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Franz X Vollenweider - One of the best experts on this subject based on the ideXlab platform.
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effect of psilocybin on empathy and moral decision making
The International Journal of Neuropsychopharmacology, 2017Co-Authors: Thomas Pokorny, Katrin H Preller, Michael Kometer, Isabel Dziobek, Franz X VollenweiderAbstract:Background: Impaired empathic abilities lead to severe negative social consequences and influence the development and treatment of several psychiatric disorders. Furthermore, empathy has been shown to play a crucial role in moral and prosocial behavior. Although the serotonin system has been implicated in modulating empathy and moral behavior, the relative contribution of the various serotonin receptor subtypes is still unknown. Methods: We investigated the acute effect of psilocybin (0.215 mg/kg p.o.) in healthy human subjects on different facets of empathy and hypothetical moral decision-making using the multifaceted empathy test (n=32) and the moral dilemma task (n=24). Results: Psilocybin significantly increased emotional, but not cognitive empathy compared with placebo, and the increase in implicit emotional empathy was significantly associated with psilocybin-induced changed meaning of percepts. In contrast, moral decision-making remained unaffected by psilocybin. Conclusions: These findings provide first evidence that psilocybin has distinct effects on social cognition by enhancing emotional empathy but not moral behavior. Furthermore, together with previous findings, psilocybin appears to promote emotional empathy presumably via activation of serotonin 2A/1A receptors, suggesting that targeting serotonin 2A/1A receptors has implications for potential treatment of dysfunctional social cognition.
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Two dose investigation of the 5-HT-agonist psilocybin on relative and global cerebral blood flow
NeuroImage, 2017Co-Authors: Candace R. Lewis, Philipp Staempfli, Leandro Michels, Rainer Kraehenmann, Katrin H Preller, Franz X VollenweiderAbstract:Psilocybin, the active compound in psychedelic mushrooms, is an agonist of various serotonin receptors. Seminal psilocybin positron emission tomography (PET) research suggested regional increases in glucose metabolism in frontal cortex (hyperfrontality). However, a recent arterial spin labeling (ASL) study suggests psilocybin may lead to hypo-perfusion in various brain regions. In this placebo-controlled, double-blind study we used pseudo-continuous ASL (pCASL) to measure perfusion changes, with and without adjustment for global brain perfusion, after two doses of oral psilocybin (low dose: 0.160 mg/kg; high dose: 0.215 mg/kg) in two groups of healthy controls (n = 29 in both groups, total N = 58) during rest. We controlled for sex and age and used family-wise error corrected p values in all neuroimaging analyses. Both dose groups reported profound subjective drug effects as measured by the Altered States of Consciousness Rating Scale (5D-ASC) with the high dose inducing significantly larger effects in four out of the 11 scales. After adjusting for global brain perfusion, psilocybin increased relative perfusion in distinct right hemispheric frontal and temporal regions and bilaterally in the anterior insula and decreased perfusion in left hemispheric parietal and temporal cortices and left subcortical regions. Whereas, psilocybin significantly reduced absolute perfusion in frontal, temporal, parietal, and occipital lobes, and bilateral amygdalae, anterior cingulate, insula, striatal regions, and hippocampi. Our analyses demonstrate consistency with both the hyperfrontal hypothesis of psilocybin and the more recent study demonstrating decreased perfusion, depending on analysis method. Importantly, our data illustrate that relative changes in perfusion should be understood and interpreted in relation to absolute signal variations.
