I'm Matt Johnson. I'm a professor of psychiatry and behavioral sciences at Johns Hopkins. I study drugs, all kinds of drugs: uppers, downers, all-arounders. The drug class that I've studied most over the last, nearly couple of decades, are the psychedelic compounds.

I developed an interest in drugs, including psychedelics, over 25 years ago in my early 20s. I was fascinated by the history of psychedelics in our culture; the fact that there was medical research in the early days; and I just had this growing fascination with psychoactive compounds in general. The idea that any of these substances, whether we're talking about cocaine, caffeine, you name it, including the psychedelics, how these things affect our behavior, how you put these small amounts of a substance in your body, and they can have, at times, radical changes in your subjective experience and what you do.

It's hard to imagine a more interdisciplinary topic in the realm of drugs than psychedelics. I mean, psychedelics crosscut so many interesting domains. They've apparently been used for time immemorial by indigenous cultures throughout many different cultures on the planet. In our own Western cultural history, they really exploded on the scene in the 1960s, and were associated with some really radical changes to society.

And what really is most interesting, to me, as someone who's really focused on the effects of drugs on behavior- whether it's the good, the bad, the ugly- psychedelics are the only drug class that I know of where you have not just one or two, but lots of stories of people saying they took this thing one time, some decades ago, maybe 50 years ago, and they say it had this profound impact on the course of their entire life. You know, I can't think of another drug class where people claim therapeutic or beneficial effects of any type when they used it only one time.

I mean, you take cannabis, you know, plenty of examples of therapeutic effects, but I've never met anybody who said they smoked pot one time 20 years ago, never touched it again, and yet they can point to how this has radically improved their life. Those stories are countless with psychedelics. Not everybody, plenty of people just try them, and they have fun, and that's it. But it's surprisingly common for people to say really outlandish things.

Like Kary Mullis won the Nobel Prize inventing PCR, which revolutionized biology. He said he wouldn't have been able to do that had he not had experience in taking psychedelics. You move into the arts and then, I mean, gosh, I mean, who hasn't heard of musicians and other artists claiming that psychedelics had a profound impact on their creativity?

I mean, I remember when I was coming of age and my late teens, discovering the music of earlier generations, and, "Hey, there's this band people have heard of, probably called The Beatles, you know? And wow, they're pretty good." But then you explore their music, and there's The Beatles before LSD, and then there's The Beatles after LSD. That's a big shift, and a lot of folks like the Beatles after LSD, especially so.

Okay, so the term 'psychedelic' was coined by Humphry Osmond, who was writing letters, back when people wrote letters, to Aldous Huxley. And they were sending letters back and forth- they had a friendship-and they were discussing, they were both profoundly intrigued by this new class of drugs. And they were trading ideas about what the ideal name for this new drug class would be. And Huxley came up with some unpronounceable term that Humphry Osmond dismissed.

And let's see if I can recall the poem that Osmond wrote to Huxley. He said, "To fathom hell or soar angelic, just take a pinch of psychedelic." And what psychedelic means, from its linguistic roots, is "mind manifesting." And so I'd say that's a pretty good term.

There's no perfect term for this drug class. Certainly hallucinogen, which is often used is not a great term 'cause very rarely do people have true hallucinations, and there's a misunderstanding of what that means. But the psychedelic, the idea that these are mind manifesting, that's consistent with this other notion that these are non-specific amplifiers. In other words, you could have a euphoric experience, you could have a hellish experience. You name it in the realm of human experience and emotions, that can be your experience, and it could be amplified. And it's very much a product of what's going on in your life at the time. It's not this reliable effect.

So it seems like manifesting the mind, digging deeper into the mind, amplifying what is already there in the mind, that sort of generally fits with clinical observations with these drugs. Terminology is so difficult in this area, and even the experts will disagree.

Psychedelic can be used to refer to what are called the 'classic psychedelic compounds': psilocybin, which is in magic mushrooms, LSD, DMT, which is in ayahuasca, mescaline, which is in peyote- those are the classic psychedelics. They affect a certain particular type of serotonin receptor, and that's their primary mechanism of action.

But then you have other drugs that are called psychedelic, and I think it's appropriate to call them psychedelic. Other scientists will disagree, but they have a different mechanism. They're not classic psychedelics. So for example, MDMA will work by releasing serotonin; so that's a different mechanism. And its effects are different than the classic psychedelics, typically not as intense, typically more focused on one's emotional experience, more of a heart trip than a head trip.

And you have other drugs, such as ketamine. So that affects the glutamate system in the brain primarily rather than the serotonin system. Even though there's evidence that the classic psychedelics downstream for serotonin, they also affect glutamate. But nonetheless, the drugs like ketamine and PCP, which are in the same class as each other, they initially affect the glutamatergic system in the brain.

