1,985 results on '"Nutt, David J"'
Search Results
2. Unique Psychological Mechanisms Underlying Psilocybin Therapy Versus Escitalopram Treatment in the Treatment of Major Depressive Disorder
- Author
-
Weiss, Brandon, Roseman, Leor, Giribaldi, Bruna, Nutt, David J., Carhart-Harris, Robin L., and Erritzoe, David
- Published
- 2024
- Full Text
- View/download PDF
3. A role for the serotonin 2A receptor in the expansion and functioning of human transmodal cortex
- Author
-
Luppi, Andrea I, Girn, Manesh, Rosas, Fernando E, Timmermann, Christopher, Roseman, Leor, Erritzoe, David, Nutt, David J, Stamatakis, Emmanuel A, Spreng, R Nathan, Xing, Lei, Huttner, Wieland B, and Carhart-Harris, Robin L
- Subjects
Biological Psychology ,Cognitive and Computational Psychology ,Biomedical and Clinical Sciences ,Psychology ,Stem Cell Research ,Neurosciences ,Brain Disorders ,Mental Health ,Underpinning research ,1.1 Normal biological development and functioning ,Neurological ,cortical expansion ,cortical functional organization ,neurodevelopment ,psychedelics ,serotonin 2A receptor ,transmodal cortex ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Neurology & Neurosurgery ,Biomedical and clinical sciences ,Health sciences - Abstract
Integrating independent but converging lines of research on brain function and neurodevelopment across scales, this article proposes that serotonin 2A receptor (5-HT2AR) signaling is an evolutionary and developmental driver and potent modulator of the macroscale functional organization of the human cerebral cortex. A wealth of evidence indicates that the anatomical and functional organization of the cortex follows a unimodal-to-transmodal gradient. Situated at the apex of this processing hierarchy - where it plays a central role in the integrative processes underpinning complex, human-defining cognition - the transmodal cortex has disproportionately expanded across human development and evolution. Notably, the adult human transmodal cortex is especially rich in 5-HT2AR expression, and recent evidence suggests that, during early brain development, 5-HT2AR signaling on neural progenitor cells stimulates their proliferation - a critical process for evolutionarily-relevant cortical expansion. Drawing on multimodal neuroimaging and cross-species investigations, we argue that, by contributing to the expansion of the human cortex, and being prevalent at the apex of its hierarchy in the adult brain, 5-HT2AR signaling plays a major role in both human cortical expansion and functioning. Due to its unique excitatory and downstream cellular effects, neuronal 5-HT2AR agonism promotes neuroplasticity, learning, and cognitive and psychological flexibility in a context-(hyper)sensitive manner with therapeutic potential. Overall, we delineate a dual role of 5-HT2ARs in enabling both the expansion and modulation of the human transmodal cortex.
- Published
- 2023
4. Psychedelics and sexual functioning: a mixed-methods study
- Author
-
Barba, Tommaso, Kettner, Hannes, Radu, Caterina, Peill, Joseph M., Roseman, Leor, Nutt, David J., Erritzoe, David, Carhart-Harris, Robin, and Giribaldi, Bruna
- Published
- 2024
- Full Text
- View/download PDF
5. Effects of DMT on mental health outcomes in healthy volunteers
- Author
-
Timmermann, Christopher, Zeifman, Richard J., Erritzoe, David, Nutt, David J., and Carhart-Harris, Robin L.
- Published
- 2024
- Full Text
- View/download PDF
6. Exploring mechanisms of psychedelic action using neuroimaging
- Author
-
Erritzoe, David, Timmermann, Christopher, Godfrey, Kate, Castro-Rodrigues, Pedro, Peill, Joseph, Carhart-Harris, Robin L., Nutt, David J., and Wall, Matthew B.
- Published
- 2024
- Full Text
- View/download PDF
7. Human brain effects of DMT assessed via EEG-fMRI
- Author
-
Timmermann, Christopher, Roseman, Leor, Haridas, Sharad, Rosas, Fernando E, Luan, Lisa, Kettner, Hannes, Martell, Jonny, Erritzoe, David, Tagliazucchi, Enzo, Pallavicini, Carla, Girn, Manesh, Alamia, Andrea, Leech, Robert, Nutt, David J, and Carhart-Harris, Robin L
- Subjects
Neurosciences ,Clinical Research ,Biomedical Imaging ,Basic Behavioral and Social Science ,Behavioral and Social Science ,Underpinning research ,1.1 Normal biological development and functioning ,Mental health ,Neurological ,Humans ,N ,N-Dimethyltryptamine ,Hallucinogens ,Magnetic Resonance Imaging ,Brain ,Electroencephalography ,psychedelics ,serotonin ,consciousness ,dimethyltryptamine ,ayahuasca - Abstract
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.
- Published
- 2023
8. A Bayesian Reanalysis of a Trial of Psilocybin versus Escitalopram for Depression.
- Author
-
Nayak, Sandeep M, Bari, Bilal A, Yaden, David B, Spriggs, Meg J, Rosas, Fernando E, Peill, Joseph M, Giribaldi, Bruna, Erritzoe, David, Nutt, David J, and Carhart-Harris, Robin
- Subjects
Depression ,Clinical Research ,Mental Health ,Clinical Trials and Supportive Activities ,Mental health ,Good Health and Well Being - Abstract
ObjectivesTo perform a Bayesian reanalysis of a recent trial of psilocybin (COMP360) versus escitalopram for Major Depressive Disorder (MDD) in order to provide a more informative interpretation of the indeterminate outcome of a previous frequentist analysis.DesignReanalysis of a two-arm double-blind placebo controlled trial.ParticipantsFifty-nine patients with MDD.InterventionsTwo doses of psilocybin 25mg and daily oral placebo versus daily escitalopram and 2 doses of psilocybin 1mg, with psychological support for both groups.Outcome measuresQuick Inventory of Depressive Symptomatology-Self-Report (QIDS SR-16), and three other depression scales as secondary outcomes: HAMD-17, MADRS, and BDI-1A.ResultsUsing Bayes factors and 'skeptical priors' which bias estimates towards zero, for the hypothesis that psilocybin is superior by any margin, we found indeterminate evidence for QIDS SR-16, strong evidence for BDI-1A and MADRS, and extremely strong evidence for HAMD-17. For the stronger hypothesis that psilocybin is superior by a 'clinically meaningful amount' (using literature defined values of the minimally clinically important difference), we found moderate evidence against it for QIDS SR-16, indeterminate evidence for BDI-1A and MADRS, and moderate evidence supporting it for HAMD-17. Furthermore, across the board we found extremely strong evidence for psilocybin's non-inferiority versus escitalopram. These findings were robust to prior sensitivity analysis.ConclusionsThis Bayesian reanalysis supports the following inferences: 1) that psilocybin did indeed outperform escitalopram in this trial, but not to an extent that was clinically meaningful--and 2) that psilocybin is almost certainly non-inferior to escitalopram. The present results provide a more precise and nuanced interpretation to previously reported results from this trial, and support the need for further research into the relative efficacy of psilocybin therapy for depression with respect to current leading treatments.Trial registration numberNCT03429075.
