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• Conference paper
  Mertens LJ, Wall MB, Roseman L, Demetriou L, Nutt DJ, Carhart-Harris RLet al., 2019,

  Therapeutic mechanisms of psychedelic drugs: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression

  , 32nd Congress of the European-College-of-Neuropsychopharmacology (ECNP), Publisher: ELSEVIER, Pages: S416-S417, ISSN: 0924-977X
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• Journal article
  Russ SL, Carhart-Harris RL, Maruyama G, Elliott MSet al., 2019,

  Replication and extension of a model predicting response to psilocybin

  , PSYCHOPHARMACOLOGY, Vol: 236, Pages: 3221-3230, ISSN: 0033-3158
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  • Citations: 32
• Journal article
  Lord L-D, Expert P, Atasoy S, Roseman L, Rapuano K, Lambiotte R, Nutt DJ, Deco G, Carhart-Harris RL, Kringelbach ML, Cabral Jet al., 2019,

  Dynamical exploration of the repertoire of brain networks at rest is modulated by psilocybin

  , NeuroImage, Vol: 199, Pages: 127-142, ISSN: 1053-8119

  Growing 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 article
  Jefsen O, Hojgaard K, Christiansen SL, Elfving B, Nutt DJ, Wegener G, Mueller HKet al., 2019,

  Psilocybin lacks antidepressant-like effect in the Flinders Sensitive Line rat

  , ACTA NEUROPSYCHIATRICA, Vol: 31, Pages: 213-219, ISSN: 1601-5215
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  • Citations: 27
• Journal article
  Madsen MK, Fisher PM, Burmester D, Dyssegaard A, Stenbk DS, Kristiansen S, Johansen SS, Lehel S, Linnet K, Svarer C, Erritzoe D, Ozenne B, Knudsen GMet 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
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  • Citations: 170
• Journal article
  Madsen MK, Fisher PM, Burmester D, Dyssegaard A, Stenbaek DS, Kristiansen S, Johansen SS, Lehel S, Linnet K, Svarer C, Erritzoe D, Ozenne B, Knudsen GMet 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
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• Journal article
  Scott G, Carhart-Harris R, 2019,

  Psychedelics as a treatment for disorders of consciousness

  , Neuroscience of Consciousness, Vol: 2019, Pages: 1-8, ISSN: 2057-2107

  Based 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 article
  Varley TF, Carhart-Harris R, Roseman L, Menon DK, Stamatakis EAet 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> <j

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• Conference paper
  Madsen MK, Burmester D, Stenbaek DS, Kristiansen S, Dyssegaard A, Lehel S, Linnet K, Johansen SS, Svarer C, Ozenne B, Erritzoe D, Fisher PM, Knudsen GMet 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
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  • Citations: 2
• Journal article
  Roseman L, Demetriou L, Wall M, Nutt D, Carhart-Harris RLet al., 2018,

  Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression

  , Neuropharmacology, Vol: 142, Pages: 263-269, ISSN: 0028-3908

  Recent evidence indicates that psilocybin with psychological support may be effective for treating depression. Some studies have found that patients with depression show heightened amygdala responses to fearful faces and there is reliable evidence that treatment with SSRIs attenuates amygdala responses (Ma, 2015). We hypothesised that amygdala responses to emotional faces would be altered post-treatment with psilocybin. In this open-label study, 20 individuals diagnosed with moderate to severe, treatment-resistant depression, underwent two separate dosing sessions with psilocybin. Psychological support was provided before, during and after these sessions and 19 completed fMRI scans one week prior to the first session and one day after the second and last. Neutral, fearful and happy faces were presented in the scanner and analyses focused on the amygdala. Group results revealed rapid and enduring improvements in depressive symptoms post psilocybin. Increased responses to fearful and happy faces were observed in the right amygdala post-treatment, and right amygdala increases to fearful versus neutral faces were predictive of clinical improvements at 1-week. Psilocybin with psychological support was associated with increased amygdala responses to emotional stimuli, an opposite effect to previous findings with SSRIs. This suggests fundamental differences in these treatments’ therapeutic actions, with SSRIs mitigating negative emotions and psilocybin allowing patients to confront and work through them. Based on the present results, we propose that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression, enabling patients to reconnect with their emotions.

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