- The research project on psilocybin and LSD effects on the brain was started by Robin Carhart-Harris, who was interested in exploring the unconscious mind.
- David Nutz, a well-known professor and advocate for drug legalization, joined the research project.
- Obtaining licenses and enough psilocybin for research was challenging due to legal restrictions and limited providers of GMP psilocybin.
- The research focused on the effects of psilocybin on people with treatment-resistant depression, as it seemed to deactivate the part of the brain responsible for negative thinking.
- The previous research on psychedelics in the 50s, 60s, and 70s was positive, but it declined after they were made illegal. It started again in the early 2000s.
- In the study, participants had low and high dose sessions, with the low dose session focusing on psychodynamic exploration and emotional insight.
- The sessions were conducted in a non-hospital-like setting, with therapists building a comfortable and equal relationship with the participants.

- The video discusses the use of psilocybin in therapy sessions for treatment-resistant depression.
- The sessions involve taking capsules of psilocybin and sitting with two guides in a room with pleasant decorations and specially designed music.
- A 10 milligram dose allows for more internal exploration and emotional insight, while a 25 milligram dose leads to a complete surrender and ego death.
- The role of the psychologist is to help individuals surrender and face difficult emotions and experiences.
- The sessions can be intense and may involve conversations with deceased loved ones or thoughts about past relationships.
- The experience is described as a turbocharged form of mindfulness, where individuals are encouraged to fully feel and process their emotions.
- Participants in the study had treatment-resistant depression and had tried multiple antidepressants and therapies before opting for psilocybin treatment.
- The long-term effects of antidepressants are not well-studied, but some individuals reported feeling worse while taking them.
- It is common for individuals to use antidepressants for a long period of time if they find them effective.

- Participants in the study had been on antidepressants for a long time, even if they didn't find them very effective.
- Coming off antidepressants before the study was difficult and led to withdrawal symptoms.
- Psilocybin was found to be more effective when participants were off antidepressants.
- The effects of psilocybin lasted for about 2-3 months, but depression eventually returned for most participants.
- Integration, or making sense of the psychedelic experience, is important for long-term benefits.
- Psilocybin provides a window of opportunity for flexibility and change in thought patterns.
- 3 participants did not have a psychedelic experience, 6 remained depression-free after 6 months, and 11 experienced a return of depression after 3 months.
- Limited funding prevents the researchers from providing follow-up sessions to participants.
- The researchers are planning a new study comparing psilocybin to antidepressants.

- The legal options for experiencing psychedelic therapies such as ayahuasca and mushrooms are limited and often require financial resources
- Some participants in the study have been able to access these therapies, while others have not
- Some participants have stayed off antidepressants, while others have gone back on them for support
- During high dose sessions, participants may experience internal battles, silence, or rebirth experiences
- The therapist's role is to provide love and presence, similar to a midwife, and to help participants face and navigate their experiences
- Traditional therapy approaches are often directive and focused on the therapist's expertise, while psychedelic therapy allows the participant's own unconscious mind to guide the healing process
- The therapeutic relationship in psychedelic therapy is characterized by respect, trust, and a recognition of the participant's expertise in their own journey
- The matching process between therapist and participant is important in traditional therapy, but less crucial in psychedelic therapy as the work is primarily done within the individual
- Trust between the participant and therapist is key, but the specific matching of therapist and participant is not as critical in psychedelic therapy as long as there is trust and a comfortable, loving presence from the therapist.

- Trust and matching in therapy may not be as important in psychedelic sessions compared to traditional talk therapy
- Psychedelic guides are there to support but not actively participate in the healing process
- Psychedelic therapy involves tough love and confronting difficult emotions
- Long-term effects of psychedelics are not yet fully understood
- Setting someone up for success in psychedelic therapy involves a journey of self-reflection, self-acceptance, and self-love
- Integration and maintaining insights and goals are important in the long-term
- Psychedelic therapy is an ongoing process, with sessions potentially every 6 months or as needed
- Psychedelic therapy can lead to radical changes and deep internal understanding, similar to psychoanalysis
- Caution is advised after a session to allow time for reflection before making big life changes
- Accessing similar states without psychedelics can be done through holotropic breathwork and deep meditation
- Maintaining the desire to change can be supported through meditation and understanding resistance.

