Winter 2024: Complimentary Therapies and Alternative Medicine

THINK. LEARN. DISCOVER.

Winter 2024

Complementary Therapies and Alternative Medicine

The Complexities of Mood Disorders

“Is this a Real Treatment?”

Feature on Dr. Husain

The Placebo Conundrum

Alumni Spotlight: Dr. Tyler’s Journey to Leadership in Public Health

Student-led initiative

IMSSA POSTER

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IN THIS ISSUE Letter from the Editors................................... 4 Director’s Message........................................ 5 Contributors................................................... 6 Infographic..................................................... 8 Features....................................................... 10 BMC Showcase............................................ 18 Viewpoints................................................... 20 Faculty Highlights........................................ 30 Alumni Spotlight.......................................... 32 Travel Bite.................................................... 34 TV Commentary............................................ 35 Diversity in Science..................................... 36 IMS Events................................................... 38

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MAGAZINE STAFF EDITORS-IN-CHIEF: Kyla Trkulja Iciar Iturmendi Sabater EXECUTIVE DIRECTORS: Janet Li Kristen Ashworth Elizabeth Karvasarski Niki Akbarian Mahbod Ebrahimi PHOTOGRAPHERS: Niki Akbarian (Director) DESIGN EDITORS: Jayne Leggatt (Director) Josephine Choi Genevieve Groulx Brendan Lazar Andrew Janeczek Anne McGrath

SOCIAL MEDIA TEAM: Elizabeth Karvasarski (Director) Lizabeth Teshler JOURNALISTS & EDITORS: Kevan Clifford Sipan Haikazian Kiko Huang Vanessa Ip Alyona Ivanova Nikou Kelardashti Lauren Levy Carmen Li ​Suraiya Mangra Karan Patel Anthaea-Grace Patricia Dennis Samantha Ricardo Denise Sabac Sara Shariati Megana Thamilselvan Rachel Yang

FEATURE INFOGRAPHIC

By Andrew Janeczek, MScBMC Candidate (2T4)

Copyright © 2023 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 Brendan Lazar, MScBMC Candidate (2T4) FOLLOW US ON SOCIAL MEDIA! www.imsmagazine.com @IMSMagazine @IMSMagazine IMS MAGAZINE WINTER 2024 NON-TRADITIONAL THERAPIES |

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LETTER FROM THE EDITORS

Letter from the

EDITORS

To illuminate the long nights of a Toronto winter, this issue of the IMS Magazine shines a light over a topic that also tends to lay in the shadows of medical science research: non-traditional approaches to medicine.

In this issue, we highlight the research conducted by Dr. Rosenblat, Dr. Husain, Dr. Goldstein and Dr. Lin. They investigate the potential of alternative psychotherapeutic approaches involving cardio-vascular exercise, nitrous-oxide, anti-inflammatory drugs, ketamine, psilocybin, and nabilone administration to improve mood disorder symptomatology across psychiatric disorders, including bipolar disorder, autism, and attention-deficit/hyperactivity disorder. The Viewpoints in this issue continue the discussion on the psychotherapeutic potential of psychedelics as well as mindfulness, reflect about placebo effects, and provide a critique on the scientific publication process. For the first time, we include a commentary on a TV show, Painkiller, and we highlight specific contributions made by women to science in the Diversity in Science piece. Last but not least, one of our writers tells us about their trip to Lille to attend the 16th International Mesothelioma Interest Group annual meeting.

We thank the returning members of the IMS Magazine team, and are especially grateful to all new student writers, copy-editors, and designers who joined our team in September. We hope that this issue will provide you with a warm and interesting read during the dark hours of winter.

Kyla Trkulja

Iciar Iturmendi Sabater

Kyla is a PhD student studying the mechanism of action of novel therapies for lymphoma under the supervision of Dr. Armand Keating, Dr. John Kuruvilla, and Dr. Rob Laister.

Iciar is a PhD student under the supervision of Dr. Meng-Chuan Lai and Dr.Hsiang-Yuan Lin. She investigates social adaptive behaviors in children and adolescents with neurodevelopmental conditions such as autism, attention-deficit hyperactivity disorder, and obsessive-compulsive disorder.

@kylatrkulja

@iciar_itur

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DIRECTOR’S MESSAGE Photo Credit: Mikaeel Valli

F

or the first time in several years, we have been able to reflect on the year behind us and appreciate how balanced it has been. Most remaining COVID-19 restrictions were lifted, and we were able to gather with family, friends, and colleagues without feeling overwhelming anxiety. As we look forward to 2024, I am hopeful that the new year will offer even more opportunities for growth and prosperity, within and beyond health.

DR. MINGYAO LIU Director, Institute of Medical Science Professor, Department of Surgery Senior Scientist, Toronto General Hospital Research Institute, University Health Network

Well-being takes many forms, so it is fitting that the Winter 2024 issue of the IMS Magazine highlights advances in Complementary Therapies and Alternative Medicine.

This issue features faculty that are thinking of innovative, creative solutions to health and disease in order to fill unmet needs from traditional treatments. Dr. Joshua Rosenblat and his team are investigating how to effectively use ketamine to improve the lives of patients with treatment-resistant depression and bipolar disorder. We also hear from Dr. Ishrat Husain, who is studying how to use the psychedelic psylocibin for treatmentresistant depression and how to approach using this therapy in settings where patients have comorbid conditions or come from a low-income country where treatment specialists may not be readily available. Dr. Benjamin Goldstein has taken his knowledge of the connection between the vascular system and mental illness to investigate the use of exercise therapy to treat adolescents with bipolar disorder. Lastly, we hear from Dr. Hsiang-Yuan Lin, who is studying numerous alternative approaches to treating developmental disorders such as attention-deficit hyperactivity disorder (ADHD) and autism, including psychedelics and repetitive transcranial magnetic stimulation.

In-line with the theme of unique and alternative opportunities, this issue also puts the spotlight on Dr. Andrea Tyler, an IMS alumnus and current Chief of Computational Biology at Canada’s National Microbiology Laboratory. Dr. Tyler shares how her education provided her with the skills needed to work in the public health sector, where she studies the genetic composition of pathogens to understand their mechanisms of action. We also welcomed our new IMS students this Fall at our Orientation, and this issue shares the highlights of the event.

I would like to thank the IMS Magazine’s new Editors-in-Chief, Kyla and Iciar, for their work directing this issue – hopefully their first of many. As always, I also extend my sincere appreciation to the journalists, editors, photographers, and design team for their contributions to this Winter 2024 issue. I hope you enjoy reading about the exciting advancements in alternative medicine, and that the hope associated with these therapies brings forth a sense of optimism to start the New Year.

Sincerely, Dr. Mingyao Liu Director, Institute of Medical Science

IMS MAGAZINE WINTER 2024 NON-TRADITIONAL THERAPIES |

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CONTRIBUTORS

Contributors Winter 2024

Kristen Ashworth is an MSc student working under the supervision of Dr. Brian Ballios at the Donald K. Johnson Eye Institute and Krembil Research Institute. Her thesis work is focused on developing a retinal organoid model in which to evaluate stem cell therapies for USH2A- and CRB1-related inherited retinal diseases. Kristen loves cross country running, reading a good book, going to Marshalls, and most importantly, doting on her two adorable golden retrievers.

Niki Akbarian is a second-year MSc student under the supervision of Dr. James Kennedy. Her research focuses on the genomic analyses of the relationship between neuroticism and Alzheimer’s Disease. Outside of academia, Niki enjoys photography, playing the piano, and watching sitcoms.

Stacey Butler is a PhD candidate. Under the supervision of Dr. Andrea Gershon, she is evaluating the quality of care for patients with respiratory disease using a population-based approach.

Kevan Clifford is a PhD candidate in the IMS program, with a crossappointment at the Centre for Addiction and Mental Health. Working under the supervision of Dr. Yuliya Nikolova, his research combines bioinformatics and neuroimaging to characterize mechanisms of brain aging at the genetic level, and outcomes on brain structure and function.

Outside of the lab, Kevan enjoys trail running, photography, and a good book.

Mahbod Ebrahimi is a second-year MSc student investigating the association between immune gene expression and schizophrenia subphenotypes under the supervison of Dr. James Kennedy. Outside of research, Mahbod enjoys a good book, playing chess, and listening to Jazz music. Mahbod is also a member of our social media team.

Sipan Haikazian is a second-year MSc student researching the efficacy and safety of maintenance ketamine infusions for relapse prevention in patients with treatment-resistant bipolar depression, under the supervision of Dr. Joshua Rosenblat. Outside of research, Sipan enjoys running, weightlifting and dancing bachata.

StaceyJButler

sipan_haikazian

mahbooli99 Nikou Kelardashti is a second-year MSc student under the supervision of Dr. Karen Davis. Her research focuses on the relationship between neural oscillations and pain-attention interaction. Outside of academia, Nikou enjoys reading poetry and classic literature, watching old movies, and going for long walks.

Carmen Li recently completed her MSc in oral immunotherapy clinical trials for children with food allergies under the supervision of Dr. Thomas Eiwegger and Dr. Theo Moraes at Sickkids Hospital.

When not researching, you can usually spot Carmen in coffee shops, picking out new novels and trying out new baking recipes. ccarmen_li

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CONTRIBUTORS Janet Z. Li is a second-year MSc student studying the brain-behavior relationships between conditioned pain modulation capability and functional connectivity of key pathways within the dynamic pain connectome, namely the descending antinociceptive pathway. She is supervised by Dr. Karen Davis at the Krembil Brain Institute in Toronto Western Hospital. Outside of research, she can be found practicing piano, figure skating, creating fashion content, and café hopping.

jan.et.li

sarashariati_

sarashariati_

Jason Lo Hog Tian is a PhD candidate examining the mechanisms linking HIV stigma and health under the supervision of Dr. Sean Rourke.

JasonLoHogTian

Anthaea-Grace Patricia Dennis is a firstyear MSc student studying machine learning techniques in biomarker discovery for Parkinson’s disease under the supervision of Dr. Antonio Strafella at Toronto Western Hospital. When not researching, AnthaeaGrace Patricia enjoys playing the violin, taking care of her cats, and reading a good book.

Denise Sabac is a second-year MSc student working with Dr. Felsky in the Krembil Centre for Neuroinformatics at CAMH. Her work aims to subtype mental illnesses in treatment-seeking youth using Similarity Network Fusion analysis of the Toronto Adolescent & Youth CAMH Cohort Study data. Aside from research, Denise enjoys playing sports, walking along sandy beaches, and drinking lots of coffee.

Sara Shariati is a second-year MSc student, investigating gene expression changes in mesothelioma patients post-radiotherapy under the supervision of Dr. Marc de Perrot at Toronto General Hospital. Outside of research, she enjoys swimming, cafe hopping, writing, and reading about sociology.

Rachel Yang is a first-year MSc student studying the capability of a nanoparticle for precise tumor magnetic resonance imaging and its potential to reduce hypoxia to complement radiotherapy. She is conducting her research under the supervision of Dr. Michael Milosevic at the Princess Margaret Cancer Research Tower. In her spare time, she takes pleasure in taking walks, running outdoors, playing songs on the piano, and engaging in spontaneous activities.

sarashariati_

IMS Design Team The IMS Design Team is a group of second year MSc students in the

Social Media Team Elizabeth Karvasarki (Lead) is a PhD IMS at Mount Sinai Catheterization Laboratory under the supervision of Dr. Susanna Mak. Her research involves investigating right ventricular and pulmonary arterial interactions in patients with pulmonary hypertension and heart failure. Outside of research, Elizabeth practices martial arts and is a 4th degree black belt.

Biomedical Communications (BMC) program. Turning scientific research into compelling and effective visualisations is their shared passion, and they are thrilled to contribute to the IMS Magazine.

Jayne Leggatt (Director) jleggatt_visuals jayneleggatt.com

Genevieve Groulx eve.groulx evegroulx.com

Josephine Choi yeon_jo.art jochoi.ca

Andrew Janeczek janeczekandrew

Brendan Lazar brendan_lazar brendanlazar.ca

Anne McGrath stellalunaa__ annecmgrath.com

Copy Editors Kiko Huang Vanessa Ip Alyona Ivanova Lauren Levy ​Suraiya Mangra Karan Patel Samantha Ricardo Megana Thamilselvan IMS MAGAZINE WINTER 2024 NON-TRADITIONAL THERAPIES |

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INFOGRAPHIC

The Low-Down On

Complementary Therapies and Alternative Medicines What are they?1,2 Complementary and alternative medicine (CAM) encompasses a group of non-conventional medical products and practices that aim to safely and effectively attenuate pain and disease in tandem or in place of traditional medical treatment.

CAMs are typically classified based on their therapeutic potential and outcome1:

Complementary medicine is typically used in complement with traditional allopathic medical treatment, whereas alternative medicine is used in place of conventional care.

What are probiotics?3

TR NU

I T I ONAL

AL

Complementary exercise and diet plans

Meditation Psychotherapy Music therapy

What is meditation?2 Practice of mentally concentrating on mental and physical feelings of calm in the present moment.

Allowing mental focus to be bodily sensations to create a sense of personal mindfulness and restfulness.

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Yoga Dance Tai Chi

Acupuncture Massage Chiropractic care

L

P S YC H

I CA

OL

Mindful eating

YS

OG

C

PH

I

Probiotics and prebiotics Phytochemicals Herbal medicines Vitamins and minerals

Foods and supplements containing live microorganisms that can benefit the gut microbiome and provide other systemic health benefits.

What is acupuncture?2 From traditional Chinese medicine.

Using a fine-point needle on targeted areas of the body, called ‘acupuncture points’.

Offers potential pain- and tensionrelieving effects, by stimulating nerves and muscles and helping to induce the release of pain-relieving hormones.

Compiled by Kristen Ashworth

L DRUG ABE L -

Psychedelics as a CAMs Treatment for Mental Health4

E US

OF F

INFOGRAPHIC

What are psychedelics?

• Psychedelics are a class of psychoactive substances that induce altered states of consciousness, perception, and mood

Types of psychedelics: • Lysergic acid diethylamide (LSD): synthetic chemical made from ergot, a fungus that commonly grows on rye.

• Psilocybin: naturally occurring psychedelic compound found in certain mushrooms (“magic mushrooms”).

