Since its discovery in the 1940s, LSD has fascinated the scientific world for its profound effects on perception, consciousness, and mental health.
In the mid-20th century, researchers explored its potential to treat conditions like depression and addiction — until cultural backlash and safety concerns pushed it out of the medical spotlight.
While interest in psychedelics has resurged in recent years, LSD remains too unpredictable for vulnerable populations, particularly those with schizophrenia.
Now, scientists at the University of California, Davis, have developed a compound that could change that narrative.
By flipping the position of just two atoms in LSD’s structure, they’ve created a new molecule — called JRT — that keeps the benefits but ditches the trip.
The result is a drug that enhances brain plasticity, improves cognitive function and shows promise for treating serious mental health conditions without the risks tied to traditional psychedelics.
Small molecular shift, big clinical potential
“Basically, what we did here is a tire rotation,” said David E. Olson, director of the UC Davis Institute for Psychedelics and Neurotherapeutics.
“By just transposing two atoms in LSD, we significantly improved JRT’s selectivity profile and reduced its hallucinogenic potential.”
In preclinical tests, JRT displayed the ability to stimulate brain cell growth and repair damaged neural pathways — core features of successful treatment for cognitive decline and mood disorders.
By avoiding the trippy side effects that limit LSD’s use in clinical settings, JRT represents a new generation of psychedelic-inspired compounds tailored for safety and precision.
Outperforms ketamine, without the psychedelic trip
JRT boosted key markers of neuroplasticity in mice, increasing dendritic spine and synapse density in the prefrontal cortex.
The drug also showed powerful antidepressant effects, being around 100 times more potent than ketamine — the current gold standard in fast-acting antidepressants.
Crucially, it didn’t trigger gene expression linked to schizophrenia or produce the hallucinogenic-like behaviors commonly observed with LSD in animal models.
“No one really wants to give a hallucinogenic molecule like LSD to a patient with schizophrenia,” Olson said.
“The development of JRT emphasizes that we can use psychedelics like LSD as starting points to make better medicines. We may be able to create medications that can be used in patient populations where psychedelic use is precluded.”
Building better drugs for schizophrenia and beyond
Named after Jeremy R. Tuck, the graduate student who first synthesized it, JRT took nearly five years to develop through a meticulous 12-step process.
The UC Davis team is now testing JRT in additional disease models and refining its design.
Their goal: unlock treatments that go beyond symptom management and actually rebuild the brain in conditions like schizophrenia, depression, and neurodegenerative diseases.
“JRT has extremely high therapeutic potential. Right now, we are testing it in other disease models, improving its synthesis, and creating new analogs of JRT that might be even better,” Olson said.
With JRT, LSD’s legacy in mental health may be coming full circle — this time, with more precision and fewer risks.
The study, co-led by Tuck and fellow former grad student Lee E. Dunlap, was published April 14 in Proceedings of the National Academy of Sciences.