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  1. Article ; Online: Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression: results from an exploratory placebo-controlled trial.

    Sloshower, Jordan / Zeifman, Richard J / Guss, Jeffrey / Krause, Robert / Safi-Aghdam, Hamideh / Pathania, Surbhi / Pittman, Brian / D'Souza, Deepak Cyril

    Scientific reports

    2024  Volume 14, Issue 1, Page(s) 8833

    Abstract: Several phase II studies have demonstrated that psilocybin-assisted therapy shows therapeutic potential across a spectrum of neuropsychiatric conditions, including major depressive disorder (MDD). However, the mechanisms underlying its often persisting ... ...

    Abstract Several phase II studies have demonstrated that psilocybin-assisted therapy shows therapeutic potential across a spectrum of neuropsychiatric conditions, including major depressive disorder (MDD). However, the mechanisms underlying its often persisting beneficial effects remain unclear. Observational research suggests that improvements in psychological flexibility may mediate therapeutic effects. However, no psychedelic trials to date have substantiated this finding in a clinical sample. In an exploratory placebo-controlled, within-subject, fixed-order study, individuals with moderate to severe MDD were administered placebo (n = 19) followed by psilocybin (0.3 mg/kg) (n = 15) 4 weeks later. Dosing sessions were embedded within a manualized psychotherapy that incorporated principles of Acceptance and Commitment Therapy. Depression severity, psychological flexibility, mindfulness, and values-congruent living were measured over a 16-weeks study period. Psychological flexibility, several facets of mindfulness, and values-congruent living significantly improved following psilocybin and were maintained through week 16. Additionally, improvements in psychological flexibility and experiential acceptance were strongly associated with reductions in depression severity following psilocybin. These findings support the theoretical premise of integrating psilocybin treatment with psychotherapeutic platforms that target psychological flexibility and add to emerging evidence that increasing psychological flexibility may be an important putative mechanism of change in psilocybin-assisted therapy for MDD and potentially, other mental health conditions.
    MeSH term(s) Humans ; Psilocybin ; Depressive Disorder, Major/drug therapy ; Depression/drug therapy ; Acceptance and Commitment Therapy ; Hallucinogens
    Chemical Substances Psilocybin (2RV7212BP0) ; Hallucinogens
    Language English
    Publishing date 2024-04-17
    Publishing country England
    Document type Randomized Controlled Trial ; Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-024-58318-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Psilocybin-assisted therapy for major depressive disorder: An exploratory placebo-controlled, fixed-order trial.

    Sloshower, Jordan / Skosnik, Patrick D / Safi-Aghdam, Hamideh / Pathania, Surbhi / Syed, Shariful / Pittman, Brian / D'Souza, Deepak Cyril

    Journal of psychopharmacology (Oxford, England)

    2023  Volume 37, Issue 7, Page(s) 698–706

    Abstract: Background: Several early phase studies have demonstrated that psilocybin-assisted therapy has rapid-acting and persisting antidepressant effects from just one or two doses. However, methodological limitations (e.g., placebo-control, blinding) limit ... ...

    Abstract Background: Several early phase studies have demonstrated that psilocybin-assisted therapy has rapid-acting and persisting antidepressant effects from just one or two doses. However, methodological limitations (e.g., placebo-control, blinding) limit interpretability of the existing literature.
    Methods: In an exploratory placebo-controlled, within-subject, fixed-order study, individuals with moderate to severe major depressive disorder were administered placebo (
    Results: Depression and anxiety significantly improved following both placebo and psilocybin with no significant difference in the degree of change between the two conditions. However, antidepressant effect sizes were larger after psilocybin (
    Conclusions: The results of this exploratory study highlight the complex interplay between expectancy, therapy effects, and drug/placebo effects in psychedelic-assisted psychotherapy studies. Nonetheless, the acute and persisting clinical improvements observed following psilocybin support further study of its potential in the treatment of major depression. Future studies should more explicitly mitigate and measure expectancy effects and assess the impact of repeated dosing and different forms of psychotherapeutic support.
    MeSH term(s) Humans ; Antidepressive Agents/pharmacology ; Antidepressive Agents/therapeutic use ; Depressive Disorder, Major/drug therapy ; Hallucinogens/pharmacology ; Hallucinogens/therapeutic use ; Psilocybin/pharmacology ; Psilocybin/therapeutic use ; Quality of Life
    Chemical Substances Antidepressive Agents ; Hallucinogens ; Psilocybin (2RV7212BP0)
    Language English
    Publishing date 2023-03-20
    Publishing country United States
    Document type Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639313-5
    ISSN 1461-7285 ; 0269-8811
    ISSN (online) 1461-7285
    ISSN 0269-8811
    DOI 10.1177/02698811231154852
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Sub-acute effects of psilocybin on EEG correlates of neural plasticity in major depression: Relationship to symptoms.

