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Journal articleRuss SL, Carhart-Harris RL, Maruyama G, et al., 2019,
Replication and extension of a model predicting response to psilocybin
, PSYCHOPHARMACOLOGY, Vol: 236, Pages: 3221-3230, ISSN: 0033-3158- Author Web Link
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- Citations: 32
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Journal articlePallavicini C, Vilas MG, Villarreal M, et al., 2019,
Spectral signatures of serotonergic psychedelics and glutamatergic dissociatives.
, Neuroimage, Vol: 200, Pages: 281-291Classic serotonergic psychedelics are remarkable for their capacity to induce reversible alterations in consciousness of the self and the surroundings, mediated by agonism at serotonin 5-HT2A receptors. The subjective effects elicited by dissociative drugs acting as N-methyl-D-aspartate (NMDA) antagonists (e.g. ketamine and phencyclidine) overlap in certain domains with those of serotonergic psychedelics, suggesting some potential similarities in the brain activity patterns induced by both classes of drugs, despite different pharmacological mechanisms of action. We investigated source-localized magnetoencephalography recordings to determine the frequency-specific changes in oscillatory activity and long-range functional coupling that are common to two serotonergic compounds (lysergic acid diethylamide [LSD] and psilocybin) and the NMDA-antagonist ketamine. Administration of the three drugs resulted in widespread and broadband spectral power reductions. We established their similarity by using different pairs of compounds to train and subsequently evaluate multivariate machine learning classifiers. After applying the same methodology to functional connectivity values, we observed a pattern of occipital, parietal and frontal decreases in the low alpha and theta bands that were specific to LSD and psilocybin, as well as decreases in the low beta band common to the three drugs. Our results represent a first effort in the direction of quantifying the similarity of large-scale brain activity patterns induced by drugs of different mechanism of action, confirming the link between changes in theta and alpha oscillations and 5-HT2A agonism, while also revealing the decoupling of activity in the beta band as an effect shared between NMDA antagonists and 5-HT2A agonists. We discuss how these frequency-specific convergences and divergences in the power and functional connectivity of brain oscillations might relate to the overlapping subjective effects of serotonergic psychedelic
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Journal articleLord L-D, Expert P, Atasoy S, et al., 2019,
Dynamical exploration of the repertoire of brain networks at rest is modulated by psilocybin
, NeuroImage, Vol: 199, Pages: 127-142, ISSN: 1053-8119Growing evidence from the dynamical analysis of functional neuroimaging data suggests that brain function can be understood as the exploration of a repertoire of metastable connectivity patterns ('functional brain networks'), which potentially underlie different mental processes. The present study characterizes how the brain's dynamical exploration of resting-state networks is rapidly modulated by intravenous infusion of psilocybin, a tryptamine psychedelic found in "magic mushrooms". We employed a data-driven approach to characterize recurrent functional connectivity patterns by focusing on the leading eigenvector of BOLD phase coherence at single-TR resolution. Recurrent BOLD phase-locking patterns (PL states) were assessed and statistically compared pre- and post-infusion of psilocybin in terms of their probability of occurrence and transition profiles. Results were validated using a placebo session. Recurrent BOLD PL states revealed high spatial overlap with canonical resting-state networks. Notably, a PL state forming a frontoparietal subsystem was strongly destabilized after psilocybin injection, with a concomitant increase in the probability of occurrence of another PL state characterized by global BOLD phase coherence. These findings provide evidence of network-specific neuromodulation by psilocybin and represent one of the first attempts at bridging molecular pharmacodynamics and whole-brain network dynamics.
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Journal articleJefsen O, Hojgaard K, Christiansen SL, et al., 2019,
Psilocybin lacks antidepressant-like effect in the Flinders Sensitive Line rat
, ACTA NEUROPSYCHIATRICA, Vol: 31, Pages: 213-219, ISSN: 1601-5215- Author Web Link
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- Citations: 27
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Journal articleMadsen MK, Fisher PM, Burmester D, et al., 2019,
Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels (vol 44, pg 1328, 2019)
, NEUROPSYCHOPHARMACOLOGY, Vol: 44, Pages: 1336-1337, ISSN: 0893-133X -
Journal articleMadsen MK, Fisher PM, Burmester D, et al., 2019,
Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels
, NEUROPSYCHOPHARMACOLOGY, Vol: 44, Pages: 1328-1334, ISSN: 0893-133X- Cite
- Citations: 170
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Journal articleScott G, Carhart-Harris R, 2019,
Psychedelics as a treatment for disorders of consciousness
, Neuroscience of Consciousness, Vol: 2019, Pages: 1-8, ISSN: 2057-2107Based on its ability to increase brain complexity, a seemingly reliable index of conscious level, we proposetesting the capacity ofthe classic psychedelic, psilocybin,to increase conscious awarenessin patients with disorders of consciousness.We alsoconfrontthe considerable ethical and practical challengesthis proposal must address, if this hypothesis is to be directly assessed.