So what does psychedelic mean, then, if it refers to multiple underlying classes, pharmacological classes of drugs that work in different ways? And the answer for me is that these are all drugs that can have a profound effect on one's sense of reality, including one's sense of self. And I would say that typically isn't the case for what we think of as the stimulants or the sedatives or the opioids. People feel different, but not as extremely as with these psychedelic compounds.

When I first started in psychedelic research in 2004, it was hard to get a paper published using the word psychedelic. Hallucinogen, by far, was the preferred term in academia in science. Thankfully, that's changed. And I think it's because enough scientists, like myself, kept trying to use the term, in arguing that it's a better term.

You know, hallucinogen, one, the reasons I don't like hallucinogen as a term, is that it focuses on the perceptual realm, which a lot of people who aren't very familiar with psychedelics, they just assume that's the primary mechanism. In other words, someone will hear about some of the research and say, "I don't get it, why would seeing things, hallucinations, what are you seeing, pink elephants, and that makes you want to quit smoking? Like, I don't get it," people will say. And that's 'cause they're focused on this perceptual aspect of psychedelics.

And probably the reason that the perceptual effects have gotten so much attention is those are the aspects that are easier to describe. Like, "Yeah, the walls look like they were waving." That's not normal. I can describe what that is. Like, what the hell is going on? Trying to wrap language around dissolving the sense of identity, having some sense of who I am beyond the normal descriptors, you know, "I'm so old, I'm a male, I'm this, I'm from this country," all these ways we define ourselves, just when they're completely stripped away and what's left, I mean, we're getting into deep philosophical realms there that are really hard to describe. It's easy to describe, "I saw some crazy-ass colors."

So I think this is sort of stuck, the focus on perceptual effects has sort of stuck as sort of the lay understanding of what these drugs do. Hallucinogen, therefore, it focuses on this one relatively arbitrary aspect of psychedelic effects. And that's why, actually, in therapy, one of the reasons we have people wear eye shades is we don't want them focusing the entire time on the wavy walls and the intense colors. And that's great. It's a six-hour drug effect. They're gonna have to get up and take a pee at some point. They'll get to see the wavy walls. You know, not everyone has those perceptual effects, but they'll have that opportunity.

By blocking out the external distractions, the idea is one can focus the experience more internally about the nature of yourself, about these patterns in your life, about the big picture of what's going on in the world. The idea is you might get stuck at the pretty colors. And the pretty colors are great, but there might be something even more valuable underneath that if you dig deeper into that experience. And so I don't like the word 'hallucinogen' in that it just focuses on that perceptual realm, which is kind of just a trivial aspect and not even the key therapeutic aspect of these compounds.

Also, hallucinogen implies that these drugs cause hallucinations, and the strict psychiatric definition of a hallucination, these drugs rarely cause those. If you have a hallucination, it means you are observing something, you're perceiving something in the environment that you actually believe is there. Someone really thinks a pink elephant, to use a classic example, is really in the room. That's a hallucination. You thought you were talking to a friend and having this long conversation, and then you look over and realize, "Oh, that friend was never there." That's a hallucination.

What you typically get with psychedelics are more visual illusions or what you could call 'pseudohallucinations.' Typically, reality testing is intact, which is a fancy way of saying the wall's waving like a blanket or like waves on the beach. That might be really impressive. But typically, the person knows, in reality, the walls really aren't waving. They realize the reason they're seeing walls waving is because they've taken this substance. So you, you really don't get, typically, true hallucinations, so it's not a great word.

Entheogen, I've never been a fan of that word to refer to a drug class. I'm a fan of using that word in its anthropological sense. In other words, so what 'entheogen' means, one of the common definitions from its linguistic roots is "awakening the divine within," or "awakening God within." So it's really referring to this sacramental, spiritual religious use of these compounds.

My beef with that is that you name the psychoactive substance, it's been used as an entheogen. You know, tobacco, coca leaves, which contain cocaine, opioids. I mean, you'd be harder pressed to find the drug that hasn't been used as part of a sacrament at some point. So I like to refer to the entheogenic use of a particular substance. It could be the entheogenic use of tobacco by indigenous tribes. It could be the entheogenic use of ayahuasca. But I don't wanna define that particular substance as entheogenic.

And then as a counterpoint, a couple of, yeah, high school kids that take some mushrooms, and they do a lot of giggling, and they see some pretty colors that really amaze them, and they don't really have anything that they would describe as a spiritual effect, that doesn't sound like an entheogen to me. So it's kind of an arbitrary- you're assigning just one portion of what these drugs can do, but you're defining the entire drug class with that one effect.

So that's why I think the psychedelic is a broad enough term to encompass all of those experiences: the perceptual effects, the potential spiritual effects, and any other personal insights etc.

The first big wave of that scientific interest for psychedelics was in the 1950s. So this was, yeah, about a decade after Albert Hofmann had first discovered the psychoactive properties of LSD. And in that following decade, essentially the pharmaceutical company, Sandoz, that he worked for in Switzerland, pretty liberally sent out samples of LSD for physicians to do research with.

