Short Wave - Could Psychedelics Become Tripless?

Episode Date: April 9, 2025

This week, we've heard from researchers trying to untangle the effects of the "trip" that often comes with psychedelics and ketamine from the ways these drugs might change the human brain. For part three of our series on psychedelic drug research, we get a glimpse into why some researchers are taking the "trip" out of these drugs altogether. You don't need to have heard the previous two episodes to understand this episode on what could be next for psychedelic medicine.Catch the rest of this series on psychedelics and related drugs this week by following us on Spotify and Apple Podcasts. They're the previous two episodes in our podcast feed.Have other questions about psychedelics and the brain? Let us know by emailing [e-mail]! See pcm.adswizz.com for information about our collection and use of personal data for sponsorship and to manage your podcast sponsorship preferences.NPR Privacy Policy

You're listening to Shortwave from NPR. Hey, Shortwavers, Regina Barber here, and we're back with the final episode in our series on the science behind psychedelics and related drugs. I'm here with producer Rachel Carlson, who reported out this whole series. Hey, Rachel. Gina, hi. So first, this episode will make sense for people who haven't heard the previous episodes. That said, in our last episode, we talked about why some researchers are interested in not just the chemical effects of drugs. psychedelics and ketamine, but all these other factors that come with them, like the trip or

therapy or even expectations patients have about the drugs themselves. Yeah. But other researchers say, while all those factors might be important, not everyone can or wants to take psychedelic drugs. Here's one of those researchers, David Olson. He's a chemical neuroscientist at UC Davis, and he told me, pretend that I've got a crystal ball and I can see into the future. And in the future, every insurance company will fully reimburse for psychedelic-assisted psychotherapy.

Even in that future, there are a lot of people who will still be left behind. For example, most practitioners would say that people who have bipolar disorder or schizophrenia shouldn't take psychedelics. That's why David's making drugs that are inspired by psychedelics, but without a trip. Wow. Okay, so tell me more. So David co-founded a company called Delix Therapeutics. They used the structure of drugs like ketamine, LSD, Ibogaine, MDMA.

And then... We just move things around a little bit here and there. Tweak their structures just a little bit to make them better versions of themselves. Okay, move things around, like Legos. Literally, Gina, in my brain, I was picturing scientists playing with these tiny little molecular blocks. And then David told me that's actually not that far off. A lot of times people will describe synthetic organic chemists as molecular architects. And what we do is really not a whole lot different than what an architect does. The only difference is we can't see what we are building.

So is taking the trip out of these drugs new? Like, I feel like I haven't really heard about this before. It's not. Actually, even the guy who first synthesized LSD in the 1930s. Albert Hoffman worked on finding derivatives of the drug that didn't give people hallucinations. Oh, wow. But some scientists say those hallucinations are the whole point. I asked Albert Garcia-Romeo about this. He's a psychologist and psychopharmacologist at Johns Hopkins University. He told me that we really do need more treatment options for conditions like depression,

especially for people who can't take classic psychedelics. But still... I'm very skeptical that you. you're going to reach the same level of effectiveness without those really profound psychological experiences that people report. Albert says these big experiences can play a role in how people feel after taking a drug like a psychedelic. So today on the show, to trip or not to trip. That is the question. We're talking about what could be next for psychedelic medicine.

I'm Rachel Carlson. And I'm Regina Barber. You're listening to Shortwave, the science podcast from NPR. Okay, Rachel, today we're talking about companies, developing new psychedelics, but psychedelics have been used for millennia. So, like, where did this idea come from? Yeah, Gina, first we have to understand what people think drugs like psychedelics and ketamine even do in the brain.

Yeah. So I want you to picture the neurons in the human brain as one big tree. Okay, I'm closing my eyes. I'm doing it. The neurons have something called dendrites. Those are like the branches of the tree. Okay. And then those branches have these tiny nubs called dendritic spines. Okay, like leaves?

Yeah, like leaves. And these leaves, or spines, are the sites where neurons in the brain communicate with each other. In a healthy brain, you can think of these really lush, leafy trees. Imagine squirrels are hopping between branches. This is really calming for me. But in many neuropsychiatric and neurodegenerative conditions, it looks like wintertime. You know, all the leaves have fallen off the trees. The arborist has come in and pruning back all the branches,

and now there's not that physical connectivity between adjacent neurons. Oh, okay. So if you increase the number of leaves, the neurons can, like, communicate with each other better. Yeah. And David says that when researchers eventually started studying the effects of ketamine on depression in animals, they saw that it seemed to help do this. And it worked much faster than the kinds of antidepressants we'd been using since the 1980s. So that's like Prozac, Zoloff, things like that.

Oh, wow. Okay. So this could be like a different kind of. of treatment, maybe for people who don't respond to those medications. Yeah, David told me that he and lots of other researchers started looking for other compounds that could also do something like this, quickly help regrow these mental forests, these sites of connection in the brain. He coined a term for drugs like this.

He called them psychoplastogens. Okay. And that includes psychedelics like LSD and psilocybin. AKA magic mushrooms. Yeah. And just to be clear, Gina, a lot of this research is happening in animals. So scientists think that something similar is. happening in humans, but they don't know enough yet about how these drugs work to say for sure.

