Why The Trip Complicates Psychedelic Research

Researchers are studying psychedelics as a possible treatment for conditions like depression, PTSD and substance use disorders. But they don't know exactly how these drugs work. Getting the answer to this question is especially difficult when people often take psychedelics like LSD and psilocybin for the "trip." This week on Short Wave, we're talking to researchers about how they're trying to untangle the effects of this "trip" from the ways psychedelics might change the human brain ... and why the answer could help direct the future of psychedelic research. 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. 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

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Speaker 00

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• 0:21Regina Barber?

  Hey, Short Wavers. Chances are you've heard about psychedelics once or twice. And Short Wave producer Rachel Carlson has been diving into the science behind them. She's joining me this week to talk all about them. Hey, Rachel.

• 0:33Speaker 02

  Hey, Gina. So psychedelics are being studied to treat lots of different kinds of conditions.

• 0:38Speaker 03

  Chronic Lyme disease, Alzheimer's disease, anorexia nervosa, chronic back pain, obsessive compulsive disorder, post-traumatic stress disorder.

• 0:48Speaker 02

  That's Albert Garcia Romeo. He's a psychologist and psychopharmacologist at Johns Hopkins University. Albert ran a study using a psychedelic called psilocybin. It's the active ingredient in magic mushrooms. And he wanted to see if it could help people who'd previously had Lyme disease.

• 1:04Regina Barber?

  Oh.

• 1:04Speaker 02

  Because you may not realize it, but Lyme disease often comes with lots of psychological symptoms in addition to all the physical ones. Lori Unruh Snyder is one of Albert's patients in that study. She's an agriculture professor. She got a tick bite. She got Lyme disease. But it took doctors four years to get to that diagnosis.

• 1:23Regina Barber?

  Wow, that's a long time.

• 1:25Speaker 02

  Yeah. And even after she took a course of antibiotics for treatment, she told me she still didn't feel like herself at all.

• 1:32Speaker 04

  I remember distinctly, I was teaching a class. I literally got up in front of the students and I, my mind just like almost blanked, stopped. I thought I was having early symptoms of like Alzheimer's or dementia and was like, something's really wrong with me.

• 1:49Regina Barber?

  So she tried psilocybin in this study. Does she feel better?

• 1:54Speaker 02

  She does. She told me she felt like she was expressing herself differently. She changed the way she taught her classes, even ones she'd been teaching for years.

• 2:02Speaker 04

  Usually as professors, after, you know, 15, 20 years teaching, you roll out the same PowerPoint as the last time. But I couldn't do that. I literally stopped myself and I said, I'm seeing things differently.

• 2:14Speaker 02

  But here's the thing, Gina. Researchers like Albert, they don't know exactly why Lori sees things differently. Is it because the drug altered her brain chemistry? Or was it the journey she took while she was on psilocybin?

• 2:27Speaker 04

  I called myself like the new Lori. Like, there's the Lori before psilocybin and Lori after. But it's like, I went through this journey of hearing those that I love that had passed, you know, saying to me, it's okay, you'll be fine.

• 2:43Regina Barber?

  Okay, so Lori has this really powerful emotional experience, and maybe that's what helped?

• 2:48Speaker 02

  Yeah, you know, people often take psychedelics looking for some kind of experience that could transform their lives or change their outlook on everything. So if you're a scientist, how do you tell if the effect of a psychedelic is because of a change in brain chemistry or because of this spiritual journey? I spoke to Boris Heifetz. He's an anesthesiologist and neuroscientist who works at Stanford. And he said, it kind of boils down to one question.

• 3:15Speaker 05

  How do you control for a transformative experience?

• 3:19Speaker 02

  And once I heard him say it that way, I couldn't get it out of my head.

• 3:23Speaker 05

  How do you control for a transformative experience?

• 3:27Speaker 02

  So I went on my own journey, not like my stuffed animals are talking to me and I can't look directly into a mirror kind of journey.

• 3:34Regina Barber?

  Not like that.

• 3:35Speaker 02

  But a reporting journey with lots of scientists who had lots of opinions.

• 3:41Regina Barber?

  So today on the show, psychedelics. How do we entangle the ways they change our experience of the world with how they might change our brains?

• 3:49Speaker 02

  Is it possible for researchers to separate those things when weighing their potential benefits? And does the difference matter?

• 3:56Regina Barber?