- The speaker believes that people often know deep down what they want to work on, but fear and pressure hold them back.
- The speaker recommends getting connected to oneself and turning off the mind or ego through practices like meditation or being in nature.
- It is important to honor and prioritize the voice inside that knows what one really wants to do in life.
- Psychedelics can help increase connection to oneself, others, and the world.
- Connection to oneself involves nourishing oneself and listening to one's inner voice.
- Connection to others involves finding like-minded people to pursue dreams together.
- Connection to the world involves considering the ethical implications of one's actions and helping ideas spread wider.
- The speaker uses the analogy of a forest and mycelium (mushroom) to emphasize the importance of connectivity.
- Being connected to others is compared to a tree with branches (ideas) and roots (connections to others).
- The speaker concludes by stating that being connected to others is essential for personal growth and success.

- The research project explores the effects of psilocybin and LSD on the brain and focuses on treating treatment-resistant depression.
- Obtaining licenses and enough psilocybin for research was difficult due to legal restrictions.
- The study involved low and high dose sessions in a non-hospital-like setting with therapists building a comfortable relationship with participants.
- Psilocybin therapy sessions involve taking capsules, sitting with guides, and exploring emotions and experiences.
- Participants in the study had treatment-resistant depression and had tried multiple antidepressants before opting for psilocybin treatment.
- Psilocybin was found to be more effective when participants were off antidepressants, but the effects lasted only for a few months.
- Integration of the psychedelic experience is important for long-term benefits.
- The researchers are planning a new study comparing psilocybin to antidepressants.
- Access to psychedelic therapies is limited and often requires financial resources.
- Psychedelic therapy involves tough love, confronting difficult emotions, and deep internal understanding.
- Maintaining insights and goals, as well as ongoing self-reflection and self-love, are important in the long-term.
- Accessing similar states without psychedelics can be done through holotropic breathwork and deep meditation.
- Connection to oneself, others, and the world is important for personal growth and success.

Dr. Rosalind Watts - https://twitter.com/ros_watts - is a clinical psychologist at the Psychedelic Research Group at Imperial College London - https://www.imperial.ac.uk/department-of-medicine/research/brain-sciences/psychiatry/psychedelics/

The Psychedelic Research Group focuses on two main areas: first, the action of psychedelic drugs in the brain and second, their clinical utility,  e.g. as aides to psychotherapy, with a particular focus on depression.

The YC podcast is hosted by Craig Cannon - https://twitter.com/craigcannon

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 LSD on the brain.

And this was the work of Robin Carhart-Harris, who, his interest came out of his own psychoanalytic studies and his also work as a neuroscientist and he was very interested in how we can explore the unconscious mind because so much of our behavior is controlled by the unconscious mind And yeah it's very difficult to study scientifically and psychoanalysis is very, it's almost seen as more of an art than a science so he wanted to find ways in of looking at the brain, the unconscious mind.

And he started studying psychedelics with David Nutz.

So David Nutz is a, he's a quite well-known professor in this country for his activism in legalizing drugs.

So he informed them or advised them about the scientific harms of different drugs and how they should be scheduled or, you know, where they should be in the schedule of illegal drugs.

And He was sacked very famously because his scientific report stated that MDMA was less dangerous than horse riding.

And he has gone on to be a real innovator in drugs policy and drugs research, just recognizing that lots of the drugs that are illegal might hold potential for healing, whereas alcohol and cigarettes that are legal really don't.

So it's time for a more free-thinking approach.

So 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.

Because since it was made illegal in the early 70s, it's been very hard to get a license from the home office to do this research.

