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InvisibleveggieM

Registered: 07/25/04
Posts: 17,501
The Search for New Psychedelics
    #28531731 - 11/06/23 01:00 PM (2 months, 20 days ago)

The Search for New Psychedelics
November 6, 2023 - Scientific American

This is Episode One of a three part series on the science of psychedelics.

As companies join the hunt, can the field of mind-altering synthetic substances stay true to its original pioneering spirit of wonder, curiosity and connection?

🔊 Science, Quickly Podcast - Audio (10:49)

Full Transcript:

Rachel Nuwer: When someone says psychedelics, what comes to mind? Maybe “magic mushrooms” or LSD? Or if you’re a real aficionado, maybe you think of more obscure substances such as dimethyltryptamine, also called DMT, or 4-Bromo-2,5-dimethoxyphenethylamine, also called 2C-B.

Unless you’re really deep in the psychedelic weeds, though, what probably doesn’t come to mind are, say, 4-Hydroxy-N-methyl-N-isopropyltryptamine, also called 4-HO-MiPT, or 2,5-dimethoxy-4-(n)-propylthiophenethylamine, also called 2C-T-7. These things are mouthfulls.

The latter two psychedelics are actually among hundreds of obscure, consciousness-altering drugs—ones that maybe just a handful of people have ever tried, let alone studied. Most are synthesized in labs, and new ones are being created all the time. Some are made by underground chemists looking for the next big high, but others are being created by bona fide scientists searching for better therapeutic agents.

For Science, Quickly, I’m science journalist and author Rachel Nuwer. Today I’ll be taking you on a mind-bending journey: the hunt for new psychedelics.

Matthew Baggott: I think the existing psychedelics are going to help a lot of people, but there are some people that will not be helped by them or that will benefit even more from other medicines.

Nuwer: That’s Matt Baggott, a neuroscientist and co-founder and CEO of a start-up called Tactogen. He and his colleagues are trying to make safer and more effective MDMA-like molecules for therapeutic and medical uses. There are at least 50 other labs and companies around the world pursuing similar goals.

Baggott: For me, three big reasons to create new psychedelics would be, one, decreasing unwanted effects ...

Nuwer: For example, bladder irritation that’s sometimes caused by ketamine or transient high blood pressure that can be triggered by MDMA. Matt thinks it could be possible to engineer new versions of these drugs that don’t cause the kinds of unwanted side effects that have nothing to do with the actual therapeutic uses of psychedelics.

The second reason for pursuing new psychedelics, he says, is ...

Baggott: Increasing the accessibility of these types of therapies.

Many of us are concerned that psychedelic therapies may end up being so resource-intensive that the insurance industry and other payers won't consider the therapies to be cost-effective, and they may be reluctant to cover them.

But if it’s not covered by the payer, then treatment will often be in the range of tens of thousands of dollars.

Nuwer: The steep price tag is because most psychedelic-assisted therapy usually requires several sessions of around eight hours each and requires two therapists to be present. So if Matt and other scientists could create molecules that are shorter-acting but still just as effective, then the costs could be reduced, and the treatments could become available to way more people.

Baggott: And then the third ... reason for developing new psychedelics is a little more speculative. I think that psychedelic-derived medicines could create whole new categories of therapy. We don't really have an established idea in our health care system of pharmacotherapies that accelerate psychotherapy. But that’s exactly how a lot of people are thinking about psychedelics. And so that’s just one example; there may be many other examples of ways that psychedelics could provide new, essentially, types of treatments.

There’s a really large possibility space here that we're only now starting to explore, and there’s a lot of promise.

Nuwer: It’s important to acknowledge, though, that Matt’s search for new psychedelics isn’t new. In a way, he and all the other researchers pursuing this path today are just following in the footsteps of those who came before. One of the greatest psychedelic pioneers of all time was the late chemist Alexander Shulgin, known as Sasha to his friends. 

Erika Dyck: Maybe there’s no one else quite like Sasha Shulgin.

Nuwer: Sasha was best known for resynthesizing MDMA, aka Ecstasy, and kicking off widespread interest in it among therapists in the late 1970s.

