Researching Psilocybin's Effects on Depression - Dr. Rosalind Watts

How did this particular research project get started? This particular research started after various other studies looking into the effects of psilocybin on the brain and NST on the brain. This was the work of Robin Kaha Harris, whose interest came out of his own psychoanalytic studies and his work as a neuroscientist. He was very interested in how we can explore the unconscious mind. So much of our behavior is controlled by the unconscious mind, and yeah, it's very difficult to study scientifically. Psychoanalysis is almost seen as more of an art than a science. So he wanted to find ways of looking at the brain and the unconscious mind.

He started studying psychedelics with David Nutt. David Nutt is a quite well-known professor in this country for his activism in legalizing drugs. He worked with the government as the drug czar, advising them about the scientific harms of different drugs and how they should be scheduled or where they should be in the schedule of illegal drugs. He was famously sacked because his scientific report stated that MDMA was less dangerous than horse-riding. He has gone on to be a real innovator in drugs policy and drugs research, recognizing that many of the drugs that are illegal might hold potential for healing, whereas legal drugs like alcohol and cigarettes often don’t. So, it was time for a more free-thinking approach.

It was David and Robin together that started this research, and it was very difficult for them because there's so much red tape around this. Since it was made legal in the early 70s, it's been hard to get a license from the home office to do this research. But once their work went through the process, it became easier for them to do another study and another study. They’ve really been on a roll, doing studies looking at the effects of psilocybin and honesty on the brain.

They realized the findings indicated it was time to start looking at psilocybin with a clinical population. The key finding was that psilocybin seems to deactivate the part of your mind or brain that is responsible for ruminating, for negative thinking on a loop. They realized that for people with depression, this could be really powerful. The study I was involved in was a clinical study looking at 20 people with treatment-resistant depression. It was the first study of its kind in the UK. There have been some studies in the U.S. looking at psilocybin with people with depression and anxiety secondary to a diagnosis of a terminal illness.

Okay, so are these the studies that were happening in the 60s and 70s, or are there more recent works? In the 60s and 70s, well, in the 50s, 60s, and 70s, there were hundreds and thousands of studies, and the findings were really very positive. It was all great, and then it became illegal, and the research just dropped away. Then it started again in the early 2000s, I think maybe around 2006, and maybe slightly earlier than that. Some of the people involved in psychedelic research in the 60s started to say, "We really need these tools; they were working. We need to get them back again.”

I think Bill Richards, a psychologist who had been working at one of the clinics in the USA, the Marriott Psychiatric Center, had this clinic there. There are some good YouTube videos showing people having LSD sessions. You can see the kind of psychiatrist sitting there with a woman who is on her LSD. They realized that it was time to go again.

So, how did they actually get this appearance? I think there are various companies now synthesizing psilocybin, and they can provide it to researchers with a license to use the schedule one drugs. However, to use them in a study, you usually need it to be GMP grade, which means it's very pure and able to be used; it’s gone through a lot of testing. So, there are very few providers of GMP psilocybin.

A lot of the difficulty in doing this research isn't just the bureaucracy—cutting through the red tape, getting the licenses, the lack of funding because the government’s office obviously doesn’t want to fund this—but it’s also actually getting the psilocybin and getting enough of it that is stable and potent.

What clued you into the fact that it was working with depression versus some other trait that it might affect? Well, I think it would be helpful for many different mental health difficulties, but with depression, it's this ruminating quality—a fixation on certain ideas and concerns. Psilocybin and psychedelics seem to be excellent when people are stuck in fixed patterns of thinking or living. Psychedelics can break that pattern; they provide a state where when you look at the brain’s communication pathways, they go from segmented lines to an explosion where parts of the brain that don’t talk to each other start talking to each other, and suddenly there’s this flexibility.

I'm curious about the experience for the following days, but I think before we jump in, we should talk about what one of these sessions actually looks like. In the last study, there was a low-dose and a high-dose session. The low-dose session was 10 milligrams, and the high-dose was 25 milligrams, and they look pretty different.

