Publications
216 results found
Eckernäs E, Koomen J, Timmermann C, et al., 2023, Optimized infusion rates for N,N-dimethyltryptamine to achieve a target psychedelic intensity based on a modeling and simulation framework., CPT Pharmacometrics Syst Pharmacol
N,N-dimethyltryptamine (DMT) is a psychedelic compound that is being studied as a therapeutic option in various psychiatric disorders. Due to its short half-life, continuous infusion of DMT has been proposed to extend the psychedelic experience and potential therapeutic effects. The primary aim of this work was to design an infusion protocol for DMT based on a desired level of psychedelic intensity using population pharmacokinetic/pharmacodynamic modeling. As a secondary aim, the impact of choosing a continuous variable or a bounded integer pharmacokinetic/pharmacodynamic model to inform such an infusion protocol was investigated. A previously published continuous variable model and two newly developed bounded integer models were used to assess optimal doses for achieving a target response. Simulations were performed to identify an optimal combination of a bolus dose and an infusion rate. Based on the simulations, optimal doses to achieve intensity ratings between 7 and 9 (possible range = 0-10) were a bolus dose of 16 mg DMT fumarate followed by an infusion rate of 1.4 mg/min based on the continuous variable model and 14 mg with 1.2 mg/min for the two bounded integer models. However, the proportion within target was low (<53%) for all models, indicating that individual dose adjustments would be necessary. Furthermore, some differences between the models were observed. The bounded integer models generally predicted lower proportions within a target of 7-9 with higher proportions exceeding target compared with the continuous variable model. However, results varied depending on target response with the major differences observed at the boundaries of the scale.
Simonsson O, Carlbring P, Carhart-Harris R, et al., 2023, Assessing the risk of symptom worsening in psilocybin-assisted therapy for depression: A systematic review and individual participant data meta-analysis., Psychiatry Res, Vol: 327
We conducted a meta-analysis using individual participant data from three, two-dose psilocybin trials for depression (N = 102) with the aim of assessing the risk of symptom worsening. Clinically significant symptom worsening occurred for a minority of participants in the psilocybin and escitalopram conditions (∼10%) and for a majority of participants in the waitlist condition (63.6%). Using data from the two trials with control arms, the psilocybin arm showed a lower likelihood of symptom worsening versus waitlist, and no difference in the likelihood of symptom worsening versus escitalopram. The limitation of a relatively small sample size should be addressed in future studies.
Dougherty RF, Clarke P, Atli M, et al., 2023, Psilocybin therapy for treatment resistant depression: prediction of clinical outcome by natural language processing., Psychopharmacology (Berl)
RATIONALE: Therapeutic administration of psychedelics has shown significant potential in historical accounts and recent clinical trials in the treatment of depression and other mood disorders. A recent randomized double-blind phase-IIb study demonstrated the safety and efficacy of COMP360, COMPASS Pathways' proprietary synthetic formulation of psilocybin, in participants with treatment-resistant depression. OBJECTIVE: While the phase-IIb results are promising, the treatment works for a portion of the population and early prediction of outcome is a key objective as it would allow early identification of those likely to require alternative treatment. METHODS: Transcripts were made from audio recordings of the psychological support session between participant and therapist 1 day post COMP360 administration. A zero-shot machine learning classifier based on the BART large language model was used to compute two-dimensional sentiment (valence and arousal) for the participant and therapist from the transcript. These scores, combined with the Emotional Breakthrough Index (EBI) and treatment arm were used to predict treatment outcome as measured by MADRS scores. (Code and data are available at https://github.com/compasspathways/Sentiment2D .) RESULTS: Two multinomial logistic regression models were fit to predict responder status at week 3 and through week 12. Cross-validation of these models resulted in 85% and 88% accuracy and AUC values of 88% and 85%. CONCLUSIONS: A machine learning algorithm using NLP and EBI accurately predicts long-term patient response, allowing rapid prognostication of personalized response to psilocybin treatment and insight into therapeutic model optimization. Further research is required to understand if language data from earlier stages in the therapeutic process hold similar predictive power.
