By progressively removing pieces from LSD, researchers obtained a molecule that produces effects opposite to those of the original compound. LSD acts on the brain by binding to several receptors found on cells and triggering several reactions at the same time.
To find out which parts of LSD are responsible for these reactions, a team from the University of California, Davis, chose a fairly direct approach: taking the molecule apart piece by piece. Its structure contains several groups of atoms linked together. The researchers removed some of them, then observed how each new version behaved.
The chemical structure of LSD, shown in the center, is simplified into several molecular analogues.
Credit: Andras Domokos and Andrian G. Basargin / UC Davis.
The differences appeared quickly. Some simplified molecules retained a strong effect on the receptor primarily associated with hallucinations caused by psychedelics. Others largely lost this property.
Two molecules obtained, named UCD0094 and UCD0076, showed a profile considered interesting during the initial experiments.
The main surprise came from UCD0076. In mice, this molecule produced effects that the researchers associate with those of antipsychotic medications. In other words, by removing certain parts of a molecule known for its psychedelic effects, the team obtained a compound with almost opposite behavior in several tests.
This difference appears to be linked to the way UCD0076 acts on serotonin. The molecule binds mainly to a receptor called 5-HT2C, one of the many contact points used by serotonin in the brain. This receptor is already of interest in research into several neurological and psychiatric disorders, particularly schizophrenia.
UCD0076 is nevertheless still an experimental molecule. The current results come from laboratory experiments and tests on mice, not trials involving patients. The researchers must now create other variants and study their safety, duration of action, and behavior in the body before a possible trial in humans can be considered.