A new study from the Center for Addiction and Mental Health (CAMH) will try to harness the antidepressant power of psilocybin mushrooms, but without the psychedelic experience.
Psilocybin is the hallucinogenic chemical compound in “magic” mushrooms that generates a psychedelic mood. However, clinical studies have shown that psilocybin mushrooms also have antidepressant effects on people whose depression is resistant to other treatments when combined with intensive psychotherapy.
For three years, CAMH researchers will try to learn whether the psychedelic experience itself is necessary to treat depression in a federally funded study that lead researcher Dr. Ishrat Hussain says is the first of its kind.
“What we’re trying to look at with this study, which I think is an obvious question in this field, is whether the psychedelic high is necessary for the therapeutic benefits,” Hussain told CTVNews.ca. “It’s supposed to be, but no one has actually designed a clinical trial to answer that question.”
Hussain and his team will compare the results in 60 adults with treatment-resistant depression. During the study, a third of the participants will receive a full dose of psilocybin plus a serotonin blocker to inhibit the drug’s psychedelic effects. Another group will be given psilocybin plus a placebo. The final group will receive placebo plus the serotonin blocker. All participants will also receive 12 hours of psychotherapy.
This is the second clinical trial of psilocybin at CAMH, which was the Canadian site for the world’s largest clinical trial of psilocybin for mental health to date, in 2021.
If the new study shows that psilocybin mushrooms have the same antidepressant effect with or without a psychedelic experience, Hussain said it could be a game-changer for people with treatment-resistant depression who aren’t candidates for a psychedelic high.
“There are certain physical and psychological contraindications to taking powerful psychoactive drugs like psilocybin,” he said. “If we can show that the psychedelic experience isn’t completely necessary, it could lead to something like a new therapeutic development for treating depression.”
“HOPE FOR INNOVATION”
Someday, Carole Daguerre may have to rely on a new treatment. In fact, Daguerre believes it is inevitable. After years of trying to treat her depression, she is in a good place. But she knows it won’t last.
“I’m going to take another dip, no question about it,” Dagger told CTVNews.ca. “It’s just going to be my life, it’s something I’m going to have to deal with.”
Dagher is a patient of Husain’s who suffers from treatment-resistant major depressive disorder and anxiety disorder. She first developed postpartum depression after the birth of her eldest daughter 12 years ago. Her symptoms were compounded by trauma from childhood experiences growing up in Beirut during the Lebanese Civil War. In the years since her initial diagnosis, she has battled suicidal thoughts, tried five classes of antidepressants, seen psychologists and tried both electroconvulsive therapy and repetitive transcranial magnetic stimulation therapy.
After those methods failed, she turned to ketamine therapy, which was approved by Health Canada to treat major depressive disorder in 2020. Ketamine is an anesthetic that produces strong psychedelic experiences in therapeutic doses. Daguerre called the experiences “terrifying” and said they were so unbearable that she almost gave up therapy before completing her eight sessions. However, she stuck with it and woke up one morning after her last session feeling restored.
“I opened my eyes in the morning and the sky was blue and the birds were chirping and I smiled for the first time in 12 years and it was a genuine smile,” she said.
She is still doing well with the help of an antidepressant and regular therapy sessions. But she’s waiting for the day her symptoms stop responding to ketamine. When that day comes, she’ll have to seek another treatment—preferably a non-high one. That’s why she sees such promise in Hussain’s research.
“Without hope for innovation, I cannot survive a single day. Deep in my heart, I have to believe that people like Dr. Hussain and hospitals like CAMH will not stop innovating. Ketamine worked now, but it may not work later,” she said. “And I much prefer not to have the psychedelic trip, but to take [psilocybin] and make him do his job.”
On the issue of access to psilocybin therapy, while Johns Hopkins University scientist David Yaden agrees that being able to offer the therapy without the psychedelic experience would make it available to more people, he worries about patients who may want or need the full experience.
Yaden is an assistant professor at the Johns Hopkins Center for Psychedelic Studies and the Study of Consciousness, who has published numerous scientific papers on the use of psilocybin as a potential treatment.
“What I worry about is an unintended side effect of characterizing the acute subjective effects of psychedelics — the trip, so to speak — as an unwanted side effect,” he told CTVNews.ca.
“As participants are screened and administered psilocybin in a supportive environment, we see that these experiences can be challenging, but are generally very positive and deeply meaningful.” That’s exactly what the data says.”
Yaden also believes, based on past studies, that a dose of psilocybin without the psychedelic side effects likely provides only short-term neurobiological benefits. In a paper published in December 2020, he and fellow Johns Hopkins researcher Roland Griffiths argue that there are long-term, complex changes that can occur in the brain only during a psychedelic experience.
Nonetheless, he said the CAMH study raises important questions in an area of research that his team would like to explore further.
“I support research like this that looks at the causal role of the acute subjective effects of psychedelics because I think it’s a very important question to research,” he said.
“This research is important for both clinical and scientific reasons. It’s great and I’m really glad it’s happening. We are also trying to do this research. I am very much for him.’
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If you or someone you know is struggling with suicidal thoughts or mental health issues, please call the National Suicide Prevention Lifeline at 800-273-8255 (or 988 as of July 16, 2022) or the Canadian Talk Suicide 1-833-456-4566. The following resources are also available to support people in crisis:
Hope for Wellness Hotline (English, French, Cree, Ojibway, and Inuktitut): 1-855-242-3310
Embrace Life Council Hotline: 1-800-265-3333
Trans Lifeline: 1-877-330-6366
Children’s Helpline: 1-800-668-6868
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