Could Psychedelics Become Tripless?

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 https://n.pr/3HOQKeK and Apple Podcasts https://n.pr/3WA9vqh. They're the previous two episodes in our podcast feed. Have other questions about psychedelics and the brain? Let us know by emailing [email protected] mailto:[email protected]! See pcm.adswizz.com https://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 https://www.npr.org/about-npr/179878450/privacy-policy

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• 0:00Speaker 00

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• 0:22Regina Barber?

  Hey, Short Wavers. 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.

• 0:34Speaker 02

  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 like 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.

• 0:56Regina Barber?

  Yeah.

• 0:57Speaker 02

  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-

• 1:12Speaker 03

  I 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.

• 1:30Speaker 02

  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.

• 1:43Regina Barber?

  Wow. Okay, so tell me more.

• 1:45Speaker 02

  So David co-founded a company called Delics Therapeutics. They use the structure of drugs like ketamine, LSD, ibogaine, MDMA, and then-

• 1:55Speaker 03

  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.

• 2:04Regina Barber?

  OK, move things around, like Legos.

• 2:07Speaker 02

  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.

• 2:16Speaker 03

  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.

• 2:33Regina Barber?

  So is taking the trip out of these drugs new? Like, I feel like I haven't really heard about this before.

• 2:37Speaker 02

  It's not, actually. Even the guy who first synthesized LSD in the 1930s, Albert Hofmann, worked on finding derivatives of the drug that didn't give people hallucinations.

• 2:47Regina Barber?

  Oh, wow.

• 2:48Speaker 02

  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.

• 3:09Speaker 04

  I'm very skeptical that you're going to reach the same level of effectiveness without those really profound psychological experiences that people report.

• 3:18Speaker 02

  Albert says these big experiences can play a role in how people feel after taking a drug like a psychedelic.

• 3:26Regina Barber?

  So today on the show, to trip or not to trip?

• 3:29Speaker 02

  That is the question. We're talking about what could be next for psychedelic medicine. I'm Rachel Carlson.

• 3:36Regina Barber?

  And I'm Regina Barber. You're listening to Short Wave, the science podcast from NPR.

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• 5:07Regina Barber?

  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?

• 5:16Speaker 02

  Yeah, Gina, first, we have to understand what people think drugs like psychedelics and ketamine even do in the brain.

• 5:22Regina Barber?

  Yeah.

• 5:23Speaker 02

  So, I want you to picture the neurons in the human brain as one big tree.

• 5:28Regina Barber?

  Okay, I'm closing my eyes, I'm doing it.

• 5:29Speaker 02

  The neurons have something called dendrites. Those are like the branches of the tree.

• 5:33Regina Barber?

  Okay.

• 5:34Speaker 02

  And then those branches have these tiny nubs called dendritic spines.

• 5:38Regina Barber?

  Okay, like leaves?

• 5:40Speaker 02

  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.

• 5:54Regina Barber?

  This is really calming for me.

• 5:55Speaker 03

  But in many neuropsychiatric and neurodegenerative conditions, it looks like wintertime. You know, all of the leaves have fallen off the trees, the arborist has come in and proven back all the branches, and now there's not that physical connectivity between adjacent neurons.

• 6:13Regina Barber?

  Oh, okay. So if you increase the number of leaves, the neurons can like communicate with each other better.

• 6:17Speaker 02

  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, Zoloft, things like that.

• 6:33Regina Barber?

  Oh, okay. So this could be like a different kind of treatment, maybe for people who don't respond to those medications.

• 6:39Speaker 02

  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.

• 6:55Regina Barber?

  Okay.

• 6:55Speaker 02

  And that includes psychedelics like LSD and psilocybin.

• 6:58Regina Barber?

  AKA magic mushrooms.

• 7:00Speaker 02

  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.

• 7:11Regina Barber?

  Okay.

• 7:12Speaker 02

  Still, David says that it got researchers thinking, what if people didn't have to take a drug every single day?

• 7:18Speaker 03

  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 rest of your life. You can take the drug, have this healing effect, and then not have to take it continually.

• 7:45Speaker 02

  There's 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.

• 8:06Regina Barber?

  Oh.

• 8:06Speaker 02

  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?

• 8:15Regina Barber?

  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?

• 8:20Speaker 02

  Yeah, exactly. Plus, right now psychedelics are mostly extremely restrictive controlled drugs.

• 8:26Speaker 03

  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.

• 8:36Regina Barber?

  Wow, okay. I'm getting why they want this option. But how do companies like Davis try to actually do this?

• 8:42Speaker 02

  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 Delux are basically trying to make drugs that are like distant cousins of magic mushrooms or ketamine. They help those trees in our brain grow new leaves, but they don't make people hallucinate.

• 9:08Regina Barber?

  Okay, so do we know if these like non-hallucinogenic drugs work?

• 9:12Speaker 02

  It's definitely still up for debate, but Delux has a drug called DLX1. 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 DLX1 made people hallucinate, and it seemed like it didn't. And now they're testing the drug on patients who have depression.

• 9:32Speaker 06

  We're seeing rapid effects during the first week of treatment, and very robust effects with big changes in depression.

• 9:40Speaker 02

  And again, there's a lot more to learn.

• 9:41Regina Barber?

  And you said other companies are doing things like this also, right?

• 9:44Speaker 02

  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.

• 10:15Regina Barber?

  I can see how that works for like companies like Delics, since they're making new drugs. But like, how does this work with companies making drugs that look more like your like classic psychedelics?

• 10:23Speaker 02

  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 Pacinic.

• 10:35Speaker 07

  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.

• 10:49Speaker 02

  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.

• 11:05Regina Barber?

  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.

• 11:17Speaker 02

  Yeah, exactly. And so it's still too early to say, but it's possible we could start to see more companies like Delics 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.

• 11:31Regina Barber?

  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.

• 11:40Speaker 02

  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 Ellie Seo both told me they're not saying that we should replace psychedelics altogether with these non-hallucinogenic compounds.

• 11:55Regina Barber?

  Okay.

• 11:56Speaker 02

  But they are saying that we should develop both things.

• 11:59Regina Barber?

  Mm hmm.

• 11:59Speaker 02

  Here's Eliseo.

• 12:00Speaker 06

  We don't deny that for someone having an introspective session, you know, looking at past events on their lives could be extremely relevant. But the common trend between those blastogens seems to be this biological effect on synapses.

• 12:20Regina Barber?

  And by that, he means the effect they have on our brains.

• 12:23Speaker 02

  Right. But again, not everyone feels like this is really the best way to approach the research.

• 12:28Regina Barber?

  Hmm.

• 12:28Speaker 02

  Remember Boris Heifetz? He's the anesthesiologist and neuroscientist at Stanford who did the ketamine study. We talked about it in our last episode.

• 12:36Regina Barber?

  Yep.

• 12:37Speaker 02

  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.

• 12:50Regina Barber?

  Huh.

• 12:50Speaker 02

  And for most patients, this whole idea of taking out the trip.

• 12:54Speaker 03

  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.

• 13:20Speaker 02

  And Gina, the thing that really sticks with me here as I've listened to scientists 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.

• 13:51Regina Barber?

  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.

• 13:58Speaker 02

  Anytime, Gina. Thank you so much for having me.

• 14:02Regina Barber?

  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 Short Wave feed. This episode was produced by Hannah Chin, and it was edited by Rebecca Ramirez and Jeff Brumfield. Tyler Jones checked the facts. Maggie Luthar was the audio engineer. Beth Donovan is our senior director, and Colin Campbell is our senior vice president of podcasting strategy. I'm Regina Barber. Thank you for listening to Short Wave from NPR.

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