A new study from the University of North Carolina at Chapel Hill School of Medicine reveals that genetic variations in serotonin receptors can significantly influence the potency of psychedelic drugs. The research, published in ACS Chemical Neuroscience, suggests that individual genetic profiles may play a crucial role in determining the effectiveness of psychedelics in therapeutic applications.
The study focused on single nucleotide polymorphisms (SNPs) in the gene coding for the serotonin 5-HT2A receptor, a primary target for psychedelic drugs like LSD, psilocybin, and mescaline. Researchers analyzed seven common alleles of the 5-HT2A receptor found in humans, with frequencies ranging from 0.003% to 7.9% in the population.
Impact of Receptor Variants on Drug Binding
In vitro experiments using human cells showed that different gene forms of the 5-HT2A receptor exhibited varying responses when binding to common psychedelics, including psilocin, mescaline, 5-MeO-DMT, and LSD. According to Gavin Schmitz, the paper’s first author, the team used assays to assess how the different gene forms of the 5-HT2A receptor behaved when binding to any of four commonly studied psychedelics. For example, the Ala447Val 5-HT2A receptor displayed a three-fold increase in potency for 5-MeO-DMT. One particular receptor showed a nine-fold increase in potency in response to mescaline.
Clinical Implications and Future Research
The findings suggest that genetic variations could contribute to the diverse range of responses observed in clinical trials of psychedelic drugs. "Clinical studies have found a wide variety of responses to psychedelic drugs, with some patients seeing huge benefits after treatment and some seeing no benefits at all. Our study suggests that genes matter in determining how sensitive we are to the effects of psychedelics," said Schmitz.
However, Schmitz cautioned that the cellular-level differences observed in the study may not directly translate to whole-brain responses in clinical settings. The precise mechanisms underlying the therapeutic effects of psychedelics remain unclear, and some researchers suggest that the 5-HT2A receptor may not be involved in the antidepressant effects of these drugs.
Consideration for Future Clinical Trials
Despite these uncertainties, the study underscores the importance of considering genetic factors in future clinical trials of psychedelic drugs. By understanding how genetic variations influence drug potency and receptor signaling, researchers may be able to personalize treatment approaches and improve outcomes for patients with psychiatric disorders. Further research is needed to explore the role of other receptor targets and to validate these findings in clinical populations.
