPSs, forcing existing sites to meet a new set of requirements (with a heavy focus on treatment) and restricting the number of sites in Ontario. In practice, these new measures may demonstrate a misunderstanding of the sites’ purpose. The relatively arbitrary 21 site cap means that numerous communities will be left in need. Moreover, harm reduction workers worry that drug users won’t use sites that push treatment services, many of which they can’t afford. An alternative approach proposed most recently by Eileen de Villa, Toronto’s Chief Medical Officer, is to end prohibition on drugs. This recommendation was outlined in a report from Toronto Public Health, which summarised findings from community dialogues conducted to explore a public health approach to drugs.8 The report calls the federal government to decriminalise possession of all drugs for personal use. It also urges formal discussion for the legal regulation of drugs in Canada. Having a regulated market for drugs is a complicated endeavour that would take considerable time to develop but would alleviate drug users’ dependence

of on the illegal market, protect them from a toxic drug supply, increase access to resources, and decrease the cost of law enforcement. Decriminalisation and legalisation are part of a public health approach that acts on determinants of health and the root causes of disease, not a dated political approach based in fear that ignores new scientific knowledge. The path to ending the opioid crisis is unclear and will likely involve a complex series of solutions for a complex problem. What is clear is that Canada’s current strategies are ineffective. We need a drug policy based on evidence and with active engagement of the general and scientific community. Without this shift, we may be looking at a new normal for opioid-related mortality. 1. Report of the International Narcotics Control Board for 2013. (United Nations, 2014). 2. Special Advisory Committee on the Epidemic of Opioid Overdoses. National report: Apparent opioid-related deaths in Canada (January 2016 to March 2018). (Ottawa: Public Health Agency of Canada, 2018). 3. Opioid-related harms in Canada: chartbook, September 2017. (CIHI, Ottawa(ON), 2017). 4. Belzak, L. & Halverson, J. The opioid crisis in Canada: a national perspective. Health promotion and chronic disease prevention in Canada : research, policy and practice 38, 224-233, doi:10.24095/ hpcdp.38.6.02 (2018). 5. Evaluation of the National Anti-Drug Strategy: Final Report. (Evaluation Division Corporate Services Branch, Department of Justice(Canada), 2018). 6. Xie, E., Green, S., Puri, N. & Sheikh, H. Updating our language around substance use disorders. Canadian Medical Association Journal 189, E1566-E1566, doi:10.1503/cmaj.733490 (2017). 7. CCENDU Bulletin: Calling 911 in drug poisoning situations. (CCENDU, Ottawa(ON), 2017). 8. A Public Health Approach to Drug Policy. (Toronto Public Health, Toronto(ON), 2018).

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Preparing for the Legalization of Marijuana By: Diana Hamdan

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s of October 17, 2018, Canada has become the second country after Uruguay to fully legalize marijuana for recreational, medical, and cultivation purposes nationwide. The Cannabis Act1, also known as Bill C-45, was a milestone for Prime Minister Justin Trudeau whose election campaign included cannabis legalization as a major platform. It enforces a stringent legal framework for regulating the production, sales, and distribution of cannabis across Canada. As such, the act mainly aims to keep cannabis out of the hands of minors, the profits out of the hands of criminals, and maximizes public safety by permitting access to legal cannabis. It comes as no surprise that the legislation was met with mixed responses and has attracted attention from all over the world. While the act outlines strict regulations dictating cannabis use and distribution, it introduces many challenges that still need to be addressed. In general, the Cannabis Act permits adults who are 18 years or older—depending on what the province deems as the legal age—to possess and share up to 30 grams of dried legal cannabis with other adults, purchase cannabis products from territorial and provincial retailers, and cultivate up to 4 cannabis plants per residence for personal use. However, different provinces and territories have the freedom to impose their own cannabis regulations. For instance, cannabis cultivation for personal use is prohibited in Quebec and Manitoba. Additionally, laws regarding illegal smoking areas and retailers where cannabis can be purchased differ between provinces. Hence, it is the responsibility of citizens to check the laws of the province, territory, or indigenous community that they reside in or visit2.

The financial impact of cannabis legalization will see the development of new markets and revenue streams for the provincial and federal governments. Cannabis sales will generate an excise tax revenue of the higher of $1 per gram or 10 percent of a product price. While 75 percent of the excised tax revenue will be allocated to provincial and territorial governments, 25 percent goes to the federal government. The federal tax portion is capped at $100 million annually, and anything in excess will be given to provinces and territories3. The legalization of marijuana will also result in a concomitant increase in demand for the cannabis labour market. In addition, tourism may also benefit since Canada has now become the only country where the same rules regarding cannabis apply equally to residents and visitors. The wide availability of legal cannabis by regulated retailers will increase the likelihood that people choose it over illegal cannabis. However, customer’s decisions are likely influenced by the price at which cannabis is sold on the black market compared to that sold by legal retailers. In 2017, the consumer price of cannabis in Canada was approximated at $7.15 per gram4, whereas the average price of legal cannabis is sells for $10.30 per gram5. The wider the price gap between the cost of black market and legal cannabis, the more likely that the black market will thrive and the less effective legalization will be. Cannabis legalization will also serve to deter criminal activity by imposing serious criminal penalties on those operating outside the law, which in turn reduces the burden of cannabis offences on the justice system. Several issues facing the legalization will need to be addressed in the near future. Developments in technology will be

necessary to deal with the practical aspects of cannabis use. Unlike breathalyzers used in alcohol testing, tools for assessing THC levels require diagnostic testing at a laboratory, making them unsuitable for use by traffic police officers. Additionally, with the introduction of cannabis as a legal product, quality control and safety concerns will be paramount. Licensing, effective product labelling, product and dosage standardization, and regulated commercial cultivation will all play key roles in ensuring consumer safety. Finally, education about both the risks and the health effects of cannabis consumption will be essential for maintaining public health. Addiction and counselling services provided through government and community programs will help to address risks of chronic use. Public education campaigns can inform users of health risks while deterring use by youths. Funds dedicated to research will be necessary over the coming years to monitor the impact of legalization on health and well-being. Cannabis legalization marks new and uncharted territory for Canada, and the success of the process will be directly tied to how effectively we address the underlying societal and public health concerns. 1. Cannabis Legalization and Regulation. Department of Justice; (modified 2018 Oct. 17). Available from: https://www.justice.gc.ca/ eng/cj-jp/cannabis/ 2. What you need to know about cannabis. Ottawa: Health Canada; (modified 2018 Sept. 6). Available from: www.canada.ca/en/ services/health/campaigns/cannabis/canadians.html#a2\ 3. 2018 Canadian federal budget plan. Government of Canada; (modified 2018 Feb. 27). Available from: https://www.budget. gc.ca/2018/docs/plan/chap-04-en.html#Cannabis-Taxation-Regulation-and-Public-Protection-Legalizing-Cannabis-in-2018 4. Cannabis consumer and producer prices. Statistic Canada; (modified 2018 Nov. 8). Available from: https://www150.statcan.gc.ca/t1/ tbl1/en/tv.action?pid=3610059801 5. What Will a Gram of Legal Weed Cost in Canada? Montreal: VICE; (modified 2018 Jul. 30). Available from: https://free.vice.com/en_ca/ article/43pn9m/what-will-a-gram-of-legal-weed-cost-in-canada

