A team of scientists has developed a fluorescent sensor that locates hallucinogenic molecules and could be used to search for new treatments in mental health.
Many psychedelic drug-related compounds such as LSD and dimethyltryptamine (DMT) hold great promise for treating disorders such as depression, post-traumatic stress disorder, and substance use disorder. These drugs are called psychoplastogens because of their ability to rapidly alter brain connections. But they are drugs that can cause hallucinations and require very careful use and monitoring by patients who take them.
Currently, it is virtually impossible to predict whether a drug will cause hallucinations without first testing it in animals, and the most effective way to do this is the rodent “head twitch” test. ” There have been scientific studies with psychedelic drugs since the 1940s, but we still do not have an effective cell assay for this, ” explains David Olson, a researcher at Davis University in California and one of the authors of this published work. in the journal Cell.
The sensor, dubbed PsychLight , is based on a serotonin receptor (a neuromodulator that allows the brain to rapidly adapt to changing conditions) called HT2AR. Both psychedelic drugs and drugs used to treat psychiatric disorders act through this receptor. Researchers have designed a modified version of the HT2A receptor with a fluorescent component, so that when the sensor binds to serotonin or a hallucinogenic ligand, it changes its conformation, causing fluorescence to increase . Non-hallucinogenic ligands can also bind to psychLight and result in a different fluorescence profile.
PsychLight applications
This sensor can be used to study how natural neuromodulators such as serotonin or hallucinogenic drugs act in different parts of the brain. It could also be used to detect candidate drugs that activate the HT2A receptor and could cause hallucinations. When psychLight is expressed in cells and those cell cultures are exposed to a hallucinogenic drug, they turn on.
A new molecule without hallucinogenic effect
One of the first tests carried out with the new sensor has shown that a new compound called AAZ-A-154 is capable of activating the HT2A receptor without causing hallucinations. This effect has since been proven in animal models and, although it has not been validated in humans, it shows promise as an antidepressant. In any case, the use of this technique to perform molecular screening needs to be further developed, and although the identification of AAZ-A-154 is a good starting point, it is difficult to transfer the results from animals to humans, so there is still a long way to fully develop the new technology.