  We're breaking down the history of psychedelics and some of the roadblocks researchers are facing when it comes to how to study them now.

• 4:04Speaker 02

  I'm Rachel Carlson.

• 4:05Regina Barber?

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

• 4:15Speaker 00

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• 5:38Regina Barber?

  OK, Rachel, I have a question. Haven't people been talking about and like studying psychedelics for a long time? Like, why is all this research happening now?

• 5:46Speaker 02

  All right, quick history lesson.

• 5:48Regina Barber?

  Yes, I love history. Let's do it.

• 5:51Speaker 02

  So psychedelic substances have been around for millennia in indigenous medicine.

• 5:54Regina Barber?

  OK.

• 5:55Speaker 02

  And in the late 1930s, this guy named Albert Hoffman first synthesized LSD. Then the actual term psychedelics was coined in the 1950s.

• 6:04Regina Barber?

  OK.

• 6:04Speaker 02

  Now, those drugs like LSD, psilocybin, and mescaline are called classic psychedelics. In the brain, they all activate something called the serotonin to a receptor. Serotonin is a chemical in our brains. It regulates things like sleep, mood, appetite. And at this specific receptor, classic psychedelics have these very powerful psychoactive effects.

• 6:26Speaker 03

  Which include feelings of sometimes ego dissolution, or what you might think are those feelings of unity, where the boundaries of self and other can sort of dissolve.

• 6:37Regina Barber?

  Yeah, I mean, this is the sort of thing that I like think of when somebody like mentions psychedelics, like this like trippy magic mushroom like experience.

• 6:44Speaker 02

  Yeah, exactly. So in the 50s and 60s, psychedelics, both in recreational use and in research, are huge. But then, in the early 70s, the US does this big crackdown on controlled substances. And that, coupled with tighter regulation on pharmaceutical testing, really shuts down most psychedelics research on humans. And the next big phase in neuropsychiatry in the 80s is super different.

• 7:09Regina Barber?

  Yeah.

• 7:10Speaker 02

  Boris told me the goal became to have sort of a one-size-fits-all mental health approach.

• 7:14Speaker 05

  You know, it's like the industrial revolution in medicine, that you can really reduce things down to a drug. You would take it every day. You know, something that you can define.

• 7:23Speaker 02

  So Gina, this is when SSRIs come on the scene. Selective serotonin reuptake inhibitors. They also target serotonin receptors. Antidepressants like SSRIs work for about 2/3 of people who take them, but there were still some major problems. They don't work for the other third, even after trying multiple different drugs.

• 7:43Regina Barber?

  Right, which leaves a lot of people like just in the lurch.

• 7:46Speaker 02

  Yeah, and I mean, there's other factors, too. You have to take them every single day. You have to be on them for at least a few weeks until you can even really feel a change.

• 7:55Regina Barber?

  Yeah.

• 7:55Speaker 02

  And so there's this urgent need for alternative treatments for mental health conditions, which is why, around 2,000 or so, researchers start studying another drug called ketamine. You might know it as a recreational drug, but it's also been used since the 1960s as an anesthetic in clinical settings.

• 8:13Regina Barber?

  So it's not a psychedelic?

• 8:14Speaker 02

  It's not a psychedelic, at least according to most people I talk to.

• 8:18Regina Barber?

  Okay.

• 8:18Speaker 02

  But it can have these similar-ish effects, depending on the dose. Like, it can make people feel numb or give them this sometimes euphoric or dissociated feeling. And as researchers started to study it more, they realized that

• 8:32Speaker 07

  Ketamine produced very rapid antidepressant effects. Effects that appeared within 24 hours as opposed to the couple of weeks that you would need for an SSRI. And this was really paradigm shifting for the field.

• 8:48Speaker 02

  That's David Olson, a chemical neuroscientist at UC Davis. He studies compounds like psychedelics. And so Gina, to summarize all this history, David told me that once people started studying ketamine, they wondered what other kinds of compounds might have similar rapid effects. And remember all that research on psychedelics that got paused?

• 9:09Regina Barber?

  Yeah, yeah.

• 9:10Speaker 02

  Okay, so that comes up again.

• 9:12Regina Barber?

  Oh, okay, so with that in mind, let's kind of like drill down into like these two questions. One, how do we effectively study such a trippy drug? And then two, once you know how to study it, how do you tell what part of the drug is actually helpful?

