Effects of a Serotonergic Psychedelic on the Lipid Bilayer.
ACS Chemical Neuroscience October 21, 2024 Debsankar S. Saha Roy, Ankit Singh, V. Vaidya et al.
The serotonergic psychedelic DOI (2,5-dimethoxy-4-iodoamphetamine) alters the physical properties of artificial lipid bilayers in ways that may contribute to its biological effects, such as enhancing neuronal plasticity. Using solid-state NMR, atomic force microscopy, and fluorescence techniques, DOI was found to induce disorder in lipid acyl chains, shrink ordered domains, reduce the force needed to form nanopores, and promote vesicle fusion to lipid bilayers. These receptor-independent effects on membranes are more than two orders of magnitude more potent than those of serotonin. The findings suggest that direct membrane actions of psychedelics, not just serotonin 2A receptor activation, could play a role in processes requiring membrane remodeling.