But he also famously created hundreds of new psychedelic drugs in a ramshackle backyard lab at his home in Lafayette, California. Sasha would actually try out his creations on himself, starting with tiny doses and working his way up. If the compound seemed interesting enough, he’d invite his late wife, Ann, and their closest friends to try it with him, and they’d all take notes.

Dyck: Without those moments, much of this psychedelic history would look quite different.

There are people working for pharmaceutical companies now who came into this, I think, with a real, genuine desire to to embody the Sasha Shulgin spirit.

He’s so visible and becomes ... a kind of iconic figure in this space who’s not only associated with the brilliance of his own chemistry and for allegedly introducing over 200 psychoactive compounds.

He’s open with the DEA.... And he creates things faster than the DEA can figure out what to do with it.

Nuwer: That’s Erika Dyck, a professor of health and social justice at the University of Saskatchewan who researches psychedelic history.

Erika says that one of the things that set Sasha apart from other psychedelic chemists of his day was the fact that he was so open about his work creating new mind-altering substances—despite this being at the height of the war on drugs. In the 1990s he and Ann even wrote two books about their experiences that contained detailed instructions in the back for making all of Sasha’s different psychedelics.

Dyck: He writes about it and sort of shares his enthusiasm for the chemistry in a way that scales things differently than a patent and scaling it in terms of its marketability, and that’s a different philosophy. It’s a different way of living in this space.

Nuwer: That’s because, unlike most other chemists, Sasha wasn’t driven by profit. He seems to have been motivated by sheer enthusiasm for drugs and their potential promise for unlocking hidden realms of consciousness and secrets of the brain.

Dyck: A lot of people describe his enthusiasm—this just giggling, infectious enthusiasm for the process of discovery that really just kind of brought him to light.

Nuwer: Sasha and Ann were friends with all kinds of luminaries of their day, including famous astronomer Carl Sagan, chemist Albert Hofmann, who discovered LSD, and author, musician and therapist Laura Huxley, the wife of writer Aldous Huxley.

Dyck: They hosted dinner parties and gatherings at their place in Lafayette and really, I think, nourished a community of psychedelic enthusiasm at a time when prohibition overwhelmed this space.

Nuwer: Sasha had fancy friends, but he wasn’t snobby. He was also happy to hobnob with students, hippies—anyone who was interested in drugs. His prolific publishing and welcoming nature inspired some people, including Matt, to get into psychedelics.

Baggott: When I started becoming interested in these molecules, it seemed like there was almost no research happening on them, and that was a big question of mine: Why is so little being done to look at these molecules that seem so promising? So a lot of what I was doing was reading what, at the time, seemed like ancient papers in the ... stacks of the University of Chicago science library.

I started to see Sasha Shulgin’s name a fair amount, as well as Dave Nichols at Purdue.

Nuwer: Matt is referring to medicinal chemist David Nichols, who published a lot with Sasha and tried to create new MDMA-like molecules himself in the 1990s.

Baggott: I wrote to both Dave Nichols and Sasha Shulgin.... They both responded to me...and I was able to get a role at the University of California, San Francisco, in a lab that Sasha was affiliated with.... And so I got to know Sasha during that time period pretty well.

Nuwer: That was the 1980s. The research methods for finding new psychedelics have come a long way since then.

Baggott: The tools at the time that were available were primitive, compared to what we have today.

Nuwer: Matt and others now usually use computer simulations to explore virtual molecules that they might be interested in making.

Baggott: These collections, these chemical libraries, can include billions of molecules. To evaluate these possible molecules, what we do is: we put digital representations of them into machine-learning models to predict if the molecules might interact with receptors of interest or other biological sites that we think are important.

So then we go on to make the most promising of these hypothetical molecules... and then we screen them to see if they really do interact with the receptors and other sites of interest that we thought they might.

Once we find a molecule that seems to work—what we call a hit—we then can make variations of it to see if we can tune the effects, make it more selective or more advantageous in some way.

That kind of process is fairly high-tech, uses a lot of computational power and often relies on contract research organizations with specialized assays.

Very, very different from Sasha working in his, like, tiny, little, almost barn-like laboratory, you know, on his own.

Nuwer: Whatever discoveries come out of today’s carefully controlled laboratory settings, a lot of experts say it’s still important to remember the more personal, adventurous, DIY Sasha Shulgin–type approach that got us to where we are today—and even to try to keep that spirit alive.

