Good news! Amazing stuff! Flipping just two atoms!
"An analogue of the psychedelic drug LSD has been found to offer the same therapeutic effects as LSD but is less likely to cause the hallucinogenic trips associated with the drug. The researchers say that their work highlights the potential of rationally designed, non-hallucinogenic psychedelic analogues in the treatment of neuropsychiatric diseases such as schizophrenia, where the use of psychedelics is not recommended. ...
Using tests, such as the mouse head twitch response assay, which, ... correlates well with human hallucinogenic potency, they found that JRT did not produce hallucinogenic-like behaviours in mice dosed with LSD. ... in contrast to LSD, JRT does not bind the 5-HT2A receptor for very long. ..."
"... researchers have developed a new, neuroplasticity-promoting drug closely related to LSD that harnesses the psychedelic’s therapeutic power 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. ...
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. ..."
From the significance and abstract:
"Significance
Psychedelic compounds, such as lysergic acid diethylamide (LSD), can promote the growth of atrophied cortical neurons, which is relevant to the treatment of numerous brain conditions.
However, their hallucinogenic properties have limited their adoption as medicines and preclude their use in certain patient populations, such as those with schizophrenia or a family history of psychosis.
By transposing only two atoms, we have created JRT, an exceptionally potent analogue of LSD with lower hallucinogenic potential, improved pharmacological selectivity, and the ability to produce a wide range of therapeutic effects.
Our work highlights the potential of rationally designed, nonhallucinogenic analogues of psychedelics for treating diseases where the use of psychedelics is contraindicated.
Abstract
Decreased dendritic spine density in the cortex is a key pathological feature of neuropsychiatric diseases including depression, addiction, and schizophrenia (SCZ).
Psychedelics possess a remarkable ability to promote cortical neuron growth and increase spine density; however, these compounds are contraindicated for patients with SCZ or a family history of psychosis.
Here, we report the molecular design and de novo total synthesis of (+)-JRT, a structural analogue of lysergic acid diethylamide (LSD) with lower hallucinogenic potential and potent neuroplasticity-promoting properties.
In addition to promoting spinogenesis in the cortex, (+)-JRT produces therapeutic effects in behavioral assays relevant to depression and cognition without exacerbating behavioral and gene expression signatures relevant to psychosis.
This work underscores the potential of nonhallucinogenic psychoplastogens for treating diseases where the use of psychedelics presents significant safety concerns."
Researchers Develop an LSD Analogue with Potential for Treating Schizophrenia (original news release)
JRT differs from LSD in the positioning of two atoms. An N and C in the ergoline structure of LSD have been swapped to make the less hallucinogenic JRT
No comments:
Post a Comment