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modulatory effect of the 5 ht1a agonist buspirone and the mixed non hallucinogenic 5 ht1a 2a agonist ergotamine on psilocybin induced psychedelic experience
European Neuropsychopharmacology, 2016Co-Authors: Thomas Pokorny, Rainer Kraehenmann, Katrin H Preller, Franz X VollenweiderAbstract:The mixed serotonin (5-HT) 1A/2A/2B/2C/6/7 receptor agonist psilocybin dose-dependently induces an altered state of consciousness (ASC) that is characterized by changes in sensory perception, mood, thought, and the sense of self. The psychological effects of psilocybin are primarily mediated by 5-HT2A receptor activation. However, accumulating evidence suggests that 5-HT1A or an interaction between 5-HT1A and 5-HT2A receptors may contribute to the overall effects of psilocybin. Therefore, we used a double-blind, counterbalanced, within-subject design to investigate the modulatory effects of the partial 5-HT1A agonist buspirone (20mg p.o.) and the non-hallucinogenic 5-HT2A/1A agonist ergotamine (3mg p.o.) on psilocybin-induced (170 µg/kg p.o.) psychological effects in two groups (n=19, n=17) of healthy human subjects. Psychological effects were assessed using the Altered State of Consciousness (5D-ASC) rating scale. Buspirone significantly reduced the 5D-ASC main scale score for Visionary Restructuralization (VR) (p<0.001), which was mostly driven by a reduction of the VR item cluster scores for elementary and complex visual hallucinations. Further, buspirone also reduced the main scale score for Oceanic Boundlessness (OB) including derealisation and depersonalisation phenomena at a trend level (p=0.062), whereas ergotamine did not show any effects on the psilocybin-induced 5D-ASC main scale scores. The present finding demonstrates that buspirone exerts inhibitory effects on psilocybin-induced effects, presumably via 5-HT1A receptor activation, an interaction between 5-HT1A and 5-HT2A receptors, or both. The data suggest that the modulation of 5-HT1A receptor activity may be a useful target in the treatment of visual hallucinations in different psychiatric and neurological diseases.
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modulatory effect of the 5 ht1a agonist buspirone and the mixed non hallucinogenic 5 ht1a 2a agonist ergotamine on psilocybin induced psychedelic experience
European Neuropsychopharmacology, 2016Co-Authors: Thomas Pokorny, Rainer Kraehenmann, Katrin H Preller, Franz X VollenweiderAbstract:Abstract The mixed serotonin (5-HT) 1A/2A/2B/2C/6/7 receptor agonist psilocybin dose-dependently induces an altered state of consciousness (ASC) that is characterized by changes in sensory perception, mood, thought, and the sense of self. The psychological effects of psilocybin are primarily mediated by 5-HT2A receptor activation. However, accumulating evidence suggests that 5-HT1A or an interaction between 5-HT1A and 5-HT2A receptors may contribute to the overall effects of psilocybin. Therefore, we used a double-blind, counterbalanced, within-subject design to investigate the modulatory effects of the partial 5-HT1A agonist buspirone (20 mg p.o.) and the non-hallucinogenic 5-HT2A/1A agonist ergotamine (3 mg p.o.) on psilocybin-induced (170 µg/kg p.o.) psychological effects in two groups ( n =19, n =17) of healthy human subjects. Psychological effects were assessed using the Altered State of Consciousness (5D-ASC) rating scale. Buspirone significantly reduced the 5D-ASC main scale score for Visionary Restructuralization (VR) ( p p =0.062), whereas ergotamine did not show any effects on the psilocybin-induced 5D-ASC main scale scores. The present finding demonstrates that buspirone exerts inhibitory effects on psilocybin-induced effects, presumably via 5-HT1A receptor activation, an interaction between 5-HT1A and 5-HT2A receptors, or both. The data suggest that the modulation of 5-HT1A receptor activity may be a useful target in the treatment of visual hallucinations in different psychiatric and neurological diseases.
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the mixed serotonin receptor agonist psilocybin reduces threat induced modulation of amygdala connectivity
NeuroImage: Clinical, 2016Co-Authors: Rainer Kraehenmann, Katrin H Preller, Andre Schmidt, Erich Seifritz, Karl J Friston, Franz X VollenweiderAbstract:Stimulation of serotonergic neurotransmission by psilocybin has been shown to shift emotional biases away from negative towards positive stimuli. We have recently shown that reduced amygdala activity during threat processing might underlie psilocybin's effect on emotional processing. However, it is still not known whether psilocybin modulates bottom-up or top-down connectivity within the visual-limbic-prefrontal network underlying threat processing. We therefore analyzed our previous fMRI data using dynamic causal modeling and used Bayesian model selection to infer how psilocybin modulated effective connectivity within the visual-limbic-prefrontal network during threat processing. First, both placebo and psilocybin data were best explained by a model in which threat affect modulated bidirectional connections between the primary visual cortex, amygdala, and lateral prefrontal cortex. Second, psilocybin decreased the threat-induced modulation of top-down connectivity from the amygdala to primary visual cortex, speaking to a neural mechanism that might underlie putative shifts towards positive affect states after psilocybin administration. These findings may have important implications for the treatment of mood and anxiety disorders.
