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Journal articleRoseman L, Nutt DJ, Carhart-Harris RL, 2018,
Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression
, Frontiers in Pharmacology, Vol: 8, ISSN: 1663-9812Introduction: It is a basic principle of the ‘psychedelic’ treatment model that the quality of the acute experience mediateslong-term improvements in mental health. In the present paper we sought to test this using data from a clinical trial assessingpsilocybin for treatment-resistant depression (TRD). In line with previous reports, we hypothesized that the occurrence andmagnitude of Oceanic Boundlessness (OBN) (sharing features with mystical-type experience) and Dread of Ego Dissolution (DED)(similar to anxiety) would predict long-term positive outcomes, whereas sensory perceptual effects would not.Material and Methods: Twenty patients with treatment resistant depression underwent treatment with psilocybin (two separatesessions: 10mg and 25mg psilocybin). The Altered States of Consciousness (ASC) questionnaire was used to assess the quality ofexperiences in the 25mg psilocybin session. From the ASC, the dimensions OBN and DED were used to measure the mystical-typeand challenging experiences, respectively. The Self-Reported Quick Inventory of Depressive Symptoms (QIDS-SR) at 5 weeks servedas the endpoint clinical outcome measure, as in later time points some of the subjects had gone on to receive new treatments,thus confounding inferences. In a repeated measure ANOVA, Time was the within-subject factor (independent variable), withQIDS-SR as the within-subject dependent variable in baseline, 1-day, 1-week, 5-weeks. OBN and DED were independent variables.OBN-by-time and DED-by-time interactions were the primary outcomes of interest.Results: For the interaction of OBN and DED with Time (QIDS-SR as dependent variable), the main effect and the effects at each timepoint compared to baseline were all significant (p = 0.002 and p = 0.003, respectively, for main effects), confirming our mainhypothesis. Furthermore, Pearson’s correlation of OBN with QIDS-SR (5 weeks) was specific compared to perceptual dimensions ofthe ASC (p < 0.05).Discussion: This repo
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Book chapterAtasoy S, Vohryzek J, Deco G, et al., 2018,
Common neural signatures of psychedelics: Frequency-specific energy changes and repertoire expansion revealed using connectome-harmonic decomposition.
, Pages: 97-120The search for the universal laws of human brain function is still on-going but progress is being made. Here we describe the novel concepts of connectome harmonics and connectome-harmonic decomposition, which can be used to characterize the brain activity associated with any mental state. We use this new frequency-specific language to describe the brain activity elicited by psilocybin and LSD and find remarkably similar effects in terms of increases in total energy and power, as well as frequency-specific energy changes and repertoire expansion. In addition, we find enhanced signatures of criticality suggesting that the brain dynamics tune toward criticality in both psychedelic elicited states. Overall, our findings provide new evidence for the remarkable ability of psychedelics to change the spatiotemporal dynamics of the human brain.
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Journal articleCarhart-Harris RL, Bolstridge M, Day CMJ, et al., 2017,
Psilocybin with psychological support for treatment-resistant depression: six-month follow-up
, Psychopharmacology, Vol: 235, Pages: 399-408, ISSN: 0033-3158RATIONALE: Recent clinical trials are reporting marked improvements in mental health outcomes with psychedelic drug-assisted psychotherapy. OBJECTIVES: Here, we report on safety and efficacy outcomes for up to 6 months in an open-label trial of psilocybin for treatment-resistant depression. METHODS: Twenty patients (six females) with (mostly) severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 and 25 mg, 7 days apart) in a supportive setting. Depressive symptoms were assessed from 1 week to 6 months post-treatment, with the self-rated QIDS-SR16 as the primary outcome measure. RESULTS: Treatment was generally well tolerated. Relative to baseline, marked reductions in depressive symptoms were observed for the first 5 weeks post-treatment (Cohen's d = 2.2 at week 1 and 2.3 at week 5, both p < 0.001); nine and four patients met the criteria for response and remission at week 5. Results remained positive at 3 and 6 months (Cohen's d = 1.5 and 1.4, respectively, both p < 0.001). No patients sought conventional antidepressant treatment within 5 weeks of psilocybin. Reductions in depressive symptoms at 5 weeks were predicted by the quality of the acute psychedelic experience. CONCLUSIONS: Although limited conclusions can be drawn about treatment efficacy from open-label trials, tolerability was good, effect sizes large and symptom improvements appeared rapidly after just two psilocybin treatment sessions and remained significant 6 months post-treatment in a treatment-resistant cohort. Psilocybin represents a promising paradigm for unresponsive depression that warrants further research in double-blind randomised control trials.
