222 results found
Mertens LJ, Wall MB, Roseman L, et al., 2020, Therapeutic mechanisms of psilocybin: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 34, Pages: 167-180, ISSN: 0269-8811
Gandy S, Forstmann M, Carhart-Harris RL, et al., 2020, The potential synergistic effects between psychedelic administration and nature contact for the improvement of mental health, Health Psychology Open, Vol: 7
Therapeutic psychedelic administration and contact with nature have been associated with the same psychological mechanisms: decreased rumination and negative affect, enhanced psychological connectedness and mindfulness-related capacities, and heightened states of awe and transcendent experiences, all processes linked to improvements in mental health amongst clinical and healthy populations. Nature-based settings can have inherently psychologically soothing properties which may complement all stages of psychedelic therapy (mainly preparation and integration) whilst potentiating increases in nature relatedness, with associated psychological benefits. Maximising enhancement of nature relatedness through therapeutic psychedelic administration may constitute an independent and complementary pathway towards improvements in mental health that can be elicited by psychedelics.
Kettner H, Gandy S, Haijen E, et al., 2019, From egoism to ecoism: psychedelics increase nature relatedness in a state-mediated and context-dependent manner, International Journal of Environmental Research and Public Health, Vol: 16, Pages: 1-23, ISSN: 1660-4601
(1) Background: There appears to be a growing disconnection between humans and their natural environments which has been linked to poor mental health and ecological destruction. Previous research suggests that individual levels of nature relatedness can be increased through the use of classical psychedelic compounds, although a causal link between psychedelic use and nature relatedness has not yet been established. (2) Methods: Using correlations and generalized linear mixed regression modelling, we investigated the association between psychedelic use and nature relatedness in a prospective online study. Individuals planning to use a psychedelic received questionnaires 2 weeks before (N = 654), plus one day, 2 weeks, 4 weeks, and 2 years after a psychedelic experience. (3) Results: Frequency of lifetime psychedelic use was positively correlated with nature relatedness at baseline. Nature relatedness was significantly increased 2 weeks, 4 weeks and 2 years after the psychedelic experience. This increase was positively correlated with concomitant increases in psychological well-being and dependent on the extent of ego-dissolution and the perceived influence of natural surroundings during the acute psychedelic state. (4) Conclusions: The here presented evidence for a context- and state-dependent causal effect of psychedelic use on nature relatedness bears relevance for psychedelic treatment models in mental health and, in the face of the current ecological crisis, planetary health.
Mertens LJ, Wall MB, Roseman L, et al., 2019, Therapeutic mechanisms of psychedelic drugs: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression, 32nd Congress of the European-College-of-Neuropsychopharmacology (ECNP), Publisher: ELSEVIER, Pages: S416-S417, ISSN: 0924-977X
Timmermann Slater CB, Roseman L, Schartner M, et al., 2019, Neural correlates of the DMT experience as assessed with multivariate EEG, Scientific Reports, Vol: 9, Pages: 1-13, ISSN: 2045-2322
Studying transitions in and out of the altered state of consciousness caused by intravenous (IV) N,N-Dimethyltryptamine (DMT - a fast-acting tryptamine psychedelic) offers a safe and powerful means of advancing knowledge on the neurobiology of conscious states. Here we sought to investigate the effects of IV DMT on the power spectrum and signal diversity of human brain activity (6 female, 7 male) recorded via multivariate EEG, and plot relationships between subjective experience, brain activity and drug plasma concentrations across time. Compared with placebo, DMT markedly reduced oscillatory power in the alpha and beta bands and robustly increased spontaneous signal diversity. Time-referenced neurophenomenological analyses revealed close relationships between changes in various aspects of subjective experience and changes in brain activity. Importantly, the emergence of oscillatory activity within the delta and theta frequency bands was found to correlate with the peak of the experience - particularly its eyes-closed visual component. These findings highlight marked changes in oscillatory activity and signal diversity with DMT that parallel broad and specific components of the subjective experience, thus advancing our understanding of the neurobiological underpinnings of immersive states of consciousness.
