Novel LSD Analog Shows Promise for Schizophrenia Treatment

Researchers from the University of California, Davis have developed a new drug closely related to LSD that shows potential in treating schizophrenia. This novel compound, known as JRT, promotes neuroplasticity while minimizing the hallucinogenic effects typically associated with psychedelic substances.

Published in the Proceedings of the National Academy of Sciences, the study outlines JRT's potential as a therapeutic option for schizophrenia, a condition where traditional psychedelics are not prescribed due to safety concerns. The researchers believe this compound may also be beneficial for other neuropsychiatric and neurodegenerative diseases characterized by synaptic loss and brain atrophy.

The design process for JRT involved a simple yet effective alteration to the molecular structure of LSD, involving the repositioning of just two atoms. This modification reduced the hallucinogenic effects while retaining the neurotherapeutic properties, such as enhancing neuronal growth and repairing damaged connections in the brain.

According to David E. Olson, the lead researcher and director of the Institute for Psychedelics and Neurotherapeutics, this adjustment significantly improved JRT's selectivity profile, allowing for therapeutic benefits without the side effects commonly linked to psychedelics.

In preclinical tests, JRT demonstrated strong neuroplastic effects and positively impacted mice models, reflecting improvements in negative and cognitive symptoms associated with schizophrenia without inducing psychotic behaviors or gene expression typically related to hallucinogenic substances.

Olson highlighted the importance of developing medications that harness the therapeutic potential of psychedelics without their adverse effects. With JRT, the team aims to create effective treatments for patient populations where traditional psychedelic use is contraindicated.

The synthesis of JRT took nearly five years, following a twelve-step process, and is named after Jeremy R. Tuck, a former graduate student involved in its development. The research team conducted extensive cellular and animal assays that underscored JRT's neuroplastic effects and favorable safety profile compared to LSD.

Key findings from their research included:

• JRT shares the same molecular weight and overall shape as LSD but possesses distinct pharmacological properties.
• JRT effectively binds to serotonin receptors, specifically the 5-HT2A receptors, crucial for promoting neuronal growth.
• JRT led to a 46% increase in dendritic spine density and an 18% increase in synapse density in the prefrontal cortex.
• Unlike LSD, JRT did not induce hallucinogenic behaviors in tested mice.
• JRT did not trigger gene expressions associated with schizophrenia, which are typically heightened with LSD.
• JRT exhibited robust antidepressant effects, being approximately 100 times more potent than ketamine, the current leading fast-acting antidepressant.
• JRT also enhanced cognitive flexibility, addressing learning deficits tied to schizophrenia.

Given its high therapeutic potential, JRT is currently undergoing further testing against other neurodegenerative and neuropsychiatric diseases, with ongoing improvements to its synthesis and the development of new analogs that may enhance its efficacy.