• Mescaline: naturally derived hallucinogen from various cactus species, such as peyote and San Pedro cacti.

• Ayahuasca: made from the Banisteriopsis caapi vine and other plant additives, it is a brown-reddish drink traditionally used in Amazonian indigenous rituals for its psychedelic effects.

How do psychedelics work in the brain?

• Psychedelics primarily exert their effects by interacting with serotonin receptors in the brain, particularly the 5-HT2A receptor • This interaction leads to altered perception, mood, and cognition • The ‘psychedelic experience’ is thought to result from the modulation of serotonin levels and patterns of neural activity in key brain regions involved in perception and mood regulation • Research suggests their potential in alleviating symptoms when used in controlled settings under professional supervision

What diseases can CAMs be used for?6 Cancer

Autoimmune diseases Digestive disorders Vision conditions

Meditation to improve well-being in those undergoing chemotherapy

Acupuncture to manage pain in conditions such as lupus and rheumatoid arthritis

Chronic pain

Chiropractic care to manage pain in conditions such as arthritis, back pain and fibromyalgia

Mental health disorders

Psychedelic medication to help treat conditions such as bipolar disorder, depression and attention deficit hyperactive disorder

Neurological disorders

Mind-body practices and yoga to help alleviate symptoms in conditions such as Parkinson’s disease, migraine, and multiple sclerosis

Probiotics to help treat gastrointestinal conditions such as IBS

Virtual reality (VR) vision stimulation and training to improve sight f or those with agerelated macular degeneration

References 1. Complementary, alternative, or Integrative Health: What’s in a name? [Internet]. U.S. Department of Health and Human Services; 2021 [cited 2023 Nov 13]. Available from: https://www.nccih.nih.gov/health/complementaryalternative-or-integrative-health-whats-in-a-name 2. Tabish SA. Complementary and Alternative Healthcare: Is it Evidence-based? International journal of health sciences. 2008 Jan;2(1).

3. Zeratsky K. Probiotics and Prebiotics: What you should know [Internet]. Mayo Foundation for Medical Education and Research; 2022 [cited 2023 Nov 13]. Available from: https://www.mayoclinic.org/healthy-lifestyle/ nutritionand-healthy-eating/expert-answers/probiotics/faq-20058065 4. Psychedelics [Internet]. 2023 [cited 2023 Nov 13]. Available from: https://adf.org.au/drug-facts/psychedelics/ 5. Tupper KW, Wood E, Yensen R, Johnson MW. Psychedelic medicine: A re-emerging therapeutic paradigm. Canadian Medical Association Journal. 2015 Oct 6;187(14):1054–9. doi:10.1503/cmaj.141124 6. Prize R. The 10 most commonly used CAM therapies and conditions [Internet]. 2018 [cited 2023 Nov 13]. Available from: https://www.drrogersprize.org/most-used-cam-therapies-and-conditions/

Graphic design by Andrew Janeczek

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FEATURE

The Potential of Ketamine in Mood Disorders An Interview with Dr. Joshua Rosenblat

By Sipan Haikazian

M

ajor depressive disorder (MDD) and bipolar disorder (BD) are mood disorders that affect around 5% and 1% of the Canadian population, respectively.1 Individuals with both illnesses endure low mood, lack of interest in previously enjoyed activities, poor concentration, changes in essential functioning including sleep and appetite, and sometimes, suicidal thoughts.

These symptoms must occur for at least two weeks at a time, although it is very common for these symptoms to persist for months.1 Individuals with BD also experience bouts of mania or hypomania: increased energy, greatly increased interest in activities, and a higher propensity to engage in risky behaviours.2 Dr. Joshua Rosenblat, a psychiatrist and researcher working for the Mood Disorder Psychopharmacology Unit (MDPU) at Toronto Western Hospital, sees and treats patients with these bouts of mental illness every day. In his practice, he often treats patients with particularly severe cases. While a wide variety of treatments exist for treating the depressive episodes, around 33% of patients diagnosed with either MDD or BD fail two full courses of antidepressant treatments, subsequently resulting in a classification of treatmentresistant depression.⁴ Dr. Rosenblat’s passion for patient mental health was founded during his rotations as a medical student at the University of Western Ontario. He participated in a rotation at the MDPU under the

mentorship of Dr. Roger McIntyre, a world-renowned clinician-scientist specializing in mood disorders. Fast forward 10 years, he now finds himself practicing in the same department where his clinical interests were first sparked. Dr. Rosenblat reflected on his career trajectory, stating: “I think what really drew me into psychiatry and field of mood disorders were that the biggest breakthroughs are still yet to come. Combining this notion with my passion for research pushed me towards the career choice”.

Indeed, many alternative treatments exist for treatment-resistant depression, including a multi-purpose drug called ketamine. Originally used as an anesthetic during the Vietnam War, ketamine was re-purposed in the 21st century as an antidepressant agent. While many antidepressant drugs target the monoamine neurotransmitter system in the brain (serotonin, dopamine, and norepinephrine), ketamine is unique for targeting the glutamate system.⁴ Multiple clinical trials have demonstrated that ketamine can rapidly reduce depressive symptoms in patients with treatmentresistant variants of both disorders, the fast-acting trait being unique among traditional treatment for depression.⁵ The drug is also well-tolerated: while ketamine does often increase blood pressure, heart rate, and feelings of dissociation, these effects are transient, with symptoms resolving within hours.⁵ Importantly, documented cases of patients transitioning from a depressed to manic state are

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exceedingly rare.⁵ In recent years, both the Food and Drug Administration (FDA) and Health Canada have approved intranasal esketamine (a form of ketamine) for use in treatment-resistant MDD (TRD).

As a medical student working in the MDPU, Dr. Rosenblat started investigating the role of inflammation in mood disorders. He describes his motivation to eventually start studying alternative treatments to MDD and BD: “After a few years of research, I found that I wanted to be on the frontier of novel treatments in mood disorders, studying and becoming an expert in the efficacy of high-impact therapy”. His graduate thesis, completed while he was in residency, focused on the efficacy of intranasal ketamine for treating depression in patients with cancer receiving end-of-life care. Since establishing his research lab at the MDPU, he has led and co-led a number of clinical trials using ketamine as an intervention, as outlined below:

Repeated Ketamine Infusions for Treatment-Resistant BD (KET-BD): A randomized, double-blind, placebocontrolled clinical trial where participants with Treatment-Resistant BD are randomized to receive four infusions over two weeks of either intravenous ketamine or a placebo known as midazolam.

The primary outcome is the change in depressive ratings after the four infusions.

FEATURE

internet-based cognitive behavioural therapy (CBT) in conjunction with six sub-anesthetic doses of intravenously administered ketamine on suicidality in TRD.

Ketamine Versus Electroconvulsive Therapy in Depression (KET-ECT):

Dr. Joshua D. Rosenblat Clinician-Scientist at the Mood Disorders Psychopharmacology Unit of Toronto Western Hospital Photo Credit: Dr. Rosenblat

Maintenance Ketamine Infusions for Treatment-Resistant BD (KETBD-SUSTAIN): An open-label, 12-week, follow-up clinical trial where participants who showed significantly decreased depressive ratings in the KET-BD trial receive up to 6 booster infusions of ketamine on a bi-weekly basis. The primary outcome is the change in depressive ratings over the 12-week time period.

Ketamine and Internet-based Cognitive Behavioural Therapy for TreatmentResistant Depression (KET-CBT): A 13-week randomized controlled clinical trial investigating the effects of Graphic design by Jo Choi

A multi-site clinical trial where patients with TRD are randomized to receive either electroconvulsive therapy or ketamine infusions. A plethora of clinical, neuroimaging, molecular, and cognitive assessments is conducted throughout the study.

Each project has a critical knowledge gap that Dr. Rosenblat is looking to address.

KET-BD and KET-BD-SUSTAIN aim to determine the short and long-term efficacy, respectively, of ketamine in treatment-resistant BD. The third trial, KET-ECT, aims to determine whether CBT could concurrently extend the antidepressant and anti-suicidal effects observed post-ketamine infusion. Dr. Rosenblat is especially interested in the investigation on the anti-suicidal effects of the trial, as patients participating in the trial will be actively suicidal and are thus in most urgent need for treatment.

Finally, KET-ECT aims to determine the comparative efficacy of two alternative treatments (ketamine vs ECT) used in moderate-severe TRD. These clinical trials will prove useful

in answering specific questions about ketamine’s antidepressant efficacy. “I think the most important question about our field is how best to optimize the use of ketamine in routine clinical practice”, Dr. Roesnblat explains. “Currently, ketamine is used as a last line of defence against depression, but the data is showing improvements with large effect sizes, so we need to determine what role ketamine plays in the treatment algorithm. What dosing and scheduling is optimal for this drug, and which patients would find the most efficacy in using this drug?”

Dr. Rosenblat is also beginning to roll out clinical trials focused on the efficacy of psilocybin in mood disorders, a novel intervention that holds much promise in the treatment of depression. With several large grants and an ever-growing research lab, Dr. Rosenblat strives to continue improving the treatment that patients with mood disorders receive through his rigorous research program and thoughtfully planned portfolio of studies.

References 1. Spijker J, De Graaf R, Bijl RV, et al. Duration of major depressive episodes in the general population: Results from the Netherlands Mental Health Survey and Incidence Study (NEMESIS). Br J Psychiatry. 2002 Sep;181(3):208–13.

2. McIntyre RS, Berk M, Brietzke E, et al. Bipolar disorders. Lancet.

2020 Dec 5;396(10265):1841–56.

3. Hidalgo-Mazzei D, Berk M, Cipriani A, et al. Treatment-resistant and multi-therapy-resistant criteria for bipolar depression: consensus definition. Br J Psychiatry. 2019 Jan;214(1):27–35.

4. Li L, Vlisides PE. Ketamine: 50 Years of Modulating the Mind. Front Hum Neurosci [Internet]. 2016 Nov 29 [cited 2023 Oct 31];10.

Available from: http://journal.frontiersin.org/article/10.3389/fnhum.2016.00612/full 5. Fancy F, Haikazian S, Johnson DE, et al. Ketamine for bipolar depression: an updated systematic review. Therapeutic Advances in Psychopharmacology. 2023 Jan;13:20451253231202724.

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FEATURE

An Innovative Journey to Navigating the Complexities of Mood Disorders

By Nikou Kelardashti

I

n the realm of psychiatry and mental health, the search for innovative approaches to improve the lives of individuals grappling with mood disorders has been an ongoing quest. Currently in Canada, 1 in 5 individuals experience a mental illness each year.1 While there are treatments available for individuals afflicted by these disorders, a significant proportion of patients do not respond well to conventional medications, or they experience adverse side-effects.2 For instance, conventional antidepressants often have delayed onset of response and low rates of remission.2 Therefore, there is an urgent need for new, fast-acting, efficient, and enduring medications for psychiatric disorders.

Dr. Ishrat Husain—Associate Professor of Psychiatry at the University of Toronto, Lead of the Mood Disorders Service, and Head of the Clinical Trials Unit at the Centre for Addiction and Mental Health (CAMH)— is a pioneering Clinician-Scientist at the forefront of research in the field. Dr. Husain is dedicated to discovering innovative treatments for mood disorders, with the overall aim of improving outcomes across diverse populations and settings.

“During my clinical training as a resident, I was astounded by the number of patients that weren’t getting better with the treatments that we had currently to offer— particularly for patients with depressive illness, whether that’s a bipolar or unipolar depression,” Dr. Husain shared. This observation ignited Dr. Husain’s passion for

exploring innovative approaches to treat these disorders, initiating the development of novel clinical trials.

Early in his career, Dr. Husain embarked on an investigation of inflammation as a potential treatment target for mood disorders. This decision was informed by evidence that a subgroup of individuals with depressive illness have an overactive inflammatory response system. Therefore, repurposing anti-inflammatory agents seemed to be a promising avenue for individuals with persistent depressive symptoms. For his doctoral research, Dr. Husain led one of the largest trials to date on repurposed anti-inflammatory agents and mood disorders. In this study, they assessed the use of minocycline and celecoxib, two anti-inflammatory drugs, as adjunct treatments for bipolar depression.3 Although their research did not show significant effects of the drugs, it did provide Dr. Husain with valuable experience in designing and leading clinical trials.

While Dr. Husain and his team were completing this trial, researchers at Imperial College London published preliminary evidence in 2016 for the safety and efficacy of psilocybin.2 Psilocybin is a serotonin receptor agonist that occurs naturally in psilocybe mushroom species, and this paper showed its promise in the treatment of treatment-resistant depression (TRD). “I was blown away by the large and sustained anti-depressant effect sizes that psilocybin therapy appeared to show,” Dr. Husain exclaimed. “I was fascinated by the potential

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of psilocybin therapy for mood disorders.”

In a Phase II international trial of psilocybin, CAMH served as the Canadian research site, with Dr. Husain leading the research team. The study assessed three psilocybin doses—25 mg, 10 mg, 1 mg (control)—which were administered alongside psychological support. The findings indicated that the 25 mg dose was significantly more effective than the lower doses in alleviating symptoms of depression, with participants in the 25 mg group achieving higher rates of response and remission.4 Through this clinical trial, Dr. Husain gained insight into the intricacies of conducting clinical trials involving psychedelic drugs.

This experience provided him with a first-hand view of the positive aspects of this treatment approach. That being said, Dr. Husain also emphasizes that mental illnesses, particularly depression, show caseby-case variation in their causes. Therefore, a more nuanced approach is needed to explore various methods of treating these conditions. “I think that if we are focused on one singular therapy that is going to help all people with treatment-resistant depression, we are setting ourselves up for failure, so we need to look at different approaches,” Dr. Husain explains. “Psychedelic therapy is interesting as it combines biological with psychological, as the drug is given alongside psychological support.”

Recognizing the importance of incorporating diverse approaches in the Graphic design by Anne Mcgrath

FEATURE

Dr. Ishrat Husain pictured in the tranquil ambiance of the psychedelic therapy room at the Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health.

Photo Credit: Niki Akbarian

treatment of depressive illnesses, Dr. Husain’s research aims to address the issue more comprehensively. This includes assessing the efficacy of repurposed drugs and exploring scalable psychological interventions that can be applied across different populations. For example, a substantial segment of his research program is being conducted in low- and middle-income countries, where his team is examining the effectiveness of psychological interventions delivered by non-specialists for treatment of bipolar and depressive disorders.

