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Working paperZeifman R, Spriggs M, Kettner H, et al., 2022,
From Relaxed Beliefs Under Psychedelics (REBUS) to Revised Beliefs After Psychedelics (REBAS): preliminary development of the RElaxed Beliefs Questionnaire (REB-Q)
, Publisher: PsyArXivBackground: The Relaxed Beliefs Under pSychedelics (REBUS) model proposes that serotonergic psychedelics decrease the precision weighting of neurobiologically-encoded beliefs, and offers a unified account of the acute and therapeutic action of psychedelics. Although REBUS has received some neuroscientific support, little research has examined its psychological validity. We conducted a preliminary examination of two psychological assumptions of REBUS: (a) psychedelics foster acute relaxation and post-acute revision of confidence in mental-health-relevant beliefs; (b) this relaxation and revision facilitates positive therapeutic outcomes and is associated with the entropy of EEG signals (an index of neurophysiological mechanisms relevant to REBUS). Method: Healthy individuals (N=11) were administered 1 mg and 25 mg psilocybin 4-weeks apart. Confidence ratings for personally held negative and positive beliefs were obtained before, during, and 4-weeks after dosing sessions. Acute entropy and self-reported subjective experiences were measured, as was well-being (before and 4-weeks after dosing sessions). Results: Confidence in negative self-beliefs decreased following 25 mg psilocybin and not following 1 mg psilocybin. Entropy and subjective effects under 25 mg psilocybin correlated with decreases in negative self-belief confidence (acute and 4-weeks after dosing). Particularly strong evidence was seen for a relationship between decreases in negative self-belief confidence and increases in well-being at 4-weeks. Conclusions: We report the first empirical evidence that the relaxation and revision of negative self-belief confidence mediates positive psychological outcomes; a psychological assumption of REBUS. Replication within larger and clinical samples remains necessary. We also introduce a new measure, the Relaxed BEliefs Questionnaire (REB-Q), for examining the robustness of these preliminary findings and the utility of the REBUS model.
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Journal articleNayak SM, Bari BA, Yaden DB, et al., 2022,
A Bayesian Reanalysis of a Trial of Psilocybin versus Escitalopram for Depression
<p>Objectives: 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
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Journal articleCarhart-Harris R, Daws RE, Nutt D, 2022,
A critique of: Skepticism About Recent Evidence that Psilocybin Opens Depressed Minds
<p>This document details an authors' response to a critique of their work entitled: Skepticism About Recent Evidence that Psilocybin Opens Depressed Minds.</p>
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Journal articleDaws R, Timmermann C, Giribaldi B, et al., 2022,
Increased global integration in the brain after psilocybin therapy for depression
, Nature Medicine, Vol: 28, ISSN: 1078-8956Psilocybin therapy shows antidepressant potential, but its therapeutic actions are not well understood. We assessed the sub-acute impact of psilocybin on brain function in two clinical trials of depression. The first was an open-label trial of orally administered psilocybin (10mg and 25mg, 7 days apart) in treatment-resistant depression (TRD). fMRI was recorded at baseline and one day after the 25mg dose. Beck’s depression inventory (BDI) was the primary outcome measure (MR/J00460X/1). The second trial was a double-blind phase 2 randomised control trial (DB-RCT) comparing psilocybin therapy with escitalopram. Major depressive disorder (MDD) patients received either: 2 x 25mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily placebo (‘psilocybin-arm’); or 2 x 1mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily escitalopram [10-20mg] (‘escitalopram-arm’). fMRI wasrecorded at baseline and 3 weeks after the 2nd psilocybin dose (NCT03429075). In both trials, the antidepressant response to psilocybin was rapid, sustained and correlated with decreases in functional MRI (fMRI) brain network modularity, implying that psilocybin’s antidepressant action may depend on a global increase in brainnetwork integration. Network cartography analyses indicated that 5-HT2A receptor rich higher-order functional networks became more functionally inter-connected and flexible post psilocybin. The antidepressant response to escitalopram was milder and no changes in brain network organisation were observed. Consistent efficacy related brain changes, correlating with robust antidepressant effects across two studies, suggest an antidepressant mechanism for psilocybin therapy: Global increases in brain network integration.
