New LSD-like drug could revolutionize mental health treatment

Scientists have long known that psychedelics like LSD can help the brain grow new connections. These drugs promote something called neuroplasticity, which helps the brain heal from mental illness. But there’s a major problem: hallucinations. Drugs like LSD come with intense mind-altering effects, which can be risky or even dangerous—especially for people with schizophrenia or a history of psychosis.

Published in the journal, Proceedings of the National Academy of Sciences, researchers at a major university have taken a bold step forward. By flipping the position of just two atoms in the LSD molecule, they’ve created a new drug, called JRT, that holds onto all the brain-healing power of LSD—but without the hallucinogenic effects.

“Basically, what we did here is a tire rotation,” said David E. Olson, director of the Institute for Psychedelics and Neurotherapeutics and a professor of chemistry, and biochemistry and molecular medicine at UC Davis. “By just transposing two atoms in LSD, we significantly improved JRT’s selectivity profile and reduced its hallucinogenic potential.”

This change is small in structure but huge in outcome. In lab experiments with mice, JRT promoted brain growth, boosted mental flexibility, and even showed powerful antidepressant effects—all without triggering behaviors linked to hallucinations or psychosis.

When the team tested JRT, the results were striking. The drug made brain cells grow and connect more easily. It increased dendritic spine density in the prefrontal cortex by 46%. These spines are tiny branches that allow brain cells to talk to each other. It also boosted the number of synapses—where messages pass between cells—by 18%.

That kind of growth matters. People with mental health conditions like depression, schizophrenia, and addiction often have fewer of these brain connections. Their brains show signs of atrophy and lost connections, especially in areas that control emotions and decision-making. JRT helps rebuild these networks.

Unlike LSD, JRT did not cause mice to act in ways linked to hallucinations. It also didn’t trigger gene patterns that are associated with schizophrenia. In fact, it showed positive effects on behaviors and thinking tasks linked to schizophrenia symptoms, especially cognitive problems and a lack of joy or motivation.

“JRT has extremely high therapeutic potential,” Olson explained. “Right now, we are testing it in other disease models, improving its synthesis, and creating new analogues of JRT that might be even better.”

Schizophrenia affects about 0.5% of the global population. The condition causes hallucinations, delusions, emotional numbness, and poor memory or attention. Current medications mainly treat the hallucinations, called “positive symptoms,” but not the emotional or cognitive symptoms.

One drug, clozapine, can help with these harder-to-treat symptoms—but it comes with serious side effects and isn’t used as a first option.

That’s where JRT could come in. It targets the 5-HT2A serotonin receptors, the same ones psychedelics use to boost brain plasticity. But instead of shutting these receptors down, like traditional antipsychotic drugs do, JRT activates them in a way that promotes healing. This difference could help fix the underlying brain changes linked to schizophrenia—without the high risk of hallucinations.

This is a huge shift in thinking. For years, experts avoided using psychedelics in patients with schizophrenia. The risks were too high. Emergency room visits linked to psychedelics often involve psychotic episodes. But JRT may change that equation.

“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.”

Creating JRT wasn’t easy. It took almost five years to complete the 12-step chemical process to make the molecule. The name JRT honors Jeremy R. Tuck, a former student in Olson’s lab who first created it.

JRT has the same molecular weight and general shape as LSD. But that small atomic switch made it behave very differently. It became highly selective for the 5-HT2A receptor—the key site for encouraging brain cell growth—while avoiding the responses that cause hallucinations.

One major test involved “head-twitch responses” in mice, a behavior linked to hallucinogenic activity. LSD triggers this response strongly. JRT did not.

JRT also passed tests for depression. In fact, it worked about 100 times more powerfully than ketamine, one of the fastest-working antidepressants on the market. Unlike ketamine, which can cause dissociation and other side effects, JRT seemed to offer its benefits without major risks.

Beyond mood, JRT improved “reversal learning”—a mental skill involving flexible thinking. This is often impaired in people with schizophrenia and other brain disorders. In mice, JRT restored this ability, suggesting it could help with attention, planning, and problem-solving in humans.

Psychedelic-like drugs that don’t cause hallucinations are known as nonhallucinogenic psychoplastogens. They are part of a new class of treatments being explored for depression, PTSD, addiction, and now schizophrenia. These molecules aim to repair the brain without disrupting reality.

Until now, most of these compounds were based on tryptamine or ibogaine structures. JRT stands out because it is based on LSD’s unique shape—a four-ringed ergoline structure. LSD is one of the most powerful psychedelics ever discovered, so adapting it safely could unlock major therapeutic benefits.

The JRT compound proves that tiny changes in molecular structure can lead to big shifts in how a drug behaves. This could inspire a wave of future drugs that borrow from psychedelics without carrying their risks.

Olson’s lab continues to refine the drug, looking to improve how it’s made and testing new versions that might work even better. They are also studying JRT in models of other brain diseases, such as Alzheimer’s and major depression.

If those results hold up in future human trials, JRT may one day help people with some of the hardest-to-treat brain conditions feel and function better — without losing touch with reality.

Note: The article above provided above by The Brighter Side of News.

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