Another complexity associated with depressive mental disorders is their frequent co-occurrence with other conditions. Consequently, Dr. Husain’s

team is engaged in various clinical trials exploring the effectiveness of psilocybin in the context of comorbid conditions, such as TRD in autism, TRD in obsessivecompulsive disorder, and TRD in chronic pain. Moreover, continuing investigations aim to uncover the mechanism of action of psilocybin and understand the nuances involved in psilocybin therapy. Dr. Husain has pursued this goal by using Positron Emission Tomography (PET) imaging before and after psilocybin therapy to investigate synaptic density as a potential pathophysiological model. Nevertheless, the mechanism of action of psilocybin remains the subject of ongoing investigation.

As a leading expert in clinical trials, Dr. Husain points out that despite clear advancements in the design of clinical trials, there remain certain limitations that need to be addressed. These include ensuring effective blinding and conducting comprehensive assessments of blinding. Additionally, researchers should consider pre-treatment expectancy as a potential moderator of outcome that should be monitored. Moreover, it is crucial for researchers to ensure that their study samples are heterogeneous with respect to gender, sex, and ethnicity to enhance the generalizability of results to the broader population.

As for raising awareness among the general population, Dr. Husain emphasizes, “[psychedelic therapy] is still very experimental, and although it is a promising area of research, the public should be made

aware that a lot of the findings that they are reading about are from studies involving highly selected groups of people in a very controlled setting, with a lot of support and oversight.” He further notes that “selfmedication is unsafe and can lead to serious safety issues.”

Lastly, Clinician-Scientists like Dr. Husain, committed to improving their patient’s well-being, provide a more optimistic perspective for the field of psychiatry. Dr. Husain elucidates, “my research is always clinically informed. It should be a bilateral relation between clinicians and researchers.

Without any sort of clinical context, how are we going to know what is important to our patients and what outcomes they are looking for?” By nurturing this collaboration between clinicians and researchers, the field of psychiatry can continue to evolve and take innovative, meaningful strides toward improving the lives of individuals grappling with mental health challenges.

References 1. Centre for addiction and Mental Health. Mental Illness and Addiction: Facts and Statistics. CAMH. 2020. https://www.camh.ca/en/ driving-change/the-crisis-is-real/mental-health-statistics 2. Carhart-Harris, RL, Bolstridge M, Rucker J, et al. Psilocybin with Psychological Support for Treatment-Resistant Depression: An Open-Label Feasibility Study. The Lancet Psychiatry, 2016;3(7):61927.

3. Husain, MI, Chaudhry IB, Khoso AB, et al. Minocycline and Celecoxib as Adjunctive Treatments for Bipolar Depression: A Multicentre, Factorial Design Randomised Controlled Trial. The Lancet Psychiatry, 2020;7(6):515-27.

4. Goodwin, GM, Aaronson ST, Alvarez O., et al. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine, 2022;387(18):1637-48.

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FEATURE VIEWPOINT

Novel Perspectives and Treatment Interventions for Bipolar Disorder in Youth The Cardiovascular Link to Brain Health, with Dr. Benjamin Goldstein

By Kevan Clifford

Dr. Goldstein is a Child and Adolescent Psychiatrist at the Centre for Addiction and Mental Health (CAMH), and Full Professor of Psychiatry and Pharmacology at the University of Toronto Temerty Faculty of Medicine.

During his undergraduate studies at the University of Pennsylvania, Dr. Goldstein conducted research on attributional styles in depression. Upon arriving at the University of Toronto for graduate school, he further examined attributional styles in relation to gender differences in depression and alcohol use. Dr. Goldstein later completed residency training at the University of Toronto. While attending his first American Psychiatric Association conference, a piece on pediatric bipolar disorder serendipitously caught his eye.

At the time, bipolar disorder in youth was not well characterized. Furthermore, the considerable stigma associated with individuals and families with bipolar

disorder was amplified in the pediatric population. The notion of children struggling with such a debilitating illness was both unexpected and saddening.

Dr. Goldstein’s interest in youth bipolar disorder quickly blossomed, and he soon found himself immersed in the field.

To get to the heart of Dr. Goldstein’s research, one must consider the connection between vascular health and bipolar disorder.1 An initial goal of his research program was to prove to the broad medical community, and society, that pediatric bipolar disorder was a valid illness. The idea was to demonstrate that cardiovascular risk factors are elevated and associated with increased severity of bipolar disorder in youth, as is the case in adults, to support the conclusion that youth bipolar disorder is similar to adult bipolar disorder. Using population-based data, Dr. Goldstein then demonstrated that adults with bipolar disorder have excessive rates of heart disease, which onsets over a decade prematurely. This was a largely untreated population sample, and analyses controlled for numerous potential confounds (e.g., sedentary lifestyle, smoking, blood pressure, and obesity). As such, the study demonstrated that risk of cardiovascular disease in bipolar disorder is above and beyond what can be explained by other factors.

Dr. Goldstein’s team further explored this connection by focusing on microvessels, which exist throughout the body. Early studies focused on neuroimaging measures of cerebral blood flow, and on

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peripheral measures of vascular reactivity.

Their current project includes these measures and further incorporates novel approaches, such as retina photography looking at blood vessels in the eye, and notably, cardiovascular magnetic resonance imaging (MRI) examining overall structure and function of the heart.

Ultimately, the study’s goal is to identify a phenotype in microvascular function unique to bipolar disorder.

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As such, the study demonstrated that risk of cardiovascular disease in bipolar disorder is above and beyond what can be explained by other factors.

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B

ipolar disorder is one of the most complex and severe psychiatric illnesses, and remains all too often misunderstood by society. Bipolar disorder in youth and adolescent populations is even less understood and comes with heightened stigmatization.

Clinical advances in this field require a keen eye for identifying gaps, and the ability to reimagine previous ideas for new applications. By embodying these attributes, Dr. Benjamin Goldstein deepens our understanding of bipolar disorder from new perspectives, resulting in novel, non-traditional treatment approaches.

New approaches to understanding a disorder often yield new treatment ideas.

The vascular connection to bipolar disorder presented an intuitive treatment option–cardiorespiratory (i.e., aerobic) exercise! However, disparities between treating physical illnesses and mental illnesses exist. It is unlikely someone with mental illness will be referred to an exercise or nutrition expert; instead, they likely receive pharmacological, and maybe psychotherapy treatment. Dr. Goldstein asserts that exercise and healthy

FEATURE VIEWPOINT

Dr. Benjamin Goldstein, MD/PhD Psychiatrist at the Centre for Addition and Mental Health (CAMH), and Full Professor of Psychiatry and Pharmacology at the University of Toronto Temerty Faculty of Medicine

lifestyle interventions should be front and center in bipolar disorder treatment, not an add-on or accessory item. This need is apparent in individuals with bipolar disorder, where high levels of sedentary behaviour are common.2 In addition to improving aerobic fitness, Dr. Goldstein suggests potential repurposing of specific medications that benefit vascular health.

Furthermore, in addition to treatment, novel cardiovascular screening approaches could aid in diagnosis and prognosis of individuals presenting with bipolar disorder symptoms.

The vascular connection has led to the development of other exciting novel treatments. Most recently is nitrous Graphic design by Genevieve Groulx

oxide, a widely used anaesthetic. Nitrous oxide regulates vascular tone and blood flow, and may be effective for treating bipolar depression. Broadly, it works as an NMDA receptor antagonist, similar to ketamine—a leading rapid acting treatment for depression. Dr. Goldstein’s group conducted a pilot study where individuals received nitrous oxide in an MRI scanner, measuring physiological changes in cerebral blood flow. The next proposed study will have two sessions per week, for two weeks, and examine patient outcomes at one month. The potential of nitrous oxide as a fast-acting, inexpensive, and effective treatment for bipolar depression is therefore generating excitement.

Moving beyond clinical and research matters, Dr. Goldstein reflected on the role of mentorship in his career. As a mentee, support from influential mentors was key in his development. Reflecting on the time, effort, and resources mentors invested in him, Dr. Goldstein offered the saying, “To whom much is given, much is expected”, explaining it inspires him to honour their generosity by working hard and advancing his research career. As a mentor himself, Dr. Goldstein deeply values seeing mentees learn, progress, and eventually go on to support others. His advice to other mentors is to encourage mentees to aim high to bring out their best, and to lead by example, in both formal research skills and reciprocal interpersonal working relationships.

Dr. Goldstein also shared insight into the unique path of Clinician-Scientists. It is no small feat to straddle the demanding worlds of being both a practicing clinician and researcher. Dr. Goldstein emphasizes that despite the very real challenges of navigating both fields, he feels it is an absolute privilege to be able to study the illness in the lab that he treats on a dayto-day basis in the clinic, and that this applies to whatever disease you choose to specialize in.

Dr. Goldstein encourages us to consider that the connection between cardiovascular health and brain health does not suddenly start in adulthood.

Rather, it is relevant and targetable in adolescence. It is crucial we optimize cardiovascular health in this age range to improve mental health in pediatric bipolar disorder, and other major psychiatric disorders. It is Dr. Goldstein’s hope that his program’s innovative work in understanding and treating bipolar disorder will help demonstrate that it is first and foremost, like any other illness, a physical illness, and should not be met with stigma or shame.

References 1. Goldstein BI, Carnethon MR, Matthews KA, McIntyre RS, Miller GE, Raghuveer G, Stoney CM, Wasiak H, McCrindle BW. Major depressive disorder and bipolar disorder predispose youth to accelerated atherosclerosis and early cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2015 Sep 8;132(10):965-86.

2. Kennedy KG, Ghugre NR, Roifman I, Qi X, Saul K, McCrindle BW, Macgowan CK, MacIntosh BJ, Goldstein BI. Impaired coronary microvascular reactivity in youth with bipolar disorder. Psychological Medicine. 2023 Oct 31:1-1.

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FEATURE

Pioneering Breakthroughs in Autism & ADHD Research with Dr. Hsiang-Yuan Lin

By Mahbod Ebrahimi

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utism and attention-deficit hyperactivity disorder (ADHD) are common neurodevelopmental conditions with a worldwide prevalence of around 1% and 6%, respectively.1 The typical symptoms of ADHD include hyperactivity, impulsivity, and/or severe inattention, while autism is typically characterized by difficulty with social interactions and restricted and repetitive patterns of behavior.1 Although ADHD and autism are distinct from each other, there is an intriguing crossover between these two conditions: ADHD is present in 30-80% of individuals with autism, and autism is present in 20-50% of individuals with ADHD.2 Both conditions are neurodevelopmental, developing during early childhood and showing overlapping symptoms, such as self-dysregulation. Further, autism and ADHD also have intricate relationships with another neurodevelopmental condition, intellectual disabilities (ID).

Dr. Hsiang-Yuan Lin, a psychiatrist and clinician-scientist with the Azrieli Adult Neurodevelopment Centre at the Centre for Addiction and Mental Health (CAMH) and assistant professor of Psychiatry and IMS, concentrates on treatment innovation for self-dysregulation in neurodevelopmental conditions by integrating clinical trials and multimodal neuroimaging and computational methods to understand atypical neurodevelopment throughout one's life, with a particular focus on autism, ID, and ADHD. Dr. Lin obtained his medical degree in 2007 and completed his residency in Child and Adult Psychiatry from National Taiwan University Hospital in Taiwan in 2013. He then received

Dr. Lin’s current research at CAMH focuses on clinical trials and neuroimaging studies with the aim of discovering novel treatment methods to improve the quality of life for people with autism, ID, or ADHD. This can be broken down into four main areas described below.

all forms of aggression, including selfinjury as well as aggression towards others.

Dr. Lin hopes to take this investigation further by collaborating with colleagues at the University of Montreal to conduct a multisite, double-blind, randomized control trial (RCT) with the objective of assessing and confirming the scalability, tolerability, and effectiveness of nabilone for treating aggression in people with intellectual and developmental disabilities.

Nabilone trial

Psilocybin-assisted therapy in autism

further training in advanced neuroimaging methods at the QIMR Berghofer Medical Research Institute in Australia.

In Dr. Lin’s efforts for treatment innovation, his lab has conducted the world's first Phase I pilot open-label clinical trial with nabilone for adults with intellectual and developmental disabilities (including autism) and severe behavioural problems. Nabilone is a synthetic cannabinoid and a THC analog that has previously been used for treating behavioural issues in dementia and Parkinson’s disease. Since the mechanism of nabilone, which involves influencing our cannabinoid receptors, is relatively well understood, Dr. Lin aimed to test the feasibility of using nabilone as a treatment to help reduce aggression in adults with ID. In this open-label pilot clinical trial, 12 participants with ID and aggressive behaviours were enrolled in and completed a 4-week medication course.

Following this period, aggression was evaluated through clinical assessments and standardized questionnaires filled out by caregivers. The results indicate a promising 60-70% decrease in aggressive behaviours.

The observed improvement encompassed

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Dr. Lin's laboratory has another intriguing project in the pipeline involving the exploration of psilocybin, a psychedelic compound present in magic mushrooms, for addressing treatment-resistant depression in autistic adults, with an additional focus on brain mechanism based on dense sampling (i.e., scanning an individual's brain at multiple time points and under varying conditions) functional MRI. Despite the burgeoning interest in psilocybin therapy, its application remains unexplored in the realm of autism treatment. Notably, this initiative marks the inaugural attempt to investigate the viability of psilocybin-assisted therapy as a potential intervention for depression in individuals on the autism spectrum. The recruitment phase for this clinical trial is slated to commence in Spring 2024.

Repetitive Transcranial Magnetic Stimulation (rTMS) in Youth with Autism In collaboration with colleagues in Taiwan, Dr. Lin and the team have conducted

FEATURE

Dr. Hsiang-Yuan Lin Clinician-Scientist, Azrieli Adult Neurodevelopmental Centre, Centre for Addiction and Mental Health, Assistant Professor, Department of Psychiatry, Institute of Medical Science, University of Toronto Photo Credit: Dr. Lin

three double-blind RCTs utilizing rTMS targeting specific brain regions in autistic youth. rTMS is a process where a machine directs a magnetic field to bring about a neurophysiological change in the brain.

