Anxiety, depression, or cluster headaches can be highly debilitating. Recent studies have argued that psychedelic compounds which stimulate serotonin receptors in the brain could act as treatments for these conditions. While clinical trials have indeed shown promising results, not everyone seems to benefit from these substances.
A new study led by the University of North Carolina Chapel Hill (UNC) has found that a reason for this could be common genetic variations in one serotonin receptor. The experts discovered that seven variants uniquely and differentially impacted this receptor’s in vitro response to four psychedelic drugs – LSD, psilocin, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and mescaline.
Serotonin receptors in the brain bind serotonin (5-hydroxytryptamine; 5-HT) and other similar amine-containing molecules, helping regulate people’s moods, emotions, cognitive processes, and even appetite. One of these receptors (5-HT2A) is responsible for mediating the effects of a variety of psychedelic drugs. However, scientists found that there are several naturally occurring, random genetic variations – known as “single nucleotide polymorphisms” (SNPs) – which can significantly alter the 5-HT2A receptor’s structure and function.
The researchers used a series of assays to investigate the effect that seven different SNPs had on in vitro binding and signaling of the 5-HT2A receptor when in the presence of psilocin, LSD, 5-MeO-DMT, and mescaline. The analysis revealed that some genetic variations – even ones at a significant distance from the binding site – fundamentally alter the ways in which this serotonin receptor interacts with the drugs. For instance, the single nucleotide polymorphism Ala230Th was found to have both increased and reduced responses to the psychedelic substances tested compared to the original version of the gene, while the His452Th mutation exhibited only reduced effects.
These findings suggest that patients with different genetic variations would react differently to psychedelic treatments. Thus, physicians should carefully consider the genetics of a patient’s serotonin receptors in order to reliably identify which psychedelic compound is likely to be the most effective treatment.
The study is published in the journal ACS Chemical Neuroscience.