Zeifman RJ, Kettner H, Pagni BA, et al., 2023, Co-use of MDMA with psilocybin/LSD may buffer against challenging experiences and enhance positive experiences, Scientific Reports, Vol: 13, Pages: 1-11, ISSN: 2045-2322
Psilocybin and lysergic acid diethylamide (LSD) experiences can range from very positive to highly challenging (e.g., fear, grief, and paranoia). These challenging experiences contribute to hesitancy toward psychedelic-assisted psychotherapy among health care providers and patients. Co-use of 3,4-Methylenedioxy methamphetamine (MDMA) with psilocybin/LSD anecdotally reduces challenging experiences and enhances positive experiences associated with psilocybin/LSD. However, limited research has investigated the acute effects of co-use of MDMA and psilocybin/LSD. In a prospective convenience sample (N = 698) of individuals with plans to use psilocybin/LSD, we examined whether co-use of MDMA with psilocybin/LSD (n = 27) is associated with differences in challenging or positive experiences. Challenging experiences were measured using the Challenging Experiences Questionnaire and positive experiences were measured using the Mystical Experience Questionnaire and single-item measures of self-compassion, compassion, love, and gratitude. Potentially confounding variables were identified and included as covariates. Relative to psilocybin/LSD alone, co-use of psilocybin/LSD with a self-reported low (but not medium–high) dose of MDMA was associated with significantly less intense total challenging experiences, grief, and fear, as well as increased self-compassion, love and gratitude. Co-use of psilocybin/LSD and MDMA was not associated with differences in mystical-type experiences or compassion. Findings suggest co-use of MDMA with psilocybin/LSD may buffer against some aspects of challenging experiences and enhance certain positive experiences. Limitations include use of a convenience sample, small sample size, and non-experimental design. Additional studies (including controlled dose–response studies) that examine the effects and safety of co-administering MDMA with psilocybin/LSD (in healthy controls and clinical samples) are warranted an
Zeifman RJ, Wagner AC, Monson CM, et al., 2023, How does psilocybin therapy work? An exploration of experiential avoidance as a putative mechanism of change., J Affect Disord, Vol: 334, Pages: 100-112
BACKGROUND: Psilocybin therapy is receiving attention as a mental health intervention with transdiagnostic potential. In line with psychotherapeutic research, qualitative research has highlighted the role of reductions in experiential avoidance (and increases in connectedness) within psilocybin therapy. However, no quantitative research has examined experiential avoidance as a mechanism underlying psilocybin therapy's therapeutic effects. METHOD: Data was used from a double-blind randomized controlled trial that compared psilocybin therapy (two 25 mg psilocybin session plus daily placebo for six weeks) with escitalopram (two 1 mg psilocybin sessions plus 10-20 mg daily escitalopram for six weeks) among individuals with major depressive disorder (N = 59). All participants received psychological support. Experiential avoidance, connectedness, and treatment outcomes were measured at pre-treatment and at a 6 week primary endpoint. Acute psilocybin experiences and psychological insight were also measured. RESULTS: With psilocybin therapy, but not escitalopram, improvements in mental health outcomes (i.e., well-being, depression severity, suicidal ideation, and trait anxiety) occurred via reductions in experiential avoidance. Exploratory analyses suggested that improvements in mental health (except for suicidal ideation) via reduction in experiential avoidance were serially mediated through increases in connectedness. Additionally, experiences of ego dissolution and psychological insight predicted reductions in experiential avoidance following psilocybin therapy. LIMITATIONS: Difficulties inferring temporal causality, maintaining blindness to condition, and reliance upon self-report. CONCLUSIONS: These results provide support for the role of reduced experiential avoidance as a putative mechanism underlying psilocybin therapy's positive therapeutic outcomes. The present findings may help to tailor, refine, and optimize psilocybin therapy and i
Szigeti B, Nutt D, Carhart-Harris R, et al., 2023, The difference between 'placebo group' and 'placebo control': a case study in psychedelic microdosing, Scientific Reports, Vol: 13, Pages: 1-10, ISSN: 2045-2322
In medical trials, ‘blinding’ ensures the equal distribution of expectancy effects between treatment arms in theory; however, blinding often fails in practice. We use computational modelling to show how weak blinding, combined with positive treatment expectancy, can lead to an uneven distribution of expectancy effects. We call this ‘activated expectancy bias’ (AEB) and show that AEB can inflate estimates of treatment effects and create false positive findings. To counteract AEB, we introduce the Correct Guess Rate Curve (CGRC), a statistical tool that can estimate the outcome of a perfectly blinded trial based on data from an imperfectly blinded trial. To demonstrate the impact of AEB and the utility of the CGRC on empirical data, we re-analyzed the ‘self-blinding psychedelic microdose trial’ dataset. Results suggest that observed placebo-microdose differences are susceptible to AEB and are at risk of being false positive findings, hence, we argue that microdosing can be understood as active placebo. These results highlight the important difference between ‘trials with a placebo-control group’, i.e., when a placebo control group is formally present, and ‘placebo-controlled trials’, where patients are genuinely blind. We also present a new blinding integrity assessment tool that is compatible with CGRC and recommend its adoption.