The primary goal of these trials was to assess whether rTMS could effectively address emotional dysregulation and repetitive behaviours frequently observed in this population. More than 200 participants were enrolled in these trials, with ~100 receiving active rTMS and ~100 receiving sham stimulation. The findings from these RCTs did not reveal significant changes in the core symptoms or overall quality of life in the autistic individuals undergoing TMS treatment, prompting the exploration of alternative brain regions Graphic design by Jo Choi

and rTMS methodological considerations.

Based on these results, the team and Dr. Lin are currently working on a pilot study focusing on stimulating the cerebellum using rTMS. The effect of TMS on the cerebellum would be especially interesting since this brain region is responsible for an array of biological functions and is very sensitive to external stimulation. A previous neurotypical adult study suggests cerebellar TMS may increase functional connectivity within the social network, making this feasibility effort an innovative and intricate approach within the scope of TMS applications.

Imaging Neuroscience

Delving into the realm of neuroimaging, Dr. Lin's research unfolds an intriguing perspective on autism and ADHD. A pivotal question driving Dr. Lin's team revolves around discovering potential disparities in the brains of individuals with varying intellectual abilities within the autism spectrum. Intellectual ability is defined by a person’s IQ measurements and adaptability.

Dr. Lin's team has discovered that the brains of individuals with autism, both intellectually capable and disabled, differ from those of the general population. Furthermore, the brains of intellectually capable individuals with autism differ from those of intellectually disabled individuals with autism. This investigation has critical significance, as most of the existing literature in autism research predominantly features individuals on the higher end of the intellectual spectrum. Furthermore, another captivating neuroimaging study that is ongoing in Dr.

Lin's lab involves unravelling the intricate relationship between the menstrual cycle, brain dynamics, and cognitive patterns in females with ADHD. This project entails the dense sampling approach, thereby observing the intricate fluctuations within the brain.

Dr. Lin and his team are continuously engaged in captivating and transformative research endeavours aimed at enhancing the lives of individuals with autism, ID, ADHD, and other neurodevelopmental conditions.

A pivotal point Dr. Lin emphasizes in both his medical practice and research is to embrace individuals’ neurodiversity. As Dr. Lin puts it, “Respect neurodiversity. We don’t want to eradicate the conditions, [rather] aim to only improve the core symptoms [for people with autism or ADHD] when these endeavours could facilitate a better quality of life. People should focus more on how we can improve and help [people with autism or ADHD] to keep their identity but also adapt to the neurotypical society in a happier and less anxious manner.” Looking ahead, Dr. Lin's future aspirations revolve around discovering innovative and effective interventions to improve self-dysregulation and elevate the well-being of individuals with neurodevelopmental conditions.

References 1. Fast K, Wentz E, Roswall J, et al. Prevalence of Attention‐deficit/Hyperactivity Disorder and Autism in 12‐year‐old Children: A Population‐based Cohort.

Developmental Medicine & Child Neurology. 2023 Sept 22.

2. Lau-Zhu A, Fritz A, McLoughlin G. Overlaps and Distinctions between Attention Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in Young Adulthood: Systematic Review and Guiding Framework for EEG-Imaging Research. Neuroscience & Biobehavioral Reviews. 2019 Jan; 96:93-115.

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BMC SHOWCASE

Master of Science in

Biomedical Communications

Sophia Huebel Neuroanatomy Self Portrait My passion is using illustration to show the beautiful complexity of the human body and the natural world. I believe that knowledge is power, and art has the ability to connect and inform people around the world. My technical skills include digital painting, 3D modeling, animation, and more.

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BMC SHOWCASE

Anne McGrath Insane in the Brain Reflecting on my childhood interests, I was clearly drawn to scientific and medical illustration before I had any idea this profession existed. A Spiderwick Chronicles field guide, the Beatrix Potter collection, and an atlas of animals all come to mind. Today I feel so lucky to have found the BMC program - it’s surreal I’ve found and can immerse myself in my passion! I hope to one day contribute the beautiful and informative visuals that originally inspired me so long ago. Science is truly beautiful, and I’m so excited to be part of it!

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VIEWPOINT

Exploring Mindfulness: Benefits, Controversies, and Its Effectiveness in Improving Mental Health

By Niki Akbarian

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indfulness practices, such as mindful meditation, breathing practices, and yoga, have garnered considerable popularity in recent years as they are often promoted as the accessible go–to tools to reduce stress and increase well–being.1 But what exactly is mindfulness, and what do mindfulness practices encompass?

At its core, mindfulness is the translation of the Buddhist and Hindu concept of Sati. Sati is the first of the seven elements of enlightenment; a journey towards liberation from the mental struggles that often oppress us, and a way to achieve profound peace, presence, and wholeness in our lives.2 Sati, and by extension, mindfulness, revolves around the awareness of one’s present state. It is the art of fully immersing oneself in the moment, embracing the here and now, as well as observing thoughts, emotions, and bodily sensations with a non-reactive and non-judgmental perspective.2 It is a practice that invites us to let go of the burdens of the past and cease anticipating the uncertain future.

Consequently, mindfulness-based practices offer structured activities that provide individuals with the time and space to focus their attention, enhance their awareness, and develop an accepting stance toward their experiences. These exercises are designed to help individuals tap into the potential benefits of mindfulness to optimize their well-being.3

Over the past few years, there has been a significant increase in the use of mindfulness practices as therapeutic tools to address mental health conditions such as anxiety, depression, obsessive compulsive disorder, and eating disorders.

Nevertheless, there is an ongoing inquiry into whether scientific evidence also supports the effectiveness of these practices for enhancing mental health, both among healthy individuals and within clinical populations.

To comprehensively evaluate the efficiency of mindfulness practices as therapeutic tools, it is essential to delve into the potential psychological and biological mechanisms that underlie the capacity of these practices to influence mental health outcomes. One significant psychological effect associated with mindfulness is a perceptual shift in how individuals react to and relate to their thoughts, emotions, and sensory experiences. This shift involves the ability to observe these mental and emotional phenomena with greater detachment and impartiality, reducing psychological distress. In addition, mindfulness practices facilitate a heightened level of self-awareness, which enhances one’s ability to identify and accurately label negative emotions and thought patterns. Recognizing and naming these mental states, in turn, can foster a more nuanced understanding of our inner world, enabling us to utilize more effective coping strategies.4

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From a biological perspective, there is evidence to suggest that mindfulness practices can lead to neuroplastic changes in various regions of the brain, including the default mode network structures, left hippocampus, and fronto-limbic network. These structural changes are associated with enhanced learning and memory abilities, improved self-regulatory capabilities, and better interoceptive awareness. In addition, mindfulness practices have been found to increase the output of the vagus nerve, a cranial nerve responsible for regulating heart rate and breathing. When the vagus nerve is stimulated, it can lead to reduced autonomic arousal and is associated with an increased relaxation response. This response can have both physiological and psychological positive effects by contributing to a sense of calm and well-being.4 Yet, another question to consider is whether the psychological and biological changes associated with mindfulness translate into noticeable improvements in the tangible symptoms and overall outcomes of mental health in non-clinical and clinical populations.

In non-clinical settings, results from a recent meta-analysis suggest that mindfulness-based practices yield improvements in mental health outcomes compared to taking no action. Among these outcomes, psychological distress exhibits the most noticeable improvement with mindfulness practices. While Graphic design by Anne McGrath

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improvements in depressive and anxiety symptoms are also often observed, overall well-being shows low to no enhancement in response to mindfulness practices.

Moreover, in comparison to other interventions aimed at improving mental health, there is no clear evidence to suggest that mindfulness practices are either superior or inferior.5 Interestingly, the effects of mindfulness practices on mental health outcomes, specifically depression and anxiety outcomes, in nonclinical populations seem to be moderated by individual-level differences. That is, individuals at higher risk or those with subclinical symptoms of mental disorders appear to obtain more substantial benefits from mindfulness practices,5 perhaps because they are more motivated and have more room for improvement. Therefore, in nonclinical settings, mindfulness practices seem to be effective in reducing psychological distress, with the extent of their effects being contingent on individual characteristics.

On the other hand, the effectiveness of mindfulness practices as treatments for psychiatric disorders in clinical settings has generated mixed findings.

One meta-analysis has indicated that, when compared to no treatment or non-specific active controls (such as placebo treatments), mindfulness-based interventions may improve clinical symptoms, particularly for depression.

Furthermore, mindfulness practices have demonstrated comparable performance

to evidence-based psychological treatments.6 However, another metaanalysis found that while mindfulness practices are superior to no treatment, there is no evidence to support that they produce treatment effects equal to or better than evidence-based psychological interventions, such as Cognitive Behavioral Therapy, for psychiatric disorders.7 In essence, mindfulness practices can be considered experimental treatments for psychiatric disorders due to the lack of research support.

To summarize, mindfulness seems to offer well-established benefits for individuals without clinical diagnoses, notably in alleviating psychological distress and subclinical symptoms of depression and anxiety. However, using mindfulness practices as the primary treatment for clinically diagnosed psychiatric disorders lacks scientific backing. In my view, even if mindfulness practices do not produce scientifically substantial effects, they can still be valuable in helping us pause, tune into our emotions and experiences, and reduce unnecessary worry. However, when dealing with more severe mental health issues, it is vital not to depend solely on mindfulness practices as treatments. It is important to seek guidance and explore evidence-based treatment options in such circumstances.

References 1. Kabat-Zinn J. Foreword: Seeds of a necessary global renaissance in the making: The refining of psychology’s understanding of the nature of mind, self, and embodiment through the lens of mindfulness and its origins at a key inflection point for the species.

Current Opinion in Psychology. 2019;28:xi–xvii. doi:10.1016/j. copsyc.2019.02.005 2. Bazzano M. After mindfulness: New perspectives on psychology and meditation. Basingstoke: Palgrave Macmillan; 2014.

3. Mindfulness exercises [Internet]. Mayo Foundation for Medical Education and Research; 2022 [cited 2023 Oct 6]. Available from:https://www.mayoclinic.org/healthy-lifestyle/consumer-health/in-depth/mindfulness-exercises/art-20046356 4. Shonin E, Van Gordon W. The mechanisms of mindfulness in the treatment of mentalillness and addiction. International Journal of Mental Health and Addiction. 2016;14(5):844–9. doi:10.1007/ s11469-016-9653-7 5. Galante J, Friedrich C, Dawson A, Modrego-Alarcón M, Gebbing P, Suárez I, et al. OP62 mindfulness-based programmes for mental health promotion in adults in non-clinical settings: A systematic review and meta-analysis of Randomised Controlled Trials. Oral Presentations. 2020; doi:10.1136/jech-2020-ssmabstracts.61 6. Goldberg SB, Tucker RP, Greene PA, Davidson RJ, Wampold BE, Kearney DJ, et al. Mindfulness-based interventions for psychiatric disorders: A systematic review and meta-analysis. Clinical Psychology Review. 2018;59:52–60. doi:10.1016/j.cpr.2017.10.011 7. Hedman-Lagerlöf M, Hedman-Lagerlöf E, Öst L-G. The empirical support for mindfulness-based interventions for common psychiatric disorders: A systematic review and meta-analysis. Psychological Medicine. 2018;48(13):2116–29. doi:10.1017/s0033291718000259

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VIEWPOINT

Adventures in Wonderland Wonderland

By Carmen H. Li

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n 2022, the Centre for Addiction and Mental Health (CAMH) received Canada’s first federal grant to study psilocybin, the active “magic mushrooms” component, for its therapeutic effect on treatment-resistant depression. The phase two trial titled “Does Psilocybin Require Psychedelic Effects to Treat Depression? (PSI-RIS)” investigates whether experiencing psilocybin’s psychedelic effects is necessary to have an antidepressant effect.1 Though preliminary results are not yet available; investigators are confident that their study will inform future clinical trials with psilocybin. Also, given the psychedelic effects of psilocybin, investigating whether a psychedelic effect is necessary may increase treatment accessibility to patients with a history of psychosis and individuals who may be cautious of a negative psychedelic experience. Why is this remarkable?

Several prior trials have reported that psilocybin has an antidepressant effect, particularly when delivered in combination with psychotherapy.2 Other recently published trials suggest that psilocybin can be as effective as other antidepressants. For example, the Psilodep-RCT study published in the New England Journal of Medicine in 2021, compared psilocybin to escitalopram for the treatment of moderate-to-severe major depressive disorder over a 6-week period. The study found that there was no significant difference in antidepressant effect between psilocybin and escitalopram in these patients.3 If psilocybin is still

effective without causing a psychedelic state, it would make the therapeutic more accessible and remove the time and resource-intensive psychotherapeutic support during treatment administration.

To backtrack, what exactly is psilocybin and how did it go from being popularized as recreational “magic mushrooms”, to being banned in the 60’s, to now being investigated as a therapeutic?

The molecular structure of psilocybin.

To understand psilocybin’s effects, it’s helpful to understand how it interacts biochemically with the brain. The feature of interest is psilocybin’s ability to increase brain plasticity.2 Psilocybin is a compound in fungi, commonly found in species of the genus Psilocybe. In the

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body, it is converted into psilocin which activates the 5 HT2A serotonin receptors in the brain for its psychedelic effect.

Notably, when the 5 HT2A receptors are blocked pharmacologically such as with Buspirone, which is a 5 HT2A receptor agonist, there is an attenuation of psilocybin’s effects.2 However, much of psilocybin’s effects on the brain are still not fully understood. As psilocybin is being researched, its mechanisms, dosages, and delivery with and without psychotherapies are being assessed for treating various mental health conditions.

If psilocybin is so impactful, why hasn’t it been investigated earlier? Humans have taken advantage of psychedelic compounds for spiritual and mental wellbeing since early civilization. For example, a 1000 CE dated ritual bundle belonging to a shaman of the pre-Inca Tiwanaku civilization in southwestern Bolivia held traces of cocaine metabolites, psilocin, and components of the psychedelic tea known as ayahuasca.4 Ancient Greeks and Romans conducted seasonal rites with a drink called kykeon, which contained fungi with LSD-like psychedelic alkaloids.5 In modern society, understanding the therapeutic potential of psilocybin and other psychedelic compounds has been a process of re-discovery. Psilocybin emerged in mainstream culture after amateur ethnomycologist R. Gordon Wasson and his partner Valentina P. Wasson, a physician, witnessed a Mazatec ritual use of psychoactive mushrooms in the Mexican village Huautla de Jimenez.6

VIEWPOINT

Albert Hofmann, a Swiss chemist, was the first to isolate psilocybin from the mushroom Psilocybe mexicana in 1959, and the compound was later used in experimental research to investigate its psychotherapeutic use.7 However, restrictive drug laws in the 1960s and the ban on psychedelics by the United Nations Convention in 1971 halted research in this direction.7 Research interest re-emerged in the early 2000s, as clinical trials showed success for treatment-resistant depression and other mental health disorders, including alcoholism, substance use disorder, and obsessive compulsive disorder.2,10 In 2023, Australia became the first country to legalize MDMA and psilocybin for post-traumatic stress disorder and treatment-resistant depression.9 In Canada, psilocybin is still only accessible through clinical trials, but there is a growing interest in wider accessibility.