- Published
- 2023
9. Body mass index (BMI) does not predict responses to psilocybin
- Author
-
Spriggs, Meg J, Giribaldi, Bruna, Lyons, Taylor, Rosas, Fernando E, Kärtner, Laura S, Buchborn, Tobias, Douglass, Hannah M, Roseman, Leor, Timmermann, Christopher, Erritzoe, David, Nutt, David J, and Carhart-Harris, Robin L
- Subjects
Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Good Health and Well Being ,Humans ,Psilocybin ,Hallucinogens ,Body Mass Index ,Bayes Theorem ,Emotions ,Serotonin ,Psychedelic therapy ,psychedelic-assisted therapy ,body mass index ,body weight ,classic psychedelic ,hallucinogen ,Bayes Factor ,5-HT2A ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundPsilocybin is a serotonin type 2A (5-HT2A) receptor agonist and naturally occurring psychedelic. 5-HT2A receptor density is known to be associated with body mass index (BMI), however, the impact of this on psilocybin therapy has not been explored. While body weight-adjusted dosing is widely used, this imposes a practical and financial strain on the scalability of psychedelic therapy. This gap between evidence and practice is caused by the absence of studies clarifying the relationship between BMI, the acute psychedelic experience and long-term psychological outcomes.MethodData were pooled across three studies using a fixed 25 mg dose of psilocybin delivered in a therapeutic context to assess whether BMI predicts characteristics of the acute experience and changes in well-being 2 weeks later. Supplementing frequentist analysis with Bayes Factors has enabled for conclusions to be drawn regarding the null hypothesis.ResultsResults support the null hypothesis that BMI does not predict overall intensity of the altered state, mystical experiences, perceptual changes or emotional breakthroughs during the acute experience. There was weak evidence for greater 'dread of ego dissolution' in participants with lower BMI, however, further analysis suggested BMI did not meaningfully add to the combination of the other covariates (age, sex and study). While mystical-type experiences and emotional breakthroughs were strong predictors of improvements in well-being, BMI was not.ConclusionsThese findings have important implications for our understanding of pharmacological and extra-pharmacological contributors to psychedelic-assisted therapy and for the standardization of a fixed therapeutic dose in psychedelic-assisted therapy.
- Published
- 2023
10. Effects of psilocybin versus escitalopram on rumination and thought suppression in depression
- Author
-
Barba, Tommaso, Buehler, Sarah, Kettner, Hannes, Radu, Caterina, Cunha, Bruna Giribaldi, Nutt, David J, Erritzoe, David, Roseman, Leor, and Carhart-Harris, Robin
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Brain Disorders ,Clinical Research ,Clinical Trials and Supportive Activities ,Depression ,Mental Health ,Good Health and Well Being ,Depressive disorders ,pharmaceutical drug trial ,randomised controlled trial ,novel central nervous system drugs ,antidepressants ,Public Health and Health Services ,Clinical sciences ,Health services and systems - Abstract
BackgroundMajor depressive disorder is often associated with maladaptive coping strategies, including rumination and thought suppression.AimsTo assess the comparative effect of the selective serotonin reuptake inhibitor escitalopram, and the serotonergic psychedelic psilocybin (COMP360), on rumination and thought suppression in major depressive disorder.MethodBased on data derived from a randomised clinical trial (N = 59), we performed exploratory analyses on the impact of escitalopram versus psilocybin (i.e. condition) on rumination and thought suppression from 1 week before to 6 weeks after treatment inception (i.e. time), using mixed analysis of variance. Condition responder versus non-responder subgroup analyses were also done, using the standard definition of ≥50% symptom reduction.ResultsA time×condition interaction was found for rumination (F(1, 56) = 4.58, P = 0.037) and thought suppression (F(1,57) = 5.88, P = 0.019), with post hoc tests revealing significant decreases exclusively in the psilocybin condition. When analysing via response, a significant time×condition×response interaction for thought suppression (F(1,54) = 8.42, P = 0.005) and a significant time×response interaction for rumination (F(1,54) = 23.50, P < 0.001) were evident. Follow-up tests revealed that decreased thought suppression was exclusive to psilocybin responders, whereas rumination decreased in both responder groups. In the psilocybin arm, decreases in rumination and thought suppression correlated with ego dissolution and session-linked psychological insight.ConclusionsThese data provide further evidence on the therapeutic mechanisms of psilocybin and escitalopram in the treatment of depression.
- Published
- 2022
11. Exploratory study of associations between monetary reward anticipation brain responses and mu-opioid signalling in alcohol dependence, gambling disorder and healthy controls
- Author
-
Turton, Samuel, Paterson, Louise M., Myers, James FM., Mick, Inge, Lan, Chen-Chia, McGonigle, John, Bowden-Jones, Henrietta, Clark, Luke, Nutt, David J., and Lingford-Hughes, Anne R.
- Published
- 2024
- Full Text
- View/download PDF
12. Neuroimaging in psychedelic drug development: past, present, and future
- Author
-
Wall, Matthew B., Harding, Rebecca, Zafar, Rayyan, Rabiner, Eugenii A., Nutt, David J., and Erritzoe, David
- Published
- 2023
- Full Text
- View/download PDF
13. A leaky umbrella has little value: evidence clearly indicates the serotonin system is implicated in depression
- Author
-
Jauhar, Sameer, Arnone, Danilo, Baldwin, David S., Bloomfield, Michael, Browning, Michael, Cleare, Anthony J., Corlett, Phillip, Deakin, J. F. William, Erritzoe, David, Fu, Cynthia, Fusar-Poli, Paolo, Goodwin, Guy M., Hayes, Joseph, Howard, Robert, Howes, Oliver D., Juruena, Mario F., Lam, Raymond W., Lawrie, Stephen M., McAllister-Williams, Hamish, Marwaha, Steven, Matuskey, David, McCutcheon, Robert A., Nutt, David J., Pariante, Carmine, Pillinger, Toby, Radhakrishnan, Rajiv, Rucker, James, Selvaraj, Sudhakar, Stokes, Paul, Upthegrove, Rachel, Yalin, Nefize, Yatham, Lakshmi, Young, Allan H., Zahn, Roland, and Cowen, Philip J.