Katrin H Preller - One of the best experts on this subject based on the ideXlab platform.
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psilocybin induces time dependent changes in global functional connectivity
Biological Psychiatry, 2020Co-Authors: Katrin H Preller, Erich Seifritz, Patricia Duerler, Joshua B Burt, Brendan Adkinson, Philipp Stampfli, Grega Repovs, John H Krystal, John D Murray, Alan AnticevicAbstract:Abstract Background The use of psilocybin in scientific and experimental clinical contexts has triggered renewed interest in the mechanism of action of psychedelics. However, its time-dependent systems-level neurobiology remains sparsely investigated in humans. Methods We conducted a double-blind, randomized, counterbalanced, crossover study comprising 23 healthy human participants who received placebo and 0.2 mg/kg of psilocybin orally on 2 different test days. Participants underwent magnetic resonance imaging at 3 time points between administration and peak effects: 20 minutes, 40 minutes, and 70 minutes after administration. Resting-state functional connectivity was quantified via a data-driven global brain connectivity method and compared with cortical gene expression maps. Results Psilocybin reduced associative, but concurrently increased sensory, brain-wide connectivity. This pattern emerged over time from administration to peak effects. Furthermore, we showed that baseline connectivity is associated with the extent of psilocybin-induced changes in functional connectivity. Lastly, psilocybin-induced changes correlated in a time-dependent manner with spatial gene expression patterns of the 5-HT2A (5-hydroxytryptamine 2A) and 5-HT1A (5-hydroxytryptamine 1A) receptors. Conclusions These results suggest that the integration of functional connectivity in sensory regions and the disintegration in associative regions may underlie the psychedelic state and pinpoint the critical role of the serotonin 2A and 1A receptor systems. Furthermore, baseline connectivity may represent a predictive marker of the magnitude of changes induced by psilocybin and may therefore contribute to a personalized medicine approach within the potential framework of psychedelic treatment.
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effect of psilocybin on empathy and moral decision making
The International Journal of Neuropsychopharmacology, 2017Co-Authors: Thomas Pokorny, Katrin H Preller, Michael Kometer, Isabel Dziobek, Franz X VollenweiderAbstract:Background: Impaired empathic abilities lead to severe negative social consequences and influence the development and treatment of several psychiatric disorders. Furthermore, empathy has been shown to play a crucial role in moral and prosocial behavior. Although the serotonin system has been implicated in modulating empathy and moral behavior, the relative contribution of the various serotonin receptor subtypes is still unknown. Methods: We investigated the acute effect of psilocybin (0.215 mg/kg p.o.) in healthy human subjects on different facets of empathy and hypothetical moral decision-making using the multifaceted empathy test (n=32) and the moral dilemma task (n=24). Results: Psilocybin significantly increased emotional, but not cognitive empathy compared with placebo, and the increase in implicit emotional empathy was significantly associated with psilocybin-induced changed meaning of percepts. In contrast, moral decision-making remained unaffected by psilocybin. Conclusions: These findings provide first evidence that psilocybin has distinct effects on social cognition by enhancing emotional empathy but not moral behavior. Furthermore, together with previous findings, psilocybin appears to promote emotional empathy presumably via activation of serotonin 2A/1A receptors, suggesting that targeting serotonin 2A/1A receptors has implications for potential treatment of dysfunctional social cognition.