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East —

Differing Approaches By: Parita Shah

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ould you want to know the truth or be lied to? The attitudes and practices in providing or withholding medical diagnoses from patients differ between cultures and countries. In western countries, approximately 80 to 90% of patients are informed about their diagnosis, whereas the figures can range from 0 to 50% in non-western cultures.1 As such, while honesty is a key element to developing a good doctor-patient relationship, truth-telling (i.e. diagnosis disclosure) should be done in the context of ethical values, legal obligations, and cultural considerations. Doctor-patient communication has evolved over the years. The traditional paternalistic model of care assigned doctors as the key decision makers; they assessed patients and prescribed medications to save life and avoid death but rarely educated patients of their diagnoses and treatment. However, with the introduction of contemporary bioethics, the traditional medical practice evolved to an 28 | IMS MAGAZINE WINTER 2019 ADDICTIONS

autonomy-based model of care.2 In this new view, patients are informed of their diagnoses and they are equally involved in the decision-making process of their treatment plan as the doctors. However, the degree to which the new autonomy-based model of care has been adopted varies across countries and cultures. In western countries, physicians are trained to tell the whole truth about their patient’s diagnosis, regardless of how bad the news. This practice is based on ethical principles, namely patient autonomy (i.e. right to make informed decisions), justice (i.e. fair treatment), beneficence (i.e. benefit others), and non-maleficence (i.e. do no harm). Truth-telling can establish a lasting doctor-patient relationship based on trust, and provide patients opportunities to actively participate in the decision-making process of their treatment plan, often resulting in better outcomes. However, in an environment that demands efficiency, explaining diagnoses and treatment options, along with addressing patient concerns, can take substantial time. Additionally, if given in haste, disclosure

can cause undue distress or anxiety for patients and their families after receiving the diagnoses. In some non-western cultures, doctors fear communicating bad news because of the belief that it would cause great psychological distress to patients. These cultures put emphasis on the role of family in patient care, operating within more paternalistic approaches to patient care. For example, in many traditional Chinese medical practices, death and related issues are taboo subjects and the emphasis on non-maleficence leads to withholding the truth to patients. Patients in these cultures may be psychosocially dependent on their family as these members act as key decision makers. As such, doctors may respect a family’s decision to withhold a diagnosis to the patient in order to protect the patient from psychological distress. However, this decision can cause more harm to the patient if their family fails to act in the patient’s best interests. Further, it can be argued that patients in these cultures only seek medical help in order to be relieved of their symptoms and are less likely to


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— West

to Truth-telling in Medicine

engage in preventative care (e.g. regular health screenings), as preventative care is more closely associated with the patient as decision-maker. While medical practice on truth-telling is culture-specific, patients’ attitudes on disclosure increasingly appear to be more influenced by personal factors rather than cultural ones. One study found that patients with above-average income, college education, and those younger than 60 years old are more likely to be interested in knowing the truth about their condition.3 Overall, most patients, regardless of their culture, want to know the truth about their illness.4,5 The consensus of patients’ desire for transparent diagnoses is in contrast to some doctors’ truth-telling practices. This incongruity points to how patients from highly family-oriented cultures may not be able to request an honest diagnosis, as this act of rebellion could insult the very people who make medical decisions on their behalf: their family. However, more research is needed to understand this possible phenomenon.

When culture demands adherence to the traditional paternalistic model, it can pose a challenge for doctors who wish to undertake the autonomy-based model of care approach. Given the challenges to truth-telling across cultures, doctors can use communication strategies to minimize the negative impact of unfavourable news on a patient’s well-being.6 For example, doctors may need to understand patients’ and their families’ perspectives in a cultural context, correct misbeliefs, be empathetic, and connect them to an interdisciplinary health support team (e.g. social workers and nurses) for ongoing psychosocial support. Further, they may need to recognize instances when withholding diagnoses can be justified. For example, if doctors have reasonable evidence that truth-telling will cause preventable harm to the patient or if the patient has made an informed request to not know the truth, then withholding diagnoses from the patient may be justifiable.7 The extent to which patients are told the truth about their illness exists on

a continuum, with western countries more likely to give a full disclosure and non-western countries more likely to give partial or no disclosure to patients. There is an increasing trend and evidence in favour of not withholding medically-indicated information from patients.2,7 If done carefully, in the context of ethical obligations and cultural considerations, revealing diagnoses to patients may be far superior in improving patient outcomes than withholding information in most situations. After all, honesty matters—to doctors, patients, and their families. 1. Gold M. Is honesty always the best policy? Ethical aspects of truth telling. Intern Med J. 2004;34(9-10):578-80. 2. Zahedi F. The challenge of truth telling across cultures: a case study. J Med Ethics Hist Med. 2011;4:11. 3. Sullivan R.J., Menapace LW, and White RM. Truth-telling and patient diagnoses. J Med Ethics. 2001;27(3):192-7. 4. Laxmi S and Khan JA. Does the cancer patient want to know? Results from a study in an Indian tertiary cancer center. South Asian J Cancer. 2013;2(2): 57-61. 5. Glass E and Cluxton D. Truth-Telling: Ethical Issues in Clinical Practice. Journal of Hospice and Palliative Nursing. 2004;6(4): 232-242. 6. Baile W.F. et al. SPIKES-A six-step protocol for delivering bad news: application to the patient with cancer. Oncologist. 2000;5(4): 302-11. 7. Braddock CH. Truth-telling and Withholding Information. 2008; Available from: https://depts.washington.edu/bioethx/topics/truth. html.

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Models of Addiction: Integrating Approaches By: Duncan Green

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iven the recent surge in addiction rates and overdoses, especially concerning opioids, it may be time to reconsider how addiction is viewed and considered by the academic and lay communities. Both groups have different opinions and perceptions on addiction. Given the terminology used regarding the recent opioid crisis—ie “epidemic” among others—the current, most widely believed model is that addiction is a disease. It is thought that excessive prescription of opioids is to blame for this surge in addiction rates. Although addiction can be a nebulous term with a variety of different criteria, it is generally accepted to be a disorder in which an individual demonstrates prolonged problematic use of a substance which negatively impacts their wellbeing and livelihood, as per the National Institute on Drug Abuse (NIDA).1 With the failure of the disease model and the associated “War on Drugs,” we should perhaps move beyond viewing addiction as a disease. Theoretical modelling of addiction may seem like an issue that is restricted to the academic field, but it directly affects how the public perceives and approaches the problem of addictions. For the past several

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decades, the prevailing model of addiction adapted by the public is the disease model of addiction, which is largely beyond the control of an individual with a history of relapse. This has also been referred to as the NIDA model, largely due to how closely associated the National Institute is with promoting the concept that drug addiction as a disease.2 Origins of the NIDA model may also be largely attributed to the “War on Drugs” campaign started during the Reagan administration in the United States. Along with the “Just Say No” campaign, this movement was an effort to prevent behaviours of drug use and drug seeking from starting in the first place. After several decades and billions of dollars, it can be concluded that the war on drugs has soundly failed. An excellent example is the increase popularity of oxycontin, a prescription opioid that has made its way into the streets.3 Another model gaining popularity within academic circles is the incentive salience model. This model portrays addiction as a disorder of motivation and cues rather than a disease that is beyond control.4 In brief, individuals with drug addictions see cues that are relevant to their addiction, such as bottles of alcohol, packs

of cigarettes, or bags of white powder. These cues activate various neural reward circuits, such as the subcortical reward pathway, and cause the individual to crave the drug. This model addresses a key problem present in the NIDA disease model: addicted individuals are largely self-medicating to ward off the effects of drug withdrawal. This is irrelevant for drugs with low withdrawal effects, such as cocaine and other stimulants, and behavioral addictions, such as gambling and internet use disorders. On a societal level, it forces a false dichotomy on the public perception of addiction. If addiction is not viewed as a disease, the alternative is to regard addiction as a failure of character and self-discipline. The incentive salience model also accounts for various sociological and environmental factors. It is commonly acknowledged that individuals living in areas with prominent drug use are much more likely to relapse into use.5 It is worth noting that individuals who live in such areas are also at a higher risk of starting drug use. This greater relapse rate may be due to the increase in availability of addiction-relevant cues and stimuli. By increasing the cravings, these cues increase


