{"id":170,"date":"2023-08-02T16:00:55","date_gmt":"2023-08-02T16:00:55","guid":{"rendered":"https:\/\/wwwtest.pharmacy.wisc.edu\/faculty\/wenthur-lab\/?p=170"},"modified":"2025-06-13T16:03:07","modified_gmt":"2025-06-13T16:03:07","slug":"transient-elevation-of-plasma-glucocorticoids-supports-psilocybin-induced-anxiolysis-in-mice","status":"publish","type":"post","link":"https:\/\/pharmacy.wisc.edu\/faculty\/wenthur-lab\/2023\/08\/02\/transient-elevation-of-plasma-glucocorticoids-supports-psilocybin-induced-anxiolysis-in-mice\/","title":{"rendered":"Transient Elevation of Plasma Glucocorticoids Supports Psilocybin-Induced Anxiolysis in Mice"},"content":{"rendered":"

Abstract<\/h2>\r\nWhile correlations between drug-induced cortisol elevation, self-reported anxiety, and treatment outcomes have been reported for human studies during psilocybin-assisted psychotherapy, the mechanistic relationship between psychedelic-associated alterations in plasma glucocorticoid responses and the time course of anxious responsiveness remains unclear.\r\n\r\nUsing rodents, both time-bound manipulation of glucocorticoid concentrations and assessment of anxiety-like behaviors can be achieved. Here, 3 mg\/kg IP psilocybin was found to have anxiolytic-like effects in C57BL\/6 male mice at 4 h after treatment. These effects were not altered by pretreatment with a 5-HT2A antagonist but were blunted by pretreatment with a glucocorticoid receptor antagonist or suppression of psilocybin-induced corticosterone elevations. Anxiolytic-like effects were also observed at 4 h following treatment with the nonpsychedelic 5-HT2A agonist lisuride at a dose causing a similar increase in plasma glucocorticoids as that seen with psilocybin, as well as following stress-induced (via repeated injection) glucocorticoid release alone. Psilocybin\u2019s anxiolytic-like effects persisted at 7 days following administration. The long-term anxiolytic effects of psilocybin were lost when psilocybin was administered to animals with ongoing chronic elevations in plasma corticosterone concentrations.\r\n\r\nOverall, these experiments indicate that acute, resolvable psilocybin-induced glucocorticoid release drives the postacute anxiolytic-like effects of psilocybin in mice and that its long-term anxiolytic-like effects can be abolished in the presence of chronically elevated plasma glucocorticoid elevations.\r\n\r\n \r\n

Cited by<\/h2>\r\nThis article is cited by 3 publications\r\n
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  1. \r\n
    Krupp, K. T., Yaeger, J. D. W., Ledesma, L. J., Withanage, M. H. H., Gale, J. J., Howe, C. B., Allen, T. J., Sathyanesan, M., Newton, S. S., & Summers, C. H. (2024). Single administration of a psychedelic [(R)-DOI] influences coping strategies to an escapable social stress.\u00a0Neuropharmacology<\/i>,\u00a0252<\/i>, 109949.\u00a0https:\/\/doi.org\/10.1016\/j.neuropharm.2024.109949<\/a><\/div><\/li>\r\n \t
  2. \r\n
    Lerer, E., Botvinnik, A., Shahar, O., Grad, M., Blakolmer, K., Shomron, N., Lotan, A., Lerer, B., & Lifschytz, T. (2024). Effects of psilocybin, psychedelic mushroom extract and 5-hydroxytryptophan on brain immediate early gene expression: Interaction with serotonergic receptor modulators.\u00a0Frontiers in pharmacology<\/i>,\u00a015<\/i>, 1391412.\u00a0https:\/\/doi.org\/10.3389\/fphar.2024.1391412<\/a><\/div><\/li>\r\n \t
  3. \r\n
    Harari, R., Chatterjee, I., Getselter, D., & Elliott, E. (2024). Psilocybin induces acute anxiety and changes in amygdalar phosphopeptides independently from the 5-HT2A receptor.\u00a0iScience<\/i>,\u00a027<\/i>(5), 109686.\u00a0https:\/\/doi.org\/10.1016\/j.isci.2024.109686<\/a><\/div><\/li>\r\n<\/ol>\r\n

    Funding Source<\/h2>\r\n
    \r\n\r\nThis work was supported through funds from the UW-Madison School of Pharmacy, grant funding to C.J.W. from the National Institute of Mental Health (R01MH122742), a fellowship for N.T.J. from the National Institute of General Medical Sciences (T32GM008688), and fellowships for Z.Z. and J.R. from the National Institute of Neurological Disorders and Stroke (T32NS105602).\r\n\r\n<\/div>","protected":false},"excerpt":{"rendered":"Abstract While correlations between drug-induced cortisol elevation, self-reported anxiety, and treatment outcomes have been reported for human studies during psilocybin-assisted psychotherapy, the mechanistic relationship between psychedelic-associated alterations in plasma glucocorticoid responses and the time course …","protected":false},"author":7,"featured_media":171,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[3],"tags":[],"class_list":["post-170","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-feature-publications"],"acf":[],"_links":{"self":[{"href":"https:\/\/pharmacy.wisc.edu\/faculty\/wenthur-lab\/wp-json\/wp\/v2\/posts\/170","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/pharmacy.wisc.edu\/faculty\/wenthur-lab\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/pharmacy.wisc.edu\/faculty\/wenthur-lab\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/pharmacy.wisc.edu\/faculty\/wenthur-lab\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/pharmacy.wisc.edu\/faculty\/wenthur-lab\/wp-json\/wp\/v2\/comments?post=170"}],"version-history":[{"count":1,"href":"https:\/\/pharmacy.wisc.edu\/faculty\/wenthur-lab\/wp-json\/wp\/v2\/posts\/170\/revisions"}],"predecessor-version":[{"id":172,"href":"https:\/\/pharmacy.wisc.edu\/faculty\/wenthur-lab\/wp-json\/wp\/v2\/posts\/170\/revisions\/172"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/pharmacy.wisc.edu\/faculty\/wenthur-lab\/wp-json\/wp\/v2\/media\/171"}],"wp:attachment":[{"href":"https:\/\/pharmacy.wisc.edu\/faculty\/wenthur-lab\/wp-json\/wp\/v2\/media?parent=170"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/pharmacy.wisc.edu\/faculty\/wenthur-lab\/wp-json\/wp\/v2\/categories?post=170"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/pharmacy.wisc.edu\/faculty\/wenthur-lab\/wp-json\/wp\/v2\/tags?post=170"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}