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Two dose investigation of the 5-HT-agonist psilocybin on relative and global cerebral blood flow
NeuroImage, 2017Co-Authors: Candace R. Lewis, Philipp Staempfli, Leandro Michels, Rainer Kraehenmann, Katrin H Preller, Franz X VollenweiderAbstract:Psilocybin, the active compound in psychedelic mushrooms, is an agonist of various serotonin receptors. Seminal psilocybin positron emission tomography (PET) research suggested regional increases in glucose metabolism in frontal cortex (hyperfrontality). However, a recent arterial spin labeling (ASL) study suggests psilocybin may lead to hypo-perfusion in various brain regions. In this placebo-controlled, double-blind study we used pseudo-continuous ASL (pCASL) to measure perfusion changes, with and without adjustment for global brain perfusion, after two doses of oral psilocybin (low dose: 0.160 mg/kg; high dose: 0.215 mg/kg) in two groups of healthy controls (n = 29 in both groups, total N = 58) during rest. We controlled for sex and age and used family-wise error corrected p values in all neuroimaging analyses. Both dose groups reported profound subjective drug effects as measured by the Altered States of Consciousness Rating Scale (5D-ASC) with the high dose inducing significantly larger effects in four out of the 11 scales. After adjusting for global brain perfusion, psilocybin increased relative perfusion in distinct right hemispheric frontal and temporal regions and bilaterally in the anterior insula and decreased perfusion in left hemispheric parietal and temporal cortices and left subcortical regions. Whereas, psilocybin significantly reduced absolute perfusion in frontal, temporal, parietal, and occipital lobes, and bilateral amygdalae, anterior cingulate, insula, striatal regions, and hippocampi. Our analyses demonstrate consistency with both the hyperfrontal hypothesis of psilocybin and the more recent study demonstrating decreased perfusion, depending on analysis method. Importantly, our data illustrate that relative changes in perfusion should be understood and interpreted in relation to absolute signal variations.
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modulatory effect of the 5 ht1a agonist buspirone and the mixed non hallucinogenic 5 ht1a 2a agonist ergotamine on psilocybin induced psychedelic experience
European Neuropsychopharmacology, 2016Co-Authors: Thomas Pokorny, Rainer Kraehenmann, Katrin H Preller, Franz X VollenweiderAbstract:Abstract The mixed serotonin (5-HT) 1A/2A/2B/2C/6/7 receptor agonist psilocybin dose-dependently induces an altered state of consciousness (ASC) that is characterized by changes in sensory perception, mood, thought, and the sense of self. The psychological effects of psilocybin are primarily mediated by 5-HT2A receptor activation. However, accumulating evidence suggests that 5-HT1A or an interaction between 5-HT1A and 5-HT2A receptors may contribute to the overall effects of psilocybin. Therefore, we used a double-blind, counterbalanced, within-subject design to investigate the modulatory effects of the partial 5-HT1A agonist buspirone (20 mg p.o.) and the non-hallucinogenic 5-HT2A/1A agonist ergotamine (3 mg p.o.) on psilocybin-induced (170 µg/kg p.o.) psychological effects in two groups ( n =19, n =17) of healthy human subjects. Psychological effects were assessed using the Altered State of Consciousness (5D-ASC) rating scale. Buspirone significantly reduced the 5D-ASC main scale score for Visionary Restructuralization (VR) ( p p =0.062), whereas ergotamine did not show any effects on the psilocybin-induced 5D-ASC main scale scores. The present finding demonstrates that buspirone exerts inhibitory effects on psilocybin-induced effects, presumably via 5-HT1A receptor activation, an interaction between 5-HT1A and 5-HT2A receptors, or both. The data suggest that the modulation of 5-HT1A receptor activity may be a useful target in the treatment of visual hallucinations in different psychiatric and neurological diseases.
