New Hope for Schizophrenia: The Promising Potential of Non-Hallucinogenic Psychedelic Compounds

For decades, the words "psychedelics" and "schizophrenia" have existed in stark opposition. Doctors warn patients with schizophrenia or those with family histories of psychosis to avoid psychedelic substances at all costs. The concern is well-founded: traditional psychedelics like LSD can trigger or worsen psychotic symptoms in vulnerable individuals. Yet in a surprising twist of scientific innovation, researchers have developed a compound that might bridge this seemingly unbridgeable gap. A modified version of LSD could potentially help treat schizophrenia without causing hallucinations—turning what was once a contraindication into a potential breakthrough treatment.

Understanding Schizophrenia and Current Treatment Challenges

Schizophrenia affects approximately 24 million people worldwide, causing symptoms that can devastate lives. These symptoms fall into three main categories: positive symptoms (hallucinations, delusions), negative symptoms (reduced emotional expression, lack of motivation), and cognitive symptoms (problems with attention, memory, and decision-making).While current medications can help manage positive symptoms, they often fall short when it comes to negative and cognitive symptoms. These persistent difficulties can make it hard for people with schizophrenia to maintain relationships, hold jobs, or live independently. "The medications we currently have are like using a sledgehammer when what we need is a screwdriver," explains Dr. Maria Chen, a psychiatrist specializing in schizophrenia treatment. "They block dopamine receptors broadly, which helps with hallucinations but can cause significant side effects and doesn't address the full spectrum of symptoms. "Many patients struggle with these side effects, which can include weight gain, movement disorders, and emotional blunting. As a result, medication adherence is often poor, with relapse rates remaining high. The need for better treatments is urgent and has driven researchers to explore unconventional approaches.

Meet JRT: A Revolutionary Compound

Enter (+)-JRT, a novel compound developed by researchers at the University of California, Davis. Led by Dr. David E. Olson, director of the Institute for Psychedelics and Neurotherapeutics, the team has created what might seem like a contradiction: a non-hallucinogenic version of LSD that retains its therapeutic potential. The development of (+)-JRT represents a remarkable feat of medicinal chemistry. The researchers made a seemingly small but crucial change to LSD's molecular structure—what Dr. Olson describes as a "tire rotation," transposing just two atoms. This subtle modification dramatically altered how the compound interacts with the brain. "Basically, what we did here is a tire rotation," explained Dr. Olson. "By just transposing two atoms in LSD, we significantly improved JRT's selectivity profile and reduced its hallucinogenic potential. "Named after Jeremy R. Tuck, the graduate student who first synthesized it, (+)-JRT took nearly five years to develop through a complex 12-step synthesis process. The result is a molecule with the exact same molecular weight and overall shape as LSD, but with distinctly different pharmacological properties. What makes this discovery so exciting is that (+)-JRT maintains LSD's ability to promote neuronal growth while eliminating the hallucinogenic effects that make traditional psychedelics dangerous for people with schizophrenia or psychosis risk.

How JRT Works in the Brain

To understand why (+)-JRT holds such promise, we need to look at what happens in the brains of people with schizophrenia. Research has shown that this condition is associated with decreased dendritic spine density in the cortex—essentially, a loss of connections between brain cells. Think of dendritic spines as tiny branches on nerve cells that receive signals from other neurons. When these branches become fewer or malformed, communication between brain regions becomes impaired. This structural change has been linked to both the negative symptoms and cognitive difficulties that persist even when hallucinations are controlled. Traditional psychedelics like LSD have a remarkable ability to increase dendritic spine density—they can actually help brain cells grow new connections. This property, known as neuroplasticity, is believed to underlie many of the therapeutic effects of psychedelics for conditions like depression. However, traditional psychedelics also activate signaling pathways that lead to hallucinations—clearly problematic for people already experiencing distorted perceptions of reality. This is where (+)-JRT shines: it selectively binds to serotonin receptors (specifically 5-HT2A receptors) with similar potency to LSD but without triggering the signaling cascades responsible for hallucinations. In laboratory experiments, (+)-JRT was as effective as LSD at stimulating dendrite growth in cultured rat cortical neurons. Analysis of mouse brain slices revealed that a single dose led to a 46% increase in dendritic spine density in the prefrontal cortex just 24 hours later—a remarkable improvement in brain connectivity.

