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Franz X Vollenweider - One of the best experts on this subject based on the ideXlab platform.
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Psilocybin assisted mindfulness training modulates self consciousness and brain default mode network connectivity with lasting effects
NeuroImage, 2019Co-Authors: Lukasz Smigielski, Matthias Scheidegger, Michael Kometer, Franz X VollenweiderAbstract:Both psychedelics and meditation exert profound modulatory effects on consciousness, perception and cognition, but their combined, possibly synergistic effects on neurobiology are unknown. Accordingly, we conducted a randomized, double-blind, placebo-controlled study with 38 participants following a single administration of the psychedelic Psilocybin (315 μg/kg p.o.) during a 5-day mindfulness retreat. Brain dynamics were quantified directly pre- and post-intervention by functional magnetic resonance imaging during the resting state and two meditation forms. The analysis of functional connectivity identified Psilocybin-related and mental state-dependent alterations in self-referential processing regions of the default mode network (DMN). Notably, decoupling of medial prefrontal and posterior cingulate cortices, which is thought to mediate sense of self, was associated with the subjective ego dissolution effect during the Psilocybin-assisted mindfulness session. The extent of ego dissolution and brain connectivity predicted positive changes in psycho-social functioning of participants 4 months later. Psilocybin, combined with meditation, facilitated neurodynamic modulations in self-referential networks, subserving the process of meditation by acting along the anterior-posterior DMN connection. The study highlights the link between altered self-experience and subsequent behavioral changes. Understanding how interventions facilitate transformative experiences may open novel therapeutic perspectives. Insights into the biology of discrete mental states foster our understanding of non-ordinary forms of human self-consciousness and their concomitant brain substrate.
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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.
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: Louisdavid 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.
David J. Nutt - 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: Louisdavid 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'.
Roland R Griffiths - One of the best experts on this subject based on the ideXlab platform.
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Psilocybin acutely alters the functional connectivity of the claustrum with brain networks that support perception memory and attention
NeuroImage, 2020Co-Authors: Frederick S Barrett, Roland R Griffiths, Samuel R Krimmel, David A Seminowicz, Brian N MathurAbstract:Abstract Psychedelic drugs, including the serotonin 2a (5-HT2A) receptor partial agonist Psilocybin, are receiving renewed attention for their possible efficacy in treating a variety of neuropsychiatric disorders. Psilocybin induces widespread dysregulation of cortical activity, but circuit-level mechanisms underlying this effect are unclear. The claustrum is a subcortical nucleus that highly expresses 5-HT2A receptors and provides glutamatergic inputs to arguably all areas of the cerebral cortex. We therefore tested the hypothesis that Psilocybin modulates claustrum function in humans. Fifteen healthy participants (10M, 5F) completed this within-subjects study in which whole-brain resting-state blood-oxygenation level-dependent (BOLD) signal was measured 100 min after blinded oral administration of placebo and 10 mg/70 kg Psilocybin. Left and right claustrum signal was isolated using small region confound correction. Psilocybin significantly decreased both the amplitude of low frequency fluctuations as well as the variance of BOLD signal in the left and right claustrum. Psilocybin also significantly decreased functional connectivity of the right claustrum with auditory and default mode networks (DMN), increased right claustrum connectivity with the fronto-parietal task control network (FPTC), and decreased left claustrum connectivity with the FPTC. DMN integrity was associated with right-claustrum connectivity with the DMN, while FPTC integrity and modularity were associated with right claustrum and left claustrum connectivity with the FPTC, respectively. Subjective effects of Psilocybin predicted changes in the amplitude of low frequency fluctuations and the variance of BOLD signal in the left and right claustrum. Observed effects were specific to claustrum, compared to flanking regions of interest (the left and right insula and putamen). This study used a pharmacological intervention to provide the first empirical evidence in any species for a significant role of 5-HT2A receptor signaling in claustrum functioning, and supports a possible role of the claustrum in the subjective and therapeutic effects of Psilocybin.