And when I say research there, it's not like research now where you need a year's worth of approvals with this highly restricted access and everything. It was like "Hey, I'm a doctor, and I'm curious to give this to some of my patients to see what's up." "Sure, here you go." You know, put it in the post from Switzerland. And so, there was a lot of sort of casual research use, but there were also some early clinical trials.

I would say one of the most important groups in the history of this work was this group led by Abram Hoffer and Humphry Osmond in Saskatchewan, Canada. And they were really the first group that I would say developed what we now call 'psychedelic therapy,' this idea of that you're not just mimicking psychosis, which is what originally was thought by the very early researchers. All this stuff did was mimic people having a psychotic break, having a schizophrenic episode.

These Saskatchewan researchers figured out if you prepare people and have a comfortable environment and just have them introspect, lay on a couch and pay attention to their experience, you had these experiences that oftentimes were anything but psychotic. I mean, they were reported to be some of the most meaningful, clear, lucid experiences of people's lives. And you could use many names, a transcendental experience, mystical experience, insightful experience.

And so there was some development, there was other groups. There was a group in Maryland called the Spring Grove group. A lot of early research there, particularly with cancer patients. But then the research was really put on hold for several decades after this period.

In the first wave of research from the 1950s through early '70s, there was this growing appreciation of some of the risks and the safeguards needed to minimize those risks. But not every investigator was aware of this. And some of them were only aware of this as time went on, so it was an evolution. But some of the research just, hey, they gave a giant dose of LSD to someone and then locked them in a padded room.

So one of the trials looking to see if LSD could help people with alcoholism, they literally tied people down in restraints to their hospital bed, gave them a massive dose of LSD, 800 micrograms, which is a really big dose. And they didn't give them any warning that, like, they took this substance that would profoundly alter their conscious experience. So we've figured out a lot since then, that sort of research. Those are the conditions under which, when you do get experiences that look more like psychosis, you treat the person like they're gonna go crazy. And a lot of times they, at least temporarily, they feel like they're going crazy.

And then there was controversies surrounding Timothy Leary at Harvard. He did some really great research early on. And even while he was at Harvard, having people over at his house on a Saturday night, and everyone taking it, including the researchers. So we've moved away from that, thankfully.

And gosh, I should mention in that earlier era, this is also when the CIA was seriously investigating these drugs as part of their MKUltra program. This is not urban legend. There's lots of declassified material through the Freedom of Information Act that has revealed this history. They were giving it, at times, to just American citizens without their knowledge or consent behind a mirror. People visiting a sex worker, for example. Glass of water they're given and big dose of LSD, and these goons from the CIA are standing behind this one-way mirror, like, just observing to see what would happen. So you had, obviously, highly unethical research like that going on.

Yeah, on a lot of these dimensions, I mean, I think it's pretty clear today what the major risks of these compounds are. And hopefully, just ethics have improved the recognition of it. This is very serious, and don't underestimate the damage you can do to someone, like slipping out LSD into their drink.

Most psychedelics aren't legal in most countries in the world. There are some exceptions, but the primary classic psychedelics we know of, psilocybin mushrooms, or so-called magic mushrooms, or LSD, ayahuasca, which contains the compound DMT, mescaline in peyote and other cacti. In most countries, these are not just illegal, but in the most restrictive class.

So for example, in the United States, they're in Schedule 1, or in the United Kingdom, they're in schedule A, same thing; it's the most restrictive class for the most dangerous compounds with the greatest abuse potential, and with no recognized medical use.

Now, there are some nuances to that. There have been some states in the U.S. that have decriminalized, or even in Oregon, recently, have legalized the use of psilocybin in the context of a therapeutic-like situation with a guide. But for the most part, these are illegal.

Now, the research that's happening now, a lot of it is exploring medical applications through the FDA process where there's FDA approval and DEA approval. So the hope is as these trials advance, and as we move into what's called 'phase 3 research,' that's the final level of a clinical trial, typically with a larger number of participants. That's the final phase that can decide whether or not this drug is gonna be approved as a medication by the FDA.

And so we're likely only two, three, four years away from multiple psychedelics potentially- depending on those phase 3 results- being approved for treatment. So if that happens, then they would be legal to be used medically, but they would still be illegal in another context. Similar to what a lot of people may not realize that cocaine is legal to use in certain medical settings. Methamphetamine is legal to use in certain medical settings. All kinds of opioids, as most of us know, are legal to use in many medical settings. So it would be moving these compounds into more of that category: legal for medical use.

The compounds that are likely to be approved, depending on the final results, in the next few years for medical use are MDMA, which some people might know as Molly or ecstasy on the street, and psilocybin, which is in so-called magic mushrooms.

Yeah, so psychedelics can prompt a wide variety of subjective changes. And so that can span thoughts: the way you think, your cognition. Feelings: very profoundly at times, the intensity of your feelings, the variability. You can swing from a terrifying experience to this beautific, sort of like most amazing experience of your life. So the variability, the intensity is there. So really any aspect of subjective experience, including self-identification, how one holds- how they define themselves, how they define reality. These are sort of the deepest aspects that I think and the aspects that are most aligned with the psychedelics' therapeutic effects.