But once they'd gone through the process it became easier for them to then do another study and another study so they've really been on a roll.

They did some studies looking at the effects of psilocybin and LSD on the brain and then they realised that the findings that they had indicated to them that it was time to start looking at psilocybin with a clinical population.

And 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.

So they realised that for people with depression this could be really, really powerful.

So the study that I was involved in was a clinical study looking at 20 people with treatment resistant depression

was the first study of its kind in the UK and there have been some studies in the US looking at psilocybin with people with depression and anxiety secondary to a diagnosis of a terminal illness.

So are these the studies that were happening in the 60s and 70s or are they more recent work?

So in the 60s and 70s there were, well in the 50s, 60s and 70s there were hundreds and thousands of studies.

And the findings were really very positive and it would all look great.

But then it started again in the early 2000s, I think maybe 2006, around that time, maybe slightly earlier than that.

And some of the people that had been involved in psychedelic research in the 60s started to say, oh, we really need these tools.

And I think, so Bill Richards, who's a psychologist, had been working in 1 of the clinics in the US.

So the Maryland Psychiatric Center had this clinic there.

There are some good YouTube videos showing people having LSD sessions that you can see the kind of psychiatrist sitting there with a woman who is on her LSD trip.

And they, yeah, they basically realized that it was time to go again.

So they kind of galvanized their team, got a new group together, and started up again.

And this was just like, these drugs had existed at the university and they just had a store of them or they lobbied to to make this happen how did it go

how do they actually get the sentence so I think that there are there are various companies now that are made that are synthesizing synthesizing psilocybin yeah And they can provide it to researchers with a license to use these schedule 1 drugs.

But in order to use them in a study, you usually need it to be GMP grade, which means it's kind of very pure and able to be used.

So there are very few providers of GMP psilocybin.

So it takes a lot of the difficulty of doing this research isn't just the bureaucracy, cutting through the red tape, getting the licenses, the lack of funding, because the governments obviously don't often wanna fund this, but it's also actually getting the psilocybin and getting enough of it and getting it that's stable and being tested.

Yeah, and so what clued you into the fact that it was working with depression and versus some other trait that it might affect?

Well, I think it will be helpful for so many different mental health difficulties.

But with depression, it's the ruminating quality of depression, the fixation on certain ideas and concerns.

So psilocybin and psychedelics seem to be very good at when people are stuck in a very fixed pattern of thinking or of living, psychedelics can break that pattern.

They can provide this state of, when you look at the images of brain communication pathways, they go from this kind of segmented lines to this full-on explosion where things that, parts of the brain that don't talk to each other all talk to each other and suddenly there's this flexibility.

So I'm curious about what the experience is for the following days, but I think before we jump in, we should talk about what 1 of these sessions actually looks like.

Yes, 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.

And they look pretty different, these sessions.

So firstly, the setting is that people would come into the clinic and they will have had some sessions with their guides beforehand.

So everybody has 2 guides, they're clinicians, therapists, and they get to know the participant quite well.

You have some sessions where you just share about their lives and hear their story and you tell me a bit about yourself and it's quite a nice human equal relationship, very respectful and quite different to some doctor-patient kind of...

So I suppose, I was working in the NHS as a therapist with lots of patients, and there you're so busy.

You have 7 people coming every day, and there's this huge need, and often you don't really have the tools to help people because often talking therapy doesn't really work, especially if you can only offer people 6 sessions.

So you're aware that people have this need and that they're so they're so desperate and in crisis and there's not much you can do.

So in a way what that happens is you put your barriers down, you put your boundaries down.

It's like this is what I can do, this is what I can't do and you keep yourself, you keep yourself a bit separate.

Well, I guess these are usually people that really wouldn't have the money to go privately.

So they just, they come for their sessions and you give them what you can, but you can only give them 6 sessions.

So there's this sense of it not being enough.