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emotions and brain function are altered up to one month after a single high dose of Psilocybin
Scientific Reports, 2020Co-Authors: Frederick S Barrett, Manoj K Doss, Nathan D Sepeda, James J Pekar, Roland R GriffithsAbstract:Psilocybin is a classic psychedelic compound that may have efficacy for the treatment of mood and substance use disorders. Acute Psilocybin effects include reduced negative mood, increased positive mood, and reduced amygdala response to negative affective stimuli. However, no study has investigated the long-term, enduring impact of Psilocybin on negative affect and associated brain function. Twelve healthy volunteers (7F/5M) completed an open-label pilot study including assessments 1-day before, 1-week after, and 1-month after receiving a 25 mg/70 kg dose of Psilocybin to test the hypothesis that Psilocybin administration leads to enduring changes in affect and neural correlates of affect. One-week post-Psilocybin, negative affect and amygdala response to facial affect stimuli were reduced, whereas positive affect and dorsal lateral prefrontal and medial orbitofrontal cortex responses to emotionally-conflicting stimuli were increased. One-month post-Psilocybin, negative affective and amygdala response to facial affect stimuli returned to baseline levels while positive affect remained elevated, and trait anxiety was reduced. Finally, the number of significant resting-state functional connections across the brain increased from baseline to 1-week and 1-month post-Psilocybin. These preliminary findings suggest that Psilocybin may increase emotional and brain plasticity, and the reported findings support the hypothesis that negative affect may be a therapeutic target for Psilocybin.
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Participant characteristics for Non-Drug, Psilocybin, LSD, ayahuasca, and DMT groups1,2,3.
2019Co-Authors: Roland R Griffiths, Matthew W. Johnson, Alan K Davis, Ethan S. Hurwitz, Robert JesseAbstract:Participant characteristics for Non-Drug, Psilocybin, LSD, ayahuasca, and DMT groups1,2,3.
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Comparison of encounter experience relative to other lifetime experiences in the Non-Drug, Psilocybin, LSD, ayahuasca, and DMT groups1,2,3.
2019Co-Authors: Roland R Griffiths, Matthew W. Johnson, Alan K Davis, Ethan S. Hurwitz, Robert JesseAbstract:Comparison of encounter experience relative to other lifetime experiences in the Non-Drug, Psilocybin, LSD, ayahuasca, and DMT groups1,2,3.
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Religious orientation before and after the encounter experience for Non-Drug, Psilocybin, LSD, ayahuasca, and DMT groups1,2,3.
2019Co-Authors: Roland R Griffiths, Matthew W. Johnson, Alan K Davis, Ethan S. Hurwitz, Robert JesseAbstract:Religious orientation before and after the encounter experience for Non-Drug, Psilocybin, LSD, ayahuasca, and DMT groups1,2,3.
Robin L. Carhart-harris - One of the best experts on this subject based on the ideXlab platform.
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Increased nature relatedness and decreased authoritarian political views after Psilocybin for treatment-resistant depression
Journal of Psychopharmacology, 2018Co-Authors: Taylor Lyons, Robin L. Carhart-harrisAbstract:Rationale:Previous research suggests that classical psychedelic compounds can induce lasting changes in personality traits, attitudes and beliefs in both healthy subjects and patient populations.Aim:Here we sought to investigate the effects of Psilocybin on nature relatedness and libertarian–authoritarian political perspective in patients with treatment-resistant depression (TRD).Methods:This open-label pilot study with a mixed-model design studied the effects of Psilocybin on measures of nature relatedness and libertarian–authoritarian political perspective in patients with moderate to severe TRD (n=7) versus age-matched non-treated healthy control subjects (n=7). Psilocybin was administered in two oral dosing sessions (10 mg and 25 mg) 1 week apart. Main outcome measures were collected 1 week and 7–12 months after the second dosing session. Nature relatedness and libertarian–authoritarian political perspective were assessed using the Nature Relatedness Scale (NR-6) and Political Perspective Questionnair...