Dyck: There’s a lot of ... profiteering out there, and ... it’s hard not to see the desires to turn psychedelics into another pharmaceutical commodity, and I worry that this will take the magic out of the mushrooms.

Legalizing the psychedelics, I hope, doesn't necessarily take away that joie de vivre that exists in that space that has different rules of engagement.

Nuwer: This is part one of a three-part series on the science of psychedelics.

For Science, Quickly, I’m Rachel Nuwer. On our next episode, we’ll be talking about the heated debate in the field about whether the tripping part of the psychedelic trip is actually necessary for therapeutic use.

Science, Quickly is produced by Tulika Bose, Jeff DelViscio, Kelso Harper, and Carin Leong and edited by Elah Feder and Alexa Lim.


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InvisibleveggieM

Registered: 07/25/04
Posts: 17,501
Re: The Search for New Psychedelics [Re: veggie]
    #28534257 - 11/08/23 01:02 PM (2 months, 18 days ago)

Do You Need to 'Trip' for Psychedelics to Work as Medicine?
November 8, 2023 - Scientific American

This is Episode Two of a three part series on the science of psychedelics.

Psychedelic researchers are engaged in heated debate over whether the mind-altering effects of the drugs are necessary for realizing their therapeutic potential.

🔊 Science, Quckly Podcast - Audio (14:09)

Full Transcript:

Rachel Nuwer: Imagine that you’re going about your day, and suddenly someone stabs a hot knife into your temple. It plunges into your brain, where it reaches a spot just behind your eye. If you feel like this is happening, you’re probably having a cluster headache. Only about one in 1,000 people experience such headaches, but for those that do, they’re excruciating.

Now imagine that you took a psychedelic drug, and all of a sudden your brain-splitting headaches went away. You’d definitely want to investigate that, right?

For Science, Quickly, I’m science journalist and author Rachel Nuwer. You’re listening to  “To Trip or Not to Trip,” part two of a three-part series on the science of psychedelics.

Torsten Passie: In 2009 we were approaching the research administration at Harvard University in Boston, where I was a visiting professor, to conduct a study on patients ... suffering from cluster headaches—because they have found, by themselves, that they could treat their condition quite well with LSD or psilocybin.

Nuwer: That’s Torsten Passie, a professor of psychiatry and psychotherapy at Hannover Medical School in Germany. He’s been researching psychedelic drugs for about 40 years.

Passie: We were sitting there in this big room with two fireplaces in front of a desk, which was very large, and on the other side were three research administrators.

So we were sitting there and, you know, we were talking with them about conducting a study about LSD. But what happened is that there was a certain pause in the conversation. And then the chief of the research administration said, in a very low voice, “You know, you know what, we had Leary here.”

Nuwer: They were referring to psychologist Timothy Leary, the notorious one-time Harvard lecturer turned psychedelic evangelist. Leary was dismissed from his position in the early 1960s for controversial experiments with psychedelics - including giving them to undergraduates - so the Harvard administrators weren’t exactly excited about the prospect of another research group dosing people on campus with LSD. In fact, they wanted Torsten and his colleagues to steer away from using anything psychedelic at all.

But Torsten was sure the psychedelic part of LSD was critical for treating cluster headaches, so he proposed a study that he thought would show the Harvard administrators he was right.

Passie: Our idea was: okay, let’s prove that we can’t induce the preventative effect against cluster headaches with a substance which is not hallucinogenic.

Nuwer: The substance they chose was 2-Bromo-LSD, a molecule that Albert Hofmann, creator of LSD, developed in the 1950s as an inactive LSD placebo.

Passie: It shouldn't be called a psychedelic because it has zero psychological effects.... You might feel a very tiny bit of an alteration, but that’s it.

Nuwer: And yet, to Torsten and his colleagues’ great surprise, 2-Bromo-LSD did seem to work on cluster headaches.

Passie: After we have treated two or three patients, it was obvious that it was even working better than LSD on the cluster headaches.

Nuwer: That’s actually a really good thing. No one wants to go on a 12-hour LSD journey every time they feel a headache coming on. That’s why millions of dollars have been invested since Torsten and his colleagues’ discovery into developing 2-Bromo-LSD as a medication.