Russ SL, Carhart-Harris RL, Maruyama G, et al., 2019, Replication and extension of a model predicting response to psilocybin, PSYCHOPHARMACOLOGY, Vol: 236, Pages: 3221-3230, ISSN: 0033-3158
Pallavicini C, Vilas MG, Villarreal M, et al., 2019, Spectral signatures of serotonergic psychedelics and glutamatergic dissociatives., Neuroimage, Vol: 200, Pages: 281-291
Classic serotonergic psychedelics are remarkable for their capacity to induce reversible alterations in consciousness of the self and the surroundings, mediated by agonism at serotonin 5-HT2A receptors. The subjective effects elicited by dissociative drugs acting as N-methyl-D-aspartate (NMDA) antagonists (e.g. ketamine and phencyclidine) overlap in certain domains with those of serotonergic psychedelics, suggesting some potential similarities in the brain activity patterns induced by both classes of drugs, despite different pharmacological mechanisms of action. We investigated source-localized magnetoencephalography recordings to determine the frequency-specific changes in oscillatory activity and long-range functional coupling that are common to two serotonergic compounds (lysergic acid diethylamide [LSD] and psilocybin) and the NMDA-antagonist ketamine. Administration of the three drugs resulted in widespread and broadband spectral power reductions. We established their similarity by using different pairs of compounds to train and subsequently evaluate multivariate machine learning classifiers. After applying the same methodology to functional connectivity values, we observed a pattern of occipital, parietal and frontal decreases in the low alpha and theta bands that were specific to LSD and psilocybin, as well as decreases in the low beta band common to the three drugs. Our results represent a first effort in the direction of quantifying the similarity of large-scale brain activity patterns induced by drugs of different mechanism of action, confirming the link between changes in theta and alpha oscillations and 5-HT2A agonism, while also revealing the decoupling of activity in the beta band as an effect shared between NMDA antagonists and 5-HT2A agonists. We discuss how these frequency-specific convergences and divergences in the power and functional connectivity of brain oscillations might relate to the overlapping subjective effects of serotonergic psychedelic
Lord L-D, Expert P, Atasoy S, et al., 2019, Dynamical exploration of the repertoire of brain networks at rest is modulated by psilocybin, NeuroImage, Vol: 199, Pages: 127-142, ISSN: 1053-8119
Growing evidence from the dynamical analysis of functional neuroimaging data suggests that brain function can be understood as the exploration of a repertoire of metastable connectivity patterns ('functional brain networks'), which potentially underlie different mental processes. The present study characterizes how the brain's dynamical exploration of resting-state networks is rapidly modulated by intravenous infusion of psilocybin, a tryptamine psychedelic found in "magic mushrooms". We employed a data-driven approach to characterize recurrent functional connectivity patterns by focusing on the leading eigenvector of BOLD phase coherence at single-TR resolution. Recurrent BOLD phase-locking patterns (PL states) were assessed and statistically compared pre- and post-infusion of psilocybin in terms of their probability of occurrence and transition profiles. Results were validated using a placebo session. Recurrent BOLD PL states revealed high spatial overlap with canonical resting-state networks. Notably, a PL state forming a frontoparietal subsystem was strongly destabilized after psilocybin injection, with a concomitant increase in the probability of occurrence of another PL state characterized by global BOLD phase coherence. These findings provide evidence of network-specific neuromodulation by psilocybin and represent one of the first attempts at bridging molecular pharmacodynamics and whole-brain network dynamics.
