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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
, NEUROPSYCHOPHARMACOLOGY, Vol: 44, Pages: 1328-1334, ISSN: 0893-133X- Cite
- Citations: 170
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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 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 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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Journal articleRoseman L, Demetriou L, Wall M, et al., 2018,
Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression
, Neuropharmacology, Vol: 142, Pages: 263-269, ISSN: 0028-3908Recent 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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Journal articleErritzoe D, Roseman L, Nour MM, et al., 2018,
Effects of psilocybin therapy on personality structure
, Acta Psychiatrica Scandinavica, Vol: 138, Pages: 368-378, ISSN: 1600-0447ObjectiveTo explore whether psilocybin with psychological support modulates personality parameters in patients suffering from treatment‐resistant depression (TRD).MethodTwenty patients with moderate or severe, unipolar, TRD received oral psilocybin (10 and 25 mg, one week apart) in a supportive setting. Personality was assessed at baseline and at 3‐month follow‐up using the Revised NEO Personality Inventory (NEO‐PI‐R), the subjective psilocybin experience with Altered State of Consciousness (ASC) scale, and depressive symptoms with QIDS‐SR16.ResultsNeuroticism scores significantly decreased while Extraversion increased following psilocybin therapy. These changes were in the direction of the normative NEO‐PI‐R data and were both predicted, in an exploratory analysis, by the degree of insightfulness experienced during the psilocybin session. Openness scores also significantly increased following psilocybin, whereas Conscientiousness showed trend‐level increases, and Agreeableness did not change.ConclusionOur observation of changes in personality measures after psilocybin therapy was mostly consistent with reports of personality change in relation to conventional antidepressant treatment, although the pronounced increases in Extraversion and Openness might constitute an effect more specific to psychedelic therapy. This needs further exploration in future controlled studies, as do the brain mechanisms of postpsychedelic personality change.
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Journal articleRucker JJH, Iliff J, Nutt DJ, 2018,
Psychiatry & the psychedelic drugs. Past, present & future
, Neuropharmacology, Vol: 142, Pages: 200-218, ISSN: 0028-3908The classical psychedelic drugs, including psilocybin, lysergic acid diethylamide and mescaline, were used extensively in psychiatry before they were placed in Schedule I of the UN Convention on Drugs in 1967. Experimentation and clinical trials undertaken prior to legal sanction suggest that they are not helpful for those with established psychotic disorders and should be avoided in those liable to develop them. However, those with so-called 'psychoneurotic' disorders sometimes benefited considerably from their tendency to 'loosen' otherwise fixed, maladaptive patterns of cognition and behaviour, particularly when given in a supportive, therapeutic setting. Pre-prohibition studies in this area were sub-optimal, although a recent systematic review in unipolar mood disorder and a meta-analysis in alcoholism have both suggested efficacy. The incidence of serious adverse events appears to be low. Since 2006, there have been several pilot trials and randomised controlled trials using psychedelics (mostly psilocybin) in various non-psychotic psychiatric disorders. These have provided encouraging results that provide initial evidence of safety and efficacy, however the regulatory and legal hurdles to licensing psychedelics as medicines are formidable. This paper summarises clinical trials using psychedelics pre and post prohibition, discusses the methodological challenges of performing good quality trials in this area and considers a strategic approach to the legal and regulatory barriers to licensing psychedelics as a treatment in mainstream psychiatry.
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