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.
Translational Psychiatry
September 12, 2024
Christopher R. Nicholas, Matthew I Banks, Richard C Lennertz et al.
10 citations
Psilocybin, a serotonergic psychedelic, can relieve symptoms in several psychiatric disorders and improve well-being, but it was unclear whether these benefits arise during the acute experience or depend on later memory of it. In 8 healthy participants, psilocybin (25 mg) was co-administered with the amnestic benzodiazepine midazolam at a dose that allowed a conscious psychedelic experience while partially impairing memory for it. Higher midazolam doses and greater memory impairment tended to associate with lower salience, insight, and well-being from psilocybin. These results suggest memory plays a role in therapeutically relevant behavioral effects of psilocybin.
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.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
August 1, 2024
Christopher G Witowski, Mika R Hess, Nate T Jones et al.
7 citations
A transdermal patch for delivering N,N-dimethyltryptamine (DMT) at low, non-hallucinogenic doses was developed and tested in mice. The patch provided consistent, extended drug release, achieving plasma levels below 60 ng/mL. Compared to intravenous administration, the patch extended DMT's half-life by 20-fold and achieved 77% bioavailability. Female and male mice showed notable differences during IV dosing, but transdermal delivery produced steady levels. A head twitch assay indicated no hallucinogenic effects at these low plasma concentrations. The patch could offer a non-invasive, outpatient treatment option for conditions where high, bolus doses are unnecessary.
Psychedelic medicine (New Rochelle, N.Y.)
September 1, 2024
Zarmeen Zahid, Ziyad W. Sultan, Bryan M Krause et al.
5 citations
In mice, the serotonergic psychedelic DOI, but not ketamine, enhanced neural plasticity and metaplasticity in the hippocampus 24 hours after a single dose. Brain slices from DOI-treated animals showed stronger synaptic responses and short-term potentiation compared to saline-treated controls, with evidence that these effects involve a presynaptic mechanism. Ketamine did not produce similar changes. These findings suggest that the therapeutic benefits of serotonergic psychedelics may be supported by a window of heightened neural plasticity, whereas ketamine's effects may rely on different mechanisms.
bioRxiv (Cold Spring Harbor Laboratory)
June 13, 2024
Christopher R. Nicholas, Matthew I. Banks, Richard C 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.
ACS Pharmacology & Translational Science
September 11, 2025
Noelle Cataldo, John A. Razidlo, Cody J. Wenthur
2 citations
Psilocybin, a serotonergic psychedelic, enhanced fear extinction and improved extinction recall 24 hours later in male mice, regardless of whether they were stress-naïve or had been exposed to acute or chronic stress beforehand. Psilocybin transiently increased the stress hormone corticosterone in stress-naïve mice but not in previously stressed animals. The findings suggest psilocybin can promote fear extinction across different stress backgrounds, supporting its potential therapeutic relevance for disorders like PTSD where prior stress is a key factor.
Scientific Reports
July 21, 2025
Suhjung Janet Lee, Claudia Epland, Noah Kaitz et al.
1 citation
Religious or spiritual self-identity strongly predicts how people with prior psychedelic interests react to art displayed in clinical dosing environments, while natural themes in art appeal broadly across groups. A mixed-methods study surveyed psychedelic society members and a non-psychedelic community group, using multivariate regression and focus groups. Spiritual/religious connectivity was the dominant factor influencing art reactions among psychedelic-interested participants, but this link was weaker in the general community group. Natural elements in art consistently corresponded with positive responses in both groups. The findings suggest that incorporating nature-themed art may help create welcoming settings for diverse populations in psychedelic therapy contexts.
Journal of Pharmacology and Experimental Therapeutics
May 13, 2024
N. Jones, John A. Razidlo, Zarmeen Zahid et al.
1 citation
No Summary
Psychedelics
April 20, 2026
Sophia M. Castillo, Noelle Cataldo, Cody J. Wenthur
Pharmacists perceive treatment costs and legal barriers as significantly greater obstacles for psychedelic-assisted therapy (PAT) than for current major depressive disorder treatments, while ethical barriers are seen as similar. Pharmacists express significantly greater support for prescription use of psychedelics over self-medication for depression in scenarios including post-suicide attempt, suicide prophylaxis, and after failing two or more antidepressants, as well as in elderly, incarcerated, active-duty military, and veteran populations. Overall, pharmacists view PAT as a helpful addition to existing depression treatments.
Bioorganic & medicinal chemistry
January 17, 2026
Uriel Matthew Enriquez, Natalie M González Velázquez, Mohammad Mosharraf Hossain et al.
Monoclonal antibodies were developed that specifically recognize (2R,6R)-hydroxynorketamine, a metabolite of ketamine linked to rapid antidepressant effects. An immunogenic bioconjugate was designed by attaching a 6-aminohexanoic acid linker to the pharmacophore and coupling it to a carrier protein. Mice immunized with this conjugate produced equivalent antibody titers to a racemic comparator. Hybridoma screening yielded the monoclonal antibody 6F11-HC1-LC2, which showed strong binding to (2R,6R)-hydroxynorketamine but no response to the (2S,6S) enantiomer in competitive ELISA. Surface plasmon resonance revealed sub-nanomolar affinity (0.4 nM) for (2R,6R)-hydroxynorketamine-BSA conjugates and over 150-fold selectivity over ketamine-BSA conjugates. These antibodies can be used in future studies to investigate the roles of hydroxynorketamine enantiomers in ketamine's antidepressant effects.
bioRxiv : the preprint server for biology
September 30, 2025
Ya'El Courtney, Josephine M Anderson, Christian Lagares-Linares et al.
preprint
In mice, the psychedelic drug LSD crosses the placenta and enters embryonic cerebrospinal fluid within minutes. A single dose during pregnancy alters the organization of the cerebral cortex in the offspring, and repeated doses shift the balance of neuron types and increase microglia. Adult offspring, especially males, show reduced prepulse inhibition and rotational stereotypy. These findings identify a mechanism by which maternal psychedelic exposure can lead to lasting changes in brain development and behavior.
bioRxiv (Cold Spring Harbor Laboratory)
July 29, 2025
May Kung Sutherland, Christopher R. Nicholas, Richard C 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.
Translational Psychiatry
February 14, 2026
Michael H Sutherland, Christopher R. Nicholas, Richard C Lennertz et al.
Psilocybin, a serotonergic psychedelic, induces neural plasticity and alters consciousness, while midazolam, a benzodiazepine, blunts plasticity and induces sedation. 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 blunted memory. Electroencephalography (EEG) data showed that 15–30 minutes after dosing, when midazolam was at its target concentration, beta power increased and spectral exponent decreased. As psilocybin's effects emerged over the next six hours, Lempel-Ziv complexity and spectral exponent increased, while broadband power decreased, especially in delta, theta, and alpha bands. The findings suggest psilocybin's effects persist with midazolam, supporting its use in mechanistic studies.