Roseman L, 2019, Functional imaging investigation of psychedelic visual imagery
Psychedelics can induce eyes-closed imagery in which various visions can be experienced. These visions vary from simple geometrical patterns, to more complex imagery, to full immersion within “other realms”. Past studies suggest that the visual cortex is involved in processing these visions, yet these studies were limited into investigation of activity. In this thesis, the aim was to expand on the involvement of the visual cortex by investigating processes that are beyond simple activation maps, such as functional connectivity and dynamics. In study 1, it was hypothesized that the visual cortex will show increased functional connectivity with many cortical and subcortical regions. This was investigated with 15 subjects that were scanned using fMRI under the influence of 75 µg of LSD or placebo. The results of this study showed increased resting state functional connectivity (RSFC) between the primary visual cortex and many cortical and subcortical regions. This result correlated with subjective ratings of psychedelic imagery and with occipital alpha power suppression measured with MEG, which is a reliable neural correlate of the intensity of the psychedelic state. It study 2, it was hypothesized that connectivity within the visual cortex would match its retinotopic architecture. Retinotopic mapping is the representation of the visual field (the world we observe) in the visual cortex – e.g. areas which are near to each other in the visual field will be near each other in the visual cortex. In this study, it was found that under LSD (same procedure as study 1), with eyes closed, connectivity patterns between different subregions of the visual cortex matched the retinotopic mapping of these regions, suggesting that the visual system behaves as if it is seeing spatially localized input, with eyes-closed under LSD. In study 3, it was hypothesized that during the onset phase of psychedelic imagery, the activation of subregions of the visual cortex
Timmermann C, Roseman L, Schartner M, et al., 2019, Neural correlates of the DMT experience as assessed via multivariate EEG
<jats:title>Abstract</jats:title><jats:p>Studying transitions in and out of the altered state of consciousness caused by intravenous (IV) N,N-Dimethyltryptamine (DMT – a fast-acting tryptamine psychedelic) offers a safe and powerful means of advancing knowledge on the neurobiology of conscious states. Here we sought to investigate the effects of IV DMT on the power spectrum and signal diversity of human brain activity (6 female, 7 male) recorded via multivariate EEG, and plot relationships between subjective experience, brain activity and drug plasma concentrations across time. Compared with placebo, DMT markedly reduced oscillatory power in the <jats:italic>alpha</jats:italic> and <jats:italic>beta</jats:italic> bands and robustly increased spontaneous signal diversity. Time-referenced analyses revealed close relationships between changes in various aspects of subjective experience and changes in brain activity. Importantly, the emergence of oscillatory activity within the delta and theta frequency bands was found to correlate with the peak of the experience, and particularly its eyes-closed visual component. These findings highlight marked changes in oscillatory activity and signal diversity with DMT that parallel broad and specific components of the relevant subjective experience and thus further our understanding of the neurobiological underpinnings of immersive states of consciousness.</jats:p>
Roseman L, Haijen E, Idialu-Ikato K, et al., 2019, Emotional breakthrough and psychedelics: Validation of the Emotional Breakthrough Inventory, Journal of Psychopharmacology, Pages: 026988111985597-026988111985597, ISSN: 0269-8811
<jats:sec><jats:title>Background:</jats:title><jats:p> Psychedelic therapy is gaining recognition and the nature of the psychedelic experience itself has been found to mediate subsequent long-term psychological changes. Much emphasis has been placed on the occurrence of mystical-type experiences in determining long-term responses to psychedelics yet here we demonstrate the importance of another component, namely: emotional breakthrough. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> Three hundred and seventy-nine participants completed online surveys before and after a planned psychedelic experience. Items pertaining to emotional breakthrough were completed one day after the psychedelic experience, as were items comprising the already validated Mystical Experience Questionnaire and the Challenging Experience Questionnaire. Emotional breakthrough, Mystical Experience Questionnaire and Challenging Experience Questionnaire scores were used to predict changes in well-being (Warwick-Edinburgh Mental Wellbeing Scale) in a subsample of 75 participants with low well-being baseline scores (⩽45). </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Factor analyses revealed six emotional breakthrough items with high internal consistency (Cronbach’s alpha=0.932) and supported our prior hypothesis that emotional breakthrough is a distinct component of the psychedelic experience. Emotional breakthrough scores behaved dose-dependently, and were higher if the psychedelic was taken with therapeutic planning and intent. Emotional breakthrough, Mystical Experience Questionnaire and Challenging Experience Questionnaire scores combined, significantly predicted subsequent changes in well-being ( r=0.45, p=0.0005, n=75), with each scale contributing significant predictive value. Emotional breakthrough and Mystical Experience Questionnaire scores
Carhart-Harris RL, Friston KJ, 2019, REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics, PHARMACOLOGICAL REVIEWS, Vol: 71, Pages: 316-344, ISSN: 0031-6997
Scott G, Carhart-Harris R, 2019, Psychedelics as a treatment for disorders of consciousness, Neuroscience of Consciousness, Vol: 2019, Pages: 1-8, ISSN: 2057-2107
Based on its ability to increase brain complexity, a seemingly reliable index of conscious level, we proposetesting the capacity ofthe classic psychedelic, psilocybin,to increase conscious awarenessin patients with disorders of consciousness.We alsoconfrontthe considerable ethical and practical challengesthis proposal must address, if this hypothesis is to be directly assessed.