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Humans have taken advantage of psychedelic compounds for spiritual and mental wellbeing since early civilization.

What lies in store for the future of psilocybin in medicine? Interestingly, psilocybin has also been investigated as a therapeutic for end-of-life anxiety and depression. In a double-blind, Graphic design by Genevieve Groulx

placebo-controlled pilot study, psilocybin was tested in 12 patients with various forms of advanced-stage cancer to reduce the psychological burden of a terminal diagnosis. Patients had a clinical diagnosis of acute stress disorder, generalized anxiety disorders, anxiety disorder due to cancer, or adjustment disorder with anxiety. In the study, psilocybin led to a significant decrease in survey-reported depression symptoms compared to placebo by the six-month follow-up visit.11 Psychedelics including psilocybin, are also being investigated as potential treatments for neurodegenerative disorders, which highlights the exciting and unexplored potential of these therapeutics for neurological conditions and the subtle aspects of well-being, such as the end-oflife care.10 Of course, while this news is exciting, there are still many barriers ahead in developing psilocybin and other psychedelics into appropriate therapies. How will public perception and stigma affect future access to these therapeutics? Further research into the long-term effects of psilocybin therapy and risk factors for individuals with a history of psychotic disorders or comorbidities is still needed. Access barriers to mental health services may also undermine the development of new, more effective interventions. Despite these uncertainties, the resurgence of research and interest in psilocybin still proves to be a step in a hopeful direction to navigate our present-day mental health crisis.

References 1. Husain MI, Blumberger DM, Castle DJ, et al. Psilocybin for treatment-resistant depression without psychedelic effects: study protocol for a 4-week, double-blind, proof-of-concept randomised controlled trial. BJPsych Open. 2023 Jul;9(4):e134.

2. Sarparast A, Thomas K, Malcolm B, et al. Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review. Psychopharmacology. 2022 Jun;239(6):1945-76.

3. Carhart-Harris R, Giribaldi B, Watts R, et al. Trial of psilocybin versus escitalopram for depression. New England Journal of Medicine.

2021 Apr 15;384(15):1402-11.

4. Miller MJ, Albarracin-Jordan J, Moore C, et al. Chemical evidence for the use of multiple psychotropic plants in a 1,000-year-old ritual bundle from South America. Proceedings of the National Academy of Sciences. 2019 Jun 4;116(23):11207-12.

5. Samorini G. The oldest archeological data evidencing the relationship of Homo sapiens with psychoactive plants: A worldwide overview. Journal of Psychedelic Studies. 2019 Jun;3(2):63-80.

6. Wasson RG. The hallucinogenic fungi of Mexico: an inquiry into the origins of the religious idea among primitive peoples. Botanical Museum Leaflets, Harvard University. 1961 Feb 17;19(7):137-62.

7. Hofmann A, Heim R, Brack A, et al. Psilocybin und Psilocin, zwei psychotrope Wirkstoffe aus mexikanischen Rauschpilzen. Helvetica Chimica Acta. 1959;42(5):1557-72.

8. Nutt D, Carhart-Harris R. The current status of psychedelics in psychiatry. JAMA psychiatry. 2021 Feb 1;78(2):121-2.

9. Ritchie OD, Donley CN, Ritchie GD. From prohibited to prescribed: The rescheduling of MDMA and psilocybin in Australia. Drug Science, Policy and Law. 2023 Sep;9:20503245231198472.

10. Kozlowska U, Nichols C, Wiatr K, et al. From psychiatry to neurology: Psychedelics as prospective therapeutics for neurodegenerative disorders. Journal of Neurochemistry. 2022 Jul;162(1):89-108.

11. Grob CS, Danforth AL, Chopra GS, et al. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer.

Archives of general psychiatry. 2011 Jan 3;68(1):71-8.

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Behind the Paywall: Navigating the Ethics and Economics of Scientific Publishing

By Sara Shariati

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few months ago, I received a message from a friend of mine in Iran, asking me to download a paper for her from Science. Their university does not have a subscription to scientific journals, and she could not afford to pay for the article. That incident made me think about how many people in developing countries and less affluent academic institutions do not have access to scientific publications. My friend told me that she usually emails the first author to get a copy of their article, but that method does not work when she needs to read a specific manuscript urgently. This incident raised many ethical questions for me related to the scientific publishing industry and access to knowledge.

The Pay-for-Access Model of Publishing In the modern era, information is the currency of utmost value and access to knowledge is paramount. While people are being told to “do their own research” and “look at the facts” before making decisions, we must acknowledge that access to scientific articles is a privilege that not everyone has. The scientific publishing industry is crucial for knowledge dissemination, but paywalls restrict people’s access to the contents of scientific journals. According to the Times Higher Education, UK universities spent an average of £4 million on journal subscriptions in 2018.1 Only affluent institutions can afford to spend such money; thus, many students in developing

nations struggle to access the top papers in their field or expand their skill set through self-learning. That is why many students appreciate websites, like Sci-hub, that provide them with access to the necessary information to continue their studies. Scihub was created to address the barriers and inequities in access to scientific knowledge, given the unwillingness of greedy scientific publishing companies to address these issues. It then should come as no surprise that this website has received a lot of backlash from these publishing companies.

While some argue that paying for access to scientific journals resembles paying for subscriptions to newspapers, there is an important distinction between the two that must be acknowledged: journalists who write news articles are paid by the newspaper, but authors of scientific papers are not paid by scientific journals. In fact, an increase in the number of subscribers to a scientific journal has no monetary benefit for the scientists whose work is published in the journal. Furthermore, reviewers of journals generally review the papers voluntarily. The expectation is that by giving their time and acting as a reviewer, scientists will benefit themselves by having other scientists review their papers in the future. This means the two most important pillars for any journal— the authors and reviewers—are not paid by the journal. Then, why should the readers pay for access to these articles? Journals claim that the money paid by subscribers is spent on in-house editors who work for the journals; however, that still does not justify the high subscription costs for these journals.

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In 2015, The Guardian reported that approximately half the scientific publishing market is controlled by three publishers: Elsevier, Springer, and Wiley-Blackwell.2 Scientific publishing is a profitable business, which comes as no surprise given that the majority of contributors to these journals are not paid by the publisher. In fact, the top scientific publishing companies report profit margins of close to 40%, higher than Apple, Google, or Microsoft.3 Despite the controversies, scientists have to continue publishing for advancement of their careers. This “publish or perish” cycle means that scientists cannot boycott the publishers; scientists need grants to continue their work and receiving grants requires past publications. Furthermore, publications in certain prestigious journals, such as Nature, Cell, and scientific publishing industry.

A journal’s “prestige” is measured by its impact factor. The impact factor measures the yearly number of citations of articles published over the last two years in a given journal. However, the impact factor has received its own share of criticisms, with many claiming that it is not a good representation of a journal’s performance or a measure of how valuable the individual articles in that journal are. First, the impact factor is affected by self-citing. Second, a high impact factor for a journal does not necessarily mean every article within it is incredibly valuable and well-written.

Regardless, publishing in the big journals is a dream most aspiring scientists have,

VIEWPOINT

Paywalls restrict our access to scientific literature.

which helps maintain the current status in the scientific publishing industry.

The Open Access Model of Publishing An alternative to the model of publishing involving paywalls, is a more recent model called “open access”. The open access (OA) movement emerged as a potential solution to the barriers to knowledge dissemination. The premise of OA is simple: make research articles freely accessible to all.

While this approach effectively dismantles the reader paywall, it introduces a new set of challenges. Specifically, the "Gold OA" model, where authors pay Article Processing Charges (APCs) to ensure free public access to their work, has shifted Graphic design by Jo Choi

the financial onus from the reader to the researcher. While seemingly equitable in theory, in practice, the APCs in many reputable OA journals can be prohibitively high. For researchers with limited funding or those from developing nations, these costs become a formidable barrier to publication. In many Western countries, fees for publication in OA journals are included in grant applications, and scientists use their grants—often provided by government agencies—to pay for these fees. Given that these grants are generally created from taxpayers' money, the public is essentially paying to read the results of the research funded by them, which is ironic because investors should have free access to the results of any project in which they are investing.

Additionally, the APC model has unintentionally given rise to predatory journals: publications that charge authors hefty fees but skimp on, or entirely bypass, the rigorous peer-review process, thus compromising the quality and integrity of scientific literature. These journals send spam emails to scientists, asking them to submit their papers for publication.

Given the lack of any review process, these journals can give rise to scientific misinformation and conspiracy theories.

Furthermore, these journals make it very difficult for readers, students, and researchers to discern credible sources of information from non-credible ones.

Essentially, no perfect solution exists at the moment for addressing the inequities and

controversies of the scientific publishing industry. Both the pay-for-access and OA models are operating simultaneously in the industry at the moment. Meanwhile, some scientists have turned to social media for dissemination of their work. The role of content creation and social media could become even more pronounced in academia over the coming years. While there is no one-size-fits-all solution, it is evident that a more equitable model— one that prioritizes broad access without compromising on quality or placing undue burden on researchers—is essential. As the global community becomes increasingly interconnected, ensuring that knowledge is shared freely and equitably is not just an academic concern but a moral imperative.

References 1. Pells, R. (2018). Top universities’ journal subscriptions ‘average £4 million.’ Times Higher Education (THE). https://www.timeshighereducation.com/news/top-universities-journal-subscriptions-average-4-million-pounds.

2. Buranyi, S. (2017). Is the staggeringly profitable business of scientific publishing bad for science? The Guardian. https://www. theguardian.com/science/2017/jun/27/profitable-business-scientific-publishing-bad-for-science.

3. Academic publishers reap huge profits as libraries go broke (2015).

CBC News. https://www.cbc.ca/news/science/academic-publishers-reap-huge-profits-as-libraries-go-broke-1.3111535.

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VIEWPOINT

“Is This a Real Treatment?”: The Placebo Conundrum Media coverage has drawn attention to the ongoing practice of prescribing placebos to treat medical conditions.1 There are competing views on the current methods and the ethical quandary. Patients and prescribers should clearly understand the positions and issues associated with placebos to resolve current conflicts. “Placebo” originally meant a “medicine given more to please than to benefit the patient” in the 19th century.2 Since then, placebos have been routinely used in clinical trials as controls to confirm the efficacy of treatments. The basic blinded study consists of groups receiving a “treatment” option that is being tested for its utility against a “placebo” control.

These studies do not evaluate the placebo itself.

The “placebo effect” refers to the positive psychological and physiological effects observed when a treatment with no active ingredients is directed at a patient’s medical condition.3 A patient who anticipates negative results experiences the nocebo effect.

Placebos take many forms, including sugar pills, vitamins, antibiotics, saline injections, and any treatment method where there are no known effects on the condition for which they are prescribed.4 Meanwhile, placebos’ utility has been shown in a range of contexts including treatment for pain, depression, irritable bowel syndrome, epilepsy, and Parkinson’s disease.3,⁵

In some situations where placebos have been prescribed and found to be effective, cognitive behavioral therapy has also been used to develop awareness, help patients change their behavior, and address their circumstances. In one study, patients with depression were found to respond better to placebo pills when they were told it was a fast-acting antidepressant.6 The researchers acknowledged that patients who believe their prescriber is invested in treating their depression may be more likely to experience positive sentiments towards their treatment, benefiting their prognosis.6 By comparison, patients with depression who were aware they were receiving an inactive control did not benefit from the placebo.6 This study suggests that, in some cases, disclosing the nature of the treatment may have negative effects. Notwithstanding the potential for placebos to ameliorate quality of life, prescribers may not fully inform their patients. Some prescribers deny that they are prescribing placebos, painting a problematic and unethical picture.

In a few surveys, primary care doctors, internists, and rheumatologists have admitted to prescribing placebos regularly.7 Recent studies have found that the use of placebos and noneffective medications is 79±7% in Canada and 52±6% in the United States.5,7 Harris, Campbell, & Raz (2015) reported that while 40% of Canadian prescribers admitted to prescribing “unwarranted” vitamins, about 75% of prescribers

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“

...placebos’ utility has been shown in a range of contexts

including treatment for pain, depression, irritable bowel

“

By Anthaea-Grace Patricia Dennis

syndrome, epilepsy, and Parkinson’s disease.

claimed they had never prescribed a placebo.5 This discrepancy suggests that prescribers do not view “impure” placebos (e.g. vitamins & antibiotics) as placebos, even when their use has no “demonstrated or expected clinical efficacy”.8 The Canadian Medical Association’s Code of Ethics provides standards for physicians, including responsibility to “communicate with and help the patient assess material risks and benefits before consenting to any treatment or intervention”.9 By comparison, the American Medical Association’s Code of Ethics explicitly states that physicians should explain the utility of the placebo Graphic design by Anne McGrath

VIEWPOINT

to the patient before prescribing it.1⁰ Both Codes suggest patients should know they are receiving a placebo.

The ethical principle of beneficence obligates prescribers to choose treatments that are best for the patient.

In 2015, 59% of Canadian doctors believed that prescribing placebos for pain management had a positive impact on a patient’s psychological and physiological health.5 Some prescribers believe that placebos will not benefit the patient if they disclose that the treatment is a placebo. However, other studies have revealed that even when patients are aware they are receiving a placebo, (referred to as an “open-label” condition), the placebo effect still occurs, negating the need for deception.11-13 In fact, research supports that open-label placebos may lead to psychological and physiological improvement, benefiting the patients more than the standard treatment.1⁴,1⁵ Doctors may be disinclined to explain the details of their decisions to their patients, dreading appointments will be longer because the patient will want to know everything about why a medicine is chosen. Despite this, lack of transparency affects more than just the time prescribers spend explaining treatments to patients. Patients have the right to “make decisions about the care a physician recommends”.1⁶ Patient autonomy allows a patient to refuse treatment and engage in unhealthy behaviors; patients should be allowed to

refuse a placebo treatment and opt for something else.

