5-MeO-DMT modifies innate behaviors and promotes structural neural plasticity in mice.
Sarah J. Jefferson, Ian Gregg, Mark Dibbs, Clara Liao, Hao Wu, Pasha A. Davoudian, Samuel C Woodburn, Patrick H. Wehrle, Jeffrey Sprouse, Alexander M. Sherwood, Alfred P. Kaye, Christopher Pittenger, Alex C. Kwan
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology August 1, 2023 DOI: 10.1038/s41386-023-01572-w (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | 5-MeO-DMT psilocybin |
| Topics | Neuroplasticity 5-MeO-DMT DMT |
| Keywords | Psychedelics Behavioral science Mental health |
| Citations | 57 |
| Key findings | 5-MeO-DMT induces a shorter-duration head-twitch response than psilocybin, suppresses mating-related ultrasonic vocalizations, and increases dendritic spine density in the medial frontal cortex through elevated spine formation without altering spine size. |
Abstract
Serotonergic psychedelics are gaining increasing interest as potential therapeutics for a range of mental illnesses. Compounds with short-lived subjective effects may be clinically useful because dosing time would be reduced, which may improve patient access. One short-acting psychedelic is 5-MeO-DMT, which has been associated with improvement in depression and anxiety symptoms in early phase clinical studies. However, relatively little is known about the behavioral and neural mechanisms of 5-MeO-DMT, particularly the durability of its long-term effects. Here we characterized the effects of 5-MeO-DMT on innate behaviors and dendritic architecture in mice. We showed that 5-MeO-DMT induces a dose-dependent increase in head-twitch response that is shorter in duration than that induced by psilocybin at all doses tested. 5-MeO-DMT also substantially suppresses social ultrasonic vocalizations produced during mating behavior. 5-MeO-DMT produces long-lasting increases in dendritic spine density in the mouse medial frontal cortex that are driven by an elevated rate of spine formation. However, unlike psilocybin, 5-MeO-DMT did not affect the size of dendritic spines. These data provide insights into the behavioral and neural consequences underlying the action of 5-MeO-DMT and highlight similarities and differences with those of psilocybin.