- Published
- 2023
- Full Text
- View/download PDF
14. Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain’s control energy landscape
- Author
-
Singleton, S Parker, Luppi, Andrea I, Carhart-Harris, Robin L, Cruzat, Josephine, Roseman, Leor, Nutt, David J, Deco, Gustavo, Kringelbach, Morten L, Stamatakis, Emmanuel A, and Kuceyeski, Amy
- Subjects
Biomedical and Clinical Sciences ,Biological Psychology ,Physical Sciences ,Psychology ,Pharmacology and Pharmaceutical Sciences ,Biomedical Imaging ,Clinical Research ,Neurosciences ,Brain Disorders ,Neurological ,Brain ,Hallucinogens ,Humans ,Lysergic Acid Diethylamide ,Psilocybin ,Receptor ,Serotonin ,5-HT2A ,Serotonin ,Serotonin 5-HT2 Receptor Agonists - Abstract
Psychedelics including lysergic acid diethylamide (LSD) and psilocybin temporarily alter subjective experience through their neurochemical effects. Serotonin 2a (5-HT2a) receptor agonism by these compounds is associated with more diverse (entropic) brain activity. We postulate that this increase in entropy may arise in part from a flattening of the brain's control energy landscape, which can be observed using network control theory to quantify the energy required to transition between recurrent brain states. Using brain states derived from existing functional magnetic resonance imaging (fMRI) datasets, we show that LSD and psilocybin reduce control energy required for brain state transitions compared to placebo. Furthermore, across individuals, reduction in control energy correlates with more frequent state transitions and increased entropy of brain state dynamics. Through network control analysis that incorporates the spatial distribution of 5-HT2a receptors (obtained from publicly available positron emission tomography (PET) data under non-drug conditions), we demonstrate an association between the 5-HT2a receptor and reduced control energy. Our findings provide evidence that 5-HT2a receptor agonist compounds allow for more facile state transitions and more temporally diverse brain activity. More broadly, we demonstrate that receptor-informed network control theory can model the impact of neuropharmacological manipulation on brain activity dynamics.
- Published
- 2022
15. Can pragmatic research, real-world data and digital technologies aid the development of psychedelic medicine?
- Author
-
Carhart-Harris, Robin L, Wagner, Anne C, Agrawal, Manish, Kettner, Hannes, Rosenbaum, Jerold F, Gazzaley, Adam, Nutt, David J, and Erritzoe, David
- Subjects
Clinical Trials and Supportive Activities ,Clinical Research ,Generic health relevance ,Good Health and Well Being ,Biomedical Research ,Digital Technology ,Drug Development ,Hallucinogens ,Humans ,Real-world data ,pragmatic trials ,psychedelics ,serotonin ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
Favourable regulatory assessments, liberal policy changes, new research centres and substantial commercial investment signal that psychedelic therapy is making a major comeback. Positive findings from modern trials are catalysing developments, but it is questionable whether current confirmatory trials are sufficient for advancing our understanding of safety and best practice. Here we suggest supplementing traditional confirmatory trials with pragmatic trials, real-world data initiatives and digital health solutions to better support the discovery of optimal and personalised treatment protocols and parameters. These recommendations are intended to help support the development of safe, effective and cost-efficient psychedelic therapy, which, given its history, is vulnerable to excesses of hype and regulation.
- Published
- 2022
16. Acute tryptophan depletion, part ll : clinical effects and implications
- Author
-
Bell, Caroline J, Hood, Sean D, and Nutt, David J
- Published
- 2005
17. Acute tryptophan depletion, part l : rationale and methodology
- Author
-
Hood, Sean D, Bell, Caroline J, and Nutt, David J
- Published
- 2005
18. LSD-induced changes in the functional connectivity of distinct thalamic nuclei
- Author
-
Delli Pizzi, Stefano, Chiacchiaretta, Piero, Sestieri, Carlo, Ferretti, Antonio, Tullo, Maria Giulia, Della Penna, Stefania, Martinotti, Giovanni, Onofrj, Marco, Roseman, Leor, Timmermann, Christopher, Nutt, David J., Carhart-Harris, Robin L., and Sensi, Stefano L.
- Published
- 2023
- Full Text
- View/download PDF
19. Self-blinding citizen science to explore psychedelic microdosing
- Author
-
Szigeti, Balázs, Kartner, Laura, Blemings, Allan, Rosas, Fernando, Feilding, Amanda, Nutt, David J, Carhart-Harris, Robin L, and Erritzoe, David
- Subjects
Clinical Research ,Clinical Trials and Supportive Activities ,Behavioral and Social Science ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Mental health ,Adult ,Affect ,Citizen Science ,Cognition ,Creativity ,Dose-Response Relationship ,Drug ,Emotions ,Female ,Hallucinogens ,Humans ,Male ,Placebo Effect ,citizen science ,expectations ,human ,medicine ,microdosing ,neuroscience ,placebo ,psychedelics ,self-blinding ,Biochemistry and Cell Biology - Abstract
Microdosing is the practice of regularly using low doses of psychedelic drugs. Anecdotal reports suggest that microdosing enhances well-being and cognition; however, such accounts are potentially biased by the placebo effect. This study used a 'self-blinding' citizen science initiative, where participants were given online instructions on how to incorporate placebo control into their microdosing routine without clinical supervision. The study was completed by 191 participants, making it the largest placebo-controlled trial on psychedelics to-date. All psychological outcomes improved significantly from baseline to after the 4 weeks long dose period for the microdose group; however, the placebo group also improved and no significant between-groups differences were observed. Acute (emotional state, drug intensity, mood, energy, and creativity) and post-acute (anxiety) scales showed small, but significant microdose vs. placebo differences; however, these results can be explained by participants breaking blind. The findings suggest that anecdotal benefits of microdosing can be explained by the placebo effect.