Russ SL, Carhart-Harris RL, Maruyama G, et al., 2019, States and traits related to the quality and consequences of psychedelic experiences, Psychology of Consciousness: Theory Research, and Practice, Vol: 6, Pages: 1-21, ISSN: 2326-5523
Many individuals experience significant positive psychological change after ingesting psychedelic agents such as psilocybin, LSD, and ayahuasca, but some do not. Such changes appear to be mediated by definable and measurable mystical experiences (MEs) during the psychedelic session, which have been shown in previous research (e.g., Griffiths, Richards, McCann, & Jesse, 2006) to be related to long-term positive personal change. Individual responses to psychedelic agents are characteristically difficult to predict, however, necessitating improved identification of predictors to (a) reduce the possibility of significant challenging experiences and sequelae and (b) increase the possibility of MEs and long-term beneficial outcomes. Our study utilized crowdsourced retrospective survey data from 143 Amazon Mechanical Turk participants who self-administered psilocybin in the past year to identify factors related to MEs and/or challenging experiences. The best performing regression model explained 66% of the variance in ME scores on the 30-item Mystical Experience Questionnaire (MacLean, Leoutsakos, Johnson, & Griffiths, 2012) and 56% of the variance in scores on the dread subscale of the Sacred Emotions Scale (Burdzy, 2014). A state of surrender at the start of the psilocybin session most strongly explained MEs, and a state of preoccupation most strongly explained challenging experiences. The trait absorption was a strong secondary predictor in both models, along with smaller predictors. Additionally, the occurrence of MEs during the psilocybin session explained long-term positive change. Based on these findings, the presented models appear to provide a powerful framework for explaining the immediate quality and long-term consequences of psychedelic experiences. Limitations as well as implications for therapeutic applications are discussed.
Erritzoe D, Smith J, Fisher PM, et al., 2019, Recreational use of psychedelics is associated with elevated personality trait openness: Exploration of associations with brain serotonin markers., J Psychopharmacol, Pages: 269881119827891-269881119827891
BACKGROUND:: Recent studies have suggested therapeutic benefits of psychedelics for a variety of mental health conditions. The understanding of how single psychedelic administrations can induce long-lasting effects are, in large, still lacking. However, recent studies in both healthy and clinical populations suggest a role for personality changes. AIM:: To test support for some of these plausible mechanisms we evaluated (cross-sectional) associations between recreational use of psychedelics and 3,4-methylene-dioxymethamphetamine (MDMA) and (a) personality measures and (b) key markers of cerebral serotonergic signalling (serotonin transporter and serotonin-2A-receptor binding). METHODS:: In 10 psychedelic-preferring recreational users, 14 MDMA-preferring users and 21 non-using controls, personality was assessed using the 'big five' instrument Revised NEO Personality Inventory (NEO-PI-R). Frontal serotonin transporter and serotonin-2A-receptor binding potentials were quantified using [11C]DASB and [18F]altanserin positron emission tomography, respectively. RESULTS:: Of the five NEO-PI-R traits, only openness to experience scores differed between the three groups; psychedelic-preferring recreational users showing higher openness to experience scores when compared with both MDMA-preferring users and controls. Openness to experience scores were positively associated with lifetime number of psychedelic exposures, and among all MDMA-preferring user/psychedelic-preferring recreational user individuals, frontal serotonin transporter binding - but not frontal serotonin-2A-receptor binding - was positively associated with openness to experience. CONCLUSION:: Our findings from this cross-sectional study support increasing evidence of a positive association between psychedelic experiences and openness to experience, and (a) expands this to the context of 'recreational' psychedelics use, and (b) links serotonergic neurotransmission to openness to experience. A modulation of perso
Carhart-Harris RL, 2019, How do psychedelics work?, Curr Opin Psychiatry, Vol: 32, Pages: 16-21
PURPOSE OF REVIEW: Psychedelics are reawakening interest from psychiatry, cognitive neuroscience and the general public with impressive outcomes in small-scale clinical trials, intriguing human brain imaging work and high-impact journalism. RECENT FINDINGS: This brief opinion piece offers a perspective on how psychedelics work in the brain that may help contextualize these developments. It attempts to link various scales of action, from the molecular (serotonin 2A receptor agonism) through to the anatomical and functional (heightened plasticity) and up to the dynamic (increased brain entropy), systems level (network disintegration and desegregation) and experiential. SUMMARY: It is proposed that psychedelics initiate a cascade of neurobiological changes that manifest at multiple scales and ultimately culminate in the relaxation of high-level beliefs. The purpose of psychedelic therapy is to harness the opportunity afforded by this belief-relaxation to achieve a healthy revision of pathological beliefs.
