Episode 16: Psychedelics, Psychedelics, Psychedelics! Treatments and the Science
Released: September 24, 2026
Podcast Transcript
Dr. Kuhathasan: Welcome back to another episode of the CAN-BIND Podcast. I’m Nirushi Kuhathasan, your host for today, and in this episode, we’re exploring a topic that has moved from the margins of medicine into the centre of mental health research: psychedelics.
Psychedelic substances have been used in different cultural and therapeutic settings. Today, scientists are taking a closer look at their potential role in treating mental health conditions. But what is it about these substances that could make them useful in mental health care? And how much do we really know about the science behind them? To help us explore these questions, I sat down with Dr. Joshua Rosenblat.
Dr. Rosenblat: My name is Josh Rosenblat. I’m a psychiatrist by training and also a researcher. I’m the head of mental health research here at University Health Network in Toronto and I’m also the CAN-BIND principal investigator for the University Health Network site.
Dr. Kuhathasan: Thank you for joining us. So can you share how you first became interested in psychedelics and what led you to begin researching them?
Dr. Rosenblat: Well, I’ve always been very interested in novel interventions for mood disorders… depression, bipolar disorder, and my initial academic journey started with investigating anti-inflammatory medications actually.
Unfortunately, as I was doing that work, I found that the effect sizes in terms of how beneficial it actually was… was relatively small. So patients were having improvements in their symptoms, there was a signal there. I found it very scientifically interesting, but I started to feel more and more that I needed to find another intervention that would be more effective, more groundbreaking.
At the same time, I was doing a side project investigating ketamine, which is arguably a psychedelic. It’s an anesthetic that we use at lower doses for depression. And in this side project, I was testing it in patients with cancer near the end of life. This really came from a single patient interaction where I saw a patient near the end of life who didn’t want to take antidepressants because they were not interested in experiencing side effects without the benefits since their life expectancy was very short, only a couple weeks long. So they felt that nothing would help them. And what she said to me stuck with me that, ‘If you could give me something that would work within a couple hours, I would take it. But if it’s going to take weeks to months for it to start working, I’m not interested’. And that’s when I came up with the idea to test ketamine because it’s a rapid-acting antidepressant that works within hours in patients with cancer near the end of life.
So we conducted this pilot study to evaluate ketamine in palliative care, and it was quite shocking to sit with these patients near the end of their life and see the dramatic reduction in depressive symptoms. So that study was published in Cancers a couple of years back, and really we saw a massive reduction in their depression severity, improvements in quality of life, improvements in clarity of thought, where they were able to make a lot of important decisions that they need to make near the end of life. So when I saw the effects of ketamine, it really pivoted my career trajectory where I decided to do a lot more research into ketamine and related psychedelics, and I started providing ketamine treatments clinically to patients that were struggling with treatment-resistant mood disorders, but also getting involved in research with real-world effectiveness studies and clinical trials.
Unfortunately, ketamine also doesn’t work for everyone. So as I was doing more and more ketamine research, I had the opportunity to participate as an investigator of an industry-supported study evaluating psilocybin, the active ingredient in magic mushrooms. So Canada only had two sites. We were one site, and we recruited three people. The Centre for Addiction Mental Health was the other Canadian site that recruited three people as well. But even just from seeing those three people participating in the study, I was quite taken aback with how strongly the effects were observed, where a couple of those patients did very well. And I started to think this is another area to explore. As I read more literature, it seemed like psilocybin, magic mushrooms, and other classic psychedelics seemed extremely promising. So this was when I started to add to the ketamine work, looking into other psychedelics such as psilocybin.
With psilocybin at that time, there had actually been no Health Canada-regulated investigator-initiated trials in the country at all.
Dr. Kuhathasan: Wow.
Dr. Rosenblat: We wanted to also be able to provide psilocybin as a treatment clinically, and we’re trying to get exemptions for our patients, so how I ended up doing my first psilocybin clinical trial was because Health Canada basically said, ‘the only way you can get psilocybin for your patients is if you do a clinical trial’.
Dr. Kuhathasan: Wow.
