Something strange happened in a chemistry lab at the University of California, Davis. A team of researchers was fiddling with LSD, not taking it, but pulling it apart at the atomic level when they made a discovery that could change how doctors treat some of the most stubborn mental illnesses on earth. What they found was not a new psychedelic. It was almost the opposite.
By making one of the smallest possible changes to LSD’s molecular structure, they produced a compound that may do something no psychiatric drug has ever done before: physically rebuild damaged brain tissue, without sending anyone on a trip.
Why Scientists Were Playing With LSD in the First Place
LSD has a reputation built almost entirely around what it does to your mind in the short term. But beneath the hallucinations and altered perception, something else happens. LSD is a powerful stimulator of brain cell growth.
When neurons in your prefrontal cortex, the brain region tied to decision-making, emotional regulation, and social behavior, become damaged or start to wither, cognitive and emotional problems follow. Chronic stress, depression, schizophrenia, and addiction all leave marks in the brain’s architecture. Dendritic spines, which are tiny branches that allow brain cells to communicate, shrink and disappear. Synaptic connections weaken or break entirely.
LSD, it turns out, pushes the brain to regrow those connections. It binds to serotonin receptors, specifically a type called 5-HT2A receptors, and kick-starts a process of neural repair that most medications cannot touch.
For years, researchers have known about LSD’s ability to promote this kind of structural repair. But there has always been an obvious problem: you cannot give a hallucinogen to someone who is already experiencing psychosis. For patients with schizophrenia or a family history of psychotic disorders, LSD is completely off the table. Any treatment that relied on its hallucinogenic properties would be unusable for the very people who might need brain repair the most.
So David Olson, a chemistry professor and director of the Institute for Psychedelics and Neurotherapeutics at UC Davis, set out to do something audacious. He wanted to keep what made LSD useful and strip away what made it dangerous.
Moving Two Atoms Changed Everything
Olson’s team spent nearly five years working on a 12-step chemical synthesis process. What they were after was a modified version of LSD that kept its brain-repairing abilities but lost its capacity to produce hallucinations.
Their solution was almost absurdly simple in description, even if brutally difficult in execution. “Basically, what we did here is a tire rotation,” said Olson. “By just transposing two atoms in LSD, we significantly improved JRT’s selectivity profile and reduced its hallucinogenic potential.” Two atoms. Same molecular weight. Same overall shape. Completely different behavior.
Swapping the position of those two atoms changed how the compound interacted with serotonin receptors. LSD forms a strong hydrogen bond at a specific point in the receptor, a molecular handshake that appears to trigger hallucinations. JRT cannot form that bond. Without it, the receptor behaves differently, and the hallucinogenic signal never fires. Researchers named the new compound JRT after Jeremy R. Tuck, the graduate student who first synthesized it in Olson’s lab.
What JRT Does Inside the Brain
In preclinical studies, JRT did something remarkable. After a single dose in mice, it produced a 46% increase in dendritic spine density and an 18% increase in synapse density in the prefrontal cortex, measured 24 hours later using high-resolution electron microscopy.
To put that in plain terms: it grew new branches on brain cells and built new communication points between neurons in one of the brain’s most important regions.
JRT also demonstrated an ability to reverse damage already done. When mice were subjected to chronic stress using a corticosterone protocol that mimics the biological effects of prolonged psychological pressure, their prefrontal cortex showed significant spine loss. A single dose of JRT restored that spine density to near-normal levels within a day.
Because JRT binds with high selectivity to serotonin receptors and lacks affinity for dopamine, histamine, and adrenergic receptors, it does not produce the sedation, weight gain, or metabolic problems that make current drugs like clozapine so difficult to use long-term.
A Drug That Schizophrenia Patients May Actually Be Able to Take
Schizophrenia is notoriously hard to treat. Current antipsychotics do a reasonable job managing hallucinations and delusions, which clinicians call “positive symptoms,” but they fall far short when it comes to cognitive fog, social withdrawal, and the inability to feel pleasure, known as anhedonia. Those are the symptoms that most erode a person’s quality of life, and most medications barely touch them.
Olson has been clear about why JRT matters for this population. “No one really wants to give a hallucinogenic molecule like LSD to a patient with schizophrenia,” he 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.”
