Neuroimaging & Brain MeasuresHealthy VolunteersLSD

Neural correlates of the LSD experience revealed by multimodal neuroimaging

In the first modern multimodal neuroimaging study of LSD, the authors report pronounced changes in cerebral blood flow, electrophysiological activity and large‑scale network communication that strongly correlated with the drug’s hallucinatory and consciousness‑altering effects. These findings clarify neural mechanisms of altered consciousness and point to potential applications of LSD in psychological research.

Authors

  • Suresh Muthukumaraswamy
  • Enzo Tagliazucchi
  • Robin Carhart-Harris

Published

PNAS
individual Study

Abstract

SignificanceLysergic acid diethylamide (LSD), the prototypical “psychedelic,” may be unique among psychoactive substances. In the decades that followed its discovery, the magnitude of its effect on science, the arts, and society was unprecedented. LSD produces profound, sometimes life-changing experiences in microgram doses, making it a particularly powerful scientific tool. Here we sought to examine its effects on brain activity, using cutting-edge and complementary neuroimaging techniques in the first modern neuroimaging study of LSD. Results revealed marked changes in brain blood flow, electrical activity, and network communication patterns that correlated strongly with the drug’s hallucinatory and other consciousness-altering properties. These results have implications for the neurobiology of consciousness and for potential applications of LSD in psychological research.

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Research Summary of 'Neural correlates of the LSD experience revealed by multimodal neuroimaging'

Introduction

Carhart-Harris and colleagues situate this study within a long hiatus in modern human LSD research: although LSD was central to mid-20th century psychiatry, contemporary neuroimaging of its acute effects had not been undertaken. Earlier work with other psychedelics (for example psilocybin and ayahuasca) and older EEG studies suggested broad reductions in oscillatory power and alterations in resting-state networks, and animal and human data implicated hippocampal/parahippocampal circuitry and high-level cortical hubs such as the posterior cingulate cortex (PCC). However, the neural correlates of LSD in humans using modern multimodal methods remained uncharacterised, and questions persisted about how psychedelic-induced changes in spontaneous brain activity relate to hallmark subjective effects such as visual hallucinations and ego-dissolution. The study therefore set out to characterise the acute brain effects of LSD in healthy volunteers using a comprehensive, placebo-controlled multimodal neuroimaging protocol. Specifically, the investigators tested whether major resting-state networks (including the default-mode network, DMN) and hippocampal/parahippocampal circuitry would be implicated, and whether changes in cerebral blood flow (ASL), BOLD resting-state functional connectivity (RSFC), and MEG-measured oscillatory power would relate to subjective ratings of visual phenomena and alterations in selfhood.

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Study Details

References (20)

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Madsen, M. K., Stenbaek, D. S., Arvidsson, A. et al. · European Neuropsychopharmacology (2021)

Transcriptomics-informed large-scale cortical model captures topography of pharmacological neuroimaging effects of LSD

Burt, J. B., Preller, K. H., Demirtaş, M. et al. · eLife (2021)

Does psychedelic therapy have a transdiagnostic action and prophylactic potential?

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73 cited
Role of the 5-HT2A receptor in acute effects of LSD on empathy and circulating oxytocin

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Increased Entropic Brain Dynamics during DeepDream-Induced Altered Perceptual Phenomenology

Greco, A., Gallitto, G., Rastelli, C. · Entropy (2021)

An Encounter with the Other: A Thematic Analysis of Accounts of DMT Experiences from a Naturalistic Field Study

Michael, P., Luke, D., Robinson, O. · Frontiers in Psychology (2021)

Catalysts for change: the cellular neurobiology of psychedelics

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31 cited
Psychedelics and health behaviour change

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From hallucinations to synaesthesia: a circular inference account of unimodal and multimodal erroneous percepts in clinical and drug-induced psychosis

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12 cited
Psychedelics and Consciousness: Distinctions, Demarcations, and Opportunities

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Effects of psilocybin microdosing on awe and aesthetic experiences: a preregistered field and lab-based study

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42 cited
Spontaneous and deliberate creative cognition during and after psilocybin exposure

Mason, N. L., Kuypers, K. P. C., Reckweg, J. T. et al. · Translational Psychiatry (2021)

86 cited
Increased sensitivity to strong perturbations in a whole-brain model of LSD

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Neural Correlates of the Shamanic State of Consciousness

Pasquini, L., Luke, D., Harris, R. E. et al. · Frontiers in Human Neuroscience (2021)

Neural and subjective effects of inhaled N,N-dimethyltryptamine in natural settings

Pallavicini, C., Cavanna, F., Zamberlan, F. et al. · Journal of Psychopharmacology (2021)

Psychedelic drugs and perception: a narrative review of the first era of research

Aday, J. S., Bloesch, E. K., Wood, J. R. et al. · Reviews In The Neuroscience (2021)