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the likelihood for the individual to seek out the drug, using them at higher doses and more frequently. While this model can compensate for areas of weakness in the NIDA model, it also has its flaws. It deemphasizes many of the systemic physiological issues in addicted individuals, such as withdrawal and long-term neural damage. Animal models observing drug dependence in the absence of drug related stimuli by drug perfusion alone also creates issues with the incentive salience model, as there are no stimuli that the animal could use as cues. Personally, my research examines the neurobiological markers of psychiatric disorders, focusing mostly on addiction and anxiety disorders. Neuroimaging has been a tool used to argue both sides of the modelling argument. Many studies show long term damage to neurochemical systems associated with drug use. This damage is portrayed as analogous to any other disease, beyond the control of the individual. Further studies have shown neural differences in the reaction to stimuli related to drug use, demonstrating differences in activation of the subcortical dopamine system. The subcortical dopamine system is largely

involved with reward reinforcement and “feel-good” responses. While these findings are replicable and strong, these findings have also been used to argue entirely opposing theories of addiction. Changes in activation of the dopamine system can be seen as either damage analogous to disease, or as a change in decision making process, thus being applicable to either model. Although the constant debate and comparisons of validity for different models of addiction seem like a theoretical exercise, there are some very important real-world implications of the models. For example, a model based solely on the assumption of addiction as a disease would potentially bias clinicians towards relying more heavily on medications as a mode of treatment. On the other hand, a model based solely on reactions towards stimuli may bias clinicians to rely more heavily on cognitive and behavioural therapies for treatments while disregarding the significant physiological issues. It is for this reason that it would be best to take an integrated approach to addiction modelling.

definition of an addiction influences not only the public perception of addiction and individuals with addictions, but also the care that addicted patients receive from clinicians. It is for this reason that we need to take a more holistic and comprehensive approach to addiction in order to accommodate aspects of both the disease model and the incentive salience model of addiction. 1. NIDA. (2015, July 29). Addiction Science. Retrieved from https:// www.drugabuse.gov/related-topics/addiction-science on 2018, November 19 2. Hall, W., Carter, A., & Forlini, C. (2015). The brain disease model of addiction: is it supported by the evidence and has it delivered on its promises? The Lancet Psychiatry, 2(1), 105–110. https://doi. org/10.1016/S2215-0366(14)00126-6 3. Manchikanti, L., Helm, S., Fellows, B., Janata, J. W., Pampati, V., Grider, J. S., & Boswell, M. V. (2012). Opioid epidemic in the United States. Pain Physician, 15(3 Suppl), ES9-38. Retrieved from http:// www.ncbi.nlm.nih.gov/pubmed/22786464 4. Huys, Q. J. M., Tobler, P. N., Hasler, G., & Flagel, S. B. (2014). The role of learning-related dopamine signals in addiction vulnerability. In Progress in brain research (Vol. 211, pp. 31–77). https://doi. org/10.1016/B978-0-444-63425-2.00003-9 5. Panebianco, D., Gallupe, O., Carrington, P. J., & Colozzi, I. (2016). Personal support networks, social capital, and risk of relapse among individuals treated for substance use issues. International Journal of Drug Policy, 27, 146–153. https://doi.org/10.1016/J. DRUGPO.2015.09.009

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Overcoming Addiction: is Admitting the First Step? By: Cricia Rinchon

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r. Benjamin Boshes, former neurology chairman emeritus at Northwestern University Medical School, once wrote, “the question of why some drug users become addicted and others do not is one which has defied understanding”.1 Six decades later, neuroscience and medical students are taught that addiction, the most severe form of substance use disorder, is a chronic brain disorder molded by biosocial factors with devastating consequences to individuals and society.2 Despite psychosocial factors, addiction’s core pathology is biological. For example, a variant in the gene encoding for the α-5 subunit of the nicotinic receptor (highly expressed in a brain area known as the habenula) has been associated with higher vulnerability to nicotine addiction.3 Ironically, in Canada, the extent that psychosocial or biological factors are emphasized in treatment depends on the type of addiction.

alcohol dependence since 1935, using a 12-step approach. It is the most common recovery resource in Canada;4 however, there is controversy surrounding its effectiveness since the Cochrane systematic review of eight trials involving 3417 people concluded that no experimental studies demonstrated the effectiveness of AA or the 12-step approach.5 Importantly, AA is a recovery resource and not an addiction treatment. Alcohol addiction, or alcohol use disorder (AUD), can be treated pharmaceutically using medications such as naltrexone, which blocks the pleasant effects of alcohol, or acamprosate, which reduces symptoms that occur in early withdrawal from alcohol such as cravings and discomfort. Both naltrexone or acomprostate are available to Ontario public drug plan beneficiaries with an AUD diagnosis. Still, a retrospective study found that between 2011 and 2012, very few beneficiaries (< 1%) are actually dispensed naltrexone or acamprosate in their subsequent year of diagnosis.6 These low rates of AUD medication may reflect lingering cultural views and medical teachings that substance problems are primarily psychosocial and not medical conditions.

When you think of helping a person addicted to alcohol, what’s the first thing Why is the opposite that comes to mind? true with regards to Alcoholics Anonymous (AA), an international self-help group, has been people addicted to offering emotional support and a model of abstinence for people suffering from nicotine? 32 | IMS MAGAZINE WINTER 2019 ADDICTIONS

When it comes to a person addicted to smoking, there seems to be a general understanding that this person would need to take some sort of medication (i.e. a nicotine patch) in lieu of smoking in order to recover successfully. In a survey of over 100 physicians in Ontario, over 90% of family physicians felt knowledgeable enough to prescribe pharmaceuticals for tobacco dependencies.7 This contrasts greatly with the ~70% of physicians who felt uncomfortable prescribing pharmaceuticals for alcohol substance dependencies and attribute their lack of knowledge about the pharmacotherapies as the primary barrier. This statistic is concerning because approximately 21.6% of Canadians meet the criteria for substance use disorder during their lifetime, and alcohol is the most prevalent substance for which people meet the criteria for abuse or dependence.8

What is the first step then? Planning, together. The purpose of this viewpoint article isn’t to discount the 12-steps mutual support group—nearly 80% of 785 respondents in a Canadian recovery survey believe that it is a very important recovery resource.4 Nor is the purpose to insist that pharmaceuticals alone are the answer. Instead, it is to highlight the importance of the Canadian healthcare system


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acknowledging substance use disorders as medical conditions that require multifaceted and personalized treatment approaches. Ultimately, a system is tragically flawed if it blames a patient for not getting “better” and propels them into a recovery program before they are in a position to “recover”. Science has progressed beyond attributing the cause of addiction to the will of individuals. The individual variations and mechanisms of addiction are progressively being revealed, and we are moving towards proving that addiction is not a condition that defies understanding.

Ultimately, a system is tragically flawed if it blames a patient for not getting “better” and propels them into a recovery program before they are in a position to “recover”.

Exciting new prospects for addiction science lay in the National Institute of Health’s long-term Adolescent Brain Cognitive Development (ABCD) study. The ABCD aims to recruit approximately 10,000 children ages nine to ten and follow them into early adulthood. The study’s goal is to increase our understanding of the many factors (sports, video games, social media, unhealthy sleep patterns, and smoking) that interact with each other and with a child’s changing biology to affect brain development, social, behavioural, academic health, and other outcomes. One of the fundamental questions this

study hopes to answer is: how does the occasional versus regular use of substances (e.g., alcohol, nicotine, marijuana) affect learning and the developing brain? Many unanswered questions will hopefully be elucidated this coming decade—leading to a future where the conventional “first step” to overcoming addiction isn’t initiated by the patient, but by the healthcare system.