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Journal articleStroud JB, Freeman TP, Leech R, et al., 2017,
Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression
, Psychopharmacology, Vol: 235, Pages: 459-466, ISSN: 0033-3158RATIONALE: Depressed patients robustly exhibit affective biases in emotional processing which are altered by SSRIs and predict clinical outcome. OBJECTIVES: The objective of this study is to investigate whether psilocybin, recently shown to rapidly improve mood in treatment-resistant depression (TRD), alters patients' emotional processing biases. METHODS: Seventeen patients with treatment-resistant depression completed a dynamic emotional face recognition task at baseline and 1 month later after two doses of psilocybin with psychological support. Sixteen controls completed the emotional recognition task over the same time frame but did not receive psilocybin. RESULTS: We found evidence for a group × time interaction on speed of emotion recognition (p = .035). At baseline, patients were slower at recognising facial emotions compared with controls (p < .001). After psilocybin, this difference was remediated (p = .208). Emotion recognition was faster at follow-up compared with baseline in patients (p = .004, d = .876) but not controls (p = .263, d = .302). In patients, this change was significantly correlated with a reduction in anhedonia over the same time period (r = .640, p = .010). CONCLUSIONS: Psilocybin with psychological support appears to improve processing of emotional faces in treatment-resistant depression, and this correlates with reduced anhedonia. Placebo-controlled studies are warranted to follow up these preliminary findings.
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Journal articleCarhart-Harris RL, Roseman L, Bolstridge M, et al., 2017,
Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms
, Scientific Reports, Vol: 7, ISSN: 2045-2322Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other ‘psychedelics’ yet were related to clinical outcomes. A ‘reset’ therapeutic mechanism is proposed.
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Journal articleWatts R, Day C, Krzanowski J, et al., 2017,
Patients' Accounts of Increased "Connectedness" and "Acceptance" After Psilocybin for Treatment-Resistant Depression
, JOURNAL OF HUMANISTIC PSYCHOLOGY, Vol: 57, Pages: 520-564, ISSN: 0022-1678 -
Journal articleCarhart-Harris RL, Goodwin GM, 2017,
The therapeutic potential of psychedelic drugs: past, present and future
, Neuropsychopharmacology, Vol: 42, Pages: 2105-2113, ISSN: 1740-634XPlant-based psychedelics, such as psilocybin, have an ancient history of medicinal use. After the first English language report on LSD in 1950, psychedelics enjoyed a short-lived relationship with psychology and psychiatry. Used most notably as aids to psychotherapy for the treatment of mood disorders and alcohol dependence, drugs such as LSD showed initial therapeutic promise before prohibitive legislature in the mid-1960s effectively ended all major psychedelic research programs. Since the early 1990s, there has been a steady revival of human psychedelic research: last year saw reports on the first modern brain imaging study with LSD and three separate clinical trials of psilocybin for depressive symptoms. In this circumspective piece, RLC-H and GMG share their opinions on the promises and pitfalls of renewed psychedelic research, with a focus on the development of psilocybin as a treatment for depression.
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Journal articleSchartner MM, Carhart-Harris RL, Barrett AB, et al., 2017,
Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin
, Scientific Reports, Vol: 7, ISSN: 2045-2322What is the level of consciousness of the psychedelic state? Empirically, measures of neural signal diversity such as entropy and Lempel-Ziv (LZ) complexity score higher for wakeful rest than for states with lower conscious level like propofol-induced anesthesia. Here we compute these measures for spontaneous magnetoencephalographic (MEG) signals from humans during altered states of consciousness induced by three psychedelic substances: psilocybin, ketamine and LSD. For all three, we find reliably higher spontaneous signal diversity, even when controlling for spectral changes. This increase is most pronounced for the single-channel LZ complexity measure, and hence for temporal, as opposed to spatial, signal diversity. We also uncover selective correlations between changes in signal diversity and phenomenological reports of the intensity of psychedelic experience. This is the first time that these measures have been applied to the psychedelic state and, crucially, that they have yielded values exceeding those of normal waking consciousness. These findings suggest that the sustained occurrence of psychedelic phenomenology constitutes an elevated level of consciousness - as measured by neural signal diversity.
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Journal articleNutt D, 2016,
Psilocybin for anxiety and depression in cancer care? Lessons from the past and prospects for the future
, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 30, Pages: 1163-1164, ISSN: 0269-8811 -
Journal articleCarhart-Harris RL, Nutt DJ, 2016,
Question-based Drug Development for psilocybin Reply
, LANCET PSYCHIATRY, Vol: 3, Pages: 807-807, ISSN: 2215-0374- Author Web Link
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