An LSD analogue for treating psychiatric diseases
Certain psychiatric diseases, such as depression and schizophrenia, feature a loss of structures called dendritic spines from neurons. Dendritic spines form the receiving end of synapses, or connections between neurons.
… the team tried switching the places of two atoms in LSD. This resulted in a compound that had the same 3D structure as LSD but altered the way it bound to its target receptor, similar to the modified DMT. The researchers developed a procedure for synthesizing the compound, which they named JRT, from commercially available starting materials… while LSD can bind to many receptor types, JRT bound only to serotonin receptors. Interactions with a specific serotonin receptor, the 5-HT2A receptor, are responsible for both the plasticity-promoting and hallucinogenic effects of psychedelics. JRT was potent at activating this receptor, although to a lesser extent than LSD. JRT promoted the growth of dendritic spines in cultured rat neurons. It did so as well or better than LSD and the antipsychotic drug clozapine. When the team administered JRT to mice, it increased the density of dendritic spines and synapses. A single dose of JRT in mice could restore the loss of dendritic spine density caused by chronic exposure to stress hormones. Further mouse testing suggested that JRT had much lower hallucinogenic potential than LSD. JRT did not produce responses in mice that are believed to correlate with the hallucinogenic action of LSD… unlike LSD, JRT did not cause sensory alterations in a mouse model. Nor did it activate genes in the brain associated with schizophrenia. JRT also produced improvements in mice in tests designed to detect potential antidepressant effects. Moreover, it did so at doses 100-fold lower than ketamine, a drug used for treatment-resistant depression. JRT promoted cognitive flexibility as well, which is often impaired in schizophrenia.
Original Article (NIH):
An LSD analogue for treating psychiatric diseases
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