One aspect that we typically talk about with drugs, in general, that's relatively low for the psychedelics, are just their effect on physiology. Compared to the intensity of the subjective effects, it's remarkable how little impact these substances have on our biological functioning. So your heart rate, your blood pressure. How do people overdose on other drug classes? They drink so much, they take so many opioids, they stop breathing. Some drug kills their liver 'cause they've taken too much of it. They had too much of a stimulant, and they have a stroke or heart attack.

Psychedelics are really robustly safe at the physiological level. There are exceptions. For example, people at very high risk for heart disease. It does raise the blood pressure and pulse somewhat, but all of those physiological effects really pale in comparison- compared to other drug classes-pale in comparison to the intensity of the subjective effects.

So it really is those levels of subjective effects that are relate to one's conception about the big picture of their life, how they define themselves, how do they define reality, which is why I think something like the mystical experience, which includes this sense of oneness, being at one with the rest of the Universe, or being at one with the rest of humanity, someone comes out of that, and that has the potential to reframe whatever disorder we're talking about.

Reframing this addiction that they've convinced themselves, "Oh, I'm just a failure, I can never do it." Having an experience like that can really reframe that as, frankly, as small potatoes, and thinking about yourself in terms of depression, and this sort of self-fulfilling prophecy. So it really are those, how one defines themselves, I think, it's at the deepest levels.

Yeah, the huge question that's always thrown out is: How do these psychedelics work? And you can just come at that from so many different angles. Kind of the biggest divide is whether we're talking about on the psychological side or the biological side. Does it work by hitting these brain receptors and then having other effects, or does it work because of the experience? And the first thing I like to say about that is these are two sides of the same coin.

Presumably, every psychological experience has a biological correlate, whether we're aware of that now. Like, you see the color green, there's something happening in your brain that's coding that experience of the color green. So we need to move away from thinking it's one or the other.

And psychedelics are really interesting 'cause I think they're just, like, they're placed right at that interesting interface. Clearly, there's this very real biological effect. Something dramatic happens to the brain when you put the psychedelic in the system, but then someone has this experience. And when they change their life because of that, that ends up sounding more like they went through a really good course of psychotherapy, or they had a life-transforming experience, the way someone might say, "Well, having children changed them, or getting married changed them, or falling in love for the first time or visiting another culture for the first time." Sort of like these life experiences that change people. So psychedelics are really interesting at that bridge, philosophically, between the biological and the psychological.

Now, to go down that biological path, what's happening, there's a lot going on, and we know a lot, but there's a whole lot more to figure out. The first thing that happens is that psilocybin, once it's circulating through your blood after you've eaten some of it, well, it actually converts to a related compound called psilocin, which is the thing that's actually hitting the brain receptors, and it activates a subtype of serotonin receptor.

So we have lots of different types of serotonin receptors in our brain. One is called the serotonin 2A receptor. And psilocybin and the other classic psychedelics can latch onto that the same way that serotonin latches onto these brain receptors. But they do something different, 'cause clearly serotonin itself, which we all have floating in our brains right now, is not psychedelic. But when this activates the receptor, something different happens within that neuron, and it propagates this effect downstream.

And we now know that, then, other neurotransmitter systems are involved. For example, we know the glutamate system is involved. So psilocybin effects serotonin, but then serotonin affects the glutamate system. And so you can think about it as if the serotonin 2A is the first domino. I think one of those set-ups with the million dominoes in the room where one knocks down the other, and then it goes up a ladder, and it spins a little thing and falls down, and all of that. The serotonin 2A is just the beginning part of the story. It's that first domino you knock over, and then you have the glutamate system.

And then at another level, maybe this is sort of panning back and viewing that whole room full of dominoes, but at another level of analysis beyond what receptors are affected, and even, like, beyond what brain areas are become more active or less active, a really interesting level of analysis is: What's the nature of the communication across the brain that's changed? This is referred to as 'resting state.' What are the brain network dynamics? What's the relationship between the activity across different areas of the brain?

And what's interesting is when the psychedelic is on, in the system, you see a massive increase in communication across brain areas that don't normally communicate. And you could tell this by the activity in those different areas is all of a sudden much more correlated with each other. And so they're normally moving and grooving and doing their own things. Much of our psyche and our mental processes are compartmentalized. You know, "You do your own thing, and you do your own thing," and we only sort of integrate it when it's necessary. But it seems like you kind of, like, have this massive increase in communication across these different silos in the brain.

That is probably an important level of analysis that is underlying, at the psychological level, claims of insight, claims of extraordinary experiences, viewing themselves from a radically different perspective, from a different lens. It's sort of this, like, massive shake-up in one's experience of reality.