In mouse studies, JRT improved both negative and cognitive symptoms of schizophrenia without worsening positive symptoms. More telling, it did not trigger the gene expression patterns associated with schizophrenia, something LSD does when administered. That distinction matters enormously. A drug that physically repairs brain tissue while simultaneously activating the genetic markers of the disease it is meant to treat would be dangerous. JRT did not do that.
Researchers also tested JRT’s impact on cognitive flexibility using a reversal learning task, a measure of how well a brain can adapt when the rules change. Mice subjected to mild, unpredictable stress showed deficits in this kind of learning. JRT restored it. Reversal learning deficits are well-documented in people with schizophrenia and bipolar disorder, which makes these findings especially relevant.
It Also Beat Ketamine at Its Own Game
Ketamine is currently the gold standard for fast-acting antidepressant treatment. It works quickly, but it comes with its own psychoactive properties and a real potential for abuse. JRT outperformed it by a considerable margin. In forced swim tests, a standard preclinical measure of antidepressant potential, JRT produced antidepressant effects at roughly 100 times lower doses than ketamine. Even more striking, the compound cleared from brain tissue and blood within two hours of administration, yet its behavioral effects lasted well beyond that window.
Researchers also tested JRT against anhedonia using multiple methods. In one experiment, mice made anhedonic by chronic stress regained normal pleasure-seeking behavior after JRT treatment. In a probabilistic reward task, a more sophisticated measure of reward responsiveness that translates more reliably from animals to humans than many other tests, both ketamine and JRT reversed stress-induced deficits in response bias. JRT’s effect persisted for at least three days after a single dose, even as daily stress continued.
Did It Actually Stop Making Mice Trip?
Researchers ran a battery of tests specifically designed to measure hallucinogenic potential, and JRT failed to register on any of them.
In the mouse head-twitch response assay, currently the best-validated animal predictor of human hallucinogen activity, JRT produced no measurable effect across any dose tested. LSD reliably triggers this response. JRT did not.
When JRT was given to mice before a dose of LSD, it actually blocked LSD’s hallucinogenic effect entirely. That finding suggests JRT may act as a partial antagonist at the 5-HT2A receptor, occupying the receptor and preventing hallucinogenic compounds from getting a foothold, while still producing its own therapeutic effects.
JRT also did not cause hyperlocomotion, the frenzied, disoriented movement that hallucinogens and stimulants produce in rodents, and did not impair prepulse inhibition, which is a measure of sensory gating that breaks down in psychosis. LSD disrupts prepulse inhibition. JRT did not.
What Still Needs to Happen Before This Reaches Patients
JRT has not been tested in humans. Every result described here comes from cell cultures and animal models, which means caution is warranted. Preclinical findings frequently fail to replicate in human trials, and psychiatric drug development has a long history of promising compounds that did not survive that translation.
There is also at least one pharmacological flag worth watching. JRT partially activates 5-HT2B receptors, and chronic stimulation of those receptors has been linked to cardiac valve damage in other compounds. Researchers have identified this, but long-term safety data do not yet exist.
Olson is also co-founder and chief innovation officer of Delix Therapeutics, a company working to bring psychoplastogens to market, a connection worth knowing when evaluating the enthusiasm around these findings. That said, the research team is moving forward. JRT is currently being tested in additional disease models, and work is underway to improve its synthesis and develop new analogues that might perform even better. “JRT has extremely high therapeutic potential,” Olson said. “Right now, we are testing it in other disease models, improving its synthesis, and creating new analogues of JRT that might be even better.”
A Different Way of Thinking About Psychiatric Drugs
Most psychiatric medications work by adjusting chemical signals in the brain, raising serotonin here, blocking dopamine there. JRT represents a different approach. Rather than changing the brain’s chemistry, it changes the brain’s structure. It builds new connections where old ones have been lost.
Mental illnesses like depression and schizophrenia are, among other things, diseases of synaptic architecture. When the physical structure of the prefrontal cortex degrades, behavior and cognition follow. A drug that can rebuild that architecture without requiring a psychedelic experience, without triggering psychosis, and without the metabolic baggage of current antipsychotics would address a problem that current medicine largely ignores.
JRT began as a curiosity. Researchers moved two atoms in a controlled lab environment to see what would happen. What happened was a compound that outgrew dendritic spines, reversed stress-induced brain damage, outperformed ketamine as an antidepressant, and may offer schizophrenia patients something they have never had before: a drug that treats what actually disables them. Human trials will tell the real story. But if those results hold, two atoms may turn out to be a very long distance.
