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Journal articleZeifman RJ, Wagner AC, Monson CM, et al., 2023,
How does psilocybin therapy work? An exploration of experiential avoidance as a putative mechanism of change
, JOURNAL OF AFFECTIVE DISORDERS, Vol: 334, Pages: 100-112, ISSN: 0165-0327 -
Journal articleWall MB, Lam C, Ertl N, et al., 2023,
Increased low-frequency brain responses to music after psilocybin therapy for depression
, JOURNAL OF AFFECTIVE DISORDERS, Vol: 333, Pages: 321-330, ISSN: 0165-0327- Author Web Link
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- Citations: 2
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Journal articleWeiss B, Erritzoe D, Giribaldi B, et al., 2023,
A critical evaluation of QIDS-SR-16 using data from a trial of psilocybin therapy versus escitalopram treatment for depression
, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 37, Pages: 717-732, ISSN: 0269-8811- Author Web Link
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- Citations: 2
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Journal articleSingleton SP, Timmermann C, Luppi AI, et al., 2023,
Time-resolved network control analysis links reduced control energy under DMT with the serotonin 2a receptor, signal diversity, and subjective experience.
, bioRxivPsychedelics offer a profound window into the functioning of the human brain and mind through their robust acute effects on perception, subjective experience, and brain activity patterns. In recent work using a receptor-informed network control theory framework, we demonstrated that the serotonergic psychedelics lysergic acid diethylamide (LSD) and psilocybin flatten the brain's control energy landscape in a manner that covaries with more dynamic and entropic brain activity. Contrary to LSD and psilocybin, whose effects last for hours, the serotonergic psychedelic N,N-dimethyltryptamine (DMT) rapidly induces a profoundly immersive altered state of consciousness lasting less than 20 minutes, allowing for the entirety of the drug experience to be captured during a single resting-state fMRI scan. Using network control theory, which quantifies the amount of input necessary to drive transitions between functional brain states, we integrate brain structure and function to map the energy trajectories of 14 individuals undergoing fMRI during DMT and placebo. Consistent with previous work, we find that global control energy is reduced following injection with DMT compared to placebo. We additionally show longitudinal trajectories of global control energy correlate with longitudinal trajectories of EEG signal diversity (a measure of entropy) and subjective ratings of drug intensity. We interrogate these same relationships on a regional level and find that the spatial patterns of DMT's effects on these metrics are correlated with serotonin 2a receptor density (obtained from separately acquired PET data). Using receptor distribution and pharmacokinetic information, we were able to successfully recapitulate the effects of DMT on global control energy trajectories, demonstrating a proof-of-concept for the use of control models in predicting pharmacological intervention effects on brain dynamics.
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Journal articleNayak SM, Bari BA, Yaden DB, et al., 2023,
A Bayesian Reanalysis of a Trial of Psilocybin versus Escitalopram for Depression.