Dr. Rosenblat: So I had a couple of patients where I was applying literally for two years. I tried to get exemptions to give these patients psilocybin outside of clinical trials because it’s very hard and expensive to do clinical trials, and Health Canada kept saying the same thing. ‘Do a clinical trial, do a clinical trial’. So that’s what led us to lead Canada’s first investigator-initiated Health Canada-regulated psilocybin clinical trial, which we published a couple of years back in Med by Cell Press, and in this study, we treated 30 Canadians with psilocybin and we found extremely good results. So that was the first sort of, soiree into psilocybin and more classic psychedelics… and just seeing is believing sometimes. Seeing the dramatic effects in that study led me to really grow our program.
So my path to psychedelic research was sort of through initially looking at other investigations, being frustrated with the lack of benefits of looking for something else, stumbling upon ketamine, finding some very robust effects with that, and then that leading towards exploring other psychedelics such as psilocybin. And now we’re exploring several other things, and we’re really building up the pipeline of different mechanistically diverse psychedelic agents that we’re investigating.
Dr. Kuhathasan: That’s really interesting and it seems to really fit into that broader momentum around psychedelic research that we’re seeing maybe more globally right now.
Dr. Rosenblat: Yes, absolutely.
Dr. Kuhathasan: So what kind of research are you doing around psychedelics right now?
Dr. Rosenblat: Yeah, so we’ve built up a fairly large pipeline of clinical trials investigating various psychedelics for various interventions. So the specific drugs that are currently under investigation are ketamine, psilocybin, nitrous oxide, and MDMA. Those are the ones that we’re studying at University Health Network right now within my program.
So with ketamine, we just completed two large trials investigating it for bipolar depression, where there’s been a lot of interest for depression, but people are worried maybe psychedelics will trigger mania or psychosis in bipolar disorder. And so we just completed a large study along with an open label extension trial after evaluating it in bipolar depression. The results aren’t published yet, but have been presented at conferences, and we found a very large effect size that was statistically significant and clinically meaningful, suggesting that it’s effective and also didn’t trigger mania or psychosis in any of the participants. Those trials have just wrapped up and we’re hoping to publish those results very soon.
We’re now getting into looking at combining ketamine with psychotherapy to try to amplify the benefits. The idea here is that ketamine creates a window of neuroplasticity where your brain is more flexible and able to make changes that it might have not been able to make before. So for patients that are not benefiting from psychotherapy, it might be because their mindset is too rigid, they’re not able to change the way they think. But the idea is that ketamine and other psychedelics might loosen this, at least temporarily, to allow you to fully engage and benefit from psychotherapy. So we have one study evaluating ketamine in combination with cognitive behavioral therapy for suicidality in patients with treatment-resistant depression. And we have another study, where we’re looking at a very difficult-to-treat group with treatment-resistant depression that also have borderline personality. So for them, we’re combining ketamine with dialectical behavioral therapy to target suicidality in this very high-risk population that is a personality disorder, plus a mood disorder. And all that work is funded through federal granting agencies, as well as provincial granting agencies. Which I think is an important distinction right now as well, where these are not industry-sponsored studies, these are purely academically, government-funded studies that were answering these questions. So that’s on the ketamine side.
The other big program that we have is psilocybin, where we have several studies. Ishrat Husain, my colleague at CAMH, who’s now at UHN as well… we’ve been collaborating in this area for years and doing these multi-site studies together. And we’re really looking at the fundamental questions here about the basics of ‘how can we optimize these treatments’. So for example, this year we’ll be finishing a study comparing ‘do you need one dose of psilocybin or two’? All previous studies have either given one or two, and we don’t know if you need one or two doses to maximize the benefits. So a very important question.
Another study we’re going to be doing soon is testing the role of psychotherapy. What’s the nature of the therapy? What’s the dose of psychotherapy that you need to have the benefits of psilocybin?
We’re quite interested in psilocybin for bipolar disorder because those patients have always been excluded previously. We did a pilot study finding that it seemed to be quite safe and efficacious, so now we’re doing larger studies where we’re doing one study looking at the neurobiological outcomes to see if we increase the volume of your emotions, as evidenced by your amygdala reacting to emotional stimuli, is that actually helpful for bipolar disorder? Because we know psilocybin increases the volume of your amygdala or your emotions, and that’s usually a bad thing with bipolar disorder, where we’re trying to use mood stabilizers to dampen the amygdala and the emotion centre. But we’re doing this very interesting MRI/fMRI study, where we’re giving people with bipolar disorder psilocybin and we’re doing the psychotherapy, and the idea is that, you know, for some people, especially treatment-resistant bipolar depression… they might not need to suppress their emotions. They might need to feel their emotions, process it in psychotherapy, and heal through that pathway.
