A team from the University of California, Davis has developed JRT, an innovative LSD analog designed to retain its therapeutic effects without causing intense hallucinations. The discovery, published in Proceedings of the National Academy of Sciences, positions this compound as a potential treatment for schizophrenia and other brain disorders associated with synaptic loss.

What is JRT and why is it different from LSD?

JRT is a structural analog of LSD created through a minimal but strategic modification: swapping the position of two atoms in its molecular structure. While it maintains the same molecular weight and overall shape as LSD, it exhibits distinct and safer pharmacological properties.​

The team led by Dr. David E. Olson optimized the compound’s selectivity for serotonin 5-HT2A receptors, which are key to promoting neuronal growth. This greater precision significantly reduces hallucinogenic potential, a major barrier to the clinical use of psychedelics in patients with psychotic disorders.

From a pharmacological perspective, JRT belongs to a new generation of compounds known as neuroplastogens: molecules capable of stimulating the formation and repair of neuronal connections without inducing intense psychedelic effects. This difference is crucial for schizophrenia patients, for whom traditional psychedelics are contraindicated for safety reasons.​

The innovation lies not only in modifying LSD but also in proving that psychedelics can serve as starting points for developing more refined and clinically viable medications.

JRT and neuroplasticity: a new path for treating schizophrenia

Schizophrenia involves not just psychotic episodes but also negative symptoms and cognitive decline that deeply affect quality of life. Many current treatments have limited efficacy against anhedonia and executive function. This is where JRT could make a difference.​

In preclinical studies, the compound increased dendritic spine density by 46% and synaptic density by 18% in the prefrontal cortex, a region linked to decision-making and emotional regulation. These structural changes led to improvements in cognitive flexibility and reversal learning, processes often impaired in schizophrenia.

Additionally, JRT did not activate gene expression patterns linked to psychosis or produce hallucinogen-like behaviors in animal models. This safety profile clearly sets it apart from conventional LSD and makes it a promising candidate for future clinical trials.​

Another key finding is its potent antidepressant effect, superior in preclinical models to ketamine—one of the most advanced rapid-acting treatments in current psychiatry. This broadens its potential beyond schizophrenia to other neuropsychiatric disorders.

The future of therapeutic psychedelics and neuroplastogens

The development of JRT marks a strategic shift in psychedelic therapeutic research. Instead of focusing on hallucinogenic experiences as the main treatment mechanism, science is now exploring how to isolate and enhance these molecules’ neurobiological benefits.​

Synthesizing JRT took nearly five years and 12 chemical steps, reflecting the complexity of turning a psychedelic substance into a pharmaceutical candidate with a better safety profile. The team is currently refining its production and developing new analogs with even greater therapeutic potential.​

If confirmed in human clinical trials, JRT could usher in a new category of psychiatry treatments focused on structural brain repair. This would benefit not only schizophrenia patients but also those with neurodegenerative diseases characterized by synaptic loss and brain atrophy.​

JRT emerges as an LSD analog designed to deliver neuroplasticity benefits without the risks of hallucinations. Its potential for treating schizophrenia and other neuropsychiatric disorders represents a significant advance in modern medicine. More than a mere chemical derivative, it signals the dawn of a new era in psychedelic-based drug development.

Reference:

• Molecular design of a therapeutic LSD analogue with reduced hallucinogenic potential. Link.

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