- Published
- 2021
20. Study Protocol for “Psilocybin as a Treatment for Anorexia Nervosa: A Pilot Study”
- Author
-
Spriggs, Meg J, Douglass, Hannah M, Park, Rebecca J, Read, Tim, Danby, Jennifer L, de Magalhães, Frederico JC, Alderton, Kirsty L, Williams, Tim M, Blemings, Allan, Lafrance, Adele, Nicholls, Dasha E, Erritzoe, David, Nutt, David J, and Carhart-Harris, Robin L
- Subjects
Clinical Research ,Clinical Trials and Supportive Activities ,Anorexia ,Eating Disorders ,Mental Health ,Neurosciences ,Serious Mental Illness ,Brain Disorders ,Nutrition ,Mental health ,Neurological ,Good Health and Well Being ,anorexia nervosa ,clinical trial ,eating disorder ,electroencephalograph ,magnetic resonance imaging ,psilocybin ,psychedelic-assisted therapy ,public patient involvement ,Clinical Sciences ,Public Health and Health Services ,Psychology - Abstract
Background: Anorexia nervosa (AN) is a serious and life-threatening psychiatric condition. With a paucity of approved treatments, there is a desperate need for novel treatment avenues to be explored. Here, we present (1) an overview of the ways through which Public Patient Involvement (PPI) has informed a trial of psilocybin-assisted therapy for AN and (2) a protocol for a pilot study of psilocybin-assisted therapy in AN currently underway at Imperial College London. The study aims to assess the feasibility, brain mechanisms and preliminary outcomes of treating anorexia nervosa with psilocybin. Methods: (1) PPI: Across two online focus groups, eleven individuals with lived experience of AN were presented with an overview of the protocol. Their feedback not only identified solutions to possible barriers for future participants, but also helped the research team to better understand the concept of "recovery" from the perspective of those with lived experience. (2) Protocol: Twenty female participants [21-65 years old, body mass index (BMI) 15 kg/m2 or above] will receive three oral doses of psilocybin (up to 25 mg) over a 6-week period delivered in a therapeutic environment and enveloped by psychological preparation and integration. We will work with participant support networks (care teams and an identified support person) throughout and there will be an extended remote follow-up period of 12 months. Our two-fold primary outcomes are (1) psychopathology (Eating Disorder Examination) across the 6-month follow-up and (2) readiness and motivation to engage in recovery (Readiness and Motivation Questionnaire) across the 6-week trial period. Neurophysiological outcome measures will be: (1) functional magnetic resonance imaging (fMRI) brain changes from baseline to 6-week endpoint and (2) post-acute changes in electroencephalography (EEG) activity, including an electrophysiological marker of neuronal plasticity. Discussion: The results of this pilot study will not only shed light on the acceptability, brain mechanisms, and impression of the potential efficacy of psilocybin as an adjunct treatment for AN but will be essential in shaping a subsequent Randomised Control Trial (RCT) that would test this treatment against a suitable control condition. Clinical Trial Registration: identifier: NCT04505189.
- Published
- 2021
21. Increased low-frequency brain responses to music after psilocybin therapy for depression
- Author
-
Wall, Matthew B., Lam, Cynthia, Ertl, Natalie, Kaelen, Mendel, Roseman, Leor, Nutt, David J., and Carhart-Harris, Robin L.
- Published
- 2023
- Full Text
- View/download PDF
22. Spatial Correspondence of LSD-Induced Variations on Brain Functioning at Rest With Serotonin Receptor Expression
- Author
-
Delli Pizzi, Stefano, Chiacchiaretta, Piero, Sestieri, Carlo, Ferretti, Antonio, Onofrj, Marco, Della Penna, Stefania, Roseman, Leor, Timmermann, Christopher, Nutt, David J., Carhart-Harris, Robin L., and Sensi, Stefano L.
- Published
- 2023
- Full Text
- View/download PDF
23. DMT alters cortical travelling waves
- Author
-
Alamia, Andrea, Timmermann, Christopher, Nutt, David J, VanRullen, Rufin, and Carhart-Harris, Robin L
- Subjects
Neurosciences ,Adult ,Alpha Rhythm ,Brain ,Consciousness ,Female ,Hallucinogens ,Humans ,Male ,Middle Aged ,N ,N-Dimethyltryptamine ,Young Adult ,DMT ,N ,N ,Dimethyltryptamine ,conscious perception ,eeg oscillations ,human ,neuroscience ,travelling waves ,visual hallucinations ,Biochemistry and Cell Biology - Abstract
Psychedelic drugs are potent modulators of conscious states and therefore powerful tools for investigating their neurobiology. N,N, Dimethyltryptamine (DMT) can rapidly induce an extremely immersive state of consciousness characterized by vivid and elaborate visual imagery. Here, we investigated the electrophysiological correlates of the DMT-induced altered state from a pool of participants receiving DMT and (separately) placebo (saline) while instructed to keep their eyes closed. Consistent with our hypotheses, results revealed a spatio-temporal pattern of cortical activation (i.e. travelling waves) similar to that elicited by visual stimulation. Moreover, the typical top-down alpha-band rhythms of closed-eyes rest were significantly decreased, while the bottom-up forward wave was significantly increased. These results support a recent model proposing that psychedelics reduce the 'precision-weighting of priors', thus altering the balance of top-down versus bottom-up information passing. The robust hypothesis-confirming nature of these findings imply the discovery of an important mechanistic principle underpinning psychedelic-induced altered states.
- Published
- 2020
24. Brain Serotonin Release Is Reduced in Patients With Depression: A [11C]Cimbi-36 Positron Emission Tomography Study With a d-Amphetamine Challenge
- Author
-
Erritzoe, David, Godlewska, Beata R., Rizzo, Gaia, Searle, Graham E., Agnorelli, Claudio, Lewis, Yvonne, Ashok, Abhishekh H., Colasanti, Alessandro, Boura, Iro, Farrell, Chloe, Parfitt, Hollie, Howes, Oliver, Passchier, Jan, Gunn, Roger N., Politis, Marios, Nutt, David J., Cowen, Philip J., Knudsen, Gitte M., and Rabiner, Eugenii A.
- Published
- 2023
- Full Text
- View/download PDF
25. Neural correlates of the DMT experience assessed with multivariate EEG
- Author
-
Timmermann, Christopher, Roseman, Leor, Schartner, Michael, Milliere, Raphael, Williams, Luke TJ, Erritzoe, David, Muthukumaraswamy, Suresh, Ashton, Michael, Bendrioua, Adam, Kaur, Okdeep, Turton, Samuel, Nour, Matthew M, Day, Camilla M, Leech, Robert, Nutt, David J, and Carhart-Harris, Robin L
- Subjects
Neurosciences ,Clinical Research ,Brain Disorders ,1.2 Psychological and socioeconomic processes ,1.1 Normal biological development and functioning ,Underpinning research ,Neurological ,Administration ,Intravenous ,Adult ,Brain ,Case-Control Studies ,Consciousness ,Electroencephalography ,Female ,Hallucinogens ,Humans ,Male ,Multivariate Analysis ,N ,N-Dimethyltryptamine - Abstract
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 and 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.
- Published
- 2019
26. Mescaline: The forgotten psychedelic
- Author
-
Vamvakopoulou, Ioanna A., Narine, Kelly A.D., Campbell, Ian, Dyck, Jason R.B., and Nutt, David J.