That study, we’ll also be finishing this year, and recruitment is going very well. And then the follow-up to that is, we were lucky to receive CIHR funding, along with our colleague Lakshmi Yatham, leading this charge to do a multi-site RCT, randomized control trial, to really test the efficacy and safety of psilocybin for bipolar 2 depression, particularly treatment-resistant depression within that population. The one that we just got funded by the federal government through the Canadian Institute of Health Research, CIHR, is a randomized control trial that will be the first RCT to evaluate add-on psilocybin to existing antidepressant treatment. So all previous randomized controlled trials have required people to stop their antidepressants. In my experience running these trials, that’s been very hard. Patients often are getting at least a partial benefit, even if they’re not fully well on their antidepressants, things like SSRIs, Prozac, Ciprolex, these types of medications, even if they’re not fully well on these antidepressants, usually they’re at least getting some benefits from it. So what we’re seeing in our trials is when we stop the antidepressants, people are getting worse, and they’re also having withdrawal, serotonin discontinuation syndrome, where they’re having things like brain zaps, worsening anxiety and depression, insomnia. So what we want to test and see: can we keep people on their antidepressant and just add psilocybin on top to boost it as an adjunctive treatment? So no one’s tested that in a randomized controlled trial. So we know patients have been asking for it, and that, theoretically, this seems like this should still be effective and safe, but we need to test this. So we’re doing the first RCT in the world to test this fundamental question. So that’s a few of the psilocybin trials.
And then nitrous oxide, and MDMA, and some other molecules… these ones are more so one-offs. I’m working with collaborators. I have a collaborator in anesthesiology, Karim Ladha, that’s really interested in nitrous oxide and repurposing anaesthetics for depression. So working with him to do this multi-site trial. Another colleague from anaesthesia, Akash Goel, looking at studying MDMA/ecstasy for chronic pain. So we’re going to be a site for that study as well.
This area really is exploding right now in Canada, and to think that just five years ago, we had zero psychedelic studies going on in Canada. So it’s been wonderful to see the tremendous growth with our first psilocybin study that I mentioned earlier, to now over 40 studies going on across the country of people studying psychedelics for various indications.
Dr. Kuhathasan: Wow, it sounds like you’ve got a lot of exciting research in the works.
Dr. Rosenblat: Mhmm, yeah, it’s exciting times to be here for sure.
Dr. Kuhathasan: So, I mean, I guess you’ve touched on this a bit, but when people think of psychedelics, they generally think of things like magic mushrooms and LSD, but what exactly then counts as a psychedelic?
Dr. Rosenblat: Yeah, that’s a great question and it’s a bit controversial. So one simple way of looking at it is based on the receptors. So there’s a category called classic psychedelics or serotonergic psychedelics, where what unites that category is they all stimulate or activate the serotonin 2A receptor. Activation of the serotonin 2A receptor is what leads to the psychedelic non-ordinary state of consciousness that is classically associated with psychedelics. Things that would be in the classic psychedelic category would be psilocybin, magic mushrooms, LSD, DMT, 5-MeO-DMT, ayahuasca… these are the things that what unites all of them is that they stimulate the serotonin 2A receptor.
However, another way of conceptualizing psychedelics is the nature of the non-ordinary state of consciousness. So for example, ketamine creates a psychedelic experience as well. It does it through antagonizing the NMDA receptor through the glutamate system, so not through the serotonin system, but the experience might actually be quite psychedelic in nature and quite comparable to a psilocybin or LSD, even though some qualitative differences. Similarly, high doses of dextromethorphan can create quite a psychedelic experience. MDMA is a bit controversial in terms of, is this a psychedelic or not, because it works through dramatically increasing release of monoamines acutely… serotonin, norepinephrine, and dopamine. So there’s questions of what counts and what doesn’t.
I lean more towards the side of, we should look at the phenomenology of the non-ordinary state of experience. So I think more important than looking at the receptors, is what is the subjective psychological experience that patients are having? And if it is this, unique, nonordinary psychedelic experience, I would call that a psychedelic, whether that’s through the NMDA receptor or the serotonin 2A receptor… but there’s different ways of slicing this.
