University of California, Davis, researchers have developed a new, neuroplasticity-promoting drug closely related to LSD with reduced hallucinogenic potential:
To design the drug, dubbed JRT, researchers flipped the position of just two atoms in LSD’s molecular structure. The chemical flip reduced JRT’s hallucinogenic potential while maintaining its neurotherapeutic properties, including its ability to spur neuronal growth and repair damaged neuronal connections that are often observed in the brains of those with neuropsychiatric and neurodegenerative diseases.
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JRT exhibited powerful neuroplastic effects and improved measures in mice relevant to the negative and cognitive symptoms of schizophrenia, without exacerbating behaviors and gene expression associated with psychosis.
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Olson said that it took his team nearly five years to complete the 12-step synthesis process to produce JRT. The molecule was named after Jeremy R. Tuck, a former graduate student in Olson’s laboratory, who was the first to synthesize it and is a co-first author of the study along with Lee E. Dunlap, another former graduate student in Olson’s laboratory.
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Key findings included:
- JRT and LSD have the exact same molecular weight and overall shape, but distinct pharmacological properties.
- JRT is very potent and highly selective for binding to serotonin receptors, specifically 5-HT2A receptors, the activation of which are key to promoting cortical neuron growth.
- JRT promoted neuroplasticity, or growth between cellular connections in the brain, leading to a 46% increase in dendritic spine density and an 18% increase in synapse density in the prefrontal cortex.
- JRT did not produce hallucinogenic-like behaviors that are typically seen when mice are dosed with LSD.
- JRT did not promote gene expression associated with schizophrenia. Such gene expression is typically amplified with LSD use.
- JRT produced robust anti-depressant effects, with it being around 100-fold more potent than ketamine, the state-of-the-art fast-acting anti-depressant.
- JRT promoted cognitive flexibility, successfully addressing deficits in reversal learning that are associated with schizophrenia.