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modulatory effect of the 5 ht1a agonist buspirone and the mixed non hallucinogenic 5 ht1a 2a agonist ergotamine on psilocybin induced psychedelic experience
European Neuropsychopharmacology, 2016Co-Authors: Thomas Pokorny, Rainer Kraehenmann, Katrin H Preller, Franz X VollenweiderAbstract:The mixed serotonin (5-HT) 1A/2A/2B/2C/6/7 receptor agonist psilocybin dose-dependently induces an altered state of consciousness (ASC) that is characterized by changes in sensory perception, mood, thought, and the sense of self. The psychological effects of psilocybin are primarily mediated by 5-HT2A receptor activation. However, accumulating evidence suggests that 5-HT1A or an interaction between 5-HT1A and 5-HT2A receptors may contribute to the overall effects of psilocybin. Therefore, we used a double-blind, counterbalanced, within-subject design to investigate the modulatory effects of the partial 5-HT1A agonist buspirone (20mg p.o.) and the non-hallucinogenic 5-HT2A/1A agonist ergotamine (3mg p.o.) on psilocybin-induced (170 µg/kg p.o.) psychological effects in two groups (n=19, n=17) of healthy human subjects. Psychological effects were assessed using the Altered State of Consciousness (5D-ASC) rating scale. Buspirone significantly reduced the 5D-ASC main scale score for Visionary Restructuralization (VR) (p<0.001), which was mostly driven by a reduction of the VR item cluster scores for elementary and complex visual hallucinations. Further, buspirone also reduced the main scale score for Oceanic Boundlessness (OB) including derealisation and depersonalisation phenomena at a trend level (p=0.062), whereas ergotamine did not show any effects on the psilocybin-induced 5D-ASC main scale scores. The present finding demonstrates that buspirone exerts inhibitory effects on psilocybin-induced effects, presumably via 5-HT1A receptor activation, an interaction between 5-HT1A and 5-HT2A receptors, or both. The data suggest that the modulation of 5-HT1A receptor activity may be a useful target in the treatment of visual hallucinations in different psychiatric and neurological diseases.
Thomas Pokorny - One of the best experts on this subject based on the ideXlab platform.
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effect of psilocybin on empathy and moral decision making
The International Journal of Neuropsychopharmacology, 2017Co-Authors: Thomas Pokorny, Katrin H Preller, Michael Kometer, Isabel Dziobek, Franz X VollenweiderAbstract:Background: Impaired empathic abilities lead to severe negative social consequences and influence the development and treatment of several psychiatric disorders. Furthermore, empathy has been shown to play a crucial role in moral and prosocial behavior. Although the serotonin system has been implicated in modulating empathy and moral behavior, the relative contribution of the various serotonin receptor subtypes is still unknown. Methods: We investigated the acute effect of psilocybin (0.215 mg/kg p.o.) in healthy human subjects on different facets of empathy and hypothetical moral decision-making using the multifaceted empathy test (n=32) and the moral dilemma task (n=24). Results: Psilocybin significantly increased emotional, but not cognitive empathy compared with placebo, and the increase in implicit emotional empathy was significantly associated with psilocybin-induced changed meaning of percepts. In contrast, moral decision-making remained unaffected by psilocybin. Conclusions: These findings provide first evidence that psilocybin has distinct effects on social cognition by enhancing emotional empathy but not moral behavior. Furthermore, together with previous findings, psilocybin appears to promote emotional empathy presumably via activation of serotonin 2A/1A receptors, suggesting that targeting serotonin 2A/1A receptors has implications for potential treatment of dysfunctional social cognition.
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modulatory effect of the 5 ht1a agonist buspirone and the mixed non hallucinogenic 5 ht1a 2a agonist ergotamine on psilocybin induced psychedelic experience
European Neuropsychopharmacology, 2016Co-Authors: Thomas Pokorny, Rainer Kraehenmann, Katrin H Preller, Franz X VollenweiderAbstract:Abstract The mixed serotonin (5-HT) 1A/2A/2B/2C/6/7 receptor agonist psilocybin dose-dependently induces an altered state of consciousness (ASC) that is characterized by changes in sensory perception, mood, thought, and the sense of self. The psychological effects of psilocybin are primarily mediated by 5-HT2A receptor activation. However, accumulating evidence suggests that 5-HT1A or an interaction between 5-HT1A and 5-HT2A receptors may contribute to the overall effects of psilocybin. Therefore, we used a double-blind, counterbalanced, within-subject design to investigate the modulatory effects of the partial 5-HT1A agonist buspirone (20 mg p.o.) and the non-hallucinogenic 5-HT2A/1A agonist ergotamine (3 mg p.o.) on psilocybin-induced (170 µg/kg p.o.) psychological effects in two groups ( n =19, n =17) of healthy human subjects. Psychological effects were assessed using the Altered State of Consciousness (5D-ASC) rating scale. Buspirone significantly reduced the 5D-ASC main scale score for Visionary Restructuralization (VR) ( p p =0.062), whereas ergotamine did not show any effects on the psilocybin-induced 5D-ASC main scale scores. The present finding demonstrates that buspirone exerts inhibitory effects on psilocybin-induced effects, presumably via 5-HT1A receptor activation, an interaction between 5-HT1A and 5-HT2A receptors, or both. The data suggest that the modulation of 5-HT1A receptor activity may be a useful target in the treatment of visual hallucinations in different psychiatric and neurological diseases.