1. Boshes B, Sewall LG, Koga M. Management of the narcotic addict in an outpatient clinic. American Journal of Psychiatry. 1956;113(2):158-62. 2. Volkow ND, Boyle M. Neuroscience of Addiction: Relevance to Prevention and Treatment. The American journal of psychiatry. 2018;175(8):729-40. 3. Fowler CD, Lu Q, Johnson PM, Marks MJ, Kenny PJ. Habenular alpha5 nicotinic receptor subunit signalling controls nicotine intake. Nature. 2011;471(7340):597-601. 4. McQuaid RJ, Malik, A., Moussouni, K., Baydack, N., Stargardter, M., &, Morrisey M. Life in Recovery from Addiction in Canada. Canadian Centre on Substance Use and Addiction. 2017. 5. Ferri M, Amato L, Davoli M. Alcoholics Anonymous and other 12‐step programmes for alcohol dependence. Cochrane Database of Systematic Reviews. 2006(3). 6. Spithoff S, Turner S, Gomes T, Martins D, Singh S. First-line medications for alcohol use disorders among public drug plan beneficiaries in Ontario. Canadian Family Physician. 2017;63(5):e277-e83. 7. Loheswaran G, Soklaridis S, Selby P, Le Foll B. Screening and Treatment for Alcohol, Tobacco and Opioid Use Disorders: A Survey of Family Physicians across Ontario. PloS one. 2015;10(4):e0124402. 8. Mental Health Indicators. Statistics Canada; 2012.

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Fighting fire with fire:

Using agonist replacement therapy to treat cannabis addiction By: Sonja Elsaid

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ot. Weed. Skunk. Dope. Mary Jane. Call it whatever you want, cannabis, is material that contains dried leaves, flowers or fruiting tops of the plant Cannabis sativa,1 usually smoked as joints (cigarettes), or in bongs (pipes). It can also be baked into foods, such as cakes, cookies, and the ever-magical brownies. Worldwide, cannabis is the third most commonly used psychoactive substance after tobacco and alcohol.1 It is estimated that over 40% of Canadians have tried cannabis at least once in their lifetime.2 Cannabis consumers often seek feelings of relaxation or euphoria and they often experience changes in perception.3 Responsible for these effects is tetrahydrocannabinol (THC), the main psychoactive ingredient in Cannabis Sativa. Sadly, it is expected that 8-12% of regular cannabis users will at some point in their lifetime develop cannabis use disorder (CUD), which can lead to cannabis addiction.1 According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) used by Canadian healthcare professionals, CUD is a recognized mental health disorder.4 Furthermore, cannabis withdrawal, which is the more severe form of CUD, can develop after the abrupt reduction 34 | IMS MAGAZINE WINTER 2019 ADDICTIONS

or cessation of prolonged cannabis use.4 Individuals in the state of withdrawal normally experience unpleasant symptoms, such as irritability, sleep difficulty, depressed mood and restlessness.4 These unpleasant conditions not only interfere with daily functioning of these individuals, but efforts to avoid them represent the driving force for continuous cannabis abuse.1 Currently, the only approved therapy for cannabis withdrawal is psychotherapy.1,⁵ However, only 20% of those treated achieve abstinence, indicating that better treatments are needed.⁵ Since successes were observed with using agonist replacement therapies for treating other substance use disorders, such as using nicotine patch to help quit smoking, scientists started testing synthetic THC in subjects with cannabis withdrawal.1 The rationale for using the agonist replacement therapy was the potential to reduce symptoms of withdrawal by providing a similar drug—synthetic THC—through a safer route of administration. Thus, instead of smoking a joint, and inhaling chemicals, synthetic THC would be ingested.1 The other benefit of this harm reducing method was to empower patients to make the necessary lifestyle changes, while distancing them

from the regular substance abuse.5 One of the first synthetic THC drugs tested for cannabis addiction was dronabinol, an oral and synthetic THC.1 Initially, dronabinol was approved for treatment of anorexia, nausea, and vomiting in cancer patients.1 Early clinical trials demonstrated that dronabinol was effective in reducing cannabis smoking by 50%. However, its poor bioavailability and slow onset of action prompted scientists to test nabilone (CesametTM), a synthetic analog with better bioavailability.1,5 Like dronabinol, nabilone was originally approved for the treatment of nausea and vomiting in cancer patients.1 In clinical trials, nabilone was effective in decreasing cannabis smoking and treating symptoms of withdrawal.1 Furthermore, nabilone is long-acting and did not exhibit addictive potential likely due to its slow onset of action.⁵ Despite these strengths, nabilone is not approved as CUD treatment, as nabilone is still composed of THC, the substance originally derived from marijuana, which led to cannabis addiction in the first place.5 Furthermore, the medical community’s fear of prescribing THC alone for any medical condition was why researchers had to look elsewhere for more sophisticated compounds to treat CUD.5,6


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Synthetic THC

The most recent variations of agonist replacement therapy is nabiximols (SativexŽ), which have been prescribed for the treatment of multiple sclerosis and cancer-related pain in 15 countries.2 Nabiximols contains THC, which aims to provide the agonist replacement therapy. However, unlike dronabinol and nabilone, nabiximols also contains cannabidiol (CBS), the other major ingredient found in marijuana.1 Importantly, CBD does not exhibit the same mind-altering properties of THC and counteracts the negative effects of THC abstinence.1 Nabiximols is administered as a buccal spray and is placed between the gums and cheek in the mouth for absorption.5 The first study was conducted on inpatients with cannabis dependence, who reported having fewer symptoms of withdrawal when treated with nabiximols.7 Furthermore, when tested in outpatients, patients taking nabiximols exhibited fewer withdrawal symptoms when abstaining from smoking cannabis.8,9 In fact, this study was conducted at the Centre of Addiction and Mental Health (CAMH) in Toronto, under the supervision of the Institute of Medical Science’s very own, Dr. Bernard Le Foll, a psychiatrist at the Addiction Division at the CAMH. Moreover, in another study at CAMH, Dr. Le Foll and his group have demonstrated

that cannabis use was reduced by 70% in those treated with nabiximols. Use of nabiximols was well tolerated and did not lead to greater incidence of abuse.9,10 Yet, despite the evidence that synthetic cannabinoids have been shown their effectiveness in treatment of cannabis addictions, Canadian and American government officials remain hesitant about giving these drugs the official indication for treatment of cannabis addictions.5 It seems that much more effort is needed for agonist replacement medications to get approved on the market.5 With the recent legalization of cannabis for recreational use in Canada, cannabis use and the number of individuals developing CUD are expected to rise, with no drugs currently indicated for treatment, except for psychotherapy.2,9 It is also worthwhile to note that psychotherapy may not be accessible to those without health insurance. Although the use of synthetic THC and nabiximols may be controversial, the benefits of cannabis agonist replacement therapy demonstrated by its superior safety, efficacy, and potential for harm reduction far outreach the cost of fear by the medical community to use

THC-containing compounds for treatment. Unfortunately, changing the opinion of the medical community and government officials to approve cannabis-derived treatments for CUD may require more time and effort.

1. Brezing CA, Levin FR. The Current State of Pharmacological Treatments for Cannabis Use Disorder and Withdrawal. Neuropsychopharmacology. 2018;43(1):173-94. 2. Bonner WIA, Andkhoie M, Thompson C, et al. Patterns and factors of problematic marijuana use in the Canadian population: Evidence from three cross-sectional surveys. Can J Public Health. 2017;108(2):e110-e6. 3. Canadian Centre on Substance Abuse. Canadian Drug Summary: Cannabis. 2018 June [10p]. Available from: http://ccsa.ca/ Resource%20Library/CCSA-Canadian-Drug-Summary-Cannabis-2018-en.pdf 4. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Washington, DC; 2013. 5. Allsop DJ, Lintzeris N, Copeland J, et al. Cannabinoid replacement therapy (CRT): Nabiximols (Sativex) as a novel treatment for cannabis withdrawal. Clin Pharmacol Ther. 2015;97(6):571-4. 6. CBC Radio Quirks and Quarks. Doctors' group wants to scrap Canada's medical cannabis program [document on the Internet]. CBC Radio; 2018 April 30 [cited 2018 Oct 20]. Available from: https://www.cbc.ca/radio/quirks/scrap-medical-weed-women-inspace-and-more-1.4636793/doctors-group-wants-to-scrap-canadas-medical-cannabis-program-1.4636810 7. Allshop DJ, Copeland J, LIntzeris N, et al. Nabiximols as an agonist replacement therapy during cannabis withdrawal: a randomized clinical trial. JAMA. 2014;71:281-291. 8. Trigo JM, Lagzdins D, Rehm J, et al. Effects of fixed or self-titrated dosages of Sativex on cannabis withdrawal and carvings. Drug Alcohol Depend. 2016;161:298-306. 9. Le Foll B. Oral communication 2018 Oct 17. 10. Trigo JM, Soliman A, Quality LC, et al. Nabiximols combined with motivational enhancement/cognitive behavioral therapy for the treatment of cannabis dependence: A pilot randomized clinical trial. PLoS ONE 13(1): e0190768. https://doi.org/10.1371/journal. pone.0190768