In a low-dose session, firstly, the setting is that people would come into the clinic and they would have had some sessions with their guides beforehand. Everyone has two guides—clinical clinicians, therapists—and they get to know the participant quite well. They have some sessions where they share about their lives and hear their story and tell a bit about themselves. It’s quite a nice, human, equal relationship—very respectful and quite different from some doctor-patient interactions.

Have you done both types of relationships? Yes, both are very different. If I was working in the NHS as a therapist with lots of patients, I would be so busy; you have seven people coming in every day. There is this huge need, and often you don’t really have the tools to help people because talking therapy doesn’t work. Especially if you can only offer people six sessions, you're aware that people have this need and they’re desperate and in crisis, and there’s not much you can do.

In a way, what happens is you put your barriers down—you keep yourself a bit separate. Well, those people often have to go private. I guess these are usually people who wouldn’t have the money to go privately. They come for their sessions, and you give them what you can. You can only give them six sessions, so there’s this sense of not being enough. It’s hard for them, hard for you, hard for everyone. They often get antidepressants because that’s something the doctor can easily prescribe, and it feels like it’s doing something, but often that doesn’t work either.

Antidepressants are prescribed at the same rate in the U.S. and here in the UK; they are prescribed incredibly frequently. I think last year was our record number of antidepressant prescriptions—64.7 million prescriptions in the UK alone. How many people live in the UK? I don’t know, but it’s a lot more than you would imagine. It’s huge—huge antidepressant usage isn’t talked about very much. As a short-term measure, to get people through crisis times, I think sometimes it can be helpful, and for some people, it works.

But for a lot of people, it’s a short-term fix; it doesn’t address the root cause, which is something’s not right. It’s not addressing that.

In these psilocybin sessions, you're more about having a conversation, like between friends, before you get going. So someone gets comfortable with you; you feel really comfortable, right? Yes, you are more going through something together, on a journey together, and you’ve been through all the different things that can happen and how to manage the session.

It’s sort of like a Q&A as well. So I show up, and I’m like, “Okay, here we go.” Yes, you would have a couple of sessions beforehand to get to know each other. You would tell me your life story, the difficult things that happened, and the things you were scared might come up because they often do. All the things you don't want to talk about might come up—all the taboos—sex, death, and all the things people hide.

When that has been openly talked about, then you’re ready to go. They come into the clinic; they have the capsules for the low-dose session—it’s just two capsules. They sit with their two guides in a room that’s full of nice decorations. It’s in a hospital, but it doesn’t look like a hospital room. They have a playlist of beautiful music that has been specially curated for this experience.

Then they sit there through the day. At a 10 milligram dose, you tend to see more psychodynamic stuff—internal exploration. People often feel more emotional, feeling they might get some insight into different parts of their life. There’s often a struggle because, at this dosage, the ego is still intact; you would still recognize who you are, but you’d be more in touch with stuff that’s going on that you don’t often think about.

You can identify what you’re feeling, but you don’t let go of it. How would you put it? The difference between a 10 milligram dose and a 25 milligram dose usually is that, at 25 milligrams, it’s so high you can’t resist it. So, with a 10 milligram dose, imagine it like this: you’ve got this cellar, and in the basement, there are all the skeletons and the monsters and all the things you’ve pushed away. Psilocybin can open the door to that stuff so you can process it and be free of it moving forward in your life.

It’s not just the monsters down there—there are also a lot of other amazing things. It can be intense; taking the psilocybin is like opening that door, and you have to let go and surrender to whatever comes up. You have to welcome it. With 10 milligrams, it opens it a little, and so things come out. You might be having a conversation with a deceased parent, or thinking about a relationship that ended. It’s a very intense turbocharged therapy session, but you can fight it; you can put the lid down and say, “I don’t want to deal with this.” With a 25 milligram dose, you can’t fight it.

Everything comes out, and you just have to surrender and trust the process. Your role as a psychologist—what are you doing throughout, you know, in a 10 and a 25 milligram session? Helping people surrender, helping them face difficult things, helping them sit through the pain and encouraging that this is the right thing to do, that they’re safe. People sometimes feel they’re dying because the ego is deactivated; that’s quite common.

