MICHAEL POLLAN: How do these psychedelics work? Well, the honest answer is we don't entirely know, but we know a few things. One is they fit a certain receptor site: the serotonin 5-HT2A receptor. And they look a lot like serotonin if you look at the molecular models of them and, in fact, LSD fits that receptor site even better than serotonin does and it stays there longer. And that's why the LSD trip can last 12 hours. What happens after that we don't really know. It's an agonist to that receptor. So it increases its activity. And this, you know the neuroscientists say lead to a cascade of effects which is shorthand for don't really know what happens next. But one thing we do know, or we think we know, is that it appears that one particular brain network is deactivated or quieted. And that is the default mode network. This was discovered not very long ago by a researcher in England named Robin Carhart-Harris who was dosing people with psilocybin and LSD and then sliding them into an MRI machine, to take an FMRI a functional magnetic resonance image. The expectation I think was that people would see an excitation of many different networks in the brain. You know, that's what the kind of mental fireworks sort of foretold, but he was very surprised to discover that one particular network was down-regulated and that was this default mode network.

So what is that? Well, it's a tightly linked set of structures connecting the prefrontal cortex to the posterior cingulate cortex, to the deeper older centers of emotion and memory. It appears to be involved in things like self-reflection, theory of mind, the ability to impute mental states to others, mental time travel, the ability to project forward in time and back, which is central to creating an identity, right? You don't have an identity without a memory and the so-called autobiographical memory, the function by which we construct the story of who we are by taking the things that happened to us and folding them into that narrative. And that appears to take place in the posterior cingulate cortex. So, you know, to the extent the ego can be said to have a location in the brain it appears to be this, the default mode network. It's active when you're doing nothing. When your mind is wandering. It can be very self-critical, it's where self-talk takes place. And that goes quiet. And when that goes quiet, the brain is sort of as one of the neuroscientists put it, let off the leash, because those ego functions, that self idea is a regulator of all mental activity and kind of, you know, the brain is a hierarchical system and the default mode network appears to be at the top. It's kind of the orchestra conductor or corporate executive. And you take that out of the picture, and suddenly you have this uprising from other parts of the brain and you have networks that don't ordinarily communicate with one another suddenly striking up conversations. So you might have the visual cortex talking to the auditory system, and suddenly you're seeing music, or it becomes palpable. You can feel it or smell it and, you know, synesthesia. So you have this temporary rewiring of the brain, in the absence of the control of the regulator. And this appears to have, you know, a beneficial effect in terms of jogging the brain out of bad patterns.

SAM HARRIS: The truth is virtually any experience you can have with psychedelics you can have without psychedelics. Because all psychedelics do, is modulate the existing neurochemistry of the brain. They're not doing something that the brain can't do on its own, you're just playing with neuro-transmitters or mimicking neurotransmitters. I have had the same experience to a more or less similar degree just through meditation, but it's clear to me that I would never have suspected that such an experience was possible but for my experimenting with MDMA in the beginning and it had not been adopted by popular culture as a party drug. So this was coming very much out of the therapeutic community. People were doing in a closeted way psychotherapy with it. And I took it as a means of discovering something about the nature of my mind. It was not a social situation. A friend and I were alone, and we took it together and just had a conversation on this drug. And what was revelatory about it was that it was an experience of absolute sobriety. There was no druggie component to it. We just became clearer and clearer and clearer in our thinking and feeling. And the crucial component of this was a loss of any feeling of self-concern. I was no longer looking at myself through my friend's eyes. I was no longer worried about what he was thinking about me. I was no longer subtly correcting course, based on changes I saw in how he was perceiving what I was saying.

There was a whole veneer of fear frankly, that I didn't know was there that got stripped away. And there was just kind of naked awareness of the present moment. And what came into that void was a very clear understanding that I loved him. The feeling that came crashing down to that point it was just, you know, boundless love for one of my best friends, and absolutely no egoic self-concern, no possibility for feeling envy, for feeling any kind of petty emotion that separated myself from him. But then I realized in the next moment, that I would feel this way for anyone who walked through the door. That there was nothing contingent on our relationship about this feeling. It was not justified by my friendship with him. This was the way I felt for every other conscious being. It frankly blew my mind. And it took me years for me to integrate this understanding of this possibility into my intellectual life.