References

If patients’ awareness of placebos within their treatment protocol does not negatively impact the placebo effect, then it is counterproductive to keep patients uninformed. Prescribers should seek patients’ consent to prescribe placebos, and if refused, provide an alternative treatment. Prescribers should limit recommendation of placebos to circumstances when placebos are likely to improve symptoms, not just placate the patient, to avoid masking conditions and delaying real treatment. Ultimately, open communication may assist in resolving the ethical dilemma of the use of placebos. Through discussion between patients and their prescribers regarding their viewpoints on placebos and patients’ desired transparency, an agreement can be reached between patients and their prescribers unique to each patient.

1. Silva B. McGill study reveals the placebo effect of personalized treatments. National Post. 2023 Jul 19; 2. Beecher HK. The powerful placebo. J Am Med Assoc. 1955 Dec 24;159(17):1602–6.

3. Newman T. Is the placebo effect real? Medical News Today. 2017 Sep 7; 4. Fent R, Rosemann T, Fässler M, et al. The use of pure and impure placebo interventions in primary care - a qualitative approach. BMC Fam Pract. 2011 Mar 24;12:11.

5. Harris CS, Campbell NKJ, Raz A. Placebo Trends across the Border: US versus Canada. PLoS ONE. 2015 Nov 25;10(11):e0142804.

6. Peciña M, Bohnert ASB, Sikora M, et al. Association Between Placebo-Activated Neural Systems and Antidepressant Responses: Neurochemistry of Placebo Effects in Major Depression. JAMA Psychiatry. 2015 Nov;72(11):1087–94.

7. Tilburt JC, Emanuel EJ, Kaptchuk TJ, et al. Prescribing “placebo treatments”: results of national survey of US internists and rheumatologists. BMJ. 2008 Oct 23;337:a1938.

8. Harris CS, Raz A. Deliberate use of placebos in clinical practice: what we really know. J Med Ethics. 2012 Jul;38(7):406–7.

9. Canadian Medical Association. CMA Code of Ethics and Professionalism [Internet]. 2018 [cited 2023 Sep 28]. Available from: https://policybase.cma.ca/viewer?file=%2Fmedia%2FPolicyPDF%2FPD19-03.pdf#page =1 10. American Medical Association. Use of Placebo in Clinical Practice [Internet]. AMA Code of Ethics. [cited 2023 Sep 26]. Available from: https://code-medical-ethics.ama-assn.org/ethics-opinions/ use-placebo-clinical-practice 11. Blease C, Colloca L, Kaptchuk TJ. Are open-Label Placebos Ethical?

Informed Consent and Ethical Equivocations. Bioethics. 2016 Jul;30(6):407–14.

12. Charlesworth JEG, Petkovic G, Kelley JM, et al. Effects of placebos without deception compared with no treatment: A systematic review and meta-analysis. J Evid Based Med. 2017 May;10(2):97–107.

13. Colloca L, Howick J. Placebos without deception: outcomes, mechanisms, and ethics. Int Rev Neurobiol. 2018 Apr 4;138:219–40.

14. Park LC, Covi L. Nonblind placebo trial: an exploration of neurotic patients’ responses to placebo when its inert content is disclosed.

Arch Gen Psychiatry. 1965 Apr;12:36–45.

15. Carvalho C, Caetano JM, Cunha L, et al. Open-label placebo treatment in chronic low back pain: a randomized controlled trial. Pain.

2016 Dec;157(12):2766–72.

16. American Medical Association. Patient Rights [Internet]. AMA Code of Ethics. [cited 2023 Sep 26]. Available from: https:// code-medical-ethics.ama-assn.org/ethics-opinions/patient-rights

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VIEWPOINT

Unlocking the Key to a Good Death The Palliative Paradox

By Rachel Yang yield better outcomes for terminal patients and their families when compared to aggressive treatment. While I am neither a medical ethicist nor a physician, I will offer a piece of my insight into this profoundly intricate and multifaceted topic.

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The issue at hand results from the overmedicalization of the end-of-life process.

“

L

osing a friend to a bacterial infection or the common flu at the age of 25 is undeniably shocking.

In a world where modern medicine and skilled physicians are expected to have the answers, such a tragedy seems unthinkable. Strikingly, just over a decade ago, the passing of a young person due to these illnesses wouldn’t have garnered as much attention, as it was commonly perceived as an inevitable part of life with limited ability to intervene with the outcome. However, the past decade has seen an astonishing surge in medical and technological advancement, resulting in a drastic shift in our readiness towards illnesses and an increase in average human life expectancy.1 With this rise in life expectancy comes a new paradigm of death. Now, we have both the privilege and the necessity to contemplate how we want the final chapters of our lives to unfold. This is especially pertinent when dealing with end-stage illnesses like cancer, where patients are now confronted with a plethora of treatment options, each presenting its own ethical quandaries.

Should one continue chemotherapy, which may offer perhaps a 25% chance of slowing tumor growth but comes with unbearable side effects that impede quality time with family? Or should one halt therapy, even if it might offer a sliver of possibility of extending survival? My perspective on this matter has been profoundly influenced

by Atul Gawande’s book, Being Mortal: Medicine and What Matters in the End. In this article, I present my argument for why, more often than not, palliative care can

When providing medical guidance, physicians rely on ethical principles to navigate their decisions.2 End-of-life care presents a challenging scenario where ethical principles of beneficence and nonmaleficence can collide because there is often no clear-cut line determining when potential benefits (i.e. extension of survival) are enough to justify the associated harm (i.e. treatment side effects).2 Physician and author Atul Gawande highlighted in his book Being Mortal: Medicine and What Matters in the End, that “whatever we can offer, our interventions, and the risks and sacrifices they entail, are justified only if they serve the larger aims of a person’s life.”3 He emphasizes the importance of discussing what a patient values most at that juncture in their life. Key questions arise, such as whether the patient seeks to minimize suffering and pain to spend their remaining time with loved ones, or whether they wish to pursue available

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treatments for a chance at prolonging survival, even if that means enduring challenging side effects. In a Canadian study, patients facing severe illness and their families emphasized the importance of trust and effective communication with their physician as a critical component of quality end-of-life care.4 Despite its apparent simplicity, discussing the topic of death is rather difficult with studies revealing that a mere 35-39% of physicianpatient discussions regarding prognosis take place. 5 Death is an ending to a life that should be approached on one’s own terms, lived with dignity and autonomy until the very end. For this reason, without delving into what matters most to the patient in their final days, they may inadvertently choose a treatment path, such as continued aggressive treatment, that does not align with their true desires.

The issue at hand results from the overmedicalization of the end-of-life process. It has become commonplace for individuals to pass away alone in hospital rooms, enduring unnecessary pain during their final days.6 Presently, a typical senior might be someone who recently experienced a

VIEWPOINT

Graphic design by Genevieve Groulx

for individuals to deeply consider their desires for their last days. It is undeniably courageous to fight for survival, both for oneself and for one’s family. Yet, in cases where the prognosis is terminal, and all promising available options have been exhausted, perhaps the wiser course of action is to explore palliative care and savour precious moments with loved ones, rather than enduring aggressive treatments and unnecessary pain during one’s final days.

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Conversely, patients in long duration of hospice care showed contrasting results, reporting lower physical distress and a higher quality of death.5

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heart attack and eventually find themselves making increasingly frequent visits to the hospital, progressing from monthly to weekly. Conversely, an individual might be diagnosed with lung cancer, and despite enduring rounds of chemotherapy, they discover that the cancer has metastasized, with their chances of long-term survival being slim to none. In both cases, these individuals find themselves in a continuous cycle of medical intervention.

The central question I wish to address here is: At what point do you say no to making repeated hospital visits and further treatment and instead, pursue palliative care and spend time with your loved ones in your final moments? In a study involving interviews with over 200 patients with advanced cancer and their primary caregivers, it was shown that aggressive therapies within a week prior were associated with higher levels of physical distress, increased psychological distress, and lower quality of death. Conversely, patients in long duration of hospice care showed contrasting results, reporting lower physical distress and a higher quality of death.5 As Gawande aptly observed, a physician’s role is not solely to ensure health and survival in a straightforward manner but to enable overall well-being.

The ultimate decision regarding one’s endof-life journey is a culmination of thought processes that have gone through extensive and rigorous deliberation; therefore, it goes without saying that there can be very valid reasons for someone to pursue additional treatment attempts, even when facing a terminal illness.7 However, my appeal is

References 1. Statista. Life expectancy (from birth) in the United States, from 1860 to 2020*. 2022. Available from: https://www. statista.com/statistics/1040079/life-expectancy-unitedstates-all-time/ 2. Varkey B. Principles of Clinical Ethics and Their Application to Practice. Med Princ Pract. 2021 [cited 2023 Oct 18]; 30(1):17-28. Available from: https://www.ncbi.nlm. nih.gov/pmc/articles/PMC7923912/ 3. Gawande A. Being Mortal: Medicine and What Matters in the End. New York: A Metropolitan Paperback, Henry Holt, and Company; 2021.

4. Heyland DK, Dorek P, Rocker G, et al. What matters most in end-of-life care: perceptions of seriously ill patients and their family members. CMAJ. 2006 [cited 2023 Nov 1]; 174(5):627-33. Available from: https://www.ncbi.nlm.nih. gov/pmc/articles/PMC1389825/ 5. Mohammed AA, Al-Zahrani O, Salem RA, et al. Aggressive Care at the End of Life; Where Are We? Indian J Palliat Care. 2019 [cited 2023 Nov 1]; 25(4):539-43.

Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812417/ 6. Rome RB, Luminais HH, Bourgeois DA, et al. The Role of Palliative Care at the End of Life. Ochsner J. 2011 [cited 2023 Oct 18]; 11(4):348-52. Available from: https://www. ncbi.nlm.nih.gov/pmc/articles/PMC3241069/ 7. Matsuyama R, Reddy S, Smith T, et al. Why Do Patients Choose Chemotherapy Near the End of Life? A Review of the Perspective of Those Facing Death From Cancer. J Clin Oncol. 2006 [cited 2023 Oct 18]; 24(21):3490-6. Available from: https://pubmed.ncbi.nlm.nih.gov/16849766/

Sickness and mortality are intrinsic aspects of the human experience. By reshaping our perspective and discourse on illness and the end-of-life, we can effectively advocate for palliative care as an acceptable and rational choice. This approach enables those who desire it to experience reduced suffering and embrace their final days in a comforting environment, enveloped by the warmth of loved ones, all while maintaining their dignity until the very end.

IMS MAGAZINE WINTER 2024 NON-TRADITIONAL THERAPIES | 29

VIEWPOINT FACULTY HIGHLIGHTS

Faculty Highlights Dr. Behdin Nowrouzi-Kia Using an occupational lens, Dr. NowrouziKia’s research program is a systematic study of occupations in

the areas of work disability prevention, return to work, and disability management. This approach is designed to produce results directly applicable to identify and assess risk and to develop interventions to optimize functioning and improve workplace health and well-being.

Dr. Charlotte Probst

Dr. Charlotte Probst is a Scientist at CAMH and an assistant professor in the Department of Psychiatry at the University of Toronto.

Her research aims to understand the mechanisms underlying the growing socioeconomic inequalities in the alcohol-related burden of disease and to develop tangible intervention strategies for their reduction.

Dr. David Lim I am a a breast surgical oncologist at Women’s College Hospital and surgeon-scientist at Women’s College Research Institute. My areas of research focus include patient-reported outcomes, surgical decisionmaking including contralateral prophylactic mastectomy and implications of neoadjuvant therapy, treatment de-escalation, outcomes after ambulatory breast surgery, disparities in cancer care and lobular breast cancer.

Dr. Michael Wainberg

Dr. Wainberg’s lab applies statistics, machine learning and other computational approaches to large datasets to learn how genetics causes brain diseases. Its overarching goal is to find new drug targets, while developing new ways to do genetic studies and extract meaning from them along the way.

Dr. Hance Clarke My research program continues to be focused on improving the lives of Canadians suffering from chronic pain and Ehlers Danlos Syndromes. The cost to our system for treating chronic pain is upwards of $40 billion annually. Our team has helped to shift and shape the national and international landscape with respect to postoperative care and persistent opioid use after surgery based on research to date from our multidisciplinary Transitional Pain Service (TPS) at the Toronto General Hospital, which was the product of decades of empirical research. The GoodHope Ehlers Danlos Syndrome clinic (UHN) is dedicated to supporting research that improves the lives of people with EDS and HSD is a critical mission of the clinic. We are developing an integrated clinical and research translational program.

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Dr. Amy Boyle

Dr. Benjamin

Dr. Julia Sorbara

Dr. Alán Aspuru-Guzik

Dr. Boyle’s Steinberg research focuses Dr. Steinberg on identifying is a pediatric inflammatory anesthesiologist biomarkers that and cell are common to biologist at The oncology and Hospital for Sick neurodegenerative Children. His diseases through PET imaging. Preclinical animal research training focused on delineating nodes models include neuroinflammation, multiple of communication between the body’s nervous sclerosis, Alzheimer’s disease, and and immune systems. His research group cancer xenografts. investigates mechanisms and therpeutic targeting pro-inflammatory cell death pathways in health and disease.

Dr. Julia Sorbara is a pediatric endocrinologist at The Hospital for Sick Children and an assistant professor in the Department of Pediatrics. Her research focuses on 1) the access to and provision of gender-affirming care for transgender and gender diverse youth and 2) pediatric bone disease.

Dr. Neil Goldenberg

The Goldenberg laboratory studies immune dysfunction in the lung vasculature, focusing primarily on pulmonary arterial hypertension. The lab uses cell culture, animal models, and patient-derived samples to study the importance of the immune system in the development of this disease, with an eye toward designing new treatments for this devastating condition. To this end, they focus our studies on cell death, inflammation, and the role of endothelial cells and vascular smooth muscle cells in the development of pulmonary hypertension.