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modulatory effect of the 5 ht1a agonist buspirone and the mixed non hallucinogenic 5 ht1a 2a agonist ergotamine on psilocybin induced psychedelic experience
European Neuropsychopharmacology, 2016Co-Authors: Thomas Pokorny, Rainer Kraehenmann, Katrin H Preller, Franz X VollenweiderAbstract:The mixed serotonin (5-HT) 1A/2A/2B/2C/6/7 receptor agonist psilocybin dose-dependently induces an altered state of consciousness (ASC) that is characterized by changes in sensory perception, mood, thought, and the sense of self. The psychological effects of psilocybin are primarily mediated by 5-HT2A receptor activation. However, accumulating evidence suggests that 5-HT1A or an interaction between 5-HT1A and 5-HT2A receptors may contribute to the overall effects of psilocybin. Therefore, we used a double-blind, counterbalanced, within-subject design to investigate the modulatory effects of the partial 5-HT1A agonist buspirone (20mg p.o.) and the non-hallucinogenic 5-HT2A/1A agonist ergotamine (3mg p.o.) on psilocybin-induced (170 µg/kg p.o.) psychological effects in two groups (n=19, n=17) of healthy human subjects. Psychological effects were assessed using the Altered State of Consciousness (5D-ASC) rating scale. Buspirone significantly reduced the 5D-ASC main scale score for Visionary Restructuralization (VR) (p<0.001), which was mostly driven by a reduction of the VR item cluster scores for elementary and complex visual hallucinations. Further, buspirone also reduced the main scale score for Oceanic Boundlessness (OB) including derealisation and depersonalisation phenomena at a trend level (p=0.062), whereas ergotamine did not show any effects on the psilocybin-induced 5D-ASC main scale scores. The present finding demonstrates that buspirone exerts inhibitory effects on psilocybin-induced effects, presumably via 5-HT1A receptor activation, an interaction between 5-HT1A and 5-HT2A receptors, or both. The data suggest that the modulation of 5-HT1A receptor activity may be a useful target in the treatment of visual hallucinations in different psychiatric and neurological diseases.
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psilocybin induced decrease in amygdala reactivity correlates with enhanced positive mood in healthy volunteers
Biological Psychiatry, 2015Co-Authors: Rainer Kraehenmann, Katrin H Preller, Matthias Scheidegger, Thomas Pokorny, Oliver G. Bosch, Erich Seifritz, Franz X VollenweiderAbstract:Abstract Background The amygdala is a key structure in serotonergic emotion-processing circuits. In healthy volunteers, acute administration of the serotonin 1A/2A/2C receptor agonist psilocybin reduces neural responses to negative stimuli and induces mood changes toward positive states. However, it is little-known whether psilocybin reduces amygdala reactivity to negative stimuli and whether any change in amygdala reactivity is related to mood change. Methods This study assessed the effects of acute administration of the hallucinogen psilocybin (.16 mg/kg) versus placebo on amygdala reactivity to negative stimuli in 25 healthy volunteers using blood oxygen level-dependent functional magnetic resonance imaging. Mood changes were assessed using the Positive and Negative Affect Schedule and the state portion of the State-Trait Anxiety Inventory. A double-blind, randomized, cross-over design was used with volunteers counterbalanced to receive psilocybin and placebo in two separate sessions at least 14 days apart. Results Amygdala reactivity to negative and neutral stimuli was lower after psilocybin administration than after placebo administration. The psilocybin-induced attenuation of right amygdala reactivity in response to negative stimuli was related to the psilocybin-induced increase in positive mood state. Conclusions These results demonstrate that acute treatment with psilocybin decreased amygdala reactivity during emotion processing and that this was associated with an increase of positive mood in healthy volunteers. These findings may be relevant to the normalization of amygdala hyperactivity and negative mood states in patients with major depression.
