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Do You Need to 'Trip' for Psychedelics to Work as Medicine?
Psychedelic researchers are engaged in heated debate over whether the mind-altering effects of the drugs are necessary for realizing their therapeutic potential.
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November 8, 2023
Do You Need to ‘Trip’ for Psychedelics to Work as Medicine?
Psychedelic researchers are engaged in heated debate over whether the mind-altering effects of the drugs are necessary for realizing their therapeutic potential.
By Rachel Nuwer edited by Elah Feder & Tulika Bose
*[An abstract, colorful illustration of wavy lines converging on a molecular diagram with the words "Science, Quickly" and "The Search for New Psychedelics" above and below the molecular diagram]*
Molly Ferguson/Scientific American
[Illustration of a Bohr atom model spinning around the words Science Quickly with various science and medicine related icons around the text]
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This is Episode Two of a three-part Fascination on the science of psychedelics. You can listen to Episode One here.
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.
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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.
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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.
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