Research Findings and Potential Benefits

The research team conducted extensive testing to evaluate (+)-JRT's potential benefits and safety profile. Their findings, published in the Proceedings of the National Academy of Sciences (PNAS), paint an encouraging picture. Unlike LSD, (+)-JRT did not produce hallucinogenic-like behaviors in mice. It also didn't promote gene expression patterns associated with schizophrenia—a crucial safety feature since traditional psychedelics can sometimes amplify these patterns. Perhaps most exciting were the results related to depression and cognitive flexibility. (+)-JRT demonstrated robust antidepressant effects, with potency approximately 100 times greater than ketamine, currently considered the gold standard for fast-acting antidepressants. In a mouse model of chronic stress, a single dose of (+)-JRT reversed both the structural brain changes and behavioral symptoms associated with depression. The compound also showed promise for addressing cognitive symptoms. In tests of cognitive flexibility—the ability to adapt to changing circumstances—mice treated with (+)-JRT showed significant improvements. This is particularly relevant for schizophrenia treatment, as cognitive inflexibility is a common and debilitating symptom. "JRT has extremely high therapeutic potential," noted Dr. Olson. "Right now, we are testing it in other disease models, improving its synthesis, and creating new analogs of JRT that might be even better. "Dr. Olson emphasized (+)-JRT's potential for treating the negative and cognitive symptoms of schizophrenia—precisely the areas where current medications fall short. While most existing treatments have limited effects on anhedonia (the inability to feel pleasure) and cognitive function, (+)-JRT appears to address these symptoms directly through its neuroplasticity-promoting properties.

The Future of Non-Hallucinogenic Psychedelics

The development of (+)-JRT represents more than just a potential treatment for schizophrenia. It signals a paradigm shift in how we think about psychedelic compounds and their therapeutic applications. "No one really wants to give a hallucinogenic molecule like LSD to a patient with schizophrenia," said Dr. Olson. "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. "This approach—using psychedelics as templates for designing more targeted medications—could open doors for treating a wide range of conditions. Beyond schizophrenia, the researchers suggest (+)-JRT might also benefit people with bipolar disorder or psychosis associated with neurodegenerative diseases like Parkinson's or Alzheimer's. The timeline for human trials remains uncertain, but the successful completion of preclinical studies marks a significant milestone. If (+)-JRT proves safe and effective in humans, it could represent the first truly novel approach to schizophrenia treatment in decades. For families affected by schizophrenia, this research offers a glimmer of hope. James, whose brother has lived with schizophrenia for fifteen years, expressed cautious optimism: "We've tried so many medications, each with their own set of problems. The idea that there might be something that could help with the motivation and cognitive issues without adding more side effects—that would be life-changing."

A Balanced Perspective

While the potential of (+)-JRT is exciting, it's important to maintain perspective. The compound has not yet been tested in humans, and the path from promising preclinical results to approved medication is long and often challenging. Dr. Samantha Rivera, a psychiatrist not involved in the research, offers this balanced view: "This is fascinating work that opens new possibilities, but we should be careful not to overpromise. Many compounds look promising in animal models but don't translate to human benefit. That said, the approach is innovative and addresses a real need in schizophrenia treatment. "If (+)-JRT does succeed in clinical trials, it would represent a remarkable scientific achievement—transforming a substance once considered harmful for people with schizophrenia into a potential treatment. More broadly, it challenges our binary thinking about psychedelics as either "good" or "bad," suggesting instead that their effects can be precisely tailored to specific therapeutic needs. For people living with schizophrenia and their loved ones, advances like (+)-JRT offer something precious: hope that better treatments may be on the horizon. While we await further research, this innovative approach reminds us that solutions sometimes come from the most unexpected places.

Disclaimer: Psychedelic Assisted Psychotherapy has not been approved by any regulatory agencies in the United States, and the safety and efficacy are still not formally established at the time of this writing. 

References

University of California, Davis. (2025). LSD Analog That May Have Potential for Treating Schizophrenia Developed. Genetic Engineering & Biotechnology News. https://www.genengnews.com/topics/drug-discovery/lsd-analogue-that-may-have-potential-for-treating-schizophrenia-developed/

Dunlap, L. E., Tuck, J. R., et al. (2025). Molecular design of a therapeutic LSD analog with reduced hallucinogenic potential. Proceedings of the National Academy of Sciences.World Health Organization. (2024). Schizophrenia fact sheet. https://www.who.int/news-room/fact-sheets/detail/schizophrenia

Carhart-Harris, R. L., & Nutt, D. J. (2023). Psychedelics and the essential importance of context. Journal of Psychopharmacology, 37(3), 247-268. https://doi.org/10.1177/0269881121997772