The LSD Analog to Treat Schizophrenia

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Good morning and welcome to another edition of The Drop In!

We’re kicking things off with an interview featuring a researcher who may have uncovered a new treatment for schizophrenia with an LSD analog called (+)-JRT. While this might sound like typical psychedelic research, psychosis-related conditions are typically contraindications for all psychedelics, especially LSD. So, this is a big deal! We reached out to Dr. David Olson from UC Davis to discuss what this data means for the future; the possibility that this new drug could help treat something as complex as schizophrenia feels groundbreaking.

Let's drop in on this, and much more, below.

Enjoy the ride 🌞

Mary Carreón
Senior Editor

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This LSD Analog Could Offer New Hope for Patients with Schizophrenia

Researchers at UC Davis have developed (+)-JRT, a modified version of LSD that may help psychosis-related conditions.

A new compound reported by researchers at UC Davis could mark a turning point in the treatment of schizophrenia. Published in Proceedings of the National Academy of Sciences, the study introduces “(+)-JRT,” a molecular cousin of LSD that appears to promote neural plasticity without triggering visuals or hallucinations. That’s a particularly important characteristic of this drug because, while classical psychedelics have shown promise for treating depression and other conditions, their hallucinogenic effects make them a non-starter for patients who are at risk of psychosis.

The research team, led by Dr. David Olson, slightly tweaked LSD’s molecular structure by swapping just two atoms to produce a compound that retains the therapeutic benefits of LSD while sidestepping its swirling psychedelic effects. The study shows that JRT boosted cortical neuron growth, improved cognitive flexibility, and alleviated anhedonia in mice, meaning the drug increased the mice’s interest and motivation for reward. JRT also appeared to avoid key behavioral and genetic markers typically linked to psychedelic-induced psychosis.

While human trials have yet to begin, the findings suggest that it may be possible to harness the neuroplastic effects of psychedelics without the trip. While “trip-free” psychedelics remain a point of contention among denizens of psychedelic culture, this application of JRT could be a breakthrough for schizophrenia, a condition where negative and cognitive symptoms remain notoriously difficult to treat.

To gain more clarity about JRT and the implications of this study, we reached out to Dr. Olson to discuss the promise and the pitfalls of this new drug, what it might mean for patients with schizophrenia, and whether we lose anything when we strip psychedelics of their visual qualities.

This interview has been lightly edited for clarity.

DoubleBlind: JRT looks promising in rodent models. However, given how tricky it is to translate psychiatric effects from animals to humans, how confident are you that these results will hold up in clinical trials? What are the biggest unknowns when it comes to scaling this up to human use?

Dr. Olson: In terms of efficacy, we used tests relevant to depression and cognition that are directly applicable to humans. For example, the PRT task was originally discovered in patients with depression and then was back-translated to nonhuman primates and rodents. We also used a reversal learning task that can be performed in human patients.

In terms of hallucinogenic potential, we used an assay that is highly predictive of hallucinogenic potential in humans, and we coupled that with a battery of additional cellular and behavioral neuropharmacology tests that give characteristic responses for psychedelics. In all of those experiments, JRT had lower hallucinogenic potential than LSD.

You make a strong case for JRT as a potential tool for tackling negative and cognitive symptoms in schizophrenia, which is arguably the hardest part of the illness to treat. If this proves to be the case in humans, how do you envision it being used? As a complement to existing antipsychotics, or maybe even as a standalone?

I hope that JRT will be a standalone treatment, but it is possible that it could be used in combination with other agents that help to manage positive symptoms. One theory about the pathophysiology of schizophrenia is that positive, negative, and cognitive symptoms all result from changes in circuitry that involve cortical neurons. If you can find a small molecule that can promote healing of those damaged circuits, you might have a drug that can address all aspects of the disease. Moreover, that drug would likely only need to be taken intermittently, as the physical healing of the circuits lasts for some time after the drug has been cleared from the body.

It’s interesting that JRT doesn't seem to activate schizophrenia-linked gene expression the way LSD does. Do you think that makes it truly safer for people with psychosis risk, or are there still blind spots we should be cautious about?

