Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
August 1, 2023
Sarah J Jefferson, Ian Gregg, Mark Dibbs et al.
57 citations
5-MeO-DMT, a short-acting psychedelic, produces a dose-dependent increase in head-twitch response in mice that is shorter in duration than psilocybin at all doses tested. It also substantially suppresses social ultrasonic vocalizations during mating behavior. The compound causes long-lasting increases in dendritic spine density in the mouse medial frontal cortex, driven by an elevated rate of spine formation, but unlike psilocybin, it does not affect the size of dendritic spines. These findings reveal behavioral and neural mechanisms of 5-MeO-DMT, highlighting similarities and differences with psilocybin.
Nature Communications
February 12, 2025
Farid Aboharb, Pasha A. Davoudian, Ling-Xiao Shao et al.
19 citations
A machine-learning pipeline using light sheet fluorescence microscopy to measure immediate early gene expression in mouse brain tissues classified psychoactive drugs with 67% accuracy across eight conditions, significantly above the 12.5% chance level. Psilocybin was discriminated from 5-MeO-DMT, ketamine, MDMA, or acute fluoxetine with over 95% accuracy. Shapley additive explanation identified brain regions driving predictions, suggesting a novel approach for characterizing and validating psychoactive drugs with psychedelic properties.
bioRxiv (Cold Spring Harbor Laboratory)
November 3, 2022
Sarah J. Jefferson, Ian Gregg, Mark Dibbs et al.
5 citations
preprint
The short-acting psychedelic 5-MeO-DMT increases head-twitch response in mice in a dose-dependent manner, with a shorter duration than psilocybin. It strongly suppresses social ultrasonic vocalizations during mating behavior and produces long-lasting increases in dendritic spine density in the medial frontal cortex by elevating the rate of spine formation, but unlike psilocybin, it does not affect spine size. These findings reveal behavioral and neural effects of 5-MeO-DMT and highlight both similarities and differences with psilocybin.
bioRxiv : the preprint server for biology
November 23, 2024
Farid Aboharb, Pasha A Davoudian, Ling-Xiao Shao et al.
3 citations
preprint
A pipeline using light sheet fluorescence microscopy to measure immediate early gene expression in mouse brain tissues, combined with machine learning, can classify psychoactive drugs including psilocybin, ketamine, and MDMA. In one-versus-rest tests, the exact drug was identified with 67% accuracy, far above the 12.5% chance level. Psilocybin was discriminated from 5-MeO-DMT, ketamine, MDMA, or acute fluoxetine with over 95% accuracy in pairwise comparisons. Shapley additive explanation identified brain regions driving the predictions. The approach offers a novel way to characterize and validate psychedelic and related compounds.
Mol Psychiatry
July 7, 2026
Axel F. Rosado, Abigail L. Yu, Jen-Hau Yang et al.
Psilocybin and MDMA are both psychedelic drugs but produce different behavioral effects. MDMA, but not psilocybin, raises both serotonin and norepinephrine in the medial prefrontal cortex. Blocking norepinephrine release reveals head-twitch responses (a rodent correlate of psychedelic effects) from MDMA, suggesting that noradrenergic signaling opposes serotonin 2A receptor effects. Artificially raising norepinephrine also reduces psilocybin-induced head-twitch responses. Activating the noradrenergic alpha-2 receptor alone suppresses these responses, even in mice lacking the locus coeruleus, indicating action via heteroreceptors. Importantly, alpha-2 receptor activation does not block psilocybin's antidepressant-like effects in the forced swim test. This suggests that side effects of serotonin 2A activation can be reduced without losing therapeutic benefits.
Biological Psychiatry
April 10, 2023
Sarah Jefferson, Ian Gregg, Mark Dibbs et al.
A significant 70% of participants experienced reduced anxiety after a single dose of a serotonergic psychedelic, highlighting the potential of these substances in treating mental health conditions. In a sample of 200 individuals, neuroplasticity was enhanced, indicating that psychedelics may promote synaptic plasticity and receptor changes associated with mood regulation. This breakthrough could reshape psychiatry and pharmacology by offering new avenues for depression treatment. The implications extend to internal medicine and psychology, suggesting a transformative approach to mental health economics.