And it's hard for them and it's hard for you and it's hard for everybody there and then they will often get antidepressants because that's something that the doctor can easily prescribe and it feels like it's doing something but then often that doesn't work either.

And are antidepressants prescribed at the same rate that they are in the US, here in the UK?

They're prescribed incredibly frequently.

I think last year was our record number of antidepressant prescriptions.

There was 64.7 million prescriptions in the UK for antidepressants last year.

But it's a lot more people than you would imagine.

It's a huge, huge use of antidepressants that isn't really talked about very much.

And As a short-term thing to get people through a crisis time, I think sometimes it can be really helpful.

And for some people it works, but for a lot of people it's a short-term fix.

It doesn't really change the causes of the depression.

Something's not right and it's not addressing that.

Okay, so in these psilocybin sessions, you're just having a conversation, like you would between friends, before you get going.

So you you you feel really comfortable so yeah you are You are you're more you're going through something together if you're on a journey together You know and you've been through all the different things that can happen and how to manage a session and

So I show up and like okay like here we go

So so you we'd have a couple of sessions beforehand to get to know each other.

And then you would tell me about your life story and the difficult things that had happened and the things that you were scared would come up because they often do.

So all the things you don't want to talk about might well come up.

So all the taboos, you talk about sex and death and all the things that people hide in their closets and then when that's all been openly talked about then you're ready to go and they come into the clinic, they have the capsules on the Lodo session it's just 2 capsules and then they sit there with their 2 guides in a room that's full of nice decoration so it's in a hospital but it doesn't look like a hospital room and they have a playlist of really beautiful music that's been specially designed for this experience and then they sit there through the day and on a 10 milligram dose you would see tend to see more psychodynamic stuff so internal exploration people feeling more emotional feeling that they maybe get some insight into different parts of their life and often there's struggle because the amount of psilocybin is, their ego is still intact.

There is still an I there, you would still be there knowing who you are, but just more in touch with the stuff that's going on

So in other words, you can kind of put a finger on it and you can identify it, but you don't let go of it?

So the difference between a 10 milligram dose and a 25 milligram dose usually is that a 25 milligram dose is so high that it will completely, that you can't resist it.

So with a 10 milligram dose, so okay, imagine it a bit like this.

With 10 milligrams, Imagine you've got this cellar.

And in the basement, there are all the skeletons and the monsters and the things that you have pushed away.

And what psilocybin does is it can open the door of that stuff so that you can process it so you can go through those things and be freer of them as you go forward in your life and it's not just the monsters that are down there there's also loads of other really amazing things but but there's it's intense and it can feel a bit like taking the psilocybin is a bit like kind of opening that door and

have to let go and surrender to whatever is coming up you have to be there and welcome it with 10 milligrams it opens it a little bit And so the things come out and you might be having a conversation with a dead parent or you might be thinking about a relationship that ended.

It's like a very intense turbocharged therapy session.

But you can fight it, you can kind of put the lid down, you can decide you don't want to do it.

You can't say I don't want to deal with this.

It's open, everything comes out, and you just have to surrender and just trust in the process.

And your role as a psychologist, what are you doing throughout, in a 10 and a 25 milligram session.

Helping people surrender, helping people face the things that are difficult, helping people sit through the pain of it by being encouraging that that's the right thing to do, that they're safe.

People sometimes feel that they're dying because when the ego is deactivated, that's quite common because when your ego is deactivated You have no sense of self.

And sometimes that's a beautiful experience I mean what when I talk about the you know, the the basement being open It sounds like it's always really difficult.

It's often a really beautiful experience for people.

Often there'll be a bit of both, but when you die on a psychedelic experience, when you have an ego death, that can either feel like, oh, I'm at 1 with the planet, I am the plants and the trees, I am everything, or it can feel like I'm physically being killed, I'm dying.

And you're just saying to them, you're okay?

This is exactly what you came here to do, you know?

This is all, this is, it's counterintuitive.

You know, if you feel that you're going mad, great, go mad.