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VIEWPOINT

Fighting Loneliness and Social Isolation in Old Age: A Policy Perspective By: Riddhita De

D

id you know that loneliness and social isolation during old age are serious problems in Canada?1 According to the most recent Canadian Census, one quarter of the population aged 65 and over live alone.2 Moreover, being over 80 years of age is considered a risk factor for chronic social isolation, as reported by the National Seniors Council of Canada.3 Many older seniors find themselves withdrawing from society based on diverse risk factors ranging from being childless,⁴ living away from family,⁴ 36 | IMS MAGAZINE WINTER 2019 ADDICTIONS

The most terrible poverty is loneliness, and the feeling of being unloved. -Mother Teresa

divorce or the passing of a spouse,⁵ or having a disability.⁵ This in turn causes elderly individuals to lose important social connections. ⁴,⁵,⁶ Additionally, people in minority groups, such as older immigrants, indigenous people, and LGBTQ individuals, may be more vulnerable to social isolation and loneliness.6 Seniors residing in rural areas may also face challenges accessing resources when compared to individuals residing in urban areas.6

While loneliness and social isolation are used interchangeably, they are in fact different yet interrelated concepts.7 Social isolation pertains to an individual having a lack of close contacts or relationships, whereas loneliness usually focuses on the negative feelings associated with social isolation.7 In a study conducted by University of Toronto researchers studying mouse models of chronic isolation, it was discovered that serotonin-producing neuronal excitability was considerably decreased in


VIEWPOINT

Call for Action The Canadian Medical Association (CMA) states that Canada’s universal healthcare system was not built to sustain and care for the aging population, especially in terms of handling chronic diseases. The CMA has identified Canada to be struggling to best serve our aging population, particularly with addressing the affiliated chronic disease burden.1⁰ Up until now, no policy level changes have occurred to address isolation and loneliness amongst seniors. There are essentially non-existent resource allocations by our government to address the issue, with the problem being mostly unknown amongst the general public.3 As a consequence of this, there are minimal public awareness campaigns, leaving the issue almost buried. This might prompt us to ask about how other countries are approaching the topic of isolation and loneliness. In fact, at the beginning of this year, the UK appointed their very first Minister of Loneliness. The minister’s duties include addressing health as well as social challenges brought on by isolation. Nine million Britons are affected by social isolation, and although the Minister’s responsibilities do not specifically focus on older adults, this is a commendable initiative brought forth by Theresa May’s government.11 For Canadians, despite there not being any single policy approach to solving the issue, beginning with small-scale regional approaches could prove to be beneficial.

Senior-focused, customized services dictated by a National Senior Care strategy could be funded and implemented by the government. First and foremost, seniors could be kept engaged through social support in the community. Social networking circles often put individuals of a similar age in touch with each other. Alternatively, another approach focuses on programs that match a senior with a local volunteer, through home or telephone visits.12 By engaging with community members, meeting other seniors, and having an individual who serves as a friend to the elderly, studies have indicated positive impacts on seniors’ quality of life.13 Through the introduction of a social network, levels of physical activity amongst older individuals could be increased, thus improving their mental health.1⁴ Furthermore, involving children into the daily activities of seniors has been shown to improve mood in this population.12 It has also been noted that due to disabilities which seniors may face or for those unable to drive, transportation services could be useful.12 Such assistance programs would encourage dialogue between individuals, as the service could act as a medium for volunteer or employee drivers to connect with seniors in the community. Besides social engagement through various initiatives, involving family physicians, geriatricians, psychiatrists, and social workers into the circle of evidence-based care, is integral. Many seniors who experience loneliness and social isolation, have poor diets and sedentary lifestyles. Since the older cohort frequently make

By applying a holistic and inclusive lens of care in the community comprised of the general public, government workers and healthcare workers, the fight against loneliness can be won.

socially-isolated mice.8 Loneliness and social isolation together has been termed an epidemic by many experts, who say the problem leads to major mental health and chronic physical health issues.9 Long term illnesses can include depression, arthritis, lung disease, stroke, and depression amongst numerous others, which undoubtedly increase the risk of mortality in the population. In addition, with the large number of baby boomers aging in Canada, there is an increasing demand for health and nursing care.1 Thus, there are significant reasons for the government to take action to prevent the already escalating healthcare costs associated with social isolation and loneliness.10

visits to their family physicians12, any suspicions of loneliness and therefore respective interventions, could be initiated by the practitioner. It is also essential that family members and friends, who may be involved in the care of seniors are educated and trained to identify signs indicative of loneliness and isolation. By applying a holistic and inclusive lens of care in the community comprised of the general public, government workers and healthcare workers, the fight against loneliness can be won. Even though national level policy changes can be both time and resource-intensive, the consequences may be far larger if the problems are not addressed starting now.

1. Alpert PT. Self-perception of Social Isolation and Loneliness in Older Adults. Home Health Care Management & Practice. 2017 Nov;29(4):249-52. 2. Statistics Canada. Living arrangements of seniors. Statistics Canada. 2011. Available from: http://www12.statcan.gc.ca/census-recensement/2011/as-sa/98-312-x/98-312-x2011003_4-eng.cfm 3. The National Seniors Council. Report on the Social Isolation of Seniors. Government of Canada. 2014. Available from: https://www. canada.ca/content/dam/nsc-cna/documents/pdf/policy-and-program-development/publications-reports/2014/Report_on_the_Social_Isolation_of_Seniors.pdf 4. Milne V, Tepper J, Nolan M. From Alzheimer’s to heart attacks, loneliness in seniors has serious health effects. Healthy Debate. 2016. Available from: http://healthydebate.ca/2016/10/topic/isolation-and-seniors 5. Menec V. Loneliness and social isolation are important health risks in the elderly. McMaster Optimal Aging Portal. 2016. Available from: https://www.mcmasteroptimalaging.org/blog/detail/professionals-blog/2016/04/08/loneliness-and-social-isolation-are-important-health-risks-in-the-elderly 6. The National Seniors Council. Report on the social isolation of seniors- Consultation Highlights. Government of Canada. 2014. Available from: https://www.canada.ca/en/national-seniors-council/ programs/publications-reports/2014/social-isolation-seniors/ page05.html 7. Alspach JG. Loneliness and social isolation: Risk factors long overdue for surveillance.2013; 33(6):8-13 8. Sargin D, Oliver DK, Lambe EK. Chronic social isolation reduces 5-HT neuronal activity via upregulated SK3 calcium-activated potassium channels. elife. 2016;5. 9. Steptoe A, Shankar A, Demakakos P, Wardle J. Social isolation, loneliness, and all-cause mortality in older men and women. Proceedings of the National Academy of Sciences. 2013 Apr 9;110(15):5797-801. 10. Canadian Medical Association. The State of Seniors Health Care in Canada. Canadian Medical Association. 2016. Available from: https://www.cma.ca/En/Lists/Medias/the-state-of-seniors-healthcare-in-canada-september-2016.pdf 11. Dakers S. The minister for loneliness will need all the friends she can get. The Guardian . 2016 . Available from: https://www. theguardian.com/society/2018/jan/23/tracey-crouch-minister-loneliness-friends-powerful-vested-interests 12. Salman S. The battle against loneliness among older people. The Guardian. 2016. Available from: https://www.theguardian.com/ healthcare-network/2017/may/10/loneliness-older-people 13. Gouveia OM, Matos AD, Schouten MJ. Social networks and quality of life of elderly persons: a review and critical analysis of literature. Revista Brasileira de Geriatria e Gerontologia. 2016 Dec;19(6):103040. 14. Pels F, Kleinert J. Loneliness and physical activity: A systematic review. International Review of Sport and Exercise Psychology. 2016 Jan 1;9(1):231-60.

