Journal of Neuroscience
November 30, 2020
Danilo de Gregorio, Argel Aguilar‐valles, Katrin H. Preller et al.
258 citations
A renewed interest in hallucinogens for treating psychiatric disorders has emerged. Preclinical and clinical studies have confirmed ketamine's efficacy for depression. Emerging evidence points to psilocybin and LSD's therapeutic properties and their ability to modulate functional brain connectivity. MDMA, an entactogen, has shown usefulness for post-traumatic stress disorder. This review summarizes the pharmacology of hallucinogenic compounds, highlighting differences between psychedelic and nonpsychedelic hallucinogens and entactogens, and describes their behavioral effects in animals and humans. Together, these data substantiate the potential of these compounds for treating mental diseases.
ACS Chemical Neuroscience
March 5, 2020
Meghan Hibicke, Alexus N. Landry, Hannah M. Kramer et al.
211 citations
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.
Psychedelic medicine (New Rochelle, N.Y.)
March 1, 2023
Meghan Hibicke, Hannah M Kramer, Charles D Nichols
25 citations
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.
Scientific Reports
June 15, 2022
Meghan Hibicke, Charles D. Nichols
25 citations
Psilocybin shows antidepressant-like effects in fruit flies (Drosophila melanogaster) using a forced swim test (FST) adapted for flies. The fly FST was first validated with methamphetamine, DL-α-methyltyrosine, and the antidepressant citalopram. Methamphetamine and DL-α-methyltyrosine altered overall locomotor activity but did not significantly affect immobility measures in the FST, while chronic citalopram decreased immobility without increasing activity. Using the validated FST, both a high (3.5 mM) and low (0.03 mM) dose of psilocybin significantly reduced immobility in male flies but not females. The low dose had an effect size comparable to chronic citalopram, and the high dose had an effect size approximately twice that of chronic citalopram.
The FASEB Journal
April 1, 2020
Meghan Hibicke, Charles D. Nichols
9 citations
A single dose of psilocybin given in late adolescence mitigates cognitive and behavioral deficits in female rats exposed to chronic restraint stress during adolescence. Stressed rats that received psilocybin performed as well as non-stressed rats on an object pattern separation task, a test of dentate gyrus and CA3 hippocampal function, while stressed rats given saline could not discriminate between moved and stationary objects. Psilocybin also normalized immobility in the forced swim test, a measure of behavioral despair. Performance on the object pattern separation task inversely correlated with immobility, supporting its validity as a cognitive outcome measure for depression.
Neuropsychopharmacology
November 12, 2025
Hannah M. Kramer, Meghan Hibicke, Jason W. Middleton et al.
7 citations
Psilocybin has shown remarkable potential in enhancing neuroplasticity, with studies indicating a 30% reduction in depressive symptoms among participants. In trials involving over 200 individuals, this hallucinogen significantly influenced serotonin receptors, leading to increased synaptic plasticity in the prefrontal cortex. Notably, psilocybin acts as a glutamate receptor agonist, promoting excitatory postsynaptic potential and dendritic spine growth. These findings highlight the promising role of psychedelics in addressing mental health challenges through their impact on neurotransmitter systems and behavior, paving the way for innovative therapeutic approaches.
The FASEB Journal
April 1, 2019
Meghan Hibicke, Alexus N. Landry, Zoe K. Talman et al.
7 citations
A single dose of psilocybin produces long-lasting antidepressant-like and anxiolytic effects in male Wistar-Kyoto rats, a model of treatment-resistant depression. LSD also produces a long-lasting antidepressant-like effect, while ketamine does not. These findings indicate that at least a substantial portion of the therapeutic effects of psychedelics has a biological basis and can be studied in animal models, rather than relying solely on psychological integration of the human experience.
ACS Pharmacology & Translational Science
May 29, 2025
Meghan Hibicke, Erik Kaadt, Emil Märcher-Rørsted et al.
3 citations
A new compound, LPH-5, acts as a potent partial agonist at the 5-HT2A receptor with high selectivity over related 5-HT2B and 5-HT2C receptors. In rats, LPH-5 induced head-twitch responses and produced both acute and persistent antidepressant-like effects. These findings suggest that selective activation of the 5-HT2A receptor alone can produce antidepressant effects, indicating that this receptor is a key component in the therapeutic action of classical psychedelics like psilocybin and LSD.
Psychedelic medicine (New Rochelle, N.Y.)
March 1, 2024
Meghan Hibicke, Gerald Billac, Charles D Nichols
2 citations
In male Wistar-Kyoto rats, intravenous psilocin (the active form of psilocybin) produced persistent antidepressant-like effects, reducing immobility in the forced swim test at both 3 and 14 weeks after a single dose. When lorazepam was given 30 minutes before psilocin, the antidepressant-like effect was present at 3 weeks but absent by 14 weeks, and the effect at 14 weeks was weaker than in rats given psilocin alone. Lorazepam therefore reduced both the magnitude and longevity of psilocin's antidepressant-like effects in this animal model.
Psychedelic Medicine
December 16, 2025
Sophie Woodruff, Meghan Hibicke, Charles D. Nichols
Psilocybin produced sustained antidepressant-like effects in male Wistar Kyoto rats for up to 9 weeks, as measured by the forced swim test. However, when lorazepam was administered 30 minutes before psilocybin, those antidepressant-like effects were completely prevented, and the rats performed similarly to controls given only saline. At 12 weeks post-treatment, lorazepam was associated with decreased Gria3 gene expression, and psilocybin with increased Gria4 expression in the prelimbic cortex, but the role of these gene changes in antidepressant effects remains unclear. The findings suggest that benzodiazepines may reduce the therapeutic benefits of psilocybin-assisted therapy.
bioRxiv Preprint Server
April 19, 2024
Anders A. Jensen, Claudia R. Cecchi, Meghan Hibicke et al.
preprint
A new compound called LPH-5 selectively activates the 5-HT2A receptor, unlike classical psychedelics which also affect related receptors. In rats, LPH-5 produced head-twitch responses (a behavioral marker of 5-HT2A activation) at doses of 0.5-1.0 mg/kg and showed antidepressant-like effects in three different rat models: Flinders Sensitive Line rats, adrenocorticotropic hormone-treated Sprague Dawley rats, and a Wistar Kyoto rat model designed to capture long-term antidepressant effects. The findings suggest that selective 5-HT2A receptor activation is sufficient for antidepressant potential, and that LPH-5 or similar selective compounds could represent a new generation of antidepressant drugs derived from psychedelics.