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.
Frontiers in Psychiatry
January 8, 2024
N. Jones, Laura M. Wagner, Molly C. Pellitteri Hahn et al.
10 citations
Psilocybin, a psychedelic compound used in psychotherapy research, is converted in the body to the active metabolite psilocin. Psilacetin (4-AcO-DMT) has long been thought to be an alternative prodrug for psilocin, but direct evidence was lacking. In mice, psilocybin produced 10–25% higher psilocin concentrations than psilacetin at 15 minutes after injection. The half-life of psilocin was about 30 minutes from either prodrug. Overall, psilacetin fumarate yielded about 70% of the psilocin exposure that psilocybin did. These results confirm that psilacetin acts as a psilocin prodrug in vivo and suggest it can be used as a substitute for psilocybin in mechanistic research with mice.
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.
Journal of Pharmacology and Experimental Therapeutics
May 13, 2024
N. Jones, John A. Razidlo, Zarmeen Zahid et al.
1 citation
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