When your ego is activated, you have no sense of self, and sometimes that’s a beautiful experience. When I talk about the basement being opened, it sounds like it’s always really difficult; but often it’s a beautiful experience for people, too. There could be a bit of both. When you die in a psychedelic experience, when you have an ego death, it can feel like, “Oh, I’m one with the planet; I am the plants and the trees; I am everything,” or it can feel like, “I’m being physically killed and dying.”

You experience physical pain sometimes. You’re just saying to them, “You’re okay. This is exactly what you came here to do.” It’s counterintuitive: if you feel you’re going mad, great, go mad; if you feel you’re dying, go die; if you’re exploding, let’s see what it’s like to explode. It’s about, in a way, the whole concept of mindfulness and meditation, allowing things in and just sitting with them rather than distracting or pushing them away or trying to always be achieving or feeling good, but never feeling what you’re feeling.

It’s about this turbocharged mindfulness: whatever is here, let it be here. Don’t fight it; don’t push it away; don’t try to nullify negative emotions—do sadness, do suffering, believe it’s there. Is there a certain vocabulary that you train someone in before they get going? I just wonder if, if someone is more precise with their language, does that affect the experience, or is it open to anyone?

Interesting. Well, often the experience has this noetic quality, which means it’s beyond words; you can’t put it into words. So I think really, people’s vocabularies don’t matter beyond that; they go to a different level. But we do talk to them a little. We don’t prepare them for any kind of experience because we don’t want to prime them in any way. We say, “If you feel that you’re dying, that’s okay; you’re not actually physically dying; we’ll look after you; it’s all fine.”

But we don’t really prepare them because we don’t know where they’re going to go. The main preparation is just one word: surrender. Are both other people in the room psychologists, or do they serve different roles? In our next study that is just about to start, we can have one lead guide and one assistant guide. It’s a kind of training program where people can get experience, and there’ll also be a psychiatrist who is not in the room most of the time, but is on-site if needed.

So what are you doing? Are you taking notes, or are you just hanging out? What do you do? Last time, we could take a notebook in. Sometimes there’s a lot of time when they just have their eye masks on and are just lying back on the bed in silence for a long time. But this time, I think we’re going to try not to do that, because it’s just good to be there fully with them. Even though it’s a long day—it might be like six hours—they might be under, just really being with them, noticing the subtle changes, listening to the music, and being in the moment.

The people who have participated in the study so far—do they have any shared qualities or traits? How does someone end up in this study? Well, in the last study, people had treatment-resistant depression, meaning they had tried at least two different treatments that hadn’t worked. When I think back at those 20 people, they weren’t all psychedelic enthusiasts. A couple had tried it before—20 years ago—and actually the one that had tried it before had a terrible LSD experience, so he was really put off by it.

The expectations about psychedelics were quite negative in many ways, and there was a lot of anxiety around them. Maybe also some people had access to media coverage of the positive possibilities of psilocybin, but it was a bit mixed; there were some expectations it might help them, but they were scared about how they were going to get to that good outcome.

They all opted in because they were absolutely desperate for something that was going to help. They had tried everything, had depression for an average of 18 years, and had tried between three and eleven types of antidepressants. Imagine trying eleven types of antidepressants, with each time going and your doctor giving you a different packet and side effects taking weeks to work. And then they don’t help after that.

They also had lots of talking therapy, up to six different courses of talking therapy, so these are people who would try anything. For some of them, ECT was the next option, which is the electric shock therapy for the brain. So people were like, “Well, I’ll try this, and then if this doesn’t work, I’ll try ECT because it’s either this or I can't carry on living like this.” Is ECT proven to be effective?

Well, it works in some very severe cases, and it might help some people. There can also be cognitive problems as a result, leading to severe memory loss difficulties. Sometimes it works for people, but it's really the last resort. So are these before you start taking psilocybin? Well, you’re taking these antidepressants—they’re super common, way too common in the UK. Are there long-term effects of taking these medications?