- Published
- 2023
- Full Text
- View/download PDF
27. Prescribed Medicinal Cannabis for the Treatment of Chronic Pain Comorbid with Depression: Real World Evidence from Project Twenty21
- Author
-
Athanasiou-Fragkouli, Alkyoni, primary, Lynskey, Michael T, additional, Schlag, Anne Katrin, additional, and Nutt, David J, additional
- Published
- 2024
- Full Text
- View/download PDF
28. LSD flattens the hierarchy of directed information flow in fast whole-brain dynamics
- Author
-
Shinozuka, Kenneth, primary, Tewarie, Prejaas, additional, Luppi, Andrea, additional, Lynn, Christopher, additional, Roseman, Leor, additional, Muthukumaraswamy, Suresh Daniel, additional, Nutt, David J., additional, Carhart-Harris, Robin, additional, Deco, Gustavo, additional, and Kringelbach, Morten L, additional
- Published
- 2024
- Full Text
- View/download PDF
29. Relationship between astrocyte reactivity, using novel 11C-BU99008 PET, and glucose metabolism, grey matter volume and amyloid load in cognitively impaired individuals
- Author
-
Livingston, Nicholas R., Calsolaro, Valeria, Hinz, Rainer, Nowell, Joseph, Raza, Sanara, Gentleman, Steve, Tyacke, Robin J., Myers, Jim, Venkataraman, Ashwin V., Perneczky, Robert, Gunn, Roger N., Rabiner, Eugenii A., Parker, Christine A., Murphy, Philip S., Wren, Paul B., Nutt, David J., Matthews, Paul M., and Edison, Paul
- Published
- 2022
- Full Text
- View/download PDF
30. A Perspective on Psychedelics as Treatments for Addictions.
- Author
-
Nutt, David J., Morgan, Celia, and Klaire, Sukhpreet
- Published
- 2024
- Full Text
- View/download PDF
31. Astrocyte reactivity with late-onset cognitive impairment assessed in vivo using 11C-BU99008 PET and its relationship with amyloid load
- Author
-
Calsolaro, Valeria, Matthews, Paul M., Donat, Cornelius K., Livingston, Nicholas R., Femminella, Grazia D., Guedes, Sandra Silva, Myers, Jim, Fan, Zhen, Tyacke, Robin J., Venkataraman, Ashwin V., Perneczky, Robert, Gunn, Roger, Rabiner, Eugenii A., Gentleman, Steve, Parker, Christine A., Murphy, Philip S., Wren, Paul B., Hinz, Rainer, Sastre, Magdalena, Nutt, David J., and Edison, Paul
- Published
- 2021
- Full Text
- View/download PDF
32. Psilocybin and MDMA reduce costly punishment in the Ultimatum Game
- Author
-
Gabay, Anthony S, Carhart-Harris, Robin L, Mazibuko, Ndaba, Kempton, Matthew J, Morrison, Paul D, Nutt, David J, and Mehta, Mitul A
- Subjects
Behavioral and Social Science ,Clinical Research ,Neurosciences ,Clinical Trials and Supportive Activities ,Generic health relevance ,Mental health ,Good Health and Well Being ,Adult ,Altruism ,Community-Based Participatory Research ,Decision Making ,Emotions ,Games ,Experimental ,Healthy Volunteers ,Humans ,Interpersonal Relations ,Male ,Middle Aged ,N-Methyl-3 ,4-methylenedioxyamphetamine ,Psilocybin ,Psychopharmacology ,Punishment ,Rejection ,Psychology ,Reward ,Social Behavior ,Socialization ,Young Adult - Abstract
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.
- Published
- 2018
33. Cerebral blood flow predicts differential neurotransmitter activity.
- Author
-
Dukart, Juergen, Holiga, Štefan, Chatham, Christopher, Hawkins, Peter, Forsyth, Anna, McMillan, Rebecca, Myers, Jim, Lingford-Hughes, Anne R, Nutt, David J, Merlo-Pich, Emilio, Risterucci, Celine, Boak, Lauren, Umbricht, Daniel, Schobel, Scott, Liu, Thomas, Mehta, Mitul A, Zelaya, Fernando O, Williams, Steve C, Brown, Gregory, Paulus, Martin, Honey, Garry D, Muthukumaraswamy, Suresh, Hipp, Joerg, Bertolino, Alessandro, and Sambataro, Fabio
- Subjects
Central Nervous System ,Humans ,Neurotransmitter Agents ,Anesthetics ,Dissociative ,Antipsychotic Agents ,Central Nervous System Stimulants ,Antidepressive Agents ,Second-Generation ,Magnetic Resonance Imaging ,Cerebrovascular Circulation ,Adult ,Female ,Male ,Young Adult ,Healthy Volunteers ,Neurophysiological Monitoring ,Brain Disorders ,Neurosciences ,Neurological ,Anesthetics ,Dissociative ,Antidepressive Agents ,Second-Generation ,Biochemistry and Cell Biology ,Other Physical Sciences - Abstract
Application of metabolic magnetic resonance imaging measures such as cerebral blood flow in translational medicine is limited by the unknown link of observed alterations to specific neurophysiological processes. In particular, the sensitivity of cerebral blood flow to activity changes in specific neurotransmitter systems remains unclear. We address this question by probing cerebral blood flow in healthy volunteers using seven established drugs with known dopaminergic, serotonergic, glutamatergic and GABAergic mechanisms of action. We use a novel framework aimed at disentangling the observed effects to contribution from underlying neurotransmitter systems. We find for all evaluated compounds a reliable spatial link of respective cerebral blood flow changes with underlying neurotransmitter receptor densities corresponding to their primary mechanisms of action. The strength of these associations with receptor density is mediated by respective drug affinities. These findings suggest that cerebral blood flow is a sensitive brain-wide in-vivo assay of metabolic demands across a variety of neurotransmitter systems in humans.
- Published
- 2018
34. Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms
- Author
-
Carhart-Harris, Robin L, Roseman, Leor, Bolstridge, Mark, Demetriou, Lysia, Pannekoek, J Nienke, Wall, Matthew B, Tanner, Mark, Kaelen, Mendel, McGonigle, John, Murphy, Kevin, Leech, Robert, Curran, H Valerie, and Nutt, David J
- Subjects
Behavioral and Social Science ,Brain Disorders ,Clinical Research ,Neurosciences ,Depression ,Mental Health ,2.1 Biological and endogenous factors ,Aetiology ,Mental health ,Neurological ,Adult ,Brain ,Female ,Humans ,Magnetic Resonance Imaging ,Male ,Middle Aged ,Psilocybin - Abstract
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.