Passie: We have no idea, really, why it works on cluster headaches in a preventative fashion, which means you take the drug three times in 10 days, and afterward, you might not feel any headache for years.

Nuwer: The substance 2-Bromo-LSD isn’t the only psychedelic that scientists have chemically edited to get rid of the trip or that’s been shown to still have some medical benefits afterward.

Some labs have shifted their entire focus to investigating whether psychedelic drugs sans trip and sans accompanying therapy could be used for all sorts of applications, including things that typically can’t just be cured by popping a pill such as post-traumatic stress disorder, or PTSD, and addiction.

But is the trip necessary for healing, or is it just a distraction? This is a heated question that’s currently dividing the field.

Torsten, for his part, thinks it’s a waste of time to try to use tripless psychedelics to try to treat any kind of neuropsychiatric condition.

Passie: People think, “Okay, let’s use other drugs which are very similar to LSD and, without hallucinogenic effects, might lead to the same behavioral changes.” There’s zero evidence for that. The only evidence is the hype. And the ... eagerness of a lot of companies to find new compounds and patent them and all that. Otherwise there’s zero evidence.

Nuwer: But others are betting big on psychedelics without the trip. There’s even a new word that’s been coined for them: psychoplastogens.

David Olson: I know of at least five academic labs who have published on these nonhallucinogenic psychoplastogens and probably over 20 companies that are developing these ... types of molecules.

Nuwer: That’s David Olson, a chemist who directs the Institute for Psychedelics and Neurotherapeutics at the University of California, Davis. He’s also co-founder of Delix Therapeutics, a biotech company that’s developing nonhallucinogenic psychedelics.

According to David, the pursuit of psychoplastogens is born out of sheer need.

Olson: Let’s talk about the scale of the problem. About one in five people will suffer from a neuropsychiatric disease at some point in their lifetime. We’re talking about a billion people worldwide. That is a huge problem. And if we ever hope to address a problem of that magnitude fully, we’re going to need medicines that are very scalable. And right now psychedelic-assisted psychotherapy is not a very scalable option because of the cost and the complexity of the treatment.

If we don’t try to decouple the beneficial effects from the hallucinogenic effects, a very small number of patients will benefit from psychedelic-assisted psychotherapy.

Nuwer: In case you don’t know, psychedelic-assisted therapy is a very involved process. It involves giving someone a psychedelic drug such as MDMA or psilocybin and then having them undergo hours of guided therapy with one or two specially trained therapists.

There are also prep sessions with the therapists beforehand and integration sessions after to help people make sense of the experience and apply the lessons or revelations they gained to their sober life.

In a way, these sessions are learning exercises: people are learning to think and react in new ways.

The question, though, is whether the active learning part of psychedelic therapy can be bypassed partially or completely but still produce positive results. David is betting that it can — based on one of the things he says psychedelics do in the brain.

Olson: They promote structural plasticity in the part of the brain called the prefrontal cortex. Now, the prefrontal cortex is really critical for diseases like depression, post-traumatic stress disorder and substance use disorder, because it’s a brain region that talks to a whole bunch of other brain regions that regulate fear, motivation and reward.

In many of these stress-related neuropsychiatric diseases, there’s physical changes in the structure of the brain, including the atrophy of neurons in the prefrontal cortex. And if you can regrow these atrophied neurons, you can reestablish synaptic connectivity and allow the PFC to talk to the other brain regions that it needs to talk to and then ameliorate disease symptoms.

Now, something that’s very unique about molecules like ketamine and psychedelics is that they are very good at promoting the growth of these neurons rapidly—within 24 hours ...

And also that their effects last long after the drugs have been cleared from the body.

Nuwer: David and his colleagues are trying to make medicines that will retain that positive effect on neural growth, preferably in the absence of a guided therapeutic trip.

Olson: That is the goal: to have medicines that are safe enough that you can put them in your medicine cabinet.

Nuwer: Not everyone agrees with this goal. GĂŒl Dölen, a neuroscientist at Johns Hopkins University, says she hates the term psychoplastogen because of what she says it wrongly implies about how psychedelics work.