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Journal articleDaws RE, Carhart-Harris R, 2022,
Psilocybin increases brain network integration in patients with depression
, NATURE MEDICINE, Vol: 28, Pages: 647-648, ISSN: 1078-8956- Cite
- Citations: 2
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Journal articleMurphy R, Kettner HS, Zeifman R, et al., 2022,
Therapeutic alliance and rapport modulate responses to psilocybin assisted therapy for depression
, Frontiers in Pharmacology, Vol: 12, Pages: 1-19, ISSN: 1663-9812Background: Across psychotherapeutic frameworks, the strength of the therapeutic alliance has been found to correlate with treatment outcomes; however, its role has never been formally assessed in a trial of psychedelic-assisted therapy. We aimed to investigate the relationships between therapeutic alliance and rapport, the quality of the acute psychedelic experience and treatment outcomes. Methods: This 2-arm double-blind randomized controlled trial compared escitalopram with psychedelic-assisted therapy for moderate-severe depressive disorder (N=59). This analysis focused on the psilocybin condition (n=30), who received two oral doses of 25 mg psilocybin, three-weeks apart, with psychological preparation, in-session support, and integration therapy. A new psychedelic therapy model, called ‘Accept-Connect-Embody’ (ACE), was developed in this trial. The primary outcome was depression severity six weeks post treatment (Quick Inventory of Depressive Symptomatology, QIDS-SR-16). Path analyses tested the hypothesis that therapeutic alliance (Scale To Assess the Therapeutic Relationship Patient Version, STAR-P) would predict depression outcomes via its influence on the acute psychedelic experience, specifically emotional-breakthrough (EBI) and mystical-type experiences (MEQ). The same analysis was performed on the escitalopram arm to test specificity. Results: The strength of therapeutic alliance predicted pre-session rapport, greater emotional-breakthrough and mystical-type experience (maximum EBI and MEQ scores across the two psilocybin sessions) and final QIDS scores (β = -0.22, R2 = 0.42 for EBIMax; β = -0.19, R2 = 0.32 for MEQMax). Exploratory path models revealed that final depression outcomes were more strongly affected by emotional breakthrough during the first, and mystical experience during the second session. Emotional breakthrough, but not mystical experience, during the first session had a positive effect on therapeutic alliance ahead o
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Journal articleWall MB, Lam C, Ertl N, et al., 2022,
Increased low-frequency brain responses to music after psilocybin therapy for depression
<jats:title>Abstract</jats:title> <jats:p>Psychedelic-assisted psychotherapy with psilocybin is an emerging therapy with great promise for depression, and modern psychedelic therapy (PT) methods incorporate music as a key element. Music is an effective emotional/hedonic stimulus that could also be useful in assessing changes in emotional responsiveness following psychedelic therapy. Brain responses to music were assessed before and after PT using functional Magnetic Resonance Imaging (fMRI) and ALFF (Amplitude of Low Frequency Fluctuations) analysis methods. Nineteen patients with treatment-resistant depression underwent two treatment sessions involving administration of psilocybin, with MRI data acquired one week prior and the day after completion of the second of two psilocybin dosing sessions. Comparison of music-listening and resting-state scans revealed significantly greater ALFF in bilateral superior temporal cortex for the post-treatment music scan, and in the right ventral occipital lobe for the post-treatment resting-state scan. ROI analyses of these clusters revealed a significant effect of treatment in the superior temporal lobe for the music scan only. Somewhat consistently, voxelwise comparison of treatment effects showed relative increases for the music scan in the bilateral superior temporal lobes and supramarginal gyrus, and relative decreases in the medial frontal lobes for the resting-state scan. ALFF in these music-related clusters was significantly correlated with intensity of subjective effects felt during the dosing sessions. These data suggest a specific effect of PT on the brain’s response to a hedonic stimulus (music), implying an elevated responsiveness to music after psilocybin therapy that was related to subjective drug effects felt during dosing.</jats:p>
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Conference paperStenbaek D, Madsen MK, Armand S, et al., 2021,
Psilocybin enhances emotional response to music in healthy individuals
, 34th European-College-of-Neuropsychopharmacology (ECNP) Congress on Early Career Scientists in Europe, Publisher: ELSEVIER, Pages: S604-S605, ISSN: 0924-977X -
Conference paperDouglass H, Spriggs MJ, Park RJ, et al., 2021,
Study protocol: psilocybin as a treatment for anorexia nervosa: a pilot study
, 34th European-College-of-Neuropsychopharmacology (ECNP) Congress on Early Career Scientists in Europe, Publisher: ELSEVIER, Pages: S257-S258, ISSN: 0924-977X -
Conference paperWall M, Lam C, Ertl N, et al., 2021,
The effect of psilocybin therapy for depression on low-frequency brain activity in response to music
, 34th European-College-of-Neuropsychopharmacology (ECNP) Congress on Early Career Scientists in Europe, Publisher: ELSEVIER, Pages: S649-S649, ISSN: 0924-977X
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