Moroz M, Carhart-Harris RL, 2018, Employing synergistic interactions of virtual reality and psychedelics in neuropsychopharmacology
The increased prevalence of various psychiatric disorders continue to concern , , . Promising results are starting to emerge from recent experimental interventions employing VR , , and psychedelics ,  individually. We propose that for certain pathologies researchers need not bother themselves as to which medium offers greater hope. Instead, we hypothesize that the most effective interventions shall necessarily come from a composite approach utilizing both.Traditional medicine adopts similar such synergistic strategies. Combining codeine and acetaminophen increases the analgesic effect. While research into the therapeutic effects of novel interventions using VR and psychedelics, independent of one another, is still in its infancy, we believe that the increased utility of a dual approach justifies closer examination without delay. We posit three main benefits from this integrated intervention. Increases in the efficacy of each individual paradigm due to synergistic coupling, and increases in specificity due to the ability to tailor bespoke therapies for particular individuals and groups, are achieved directly. Such increases in efficacy consequently lead to the third benefit of allowing a therapeutic effect to be achieved while using lower doses of a given psychedelic compound .
Haijen ECHM, Kaelen M, Roseman L, et al., 2018, Predicting responses to psychedelics: a prospective study, Frontiers in Pharmacology, Vol: 9, ISSN: 1663-9812
Responses to psychedelics are notoriously difficult to predict, yet significant work is currently underway to assess their therapeutic potential and the level of interest in psychedelics among the general public appears to be increasing. We aimed to collect prospective data in order to improve our ability to predict acute- and longer-term responses to psychedelics. Individuals who planned to take a psychedelic through their own initiative participated in an online survey (www.psychedelicsurvey.com). Traits and variables relating to set, setting and the acute psychedelic experience were measured at five different time points before and after the experience. Principle component and regression methods were used to analyse the data. Sample sizes for the five time points included N= 654, N= 535, N= 379, N= 315, and N= 212 respectively. Psychological well-being was increased two weeks after a psychedelic experience and remained at this level after four weeks. This increase was larger for individuals who scored higher for a ‘mystical-type experience’, and smaller for those who scored higher for ‘challenging experience’. Having ‘clear intentions’ for the experience was conducive to mystical-type experiences. Having a positive ‘set’, as well as having the experience with intentions related to ‘recreation’, were both found to decrease the likelihood of having a challenging experience. The trait ‘absorption’ and higher drug doses promoted both mystical-type and challenging experiences. When comparing different types of variables, traits variables seemed to explain most variance in the change in well-being after a psychedelic experience. These results confirm the importance of extra-pharmacological factors in determining responses to a psychedelic. We view this study as an early step towards the development of empirical guidelines that can evolve and improve iteratively with the ultimate purpose of guiding
Roseman L, Demetriou L, Wall M, et al., 2018, Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression, Neuropharmacology, Vol: 142, Pages: 263-269, ISSN: 0028-3908
Recent evidence indicates that psilocybin with psychological support may be effective for treating depression. Some studies have found that patients with depression show heightened amygdala responses to fearful faces and there is reliable evidence that treatment with SSRIs attenuates amygdala responses (Ma, 2015). We hypothesised that amygdala responses to emotional faces would be altered post-treatment with psilocybin. In this open-label study, 20 individuals diagnosed with moderate to severe, treatment-resistant depression, underwent two separate dosing sessions with psilocybin. Psychological support was provided before, during and after these sessions and 19 completed fMRI scans one week prior to the first session and one day after the second and last. Neutral, fearful and happy faces were presented in the scanner and analyses focused on the amygdala. Group results revealed rapid and enduring