And so, here we've gone through the receptor level to the brain activation level to the network communication levels of the brain, to what's the psychological experience that unfolds from that. And then, presumably, the way we get long-term behavior change is that that person starts to change their life. They actually learn lessons. And there also seems like there may be, based on animal research, increased plasticity, neuroplasticity in the system so that in the days following the psychedelic experience, people are more primed to learn new things.

You know, there's a greater sticking power, there's a greater ability to establish a new and hopefully a more optimal normal state. And then if that is sort of reinforced and maintained, then that just becomes the new habit. And that's why we are seeing people six months later that are feeling better, whether they're smoking less, or they're less depressed.

So a major difference between the classic psychedelics and MDMA is in how they're interacting with the serotonin system. They're both interacting with the serotonin system, but in very different ways. I mean, we should keep in mind that typical antidepressants also interact with the serotonin system, but in a very different way.

So the classic psychedelics, they're mimicking the effects of serotonin on that receptor site. So the way neurotransmission works, brain communication works, is you have one neuron here, one brain cell and neuron here, and one here. And in order to have a signal propagate, a communication, a messenger is sent across this little gap in-between those two neurons, and those what we call neurotransmitters. A little serotonin is released into this space, and it travels over and it activates, it sits in this little pocket on this side. This is like, you know, baseball, the receptor is the the catcher's mitt.

In the case of the classic psychedelics, it's normally a regular baseball that is thrown into that catcher's mitt, Now we imagine we've swapped out, we've taken the pitcher, and we've taken the regular white baseball, and now we've put like this tie-dye baseball in there- this is like the psilocybin baseball. Now that's being thrown out into that space in between the two cells. And that's being captured in that catcher's glove. And that has a different reaction on the, I guess, the catcher in this analogy, than serotonin itself would.

MDMA is very different. MDMA is working with natural serotonin. It's causing not this differential effect on the catcher's side, but it's causing the pitcher, the neuron that's normally sending out serotonin into that space between the two neurons, it's causing the pitcher to just throw out a massive increase in balls. So now, the catcher is on the mound, and they're just getting balls thrown at them left and right 'cause this pitcher's just going crazy, throwing out way more serotonin, or more normal baseballs than normally would. And so that has a different effect on the system than the classic psychedelics.

So there's a fundamentally different way in which the biology works, and most experienced users will tell you it feels fundamentally different. And there's more commonalities between the classic psychedelics, let's say LSD and magic mushrooms or psilocybin, shades of difference, but in the grand scheme of things, those are very similar compared to, on the other hand, MDMA.

And we have some edge cases, some more exotic compounds, 5-methoxy-DMT. We're still early in the research. It might be that serotonin 2A plays less of a role in the primary effects of 5-methoxy-DMT, but that's not definitively shown yet. A lot of these compounds, well we have a simplistic story about serotonin 2A being the primary receptor, but, in fact, most of them hit a large number of receptors to a different degree, so it can be a complex process.

There's substantial evidence that 2A is the key receptor that mediates the effects of classic psychedelics. How do we know that? We know that there are these compounds called 'antagonists' that people can take, and that will block a specific receptor. And so there are compounds, like ketanserin, that will block the serotonin 2A and not other receptors. It does a little bit, but it's primary blocking action is on the serotonin 2A.

And if you block serotonin 2A, all of a sudden, you can give a big old dose of psilocybin to people, and they don't feel anything. And the same thing happens in rats. You can train rats to say, "When I've given you an injection of psilocybin in the belly, 10 minutes before your session, we put you in a sort of a skinner box where you can press levers- give you psilocybin on those days, the left lever is the one that gives you a little food pellet if you press it. And on other days where you just give you a saline injection, a placebo, essentially, in the belly, on those days, the right lever is what gives you, is produces the food pellet."

And then if we do that for a few weeks, all of a sudden, that animal is able to reliably tell us whether they've gotten psilocybin or not, which is really remarkable. And then you could do interesting things, like give another compound, like LSD, and all of a sudden, they'll treat it as if it was psilocybin. So it's a powerful pharmacological assay in animals.

And so if we block the serotonin 2A receptor in those rats, they are no longer able to distinguish, to discriminate between a psychedelic and a saline injection- very consistent with the human work. And there's other layers. You can create rodents that are so-called 'knockouts,' where, from birth, they're lacking the serotonin 2A receptor. And in those genetically modified knockouts, psychedelics don't work.

So there's all kinds, and there's also a very, very tight correlation amongst the existing classic psychedelics. If you plot how many milligrams you need to give, so this is the potency, whether you need to give 400 milligrams or just a 10th of a milligram in the case of LSD, and you correlate that with the affinity for this serotonin 2A receptor, which is like the stickiness for that receptor, how is it likely that that compound, that drug is gonna stick into that receptor? That's an astonishingly tight correlation.

So there really is substantial evidence that the serotonin 2A is the primary site of action for these psychedelics. And it's probably the case that these other receptor sites add some coloring to the effect, but we know that, in different ways, if you take out 2A, you don't have any substantial experience there.