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spatiotemporal brain dynamics of emotional face processing modulations induced by the serotonin 1a 2a receptor agonist psilocybin
Cerebral Cortex, 2014Co-Authors: Fosco Bernasconi, Thomas Pokorny, Michael Kometer, Andre Schmidt, Erich Seifritz, Franz X VollenweiderAbstract:Emotional face processing is critically modulated by the serotonergic system. For instance, emotional face processing is impaired by acute psilocybin administration, a serotonin (5-HT) 1A and 2A receptor agonist. However, the spatiotemporal brain mechanisms underlying these modulations are poorly understood. Here, we investigated the spatiotemporal brain dynamics underlying psilocybin-induced modulations during emotional face processing. Electrical neuroimaging analyses were applied to visual evoked potentials in response to emotional faces, following psilocybin and placebo administration. Our results indicate a first time period of strength (i.e., Global Field Power) modulation over the 168-189 ms poststimulus interval, induced by psilocybin. A second time period of strength modulation was identified over the 211-242 ms poststimulus interval. Source estimations over these 2 time periods further revealed decreased activity in response to both neutral and fearful faces within limbic areas, including amygdala and parahippocampal gyrus, and the right temporal cortex over the 168-189 ms interval, and reduced activity in response to happy faces within limbic and right temporo-occipital brain areas over the 211-242 ms interval. Our results indicate a selective and temporally dissociable effect of psilocybin on the neuronal correlates of emotional face processing, consistent with a modulation of the top-down control.
Robin L Carhartharris - One of the best experts on this subject based on the ideXlab platform.
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dynamical exploration of the repertoire of brain networks at rest is modulated by psilocybin
NeuroImage, 2019Co-Authors: Louis-david Lord, Leor Roseman, David J. Nutt, Robin L Carhartharris, Paul Expert, Selen Atasoy, Kristina M Rapuano, Renaud Lambiotte, Gustavo Deco, Morten L KringelbachAbstract:Abstract 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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replication and extension of a model predicting response to psilocybin
Psychopharmacology, 2019Co-Authors: Suzanne L Russ, Robin L Carhartharris, Geoffrey M Maruyama, Melody S ElliottAbstract:Recent research demonstrated the potential of psychedelic drugs as treatment for depression and death-related anxiety and as an enhancement for well-being. While generally positive, responses to psychedelic drugs can vary according to traits, setting, and mental state (set) before and during ingestion. Most earlier models explain minimal response variation, primarily related to dosage and trust, but a recent study found that states of surrender and preoccupation at the time of ingestion explained substantial variance in mystical and adverse psilocybin experiences. The current study sought to replicate the previous model, extend the model with additional predictors, and examine the role of mystical experience on positive change. A hierarchical regression model was created with crowdsourced retrospective data from 183 individuals who had self-administered psilocybin in the past year. Scales explored mental states before, during, and after psilocybin ingestion, relying on open-ended memory prompts at each juncture to trigger recollections. Controlled drug administration was not employed. This study replicated the previous model, finding a state of surrender before ingestion a key predictor of optimal experience and preoccupation a key predictor of adverse experience. Additional predictors added to the explanatory power for optimal and adverse experience. The model supported the importance of mystical experiences to long-term change. Mental states of surrender or preoccupation at the time of ingestion explain variance in mystical or adverse psilocybin experiences, and mystical experiences relate to long-term positive change. The capacity to recognize this optimal preparatory mental state may benefit therapeutic use of psilocybin in clinical settings.