Wall MB, Lam C, Ertl N, et al., 2023, Increased low-frequency brain responses to music after psilocybin therapy for depression., J Affect Disord, Vol: 333, Pages: 321-330
BACKGROUND: Psychedelic-assisted psychotherapy with psilocybin is an emerging therapy with great promise for depression, and modern psychedelic therapy (PT) methods incorporate music as a key element. Music is an effective emotional/hedonic stimulus that could also be useful in assessing changes in emotional responsiveness following PT. METHODS: Brain responses to music were assessed before and after PT using functional Magnetic Resonance Imaging (fMRI) and ALFF (Amplitude of Low Frequency Fluctuations) analysis methods. Nineteen patients with treatment-resistant depression underwent two treatment sessions involving administration of psilocybin, with MRI data acquired one week prior and the day after completion of psilocybin dosing sessions. RESULTS: Comparison of music-listening and resting-state scans revealed significantly greater ALFF in bilateral superior temporal cortex for the post-treatment music scan, and in the right ventral occipital lobe for the post-treatment resting-state scan. ROI analyses of these clusters revealed a significant effect of treatment in the superior temporal lobe for the music scan only. Voxelwise comparison of treatment effects showed relative increases for the music scan in the bilateral superior temporal lobes and supramarginal gyrus, and relative decreases in the medial frontal lobes for the resting-state scan. ALFF in these music-related clusters was significantly correlated with intensity of subjective effects felt during the dosing sessions. LIMITATIONS: Open-label trial. Relatively small sample size. CONCLUSIONS: These data suggest an effect of PT on the brain's response to music, implying an elevated responsiveness to music after psilocybin therapy that was related to subjective drug effects felt during dosing.
Weiss B, Erritzoe D, Giribaldi B, et al., 2023, A critical evaluation of QIDS-SR-16 using data from a trial of psilocybin therapy versus escitalopram treatment for depression., J Psychopharmacol, Vol: 37, Pages: 717-732
BACKGROUND: In a recent clinical trial examining the comparative efficacy of psilocybin therapy (PT) versus escitalopram treatment (ET) for major depressive disorder, 14 of 16 major efficacy outcome measures yielded results that favored PT, but the Quick Inventory of Depressive Symptomatology, Self-Report, 16 items (QIDS-SR16) did not. AIMS: The present study aims to (1) rationally and psychometrically account for discrepant results between outcome measures and (2) to overcome psychometric problems particular to individual measures by re-examining between-condition differences in depressive response using all outcome measures at item-, facet-, and factor-levels of analysis. METHOD: Four depression measures were compared on the basis of their validity for examining differences in depressive response between PT and ET conditions. RESULTS/OUTCOMES: Possible reasons for discrepant findings on the QIDS-SR16 include its higher variance, imprecision due to compound items and whole-scale and unidimensional sum-scoring, vagueness in the phrasing of scoring options for items, and its lack of focus on a core depression factor. Reanalyzing the trial data at item-, facet-, and factor-levels yielded results suggestive of PT's superior efficacy in reducing depressed mood, anhedonia, and a core depression factor, along with specific symptoms such as sexual dysfunction. CONCLUSION/INTERPRETATION: Our results raise concerns about the adequacy of the QIDS-SR16 for measuring depression, as well as the practice of relying on individual scales that tend not to capture the multidimensional structure or core of depression. Using an alternative approach that captures depression more granularly and comprehensively yielded specific insight into areas where PT therapy may be particularly useful to patients and clinicians.