Okay. Still, David says that it got researchers thinking, what if people didn't have to take a drug every single day? Moving us, you know, more towards a healing-based approach, where if you take a drug once or a few times, that could lead to long-lasting therapeutic benefit. So now you're not thinking about taking a drug every single day for the drug. rest of your life. You can take the drug, have this healing effect, and then not have to take it continually. There is a version of ketamine that the FDA approved in 2019 to treat depression that

didn't respond to our current treatments like SSRIs. It's a nose spray called spravato. But even that requires patients to go to a clinic. They have to stay there for at least a couple of hours while they get the treatment. And they need someone else to drive them home because ketamine can make people dissociate. Oh. So researchers like David are trying to figure out, are there drugs that have similar effects on the brain without all the trippy side effects? Right.

And we've already talked about how a lot of people can't take psychedelics. So that's part of the motivation here too, right? Yeah, exactly. Plus, right now, psychedelics are mostly extremely restrictive, controlled drugs. We need to have something that is so safe that you can simply pick it up at your local pharmacy, bring it home and put it in your medicine cabinet. Wow. Okay, I'm getting why they want this option. But how do companies like Davis try to actually do this? Yeah, I mean, testing whether something could potentially make a person hallucinate is really tricky, as I'm sure you can imagine.

Researchers know certain receptors in our brains are involved in the hallucinogenic effect of psychedelics and ketamine. So companies like Delix are basically trying to make drugs that are like distant cousins of magic mushrooms or ketamine. They help those treatments. in our brain grow new leaves, but they don't make people hallucinate. Okay, so do we know if these non-hallucinogenic drugs work? It's definitely still up for debate, but Delix has a drug called DLX-1. It's in clinical trials now. I talked to the company's head of research and development, Eliseo Salinas.

He told me that the company did a clinical trial to test whether DLX-1 made people hallucinate, and it seemed like it didn't. And now they're testing the drug on patients who have depression. We're seeing rapid effects during the first week of treatment and very robust effects with big changes in depression. And again, there's a lot more to learn. And you said other companies are doing things like this also, right? They are. Companies want to develop drugs.

They can patent so they can get funding for more research. So there are a bunch of groups in this space. Some are just making more traditional psychedelics. Some are trying to make shorter acting psychedelics or engineer out potentially negative side effects. like some psychedelics bind to certain heart receptors, so they might want to take that side effect out. And all this kind of exploded around 2019, 2020, with lots of these companies popping up and eventually trying to file these patents for their respective drugs. I can see how that works for companies like Delics since they're making new drugs, but like how does this work with companies making drugs that look more like your classic psychedelics? Yeah, it can get a little complicated since traditional psychedelics have been around for a really long time.

and a lot of them come from nature. So I talked to a patent lawyer about this. He focuses on psychedelics. His name's Graham Pachennick. With psychedelics, a lot of the work that was going on was going on in the underground. So there may be ways of using a psychedelic that people have been doing, but they weren't in the certainly peer-reviewed literature. So Graham told me patent examiners may not always have access to all of the past research out there.

And there are people who've argued some companies have gone too far by trying to patent. things that they say shouldn't really be patented, like the way the room is set up while patients are getting treatment. Well, like even the way the room is set up. That's fascinating. But like you said, there are also like some benefits with a patent. Like you can help companies get funding to research new drugs and like bring them to the public. Yeah, exactly. And so it's too early to say, but it's possible we could start to see more companies like Delix in the future if investors are more inclined to put money into drugs that kind of work like psychedelics, but don't involve actual psychedelics.

Okay, but Rachel, this week we also have been talking about whether the trip could actually be, like, helping patients, like the whole journey that comes with taking a drug like psilocybin. Yeah. Some people definitely feel strongly that the whole experience that comes with these drugs is key when it comes to treating patients. Even David and Eliseo both told me they're not saying that we should replace psychedelics altogether with these non-halucinogenic compounds. Okay. But they are saying that we should develop both things. Here's Eliseo. We don't deny that for someone having an introspective session, looking at past events

on their lives could be extremely relevant. But the common trend between those plastogen seems to be this biological effect on synapsis. And by that, he means the effect they have on our brains. Right. But again, not everyone feels like this is really the best way to approach the research. Remember Boris Haifitz? He's the anesthesiologist and neuroscientist at Stanford who did the ketamine study. We talked about it in our last episode. Yep. He and David are collaborators. And he told me that these new drugs like the ones David's making could be great. But even then, if they do work, he still thinks these experiences people seem to have around psychedelics are really important. And for most patients, this whole idea of taking out the trip. I don't think that's going to work. I think that that's ignoring all of the rest of the components,

the experiential component at the center of it, as well as the preparation that goes into it and what you make of the experience, the actual integration. And a lot of that is really dictated by human relationships, social support, and the context of drug use. And these are devilishly difficult things to define in a precise way. And, Gina, the thing that really sticks with me here as I've listened to scientists, like have this conversation in their own research and with each other, is that we're learning so much about the human brain right now. But there's also a ton that we don't know. So I think this research in psychedelics is encouraging neuroscientists

to confront how we study the brain at all, how we study our unique experiences, and where these two things, our chemical biological processes and our personal emotional ones intersect. Rachel, thank you so much for joining me this week, to talk about all of this. Like, you've really made me think I've learned a lot. Anytime, Gina.

Thank you so much for having me. And for listeners who didn't hear the first two episodes, we definitely recommend checking them out. There's a lot of nuance. They're just the previous two episodes in the shortwave feed. This episode was produced by Hannah Chin, and it was edited by Rebecca Ramirez and Jeff Brumfield. Tyler Jones checked the facts.

Maggie Luther was the audio engineer. Bet Donovan is our senior director, and Colin Campbell is our senior vice president of podcasting Stret. I'm Regina Barber. Thank you for listening to Shorewave from NPR.