Imma Perfetto
Cosmos science journalist
Scientists have cooked up a non-hallucinogenic version of LSD which they say has “extremely high therapeutic potential” for conditions like schizophrenia.
Lysergic acid diethylamide, or LSD, gained a reputation for its potent hallucinogenic effects following its synthesis in 1938 by Swiss chemist Albert Hofmann, and his “accidental” discovery of it’s psychedelic properties 5 years later.
It was reported in Isis, the journal of the History of Science Society, that by the late 1950s psychiatrists and psychologists “were administering it to cure neuroses and alcoholism and to enhance creativity.” Eventually the drug was regulated after use raised significant medical concerns.
But perhaps less known is the psychedelic’s ability to promote neuroplasticity – the growth of neurons and the repair of damaged neuronal connections.
Such damage is often seen in the brains of people with neuropsychiatric and neurodegenerative diseases, so researchers are eager to explore the potential of psychedelics as new treatments.
However, as David Olson, director of the Institute for Psychedelics and Neurotherapeutics at the University of California Davis, points out: “no one really wants to give a hallucinogenic molecule like LSD to a patient with schizophrenia.”
Schizophrenia is a debilitating neuropsychiatric disease that affects about 0.5% of people.
Structural changes to neurons in the brain’s cerebral cortex are believed to contribute to the symptoms of the disease, which includes hallucinations and delusions, anhedonia (diminished ability to feel pleasure) and avolition (diminished motivation), and impairments in attention and working memory.
Olsen and his team designed a new drug to harness LSD’s therapeutic properties, while minimising its hallucinogenic potential, according to a new study in the journal Proceedings of the National Academy of Sciences.
The molecule, JRT, is identical to LSD except for the position of 2 atoms, which have been flipped. It took nearly 5 years to complete the 12-step synthesis process to produce JRT.
Experiments in cell cultures revealed that JRT is very potent and highly selective at binding to serotonin receptors, specifically 5-HT2A receptors which are key to promoting cortical neuron growth.
When administered to mice, the drug promoted the growth of neuronal connections in the prefrontal cortex. It did not induce hallucinogenic-like behaviours that are typically seen when mice are dosed with LSD.
“The development of JRT emphasizes that we can use psychedelics like LSD as starting points to make better medicines,” says Olson.
“We may be able to create medications that can be used in patient populations where psychedelic use is precluded.”
Olsen, who is also co-founder and chief innovation officer of Delix Therapeutics, a company that aims to bring “neuroplastogens” like JRT to the market, says that JRT has extremely high therapeutic potential.
“Right now, we are testing it in other disease models, improving its synthesis, and creating new analogues of JRT that might be even better,” he says.
