Dimethyltryptamine (DMT) and ibogaine elicit membrane effects in HEK cells expressing human 5-HT2A receptor

Dimethyltryptamine (DMT) and ibogaine both trigger measurable membrane effects in HEK cells engineered to express the human 5-HT2A (serotonin 2A) receptor. Whole-cell electrophysiology shows responses occur in 5-HT2A receptor transfected cells but not in non-transfected controls, supporting that the observed currents are driven by 5-HT2A receptor activation. The study also compares receptor genotypes using the wildtype receptor and the I197V single nucleotide polymorphism (SNP) variant. In cells with the I197V variant, DMT responses show a shorter effective duration, while response amplitude does not differ across drug or receptor genotype. Current-voltage (I-V) curves indicate drug exposure effects at the highest tested concentration for both DMT and ibogaine, suggesting these psychedelics can produce downstream ion channel activity via 5-HT2A receptor engagement. The work proposes HEK-5-HT2A systems as a screening approach for novel 5-HT2A compounds and for evaluating SNP-dependent differences in drug effects.