GĂŒl Dölen: It suggests that what psychedelics are doing is just inducing plasticity and ...that’s their therapeutic action. And the fact is, is that there are drugs like that—psychoactive plastogens—and all of the ones that we know that do that are addictive drugs like cocaine, heroin, amphetamine, alcohol, nicotine. These are all robust inducers of plasticity.

Nuwer: GĂŒl and some other scientists think that the trip and the targeted therapy that it’s paired with are what differentiate the effects of psychedelic drugs from more addictive ones that induce plasticity all over the brain. That’s because the combination of trip and drug promotes learning, and it’s this learning, they think, that’s key to achieving the long-lasting results seen in some clinical trials with psychedelics.

Dölen: Learning is such a huge component of what makes us who we are: our personalities, our abilities..., even the way we walk is a learned phenomenon. And so I think that any account of neuropsychiatric disease has to take that into consideration.

Nuwer: In June, GĂŒl had a major study come out in Nature that drew a link between critical periods and psychedelics. Critical periods are finite windows of time, usually in childhood, when the brain is more malleable and open to learning. They exist so we can learn all the things we’ll need to know to successfully navigate our environment in adulthood.

Dölen: [6:38] What our study suggests is that what the psychedelics are doing is reopening those windows of time where you can learn like you did when you were a child. And so the idea that you could engineer that response to just a single pill like a Tylenol for pain seems very, very unlikely.

Nuwer: GĂŒl and her colleagues came to this conclusion after giving adult mice a psychedelic drug and then exposing them to certain activities. Afterward the rodents’ brain returned to an open state of learning as though they were a juvenile mouse.

On the other hand, when the mice were given cocaine—a psychoactive drug that increases general plasticity but is not a psychedelic—their critical period did not reopen. The mice’s critical period also did not reopen when they weren’t put through the learning exercise, even if they were on a psychedelic.

These findings suggest that it’s not just the psychedelics that are contributing to targeted changes in the brain but also what someone does while on the drugs.

Dölen: What our results really show for the first time is that psychedelics’ activities are context-dependent.... So when we give a psychedelic in a therapeutic context, it has a very different effect than if we give it, say, at a rave.

Dolen: I think that the ... cleanest way of describing it is that if the therapeutic effects have a component that [is]are specific to a context, specific to some learned set of habits, then you probably need the trip.

Nuwer: Learning isn’t needed for everything, though—pain relief for cluster headaches is a great example. But for everything that does require some element of learning, GĂŒl thinks psychoplastogens are not the way to go and could even be dangerous.

Dölen: We could be engineering these ... drugs to lose their therapeutic properties and add in abuse liability that essentially turns these drugs into a new class of highly addictive drug that has little to no therapeutic efficacy. So that would be, I think, a real face-plant for the field, if we ended up doing that.

Nuwer: David gets that not everyone is onboard with psychoplastogens. But he still thinks that there’s value in pursuing them.

Olson: This is not an either-or story. This is really an “and” story. I think that we need to develop all of these types of medicines because, you know, patients are desperate. We haven’t had any real innovations in psychiatry for nearly 30 years. And so we should be developing both hallucinogenic and nonhallucinogenic medicines based on the science of psychedelics.

Nuwer: For some conditions, psychedelic-assisted therapy with the trip might be absolutely necessary. For others, such as cluster headaches, a psychoplastogen might be enough. It’s going to take researchers probably the next few decades to untangle the details of which type of drug works for whom and for what. In the meantime, the debate will no doubt go on.

This was part two of a three part series on the science of psychedelics. On the next and last episode, we’ll talk about the dream experiments that psychedelic researchers are most excited about for the future.

For Science, Quickly, I’m Rachel Nuwer.

Science, Quickly is produced by Tulika Bose, Jeff DelViscio, Kelso Harper, and Carin Leong and edited by Elah Feder and Alexa Lim.


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InvisibleveggieM

Registered: 07/25/04
Posts: 17,501
Re: The Search for New Psychedelics [Re: veggie]
    #28536911 - 11/10/23 10:03 AM (2 months, 16 days ago)

Funding for Research on Psychedelics Is on the Rise, Along with Scientists' Hopes for Using Them
November 10, 2023 - Scientific American

This is Episode Three of a three-part series on the science of psychedelics.

