Dimethyltryptamine (DMT) and ibogaine elicit membrane effects in HEK cells transiently transfected with the human 5-HT2A receptor.
Jannik Nicklas Eliasen, Uffe Kristiansen, Kristi A. Kohlmeier
Brain Research March 1, 2025 DOI: 10.1016/j.brainres.2024.149425 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Laboratory experiment Peer reviewed |
|---|---|
| Population | HEK cells transiently transfected with human wildtype or I197V mutated 5-HT2AR |
| Interventions | Dimethyltryptamine (DMT) Ibogaine |
| Topics | 5-MeO-DMT DMT Ibogaine Serotonin |
| Keywords | Psychedelic compounds Neuroscience neurobiology Brain science Neural research Pharmacology drug interactions Pharmaceutical science Affective disorders G protein-coupled receptor I–v curves Membrane currents Single nucleotide polymorphism Psychedelics hallucinogens Entheogens |
| Citations | 2 |
| Key findings | Transfection of 5-HT2AR in HEK cells enables activation of downstream ion channels by DMT and ibogaine, with the I197V SNP shortening the DMT response duration. |
Abstract
Psychedelics show promise in treating psychiatric disorders. Therapeutic effects appear to involve activation of the 5-Hydroxytryptamine 2A receptor (5-HT2AR), a G protein-coupled receptor (GPCR). Several SNPs of the 5-HT2AR naturally occur, which are associated with differences in receptor function and altered responsiveness to treatments. New compounds suspected to act at the 5-HT2AR are actively being generated. HEK cells are not commonly used to study membrane effects induced by agonists of GPCRs. In this study, for the first time, membrane actions of two psychedelics, dimethyltryptamine (DMT) and ibogaine on HEK cells transiently transfected with either the human wildtype (WT) or the human I197V mutated 5-HT2AR were investigated using whole-cell electrophysiology. Membrane effects were observed in both genotypes and with both drugs in most cells, while no responses were observed in non-transfected HEK cells suggesting that responses were due to 5-HT2AR activation. In HEK cells transfected with the I197V SNP, a significantly shorter duration of the DMT response was observed, however there were no differences in drug-elicited amplitudes between drug or receptor genotype. I-V curves showed a significant effect of drug exposure for both DMT and ibogaine at the highest concentration evaluated. Taken together, our data show transfection of the 5-HT2AR, a GPCR, in HEK cells is able to activate downstream ion channels following exposure to two different 5-HT2AR agonists. Accordingly, investigations of novel compounds suspected to act at 5-HT2ARs can include examination of elicitation of ionic currents in 5-HT2AR transfected HEK cells, and drug effects at SNPs can also be evaluated.
Comparable studies
Other experimental studies on ibogaine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ibogaine, a noncompetitive inhibitor of serotonin transport, acts by stabilizing the cytoplasm-facing state of the transporter. In vitro (SERT) | 2007 | Laboratory study | |
| Mechanisms of action of ibogaine and harmaline congeners based on radioligand binding studies. | 1992 | Laboratory study | |
| The mechanistic basis for noncompetitive ibogaine inhibition of serotonin and dopamine transporters. | 2012 | Experimental study | |
| Identification of a primary metabolite of ibogaine that targets serotonin transporters and elevates serotonin. | 1995 | Experimental study | |
| Ibogaine and its congeners are sigma 2 receptor-selective ligands with moderate affinity. | 1995 | Laboratory study |
Citations in the library
Cited by 2
- The psychoactive compound ibogaine sex-dependently alters the firing rate and afterhyperpolarization of Ih-negative neurons in the mouse ventral tegmental area Neuroscience October 5, 2025
- Characteristics of Ongoing Clinical Trials of Psychogenic Substances for Psychiatric Disorders. Journal of Clinical Psychopharmacology
Cites 23
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Science February 13, 2009
- Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Nature Neuroscience June 1, 2023
- Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up Journal of Psychopharmacology February 1, 2022
- Human Pharmacology of Ayahuasca: Subjective and Cardiovascular Effects, Monoamine Metabolite Excretion, and Pharmacokinetics Journal of Pharmacology and Experimental Therapeutics June 18, 2003
and 18 more in the library