Delli Pizzi S, Chiacchiaretta P, Sestieri C, et al., 2023, Spatial Correspondence of LSD-Induced Variations on Brain Functioning at Rest With Serotonin Receptor Expression., Biol Psychiatry Cogn Neurosci Neuroimaging, Vol: 8, Pages: 768-776
BACKGROUND: Lysergic acid diethylamide (LSD) is an atypical psychedelic compound that exerts its effects through pleiotropic actions, mainly involving 1A/2A serotoninergic (5-HT) receptor subtypes. However, the mechanisms by which LSD promotes a reorganization of the brain's functional activity and connectivity are still partially unknown. METHODS: Our study analyzed resting-state functional magnetic resonance imaging data acquired from 15 healthy volunteers undergoing LSD single-dose intake. A voxelwise analysis investigated the alterations of the brain's intrinsic functional connectivity and local signal amplitude induced by LSD or by a placebo. Quantitative comparisons assessed the spatial overlap between these 2 indices of functional reorganization and the topography of receptor expression obtained from a publicly available collection of in vivo, whole-brain atlases. Finally, linear regression models explored the relationships between changes in resting-state functional magnetic resonance imaging and behavioral aspects of the psychedelic experience. RESULTS: LSD elicited modifications of the cortical functional architecture that spatially overlapped with the distribution of serotoninergic receptors. Local signal amplitude and functional connectivity increased in regions belonging to the default mode and attention networks associated with high expression of 5-HT2A receptors. These functional changes correlate with the occurrence of simple and complex visual hallucinations. At the same time, a decrease in local signal amplitude and intrinsic connectivity was observed in limbic areas, which are dense with 5-HT1A receptors. CONCLUSIONS: This study provides new insights into the neural processes underlying the brain network reconfiguration induced by LSD. It also identifies a topographical relationship between opposite effects on brain functioning and the spatial distribution of different 5-HT receptors.
Luppi AI, Hansen JY, Adapa R, et al., 2023, In vivo mapping of pharmacologically induced functional reorganization onto the human brain's neurotransmitter landscape., Sci Adv, Vol: 9
To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain's rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically induced macroscale functional reorganization, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from positron emission tomography, and the regional changes in functional magnetic resonance imaging connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, lysergic acid diethylamide (LSD), psilocybin, N,N-Dimethyltryptamine (DMT), ayahuasca, 3,4-methylenedioxymethamphetamine (MDMA), modafinil, and methylphenidate. Our results reveal a many-to-many mapping between psychoactive drugs' effects on brain function and multiple neurotransmitter systems. The effects of both anesthetics and psychedelics on brain function are organized along hierarchical gradients of brain structure and function. Last, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganization of the brain's functional architecture.
Weiss B, Ginige I, Shannon L, et al., 2023, Personality change in a trial of psilocybin therapy vs escitalopram treatment for depression, Psychological Medicine, ISSN: 0033-2917
Background:Psilocybin Therapy (PT) is being increasingly studied as a psychiatric intervention. Personality relates to mental health and can be used to probe the nature of PT's therapeutic action.Methods:In a phase 2, double-blind, randomized, active comparator controlled trial involving patients with moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, over a core 6-week trial period. Five-Factor model personality domains, Big Five Aspect Scale Openness aspects, Absorption, and Impulsivity were measured at Baseline, Week 6, and Month 6 follow-up.Results:PT was associated with decreases in neuroticism (B = −0.63), introversion (B = −0.38), disagreeableness (B = −0.47), impulsivity (B = −0.40), and increases in absorption (B = 0.32), conscientiousness (B = 0.30), and openness (B = 0.23) at week 6, with neuroticism (B = −0.47) and disagreeableness (B = −0.41) remaining decreased at month 6. Escitalopram Treatment (ET) was associated with decreases in neuroticism (B = −0.38), disagreeableness (B = −0.26), impulsivity (B = −0.35), and increases in openness (B = 0.28) at week 6, with neuroticism (B = −0.46) remaining decreased at month 6. No significant between-condition differences were observed.Conclusions:Personality changes across both conditions were in a direction consistent with improved mental health. With the possible exception of trait absorption, there were no compelling between-condition differences warranting conclusions regarding a selective action of PT (v. ET) on personality; however, post-ET changes in personality were significantly moderated by pre-trial positive expectancy for escitalopram, whereas expectancy did not moderate response to PT.