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FACULTY SPOTLIGHT

Photo by Mikaeel Vali

Dr. Thomas Waddell MD, MSc, PhD, FRCSC, FACS Head, Division of Thoracic Surgery, UHN Thomson Family Chair in Translational Research Professor and Pearson-Ginsberg Chair, Division of Thoracic Surgery Senior Scientist, Toronto General Research Institute and McEwen Centre for Regenerative Medicine Professor and Chair, Division of Thoracic Surgery, UofT

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FACULTY SPOTLIGHT

Dr. Thomas Waddell By: Brenda Varriano and Frank Pang

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n organ critical for survival is the lungs—giving us the breath of life. Historically, lung disease meant death. Today, the availability of organ transplantation provides a new hope for life. However, organ transplantation remains complicated, with success relying on a multitude of factors, including availability and acceptance of donor lungs in a recipient. At frontier in the field of lung transplantation is Dr. Tom Waddell, a clinician-scientist whose research interests lie in improving lung transplantation and regenerative medicine. With appointments in the Institute of Medical Science, Toronto General Hospital and McEwen Centre for Regenerative Medicine, his accomplishments are vast. Some of his achievements include, but are not limited to, the Blalock Scholarship from the American Association for Thoracic Surgery, the CIHR New investigator Award, a CFI New Opportunities Fund Award, the George Armstrong Peters Prize, and the Lister Award in 2011 for his international recognition in the field of plastic surgery. IMS Magazine had the privilege to interview Dr. Waddell, who discussed the challenges in the field of lung transplantation and advice for students and other upcoming researchers. In Dr. Waddell’s opinion, a major challenge in lung transplantation is to find safe and reliable methods to induce patient tolerance, or bodily acceptance, of a donor organ. Tolerance and compatibility prevent triggering the immune response which would normally lead to graft rejection.

There are two schools of thought which aim to tackle is issue of patient tolerance for organ donors. The newer school focuses on ideas of regenerative medicine. These include growing a recipient’s own cells in vitro before reintroducing them, and establishing a universal cell source for all patients. Success of both ideas rely on the principle of tolerance of a patient towards his or her own cells. The second, older school of thought, aims to find methods to alter a recipient’s tolerance to grafts without immunosuppression. Despite the differences in these approaches, there are still common challenges, including a lack of knowledge concerning immune signaling pathways and the resistance of the healthcare system when integrating new technologies into clinical practice. While some clinical trials have already looked as modulating patients’ tolerance for organ transplantation, the translation from bench-to-beside still has a long way to go. To explain the issue with integrating new technologies and treatments into the healthcare system, Dr. Waddell made an analogy with the transition from steam to electric power in wool factories. The output (production of wool) did not immediately increase after this change, because the machines did not differ in their output, but in the methods to do so. Therefore, in order to successfully introduce technology in medicine, the output must be different and improve on what has already been done and shown to be most effective in mitigating patient care.

What can scientists create that will enable physicians to do what has never been done before? To overcome this challenge, there is a need to improve collaboration and coordination between basic and clinical scientists. Typically, basic science moves at a much quicker pace when compared to clinical science. This creates a gap between current knowledge in the respective fields. To manage this gap, Dr. Waddell emphasizes on the importance of idea sharing between basic and clinician scientists on a regular basis. A supportive environment where ideas can be shared and critiqued freely is necessary. Overall, these changes will greatly benefit healthcare and patient care as a whole. The focus on translational research has stuck with Dr. Waddell since his time as an IMS student. He also hasn’t forgotten what it was like to be a graduate student, offering advice for young aspiring scientists. While having an end goal is important, Dr. Waddell emphasized that students should keep their mind open and enjoy the process. Furthermore, he noted the importance of having strong mentor-mentee relationships not only to gain scientific knowledge, but also to broaden their philosophical views on life. Without a doubt Dr. Waddell is the epitome of research and surgical advances in the field of lung transplant. With his advice and views, we hope that students leave inspired and eager to tackle the field of medical science.

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FACULTY SPOTLIGHT

Understanding the Science of Starving with Dr. Allan Kaplan By: Parnian Pardis

Photo credit: Dorsa Derakhshan

Dr. Allan Kaplan Vice Dean, Graduate and Academic Affairs, and Professor of Psychiatry, Faculty of Medicine Senior Clinician/Scientist, Center for Addiction and Mental Health Full Member, Graduate Faculty, School of Graduate Studies, Institute of Medical Science

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FACULTY SPOTLIGHT

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ne encounter with a patient catapulted Dr. Allan Kaplan into a lifetime of researching and treating individuals with eating disorders. Inspired by Dr. Paul Garfinkel, Dr. Kaplan transferred from Internal Medicine into Psychiatry during his first year of residency with the Royal College. “The rest was history,” says Dr. Kaplan. Many years later, Dr. Kaplan is now the Vice Dean of Graduate Academic Affairs and Professor of Psychiatry at the University of Toronto, as well as Senior Clinician Scientist at the Centre for Addiction and Mental Health. “Anorexia [nervosa] has been in the medical literature for at least 400-500 years. It’s been mislabeled through the course of history, but the core illness and symptoms have stood the test of time,” asserts Dr. Kaplan. Struck by the complexity of anorexia nervosa, Dr. Kaplan contemplated how the brain allows individuals to survive despite self-induced starvation. In 1995, Dr. Kaplan and colleagues were approached by Madame Price with an exciting proposition that shaped the “Price Study” during a scientific meeting in Switzerland. The relationship between anorexia nervosa and an underlying genetic process had yet to be established. With subsequent funding from Madame Price and the National Institute of Health, research of its genetics was made possible. The Eating Disorders Working Group of the Psychiatric Genomics Consortium conducted the first genome-wide association study (GWAS) of anorexia nervosa.1 This GWAS of 12 case-control cohorts, including 3 495 anorexia nervosa cases and 10 982

controls, identified a locus on chromosome 12 (rs4622308) as a common genetic variant associated with anorexia nervosa. Amy Miles, a Doctoral student under the supervision of Dr. Kaplan, investigated this further. Fat loss from the body is accompanied by fat loss from the brain— white matter architecture is disrupted because myelin in the brain is composed entirely of lipid molecules.2,3 Using diffusion tensor imaging (DTI), Miles analyzed the integrity of white matter in four groups of females: 1) underweight at time of imaging; 2) anorexia nervosa recoverees; 3) healthy siblings of individuals in the first group; and 4) unrelated healthy controls. Interestingly, abnormalities in white matter architecture were identified within all but the unrelated healthy controls. This result suggests permanent “scarring” in recoverees from anorexia nervosa and alludes to the inheritance of a genetic predisposition to anorexia nervosa in healthy sibling controls. “This is the first study to show that there are abnormalities in this group of healthy siblings…so what is inherited and what’s the impact of that?” asks Dr. Kaplan. Impaired cognitive functioning has reported in individuals diagnosed with anorexia nervosa. As a follow-up, Miles is employing neuropsychological tests to evaluate subjects’ cognitive function and explore the manifestation of this genetic predisposition.