JASON SILVA: There was a great essay written by Timothy Leary that I think is fabulous, a piece in the '60s called "Programming the Psychedelic Experience," in which he defined the psychedelic experience as a period of increased reactivity to stimuli, both from within and from without. So there's this increased suggestibility. It's almost like we dissolve the boundaries and the filters that keep us from sort of being flooded by sense impressions. And so one is in a kind of delicate suggestible state. So you wouldn't wanna be like driving or having to worry about crossing the street with a red light or a green light when you're tripping. But the psychotherapeutic use of being in a state of increased adjustability is that if you pattern the input signals, if you sequence and control what you're subjected to during this period of heightened sensibility to stimuli, you could steer awareness towards useful spaces of mind. You could navigate that evanescent flux of sensation and perception that Erik Davis says is all we have and all we are, towards places of ecstatic illumination.

Text: Who can benefit from the use of psychedelics?

HARRIS: For some people taking a drug is the only way they're gonna notice that it's possible to have a very different experience of the world. They're sufficiently lumping and uninquisitive about the nature of their own minds. That if you tell them to meditate, if you teach the mindfulness, you tell them how to follow their breath, they will look inside for 30 seconds or 30 minutes and see nothing of interest, and walk away feeling that there's no there there. Either it doesn't work for them or that everyone else must be just faking it, or it requires a certain talent and a certain degree of luck, therefore, to have enough concentration, to connect with any quote spiritual practice, the first time or even the 10th time or even after a year of attempting it, because it's just these practices are difficult. And the conditioning of our minds to just ceaselessly talk is deep. So where drugs have been indispensable for many people is in advertising the possibility of a change in consciousness. And so I don't think they're durable methods for people that you, I don't think you need or should just keep taking drugs month after month, year after year as a mode of spiritual inquiry. But there's certainly a period in many people's lives at the beginning where you wouldn't have, you wouldn't even see a glimmer of reason to suspect that a radical change in the nature of your experience would be possible.

POLLAN: Many of the disorders that psychedelics appears to treat well, are manifestations of a stuck brain. A brain that is locked in loops, a mind that's telling itself destructive stories. Like I can't get through the day without a cigarette. I'm unworthy of love. My work is shit. You know, these kind of evidence of habitual thinking in a really negative loop are relieved. And it may be that an overactive ego is what punishes us. And that relief from that dictator is exactly what some people need to free themselves from habits, mental habits and behavioral habits. I remember talking to smoking addicts, and one in particular, cause I was a little baffled at how could a single psychedelic experience break you know, what was a lifelong or a very, you know, very long-term 30-year smoking habit in a woman who was 60. She was Irish, she was a book editor, and she wanted to quit smoking and had tried everything without success. And she had a psilocybin trip. This was at Johns Hopkins. And she said, "I sprouted wings. And I flew all through European history and I saw the battle of Waterloo and saw Shakespeare, and I died three times, and I saw the smoke from my body rise from the Ganges on the funeral pyres. And I thought to myself 'there's so many amazing things to do and see in the world that it was really stupid to kill yourself with smoking.'" And she stopped. Now, I was very struck by the fact that surely she had had that insight before, that life is too interesting to shorten it by smoking. But for some reason, in the midst of the psychedelic trip, those seemingly ordinary even banal insights take on an authority. They're sticky, they're sturdy. And they're suddenly something that doesn't just seem like an insight or an opinion. It seems like a revealed truth, you know, absolute knowledge. And this is very common on psychedelics.

And it's very common in the mystical experience. William James said that the Noetic quality is what he called it. This idea that what you learn in that experience, has a special absolute authority, it's just a factor in mystical experience. So this is what I think allows many of the addicts to break their habit. The kind of resolution that most of us make every day and break the next day, becomes something that they can actually live by. And I thought that was quite extraordinary. And I heard that from many people and they would all say the same thing. I realized, you know, I acquired a new perspective on the scene of my life. It was like the camera had been pulled further back than it's ever been. And I saw myself and I saw what I was doing. And I realized this is really stupid. So perspective. I mean a perspectival shift can be very powerful. Other indications that the drugs show promise for, and this is psilocybin mostly that's the psychedelic that's been studied the most, depression, anxiety, obsession, addiction. There've been trials of alcoholics, of cocaine addicts and smokers, all showing great promise. And there're future trials for eating disorders. And, you know, a new trial of obsessive-compulsive is being planned. So this is a very exciting time. And again, the drugs still have to go further to prove themselves in larger groups of people. And we have to figure out exactly the optimal way to offer it to people, but we've got some new tools and we've had so little innovation in mental healthcare, since the early nineties, really since, you know, the introduction of the SSRI antidepressants, whose effectiveness is starting to fade and fail. And I don't think people fully realize how lousy the tools we have to treat psychiatric illness are right now, and how many side effects they have. They put on weight. They cost people their libido, they're hard to get off of, and they only treat symptoms.