As interest and support for psychedelic research grows, scientists share their hopes for the future.

🔊 Science, Quckly Podcast - Audio (11:34)

Full Transcript:

GĂŒl Dölen: I remember when I first applied to the NIH, my program officer was like, “No, nobody will ever give psychedelics as a therapy. You’re barking up the wrong tree. You should be studying why these things are bad for the brain.”

Nuwer: This was back in 2014, when Johns Hopkins neuroscientist GĂŒl Dölen was trying to get funding to study whether psychedelic drugs might be master keys for reopening critical periods in the brain.

Dölen: I was like, “No, I think this is a great idea, and if we’re right about it, we’re going to win the Nobel Prize. I want to get credit for having this idea right now and will not change my grant to accommodate your view.” And so I was very stubborn, and I didn’t get the grant, and I didn’t get many, many, many other ones after that.

Nuwer: For Science Quickly, I’m science journalist and author Rachel Nuwer. You’re listening to part three of a three-part series on the science of psychedelics.

If GĂŒl was submitting the same grant application today, she’d probably have a much stronger shot at getting it.

Dölen: There’s definitely been a sea change in terms of the attitudes toward funding psychedelics.

Nuwer: As funding opportunities for psychedelic science increase, researchers are beginning to put serious thought into mind-bending studies that previously would have seemed like fantasy.

GĂŒl, for example, is currently seeking funding for a study she’s designed to see if psychedelics could be used to reopen a motor-learning critical period that would allow stroke patients to regain lost function.

Dölen: If it ends up being the case that psychedelics are able to do this, then it offers therapy for roughly 500,000 [or] 400,000 people a year in the United States alone who have a stroke but then don’t recover full function.

Nuwer: I was curious about what other researchers are most excited about in the field, so I reached out to several other leading thinkers to see what kind of psychedelic investigations they’re envisioning for the future.

Albert Garcia-Romeu is a research scientist at the Johns Hopkins University School of Medicine. He works mainly on using psychedelics in a clinical setting. Until now, studies of psychedelic-assisted therapy had mostly focused on post-traumatic stress disorder, depression, addiction and end-of-life anxiety, but there could be all sorts of other applications.

Albert Garcia-Romeu: Now you’re starting to see this multiply out into lots of different clinical areas, including things like anorexia nervosa. I’m doing a study [of] early-stage Alzheimer’s disease.

I have a study under development for people with long COVID. There’s lots of different directions to take the work, which is pretty neat, being a scientist, because it kind of makes you feel like you’re a kid in a candy shop.

Nuwer: Albert is also interested in studying how psychedelics might affect well people—that is, people who don’t have any particular disease but who just want to use the substances for things such as inner exploration, spirituality, personal enhancement, connection or just having fun.

Garcia-Romeu: It’s something that’s been around as long as written history, and so it really makes us think, “How can these substances be used outside of the medical framework?”

Nuwer: Albert imagines a study, for example, in which psychedelics are given to people to see if the drugs could help enhance creativity. Surprisingly, there is a precedent for this. Back in the 1960s, researchers at Stanford University actually gave healthy people LSD and mescaline to test this question.

Garcia-Romeu: They were taking all these kind of educated professionals and having them come in and [saying], “Think about one of the challenging problems that you’re facing in your work now.

Now we’re going to go ahead and give you one of these drugs and see if that can help you to have some further insight or come up with some potential solutions for that.”

It definitely yielded some really interesting and fruitful results where people did come out of that with things like patents and designs for new types of devices and, and buildings. And so ... that’s something that I think is incredibly interesting, especially being at, you know, a place like Hopkins.

You can talk to physicists, astrophysicists, people who are doing all sorts of different work on cancer biology and really see, like, wow, there’s a possibility here that we could take some of these people and put them through a protocol that would help them to think about the problems that they’re working on from a different perspective. And that, in turn, may yield some really, really fascinating and innovative new ways of dealing with problems that we’re now facing.

We’re in an era right now of all of these different types of crises.

And so in the midst of all this, how can we also position psychedelics as allies or as tools that we can use to hopefully better navigate this rapidly changing and pretty chaotic era that we find ourselves in?

Nuwer: Psychedelics might also be used to help us get through difficult times by allowing researchers to dissect and better understand another very important component of the human experience: happiness.