Dr. Kuhathasan: So are there specific parts of the brain that are always involved when someone takes a psychedelic?
Dr. Rosenblat: Yeah, that’s another really fascinating part about psychedelics is that there are these serotonin receptors fairly widely expressed throughout the brain. So yes, there are certain areas that have greater density of serotonin receptors, but we really see serotonin and NMDA receptors expressed broadly throughout the brain. And that matches up with when we look at the MRI studies and the fMRI studies and the EEG studies, where to simplify it a bit, it’s this idea that you’re setting a bit of a reset switch where you’re increasing activity of the default mode network and then decreasing it. So you’re just allowing for new neuronal connections to grow through increased neuroplasticity as well. So the mechanism of action is a big hot area that we’re investigating right now. And I should mention, in all of our studies, we do MRIs at baseline and also after treatment because we also want to really know what’s going on in the brain. Not just does it work, but how does it work?
Dr. Kuhathasan: So what does it actually look like when a patient is participating in maybe a psilocybin study or a psychedelic science study of some sort?
Dr. Rosenblat: Great question. So within our program, we’re always combining psilocybin with psychotherapy. So after a patient has been screened and found eligible and wants to proceed with the clinical trial, they would start with meeting the trained psychedelic therapist. Usually this would be two therapists, a psychiatrist and a non-physician psychotherapist… is the typical dyad pair that we have at our site. And they would meet with the patient at least twice before receiving the psilocybin.
During these what we call preparation psychotherapy sessions, the patient would get to know the therapist, the therapist would get to know the patient, understand their life narrative, what’s brought them here, what it’s been like to live with their mental illness, and they would also work on setting intentions. What do they want to get out of the psilocybin experience? What are they hoping will change in their life? What are they hoping to heal from? These are all the types of intentions that they can set going in so that they have that in mind for what they hope to get from the psilocybin experience. We also go through education to help alleviate anxiety as well, helping to prepare patients, describing what the psychedelic dosing experience would be like, what the day will look like. In the preparation sessions, we’re also meeting with them typically in the psilocybin dosing room so they can become familiar with the space and there’s no surprises on dosing day from that perspective. And then after they’ve had those preparation psychotherapy sessions, they would come for the dosing session.
For the dosing session, they would actually be in the clinic, in the dosing room for about 8 hours that day. So it is a long day. So they would ingest the psilocybin orally, in a capsule or in a liquid. The effects would start around 30 minutes, they peak around 90 minutes, and then they’re resolved by 4 hours. So about a 4-hour experience with the majority of the intense experience being 1 or 2 hours.
During that 6-hour experience, they’re in the dosing room laying down on the couch or the bed, with an eye covering on and headphones listening to a pre-selected playlist. The therapists sit there next to them to support them through any difficult moments, but there isn’t actually a lot of ‘therapy’ going on during the dosing session, where the therapists are trying to not interfere with where the medicine is taking them. So it’s this idea that we’re coaching participants to surrender to the experience. Where if you see an open door, walk through it. If you see stairs, walk up it. Just go wherever the medicine is taking you. So we’re not tour guides to say go there or there, but just open to seeing wherever the medicine takes you and wherever the music takes you as well.
So that would be the dosing session. At the end of the day, there’s a short debrief, but not a long debrief because that’s saved more so for the day after, where there’s the first integration session. Where that first integration session is really about revisiting the experience. One of the most common reports is this idea of ineffability, where it’s very hard to put to words what the experience was like. So the therapist helped the patient to put it to words to help consolidate those memories, and hold on to what the experience was like. And then you want to return to those intentions, make meaning, think about what I want to change in my life moving forward.
In some of our studies, we have a second dose as well. So then it would be sort of going through that again. What do you want to get from the second dose? Having the dose supported in a similar manner, and then having the integration sessions after that as well. So that’s the basic journey that people would go through. And then we often talk about that integration is not just the integration within the clinical trial, but can be an ongoing process for the rest of your life, where a lot of our patients start journaling or start psychotherapy outside of the trial to continue to try to integrate and make sense, and work on the intentions that they set within the trial. So that’s basically what it looks like when someone comes through one of our psilocybin therapy trials.
Dr. Kuhathasan: So these experiences are really unique to the individual then.