BEN GOERTZEL: There's a tremendous amount of insight that can be plumbed using these various substances. There's also a lot of risks there, as with most valuable things. I mean, I've had friends and family members, you know, literally, be pushed over the verge of insanity by excessive and poorly thought out use of psychedelics. So I mean, it's a great potential benefit and a great potential risk. And I think it's generally a terrible thing that these substances are illegal in most modern governments because that means that we're not developing the right set of cultural institutions to guide people in really productive use of these substances.

Text: The history of psychedelics.

SILVA: There's a lot of talk nowadays about the psychotherapeutic use of psychedelics. We're kind of going through a psychedelic renaissance. It's been a while since the 1960s. These substances have been repressed, but, you know mankind has been using and experimenting with entheogenic or God facilitating substances for millennia.

POLLAN: Psychedelics have been used in societies, in Central America and South America, and the old world as well for thousands of years. And they were used in healing, as a sacrament in religions, for divination and purposes like that. So there's an ancient history of psychedelics that goes way back. And then there is the kind of mid-century, 20th-century history, which begins with Albert Hoffman, who is a brilliant chemist with the Sandoz company in Switzerland. And he in effect invents LSD. First in 1938 but he doesn't know what he has yet. But then in 1943 in the middle of World War II, he got this premonition that this was a particularly interesting and beautiful molecule and he should take a second look at it. And he resynthesized it and accidentally ingested some of it perhaps through his skin or by touching his eye, and realized that this was a powerful psychoactive molecule. Sandoz is the company he worked for really didn't know what was it good for? How could you use this drug? How could you monetize it as we would say? So Sandoz does something very interesting. They organize, you know, basically a crowd-searched research project, where they offer LSD to any researcher, therapist who wants it for free. And this led to this very fertile period of research in the '50s. LSD becomes, it's considered by many a psychiatric wonder drug. So here you have this very exciting promising period of research, that's going on without any government interference, without a lot of controversy, but in the '60s everything goes haywire. And what happens in the '60s, is that basically the drugs escaped the lab and become a very important ingredient in the creation of the counterculture.

Timothy Leary has something to do with this. He is a psychologist who ends up at Harvard in 1960, but the summer before he gets there he is introduced to psilocybin while in Mexico and has a profound experience. He was by the pool in Cuernavaca and he said he learned more in those four hours on psilocybin than he'd learned 15 years as a therapist. But, like several people who've studied psychedelics, Leary gets intoxicated by them, by the promise, not just to heal but to change society. And this is a very dangerous thought. And Leary then becomes a psychedelic evangelist, you know, turn on, tune in, drop out. Everybody should use acid. If we can turn on 4 million people we can blow the mind of America. And it becomes very threatening to the powers that be. I mean, Richard Nixon called Leary the most dangerous man in America. He felt that LSD and other drugs were sapping the will of American boys to fight in Vietnam. And he may well have been right. I mean LSD encourages people to think for themselves, to not accept the frames of social values, the games that we play socially, and in important ways LSD did fuel the counterculture and was very threatening to adult society, and to the powers that be. By the end of the decade, they're made illegal, a schedule one drug beginning in 1970. The research gradually atrophies and dies by the mid-seventies, early seventies, which is unprecedented in science, that you would have this incredibly promising avenue of inquiry, scientific inquiry, that's stopped for reasons that have nothing to do with the science. I think there's a lot more we need to learn, but beginning in 1999, with some private funding from some people in Silicon Valley and elsewhere, Johns Hopkins undertakes to begin studying psychedelics again. So profound effects from a single application of a non-toxic drug is a big deal. And I think portends a potential revolution in the way we practice mental healthcare.