• 9:25Speaker 02

  Right, so for the first question, this is really a challenge for all experiments. You want to make sure that you're testing one thing and then comparing it to a control or a placebo to see if it's really the thing you're testing that causes an effect versus like some other factor.

• 9:40Regina Barber?

  Right.

• 9:40Speaker 02

  And that's even harder when it comes to these drugs in particular.

• 9:44Speaker 03

  You typically are going to know within 30 or 45 minutes, I didn't get a placebo, I got something that's pretty much stronger than that or that's, you know, influencing my perception of reality in a way that's unusual.

• 9:56Speaker 02

  Albert told me about a few ways researchers can address this problem. So one is to give people another drug called an active comparator. Usually it's one that can kind of mimic certain effects of something like a psychedelic without having to give people one.

• 10:09Regina Barber?

  Oh, okay.

• 10:10Speaker 02

  Or another strategy is just to give everyone the drug, sometimes at different doses to see what's most effective. And then you can sort of parse out a threshold for what might work and what might not.

• 10:20Regina Barber?

  Okay.

• 10:21Speaker 02

  So remember Lori?

• 10:22Regina Barber?

  Yeah.

• 10:23Speaker 02

  Every person in the study she was in got psilocybin. So they knew that they were going to get it. Lori told me she met with therapists before and after her treatments and they were in the room with her over the course of her experience with psilocybin.

• 10:35Regina Barber?

  And that therapy component is pretty common, right? Since like people can have like intense experiences with these drugs, like a bad trip.

• 10:42Speaker 02

  Yeah, exactly. Most studies have some kind of therapeutic support involved. And for Lori, on that day that she got her first round of psilocybin, she walked into the room.

• 10:51Speaker 04

  It was very tranquil. It was like a white couch and they had blankets and towels and tissues and pillowcase that was super soft and comfy. And the light was dim.

• 11:04Speaker 02

  She said she felt like she was preparing herself for this big, important moment.

• 11:08Speaker 04

  I would say in my mind, how I perceived it, like sacred, like I'm just not taking a white pill and that's it.

• 11:15Regina Barber?

  Hmm. And this isn't necessarily unique to psychedelics, right? Because I feel like just the experience of feeling like you're about to make this like change in your life could also play a role.

• 11:24Speaker 02

  Exactly. And this doesn't take away from the study or what Lori experienced. And the fact that she told me she felt so much better after. But it does mean when patients in studies do feel better, it's harder to say what helped them feel better. And then that can make it hard to know how to give other people that same experience. Here's Boris again.

• 11:44Speaker 05

  It's very difficult to study experience because really a lot of things are happening. You're getting a drug, you're learning something, there's a learning process, there's hope, expectation. And then there is this like wild, phantasmagoric, you know, thing that happens for eight hours in the middle of it.

• 12:00Regina Barber?

  Okay, so there's this like big debate, right? Like, is it the trip? Or is it the drug? And does it even matter if we try to separate these things?

• 12:07Speaker 02

  Yeah. So when I asked David this question, like, why does it matter? He reminded me that not everyone wants to trip or should trip, depending on their medical history. For example, most professionals say that if a person has a family history of schizophrenia or bipolar disorder, they probably shouldn't use psychedelics or ketamine. So if researchers can figure out what matters, like if you don't actually need to trip to get these potentially positive effects, scientists could get more effective treatments for more people.

• 12:37Regina Barber?

  So how are they going to try to settle that debate?

• 12:40Speaker 02

  Some researchers, like Boris and David, are asking, what happens if you remove the trip altogether?

• 12:46Regina Barber?

  Whoa.

• 12:46Speaker 02

  They're doing this in really different ways, but they both hope it's going to bring us closer to answering the question. That'll be next time on the show.

• 12:54Regina Barber?

  I'm Regina Barber.

• 12:56Speaker 02

  And I'm Rachel Carlson.

• 12:57Regina Barber?

  And if you liked this episode, make sure you never miss a new one, especially episodes two and three of this psychedelic series, by following us on whatever podcasting platform you're listening from.

• 13:08Regina Barber?

  This episode was produced by Hannah Chen and edited by Rebecca Ramirez and Jeff Brumfield. Tyler Jones checked the facts. Kwasi Lee was the audio engineer. Beth Donovan is our senior director and Colin Campbell is our senior vice president of podcasting strategy. Thank you for listening to Short Wave, the science podcast from NPR.

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