Dr. Rosenblat: That’s right. They’re extremely diverse, and that’s one of the challenges even in the psychoeducation where we’re not able to say ‘this is what’s going to happen’, but ‘these are the types of experiences that have been reported by thousands of other people’ as are what we share with people.
Dr. Kuhathasan: So then would you say that those therapeutic benefits that patients experience are coming from genuine neural rewiring, or is it maybe more the subjective experiences that they may induce?
Dr. Rosenblat: I think it’s too early to say. There’s so much work to do right now. So the mechanism of action is still being hotly debated right now. In the drop-down list of potential mechanisms, certainly things like neuroplasticity are very high, where we know that psilocybin and ketamine have very potent effects on the receptors for brain-derived neurotrophic factor that really facilitates neuroplasticity, meaning the ability for the brain to rewire itself. I sometimes use the analogy of your brain being a garden when you’re depressed and there’s these two steps, where you need to pull out the weeds that are all the negative thoughts, and you need to plant some seeds to allow for some beautiful flowers to grow. So similarly here, we know that with ketamine and psilocybin, there’s this rapid effect where you’re interrupting thought patterns and neural signalling acutely and then you’re also increasing neuroplasticity, so planting down those seeds. And the idea is that, hopefully in the psychotherapy part, we can help support and foster some beautiful flowers to grow in terms of more healthy and adaptive ways of thinking is the idea here.
Dr. Kuhathasan: It’s a really beautiful analogy. How long do those changes that psychedelics induce actually last in the brain?
Dr. Rosenblat: Yeah, it’s a great question and it’s one that we don’t know the answer for yet because we don’t have the long-term studies. It certainly seems that the benefits seem to last on the order of weeks to months. There has been some studies suggesting that the benefits could even be longer than that. In my population of people with really difficult-to-treat depression, I do find that over the course of months, we do start to see symptoms returning for the majority of people, but it really is an unanswered question right now. And in terms of the brain changes, most of the brain imaging studies to date have just looked at before the dose and a couple of days after the dose. We don’t have a lot past that. In our studies now, we’re looking at a month later, but even that doesn’t really tell you the story of what’s happening six months later, a year later. So we need those longer term studies as well that we hope to do.
Dr. Kuhathasan: So we’ve spoken a little bit about depression and how psychedelics are used for that, but what other mental health conditions might they be working for? Where do you think they might be less effective?
Dr. Rosenblat: Psychedelics are being studied for so many different indications right now, both psychiatric and physical. And we’re starting to reconceptualize maybe psilocybin and related psychedelics might not just be an antidepressant, but an ‘anti-distressant’, where what we’re seeing that unites all these conditions is they’re all associated with significant distress. And it seems like psilocybin and related psychedelics have a positive impact for improving quality of life and function, regardless of what diagnostic box you fall in. I don’t think it’s a panacea that’s going to work for everything. I think we still have to figure out what it works for and what it doesn’t, but we’ve proposed this new term of psychedelics being an ‘anti-distressant’, that I think might speak to the transdiagnostic benefits that we’re seeing, and it’s being evaluated for things like anxiety, PTSD, OCD, pain, Lyme disease, all these different things it’s being evaluated for.
Dr. Kuhathasan: Right. We’ve talked a lot about the therapeutic potential with psychedelics, but I want to shift gears a little bit and ask you about some of the dangers maybe. I know some people say that they’re dangerous and they can lead to hallucinations or psychosis. How real are those risks and how do you think they might be managed in research, and maybe even in therapy?
Dr. Rosenblat: Yeah, certainly given all the hype and enthusiasm around psychedelics, we often need to sound the alarm that these are not innocuous substances that you can just take on your own in the basement sitting on your couch or something like that, where there is very significant side effects that people experience during the psychedelic experience. I think we’re living in a time right now where there’s so many people that have very loud voices and experimenting with psychedelics and sharing their stories online about how magnificent it was. However, in my experience with people with severe depression, suicidal thoughts, bipolar disorder, the things that come up during the psychedelic experience can be quite scary. So there is this loss of control and bringing your mind to places that you might have consciously or unconsciously been avoiding, potentially going back to previous trauma, having hallucinations, feeling unsafe, feeling anxious, having a panic attack… all these things are very well known potential side effects of psilocybin, and they all typically resolve within six hours, but if people are planning to experiment and do this on their own, that’s a big concern.