Recognizing its neurobiology destigmatizes this eating disorder and prevents parents from assuming responsibility for its cause. Parents can become better equipped to combat the genetic risks by shaping the environment for their daughters. Encouraging kids to partake in activities that will enhance their self-esteem becomes essential. The next step in anorexia nervosa research is to identify which genes are responsible for these white matter abnormalities. With this knowledge, there is the potential to repurpose drugs for the management of anorexia nervosa. However, these large-scale studies cannot be conducted alone. Dr. Kaplan emphasizes the need for collaboration as he also works with groups around the world to receive DNA samples. He also reiterates several times during our interview that research is a long journey. Although faced with setbacks, the team persevered and found what they believe is irrefutable evidence signaling genetic risk for anorexia nervosa. “And we’re still not there, but we’re getting a lot closer,” says Dr. Kaplan.

1. Duncan L, Yilmaz Z, Gaspar H, et al. Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa. Am J Psychiatry. 2017;174(9):850-858. 2. Swayze VW, Andersen AE, Andreasen NC, et al. Brain tissue volume segmentation in patients with anorexia nervosa before and after weight normalization. Int J Eat Disord. 2003;33(1):33-44. 3. Travis KE, Golden NH, Feldman HM, et al. Abnormal white matter properties in adolescent girls with anorexia nervosa. Neuroimage Clin. 2015;9:648-659.

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STUDENT SPOTLIGHT

Taking a step out of the lab with Dr. Hemington: Making your years at IMS count By: Darby Lowe

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s a recent Institute of Medical Science (IMS) graduate, Dr. Kasey Hemington knows what it means to make her years at IMS count. In the Summer of 2018, Dr. Hemington defended her PhD thesis on the neural correlates of chronic pain based on her neuroimaging work out of Dr. Karen Davis’ lab at Toronto Western Hospital. Specifically, she investigated the differences between brain networks in individuals with and without chronic pain. During this time, she discovered that those with chronic pain exhibit different interactions in specific neural networks. When asked what interested her in this topic, Dr. Hemington pointed to the complexity of pain and how it involves a variety of brain networks and psychological constructs. Because of the complexity of the topic, she described how “the questions that you can ask about chronic pain never end.” Dr. Hemington’s curiosity and excitement about the unknown was not only exhibited in the lab, but also extended widely throughout the rest of her academic career.

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Early in her graduate career, Dr. Hemington joined the IMS Magazine team not knowing that she would eventually become one of the Editors-in-Chief a few years later. When she first began contributing to the magazine, her experience offered her insight into the vast scientific diversity that exists at IMS and it was what sparked her curiosity for the issues that existed beyond her scientific purview. She recounted how being a journalist for IMS Magazine and being able to interview various IMS members was, and remains to be, one of her favorite experiences: “It seems like a treat that you would get…the privilege to sit down with such amazing IMS faculty.” IMS Magazine provided Dr. Hemington a creative outlet to explore the art of science communication through writing and editing, as well as through her interactions with the Biomedical Communications team at the University of Toronto’s Mississauga campus. Moreover, her rewarding time as an Editor-in-Chief allowed her to understand the professional landscape of, and difficulties that exist in, communicating science.

Alongside her work with IMS Magazine, Dr. Hemington’s portfolio began to involve knowledge translation. “When you’re in grad school you get certain things out of being in the lab and you need to figure out what…to do to be a balanced person overall,” she remarked. Managing to strike a balance, Hemington’s extra-curricular involvement shined while she remained academically strong. She was a part of the organizing committee for the Annual Toronto Brain Bee, a neuroscience-based competition for high school students. She aided with a project together with fellow lab colleague, Rachel Bosma, that aimed to inspire translational pain research by encouraging clinician-scientist communication. Further exploring science communication, she was an associate editor for an e-book entitled “The Basic Science of Pain” written by Dr. Philip Peng. Dr. Hemington’s involvement in academia and the community demonstrate both her commendable initiative and the variety of opportunities available to students by the IMS. Currently, Dr. Hemington is working in data science, alongside initiatives to address the demands of


STUDENT SPOTLIGHT

Kasey Hemington, PhD Photo sent by Kasey Hemington

science communication. Working in science communication doesn’t seem like the most obvious next step for a PhD graduate who just finished her research in the field of chronic pain and neuroimaging. When asked about what influenced her decision to pursue the niche of science communication, Dr. Hemington expressed that “once you… establish your own brand in what you’re good at…you get more and more into that area.” She established a brand for herself in knowledge translation, ultimately driven by her interest in the artistic expression of science and the demand for this field in science. Despite the potential burden placed on a scientist, from conducting research to being one’s own public relations representative, she views science communication as an “important side of science and one that will continue to be more and more important.” With her collective experience, Dr. Hemington went on to co-create a platform called BrainPost that was launched this past January of 2018 with co-creator and previous IMS student, Leigh Christopher. BrainPost is an e-newsletter for both scientists and non-scientists alike that publishes online and distributes weekly summaries of

recent neuroscience articles. All content is reviewed by the original authors before circulation, ensuring the validity and consistency of the summaries. She describes how Christopher’s and her time as students at IMS, as well as her work as a writer and editor for the IMS Magazine, supported the skillsets and confidence that drove them to create something completely from scratch. They wondered: “Why can’t students just create what they feel there needs to be…in terms of science communication?” The blog was created due to frustrations with media representations of scientific studies that lack insight into the methods and limitations, while focusing heavily on firm conclusions. Additionally, as scientists, they were motivated by the difficulties in keeping up with science outside of their specific focuses, hoping that the blog would allow scientists of all domains to efficiently consume broader information. In general, BrainPost aims to communicate science in a digestible, yet truthful manner, as Dr. Hemington believes “the more you share that side of science with people–the complex environment from which these conclusions were made–the more that the public will trust science.” In closing the interview, I asked a typical question of someone early in their

post-graduate career: what advice would she give to those of us just starting our academic journey? Dr. Hemington revealed how graduate school allowed her to feel “very well equipped to handle anything in life.” Most importantly, she describes how graduate school teaches you resilience and perseverance which you will carry through the rest of life’s endeavors: “I don't know anyone else better at persevering than grad students.” In her opinion, graduate school “trains you with the mentality to push forward and be resilient and [know] that anything is possible.” Above all, she emphasizes that “no one has rushed their PhD in two years,” recommending that students take their time and enjoy the process of it all. If you are interested in learning more about BrainPost, you can visit their website at www.BrainPost.co, or their Twitter/ Faceook page @BrainPostCo. Additionally, as part of a current project inspired by BrainPost, Dr. Hemington is seeking contributions from students and scientists who would like to share their scientific expertise. If you are interested in sharing your expertise for her upcoming project, or with comments regarding BrainPost, please be in touch!

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FUTURE DIRECTIONS

PAUL KELLY Photo courtesy of TVASurg

By: Contessa Giontsis

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even years ago, Paul Kelly graduated from the Masters of Science in Biomedical Communications (MScBMC) program, at the University of Toronto. His studies have ended, but his involvement in BMC and IMS continue. He is currently a member of the BMC Alumni Association, and a strong advocate for the BMC program. “I always sell the Toronto program to anybody who asks”, he says. “They really do have a uniqueness amongst the other programs.” According to Kelly, not only does BMC have a diversity of skill sets and tools, but the professors are incredibly talented and modest with an “impressive non-stop commitment to learning.” Currently, Kelly is applying his 3D visualization and communication skills at The Toronto Video Atlas of Surgery (TVASurg). This team creates surgical educational videos that show proper surgical technique. Patient CT and MRI scans are used to build 3D reconstructions of gross anatomy, which are then compiled in a 3D animation. Despite the iterative design phase, Kelly enjoys every aspect of his work and has high hopes for the future. “Our goal is to expand the atlas from abdominal procedures to the entire