    Skosnik, Patrick D / Sloshower, Jordan / Safi-Aghdam, Hamideh / Pathania, Surbhi / Syed, Shariful / Pittman, Brian / D'Souza, Deepak C

    Journal of psychopharmacology (Oxford, England)

    2023  Volume 37, Issue 7, Page(s) 687–697

    Abstract: Background: Evidence suggests that serotonergic psychedelics (e.g. psilocybin), have rapid-acting and long-lasting antidepressant effects after a single dose. However, the mechanism underlying these effects remain unclear. One proposed mechanism is that ...

    Abstract Background: Evidence suggests that serotonergic psychedelics (e.g. psilocybin), have rapid-acting and long-lasting antidepressant effects after a single dose. However, the mechanism underlying these effects remain unclear. One proposed mechanism is that these drugs promote neuroplasticity. However, this has not been conclusively demonstrated in humans.
    Aims: We hypothesized that relative to placebo, psilocybin would: (1) increase electroencephalographic (EEG) correlates of neuroplasticity, (2) reduce depression symptoms, and (3) changes in EEG would correlate with improvements in depression.
    Methods: In this double-blind, placebo-controlled, within-subject study, individuals with major depressive disorder (MDD;
    Results: EEG theta power doubled in amplitude 2 weeks after a single psychedelic dose of psilocybin but not after placebo. Further, improvements in depression symptoms 2 weeks after psilocybin were correlated with increases in theta power.
    Conclusions: The increased theta power observed represents evidence of sustained changes in the brain following psilocybin. Given the correlation with enhancement in depressive symptoms, changes in theta may represent an EEG biomarker of the sustained effects of psilocybin, and may shed light on potential mechanisms of psilocybin's antidepressant effect. Taken together, these results complement the emerging notion that psilocybin, and perhaps other psychedelics, can produce long-term alterations in neuroplasticity.
    MeSH term(s) Humans ; Psilocybin/pharmacology ; Psilocybin/therapeutic use ; Depressive Disorder, Major/drug therapy ; Hallucinogens/pharmacology ; Hallucinogens/therapeutic use ; Depression ; Electroencephalography ; Antidepressive Agents/therapeutic use ; Neuronal Plasticity
    Chemical Substances Psilocybin (2RV7212BP0) ; Hallucinogens ; Antidepressive Agents
    Language English
    Publishing date 2023-06-30
    Publishing country United States
    Document type Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639313-5
    ISSN 1461-7285 ; 0269-8811
    ISSN (online) 1461-7285
    ISSN 0269-8811
    DOI 10.1177/02698811231179800
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Analysis of circulating exosomes reveals a peripheral signature of astrocytic pathology in schizophrenia.

    Ranganathan, Mohini / Rahman, Mohamed / Ganesh, Suhas / D'Souza, Deepak C / Skosnik, Patrick D / Radhakrishnan, Rajiv / Pathania, Surbhi / Mohanakumar, Thalachallour

    The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry

    2021  Volume 23, Issue 1, Page(s) 33–45

    Abstract: Objectives: Extracellular vesicles, including exosomes, cross the blood brain barrier with their contents intact and can be assayed peripherally. Circulating exosomes have been studied in other neurodegenerative disorders, but there is scarce data in ... ...

    Abstract Objectives: Extracellular vesicles, including exosomes, cross the blood brain barrier with their contents intact and can be assayed peripherally. Circulating exosomes have been studied in other neurodegenerative disorders, but there is scarce data in schizophrenia. This study aimed to examine neuropathology-relevant protein biomarkers in circulating plasma-derived exosomes from patients with schizophrenia and age- and sex-matched healthy controls.
    Methods: Nanoparticle tracking analysis was used to determine the size and concentration of exosomes. Exosomal membrane marker (CD9) and specific target cargo protein (glial fibrillary acid protein[GFAP], synaptophysin, and α-II-Spectrin) immunopositivity was examined using Western blot analyses with band intensity quantified. Methods were consistent with the 'Minimal information for studies of extracellular vesicles 2018' (MISEV2018) guidelines.
    Results: Exosomal GFAP concentration was significantly higher and α-II-Spectrin expression significantly lower in plasma obtained from schizophrenia patients. No group differences were observed between in plasma exosomal concentration and size or in CD9, calnexin, or synaptophysin levels.
    Conclusions: Our results demonstrate a differential pattern of exosomal protein expression in schizophrenia compared to matched healthy controls, consistent with the hypothesised astroglial pathology in this disorder. These results warrant further examination of circulating exosomes as vehicles of novel peripheral biomarkers of disease in schizophrenia and other neuropsychiatric disorders.
    MeSH term(s) Astrocytes ; Biomarkers ; Exosomes ; Humans ; Proteomics ; Schizophrenia
    Chemical Substances Biomarkers
    Language English
    Publishing date 2021-04-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2051402-5
    ISSN 1814-1412 ; 1562-2975
    ISSN (online) 1814-1412
    ISSN 1562-2975
    DOI 10.1080/15622975.2021.1907720
    Database MEDical Literature Analysis and Retrieval System OnLINE

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