Aday JS, Carhart-Harris RL, Woolley JD, 2023, Emerging Challenges for Psychedelic Therapy., JAMA Psychiatry, Vol: 80, Pages: 533-534
Singleton SP, Timmermann C, Luppi AI, et al., 2023, Time-resolved network control analysis links reduced control energy under DMT with the serotonin 2a receptor, signal diversity, and subjective experience., bioRxiv
Psychedelics offer a profound window into the functioning of the human brain and mind through their robust acute effects on perception, subjective experience, and brain activity patterns. In recent work using a receptor-informed network control theory framework, we demonstrated that the serotonergic psychedelics lysergic acid diethylamide (LSD) and psilocybin flatten the brain's control energy landscape in a manner that covaries with more dynamic and entropic brain activity. Contrary to LSD and psilocybin, whose effects last for hours, the serotonergic psychedelic N,N-dimethyltryptamine (DMT) rapidly induces a profoundly immersive altered state of consciousness lasting less than 20 minutes, allowing for the entirety of the drug experience to be captured during a single resting-state fMRI scan. Using network control theory, which quantifies the amount of input necessary to drive transitions between functional brain states, we integrate brain structure and function to map the energy trajectories of 14 individuals undergoing fMRI during DMT and placebo. Consistent with previous work, we find that global control energy is reduced following injection with DMT compared to placebo. We additionally show longitudinal trajectories of global control energy correlate with longitudinal trajectories of EEG signal diversity (a measure of entropy) and subjective ratings of drug intensity. We interrogate these same relationships on a regional level and find that the spatial patterns of DMT's effects on these metrics are correlated with serotonin 2a receptor density (obtained from separately acquired PET data). Using receptor distribution and pharmacokinetic information, we were able to successfully recapitulate the effects of DMT on global control energy trajectories, demonstrating a proof-of-concept for the use of control models in predicting pharmacological intervention effects on brain dynamics.
Girn M, Rosas FE, Daws RE, et al., 2023, A complex systems perspective on psychedelic brain action., Trends Cogn Sci, Vol: 27, Pages: 433-445
Recent findings suggesting the potential transdiagnostic efficacy of psychedelic-assisted therapy have fostered the need to deepen our understanding of psychedelic brain action. Functional neuroimaging investigations have found that psychedelics reduce the functional segregation of large-scale brain networks. However, beyond this general trend, findings have been largely inconsistent. We argue here that a perspective based on complexity science that foregrounds the distributed, interactional, and dynamic nature of brain function may render these inconsistencies intelligible. We propose that psychedelics induce a mode of brain function that is more dynamically flexible, diverse, integrated, and tuned for information sharing, consistent with greater criticality. This 'meta' perspective has the potential to unify past findings and guide intuitions toward compelling mechanistic models.
Herzog R, Mediano PAM, Rosas FE, et al., 2023, A whole-brain model of the neural entropy increase elicited by psychedelic drugs., Sci Rep, Vol: 13
Psychedelic drugs, including lysergic acid diethylamide (LSD) and other agonists of the serotonin 2A receptor (5HT2A-R), induce drastic changes in subjective experience, and provide a unique opportunity to study the neurobiological basis of consciousness. One of the most notable neurophysiological signatures of psychedelics, increased entropy in spontaneous neural activity, is thought to be of relevance to the psychedelic experience, mediating both acute alterations in consciousness and long-term effects. However, no clear mechanistic explanation for this entropy increase has been put forward so far. We sought to do this here by building upon a recent whole-brain model of serotonergic neuromodulation, to study the entropic effects of 5HT2A-R activation. Our results reproduce the overall entropy increase observed in previous experiments in vivo, providing the first model-based explanation for this phenomenon. We also found that entropy changes were not uniform across the brain: entropy increased in all regions, but the larger effect were localised in visuo-occipital regions. Interestingly, at the whole-brain level, this reconfiguration was not well explained by 5HT2A-R density, but related closely to the topological properties of the brain's anatomical connectivity. These results help us understand the mechanisms underlying the psychedelic state and, more generally, the pharmacological modulation of whole-brain activity.