So only what are we call the classic psychedelics hit 2A. So the primary examples being LSD, psilocybin, mescaline, DMT. Drugs like ketamine and PCP affect the glutamate system primarily as their first sort of site of action. And then you have other compounds: MDMA releases serotonin, so that's a different form of action on the serotonin system.

You have compounds like salvinorin A, which I did the first human trials that were blinded that actually found an effect of that as the primary agent in salvia divinorum. That activates a type of opioid receptor called the kappa opioid receptor, which is different. Most of the opioids we think of are mu opioids: morphine, heroin, oxycodone, very addictive compounds. The kappa opioid system is very different and leads to a very different variety of psychedelic effects. So that has its own distinct pathway.

Ibogaine, that's an interesting one. That affects a lot of these various mechanisms that are at play with different psychedelics. So it's almost like a jack of all trades psychedelic with different points of entry. It's pharmacologically pretty promiscuous. Ibogaine is of interest because of the anecdotes of people overcoming opioid addiction with it. And there does seem to be some really compelling evidence, even in animals, in rats. Ibogaine will substantially decrease their self-administration of drugs, like opioids and cocaine.

It seems to normalize the wild fluctuations that happen within addiction and our so-called reward system, our mesolimbic system, the rewards pathway. And that becomes dysregulated in addiction. Even in an animal like a rat, you'll see these wild fluctuations of dopamine. And with ibogaine, you'll see this kind of more normalizing, kind of tamping down those wild fluctuations into more of the normal range.

However, there are concerns with ibogaine that it can hurt someone with heart disease, and that's more of a concern than with the classic psychedelics. There's concerns about prolonging the so-called QT interval in the heart. So there's debate about whether there's a clinical future for ibogaine. Some people argue that its top potential toxic effects are such that it's not gonna be ever approved as an FDA treatment. There's others that disagree.

I'm actually most interested in using something like psilocybin and LSD to treat opioid addiction because compared to ibogaine, these are remarkably low in physical toxicity. And I think some of these mechanisms may, in fact, be shared. It may be that some of those properties that we think that are unique to ibogaine aren't so unique and maybe that we're seeing them with psilocybin and the other classic psychedelics as well- but we'll need more research to figure that out.

One of the pitfalls of this clinical work is that you'd be hard pressed to find a more intimate and vulnerable psychological intervention for a person. People are at their most vulnerable in these psychedelic experiences, and you can't overstate the weight that comes with being in one of these sessions, having orchestrated one of these sessions as a guide, as a scientist.

Some people will describe as the most important experience of their life. That's just a situation that is ripe for abuses if we don't have the right safeguards there. So all of the abuses that we normally know about, sexual abuse being right up there, and that's why it's important to have certain mechanisms in place. I think it's better to have multiple guides that are witnessing the session, whether they're both in the room or one is outside, at least watching on camera. But we need to make sure multiple people are involved.

We need to limit the use of therapeutic touch and have informed consent surrounding that. So holding someone's hand, holding their shoulder, but not doing extensive body work as some folks would like to call it during the session, because that's just gonna, for some people, that's gonna lead to boundary issues.

And unfortunately, I think in this area with psychedelics, clinicians can get into, and scientists can get into a space that I call 'psychedelic exceptionalism,' where the idea is that these experiences are so big, and this is so far beyond what we normally deal with in medicine, in clinical psychology, you name it, that new rules apply. Tim Leary said this a lot: "This is too big for the science game." This is like our normal games can't contain this.

We need to take the opposite approach and say, "Because of that vulnerability, because of the incredible gravity of these sessions, we need to even more tenaciously cling to those clinical boundaries," that ethics training that you learn when you're becoming a physician or a clinical psychologist or a social worker or a nurse, all of these professions. We need to really a adhere to those, what might seem like boring old ethical codes because they're gonna really be tested here.

So the second pitfall would be 'metaphysical neutrality.' Essentially, when people butt up against those big picture questions, what's happening in these sessions is an experience of God, is an experience of ancestors, visiting different dimensions, you name it, all kinds of explanations that are provided, we just have to really let the patient drive the bus in terms of making any of those claims. We have to be metaphysically neutral.

That doesn't mean we should correct someone. If someone thought that was an experience of Jesus or the Buddha, it's not on us to say, "No, no, no, no, no, that wasn't. We're being neutral here." What it means is we're just not making that inference for them. That we're just supporting whatever their process and their conclusions from this; it's not our job.

And a very concrete aspect of this is really staying away from the imposition of religious icons in these sessions. Unfortunately, it's become commonplace and typical to have a Buddhist statue in these rooms. I have nothing personally against Buddhist statues. They're very pleasant, but I don't think it's appropriate in mainstreaming this treatment. I say BYOB, "bring your own Buddha" or any other meaningful object, be it a crucifix, be it a flying spaghetti monster painting. Whatever it is for you, the pictures of yourself and your kids, bring those meaningful objects.