Within our clinical trials, during the dosing session, you’re being supported by very extensively trained healthcare providers that are trained in how to support people through getting through difficult psychological destinations and journeys. And then they would support them through the integration, where we don’t want to just sort of leave people raw, but we want to help them integrate the experience because good and bad things can come up. We believe that both the good and bad things that come up could be useful in integration, and there may be a reason why that experience came up from the perspective that we need to digest this, work through it, integrate it, make meaning of it, and then, work through the challenging aspects of it.
The other risk that people have been sounding alarm on is suicidality, where if you have suicidal thoughts, and you’re going through a terrifying experience, this might worsen your suicidal thoughts. And this is something that’s starting to be found in clinical trials as well, that a small portion of people have worsening suicidal thoughts the days after a dosing session. So again, this is why it’s so important to be well supported. This is not surprising to me. We know that suicidal thoughts is a side effect of antidepressants as well. If we’re going to be really strongly playing with someone’s neurochemistry, we need to be prepared for good and bad outcomes, and it’s okay if we’re there to support people and get them through those difficult periods. So lots of side effects. Certainly, yeah, the hallucinations, the non-ordinary state of consciousness, dissociation, potential anxiety, panic, and suicidality even. All these things are potential side effects that we need to be very mindful of. So right now in the very heavily controlled setting of a supportive environment where we have a custom-built room and custom-trained therapists is very different from just taking this on your own recreationally, for example.
Dr. Kuhathasan: It sounds like you really have to balance optimism around the potential of psychedelics with the need for rigorous science and caution even.
Dr. Rosenblat: Exactly, exactly. And you know, I’m grateful that the Canadian government with the federal funding agencies are on the same page about that. That they want to support high-quality research in this area. Because they’re seeing just what we’re seeing as well… that there’s so much enthusiasm, but we actually need the science. And we’re going into the science from a very different perspective now, compared to the 50s and 60s, where historically, there was the approach of we’re going to do these studies to prove that psilocybin works. But right now, we’re taking the approach of, we want to test and see. Does it work? Is it safe? So we’re really having a more agnostic approach. Not going into the study saying we need to prove this works, but going into the study saying does it work? Is it safe? How can we optimize the protocol to optimize safety and efficacy, is what we’re really trying to do.
Dr. Kuhathasan: Regarding perceptions around psychedelic science, I’d like to know your thoughts on how you think the media represents psychedelics. Do you think they’re maybe being oversold as a mental health silver bullet of sorts or…?
Dr. Rosenblat: Absolutely. And we’re seeing both ends. It’s interesting to see how the pendulum swings both ways, where I’d say particularly, over this past decade, there’s been so much enthusiasm. Part of this has been driven by Michael Pollan’s book, How to Change Your Brain, and it’s been good for the field from one perspective, that everyone’s talking about this research, and at the same time, it’s created challenges, where people are watching the Netflix series, they’re reading the books, and they’re saying ‘Wow, this is going to cure everything’. So balancing that hope and optimism with realistic considerations of, this is another treatment that needs to be evaluated rigorously and carefully.
It’s been interesting, I’d say, in these last couple of years where the pendulum is starting to swing, where the media is quite interested in negative experiences with psychedelics. So we’re starting to see people come forward and sharing their stories where they had a negative experience either using psychedelics recreationally or within a clinical trial and they’re really sounding the alarm for the potential dangers of it. And that’s very important to counterbalance and I think the way the media is, you know, unfortunately sometimes this really gets amplified because it’s a hot story, but it’s like, ‘oh look this is a dangerous thing and pharmaceutical companies are trying to develop it and people are getting hurt’ and all these things. So yeah the pendulum swings back and forth, where right now I think we’re seeing a lot of still the media supporting the hype of it, but also media coverage supporting that this is a dangerous and scary thing that should be abandoned.
Dr. Kuhathasan: So from your perspective as a researcher, what’s the most surprising thing that you’ve learned about psychedelics? Maybe about how it’s affected the mind or even just maybe social perception around it?