, Psychedelic Med (New Rochelle), Vol: 1, Pages: 18-26OBJECTIVES: To perform a Bayesian reanalysis of a recent trial of psilocybin (COMP360) versus escitalopram for Major Depressive Disorder (MDD) in order to provide a more informative interpretation of the indeterminate outcome of a previous frequentist analysis. DESIGN: Reanalysis of a two-arm double-blind placebo controlled trial. PARTICIPANTS: Fifty-nine patients with MDD. INTERVENTIONS: Two doses of psilocybin 25mg and daily oral placebo versus daily escitalopram and 2 doses of psilocybin 1mg, with psychological support for both groups. OUTCOME MEASURES: Quick Inventory of Depressive Symptomatology-Self-Report (QIDS SR-16), and three other depression scales as secondary outcomes: HAMD-17, MADRS, and BDI-1A. RESULTS: Using Bayes factors and 'skeptical priors' which bias estimates towards zero, for the hypothesis that psilocybin is superior by any margin, we found indeterminate evidence for QIDS SR-16, strong evidence for BDI-1A and MADRS, and extremely strong evidence for HAMD-17. For the stronger hypothesis that psilocybin is superior by a 'clinically meaningful amount' (using literature defined values of the minimally clinically important difference), we found moderate evidence against it for QIDS SR-16, indeterminate evidence for BDI-1A and MADRS, and moderate evidence supporting it for HAMD-17. Furthermore, across the board we found extremely strong evidence for psilocybin's non-inferiority versus escitalopram. These findings were robust to prior sensitivity analysis. CONCLUSIONS: This Bayesian reanalysis supports the following inferences: 1) that psilocybin did indeed outperform escitalopram in this trial, but not to an extent that was clinically meaningful--and 2) that psilocybin is almost certainly non-inferior to escitalopram. The present results provide a more precise and nuanced interpretation to previously reported results from this trial, and support the need for further research into the relative efficacy of psilocybin therapy for depression with respe
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Journal articleForstmann M, Kettner HS, Sagioglou C, et al., 2023,
Among psychedelic-experienced users, only past use of psilocybin reliably predicts nature relatedness
, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 37, Pages: 93-106, ISSN: 0269-8811- Author Web Link
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- Citations: 1
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Journal articleShukuroglou M, Roseman L, Wall M, et al., 2023,
Changes in music-evoked emotion and ventral striatal functional connectivity after psilocybin therapy for depression
, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 37, Pages: 70-79, ISSN: 0269-8811- Author Web Link
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- Citations: 2
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Journal articleDouglass H, Spriggs M, Godfrey K, et al., 2023,
Psilocybin as a treatment for anorexia nervosa: 6-week and 3-month follow-up results
, Neuroscience Applied, Vol: 2, Pages: 102878-102878, ISSN: 2772-4085 -
Journal articleSpriggs MJ, Giribaldi B, Lyons T, et al., 2022,
Body mass index (BMI) does not predict responses to psilocybin
, Journal of Clinical Psychopharmacology, Vol: 37, Pages: 107-116, ISSN: 0271-0749Background:Psilocybin is a serotonin type 2A (5-HT2A) receptor agonist and naturally occurring psychedelic. 5-HT2A receptor density is known to be associated with body mass index (BMI), however, the impact of this on psilocybin therapy has not been explored. While body weight-adjusted dosing is widely used, this imposes a practical and financial strain on the scalability of psychedelic therapy. This gap between evidence and practice is caused by the absence of studies clarifying the relationship between BMI, the acute psychedelic experience and long-term psychological outcomes.Method:Data were pooled across three studies using a fixed 25 mg dose of psilocybin delivered in a therapeutic context to assess whether BMI predicts characteristics of the acute experience and changes in well-being 2 weeks later. Supplementing frequentist analysis with Bayes Factors has enabled for conclusions to be drawn regarding the null hypothesis.Results:Results support the null hypothesis that BMI does not predict overall intensity of the altered state, mystical experiences, perceptual changes or emotional breakthroughs during the acute experience. There was weak evidence for greater ‘dread of ego dissolution’ in participants with lower BMI, however, further analysis suggested BMI did not meaningfully add to the combination of the other covariates (age, sex and study). While mystical-type experiences and emotional breakthroughs were strong predictors of improvements in well-being, BMI was not.Conclusions:These findings have important implications for our understanding of pharmacological and extra-pharmacological contributors to psychedelic-assisted therapy and for the standardization of a fixed therapeutic dose in psychedelic-assisted therapy.
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Journal articleGoodwin GM, Aaronson ST, Alvarez O, et al., 2022,
Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression.
, N Engl J Med, Vol: 387, Pages: 1637-1648BACKGROUND: Psilocybin is being studied for use in treatment-resistant depression. METHODS: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits). RESULTS: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P<0.001) and between the 10-mg group and 1-mg group was -2.5 (95% CI, -6.2 to 1.2; P = 0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups. CONCLUSIONS: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including compariso
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