And we just have to check ourselves into playing guru, playing priest, playing at this metaphysical level where we're filling in those answers for patients.

And then the third pitfall is being loose with the term consciousness, and the conclusions we're making about what psychedelics have scientifically told us about consciousness. One part of that is we just need more precision in our language. Consciousness is a pretty sloppy term; it means many things.

Kind of the most impressive use of the term is what we refer to as 'phenomenal consciousness.' And this relates to the so-called hard problem of consciousness. That is like: Why is there an experience at all? Why is not the universe just made out of these objects? Whether they're people, animals, other things that are interacting. Why is there an inside experience to anybody?

It appears impossible to answer that question. That's why philosophers call it "the hard problem of consciousness." So, never say never. I'm open to psychedelic research addressing the hard problem of consciousness. Right now, I don't think anyone can think of a way in which psychedelics can do that, but it's a worthy effort. But we need to check ourselves.

Other things, when we use the term consciousness, sometimes we mean self-identity, having a self-concept. That relates to these experiences of unity or so-called 'ego death.' I think there's a lot that we can learn with psychedelics on that aspect of consciousness because sometimes people don't have a sense of self, or at least they have a radically altered sense of self. So we can learn a lot more about the brain mechanisms underlying the sense of self.

And there's other things called consciousness, 'access consciousness.' This is sort of you have- you weren't thinking about your grandmother two seconds ago, but now you are 'cause I used the word grandmother. That's come from somewhere in your brain. There was a memory there. It wasn't in your awareness at the moment, but now it is. What is that process of being called forth of things being brought into awareness? That's also in the category where I think psychedelics can be brought to bear in answering some of these questions.

However, most of the work that's been done with psychedelics in terms of the brain mechanisms, it has not addressed any of these questions of consciousness. Most of those, most of the psychedelic work in the brain has addressed how psychedelics work in the brain. And I think when we automatically make that leap of, "Well, psychedelics seem so fundamentally important to consciousness that if we figure out how psychedelics are working, that's telling us something fundamental about how consciousness is working," we're on a slippery slope there, we can start to fool ourselves. So we really have to have more precision in our language, and drill down more rigorously on these questions of consciousness.

The hard problem of consciousness refers to this seemingly unsolvable problem of: How and why is anybody aware? Why is there an experience there? The only evidence that we have for phenomenal consciousness, the idea that there is some experience being had is that I feel that I'm having this experience. I feel that I'm conscious. And because other creatures walking around that look like me, other human beings, it's a presumption, probably pretty good one, that they were having a similar experience- but there's really no evidence. Like, how would I prove that you are conscious? That seems outside of the bounds of empirical science.

What experiment could you ever do to prove that there is an experience to be like somebody else? And that's what the hard problem is. That's one way it's been expressed. What is it like to be a bat? That's a classic example by Nagel. What is it like to be my dog? What is it like to be another person? Presumably, there is something that it's like to be you, but there seems to be no way, scientifically, to account for why that is- so that's the hard problem of consciousness.

How do you explain this? And a lot of is made out of psychedelics and their ability to inform the nature of consciousness. And so this would be the ultimate kind of task. If psychedelics could help us to crack the hard problem of consciousness, I mean, perhaps that's the biggest question out there. I mean, it's up there with like, where did the Universe come from? What is the nature of reality? It's really one of the biggies.

In fact, some of the really interesting questions about: Is mind, or subjective experience, something that pops out of the physical world? Do we live in this material world where sort of experience is just some sort of epiphenomenon? Or, perhaps, consciousness or experience is something more fundamental to the very nature of reality. And you can go into realms of philosophical ideas, such as panpsychism, the idea that consciousness really pervades. It doesn't just emerge, but it pervades the material universe in that these are two different sides of the same coin.

But it seems pretty routine for people to kind of grapple with those big questions. That's why I'm- I think it's really important that we separate, you know, "Hey, a bunch of people say, based on their experiences, that they believe psychedelics open some window into consciousness or give them sort of insights into the nature of consciousness." But that doesn't constitute scientific evidence that what they're saying is actually true.

So it's kind of a weak argument, really. Just the fact that people tend to think that psychedelics have provided them with answers about the nature of consciousness, it makes it intriguing to see if we can go further, if we can do anything to really objectively harness psychedelics to solve some problems of consciousness. So that's why the inclination is there to explore psychedelics in the experience of consciousness.

But we should just be very well-grounded. And like with any scientific question, we shouldn't hold our breaths for the answer. It's like just pursuing that journey of questioning will no doubt come up with important answers. They might not be to the questions we were asking, but maybe they're to other questions. And so, if I could think of an experiment I could do with psychedelics to address that question, I would have already done that experiment. And right now, I don't think anyone can, but I think we should remain open to the possibility that psychedelics could be used to address the hard problem. But we need to think about it because that really seems like a difficult problem to crack.