Timmermann Slater CB, Roseman L, Haridas S, et al., 2023, Human brain effects of DMT assessed via EEG-fMRI, Proceedings of the National Academy of Sciences of USA, Vol: 120, Pages: 1-12, ISSN: 0027-8424
Psychedelics have attracted medical interest, but their effects on human brain function are incompletely understood. In a comprehensive, within-subjects, placebo-controlled design, we acquired multimodal neuroimaging [i.e., EEG-fMRI (electroencephalography-functional MRI)] data to assess the effects of intravenous (IV) N,N-Dimethyltryptamine (DMT) on brain function in 20 healthy volunteers. Simultaneous EEG-fMRI was acquired prior to, during, and after a bolus IV administration of 20 mg DMT, and, separately, placebo. At dosages consistent with the present study, DMT, a serotonin 2A receptor (5-HT2AR) agonist, induces a deeply immersive and radically altered state of consciousness. DMT is thus a useful research tool for probing the neural correlates of conscious experience. Here, fMRI results revealed robust increases in global functional connectivity (GFC), network disintegration and desegregation, and a compression of the principal cortical gradient under DMT. GFC × subjective intensity maps correlated with independent positron emission tomography (PET)-derived 5-HT2AR maps, and both overlapped with meta-analytical data implying human-specific psychological functions. Changes in major EEG-measured neurophysiological properties correlated with specific changes in various fMRI metrics, enriching our understanding of the neural basis of DMT’s effects. The present findings advance on previous work by confirming a predominant action of DMT—and likely other 5-HT2AR agonist psychedelics—on the brain’s transmodal association pole, i.e., the neurodevelopmentally and evolutionarily recent cortex that is associated with species-specific psychological advancements, and high expression of 5-HT2A receptors.
Eckernas E, Timmermann C, Carhart-Harris R, et al., 2023, N,N-dimethyltryptamine affects electroencephalography response in a concentration-dependent manner-A pharmacokinetic/pharmacodynamic analysis, CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY, ISSN: 2163-8306
Ruffini G, Damiani G, Lozano-Soldevilla D, et al., 2023, LSD-induced increase of Ising temperature and algorithmic complexity of brain dynamics, PLoS Computational Biology, Vol: 19, Pages: 1-29, ISSN: 1553-734X
A topic of growing interest in computational neuroscience is the discovery of fundamental principles underlying global dynamics and the self-organization of the brain. In particular, the notion that the brain operates near criticality has gained considerable support, and recent work has shown that the dynamics of different brain states may be modeled by pairwise maximum entropy Ising models at various distances from a phase transition, i.e., from criticality. Here we aim to characterize two brain states (psychedelics-induced and placebo) as captured by functional magnetic resonance imaging (fMRI), with features derived from the Ising spin model formalism (system temperature, critical point, susceptibility) and from algorithmic complexity. We hypothesized, along the lines of the entropic brain hypothesis, that psychedelics drive brain dynamics into a more disordered state at a higher Ising temperature and increased complexity. We analyze resting state blood-oxygen-level-dependent (BOLD) fMRI data collected in an earlier study from fifteen subjects in a control condition (placebo) and during ingestion of lysergic acid diethylamide (LSD). Working with the automated anatomical labeling (AAL) brain parcellation, we first create "archetype" Ising models representative of the entire dataset (global) and of the data in each condition. Remarkably, we find that such archetypes exhibit a strong correlation with an average structural connectome template obtained from dMRI (r = 0.6). We compare the archetypes from the two conditions and find that the Ising connectivity in the LSD condition is lower than in the placebo one, especially in homotopic links (interhemispheric connectivity), reflecting a significant decrease of homotopic functional connectivity in the LSD condition. The global archetype is then personalized for each individual and condition by adjusting the system temperature. The resulting temperatures are all near but above the critical point of the model i
