The search for drugs that can safely and effectively treat disorders like schizophrenia and cognitive decline, has led researchers in an interesting direction. Existing pharmaceutical options for treatment are not very effective, and they come with major side effects, so are only administered as a last resort. Schizophrenia and other brain impairment problems are caused when the connections between brain cells (neurons) do not work properly. These connections are called synapses, and the ability to form new ones – especially in response to learning or when old ones have degenerated – is called neuroplasticity. The infamous hallucinogenic drug LSD is extremely good for enhancing neuroplasticity, but you certainly wouldn’t give it to a schizophrenic for obvious reasons. However, scientists at the University of California have created a new molecule called JRT that is identical to LSD except there are no “high” effects. They did this by replacing two key atoms.

Their study tested JRT in mice and found that the connections between neurons that drive cognitive function increased by 46%. In addition, there was an 18% increase in the synapses of the pre-frontal cortex of the brain where attention and memory processing are focused. JRT also promoted cognitive flexibility, which is the ability to see a new way of doing things. Lack of this flexibility is strongly associated with schizophrenia. An extra benefit was that JRT produced robust anti-depressant effects which are far more potent than ketamine - the current choice for a fast-acting anti-depressant. 

However, unlike with LSD, with JRT there was no indication whatsoever that the mice were undergoing hallucinogenic effects. “By just transposing two atoms in LSD, we eliminated the hallucinogenic potential of JRT. The development of JRT shows how we can use psychedelics as starting points to make better medicines.” Though the principle target of this study was schizophrenia, the improvement in neuroplasticity could be very helpful in treating other neurological diseases that are characterized by synaptic loss and brain atrophy. This is particularly interesting for the treatment of cognitive decline, and that is the next phase of this team’s exciting research.