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Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms
Scientific Reports, 2017Co-Authors: Robin L. Carhart-harris, Mendel Kaelen, Mark Bolstridge, Leor Roseman, Lysia Demetriou, Matthew B Wall, J Nienke Pannekoek, Mark Tanner, John Mcgonigle, Kevin MurphyAbstract:Psilocybin 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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Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study
The Lancet Psychiatry, 2016Co-Authors: Robin L. Carhart-harris, Mendel Kaelen, Mark Bolstridge, Camilla M.j. Day, Michael Bloomfield, James A Rickard, Ben Forbes, David Erritzoe, James Rucker, Amanda FeildingAbstract:Background Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of Psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of Psilocybin in patients with unipolar treatment-resistant depression. Methods In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of Psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of Psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797. Findings Psilocybin's acute psychedelic effects typically became detectable 30–60 min after dosing, peaked 2–3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0–1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1 week (mean QIDS difference −11·8, 95% CI −9·15 to −14·35, p=0·002, Hedges' g=3·1) and 3 months (−9·2, 95% CI −5·69 to −12·71, p=0·003, Hedges' g=2) after high-dose treatment. Marked and sustained improvements in anxiety and anhedonia were also noted. Interpretation This study provides preliminary support for the safety and efficacy of Psilocybin for treatment-resistant depression and motivates further trials, with more rigorous designs, to better examine the therapeutic potential of this approach. Funding Medical Research Council.
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Finding the self by losing the self: Neural correlates of ego-dissolution under Psilocybin
Human Brain Mapping, 2015Co-Authors: Alexander V. Lebedev, Gidon Rosenthal, Amanda Feilding, David J. Nutt, Martin Lövdén, Robin L. Carhart-harrisAbstract:Ego-disturbances have been a topic in schizophrenia research since the earliest clinical descriptions of the disorder. Manifesting as a feeling that one's "self," "ego," or "I" is disintegrating or that the border between one's self and the external world is dissolving, "ego-disintegration" or "dissolution" is also an important feature of the psychedelic experience, such as is produced by Psilocybin (a compound found in "magic mushrooms"). Fifteen healthy subjects took part in this placebo-controlled study. Twelve-minute functional MRI scans were acquired on two occasions: subjects received an intravenous infusion of saline on one occasion (placebo) and 2 mg Psilocybin on the other. Twenty-two visual analogue scale ratings were completed soon after scanning and the first principal component of these, dominated by items referring to "ego-dissolution", was used as a primary measure of interest in subsequent analyses. Employing methods of connectivity analysis and graph theory, an association was found between Psilocybin-induced ego-dissolution and decreased functional connectivity between the medial temporal lobe and high-level cortical regions. Ego-dissolution was also associated with a "disintegration" of the salience network and reduced interhemispheric communication. Addressing baseline brain dynamics as a predictor of drug-response, individuals with lower diversity of executive network nodes were more likely to experience ego-dissolution under Psilocybin. These results implicate MTL-cortical decoupling, decreased salience network integrity, and reduced inter-hemispheric communication in Psilocybin-induced ego disturbance and suggest that the maintenance of "self"or "ego," as a perceptual phenomenon, may rest on the normal functioning of these systems. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.
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The effects of Psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers
Frontiers in Human Neuroscience, 2014Co-Authors: Leor Roseman, Amanda Feilding, David J. Nutt, Robert Leech, Robin L. Carhart-harrisAbstract:Perturbing a system and observing the consequences is a classic scientific strategy for understanding a phenomenon. Psychedelic drugs perturb consciousness in a marked and novel way and thus are powerful tools for studying its mechanisms. In the present analysis, we measured changes in resting-state functional connectivity (RSFC) between a standard template of different independent components analysis (ICA)-derived resting state networks (RSNs) under the influence of two different psychoactive drugs, the stimulant/psychedelic hybrid, MDMA, and the classic psychedelic, Psilocybin. Both were given in placebo-controlled designs and produced marked subjective effects, although reports of more profound changes in consciousness were given after Psilocybin. Between-network RSFC was generally increased under Psilocybin, implying that networks become less differentiated from each other in the psychedelic state. Decreased RSFC between visual and sensorimotor RSNs was also observed. MDMA had a notably less marked effect on between-network RSFC, implying that the extensive changes observed under Psilocybin may be exclusive to classic psychedelic drugs and related to their especially profound effects on consciousness. The novel analytical approach applied here may be applied to other altered states of consciousness to improve our characterization of different conscious states and ultimately advance our understanding of the brain mechanisms underlying them.