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human body.” Having recently collaborated with OB/GYN surgeons from St. Michael’s Hostpial, Mount Sinai Hospital, and Sunnybrook Health Sciences Centre, TVASurg is determined to achieve its goal and influence future surgical training. However, getting this far in his career was not easy. Surprisingly, Kelly struggled with surgical illustration in his first year at BMC. Having to repeatedly go back to the drawing board was a “shock to the system” he recalls. Unsatisfied with his performance, Kelly decided to take the advanced surgical illustration course in his second year and master this challenge. His determination paid off. Not only did he create a beautiful series of surgical illustrations, Kelly also learned how to handle setbacks: “I think it comes to a personal decision to say, ‘I am not going to take this as an indication that I am inept, but that I am in an environment where I have the best possible chance to improve.’ ” Kelly’s advice to IMS students is simple: “Find what you are passionate about”. He believes that sharing his passion and getting others to express theirs is important in maintaining a high level of excitement and productivity in research and in helping students find what it is that inspires them. In return, the IMS has provided Kelly with something invaluable—a sense

of community. “IMS has given me this connection to people who share similar ideas, thoughts, feelings and that is a great feeling.” Kelly strongly believes that BMC can help the IMS achieve its primary goal which is to help clinicians engage in excellent, cutting edge research. “There will always be a benefit for researchers to work with BMC grads to create visual assets,” he says, “because the world is more visual in the way people receive information.” If visuals can help researchers get the attention of the public or policy makers, it can take translational research to a new level. 50 years from now, Kelly is excited to see the IMS integrating with other disciplines: “It’s inevitable that there will be more interaction and more collaboration between different departments.” Kelly dreams of students in bioengineering, BMC, and medicine all working together on collaborative projects. “In my opinion, we could push research and translational research much further if we have multiple minds working together.” Considering how much the IMS has accomplished in their first 50 years of existence, one can only image what the IMS can achieve over the next 50 years.


TRAVEL BITES

Different Perspectives in

Photo credits: IMS Photography team

Canada’s Capital

By: Sumaya Dano

Canada’s capital is where the annual Canadian Society of Transplant (CST) conference took place this year, and it was beautiful for a great little get-away starting off with a scenic train ride by VIA rail. The conference was located at the Westin hotel, which was the perfect location to visit the Rideau Center and the parliament. The location of the conference was also ideal to explore downtown Ottawa, especially the famous ByWard market, which is one of the oldest public markets in Canada (and also where you can find delicious beaver tails!). It was interesting to see how bilingual the conference was, and how researchers were able to communicate with each other in English and French. Another fascinating aspect of the conference was the different perspectives and topics addressed compared to previous CST conferences. One new component of the conference I truly enjoyed was the emphasis on patient engagement. Patients from all over the world, including a heart-transplant recipient from England, who came to the conference to present their perspectives on transplant, and share their experiences and challenges. Along with presentations about kidney allocation and optimizing post-transplant outcomes, a few presentations also addressed the barriers facing patients towards transplantation. Transplant recipients and their family members shared insightful aspects about the financial barriers in becoming a living donor for transplantation. One particularly interesting story was from a kidney transplant donor from Quebec. She described the tedious process that was involved in becoming a living donor candidate and how she was lucky to work at a company that was supportive of her life adjustments. She was finally deemed as a match for her son and donated her kidney. However, despite the minimal health risks of

donating a kidney, she mentioned that her life insurance rates increased significantly. People generally are able to live healthy lives with one kidney, but the donor’s insurance did not reflect the numerous studies that suggest no significant negative outcomes of kidney donation. The insurance issue raised after kidney donation was an interesting aspect I did not realize also played a role in the overall financial burden to becoming a donor. Such experiences and stories are not things I would necessarily think of when it comes to the outcomes and impacts of kidney transplantation, which made the guest speaker’s talks all the more thought-provoking. During the oral presentations it was great to see the diversity in transplantation research including research conducted on different organs. However, there were also posters that had more clinical themes and others that focused on the psychosocial aspects. After speaking to a few presenters at the conference, they mentioned how mental health and other psychological themes have become increasingly present in these conferences, which is another important perspective that was incorporated in this meeting this year. This year’s CST conference was a great trip to Ottawa and an excellent opportunity to network and be exposed to different ideas. Not only did the conference give me the opportunity to speak to people who were doing similar research as myself, but it also enabled me to hear from transplant recipients and learn about what their priorities and perspectives in transplant. This was very interesting, because after all, the ultimate goal of the research we do is to improve the quality of life of these patients. I was also able to hear from researchers who are working on projects related to transplantation beyond my research area. CST was a great experience in Ottawa, giving me the opportunity to share my research and contribute to all the different perspectives addressed in CST.

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PAST EVENTS platform for cell proliferation. Dr. Shoichet retold the journey from the initial discovery in the lab to the development of her own company, AmacaThera, dedicated to developing and commercializing injectable hydrogel for a wide range of medical applications. This demonstration of taking a laboratory finding to a wider audience is a perfect example of the translational research that the lecture series showcases. Dr. Shoichet explained that previous experiments have shown that the hydrogel can deliver neuronal stem and progenitor cells (NSCs) to the retina in an animal model of blindness. HAMC had improved survival and integration of transplanted NSCs leading to improved visual function. Dr. Shoichet’s delivery method could solve the transplantation problem that has hindered stem cell research since its inception.

IMS 50 Ori Rotstein Lecture in

Translational Research By: Jason Lo

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n October 4th, 2018, the Institute of Medical Science (IMS) held its eighth annual Ori Rotstein Lecture in Translational Research, showcasing current research and innovation in areas of surgery and translational medicine. The lecture is named in honour of Dr. Rotstein, who served as IMS Director from 2001— 2011, helping to shape the IMS into the success that it is today. Dr. Mingyao Liu, current Director of IMS, was the first speaker to arrive on stage. With this being the final event celebrating 50th anniversary of the IMS, Dr. Liu recounted all the events that took place this past year including IMS50 editions of Scientific Day and Student Undergraduate Research Program Research Day, an international conference, and a 50th anniversary gala. Dr. Liu highlighted that the department is second in the world for publishing research papers, giving the young

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scientists in the crowd another reason to be proud of where they stood that day. Just as Dr. Liu was finishing his last sentence, keynote speaker Dr. Molly Shoichet rushed through the door, fresh from the airport, and took to the stage. Dr. Shoichet was the first Chief Scientific Officer of Ontario and holds the Tier 1 Canada Research Chair in Tissue Engineering, as well as a full professorship at the University of Toronto. She has also been honoured with the Order of Ontario and the Queen Elizabeth II Diamond Jubilee Award for her innovative contributions. Students marveled at all that could be accomplished within a lifetime. Dr. Shoichet’s speech, Harnessing the Power of Stem Cells to Repair the Central Nervous System focused on her team’s development of the hyaluronan and methylcellulose (HAMC) based injectable hydrogel—designed to be fast gelling, HAMC is an ideal vehicle for uniform stem cell delivery and a supporting

After the riveting keynote speech, Dr. Rotstein led a panel discussion entitled Science and Society in the Media with panelists Dr. Ana Andrezza (Assistant Professor, Departments of Pharmacology & Toxicology and Psychiatry, CAMH), Dr. Andreas Laupacis (Professor, Department of Medicine, Li Ka Shing Knowledge Institute), Dr. Andy Smith (President and CEO of Sunnybrook Health Sciences Centre), Dr. Jim Woodgett (Professor, Department of Medical Biophysics, Lunenfeld-Tanenbaum Research Institute), and keynote speaker Dr. Molly Shoichet. Combatting poor scientific reporting is a pressing issue in today’s society, and Dr. Smith emphasized that scientists should develop their scientific reporting skills in their respective fields. Dr. Woodgett also encouraged the young scientists in the room to develop fact-based arguments. The panel exuded a sentiment of empowerment for students to not shy away from the media and an audience. With that came the end of the special 50th edition of the Ori Rotstein Lecture and the 50th anniversary celebrations. The innovative hardwork and insight of the panelists and keynote speaker reminded all in attendance of the difference they can make. To be part of such a thriving department is a privilege—here’s to 50 more years of the IMS.


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Photos by Nathan Chan

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