Carhart-Harris RL, 2023, Translational Challenges in Psychedelic Medicine, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 388, Pages: 476-477, ISSN: 0028-4793
Luppi AI, Vohryzek J, Kringelbach ML, et al., 2023, Distributed harmonic patterns of structure-function dependence orchestrate human consciousness., Commun Biol, Vol: 6
A central question in neuroscience is how consciousness arises from the dynamic interplay of brain structure and function. Here we decompose functional MRI signals from pathological and pharmacologically-induced perturbations of consciousness into distributed patterns of structure-function dependence across scales: the harmonic modes of the human structural connectome. We show that structure-function coupling is a generalisable indicator of consciousness that is under bi-directional neuromodulatory control. We find increased structure-function coupling across scales during loss of consciousness, whether due to anaesthesia or brain injury, capable of discriminating between behaviourally indistinguishable sub-categories of brain-injured patients, tracking the presence of covert consciousness. The opposite harmonic signature characterises the altered state induced by LSD or ketamine, reflecting psychedelic-induced decoupling of brain function from structure and correlating with physiological and subjective scores. Overall, connectome harmonic decomposition reveals how neuromodulation and the network architecture of the human connectome jointly shape consciousness and distributed functional activation across scales.
Zeifman R, Spriggs M, Kettner H, et al., 2023, From Relaxed Beliefs Under Psychedelics (REBUS) to Revised Beliefs After Psychedelics (REBAS), Scientific Reports, ISSN: 2045-2322
Objectives: This was a cross sectional study aimed at describing chest x-ray findings among children hospitalised with clinically diagnosed severe pneumonia and hypoxaemia (SpO2<92%) in three tertiary facilities in Uganda.Methods: We studied chest x-rays of 375 children aged 28 days to 12 years enrolled into the Children’s Oxygen Administration Strategies Trial (COAST)(ISRCTN15622505). Radiologists blinded to the clinical findings reported chest x-rays using the standardized World Health Organization methodology for paediatric chest Xray reporting. We summarised clinical data and chest x-ray findings using descriptive statistics. Chi-square and proportion tests were used to compare proportions and quantile regression compared medians. Results: We found 172, (45.8%) children had radiological pneumonia, 136 (36.3%) normal chest radiographs while 123 (32.8%) non-pneumonia findings, the major one being cardiovascular abnormalities,106 (28.3%); 56 (14.9%) chest radiographs had both pneumonia and other abnormalities. There was no difference in the prevalence of radiological pneumonia, cardiovascular abnormalities, and mortality between the group with severe hypoxaemia (SpO2<80%) and that with mild hypoxaemia (SpO280 to <92%), (95% CI: -13.2,7.1, -6.1,15.9) and -37.2, 20.4) respectively. Conclusion: This study highlights a relatively high prevalence of cardiovascular abnormalities in children who fulfill the WHO clinical criteria for severe pneumonia and have hypoxaemia. We recommend that chest x-ray examinations be routinely done for all children in this population because information concerning cardiovascular and respiratory systems can be obtained in one sitting and guide management better. We hope that these findings can prompt discussions into refining the clinical criteria used to classify and manage pneumonia in children in limited resource settings.