I know so many people who are manipulating their brains who don’t necessarily have depression. They’re taking nootropics, focus drugs, or whatever it might be. Have you found any long-term effects of psilocybin? Not so much. There has been some research into the effects of antidepressant drugs, but often it’s very short-term; it looks at them for a short period without much follow-up because that serves the purposes of the people making these drugs.

So I don’t know of long-term follow-up research. I only know about experiences of people I’ve spoken to in my clinical work as a clinical psychologist; people have said, “They make me feel worse.” Even in terms of long-term—if they work well for people and they keep taking them, if they don’t work, then they stop taking them. So we would be interested in the long-term effects of antidepressants for those for whom they are effective.

But for those people who are affected, they are a complete lifeline. I don’t know about the research on that. I don’t understand it to the same degree as you do. Is it common for someone, if they do find an antidepressant to be effective, to maintain use forever? It is quite common for people to use it for a long time.

For example, one of our participants had been on antidepressants even though they hadn’t really helped him. They helped him a little bit, so the way he described it was that life was really unbearable, and the antidepressants took off the peaks and troughs. So, even though he still felt very depressed, they kept him going. He wouldn’t say they worked, but he took them anyway out of necessity.

The real reason—this is the real thing that I do—gets talked about enough. Often, people stay on the antidepressants because when they try to go off them, it’s awful. There was one participant who had been on antidepressants for 20 years, and in our study, people had to come off their antidepressants to participate because psilocybin is not nearly as effective when you are taking them.

Coming off his antidepressants before the study was a challenging experience for him—he was tearful the whole time. People described electric shocks going off in their brain, and sometimes bedwetting happened as they withdrew. For some people, you have to withdraw them for quite a while, so you can’t go into a psilocybin session with someone so turbulent.

That was a shock for us; one of the big shocking findings was withdrawing from antidepressants was absolute hell for these people. I think that’s why some people stay on them because coming off is too difficult. A lot of people, we can obviously talk about the effects of psilocybin, but it seems for most people, the effects last about two or three months before the depression starts to come back.

I think the return of depression has many reasons, but partly it’s because this isn't psychedelic therapy. We’re not giving people integration; we’re not giving them the full package. A psychedelic intervention has to have three sections: preparation, the session itself, and integration. Preparation is, as we’ve talked about, getting to know each other, building trust. The session itself involves surrendering and being there together, and then integration is about the participant weaving a narrative about what on earth they experienced.

They may have had mystical or spiritual experiences; they might have profound insights into their life. It’s a weird, wonderful world, and they need to piece it together in a way that makes sense to them, so that in the months and years that follow, they know what that experience means, and it helps them live their life. Because there’s no use in having this incredible opening if you then go back to your same old life.

What psychedelics do is give you this window of opportunity. Imagine this analogy from one of my colleagues: envision a snowy mountain and go sledding down the same track. Anytime you get on that mountain, you go into the same track—just like a mental prison where you’re stuck in those same ruminating thoughts.

Then with psilocybin or psychedelics, it’s as if a snowplow comes and wipes everything clean. In this state of brain connectivity or the entropic brain—the integrated brain—it provides this opportunity for flexibility; you can kind of sled anywhere you want to go. After a psychedelic experience, people often feel amazing for a number of weeks or even months, and this flexibility allows for trying new habits or relationships.

If, in that window of opportunity, they start new habits, they change their relationships, and they make life changes, we think that could make the effects last longer. But if you just give someone a psychedelic and don’t encourage them to maximize that window, what we found with our participants is that depression came back after three months or so.

It makes sense; your life is already structured, and it’s not like your memory is wiped clean, so you can fall back into your habits. The actual effects—what have some things happened? So of our 20, well, the first thing to say is that they all said they would prefer it to any other treatment they tried.

Three of them didn’t have a real effect, but even though it hadn't worked for them, they felt that the process was different. It’s distinct from getting a pack of pills; you’re sitting there talking to people, getting to know them, and listening to your life story. It’s very human.