improvements in depressive symptoms post psilocybin. Increased responses to fearful and happy faces were observed in the right amygdala post-treatment, and right amygdala increases to fearful versus neutral faces were predictive of clinical improvements at 1-week. Psilocybin with psychological support was associated with increased amygdala responses to emotional stimuli, an opposite effect to previous findings with SSRIs. This suggests fundamental differences in these treatments’ therapeutic actions, with SSRIs mitigating negative emotions and psilocybin allowing patients to confront and work through them. Based on the present results, we propose that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression, enabling patients to reconnect with their emotions.
Erritzoe D, Roseman L, Nour MM, et al., 2018, Effects of psilocybin therapy on personality structure, Acta Psychiatrica Scandinavica, Vol: 138, Pages: 368-378, ISSN: 1600-0447
ObjectiveTo explore whether psilocybin with psychological support modulates personality parameters in patients suffering from treatment‐resistant depression (TRD).MethodTwenty patients with moderate or severe, unipolar, TRD received oral psilocybin (10 and 25 mg, one week apart) in a supportive setting. Personality was assessed at baseline and at 3‐month follow‐up using the Revised NEO Personality Inventory (NEO‐PI‐R), the subjective psilocybin experience with Altered State of Consciousness (ASC) scale, and depressive symptoms with QIDS‐SR16.ResultsNeuroticism scores significantly decreased while Extraversion increased following psilocybin therapy. These changes were in the direction of the normative NEO‐PI‐R data and were both predicted, in an exploratory analysis, by the degree of insightfulness experienced during the psilocybin session. Openness scores also significantly increased following psilocybin, whereas Conscientiousness showed trend‐level increases, and Agreeableness did not change.ConclusionOur observation of changes in personality measures after psilocybin therapy was mostly consistent with reports of personality change in relation to conventional antidepressant treatment, although the pronounced increases in Extraversion and Openness might constitute an effect more specific to psychedelic therapy. This needs further exploration in future controlled studies, as do the brain mechanisms of postpsychedelic personality change.
Carhart-Harris RL, 2018, The entropic brain - revisited, NEUROPHARMACOLOGY, Vol: 142, Pages: 167-178, ISSN: 0028-3908
Lyons T, Carhart-Harris RL, 2018, More realistic forecasting of future life events after psilocybin for treatment-resistant depression, Frontiers in Psychology, Vol: 9, ISSN: 1664-1078
Background: Evidence suggests that classical psychedelics can promote enduring changes in personality, attitudes and optimism, as well as improvements in mental health outcomes.Aim: To investigate the effects of a composite intervention, involving psilocybin, on pessimism biases in patients with treatment-resistant depression (TRD).Methods: Patients with TRD (n = 15) and matched, untreated non-depressed controls (n = 15) performed the Prediction Of Future Life Events (POFLE) task. The POFLE task requires participants to predict the likelihood of certain life events occurring within a 30-day period, after which the actual rate of event occurrence is reported; this gives an index of potential pessimism versus optimism bias. Psilocybin was administered in two oral dosing sessions (10 and 25 mg) one week apart. Main outcome measures were collected at baseline and one week after the second dosing session.Results: Patients showed a significant pessimism bias at baseline [t(14) = -3.260, p = 0.006; 95% CI (-0.16, -0.03), g = 1.1] which was related to the severity of their depressive symptoms (rs = -0.55, p = 0.017). One week after psilocybin treatment, this bias was significantly decreased [t(14) = -2.714, p = 0.017; 95% CI (-0.21, -0.02), g = 0.7] and depressive symptoms were greatly improved [t(14) = 7.900, p < 0.001; 95% CI (16.17, 28.23), g = 1.9]; moreover, the magnitude of change in both variables was significantly correlated (r = -0.57, p = 0.014). Importantly, post treatment, patients became significantly more accurate at predicting the occurrence of future life events [t(14) = 1.857, p = 0.042; 95% CI (-0.01, 0.12), g = 0.6] whereas no such change was observed in the control subjects.Conclusion: These findings suggest that psilocybin with psychological support might correct pessimism biases in TRD, enabling a more positive and accurate outlook.