Forstmann M, Kettner HS, Sagioglou C, et al., 2023, Among psychedelic-experienced users, only past use of psilocybin reliably predicts nature relatedness, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 37, Pages: 93-106, ISSN: 0269-8811
Carhart-Harris RL, Chandaria S, Erritzoe DE, et al., 2023, Canalization and plasticity in psychopathology, NEUROPHARMACOLOGY, Vol: 226, ISSN: 0028-3908
Cieri F, Carhart-Harris RL, Mathys C, et al., 2023, Editorial: Frontiers in psychodynamic neuroscience, Frontiers in Human Neuroscience, Vol: 17
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Savoldi R, Roazzi A, Escobar JAC, et al., 2023, The Structural Organization and Construct Validity Evidence of the Brazilian Versions of the Mysticism Scale and the Ego-Dissolution Inventory in a Major Religion of the Ayahuasca, International Journal of Latin American Religions
Mystical experiences and ego dissolution are essential to understanding the lasting psychological effects of psychedelics or even natural religious experience. The main objective of the article is to present evidence of construct validity in the adaptation to Brazilian Portuguese of the Hood Mysticism Scale (HMS) and the Ego-Dissolution Inventory (EDI)-8 through two psychometric techniques: the smallest space analysis technique and the factorial analysis. Design: a cross-sectional survey. The sample consisted of 1414 members of the União do Vegetal religion. The smallest space analysis (SSA) identified three distinct regions in HMS: introversive mysticism, extroversive mysticism, and interpretation. The SSA for EDI-8 suggests four distinct regions, which were conceptualized as (1) loss of ego, (2) total dissolution, (3) ego quiet, and (4) internal–external unity. In addition, a confirmatory factor analysis (CFA) was used to test the factorial replicability of the HMS and EDI-8. The CFA presented acceptable support for the dimensional structures tested. Conclusion: Results show good reliability and validity indicators, which endorse the Portuguese HMS and EDI-8 application in future research.
Hipólito I, Mago J, Rosas FE, et al., 2023, Pattern breaking: a complex systems approach to psychedelic medicine., Neurosci Conscious, Vol: 2023
Recent research has demonstrated the potential of psychedelic therapy for mental health care. However, the psychological experience underlying its therapeutic effects remains poorly understood. This paper proposes a framework that suggests psychedelics act as destabilizers, both psychologically and neurophysiologically. Drawing on the 'entropic brain' hypothesis and the 'RElaxed Beliefs Under pSychedelics' model, this paper focuses on the richness of psychological experience. Through a complex systems theory perspective, we suggest that psychedelics destabilize fixed points or attractors, breaking reinforced patterns of thinking and behaving. Our approach explains how psychedelic-induced increases in brain entropy destabilize neurophysiological set points and lead to new conceptualizations of psychedelic psychotherapy. These insights have important implications for risk mitigation and treatment optimization in psychedelic medicine, both during the peak psychedelic experience and during the subacute period of potential recovery.
Luppi AI, Rosas FE, Noonan MP, et al., 2022, Oxygen and the Spark of Human Brain Evolution: Complex Interactions of Metabolism and Cortical Expansion across Development and Evolution., Neuroscientist
Scientific theories on the functioning and dysfunction of the human brain require an understanding of its development-before and after birth and through maturation to adulthood-and its evolution. Here we bring together several accounts of human brain evolution by focusing on the central role of oxygen and brain metabolism. We argue that evolutionary expansion of human transmodal association cortices exceeded the capacity of oxygen delivery by the vascular system, which led these brain tissues to rely on nonoxidative glycolysis for additional energy supply. We draw a link between the resulting lower oxygen tension and its effect on cytoarchitecture, which we posit as a key driver of genetic developmental programs for the human brain-favoring lower intracortical myelination and the presence of biosynthetic materials for synapse turnover. Across biological and temporal scales, this protracted capacity for neural plasticity sets the conditions for cognitive flexibility and ongoing learning, supporting complex group dynamics and intergenerational learning that in turn enabled improved nutrition to fuel the metabolic costs of further cortical expansion. Our proposed model delineates explicit mechanistic links among metabolism, molecular and cellular brain heterogeneity, and behavior, which may lead toward a clearer understanding of brain development and its disorders.
Cherniak AD, Brulin JG, Mikulincer M, et al., 2022, Psychedelic Science of Spirituality and Religion: An Attachment-Informed Agenda Proposal, INTERNATIONAL JOURNAL FOR THE PSYCHOLOGY OF RELIGION, ISSN: 1050-8619
Shukuroglou M, Roseman L, Wall M, et al., 2022, Changes in music-evoked emotion and ventral striatal functional connectivity after psilocybin therapy for depression, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 37, Pages: 70-79, ISSN: 0269-8811
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