It can be crippling for those who suffer from conditions like depression, anxiety, and cluster headaches. In clinical research, psychedelic substances have demonstrated benefits as therapies for several ailments, but not in all cases.
Researchers now reveal in ACS Chemical Neuroscience that one cause might be widespread genetic differences in one serotonin receptor. The in vitro response of the receptor to the hallucinogenic substances psilocin, LSD, 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT), and mescaline was discovered to be singularly and variably influenced by seven variations.
Several encouraging findings from clinical trials have recently rekindled interest in and study of the use of psychedelic substances that activate serotonin receptors in the brain.
Serotonin (5-hydroxytryptamine, 5-HT) and other amine-containing compounds can bind to these receptors, which can assist control people’s mood, perceptions, cognition, emotions, and hunger. The serotonin receptor 5-HT2A in particular is in charge of mediating the effects of psychedelic substances.
Single nucleotide polymorphisms are a class of naturally occurring, random genetic variations that can affect the structure and function of the 5-HT2A receptor. Bryan Roth and associates were interested in determining how alterations in the serotonin 5-HT2A receptor affect the in vitro action of four psychedelic drugs.
Seven distinct SNPs were tested for their impact on the binding and signaling of the 5-HT2A serotonin receptor in vitro in the existence of psilocin, LSD, 5-MeO-DMT, and mescaline.
According to their findings, some gene changes, even those far from the binding region, can change how the receptor reacts to psychedelic substances. For instance, the His452Th mutation solely showed decreased effects, while the single nucleotide polymorphism Ala230Th had both enhanced and decreased responses to the medications tested relative to the normal version of the gene.
According to their findings, the scientists predict that individuals with various genetic variants will respond to psychedelic-assisted therapy in various ways. They advise doctors to consider a patient’s genetic makeup when deciding which psychedelic substance is most likely to be a successful treatment.
Schmitz, G. P., et al. (2022) 5-HT2A SNPs Alter the Pharmacological Signaling of Potentially Therapeutic Psychedelics. ACS Chemical Neuroscience. doi.org/10.1021/acschemneuro.1c00815.