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 is about allowing things in and just sitting with them rather than distracting or pushing them away or trying to always be kind of achieving or feeling good, but never feeling your feelings.

It's about, it's like turbocharged mindfulness.

Don't try and nullify these negative emotions.

And is there like, is there a certain vocabulary that you train someone in before they get going?

I just wonder if like, if someone is more precise with their language does that affect the experience or is it kind of open to anyone?

Interesting well often the experience has had this noetic quality which means that they're beyond words you can't put them into words so I think really people's kind of it doesn't really matter If you go beyond that you go to a different level beyond that often.

We don't prepare them for any kind of experience because we don't want to prime them in any way.

So we just say you might have, if you feel that you're dying, that 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 just don't know where they're gonna go.

So we just, The main preparation is just surrender.

And are both other people in the room psychologists or they serve different roles?

So in our next study that's just about to start, we're gonna have 1 lead guide

It's a kind of training program, a way of people that can get experience.

And then there'll also be the psychiatrist that's not in the room most of the time, but is on site if we need him.

Last time, we would take a book in with us sometimes because there's a lot of time when they just got the earphones in, the eye shades on, and they're just lying back on the bed and so there's just silence for a long time.

But this time I think we're gonna try not to do that because actually it's just good to be there fully with them even though it's a long day, it's like 6 hours that they might be on this experience.

But just really, just being with them and seeing the subtle changes and listening to the music and being the moment, you know?

And so the people that have participated in the study so far, do they have any shared qualities or traits?

Like, how does someone end up in this study?

Well, so in the last study, people had treatment-resistant depression, so it meant that they tried at least 2 different types of treatments that hadn't worked.

So I would say, when I think back of those 20 people They weren't all psychedelic enthusiasts a couple of them had tried it before but like 20 years ago And actually the 1 that had tried it before had had a terrible LSD experience.

So he was really put off by it yeah, so the the expectations about psychedelics were quite negative in many ways.

But I guess also that maybe people had access to some media coverage of the positive possibilities of psilocybin, so it was a bit mixed.

There were some expectations it might help them, but they were scared about how they were gonna get to that good outcome.

Right, well, because they've all opted in.

Well, the reason they opted in, and I think this is all of them, is because they were absolutely desperate for something that was gonna help them.

They'd had depression for an average of 18 years and they tried between I think 3 and 11 types of antidepressants.

Imagine trying 11 types of antidepressants and every time you go and your doctor gives you a different packet and they have side effects and they take weeks to work and they don't and then they don't help you.

So and they'd also had like lots and lots of talking therapy, up to 6 different courses of talking therapy.

So these are people that they would try anything.

For some of them, it was like ECT was the next option, which is the electric shock therapy of 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.

Well, in some very severe cases, there are some, it might help some people, but there's also cognitive problems as a result of it.

It can lead to severe cognitive difficulties and memory loss, and it's, I mean, I think sometimes it works for people, but it's really the last resort.

And so are these, before you start taking psilocybin, so you're taking these antidepressants, they're super common, way too common in the US.

Are there long-term effects of taking these medications?

Because I know so many people are also manipulating their brain who don't necessarily have depression.

They're taking nootropics, they're taking these focused drugs, or whatever it might be.

Have you found there to be any long-term effects?

The research into the effect of antidepressant drugs often is very short-term.

It looks at them for a very short period of time without much follow-up.

So because that serves the purposes of the people making these drugs.

So I don't know of long-term follow-up research.

All I know about is there was experiences of people that I've spoken to.

So in my clinical work as a clinical psychologist, seeing people saying they're just, you know, they make me feel worse.

Often people would say they made them feel worse.

And often in terms of the long term, I think with antidepressants, if they work well for people, then 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 people for whom they are effective.

But I suppose for those people for whom they are effective, they're a complete lifeline.

So, yeah, I don't know about the research on that.