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effects of psilocybin therapy on personality structure
Acta Psychiatrica Scandinavica, 2018Co-Authors: David Erritzoe, Mendel Kaelen, Leor Roseman, David J. Nutt, Matthew M Nour, K Maclean, Robin L CarhartharrisAbstract:Objective To explore whether psilocybin with psychological support modulates personality parameters in patients suffering from treatment-resistant depression (TRD). Method Twenty 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. Results Neuroticism 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. Conclusion Our 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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psilocybin with psychological support improves emotional face recognition in treatment resistant depression
Psychopharmacology, 2018Co-Authors: J B Stroud, David J. Nutt, Robert Leech, Tom P Freeman, Chandni Hindocha, Will Lawn, H V Curran, Robin L CarhartharrisAbstract:RATIONALE: 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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psilocybin with psychological support for treatment resistant depression six month follow up
Psychopharmacology, 2018Co-Authors: Robin L Carhartharris, Mark Bolstridge, David Erritzoe, James Rucker, Rosalind Watts, Camilla M Day, Mendel KaelenAbstract:Recent clinical trials are reporting marked improvements in mental health outcomes with psychedelic drug-assisted psychotherapy. Here, we report on safety and efficacy outcomes for up to 6 months in an open-label trial of psilocybin for treatment-resistant depression. 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. 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. 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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dynamical exploration of the repertoire of brain networks at rest is modulated by psilocybin
NeuroImage, 2019Co-Authors: Louis-david Lord, Leor Roseman, David J. Nutt, Robin L Carhartharris, Paul Expert, Selen Atasoy, Kristina M Rapuano, Renaud Lambiotte, Gustavo Deco, Morten L KringelbachAbstract:Abstract 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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psilocybin lacks antidepressant like effect in the flinders sensitive line rat
Acta Neuropsychiatrica, 2019Co-Authors: Oskar Hougaard Jefsen, David J. Nutt, Kristoffer Hojgaard, Sofie Laage Christiansen, Betina Elfving, Gregers Wegener, Heidi Kaastrup MullerAbstract:OBJECTIVE Psilocybin is a serotonin receptor agonist with a therapeutic potential for treatment-resistant depression and other psychiatric illnesses. We investigated whether the administration of psilocybin had an antidepressant-like effect in a rat model of depression. METHODS Using the Flinders Sensitive Line (FSL) rat model of depression, we assessed the antidepressant-like effect of psilocin and psilocybin, measured as a reduction in immobility time in the forced swim test (FST). We measured locomotor activity in an open field test (OFT) to control for stimulant properties of the drugs. We performed a set of experiments to test different doses, treatment paradigms, and timing of the tests in relation to the drug administration. RESULTS Psilocin and psilocybin showed no effect on immobility, struggling, or swimming behaviour in the FST and no effect on locomotor activity in the OFT. FSL rats did show significantly more immobility than their control strain, the Flinders Resistant Line, as expected. CONCLUSION Psilocin and psilocybin showed no antidepressant-like effect in the FSL rats, despite a positive effect in humans. This suggests that other animal models of depression and other behavioural tests may be more appropriate for translational studies in the effects of psilocybin.
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effects of psilocybin therapy on personality structure
Acta Psychiatrica Scandinavica, 2018Co-Authors: David Erritzoe, Mendel Kaelen, Leor Roseman, David J. Nutt, Matthew M Nour, K Maclean, Robin L CarhartharrisAbstract:Objective To explore whether psilocybin with psychological support modulates personality parameters in patients suffering from treatment-resistant depression (TRD). Method Twenty 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. Results Neuroticism 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. Conclusion Our 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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psilocybin with psychological support improves emotional face recognition in treatment resistant depression
Psychopharmacology, 2018Co-Authors: J B Stroud, David J. Nutt, Robert Leech, Tom P Freeman, Chandni Hindocha, Will Lawn, H V Curran, Robin L CarhartharrisAbstract:RATIONALE: 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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increased amygdala responses to emotional faces after psilocybin for treatment resistant depression
Neuropharmacology, 2017Co-Authors: Leor Roseman, David J. Nutt, Lysia Demetriou, Matthew B Wall, Robin L CarhartharrisAbstract: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. TRIAL REGISTRATION: ISRCTN, number ISRCTN14426797. This article is part of the Special Issue entitled 'Psychedelics: New Doors, Altered Perceptions'.
