ACS Pharmacology & Translational Science
August 2, 2023
Zarmeen Zahid, Zhen Zheng, N. Jones et al.
50 citations
Psilocybin reduces anxiety-like behavior in male mice four hours after treatment, an effect that depends on a temporary spike in the stress hormone corticosterone. Blocking the corticosterone rise or the glucocorticoid receptor eliminated the short-term anxiolytic effect. A nonpsychedelic drug that also raised corticosterone produced similar anxiety reduction, as did stress-induced hormone release alone. The anxiolytic effect lasted seven days after a single psilocybin dose, but this long-term benefit was lost in mice with chronically elevated corticosterone. The findings suggest that an acute, resolvable glucocorticoid surge is necessary for psilocybin's postacute anxiety relief, while chronic stress hormone elevation undermines its lasting effects.
Molecular Biology of the Cell
May 27, 2021
Matthew I. Banks, Zarmeen Zahid, N. Jones et al.
37 citations
Psychedelics may promote neural plasticity, which is thought to underlie their therapeutic effects in psychiatric disorders. The drugs activate signaling pathways that can produce long-term structural changes in the brain, though these mechanisms are complex and not yet fully understood. Stress and inflammation also play roles in both acute and long-term effects. Beyond altering brain structure, psychedelics challenge and expand understanding of the neural basis of psychiatric disorders, consciousness, and human behavior.
bioRxiv (Cold Spring Harbor Laboratory)
August 14, 2020
N. Jones, Zarmeen Zahid, Sean M. Grady et al.
9 citations
preprint
Acute release of the stress hormone corticosterone modifies the lasting behavioral effects of psilocybin in male mice. Psilocybin caused an initial anxiety-like response and a rise in plasma corticosterone, followed by a later reduction in anxiety in the novelty suppressed feeding test. Both the acute and delayed effects disappeared when mice were first given chronic oral corticosterone to suppress their own stress-axis. One week later, psilocybin-treated mice spent more time in the center of an open field, but this long-term anxiolytic effect was also blocked by prior chronic corticosterone exposure. Brief isoflurane anesthesia after psilocybin eliminated these interactions. The findings identify glucocorticoid release as a biological modifier of psilocybin's post-acute and long-term behavioral effects in mice.
bioRxiv (Cold Spring Harbor Laboratory)
June 13, 2024
Christopher R. Nicholas, Matthew I. Banks, Richard Lennertz et al.
3 citations
preprint
Co-administering the amnestic benzodiazepine midazolam with psilocybin in 8 healthy participants partially impaired memory for the psychedelic experience while still allowing a conscious experience to occur. The degree of memory impairment was inversely associated with salience, insight, and well-being induced by psilocybin. These results suggest that memory of the acute psychedelic experience contributes to therapeutically relevant behavioral effects. Because midazolam blocks memory by blocking cortical neural plasticity, it may also help evaluate how the pro-neuroplastic properties of psychedelics contribute to their therapeutic activity.
bioRxiv (Cold Spring Harbor Laboratory)
July 29, 2025
May Kung Sutherland, Christopher R. Nicholas, Richard Lennertz et al.
preprint
Psilocybin, a serotonergic psychedelic, induces neural plasticity and alters consciousness, while midazolam, a benzodiazepine, blunts plasticity and causes sedation and amnesia. In an open-label pilot study, 25 mg of oral psilocybin was given alongside intravenous midazolam at doses that allowed a full psychedelic experience but reduced memory of it. EEG recordings showed that 15-30 minutes after dosing, when midazolam was at its target concentration, beta power increased and the spectral exponent decreased. As psilocybin's effects emerged over the next six hours, Lempel-Ziv complexity and spectral exponent increased while broadband power decreased. These findings suggest psilocybin's effects persist even with midazolam, supporting its use in mechanistic studies.