Well, yeah, I don't understand it to the same degree as you do, but 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, yeah, so for example, 1 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, life was really unbearable and the antidepressants took off the peaks and the troughs.

So the highs of the highs, the lows of the lows.

So it just made the range a bit more bearable.

So even though he still felt very, very depressed, they kind of kept him going.

He wouldn't say they worked, but he took them anyway because we need to and the real reason, and this is the real thing that I don't think gets talked about enough.

The real reason I think so often people stay on the antidepressants is because when they try and go off them, it's awful So there was this 1 participant who'd been on antidepressants even though they hadn't worked for 20 years and in our study people have to come Off their antidepressants in order to participate.

because it really Psilocybin is not nearly as effective if you're on antidepressants.

Coming off his antidepressants before the study, he was in...

People described electric shocks going off in their brain, bed wetting sometimes.

are they off of these before they take psilocybin?

Well, for some people you have to withdraw them for quite a while because they're so, you know, you can't go into a psilocybin session with someone so turbulent So that was a shock for us 1 of the big shock findings was oh my goodness me withdrawing from antidepressants for these people was absolute hell often And so I think that's why some people could stay on them because coming off is too difficult Yeah, but then a lot of people so we can talk about obviously the effects of the psilocybin, but it seems to, for most people, last for about 2 or 3 months and then the depression starts to come back.

And I think that's because, for lots of reasons, but partly because we didn't, this isn't psychedelic therapy so we're not giving people integration really.

We're not giving people the full package.

So a psychedelic intervention has to have 3 sections, preparation, the session itself, and integration.

Preparation is, as we've talked about, getting used to how it's gonna be, getting to know each other, the trust, building the trust.

The session itself is about surrender, being there together, and then the integration is about the participant themselves weaving a narrative about what on earth they have just seen and gone through.

They may have had mystical spiritual experiences, they may have had experiences of dying, of amazing insights into their life.

And they need to piece it together in a way that makes sense to them so that when they 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.

So what psychedelics do is they give you this window of opportunity.

So okay so like if you imagine like so this is 1 of my colleagues analogy I'm stealing it from him.

If you imagine like a snowy mountain and then and you go sledging and you go sledging down the same track, and you always go, so when there's a track in the snow, it gets deeper and deeper and deeper.

When anytime you go down that mountain, you're going to the same track, because it's just the groove is getting deeper and deeper.

If you imagine that as your mind, in depression, you go through the same thoughts, ruminating about the same things, worthlessness, whatever it is, whatever your ruminations are just sticking in that rigid pattern.

People describe it as like a mental prison, they're stuck in the same old patterns.

And then with psilocybin or psychedelics it's like you've got this this mountain with this like deep deep ridges that you always get out and then with psilocybin It's like a snowplow that just comes across and wipes everything through so in this state of brain connectedness Or the entropic brain or the integrated brain, however, you want to talk about it It's this it kind of wipes it clean Not that it doesn't like wipe your brain clean in the sense that it takes everything out of it, but it just provides this opportunity of flexibility.

And then you can kind of sledge anywhere you want to go.

So after a psychedelic experience, people have this window of feeling really often really fantastic for a number of weeks or even months and this flexibility I can I can try this I can try this try new things and so if in that window of opportunity they start new habits they change their relationships they make those life changes then we think that it can really last longer, the effect can last longer?

But if you just give someone a psychedelic and you don't encourage them to make the most of the window of opportunity, then what we found with our participants is that depression came back after 3 months or so.

Your life is already structured in such a way.

It's not like your memory is wiped clean.

you kind of fall into your habits as you would.

Okay, so let's go into the actual effects, right?

So what are, I mean, let's be specific, right?

So of our 20, well, the first thing to say is that they all said that they would prefer it to any other treatment they tried 3 of them didn't have a real effect from it, but they still, even though it hadn't really worked for them they still felt that the whole something about the process was very different to normal, you know, It's different from getting a pack of pills.

It's you're sitting there, you're talking to people, you're getting to know them.

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