- Published
- 2017
35. Altered Insula Connectivity under MDMA
- Author
-
Walpola, Ishan C, Nest, Timothy, Roseman, Leor, Erritzoe, David, Feilding, Amanda, Nutt, David J, and Carhart-Harris, Robin L
- Subjects
Clinical Research ,Neurosciences ,Basic Behavioral and Social Science ,Drug Abuse (NIDA only) ,Substance Misuse ,Behavioral and Social Science ,Mental health ,Adult ,Brain Mapping ,Cerebral Cortex ,Double-Blind Method ,Female ,Follow-Up Studies ,Hallucinogens ,Humans ,Image Processing ,Computer-Assisted ,Linear Models ,Magnetic Resonance Imaging ,Male ,Middle Aged ,N-Methyl-3 ,4-methylenedioxyamphetamine ,Nerve Net ,Rest ,Young Adult ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
Recent work with noninvasive human brain imaging has started to investigate the effects of 3,4-methylenedioxymethamphetamine (MDMA) on large-scale patterns of brain activity. MDMA, a potent monoamine-releaser with particularly pronounced serotonin- releasing properties, has unique subjective effects that include: marked positive mood, pleasant/unusual bodily sensations and pro-social, empathic feelings. However, the neurobiological basis for these effects is not properly understood, and the present analysis sought to address this knowledge gap. To do this, we administered MDMA-HCl (100 mg p.o.) and, separately, placebo (ascorbic acid) in a randomized, double-blind, repeated-measures design with twenty-five healthy volunteers undergoing fMRI scanning. We then employed a measure of global resting-state functional brain connectivity and follow-up seed-to-voxel analysis to the fMRI data we acquired. Results revealed decreased right insula/salience network functional connectivity under MDMA. Furthermore, these decreases in right insula/salience network connectivity correlated with baseline trait anxiety and acute experiences of altered bodily sensations under MDMA. The present findings highlight insular disintegration (ie, compromised salience network membership) as a neurobiological signature of the MDMA experience, and relate this brain effect to trait anxiety and acutely altered bodily sensations-both of which are known to be associated with insular functioning.
- Published
- 2017
36. Medicinal cannabis for treating post-traumatic stress disorder and comorbid depression: real-world evidence
- Author
-
Lynskey, Michael T., primary, Athanasiou-Fragkouli, Alkyoni, additional, Thurgur, Hannah, additional, Schlag, Anne Katrin, additional, and Nutt, David J., additional
- Published
- 2024
- Full Text
- View/download PDF
37. Using real world evidence to optimize care: the case of medical cannabis
- Author
-
Schlag, Anne Katrin, primary, Nutt, David J, additional, and Lynskey, Michael, additional
- Published
- 2024
- Full Text
- View/download PDF
38. Brain dynamics predictive of response to psilocybin for treatment-resistant depression
- Author
-
Vohryzek, Jakub, primary, Cabral, Joana, additional, Lord, Louis-David, additional, Fernandes, Henrique M, additional, Roseman, Leor, additional, Nutt, David J, additional, Carhart-Harris, Robin L, additional, Deco, Gustavo, additional, and Kringelbach, Morten L, additional
- Published
- 2024
- Full Text
- View/download PDF
39. Open letter from UK based academic scientists to the secretaries of state for digital, culture, media and sport and for health and social care regarding the need for independent funding for the prevention and treatment of gambling harms
- Author
-
Wardle, Heather, Banks, James, Bebbington, Paul, Blank, Lindsey, OBE, Henrietta Bowden Jones, Bramley, Stephanie, Bunn, Christopher, Casey, Emma, Cassidy, Rebecca, Chamberlain, Samuel R, Close, James, Critchlow, Nathan, Dobbie, Fiona, Downs, Carolyn, Dymond, Simon, Fino, Emanuele, Goyder, Elizabeth, Gray, Cindy, Griffiths, Mark, Grindrod, Peter, Hogan, Lee, Hoon, Alice, Hunt, Kate, James, Richard, John, Bev, Manthorpe, Jill, McCambridge, Jim, McDaid, David, McKee, Martin, McManus, Sally, Moss, Antony, Norrie, Caroline, Nutt, David J, Orford, Jim, Pryce, Rob, Purves, Richard, Reith, Gerda, Roberts, Amanda, Roberts, Emmett, Roderique-Davies, Gareth, Rogers, Jim, Rogers, Robert D, Sharman, Stephen, Strang, John, Tunney, Richard, Turner, John, West, Robert, and Zendle, David
- Published
- 2020
40. Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression
- Author
-
Roseman, Leor, Nutt, David J, and Carhart-Harris, Robin L
- Subjects
Brain Disorders ,Depression ,Clinical Trials and Supportive Activities ,Mental Health ,Clinical Research ,Mental health ,Good Health and Well Being ,depression ,mystical experience ,peak experience ,psilocybin ,psychedelics ,serotonin ,therapy ,Pharmacology and Pharmaceutical Sciences - Abstract
Introduction: It is a basic principle of the "psychedelic" treatment model that the quality of the acute experience mediates long-term improvements in mental health. In the present paper we sought to test this using data from a clinical trial assessing psilocybin for treatment-resistant depression (TRD). In line with previous reports, we hypothesized that the occurrence and magnitude of Oceanic Boundlessness (OBN) (sharing features with mystical-type experience) and Dread of Ego Dissolution (DED) (similar to anxiety) would predict long-term positive outcomes, whereas sensory perceptual effects would have negligible predictive value. Materials and Methods: Twenty patients with treatment resistant depression underwent treatment with psilocybin (two separate sessions: 10 and 25 mg psilocybin). The Altered States of Consciousness (ASC) questionnaire was used to assess the quality of experiences in the 25 mg psilocybin session. From the ASC, the dimensions OBN and DED were used to measure the mystical-type and challenging experiences, respectively. The Self-Reported Quick Inventory of Depressive Symptoms (QIDS-SR) at 5 weeks served as the endpoint clinical outcome measure, as in later time points some of the subjects had gone on to receive new treatments, thus confounding inferences. In a repeated measure ANOVA, Time was the within-subject factor (independent variable), with QIDS-SR as the within-subject dependent variable in baseline, 1-day, 1-week, 5-weeks. OBN and DED were independent variables. OBN-by-Time and DED-by-Time interactions were the primary outcomes of interest. Results: For the interaction of OBN and DED with Time (QIDS-SR as dependent variable), the main effect and the effects at each time point compared to baseline were all significant (p = 0.002 and p = 0.003, respectively, for main effects), confirming our main hypothesis. Furthermore, Pearson's correlation of OBN with QIDS-SR (5 weeks) was specific compared to perceptual dimensions of the ASC (p < 0.05). Discussion: This report further bolsters the view that the quality of the acute psychedelic experience is a key mediator of long-term changes in mental health. Future therapeutic work with psychedelics should recognize the essential importance of quality of experience in determining treatment efficacy and consider ways of enhancing mystical-type experiences and reducing anxiety. Trial Registration: ISRCTN, number ISRCTN14426797, http://www.isrctn.com/ISRCTN14426797.