The work, so far, that most advanced research, is using psychedelics in the treatment of depression and end of life or, in the context of serious illness, such as cancer, anxiety, and depression, within that context, and then depression outside of medical illness, and then a variety of forms of addiction.

Other disorders that either I'm studying or colleagues are studying are obsessive compulsive disorder, anorexia, different forms of addiction, including cocaine addiction, alcohol addiction. I'm about to start work on using psilocybin to treat PTSD. And based on that rat research of neuroplasticity, of athletes that have sustained injury through repetitive head impact that are claiming that using psychedelics have restored cognitive ability, as well as doing things like helping them with depression and addiction. So I'm interested in pursuing that work. So there's just a whole lot that's out there.

So some of those areas are being researched, and we don't have results yet, and so we can't get ahead of the data. I think there's a good rationale to study all of these things. Some of them might work out, hopefully, and some of them, we might run up against a boundary. It might be good for this, this, and that, but not this and that.

我的看法是，这需要额外的谨慎。这不是你开始的地方。首先，看看在成年人身上效果如何，对于发育中的大脑确实有额外的担忧，但对于未经治疗的精神疾病也有担忧，对吧？包括自杀、过量服用等等。所以，不探索这也是有风险的，但要非常非常谨慎。

从最大的角度来看，除了迷幻药治疗某种疾病的能力之外，我认为它们有望真正帮助我们理解精神疾病的本质。我们看到同一种干预措施对抑郁和焦虑有帮助，无论是在癌症背景下还是在癌症之外，对不止一种形式的成瘾，而是多种形式的成瘾都有帮助，这真是闻所未闻，它应该向我们大声疾呼，去寻找这些所谓的“跨诊断过程”。

比如，这些不同疾病的潜在共同点是什么？它们之间有什么共同之处，以至于迷幻药治疗能够解决它们？我开始认为——也许是因为理解成瘾是我的基础——我把所有这些疾病都看作是不同形式的成瘾。

无论是对一种物质，如烟草、酒精、可卡因，还是对一种思考自己的方式，如抑郁症中的自我迫害思想，我们都有，但在抑郁症患者中过度表达，一旦你陷入其中，它就变成了自我实现的预言。一旦你花很多时间称自己为失败者，然后这会影响到其他人，你就会螺旋式下降——这就是一种成瘾。

这是一种狭隘的精神和行为模式。你被限制了。现实曾经是这样的，现在你的现实是这样的。无论那是导向一种物质，还是一种特定的、次优的思考自己的方式。而迷幻药，如果在正确的环境中做得好，有能力将人们从那种狭隘的故事中彻底解放出来。

所以我认为，从宏观上看，它在帮助我们弄清精神疾病的本质，以及如何预防这些疾病方面，拥有巨大的潜力。我们如何走向一个不仅主要关注治疗疾病的社会？而是，对于心理健康的人来说，是什么创造了健康？我们如何在精神卫生保健中进行预防性护理？

这真的触动了我，因为我做了很多用迷幻药治疗疾病的研究，也做了很多其他研究，我们只是治疗所谓的“健康正常人”，好像他们没有任何问题。但你猜怎么着？你给一个在准备好的环境中、处于准备好状态的人类一剂大剂量的迷幻药，天哪，那些东西，那些问题，无论你是否可被诊断，过去的创伤，各种类型的成瘾，它们都会浮出水面。

所以我认为，从宏观上看，迷幻药可以帮助我们走向一个开始理解人类保持精神健康需要什么的世界。我们可以在预防精神上做些什么？也许迷幻药会在其中扮演一些角色，但也许它们也会指向其他技术，让我们能够保持健康。

一些参与者在体验后会说，一次六小时的裸盖菇素体验就像1000小时的治疗。迷幻药起作用时，似乎是因为它们更接近心理问题的根源，而不是在表面层面治疗它们，而大多数精神科药物治疗精神健康障碍的方式，更多是在表面层面。

但这就是为什么到目前为止，似乎只需要在正确的环境中接触一、二、三次迷幻药，就可能足以真正治疗这些疾病。在某些情况下，它看起来更像是一种治愈，不总是这样，但我不会轻易使用这个词。但有时它看起来像是一种治愈，因为它真的看起来像是人们解决了深层的、潜在的心理问题，而这些问题以各种症状表现出来，无论是什么疾病。

我不知道有任何证据表明大型制药公司一直在阻挠或害怕迷幻药研究。它们传统上当然没有投资于此。我认为它们在观望。主要是小型风险投资初创公司在探索迷幻药，并投资于它们通过FDA途径的潜在发展。

但这一直是精神健康药物的趋势。让小公司进行这些投资，如果它们早期取得了有希望的发现，那么大型制药公司就会进来，支付数百万美元收购这些公司，并继续推进。所以我认为它们在伺机而动，但这是一种非常不同的商业模式，你不会通过每天卖药来赚大钱。

如果它有效，你希望一生中只卖给某人一、二、三颗药。所以更多的商业模式，将是基础设施和通过这些体验的专业指导。