Alán AspuruGuzik is a professor of Chemistry and Computer Science at the University of Toronto and is also the Canada 150 Research Chair in Theoretical Chemistry and a Canada CIFAR AI Chair at the Vector Institute.

He is a CIFAR Lebovic Fellow in Biologically Inspired Solar Energy Program. Alán is the director of the Acceleration Consortium, a University of Toronto-based strategic initiative that aims to gather researchers from industry, government, and academia around a pre-competitive researc topics related to the lab of the future.

Dr. Gilla Shapiro

Gilla Shapiro is a clinical and health psychologist at the Department of Supportive Care, Princess Margaret Cancer Centre, and an Assistant Professor (status) at the Department of Psychiatry and Dalla Lana School of Public Health, University of Toronto.

Dr. Shapiro completed a PhD at McGill University and a dual-degree MPA/MPP at the London School of Economics and the Hertie School of Governance. Her work focuses on understanding health decision making and behaviour, improving mental health, identifying the social determinants of health, and promoting health equity. Dr. Shapiro has published over 60 peer-reviewed manuscripts, book chapters, and commissioned reports. Her research is currently funded by the Canadian Institutes of Health Research and Canadian Immunization Research Network.

VIEWPOINT FACULTY HIGHLIGHTS

Dr. Mammatha Bhat

Dr. Mamatha Bhat is a hepatologist and clinician-scientist at UHN’s Ajmera Transplant Centre, and associate professor of medicine at the University of Toronto. The goal of her translational research program is to improve long-term outcomes of liver transplantation for cancer and MASLD using tools of artificial intelligence with bioinformatics.

Dr. Michelle Nadler

Dr. Nadler has an academic focus on knowledge translation (implementation) related to a) physical activity/ rehab for oncology-related effects of treatment including cardio-oncology and b) breast cancer screening.

Dr. Monica Serban

Dr. Monica Serban is a Medical Physicist and Clinician Investigator at the Princess Margaret Cancer Centre and Assistant Professor at University of Toronto, Department of Radiation Oncology. Her research focuses on cervix cancer radiotherapy, machine learning to improve morbidity outcomes and advanced image processing and dose computation methods.

Graphic design by Genevieve Groulx

Dr. Melanie Penner

Dr. Penner’s clinical and research interests are focused on autism and other neurodevelopmental conditions. In particular, she is interested in service delivery for this population, including evaluating the impact of new care models.

Dr. Penner has done research and educational work to expand Ontario’s diagnostic capacity for autism diagnoses in the community setting, aiming to decrease wait times and facilitate earlier access to essential therapies.

Dr. Jennifer Kwan

Dr. Jennifer Kwan is a breast radiation oncologist and clinician-scientist at the Princess Margaret Cancer Centre. Her

research focuses on developing novel personalized biomarkers and therapeutics for long-term and late effects of cancer treatment.

Dr. Raphael Schneider

Dr. Schneider is a neurologist at the BALRO MS clinic and associate scientist at the Keenan Research Centre for Biomedical Science (Unity Health Toronto).

His main research interests are neuroimmunology and fluid biomarker discovery for people with multiple sclerosis.

Dr. Michael Velec

Dr. Omair Husain

Dr. Evan Tannenbaum

Dr. Miranda Witheford

Dr. Velec is Dr Husain is a radiation therapist clinician scientist and clinicianat CAMH and scientist at the has experience of Princess Margaret leading clinical Cancer Centre. research studies His research in psychotic focuses on MRI-guided and adaptive radiation spectrum disorders, including clinical trials of therapy to account for organ motion during novel pharmacological agents and psychosocial treatment and improve tumor control while interventions. His work also includes sophisticated minimizing side effects. neuroimaging studies that aim to elucidate the neurobiology of psychotic spectrum disorders.

I am a General OB/GYN, practicing at Mount Sinai hospital. My research focuses on medical education, including curriculum development, assessment, and simulation.

Dr. Tom Wright

Using visual electrophysiology techniques including electroretinograms and visual evoked potentials as well as high resolution retinal imaging, Dr. Wright runs a clinical diagnostic service providing diagnostic support and disease monitoring for patients with inheritable and acquired retinal disease. His research applies machine learning techniques to optimise disease detection.

Dr Witheford is a vascular surgeon at Toronto General Hospital with a practice in complex endovascular aortic repair. Her lab is developing AI-based models of aortic repair failure, reflecting the intersection of aortic-stent interactions, patient pathophysiology and social disadvantage.

Dr. Yat Tsang Yat is an Associate Professor at the Department of Radiation Oncology in University of Toronto.

His research focus includes a broad range of radiation oncology topics, including radiotherapy trial quality assurance, ultra-hypofractionated/ stereotactic radiotherapy treatment outcomes, and strategies to futureproofing radiation therapist practice.

IMS MAGAZINE WINTER 2024 NON-TRADITIONAL THERAPIES | 31

ALUMNI SPOTLIGHT

Dr. Tyler’s Journey to Leadership in Public Health

By Denise Sabac

D

r. Andrea Tyler is the chief of Computational Biology at the National Microbiology Laboratory (NML) and an alum of the Institute of Medical Science (IMS) program at the University of Toronto. In addition, she is a kind and motivated individual who enthusiastically offered to share her story with us to inspire current and future students in the program.

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In an ideal world, when we are unsure why someone is sick, we could ‘get a cerebrospinal fluid sample and run a meta genomics assay on it to help identify what the disease-causing agent is.’

Andrea Tyler completed her Doctor of Philosophy (Ph.D.) at the University of Toronto in 2013. After specializing in microbiology during her undergraduate studies, she chose to investigate inflammatory bowel disease for her Ph.D. work. After four short years, she moved back to her hometown in Winnipeg to pursue a unique opportunity to complete her post-doctoral studies at Canada’s NML. The NML is part of the Public Health Agency of Canada and conducts research that supports preparedness and response to infectious and chronic disease control.1 Accordingly, Andrea Tyler was fascinated by the potential to work in a Biosafety Level 4 laboratory (highest level of risk) and investigate an array of pathogens. While Dr. Tyler faced some uncertainty regarding what she would do after graduating from IMS, once this laboratory caught her attention during her graduate studies, she immediately knew this was the right fit for her.

whole genome sequencing of Canadian TB islets to assess whether genetic data can improve our ability to track outbreaks and predict bacterial phenotypes. After completing this work, she continued her involvement at the NML by accepting a position in the bio-forensics group.

Subsequently, she was promoted to her current position as the chief of the department of Computational Biology.

As a Postdoctoral Fellow at the NML, Dr. Tyler studied Mycobacterium tuberculosis (TB). More specifically, she conducted

Currently, her research focuses on understanding the genetic composition of pathogens that threaten public health.

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During our interview, Dr. Tyler provided some examples of her work during the COVID-19 pandemic to explain her responsibilities at the NML. She mentioned that throughout the pandemic, her work emphasized increasing whole genome sequencing of the SARS-CoV-2 pathogen across Canada to understand its molecular mechanisms. Further, she was interested in more broadly using data from these sequencing projects for public health use rather than just niche areas of research. Following this mandate, she became involved in the processing of about 600,000 isolates across Canada.

Furthermore, Dr. Tyler developed the pipelines and tools needed to process this abundant data and make it accessible for use. Despite the demanding nature of this project alone, Dr. Tyler also develops similar pipelines for other pathogens.

Every day, she works towards improving the health of our nation one sequencing analysis at a time.

Dr. Tyler also emphasized her interest and appreciation for the computational nature of her work; she enjoys the fastpaced nature of statistical methods and their ability to keep up with the rapidly evolving healthcare needs of our country.

She also expressed her appreciation for her team and other collaborators who support her work. As leader of the Computational Biology team, Dr. Tyler supervises a group of scientists that support her ability to meet public health needs through high-impact research. Furthermore, she works with epidemiologists and public Graphic design by Anne McGrath

ALUMNI SPOTLIGHT

Dr. Andrea Tyler, PhD

Photo Credit: Dr. Tyler

health partners who inform her work and facilitate its influence on public health policies. In the future, Dr. Tyler hopes to create new collaborations that will support her research interests to pursue agnostic pathogen detection within metagenomic samples. She describes that in an ideal world, when we are unsure why someone is sick, we could “get a cerebrospinal fluid (CSF) sample and run a meta genomics assay on it to help identify what the disease-causing agent is.” In summary, Dr. Tyler will continue to create meaningful partnerships that support her involvement in clinically focused and influential research.

When I asked about her ability to navigate this demanding role, Dr. Tyler mentioned that she “got a lot of transferable skills from IMS,” which benefitted her success.

She explained that because a lot of her

Ph.D. work was self-directed, she acquired the ability to learn new computational skills independently, which supported her continued growth. On the other hand, one challenge she faced was navigating career development and self-promotion, which Dr. Tyler defines as knowing how to convey to others the skills that one possesses. While this was difficult for her at first, she gradually acquired the vocabulary and confidence needed to communicate her strengths, which she believes was foundational to acquiring her current position. Furthermore, by growing her communication skills, she can instill an encouraging and supportive environment in her lab by reminding her staff of their capabilities and amazing work. Lastly, adopting this managerial role was new to her. Previously, she was accustomed to doing all the “nitty gritty” work herself and misses that aspect sometimes; however, she expressed that these sentiments are replaced by fulfillment from seeing the great work completed by the people she is supervising.

Dr. Tyler also expressed that she enjoys working for the government. She explained that her lab is “not dependent on grant-based funding to maintain operations,” which minimizes the stress of supervising an academic team. In addition, she explained that by working in the public health sector, she enjoys seeing the direct impact of her research on public health policy. Another benefit that she conveyed is the flexibility of her work; if there is a specific topic that she wishes to investigate further, she can pursue grant

applications to support new projects in addition to her existing research. Last, she conveyed her appreciation for the strong work-life balance that her current role offers. Dr. Tyler can work from home most days, although she also thanks the computational nature of her work for that possibility. Further, her workdays typically end at 4 p.m., allowing her to disconnect at the end of the day–at least most days.

Because she works in a managerial role in the public health sector, Dr. Tyler must still be available to attend to work emergencies.

During the pandemic, she explained that such emergencies were more frequent, while today, they are rare. Nevertheless, Dr. Tyler’s appreciation for her current role was evident throughout our discussion.

Lastly, I asked Dr. Tyler what she desired to convey to current IMS students, and her response emphasized the importance of networking. She mentioned that students should “make the most of opportunities to meet new people.” Dr. Tyler initially got into NML through a collaborator that she worked with in graduate school, so she encourages students to take the opportunity to network “because you never know what doors it could open.” At large, she conveys that relationships are foundational to her success and encourages students to make meaningful partnerships along their journey.

References 1. Canada PHA of. Government of Canada. / Gouvernement du Canada; 2023 https://www.canada.ca/en/public-health/programs/ national-microbiology-laboratory.html

IMS MAGAZINE WINTER 2024 NON-TRADITIONAL THERAPIES | 33

TRAVEL BITES

Lille’s charm was its cobblestoned streets and captivating architecture.

Echoes of Hope: Navigating Mesothelioma Breakthroughs in Lille

By Sara Shariati

I

n the realm of medicine, an archetypal debate has always existed between prevention and treatment, especially concerning life-threatening illnesses that are costly to manage. Mesothelioma management and care embody this debate.

Mesothelioma is a rare but aggressive cancer with very poor prognosis, found in the lungs’ lining. Mainly found in the elderly, this cancer’s roots often trace back to asbestos exposure.

For years, the bleak treatment landscape for mesothelioma directed the medical community’s energy towards prevention, pushing researchers to continually emphasize the ominous link between asbestos and the disease. Their fervent advocacy bore fruit, culminating in a ban on asbestos in many countries, including Canada, by the late 20th century.

However, times are changing. With breakthroughs in mesothelioma research, the pendulum has swung from prevention to exploring innovative treatments. Since the world has largely turned its back on asbestos, mesothelioma researchers have channeled their energies into crafting new lifelines for the patients. These

promising rays of hope took center stage at the 16th International Conference of the International Mesothelioma Interest Group (iMig 2023).

This June, I embarked on a transformative journey. Lille, a historic city in northern France, played host to my first-ever international research conference. There, scientists from across the globe painted a hopeful future, detailing advancements ranging from novel chemotherapy and immunotherapy drugs to radiotherapy and cutting-edge surgical procedures. What truly captivated me was the potential of harnessing gene expression profiles and cell surface markers to move towards personalized treatments for mesothelioma patients. Genomic sequencing of biopsy samples can now help physicians and researchers determine which treatment options might be most effective for the specific patient in question.

The collective efforts of researchers have not only pushed mesothelioma patients closer to personalized medicine than ever before, but they have also increased the average life expectancy for patients from a scant 5 years to an encouraging

34 | IMS MAGAZINE WINTER 2024 NON-TRADITIONAL THERAPIES

This microscope, displayed at Musée de l’Hospice Comtesse, is one of the seven built between 1751 and 1754 at the request of the physicist Duc de Chalnes, a member of the Royal Academy of Sciences.

12—which is something Dr. Cherperee, iMig 2023 Chair, shone a light on in his opening remarks at the conference. It is astonishing to think about the quick pace of advancements in the field of mesothelioma.

While iMig 2023 was fascinating, attending this comprehensive conference was not the only highlight of my trip to Lille. Post-conference, I walked along the old and storied streets of Lille and went to a couple of its local cafes. Lille’s culinary delights—savory crepes, sweet waffles, and the traditional Flemish dish, carbonade flamande—added flavor to my trip. The Musée de l’Hospice Comtesse, a hospital dating back to 1237, was my favorite tourist attraction in the city. Initially built as a sanctuary by nuns dedicated to caring for the sick, this building later served as a refuge durwwing the tumultuous French Revolution. It now stands as a museum, housing glimpses of Lille’s past and artifacts like an 18th-century microscope.

When looking back on my trip, I see that Lille has gifted me memories rich in knowledge, beauty, and flavour that I will cherish forever.

Graphic design by Andrew Janeczek

TV COMMENTARY

Painkiller: The Dark Side of Big Pharma Revealed

By Manhbod Ebrahimi

P

ainkiller, a recent Netflix drama mini-series, portrays the true story behind the development of the highly addictive drug, OxyContin, and the people who pushed for its popularity. The series elegantly displays how a hunger for money could potentially destroy thousands of lives. At its core, Painkiller is about critical moments leading up to the opioid epidemic and how it could have been avoided, but was not.