- Published
- 2017
41. GABA-A receptor differences in schizophrenia: a positron emission tomography study using [11C]Ro154513
- Author
-
Marques, Tiago Reis, Ashok, Abhishekh H., Angelescu, Ilinca, Borgan, Faith, Myers, Jim, Lingford-Hughes, Anne, Nutt, David J., Veronese, Mattia, Turkheimer, Federico E., and Howes, Oliver D.
- Published
- 2021
- Full Text
- View/download PDF
42. Effects of discontinuation of serotonergic antidepressants prior to psilocybin therapy versus escitalopram for major depression.
- Author
-
Erritzoe, David, Barba, Tommaso, Spriggs, Meg J, Rosas, Fernando E, Nutt, David J, and Carhart-Harris, Robin
- Subjects
PSILOCYBIN ,ANTIDEPRESSANTS ,MENTAL depression ,SEROTONIN uptake inhibitors ,ESCITALOPRAM ,HALLUCINOGENIC drugs - Abstract
Background: There is growing evidence for the therapeutic effects of the psychedelic drug psilocybin for major depression. However, due to the lack of safety data on combining psilocybin with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and concerns that there may be a negative interaction on efficacy, participants enrolling in psychedelic trials are usually required to discontinue SNRI/SNRIs prior to enrolling. Aims: Using data from a recent clinical trial examining the comparative efficacy the psychedelic drug psilocybin (P) combined with approximately 20 h of psychological support to a 6-week (daily) course of the SSRI escitalopram plus matched psychological support for major depressive disorder, we explored the effects of discontinuing SSRI/SNRIs prior to study enrolment on study outcomes. Methods: Exploratory post hoc analyses using linear mixed effects model were performed to investigate the discontinuation effect on various validated depression symptom severity scales and well-being. The impact of SSRI/SNRIs discontinuation on the acute psychedelic experience was also explored. Results/outcomes: In the psilocybin group, there was a reduced treatment effect on all outcome measures for SSRI/SNRIs discontinuers compared with unmedicated patients at trial entry. However, no effects of discontinuation on measures of the acute psychedelic experience were found. Conclusion: Discontinuation of SSRI/SNRIs before psilocybin might diminish response to treatment; however, as we did not test SSRI/SNRI continuation in our trial, we cannot infer such causation. Moreover, the exploratory nature of the analyses makes them hypothesis generating, and not confirmatory. A controlled trial of SSRI/SNRI discontinuation versus continuation prior to psilocybin is urgently required. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
43. The flattening of spacetime hierarchy of the N,N-dimethyltryptamine brain state is characterized by harmonic decomposition of spacetime (HADES) framework.
- Author
-
Vohryzek, Jakub, Cabral, Joana, Timmermann, Christopher, Atasoy, Selen, Roseman, Leor, Nutt, David J, Carhart-Harris, Robin L, Deco, Gustavo, and Kringelbach, Morten L
- Subjects
SPACETIME ,HALLUCINOGENIC drugs - Abstract
The human brain is a complex system, whose activity exhibits flexible and continuous reorganization across space and time. The decomposition of whole-brain recordings into harmonic modes has revealed a repertoire of gradient-like activity patterns associated with distinct brain functions. However, the way these activity patterns are expressed over time with their changes in various brain states remains unclear. Here, we investigate healthy participants taking the serotonergic psychedelic N,N -dimethyltryptamine (DMT) with the Harmonic Decomposition of Spacetime (HADES) framework that can characterize how different harmonic modes defined in space are expressed over time. HADES demonstrates significant decreases in contributions across most low-frequency harmonic modes in the DMT-induced brain state. When normalizing the contributions by condition (DMT and non-DMT), we detect a decrease specifically in the second functional harmonic, which represents the uni- to transmodal functional hierarchy of the brain, supporting the leading hypothesis that functional hierarchy is changed in psychedelics. Moreover, HADES' dynamic spacetime measures of fractional occupancy, life time and latent space provide a precise description of the significant changes of the spacetime hierarchical organization of brain activity in the psychedelic state. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
44. The development and validation of a human screening model of tobacco abstinence
- Author
-
Grabski, Meryem, Curran, H. Valerie, Nutt, David J., Husbands, Stephen M., Ferguson, Stuart G., and Munafò, Marcus R.
- Published
- 2020
- Full Text
- View/download PDF
45. LSD alters eyes‐closed functional connectivity within the early visual cortex in a retinotopic fashion
- Author
-
Roseman, Leor, Sereno, Martin I, Leech, Robert, Kaelen, Mendel, Orban, Csaba, McGonigle, John, Feilding, Amanda, Nutt, David J, and Carhart-Harris, Robin L
- Subjects
Neurosciences ,Clinical Research ,Eye Disease and Disorders of Vision ,Female ,Hallucinogens ,Humans ,Lysergic Acid Diethylamide ,Magnetic Resonance Imaging ,Male ,Neural Pathways ,Visual Cortex ,LSD ,fMRI ,hallucinations ,imagery ,psychedelics ,serotonin 5-HT2 receptor agonists ,visual cortex ,Cognitive Sciences ,Experimental Psychology - Abstract
The question of how spatially organized activity in the visual cortex behaves during eyes-closed, lysergic acid diethylamide (LSD)-induced "psychedelic imagery" (e.g., visions of geometric patterns and more complex phenomena) has never been empirically addressed, although it has been proposed that under psychedelics, with eyes-closed, the brain may function "as if" there is visual input when there is none. In this work, resting-state functional connectivity (RSFC) data was analyzed from 10 healthy subjects under the influence of LSD and, separately, placebo. It was suspected that eyes-closed psychedelic imagery might involve transient local retinotopic activation, of the sort typically associated with visual stimulation. To test this, it was hypothesized that, under LSD, patches of the visual cortex with congruent retinotopic representations would show greater RSFC than incongruent patches. Using a retinotopic localizer performed during a nondrug baseline condition, nonadjacent patches of V1 and V3 that represent the vertical or the horizontal meridians of the visual field were identified. Subsequently, RSFC between V1 and V3 was measured with respect to these a priori identified patches. Consistent with our prior hypothesis, the difference between RSFC of patches with congruent retinotopic specificity (horizontal-horizontal and vertical-vertical) and those with incongruent specificity (horizontal-vertical and vertical-horizontal) increased significantly under LSD relative to placebo, suggesting that activity within the visual cortex becomes more dependent on its intrinsic retinotopic organization in the drug condition. This result may indicate that under LSD, with eyes-closed, the early visual system behaves as if it were seeing spatially localized visual inputs. Hum Brain Mapp 37:3031-3040, 2016. © 2016 Wiley Periodicals, Inc.