Dr. Rosenblat: Yeah, it’s a great question. I think one of the most surprising things I’m seeing more and more is that… particularly I’m going to speak to psilocybin right now, because it’s quite different from ketamine. I’m finding that psilocybin is not necessarily a rapid-acting antidepressant, where we’re talking about it as a rapid-acting antidepressant, like ketamine, but it’s quite different. What I’m seeing in my trial participants is that it’s more of a journey, where patients have their experiences with psilocybin, but then there’s a lot of work to do in the psychotherapy. So we’re seeing people have gradual, further and further benefits over weeks to months following dosing sessions, versus quite different from ketamine where it’s typically, you know, you give the infusions and it either works or it doesn’t… is what we’ve seen. So that’s been something that’s been very interesting and surprising and important to, you know, provide support to patients that they might feel, especially from what they see in the media, that ‘I’m going to take this one dose of magic mushrooms and be cured by tomorrow’. But I find it’s a much more involved process of making meaning of the experience, shifting, returning to the intentions that you set. So it’s often taking quite a bit longer for people to maximally experience the healing that these molecules, I believe, can offer.
Dr. Kuhathasan: So out of curiosity, how do you think psychedelics will fit into mental health maybe in the next 10 to 20 years?
Dr. Rosenblat: Yeah, that’s a great question. I mean, the first hurdle is to have FDA and Health Canada approval. So ketamine is available off-label, esketamine is approved for depression… Spravato nasal spray. But speaking specifically around classic psychedelics, psilocybin specifically, Compass Pathways is the company developing it, and they just had a press release that they completed their second phase three trial. So typically, you need two positive phase three trials that show efficacy and safety for a drug to be approved. There are some shifts right now with the FDA now saying they may actually only require one.. but nevertheless, Compass has two positive phase three trials now. So they’re looking at putting in their application in the fourth quarter of this year, 2026. So we might see psilocybin approved for treatment-resistant depression as early as next year.
So once it’s approved, then there’s the navigation of where does this fit within the trajectory. The trial specifically enrolled people that had failed 2 to 4 antidepressants. So that’s sort of the natural place. But I think for most of us, we’re thinking that this will be a bit further down the line also because it’s so costly. But there’s good arguments to be made either way. USONA is another group that’s developing psilocybin for major depressive disorder, not for treatment-resistant depression, and it’s interesting to conceptualize that as well… where if you think about, let’s say someone’s 21 and they go to their doctor with the first episode of depression, and they can either start on an antidepressant that they’ll need to take daily for the next year, or they could go for a weekend of psilocybin and have a single dose. And from a patient-centred perspective, there’s a good argument to be made that both should be offered. If both of them are effective, someone might prefer to just take a single dose of psilocybin rather than a daily antidepressant. So lots of discussion right now. So time will tell where this will fit, but I think at least initially, this is going to be more so something for people with difficulty to treat depression that have tried a bunch of things.
Dr. Kuhathasan: Right. So for anyone who’s interested in actually accessing psychedelic treatment in Canada, where do they go?
Dr. Rosenblat: For classic psychedelics it still is essentially only through clinical trials. There is a special access program through Health Canada but their first response always is saying, ‘is there a clinical trial available’. So if you go on clinicaltrials.gov you can see all the listings of clinical trials across the country. If you just search in Canada and for psilocybin, or even psychedelics, that would be the easiest route to go if people are looking to explore psychedelic or psilocybin treatment.
Dr. Kuhathasan: Thank you so much, Dr. Rosenblat, for taking the time to actually address all of these questions and for telling us a little bit more about psychedelic science and where the research is headed.
Dr. Rosenblat: My pleasure.
Additional Reading:
Insights on Psilocybin for Clinicians: jamanetwork.com/journals/jama/fullarticle/2853938
Insights on Psilocybin for Patients: jamanetwork.com/journals/jama/fullarticle/2854042
Ketamine for Bipolar Depression: jamanetwork.com/journals/jamapsychiatry/fullarticle/2853662
Blinding in Psychedelic Clinical Trials: jamanetwork.com/journals/jamapsychiatry/fullarticle/2847667
The CAN-BIND Podcast is produced by the CAN-BIND Knowledge Translation (KT) & Outreach Platform, co-led by Dr. Sagar Parikh and Dr. Fabiano Gomes and managed by Dr. Nirushi Kuhathasan. This episode was hosted by Dr. Nirushi Kuhathasan and featured Dr. Joshua Rosenblat with additional support from the broader KT team.