The Sackler family, famously known for their big donations to museums and universities, were and currently are the owners of a privately held family business, Purdue Pharma, which is the company behind the development of the prescription painkiller OxyContin. Upon its release in 1995, OxyContin soon became a blockbuster drug and has reportedly generated over 35 billion dollars for Purdue. But OxyContin is no ordinary drug. Its main ingredient is oxycodone, a chemical relative of heroin, which is up to twice as strong as morphine.

Before the launch of OxyContin, doctors were generally reluctant to prescribe strong opioids (except for end-of-life palliative care and some types of cancer) due to the well-established fears of addiction to these drugs. However, Purdue started a massive promotional campaign that aimed to change how doctors prescribe opioids. OxyContin was designed so that people in need of relief from pain could not refuse the prescription, and Purdue strategically recruited attractive sales representatives to persuade and Graphic design by Brendan Lazar

pressure doctors to not only prescribe the drug, but in the highest possible doses.

This deliberate and strategic marketing campaign is extensively shown in the miniseries through the lens of two fictional sales representatives (played by West Duckovny and Dina Shihabi) who travel across the US to make sure doctors prescribe OxyContin with the highest possible does, no matter the cost. Painkiller demonstrates the power of marketing and persuasion tactics to its limits, potentially a reason why many people might not trust big pharmaceutical companies.

The Sackler family had to overcome many hurdles before launching OxyContin.

One of the major roadblocks was the FDA approval (the administration responsible for drug efficacy and safety before public distribution). At first, a single FDA examiner, Curtis Wright, became a serious roadblock to the drug’s application approval. However, in a mysterious way, Wright soon signed off on the drug’s efficacy and approved OxyContin’s application because of the following statement: “Delayed absorption, as provided

by OxyContin tablets, is believed to reduce the abuse liability of the drug.” The words “is believed,” a completely subjective statement, were the anchoring claim from Purdue.

It would be mind-blowing how a drug on the scale of OxyContin could be approved without major scientific-based research today. If this fact was not shocking enough, Curtis Wright left the FDA and joined Purdue Pharma one year after approving the application for OxyContin.

Since 1999, over three hundred thousand Americans have died from overdoses related to OxyContin and other prescription opioids1. For many people, prescription painkillers are too expensive or too difficult to obtain, so they turn to heroin1. In fact, according to the American Society of Addiction Medicine, four out of five people who use heroin today started with prescription painkillers1. In the show, the journey of addiction is shown by the story of the fictional character Glen Kryger (played

by Taylor Kitsch), a family man and the owner of a mechanic shop who gets injured on the job. He undergoes surgery, and to relieve his pain, one doctor prescribes him OxyContin. Through six episodes, Glen slowly becomes more and more dependent on the drug. With this addiction, we can see how Glen loses his family, his job, and eventually his life.

In my opinion, Painkiller brilliantly displays the story of greed, corruption, and manipulation. Of how big pharmaceutical companies might only care about their own agenda, which in many cases is making profit, could overrule any ethical standpoints.

This point is captured by one of the show’s executive producers Alex Gibney where he says: “I realized that this opioid crisis I’ve been hearing so much about was not just a crisis, it was really a crime”.

References 1. 1-Keefe, P. R. (2017, October 23). The family that built an empire of pain. The New Yorker. https://www.newyorker.com/magazine/2017/10/30/the-family-that-built-an-empire-of-pain

IMS MAGAZINE WINTER 2024 NON-TRADITIONAL THERAPIES | 35

DIVERSITY IN SCIENCE

“

By Janet Z. Li

E

very year, on February 11th, we celebrate the International Day of Women and Girls in Science; a day implemented by UNESCO in collaboration with UN-Women to promote the role of women and girls in scientific fields and recognize those already successful in the field.1 In certain areas of the world, the ratio of women to men in STEM careers is as high as 43%, such is the case of the employees in the European Union.2 Despite a couple of outlier ratios, in the vast majority of workforce populations, women are still likely to make up less than 25% of their industries.2 In the last decade, the number of women enrolling in STEM programs at universities has increased, with provinces like Ontario quoting up to an 8% raise since the early 2010s.3 We owe much of this positive trajectory to pioneering women from decades past and present who have proved that women are marking remarkable strides, shattering the glass ceiling, and redefining the boundaries of what is possible. Scientists such as Marie Curie and Drs. Jennifer Doudna and Emmanuelle Charpentier, but also tech titans like Susan Wojcicki, the CEO of YouTube, have inspired a generation of girls to pursue their STEM dreams and ambitions.

While strides have been made, the underrepresentation of women in STEM fields is still a persistent issue that frequently gets dismissed. Adversities that women encounter in STEM, from gender bias and work-life balance challenges to lack of representation in leadership

It's our time to shine

roles, continue to impede their career progressions. The most vocalized issue of this topic is gender bias, encompassing but-topics such as hiring bias, promotion bias, and unequal pay. Studies show that 34% of women were more likely to state that STEM positions are “hard to understand” when compared to men’s responses.⁴ Accordingly, less than a quarter of young women describe technologybased courses as their favorite subjects in school, and males are significantly more likely to say that they believe they would excel in a STEM job following school.⁴ To further the gap, added pressure comes from expectations that are placed upon these women when stepping into what society deems as ‘prestigious’ and ‘technical’ jobs. The ‘confidence gap’ – where women with a fondness for STEM fields are discouraged or lose interest– is widening despite improvement in other aspects of this fight for equality.⁴,⁵ In general, many girls lose confidence in their math abilities by third grade, and this disparity only becomes stronger when factoring in additional aspects such as race and sociodemographic background.⁴ While women of Asian background have seen a small but visible increase of representation over the years, Black and Hispanic female workers remain severely underrepresented in the STEM workforce.⁶ A transformation of STEM careers is underway. Many think of it as a top-tobottom trickle-down effect, suggesting that change in leaders of the field–the role models of future generations–is the ideal

36 | IMS MAGAZINE WINTER 2024 NON-TRADITIONAL THERAPIES

“

Who Run the World?

Girls.

kickstart to rebranding these fields as a whole.⁴ Here are a few standouts whose work over the years has provided the hopes and dreams of countless women, despite nominal mainstream recognition:⁷

Katherine Johnson, NASA Space Scientist In 2015, she was awarded the Presidential Medal of Freedom for her lifetime’s work in physics, math, and space research.

Katherine was, and still is, one of very few African American women to be recognized for her ground-breaking work in a STEM-related field.

Radia Perlman, Mother of the Internet Computer scientist from MIT, she developed the algorithm behind the Spanning Tree Protocol, a innovation that provides the basis for the eventual development of today’s Internet.

Colleagues described her as quiet and determined, a shining example of how hard work could lead to breakthrough a success in a fast-paced industry.

Florence Nightingale, Lady with the Lamp During the Crimean War, she was credited for singlehandedly reducing the death rate from 42% down to 2% as a nurse.

DIVERSITY IN SCIENCE

amongst young women around the world.

Her background in Chinese medicine served as a integral part of her artemisinin combination therapy against malaria.

Ginni Rometty, CEO of IBM

Not only was she well-known for her in-field medical skills, but she was also a renowned statistician and systems designer. Her proportional pie chart format is still used today as the Diagram of the Causes of Mortality.

Adriana Ocampo, Planetary Geologist Dr. Ocampo has been named one of the 50 most Important Women in Science for her work with NASA, including but not limited to the Juno mission to Jupiter and the New Horizons mission to Pluto.

Tu YouYou, Nobel Prize Malariologist The first Chinese woman to win a science-based Nobel Prize, and without a doctorate, medical degree, or training abroad, she is a beacon of inspiration Graphic design by Jo Choi

Since 2012, she has been the CEO of the multinational technology company IBM bringing a new tech-savvy front to the company with her systems engineering background. She’s been described as inspirational and dedicated by those around her, and her famous philosophy of “leading with good power” is also a top selling book.⁸

Barbara McClintock, Nobel Prize Geneticist One of few women to have received by herself a Nobel Prize for Medicine to commemorate her discovery of genetic material being fluid. Her feminist perspectives and mindset regarding science being open ended and unresolved are also well known amongst the STEM community.

Women continue to overcome adversities and transcend in STEM careers, driving innovation and progress every day. As we continue to acknowledge and address the challenges faced by women in STEM, society can create more equitable environments where all individuals,

regardless of sex, can thrive. Leaders and the greater community at large both need to foster inclusive workspaces, challenge stereotypes, and provide strong support systems to better empower women in STEM. The trailblazing work of many women of the past has paved the way for future generations of young women and underrepresented minorities to excel in careers that they love. Beyoncé was right; girls do in fact run the world, and it’s our time to shine.

References 1. International Day of Women and Girls in Science [Internet]. Wikipedia. 2023 [cited 2023 Nov 6]. Available from: https://en.wikipedia. org/wiki/International_Day_of_Women_and_Girls_in_Science 2. Women in STEM in 2023 | Randstad Canada [Internet]. www. randstad.ca. [cited 2023 Nov 6]. Available from: https://www.randstad.ca/employers/workplace-insights/women-in-the-workplace/ women-in-stem-where-we-are-now/#:~:text=This%20also%20 means%20men%20still 3. Robertson Y. Partnering to Empower Women and Girls in STEM Ontario’s Universities [Internet]. Ontario’s Universities - Partnering for a better future. 2022 [cited 2023 Nov 6]. Available from: https:// ontariosuniversities.ca/partnering-to-empower-women-and-girlsin-stem#: ~:text=According%20to%20recent%20Ontario%20 university 4. American Association of University Women. The STEM Gap: Women and Girls in Science, Technology, Engineering and Math – AAUW : Empowering Women since 1881 [Internet]. AAUW. 2020. Available from: https://www.aauw.org/resources/research/ the-stem-gap/ 5. Women in STEM face a “confidence gap.” Here’s what that means, and how to fix it [Internet]. Salon. 2021. Available from: https:// www.salon.com/2021/03/28/women-in-stem-face-a-confidencegap-hereswhat-that-means-and-how-to-fix-it/ 6. Fry R, Kennedy B, Funk C. STEM Jobs See Uneven Progress in Increasing Gender, Racial and Ethnic Diversity. Pew Research Center [Internet]. 2021 Apr 1; Available from: https://www.pewresearch. org/science/2021/04/01/stem-jobs-see-uneven-progress-in-increasing-gender-racial-and-ethnic-diversity/ 7. 13 Women in STEM Who Changed the World [Internet]. International Women’s Day. International Women’s Day; 2015. Available from: https://www.internationalwomensday.com/Activity/7213/13Women-in-STEM-Who-Changed-the-World 8. IBM’s Ginni Rometty: Leading with Good Power - Case - Faculty & Research - Harvard Business School [Internet]. www.hbs. edu. Available from: https://www.hbs.edu/faculty/Pages/item. aspx?num=63968

IMS MAGAZINE WINTER 2024 NON-TRADITIONAL THERAPIES | 37

PAST EVENTS

IMS Orientation 2023

By Kristen Ashworth

O

n September 8, 2023, the Institute of Medical Science (IMS) welcomed the new fall IMS graduate cohort with its semi-annual IMS Orientation coordinated by the Institute of Medical Science Students’ Association (IMSSA) core executive team. The morning was hosted at the beautiful Faculty Club, and was action-packed – filled with faculty introductions, ice-breaker activities, program and club presentations, and of course, a delicious breakfast!

The day was kick-started by an address from IMS Director Dr. Minyao Liu and SGS Vice Dean Dr. John Peever, both of whom highlighted the commendable nature of the IMS community, which maintains both exceptional prestige and a tight-knit community cultivated amongst IMS students and faculty alike.

Following these remarks, students were informally enacted into the program by taking the IMS Graduate Student Oath.

Originally created in 2008 by then-IMS director (2000-2010), alumnus, and established faculty member Dr. Ori Rotstein (MD, MSc), this pledge has been a landmark tradition of the IMS

Orientation – and has even been adopted by other graduate institutions around the world since its founding. The purpose of the oath is to remind and ground students in the principles and morals of scientific pursuit. It encourages students to commit and stay true to the values of honesty, integrity, and ethical clarity as they embark on their research careers at IMS. A fun ice-breaker activity mid-way through the morning allowed students to mix and mingle at tables associated with the general vicinity in which they reside in Toronto and the Greater Toronto Area.

The activity allowed students to connect with their geographical neighbours – and perhaps meet a new commuting buddy along the way!

The subsequent presentations introduced students to the wide array of clubs and associations that IMS has to offer, including IMSSA, the Peer-to-Peer

38 | IMS MAGAZINE WINTER 2024 NON-TRADITIONAL THERAPIES

Mentorship Program, U of T Talks, Let’s Talk Grad Wellness, and Raw Talk Podcast, to name a few.

As in years past, the IMS Magazine was showcased both in presentation form and at a booth in the main foyer. Our team was thrilled to meet many eager students who were interested in joining our team this year, and we hope to see you again soon!

A warm welcome to all of our new IMS students, and cheers to a wonderful year ahead.

Photos taken at the Orientation, including complimentary student portraits, may be accessed at the following link for a limited time. https://drive.google.com/drive/ folders/17yLugAwY-3yXLelNUhN5GKM8 mZ6yYKzn?usp=sharing Graphic design by Jayne Leggatt

Behind every discovery, there’s a story.

New episodes available every other Wednesday.

Raw Talk is a graduate student-run podcast at the University of

Toronto about medical science, and the people who make it happen.

We focus on the journeys, perspectives, and expertise of health researchers, professionals, students, patients, and community members at the University of Toronto and beyond.

Listen wherever you get your podcasts or at

www.rawtalkpodcast.com

Follow us for updates, photos, and videos @rawtalkpodcast

Get started with some of our favourite episodes: Ep. 102

Ep. 101

Ep. 100

Ep. 99

Ep. 98

Ep. 97

Healthcare Behind Bars

Refugee Healthcare in Canada

The Many Faces of Burnout in Healthcare

Podium Pills: Fame or Folly?

100 Years Later: Insulin and Beyond

Let’s Talk Grad School

IMS MAGAZINE WINTER 2024 NON-TRADITIONAL THERAPIES | 39

READ IT ONLINE issuu.com/imsmagazine imsmagazine.com @IMSMagazine