Sonja Lyubomirsky: My name is Sonja Lyubomirsky, and I’m a professor of psychology at the University of California of Riverside. I’ve been studying happiness for almost 35 years.

My lab does what we call happiness intervention.

And we do randomized controlled trials. They’re kind of like clinical trials, but instead of testing a new vaccine, we’re testing, like, a happiness strategy, like gratitude or kindness.

Nuwer: After years of research, Sonja realized that strategies for making people feel happier tend to boil down to one key thing: making them feel more connected to other people.

Lyubomirsky: So I became interested in connection and “How do we foster connection?”

Nuwer: But this created a challenge for Sonja.

Lyubomirsky: It’s really hard to study this in the lab: You know, how—how can you actually foster, like, sort of bottle that feeling of sort of deep connection with someone when you truly feel understood and loved?

Nuwer: In pondering how to go about studying this in the lab, it dawned on Sonja that the psychedelic drug MDMA could provide a perfect solution.

Lyubomirsky: It turns out that MDMA is a substance that can actually kind of provide a little shortcut for scientists.

There are really two ways that I see studying MDMA. One is how you can sort of use it to bottle this sense of connection and feeling understood and empathy, and then that enables you to study the psychological mechanisms and the brain pathways.

But the other way is: You could try to use it to improve people’s lives, right? There’s sort of this epidemic of loneliness we have. People are feeling disconnected.

Can we actually improve people’s lives—and not just people who have mental health conditions but just people who are maybe a little bit lonely or people who want to improve their relationships?

Nuwer: In 2022 Sonja thought MDMA could be such a powerful investigative tool for psychologists and social scientists that she authored a paper proposing a new field called psychedelic social science.

She imagines future research using MDMA and other psychedelics to study everything from the fundamental components of positive relationships to whether it might be possible to shift someone’s extremist views.

Lyubomirsky: I hope that there are young people in the field who want to kind of take the helm and lead it and develop it.

Nuwer: Psychedelics could eventually also help to answer fundamental questions about existence and who or what we really are.

David Presti: Deepening our understanding of the nature of mind and consciousness is among the most exciting frontiers of contemporary science, and there are so many mysteries there. And there’s every reason to believe that whatever the psychedelic materials are tapping into when it comes to their impact on the brain, the nervous system, the body is interacting with the mind and our conscious awareness, and all the aspects of what mind may be, in a way that is radically different from anything else we’ve ever researched.

Nuwer: That’s David Presti, a neurobiologist at the University of California, Berkeley. As psychedelics open up new frontiers of neuroscience, David says it’s important for researchers to try to put aside their preexisting assumptions about what he calls ‘the deep mysteries of the mind.’

Presti: I really think there’s a capacity to contribute to taking our understanding of the relationship between mind and brain and body and physical reality writ large to a deeper level of insight if we are open to that.

Nuwer: David also encourages psychedelic scientists to strike up dialogues with experts in religion or spirituality.

Presti: At the core of many religious traditions, there is a kind of an appreciation for the deep mystery of reality and who we are within that deep mystery of reality. This is an incredibly important system of narratives that play out and have huge impact in human society all over the planet.

To begin to appreciate that within the context of biophysical science would be a really beautiful thing because there has been so much belief that has evolved over the last several hundred years of this disconnection between what we call science and what we call religion, and there’s no reason that has to be the case.

Both science and religion deal with the deep mystery of reality and our place in it. And so I see this as really all one question that can provide a platform for much more engagement between religious narratives and scientific narratives.

Nuwer: David hopes that these kinds of collaborations seeded by psychedelics will also lead to practical results in terms of how humans treat each other, other species and the planet.

Presti: Beginning to see how deeply interconnected and really sentient in some way—very different from ours but a kind of sentience, it’s there—that may allow us a springboard for developing greater respect and greater thoughtfulness for how we interact with these sentient systems.

I can only hope so.

Nuwer: For Science, Quickly, I’m Rachel Nuwer. You’ve just listened to part three of a three-part series on the science of psychedelics.

Science, Quickly is produced by Tulika Bose, Jeff DelViscio, Kelso Harper, and Carin Leong and edited by Elah Feder and Alexa Lim.


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