What you need to know
Major depressive disorder commonly occurs alongside substance use disorders, especially alcohol use disorder, according to a recent review of the research (Hunt, 2020). This review also found that people with both conditions have more severe symptoms, greater difficulty functioning and more frequent hospitalizations. They are also at greater risk of dying than those with major depression alone. A pilot study is examining the potential of the psychedelic agent, psilocybin, to treat people diagnosed with both major depressive disorder (MDD) and alcohol use disorder (AUD). In this issue of Research As It Happens, we feature a conversation with PhD student, Jacob Cohen, who discusses this pilot study, led by Dr. Bernard Le Foll at the Centre for Addiction and Mental Health. * Jacob’s responses were edited for clarity.
What is the context for this study?
Jacob Cohen: In the last few years, there has been a re-emergence of interest in studying the mental health benefits of psychedelic agents. Many trials so far have shown that, unlike current treatments—such as antidepressant and psychological treatments—psychedelics have rapid and sustained effects. With psychedelics, the trials report huge decreases in symptoms after just one or two doses, whereas the benefits of currently available treatments can take months to manifest. People are recovering faster and staying that way over a longer period.
Tell us about your study.
Jacob Cohen: Major Depressive Disorder and Alcohol Use Disorder are huge problems not only in Canada but also worldwide. Psilocybin is a psychedelic agent that some researchers are testing as a potential treatment for these conditions. However, no published studies have evaluated its safety and efficacy for treatment of people with both conditions—what is called a comorbid disorder.
We are conducting a pilot study to test the safety and efficacy of psilocybin for comorbid MDD and AUD. Researchers at Johns Hopkins University are currently testing psilocybin for comorbid disorder, but they are only using one dose. What is different about our study is that we are going to administer two doses, which in some depression studies was shown to be really effective. Our study is also unique in that participants will also receive psychotherapy, which we know is more effective for both of these conditions.
What is the target population?
Jacob Cohen: We have inclusion and exclusion criteria, but broadly, the target population is anyone who has a dual diagnosis of MDD and AUD and is between the ages of 18 and 65. We are aiming to get 40 participants. Ideally, we will have an equal number of males and females.
Where are you recruiting participants?
Jacob Cohen: We will mostly recruit in Toronto because we have the Concurrent Outpatient Medical & Psychosocial Addiction Support Services (COMPASS) program at CAMH, where there is a dual MDD and AUD clinic. But I think it will be open—if you can travel to Toronto, it should be open.
What are the study methods?
Jacob Cohen: First, we screen each participant to make sure they have both disorders. In Week 1, researchers prepare each participant for their first treatment session, where we discuss what they are about to experience and their expectations. In that session, the participant is in a room with two therapists and receives a dose of psilocybin or placebo, followed by a psychotherapy session. The psychotherapy consists of a validated therapy approach that is similar to acceptance and commitment therapy.
A day—or a few days—later, participants return for an integration session, where the research team reviews the experience with them and what it meant to them. On the third week, each participant returns for another preparation and dosing session, followed a few days later by an integration session. The goal of the integration sessions is to review the participant’s experience during the dosing session thoroughly and, in some cases, apply therapeutic techniques to reinforce particular aspects of the experience and embrace desirable patterns of thought and behaviour. Then they have weekly follow-ups until Week 6, when they have their final visit. At this time, we measure their depression symptoms, alcohol cravings and the total alcohol they drank per day.
What are you hoping will come out of this research?
Jacob Cohen: If this can work in a comorbid disease and work quickly, and if it is safe, not only could it save the system a lot of time and money, but it could also save patients time and money. They will be able to have only one or two sessions and then they will be well for a long time, versus coming in and out of therapy and switching medications, which is not always effective. For those who are suffering, if psilocybin works quickly, it could potentially save lives. It could also be a game changer for people living in rural and remote regions that have limited access to psychiatric and psychological treatments. It’s a really exciting thing to be part of.
What are the limitations of this study?
Jacob Cohen: This is just going to be a pilot trial, so our sample size is only 40 participants, and we are not going to be able to recruit from as diverse backgrounds as we want. Since it is a small sample, we might also have a hard time comparing males versus females—we know there are some sex differences with psychedelic effects and actions. We’re hoping to do larger trials if this pilot proves it is safe and effective in the smaller sample size.
What do you see as this study’s potential contribution to Ontario’s mental health and addiction sector?
Jacob Cohen: A lot of previous research has shied away from looking at comorbid disorders because it is very complex. If we can show that psilocybin is effective in something as complicated as a comorbid disorder, I think it could open the field up and give not just researchers and clinicians hope, but also patients.
Right now, psilocybin use is only legal under two conditions. One is for end-of-life conditions—cancer patients and people nearing the end of their lives, but it’s a really long and complicated process to get approval. The other condition psilocybin can be used for is in clinical trials. If we can show that the treatment works, it is more evidence to get regulatory bodies moving on opening this treatment up.
Are there areas that you would like to see this work expanded on?
Jacob Cohen: There are a million directions we can go because we are coming in at the start of a re-emergence of interest—among regulatory bodies and the public—in psychedelic research. There is still a lot that we do not completely know, from its mechanisms to its efficacy. Also, today we have better chemistry, so some people are designing molecules that do not actually make you have a psychedelic trip but can be equally effective. With bigger sample sizes, we’ll be able to examine efficacy and safety for different disorders and compounds, as well as sex differences, age differences and ethnic differences. It is really a wide-open field.
This study is funded by the Canadian Institutes of Health Research and will potentially start within the next few months.
About the researchers
*The following individuals are involved in this pilot study:
- Bernard Le Foll
Clinician Scientist and Head, Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, CAMH
Lead, Clinical Research Innovation Service, Addiction Division, CAMH
Head, Alcohol Research and Treatment Clinic, CAMH
Chair, Addiction Psychiatry, Department of Psychiatry, University of Toronto
Professor, departments of Family and Community Medicine, Pharmacology and Toxicology, Psychiatry, Institute of Medical Sciences and Dalla Lana School of Public Health, University of Toronto - Jacob Cohen PhD(C)
The Centre for Addiction and Mental Health
Department of Pharmacology & Toxicology, University of Toronto - Clement Ma
Independent Scientist, CAMH
Assistant Professor of Biostatistics, University of Toronto
Assistant Professor, Biostatistics Division, Dalla Lana School of Public Health - Ishrat Husain
Clinician-Scientist and Lead, Mood Disorders Service, CAMH
Scientific Head, Clinical Trials Unit, CAMH
Associate Professor, Neurosciences and Clinical Translation, Department of Psychiatry, University of Toronto - Matthew Sloan
Clinician-Scientist, Addiction Assessment Clinic, CAMH
Assistant Professor, Brain and Therapeutics, Addictions Program, Department of Psychiatry, University of Toronto
Assistant Professor, Department of Psychology, University of Toronto - Ahmed Hassan
Clinician-Scientist and Addiction Psychiatrist, Addiction Medicine Service, CAMH
Assistant Professor, Neurosciences and Clinical Translation, Department of Psychiatry, University of Toronto - David Castle
Professor of Psychiatry, Centre for Mental Health Service Innovation, University of Tasmania - David Nutt
Professor of Psychiatry and Director, Neuropsychopharmacology Unit, Imperial College London, United Kingdom.
References
Hunt, G. E. (2020). Prevalence of comorbid substance use in major depressive disorder in community and clinical settings, 1990–2019: Systematic review and meta-analysis. Journal of Affective Disorders, 266, 288-293. doi: https://doi.org/10.1016/j.jad.2020.01.141