Psilocybin and LSD produce antidepressant-like effects in rats that last longer than those of ketamine. A single dose of psilocybin or LSD led to persistent antidepressant-like effects in a rat model, while ketamine’s effects were only temporary. This suggests that classic psychedelics may offer more sustained therapeutic benefits than ketamine, and that a profound subjective experience may not be required for these effects.
A single dose of psilocybin rescued cognitive function and reduced passive coping behavior in adult female rats that had experienced chronic stress during adolescence, effects that persisted for at least five weeks. Psilocybin did not alter these behaviors in non-stressed rats. The degree of immobility in the forced swim test correlated with impaired object pattern separation ability. No long-term changes in mRNA expression for synaptic plasticity-related genes were observed across several brain regions, though stress contributed to variability in the gene for glutamate metabotropic receptor 2 in the hippocampus. These findings suggest psilocybin produces enduring antidepressant-like effects without lasting alterations in synaptic density gene expression.
A single dose of psilocybin or the selective 5-HT2A receptor agonist 25CN-NBOH reduces immobility in the forced swim test in rats for at least three months, with no decrease in effect size over that period. Both drugs produced similar behavioral effects, indicating that 5-HT2A receptor activation alone is sufficient for long-lasting changes. In the medial prefrontal cortex, layer 5 excitatory pyramidal neurons showed altered resting membrane potential, firing rates, and synaptic excitation months after treatment. However, no changes were found in synaptic density, spine classification, or expression of presynaptic and postsynaptic markers. The results suggest that enduring functional plasticity, rather than structural plasticity, underlies the long-term behavioral effects of psychedelics.
Early-career researchers in psychedelic science discuss the challenges and opportunities of building a career in this emerging field. They describe obstacles such as stigma, funding hurdles, and professional uncertainty alongside the potential for innovation and profound impact. The roundtable highlights the need for mentorship, interdisciplinary collaboration, and perseverance to advance the field and develop sustainable professional paths.