Deco G, Cruzat J, Cabral J, et al., 2018, Whole-brain multimodal neuroimaging model using serotonin receptor maps explains non-linear functional effects of LSD, Current Biology, Vol: 28, Pages: 3065-3074.E6, ISSN: 0960-9822
Understanding the underlying mechanisms of the human brain in health and disease will require models with necessary and sufficient details to explain how function emerges from the underlying anatomy and is shaped by neuromodulation. Here, we provide such a detailed causal explanation using a whole-brain model integrating multimodal imaging in healthy human participants undergoing manipulation of the serotonin system. Specifically, we combined anatomical data from diffusion magnetic resonance imaging (dMRI) and functional magnetic resonance imaging (fMRI) with neurotransmitter data obtained with positron emission tomography (PET) of the detailed serotonin 2A receptor (5-HT2AR) density map. This allowed us to model the resting state (with and without concurrent music listening) and mechanistically explain the functional effects of 5-HT2AR stimulation with lysergic acid diethylamide (LSD) on healthy participants. The whole-brain model used a dynamical mean-field quantitative description of populations of excitatory and inhibitory neurons as well as the associated synaptic dynamics, where the neuronal gain function of the model is modulated by the 5-HT2AR density. The model identified the causative mechanisms for the non-linear interactions between the neuronal and neurotransmitter system, which are uniquely linked to (1) the underlying anatomical connectivity, (2) the modulation by the specific brainwide distribution of neurotransmitter receptor density, and (3) the non-linear interactions between the two. Taking neuromodulatory activity into account when modeling global brain dynamics will lead to novel insights into human brain function in health and disease and opens exciting possibilities for drug discovery and design in neuropsychiatric disorders.
Carhart-Harris RL, 2018, Serotonin, psychedelics and psychiatry, World Psychiatry, Vol: 17, Pages: 358-359, ISSN: 1723-8617
In recent years, the scientific study of meditation and psychedelic drugs has seen remarkable developments. The increased focus on meditation in cognitive neuroscience has led to a cross-cultural classification of standard meditation styles validated by functional and structural neuroanatomical data. Meanwhile, the renaissance of psychedelic research has shed light on the neurophysiology of altered states of consciousness induced by classical psychedelics, such as psilocybin and LSD, whose effects are mainly mediated by agonism of serotonin receptors. Few attempts have been made at bridging these two domains of inquiry, despite intriguing evidence of overlap between the phenomenology and neurophysiology of meditation practice and psychedelic states. In particular, many contemplative traditions explicitly aim at dissolving the sense of self by eliciting altered states of consciousness through meditation, while classical psychedelics are known to produce significant disruptions of self-consciousness, a phenomenon known as drug-induced ego dissolution. In this article, we discuss available evidence regarding convergences and differences between phenomenological and neurophysiological data on meditation practice and psychedelic drug-induced states, with a particular emphasis on alterations of self-experience. While both meditation and psychedelics may disrupt self-consciousness and underlying neural processes, we emphasize that neither meditation nor psychedelic states can be conceived as simple, uniform categories. Moreover, we suggest that there are important phenomenological differences even between conscious states described as experiences of self-loss. As a result, we propose that self-consciousness may be best construed as a multidimensional construct, and that “self-loss,” far from being an unequivocal phenomenon, can take several forms. Indeed, various aspects of self-consciousness, including narrative aspects linked to autobiographical memory, self-
Near-death experiences (NDEs) are complex subjective experiences, which have been previously associated with the psychedelic experience and more specifically with the experience induced by the potent serotonergic, N,N-Dimethyltryptamine (DMT). Potential similarities between both subjective states have been noted previously, including the subjective feeling of transcending one’s body and entering an alternative realm, perceiving and communicating with sentient ‘entities’ and themes related to death and dying. In this within-subjects placebo-controled study we aimed to test the similarities between the DMT state and NDEs, by administering DMT and placebo to 13 healthy participants, who then completed a validated and widely used measure of NDEs. Results revealed significant increases in phenomenological features associated with the NDE, following DMT administration compared to placebo. Also, we found significant relationships between the NDE scores and DMT-induced ego-dissolution and mystical-type experiences, as well as a significant association between NDE scores and baseline trait ‘absorption’ and delusional ideation measured at baseline. Furthermore, we found a significant overlap in nearly all of the NDE phenomenological features when comparing DMT-induced NDEs with a matched group of ‘actual’ NDE experiencers. These results reveal a striking similarity between these states that warrants further investigation.
