Brain research
March 1, 2025
Jannik Nicklas Eliasen, Uffe Kristiansen, Kristi A Kohlmeier
2 citations
Psychedelics like DMT and ibogaine activate the 5-HT2A receptor, a G protein-coupled receptor, to produce therapeutic effects. Naturally occurring genetic variations (SNPs) in this receptor alter its function and drug responsiveness. Using whole-cell electrophysiology on HEK cells expressing either the normal or a mutated (I197V) human 5-HT2AR, membrane currents were observed in both genotypes with both drugs, but not in cells lacking the receptor, confirming the responses depend on 5-HT2AR activation. The I197V mutation shortened the DMT response duration without affecting amplitude. These findings demonstrate that 5-HT2AR-transfected HEK cells can be used to test novel compounds and evaluate SNP effects on drug-induced ion currents.
Neuroscience
October 5, 2025
Jannik Nicklas Eliasen, Amir Rezagholizadeh, Helene Påbøl Jacobsen et al.
1 citation
Ibogaine, a psychedelic alkaloid from root bark, shows potential for treating depression and substance use disorder, but its cellular effects are unclear. In this study, ibogaine (100 µM) was applied to putative GABAergic neurons in the ventral tegmental area (VTA) from male and female mice. No effects were observed on membrane currents, membrane potential, or spontaneous excitatory postsynaptic currents in either sex. However, ibogaine increased intracellular calcium in both sexes, decreased action potential firing rate in males only, and altered afterhyperpolarization kinetics in females only. At baseline, male VTA neurons fired at higher frequencies than female ones. These sex-differentiated effects may contribute to ibogaine's therapeutic actions.
Journal of Neurochemistry
May 1, 2026
Jannik Nicklas Eliasen, Amir Rezagholizadeh, Helene Påbøl Jacobsen et al.
Dimethyltryptamine (DMT), a classic psychedelic with potential anti-depressive and anti-addictive properties, alters the electrical activity of certain neurons in the ventral tegmental area (VTA) of the mouse brain, with effects differing by sex. In an ex vivo study on I_h-negative neurons, a low concentration (500 nM) of DMT had no effect on electrophysiological properties in either sex. A high concentration (90 μM) increased action potential firing and changed membrane conductance at subthreshold potentials, but only in female neurons. DMT also raised cytosolic calcium levels in both sexes at the high concentration. The findings suggest that DMT activates mechanisms in females beyond the calcium changes seen in males, highlighting the importance of sex and dose in understanding its therapeutic potential.