- Published
- 2016
46. Neural correlates of the LSD experience revealed by multimodal neuroimaging
- Author
-
Carhart-Harris, Robin L, Muthukumaraswamy, Suresh, Roseman, Leor, Kaelen, Mendel, Droog, Wouter, Murphy, Kevin, Tagliazucchi, Enzo, Schenberg, Eduardo E, Nest, Timothy, Orban, Csaba, Leech, Robert, Williams, Luke T, Williams, Tim M, Bolstridge, Mark, Sessa, Ben, McGonigle, John, Sereno, Martin I, Nichols, David, Hellyer, Peter J, Hobden, Peter, Evans, John, Singh, Krish D, Wise, Richard G, Curran, H Valerie, Feilding, Amanda, and Nutt, David J
- Subjects
Eye Disease and Disorders of Vision ,Clinical Research ,Biomedical Imaging ,Neurosciences ,Underpinning research ,1.1 Normal biological development and functioning ,Neurological ,Mental health ,Brain ,Brain Mapping ,Cerebrovascular Circulation ,Connectome ,Consciousness ,Hallucinations ,Hallucinogens ,Humans ,Lysergic Acid Diethylamide ,Magnetic Resonance Imaging ,Magnetoencephalography ,Multimodal Imaging ,Nerve Net ,Oxygen ,Receptor ,Serotonin ,5-HT2A ,Serotonin 5-HT2 Receptor Agonists ,Spin Labels ,Synaptic Transmission ,LSD ,brain ,consciousness ,psychedelic ,serotonin - Abstract
Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging. Here, three complementary neuroimaging techniques: arterial spin labeling (ASL), blood oxygen level-dependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in brain activity after LSD that correlated strongly with its characteristic psychological effects. Increased visual cortex cerebral blood flow (CBF), decreased visual cortex alpha power, and a greatly expanded primary visual cortex (V1) functional connectivity profile correlated strongly with ratings of visual hallucinations, implying that intrinsic brain activity exerts greater influence on visual processing in the psychedelic state, thereby defining its hallucinatory quality. LSD's marked effects on the visual cortex did not significantly correlate with the drug's other characteristic effects on consciousness, however. Rather, decreased connectivity between the parahippocampus and retrosplenial cortex (RSC) correlated strongly with ratings of "ego-dissolution" and "altered meaning," implying the importance of this particular circuit for the maintenance of "self" or "ego" and its processing of "meaning." Strong relationships were also found between the different imaging metrics, enabling firmer inferences to be made about their functional significance. This uniquely comprehensive examination of the LSD state represents an important advance in scientific research with psychedelic drugs at a time of growing interest in their scientific and therapeutic value. The present results contribute important new insights into the characteristic hallucinatory and consciousness-altering properties of psychedelics that inform on how they can model certain pathological states and potentially treat others.
- Published
- 2016
47. Psychological and physiological effects of extended DMT
- Author
-
Luan, Lisa X, primary, Eckernäs, Emma, additional, Ashton, Michael, additional, Rosas, Fernando E, additional, Uthaug, Malin V, additional, Bartha, Alexander, additional, Jagger, Samantha, additional, Gascon-Perai, Kiara, additional, Gomes, Lauren, additional, Nutt, David J, additional, Erritzøe, David, additional, Carhart-Harris, Robin L, additional, and Timmermann, Christopher, additional
- Published
- 2023
- Full Text
- View/download PDF
48. Pharmacological Dissection of Antipsychotics
- Author
-
Nutt, David J., primary
- Published
- 2023
- Full Text
- View/download PDF
49. LSD-induced changes in the functional connectivity of distinct thalamic nuclei
- Author
-
Pizzi, Stefano Delli, primary, Chiacchiaretta, Piero, additional, Sestieri, Carlo, additional, Ferretti, Antonio, additional, Tullo, Maria Giulia, additional, Penna, Stefania Della, additional, Martinotti, Giovanni, additional, Onofrj, Marco, additional, Roseman, Leor, additional, Slater, Christopher Bernhard Timmermann, additional, Nutt, David J., additional, Carhart-Harris, Robin, additional, and Sensi, Stefano L., additional
- Published
- 2023
- Full Text
- View/download PDF
50. The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level–Dependent Resting State Functional Connectivity
- Author
-
Carhart-Harris, Robin L, Murphy, Kevin, Leech, Robert, Erritzoe, David, Wall, Matthew B, Ferguson, Bart, Williams, Luke TJ, Roseman, Leor, Brugger, Stefan, De Meer, Ineke, Tanner, Mark, Tyacke, Robin, Wolff, Kim, Sethi, Ajun, Bloomfield, Michael AP, Williams, Tim M, Bolstridge, Mark, Stewart, Lorna, Morgan, Celia, Newbould, Rexford D, Feilding, Amanda, Curran, H Val, and Nutt, David J
- Subjects
Basic Behavioral and Social Science ,Behavioral and Social Science ,Clinical Research ,Mental Health ,Neurosciences ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,1.1 Normal biological development and functioning ,Underpinning research ,Neurological ,Adult ,Affect ,Amygdala ,Cerebrovascular Circulation ,Double-Blind Method ,Female ,Healthy Volunteers ,Hippocampus ,Humans ,Magnetic Resonance Imaging ,Male ,Middle Aged ,N-Methyl-3 ,4-methylenedioxyamphetamine ,Oxygen ,Prefrontal Cortex ,Serotonin Agents ,Temporal Lobe ,Young Adult ,5-HT ,MDMA ,PTSD ,Serotonin ,fMRI ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
BackgroundThe compound 3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine releaser that produces an acute euphoria in most individuals.MethodsIn a double-blind, placebo-controlled, balanced-order study, MDMA was orally administered to 25 physically and mentally healthy individuals. Arterial spin labeling and seed-based resting state functional connectivity (RSFC) were used to produce spatial maps displaying changes in cerebral blood flow (CBF) and RSFC after MDMA administration. Participants underwent two arterial spin labeling and two blood oxygen level-dependent scans in a 90-minute scan session; MDMA and placebo study days were separated by 1 week.ResultsMarked increases in positive mood were produced by MDMA. Decreased CBF only was observed after MDMA, and this was localized to the right medial temporal lobe (MTL), thalamus, inferior visual cortex, and the somatosensory cortex. Decreased CBF in the right amygdala and hippocampus correlated with ratings of the intensity of global subjective effects of MDMA. The RSFC results complemented the CBF results, with decreases in RSFC between midline cortical regions, the medial prefrontal cortex, and MTL regions, and increases between the amygdala and hippocampus. There were trend-level correlations between these effects and ratings of intense and positive subjective effects.ConclusionsThe MTLs appear to be specifically implicated in the mechanism of action of MDMA, but further work is required to elucidate how the drug's characteristic subjective effects arise from its modulation of spontaneous brain activity.
- Published
- 2015
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.