All of these people had had therapy before, and they perceived this as different from talking therapy. Yes, this difference in the relationship—it’s not about a therapist sitting there trying to help but not really having time to help. It’s different because you’re going into this unknown thing together, and that process bonds everyone.

For three people, it didn’t work; they didn’t have a psychedelic experience in that they didn’t really see anything, even though they were on the same high dose as everyone else. I have some ideas about that, but we need more research to work it out.

For six of them, at the six-month follow-up, they were still depression-free—so for six of them, it was life-changing. We’ve stayed in touch with people now, and we know that, actually, of those six people, most of them had some of their depression come back at some point—around the year point—but they managed to keep themselves well through finding access to the experience again.

But, they needed someone with them. Let me tell you about the other eleven: most people were well for three months—depression-free or with very mild symptoms—but then after three months, the depression started coming back.

It didn’t go quite back to where they were before, but it did start to come back. Now, if you think of how many people this affects… we’ve had 17 out of 20 people, all of whom nothing worked for for years. They have these experiences in a day—just sitting in a room with us—and they feel better for months. Their partners described them as having a sparkle in their eye they hadn’t had for decades.

They’re starting new hobbies and playing with their children more. It’s beautiful to see, but when the depression returns, we have to say, “I’m really sorry, but we can’t give you another session.” This is our research study with no funding. Our entire team works for free because we don’t have much support. The budget we do have goes towards moving the research forward.

For the next study, we’re looking at psilocybin versus antidepressants, comparing the two, which is an important thing to do. We’re filling our budgets on that study, which means we cannot give follow-up doses to the previous people. Ethically, it’s tough to open people’s eyes to something that works when one person said it was like turning on the lights in a dark house, and then the lights fade again.

But they still say that now they know they’ve tried something that worked; they hold hope that they can access it again. A few have been able to, which is good; all this totally makes sense. It’s like exercise—if I were to go for a run every three months, that would be all I needed to stay in shape. It’s incredibly effective, but it also makes sense you have to keep at it.

So, are they swapping it out? People talk about going on these ayahuasca retreats and list the other comparables. The only legal way of having this experience is that there are a couple of places where mushrooms are legal and retreats, but those are very far away.

A couple of our participants were able to access those, but the rest of them have not been able to. Is it common for them to get back onto the antidepressants, or what are they trying to do? A lot of them have stayed off the antidepressants, but some have gone back on just because they need something to help them get through. Life is really tough.

When things happen, they need something; that’s the only treatment currently available. Could you walk me through how the conversation might flow during a session?

Well, during a high-dose session, it’s quite different every time. You just don’t know what to expect. It would be typical to have the participant lying there, and I’m sitting there, sometimes holding their hand if they’re going through something painful, sometimes not. A lot of that time is silence; they are battling things within themselves.

You see very little because they’re lying there, internalized. Sometimes they might say, “Oh, I don’t want to go there; I can’t.” They’re kind of struggling with something, and you’re just helping them face whatever is there.

Sometimes people are having a rebirth experience, so you’re a bit more like a midwife than a therapist. You know, there may be sounds and noises, and you’re reassuring them, but it’s not an intellectual conversation. We want to get out of the mind and right to the heart and into the body.

What does that look like? It should look like you’re back in the mind, but the brilliant thing about psychedelics is they turn off those kinds of ego frontal parts. You can go into the body and heart. You’ve had to re-train yourself; it’s completely against everything you studied, I imagine.

So, are you asking different kinds of questions or is it just encouragement? Honestly, it’s love. It really is. I know that sounds really ridiculous, but when you boil it down, that’s what it is—presence and love.

It’s the same feeling when you think about your own experience of having a baby and looking after a small child. I’ve been guiding while on maternity leave taking care of my three-month-old at home. For the first time when I first started doing this, my child is nearly three now. I think my parenting work helps me understand what presence is needed. It doesn’t just have to be men or women—both can provide that kind of unconditional positive regard; humanistic psychologists talked about unconditional positive regard, which is a broad approach of accepting whoever you are—but it’s one step beyond that because when you see people in pain, you feel this sense of love in a different way.