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Journal articleRuss SL, Carhart-Harris RL, Maruyama G, et al., 2019,
States and traits related to the quality and consequences of psychedelic experiences
, Psychology of Consciousness: Theory Research, and Practice, Vol: 6, Pages: 1-21, ISSN: 2326-5523Many individuals experience significant positive psychological change after ingesting psychedelic agents such as psilocybin, LSD, and ayahuasca, but some do not. Such changes appear to be mediated by definable and measurable mystical experiences (MEs) during the psychedelic session, which have been shown in previous research (e.g., Griffiths, Richards, McCann, & Jesse, 2006) to be related to long-term positive personal change. Individual responses to psychedelic agents are characteristically difficult to predict, however, necessitating improved identification of predictors to (a) reduce the possibility of significant challenging experiences and sequelae and (b) increase the possibility of MEs and long-term beneficial outcomes. Our study utilized crowdsourced retrospective survey data from 143 Amazon Mechanical Turk participants who self-administered psilocybin in the past year to identify factors related to MEs and/or challenging experiences. The best performing regression model explained 66% of the variance in ME scores on the 30-item Mystical Experience Questionnaire (MacLean, Leoutsakos, Johnson, & Griffiths, 2012) and 56% of the variance in scores on the dread subscale of the Sacred Emotions Scale (Burdzy, 2014). A state of surrender at the start of the psilocybin session most strongly explained MEs, and a state of preoccupation most strongly explained challenging experiences. The trait absorption was a strong secondary predictor in both models, along with smaller predictors. Additionally, the occurrence of MEs during the psilocybin session explained long-term positive change. Based on these findings, the presented models appear to provide a powerful framework for explaining the immediate quality and long-term consequences of psychedelic experiences. Limitations as well as implications for therapeutic applications are discussed.
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Journal articleVarley TF, Carhart-Harris R, Roseman L, et al., 2019,
Serotonergic Psychedelics LSD & Psilocybin Increase the Fractal Dimension of Cortical Brain Activity in Spatial and Temporal Domains
<jats:title>Abstract</jats:title><jats:p>Psychedelic drugs, such as psilocybin and LSD, represent unique tools for researchers in-vestigating the neural origins of consciousness. Currently, the most compelling theories of how psychedelics exert their effects is by increasing the complexity of brain activity and moving the system towards a critical point between order and disorder, creating more dynamic and complex patterns of neural activity. While the concept of criticality is of central importance to this theory, few of the published studies on psychedelics investigate it directly, testing instead related measures such as algorithmic complexity or Shannon entropy. We propose using the fractal dimension of functional activity in the brain as a measure of complexity since findings from physics suggest that as a system organizes towards criticality, it tends to take on a fractal structure. We tested two different measures of fractal dimension, one spatial and one temporal, using fMRI data from volunteers under the influence of both LSD and psilocybin. The first was the fractal dimension of cortical functional connectivity networks and the second was the fractal dimension of BOLD time-series. We were able to show that both psychedelic drugs significantly increased the fractal dimension of functional connectivity networks, and that LSD significantly increased the fractal dimension of BOLD signals, with psilocybin showing a non-significant trend in the same direction. With both LSD and psilocybin, we were able to localize changes in the fractal dimension of BOLD signals to brain areas assigned to the dorsal-attentional network. These results show that psychedelic drugs increase the fractal character of activity in the brain and we see this as an indicator that the changes in consciousness triggered by psychedelics are associated with evolution towards a critical zone.</jats:p><jats:sec><jats:title>Author Summary</jats:title><
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Conference paperMadsen MK, Burmester D, Stenbaek DS, et al., 2019,
Psilocybin occupancy of brain serotonin 2A receptors correlates with psilocin levels and subjective experience: a [11C]Cimbi-36 PET study in humans
, 31st Congress of the European-College-of-Neuropsychopharmacology (ECNP), Publisher: ELSEVIER, Pages: S304-S305, ISSN: 0924-977X- Cite
- Citations: 2
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