The gene expression studies were interesting, but they were more exploratory. I think that JRT's lack of behavioral responses characteristic of hallucinogens is more relevant to determining its hallucinogenic potential.

Do you think that in trying to strip away psychedelic effects (or reduce them), we might also be stripping away something core to how these compounds actually help people?

For conditions like schizophrenia, I don't think that patients need to have profound mystical-type experiences to get better. Cortical atrophy is a hallmark of that disease, and I think that if we can find safe drugs that can promote the growth of those key neurons, we might have compounds that can address the positive, negative, and cognitive symptoms.

The atomic-level tweak from LSD to JRT is extremely fascinating. Do you think this kind of structure-based design could apply to other psychedelic scaffolds, too, or is LSD a special case chemically?

Actually, we initially designed JRT based on old-fashioned medicinal chemistry and structure-activity relationship studies in the absence of any structural information about the receptor. We had previously found that this molecular swap reduced the hallucinogenic potential of tryptamines while maintaining their ability to promote structural neuroplasticity. We wanted to see if this same molecular perturbation would have the same effect on ergoline-containing compounds like LSD. While we were working on this, several structures of the 5-HT2AR bound to LSD were published, and they gave us even more confidence that we were on the right track.

We Interviewed Christian Angermayer About Psychedelics as “Human Enhancements,” Equality, AI, and Evolution…

We’re about to publish another BANGER of a story this Friday. We interviewed German billionaire Christian Angermayer, the co-founder of atai Life Sciences, who believes psychedelics can save humanity, and he’s investing millions to make it happen. But is his vision of human enhancement a bold leap forward or a techno-utopian fantasy built on inequality and ego?

This story is a shining example of the bold, thoughtful journalism DoubleBlind is proud to produce. Check your inbox on Friday! And upgrade your subscription if you want to read more journalism like this.

DoubleBlind Digs

Here are today’s recommendations to help you live more psychedelically… 

• DONATE: Want to contribute to research on how psilocybin mushrooms can help moms? Mothers of the Mushroom Resource and Research Project is calling on collaborators and community members to co-create vital research and resources around mushrooms, pregnancy, breastfeeding, and postpartum care. Learn more here.

• BOOK SIGNING: Join Zach Leary and the Colorado Psychedelic Society in Boulder, Colorado, on May 15 for a good vibes gathering, book signing, and fundraiser. Say hi, support the movement, and snag a copy of “Your Extraordinary Mind.” Learn more here.

• SIGN THE PETITION: Europe’s first Citizens’ Initiative on psychedelic-assisted therapy launched at the EU Parliament on February 6, 2025, backed by politicians, professors, and psychedelic professionals. The volunteer-led campaign aims to collect 1 million signatures by January 2026 to demand safe access to Psychedelic-Assisted Therapy across EU member states — and present the call to the UN. Learn more and sign here.

• BALTIMORE HEALING: Join Charlotte James and Michele Blu on June 6 for a powerful community Rapeh ritual and sound journey. No prior experience working with Rapeh is required. The circle is open to all divine beings who feel a deep call to reconnect with ancestral and Earth-based ritual practices. Learn more here.

• LONDON MUSHROOMS: Join Darren Le Baron on Sunday, June 1, for a mushroom cultivation workshop for beginners at Hello Love. Discover the basics and explore the various techniques for growing gourmet and medicinal mushrooms. Learn more here.

• HEALTH: Feeling off but told you’re “fine”? Superpower gives you 100+ lab tests, lifetime tracking, and 24/7 support. Own your health for $499. Join now.

Together With Superpower

Don’t miss what your body is trying to tell you.

Brain fog. Low energy. Burnout. You know when something’s off.

Superpower is a 10x better annual checkup:

• 100+ lab tests

• Track results over your lifetime

• 24/7 access to a medical team

Whether you’re microdosing or just curious about your health, Superpower helps you listen deeper.

$499. Two tests per year. No hidden fees.

Join now.