It’s just human; it’s not like falling in love with a patient; it’s like human compassion and feeling of shared humanity—being with them—because they are vulnerable. There’s just something special about the kind of therapeutic relationship. It’s very different.

As someone who has been on the other side of therapy, how does it contrast? So, I did some research into this. I interviewed people who got involved in the study and asked them to compare it to any therapy they had before. I thought it would just surprise me because I’d been working with cognitive behavioral therapy (CBT) for years.

I thought it had been somewhat helpful; I knew it wasn’t that helpful, and people weren’t always improving. But what people in our study said was that once they had the psilocybin, what it was like to have something different; they looked back on their talking therapy and felt it was quite inadequate.

Sometimes having a bad experience with prior therapy shows that not every therapist is brilliant, and I know colleagues who are fantastic. However, there is pressure to be directive; even if you follow CBT, you think you know the answer and want to get them there, but with psilocybin, it’s completely different.

The expert is themselves. Their healing power flows from the unconscious mind; their own unconscious mind is writing itself. If you think about the body as a system, whatever things need dealing with in the system, psilocybin helps to find them.

The unconscious mind is intelligent; it knows which parts of the system have glitches and need changing. This is where the brain connectivity comes into play, and it’s almost like a scanning process: “Where do we need to go?” This means regarding the relationship with them, there’s complete respect because they are on a journey.

You can’t go on it for them; it’s not directive; it’s an individual experience. If, say, you were to come for a session, I would have no idea what the right thing is unless I tried. Whenever I had ideas, in the beginning, they were always wrong because the person’s own mind is infinitely more intelligent than I am.

For example, how do you find the right fit? It’s crucial, especially for long-term therapy where you’re doing weekly sessions for years. That relationship is significant, but with psychedelics, the work is done internally.

You have to trust one another, and that's usually okay, as long as there’s a kind of synergy. Not all therapists would be effective; it takes a particular approach. You don’t need to be the expert; comfort with emotions, not knowing, and being patient are essential.

Not everyone will trust the process enough to proceed. While it won't suit everyone, for the people we screened through the study, things real aligned well. I can think of one person who wasn’t fully trusting but still had a good outcome.

Often, there are people online who offer something and put out an idea that you’re looking for confirmation. You might look for someone so close who only provides validation and that can be limiting.

That is another benefit of psychedelics, though. Sometimes—and I can admit this—a therapist may feel so exhausted that they could fall back on just being nice. It becomes, “I hear you, and I’m there for you,” but when I talk about the love of a psychedelic session, it’s like tough love.

There’s no validation or confirmation; it’s challenging them to face what’s hard, and psilocybin can feel confronting. You’ve seen it; there is a period where it works, and then it stops.

In terms of setting someone up for success in the next study, what are you planning? If someone gave me a license for psilocybin, I could set something up that would work. There are loads of ideas based on decades of knowledge about how these tools work; it’s a long journey of deeper self-reflection.

For example, I’d mix psychological models and use meditation in the process. In a perfect world, it would be a long road towards self-acceptance and love. People would take the time to reflect on their relationships with themselves and others, connecting with people about goals, dreams, and what they feel is within them.

Connection becomes key. When you turn off the chatter in your head, you can center on the real voice inside you. You find the voices that guide you toward the life you want to lead. Also, people can get trapped; we can be so disconnected from ourselves and each other, filled up with countless distractions and addictions.

When you turn all that off, you can turn your focus inward and honor your true voice. So, with psychedelics, people become more connected to themselves and to those around them.

Reconnect to those connections—how to sustain that feeling? Those can be difficult to maintain, but it’s crucial to keep this connection. Those involved in the process have indicated that this connection is vital.

You might also work to connect with others and find community. Think about what you want to achieve with your purpose, and that ethical foundation can help, too—consider the roots of the work.

I think the metaphor of mushrooms in a forest is a great one. You have all the trees above ground, while two-thirds of the forest are roots unseen. The trees communicate through mycelium—it’s all interconnected underground. Our connections are important too; to make your own tree robust, prioritize connecting to your roots.

I think that’s a great place to stop. Thank you so much for your time.