Psilocybin induces acute and persisting alterations in immune status in healthy volunteers: An experimental, placebo-controlled study

Mason, N.L.; Szabo, A.; Kuypers, K.P.C.; Mallaroni, P.A.; de la Torre Fornell, R.; Reckweg, J.T.; Tse, D.H.Y.; Hutten, N.R.P.W.; Feilding, A.; Ramaekers, J.G.

doi:10.1016/j.bbi.2023.09.004

Cited by 19 publications

(10 citation statements)

References 98 publications

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“…However, the levels of IL-6 and CRP remain reduced, suggesting a long-term antiinflammatory effect. This persistent reduction correlates with sustained improvements in mood and prosocial behavior [20].…”

Section: Anti-inflammatory Effectmentioning

confidence: 82%

“…This inflammation is characterized by elevated levels of pro-inflammatory cytokines like IL-1α, IL-1β, IL-6, and TNF-α, along with acute-phase proteins such as C-reactive protein (CRP). These markers are not only elevated due to psychosocial stressors but also play a role in the onset and maintenance of depressive disorders [2,20].…”

Section: Anti-inflammatory Effectmentioning

confidence: 99%

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Psilocybin Therapy for Depression: A Review of Current Molecular Knowledge

Verheijen

2024

Journal of the Netherlands Society of Toxicology

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Depression, affecting over 264 million people globally, presents significant treatment challenges, often due to the limited efficacy and adverse effects of traditional antidepressants and the accessibility issues associated with psychotherapy. Recent advancements in psychedelic-assisted therapy, particularly using psilocybin, a naturally occurring compound found in “magic mushrooms”, shows promising potential for treating major depressive disorder (MDD) and treatment-resistant depression (TRD). This review explores the historical context, clinical trial outcomes, and the biological mechanisms underlying psilocybin’s effects. Clinical studies from 2016 to 2023 indicate that psilocybin, in combination with psychological support, significantly reduces depressive symptoms, with benefits lasting up to several months after a single dose treatment. The molecular action of psilocybin involves its conversion to psilocin, which interacts with serotonin receptors, notably the 5-HT2A receptor, influencing neurotransmitter systems and promoting anti-inflammatory responses and neuroplasticity. The review also discusses the safety profile of psilocybin, highlighting its low risk for dependency and minimal adverse effects compared to traditional treatments. Finally, the therapeutic advantages of psilocybin over conventional antidepressants are evaluated, emphasizing its rapid and sustained antidepressant effects, which contribute to its potential as a groundbreaking treatment for depression.

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Section: Anti-inflammatory Effectmentioning

confidence: 82%

Section: Anti-inflammatory Effectmentioning

confidence: 99%

Psilocybin Therapy for Depression: A Review of Current Molecular Knowledge

Verheijen

2024

Journal of the Netherlands Society of Toxicology

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“…Acute administration of psilocybin has anxiolytic effects in humans [ 58 , 59 ]. We thus tested whether acute stress exposure changes fish’s swim patterns in our setup and whether psilocybin can prevent such stress-induced behavioral changes.…”

Section: Resultsmentioning

confidence: 99%

High-resolution tracking of unconfined zebrafish behavior reveals stimulatory and anxiolytic effects of psilocybin

Braun,

Rosenberg,

Rabaniam

et al. 2024

Mol Psychiatry

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Serotonergic psychedelics are emerging therapeutics for psychiatric disorders, yet their underlying mechanisms of action in the brain remain largely elusive. Here, we developed a wide-field behavioral tracking system for larval zebrafish and investigated the effects of psilocybin, a psychedelic serotonin receptor agonist. Machine learning analyses of precise body kinematics identified latent behavioral states reflecting spontaneous exploration, visually-driven rapid swimming, and irregular swim patterns following stress exposure. Using this method, we found that acute psilocybin treatment has two behavioral effects: [i] facilitation of spontaneous exploration (“stimulatory”) and [ii] prevention of irregular swim patterns following stress exposure (“anxiolytic”). These effects differed from the effect of acute SSRI treatment and were rather similar to the effect of ketamine treatment. Neural activity imaging in the dorsal raphe nucleus suggested that psilocybin inhibits serotonergic neurons by activating local GABAergic neurons, consistent with psychedelic-induced suppression of serotonergic neurons in mammals. These findings pave the way for using larval zebrafish to elucidate neural mechanisms underlying the behavioral effects of serotonergic psychedelics.

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“…A few clinical investigations have explored inflammatory biomarkers after exposure to psychedelic substances through the analysis of peripheral fluids, yielding heterogeneous findings. 126 , 127 , 128 , 129 , 130 To date, there is not enough clinical evidence to support the intrinsic role of psychedelics as anti-inflammatory agents. By contrast, animal models of inflammatory diseases and cultured rat aortic smooth muscle cells have shown that tumor necrosis factor-α (TNF-α)-induced secretion of pro-inflammatory cytokines, adhesion molecules, and the nuclear translocation of the nuclear factor κB (NF-κB) are all prevented by 5-HT2AR activation following DOI exposure.…”

Section: What Do Psc-derived Brain Cells Bring To Psychedelic Studies?mentioning

confidence: 99%

Human pluripotent stem cells as a translational toolkit in psychedelic research in vitro

Salerno,

Rehen

2024

iScience

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Psilocybin induces acute and persisting alterations in immune status in healthy volunteers: An experimental, placebo-controlled study

Cited by 19 publications

References 98 publications

Psilocybin Therapy for Depression: A Review of Current Molecular Knowledge

Psilocybin Therapy for Depression: A Review of Current Molecular Knowledge

High-resolution tracking of unconfined zebrafish behavior reveals stimulatory and anxiolytic effects of psilocybin

Human pluripotent stem cells as a translational toolkit in psychedelic research in vitro

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