Carhart-Harris RL, Roseman L, Haijen E, et al., 2018, Psychedelics and the essential importance of context, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 32, Pages: 725-731, ISSN: 0269-8811
Lyons T, Carhart-Harris RL, 2018, Increased nature relatedness and decreased authoritarian political views after psilocybin for treatment-resistant depression, Journal of Psychopharmacology, Vol: 32, Pages: 811-819, ISSN: 1461-7285
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 Questionnaire (PPQ-5), respectively.Results:Nature relatedness significantly increased (t(6)=−4.242, p=0.003) and authoritarianism significantly decreased (t(6)=2.120, p=0.039) for the patients 1 week after the dosing sessions. At 7–12 months post-dosing, nature relatedness remained significantly increased (t(5)=−2.707, p=0.021) and authoritarianism remained decreased at trend level (t(5)=−1.811, p=0.065). No differences were found on either measure for the non-treated healthy control subjects.Conclusions:This pilot study suggests that psilocybin with psychological support might produce lasting changes in attitudes and beliefs. Although it would be premature to infer causality from this small study, the possibility of drug-induced changes in belief systems seems sufficiently intriguing and timely to deserve further investigation.
Gabay AS, Carhart-Harris RL, Mazibuko N, et al., 2018, Psilocybin and MDMA reduce costly punishment in the Ultimatum Game, SCIENTIFIC REPORTS, Vol: 8, ISSN: 2045-2322
Disruptions in social decision-making are becoming evident in many psychiatric conditions. These are studied using paradigms investigating the psychological mechanisms underlying interpersonal interactions, such as the Ultimatum Game (UG). Rejection behaviour in the UG represents altruistic punishment – the costly punishment of norm violators – but the mechanisms underlying it require clarification. To investigate the psychopharmacology of UG behaviour, we carried out two studies with healthy participants, employing serotonergic agonists: psilocybin (open-label, within-participant design, N = 19) and 3,4-methylenedioxymethamphetamine (MDMA; placebo-controlled, double-blind, crossover design, N = 20). We found that both MDMA and psilocybin reduced rejection of unfair offers (odds ratio: 0.57 and 0.42, respectively). The reduction in rejection rate following MDMA was associated with increased prosociality (R2 = 0.26, p = 0.025). In the MDMA study, we investigated third-party decision-making and proposer behaviour. MDMA did not reduce rejection in the third-party condition, but produced an increase in the amount offered to others (Cohen’s d = 0.82). We argue that these compounds altered participants’ conceptualisation of ‘social reward’, placing more emphasis on the direct relationship with interacting partners. With these compounds showing efficacy in drug-assisted psychotherapy, these studies are an important step in the further characterisation of their psychological effects.
Carrillo F, Sigman M, Fernandez Slezak D, et al., 2018, Natural speech algorithm applied to baseline interview data can predict which patients will respond to psilocybin for treatment-resistant depression, JOURNAL OF AFFECTIVE DISORDERS, Vol: 230, Pages: 84-86, ISSN: 0165-0327
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