Trends in the Top-Cited Articles on Classic Psychedelics

Lawrence, D. W., Sharma, B., Griffiths, R. R. et al. · Journal of Psychoactive Drugs (2021)

LSD alters dynamic integration and segregation in the human brain

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141 cited
EEG Gamma Band Alterations and REM-like Traits Underpin the Acute Effect of the Atypical Psychedelic Ibogaine in the Rat

González, J., Cavelli, M., Castro-Zaballa, S. et al. · ACS Pharmacology and Translational Science (2021)

17 cited
The entropic tongue: Disorganization of natural language under LSD

Sanz, C., Pallavicini, C., Carrillo, F. et al. · Consciousness and Cognition (2021)

24 cited
Effect of lysergic acid diethylamide (LSD) on reinforcement learning in humans

Kanen, J. W., Luo, Q., Kandroodi, M. R. et al. · Psychological Medicine (2020)

The History of Psychedelics in Psychiatry

Nichols, D. E., Walter, H. · Pharmacopsychiatry (2020)

The potential synergistic effects between psychedelic administration and nature contact for the improvement of mental health

Gandy, S., Forstmann, M., Carhart-Harris, R. L. et al. · Health Psychology Open (2020)

Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine

Hibicke, M., Gobbi, G. · Journal of Neuroscience (2020)

145 cited
Ketamine and Serotonergic Psychedelics: Common Mechanisms Underlying the Effects of Rapid-Acting Antidepressants

Kadriu, B., Greenwald, M., Ba et al. · International Journal of Neuropsychopharmacology (2020)

MDMA-induced changes in within-network connectivity contradict the specificity of these alterations for the effects of serotonergic hallucinogens

Holze, F., Dolder, P. C., Ley, L. et al. · Neuropsychopharmacology (2020)

Pivotal Mental States

Brouwer, A., Carhart-Harris, R. L. · Journal of Psychopharmacology (2020)

Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern-era clinical studies

Andersen, K. A. A., Carhart-Harris, R. L., Nutt, D. J. et al. · Acta Psychiatrica Scandinavica (2020)

DMT alters cortical travelling waves

Alamia, A., Timmermann, C., Carhart-Harris, R. L. · eLife (2020)

Acute subjective effects in LSD- and MDMA-assisted psychotherapy

Schmid, Y., Gasser, P., Oehen, P. et al. · Journal of Psychopharmacology (2020)

72 cited
The Acute Effects of the Atypical Dissociative Hallucinogen Salvinorin A on Functional Connectivity in the Human Brain

Doss, M. K., May, D. G., Johnson, M. W. et al. · Scientific Reports (2020)

Serotonergic psychedelics LSD & psilocybin increase the fractal dimension of cortical brain activity in spatial and temporal domains

Varley, T. F., Carhart-Harris, R., Roseman, L. et al. · NeuroImage (2020)

Hallucinations Under Psychedelics and in the Schizophrenia Spectrum: An Interdisciplinary and Multiscale Comparison

Leptourgos, P., Fortier-Davy, M., Carhart-Harris, R. L. et al. · Schizophrenia Bulletin (2020)

Classic Psychedelics as a Psychotherapeutic Aid in the Treatment of Stimulant Use Disorder: a Case Report

Johnson, S., Black, Q. C. · International Journal of Mental Health and Addiction (2020)

1 cited
Psychedelic drugs: neurobiology and potential for treatment of psychiatric disorders

Vollenweider, F. X., Preller, K. H. · Nature Reviews Neuroscience (2020)

Psilocybin acutely alters the functional connectivity of the claustrum with brain networks that support perception, memory, and attention

Barrett, F. S., Krimmel, S. R., Griffiths, R. R. et al. · NeuroImage (2020)

Are Psychedelics Something New in Teaching Psychopharmacology?

Louie, A. K., Beresin, E. V., Coverdale, J. et al. · Academic Psychiatry (2020)

P300-mediated modulations in self-other processing under psychedelic psilocybin are related to connectedness and changed meaning: A window into the self-other overlap

Smigielski, L., Kometer, M., Scheidegger, M. et al. · Human Brain Mapping (2020)

2 cited
Modulatory effects of ayahuasca on personality structure in a traditional framework

Netzband, N., Ruffell, S., Linton, &. S. et al. · Psychopharmacology (2020)

A potential role for psilocybin in the treatment of obsessive-compulsive disorder

Jacobs, E. · Journal of Psychedelic Studies (2020)

Integrating psychotherapy and psychopharmacology: psychedelic-assisted psychotherapy and other combined treatments

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Updating the dynamic framework of thought: Creativity and psychedelics

Girn, M., Mills, C., Roseman, L. et al. · NeuroImage (2020)

Compassionate use of psychedelics

Greif, A., Šurkala, M. · Medicine Health Care and Philosophy (2020)

Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin

Mason, N. L., Kuypers, K. P. C., Reckweg, J. et al. · Neuropsychopharmacology (2020)

Psychedelic treatment of functional neurological disorder: a systematic review

Butler, M., Seynaeve, M., Nicholson, T. R. et al. · Therapeutic Advances in Psychopharmacology (2020)

LSD flattens the functional hierarchy of the human brain

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Isness: Using Multi-Person VR to Design Peak Mystical Type Experiences Comparable to Psychedelics

Glowacki, D. R., Wonnacott, M. D., Freire, R. et al. · Association for Computing Machinery (2020)

32 cited
Subacute Effects of the Psychedelic Ayahuasca on the Salience and Default Mode Networks

Pasquini, L., Palhano-Fontes, F., Araújo, D. B. · Journal of Psychopharmacology (2020)

Decreased directed functional connectivity in the psychedelic state

Barnett, L., Muthukumaraswamy, S., Carhart-Harris, R. L. · NeuroImage (2020)

Psychedelics and Psychedelic-Assisted Psychotherapy

Reiff, C. M., Richman, E. E., Nemeroff, C. B. et al. · American Journal of Psychiatry (2020)

Emotions and brain function are altered up to one month after a single high dose of psilocybin

Barrett, F. S., Doss, M. K., Sepeda, N. D. et al. · Scientific Reports (2020)

Therapeutic Use of LSD in Psychiatry: A Systematic Review of Randomized-Controlled Clinical Trials

Fuentes, J. J., Fonseca, F., Elices, M. et al. · Frontiers in Psychiatry (2020)

Therapeutic mechanisms of psilocybin: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression

Mertens, L. J., Wall, M. B., Roseman, L. et al. · Journal of Psychopharmacology (2020)

155 cited
Neuropharmacological modulation of the aberrant bodily self through psychedelics

Ho, J. T., Preller, K. H., Lenggenhager, B. · Neuroscience and Biobehavioral Reviews (2020)

Embedding existential psychology within psychedelic science: reduced death anxiety as a mediator of the therapeutic effects of psychedelics.

Moreton, S. G., Szalla, L., Menzies, R. E. et al. · Psychopharmacology (2019)

47 cited
Neural correlates of the DMT experience assessed with multivariate EEG

Timmermann, C., Roseman, L., Schartner, M. et al. · Scientific Reports (2019)

Spectral signatures of serotonergic psychedelics and glutamatergic dissociatives

Pallavicini, C., Vilas, M. G., Villarreal, M. et al. · NeuroImage (2019)

51 cited
Acute effects of lysergic acid diethylamide (LSD) on resting brain function

Felix, M., Stefan, B. · Swiss Medical Weekly (2019)

Psilocybin-assisted mindfulness training modulates self-consciousness and brain default mode network connectivity with lasting effects

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REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics

Carhart-Harris, R. L., Friston, K. J. · Pharmacological Reviews (2019)

Psychedelic drugs-a new era in psychiatry?

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Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function

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Pharmacokinetics and subjective effects of a novel oral LSD formulation in healthy subjects

Holze, F., Duthaler, U., Vizeli, P. et al. · British Journal of Clinical Pharmacology (2019)

Effects of the psychedelic amphetamine MDA (3, 4-methylenedioxyamphetamine) in healthy volunteers

Baggott, M. J., Garrison, K. J., Coyle, J. R. et al. · Journal of Psychoactive Drugs (2019)

Neurochemical models of near-death experiences: A large-scale study based on the semantic similarity of written reports

Martial, C., Cassol, H., Charland-Verville, V, Erowid, E. et al. · Consciousness and Cognition (2019)

States and traits related to the quality and consequences of psychedelic experiences

Russ, S. L., Carhart-Harris, R. L., Maruyama, G. et al. · Psychology of Consciousness Theory Research and Practice (2019)

Effective connectivity changes in LSD-induced altered states of consciousness in humans

Preller, K. H., Razi, A., Zeidman, P. et al. · PNAS (2019)

How do psychedelics work?

Carhart-Harris, R. L. · Current Opinion in Psychiatry (2019)

The effects of microdose LSD on time perception: a randomised, double-blind, placebo-controlled trial

Yanakieva, S., Polychroni, N., Family, N. et al. · Psychopharmacology (2018)

Current perspectives on psychedelic therapy: use of serotonergic hallucinogens in clinical interventions

Richards, W. A., Garcia-Romeu, A. · International Review of Psychiatry (2018)

A sub-set of psychoactive effects may be critical to the behavioral impact of ketamine on cocaine use disorder: results from a randomized, controlled laboratory study

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Ketamine for the treatment of addiction: Evidence and potential mechanisms

Ezquerra-Romano, I. I., Lawn, W., Krupitsky, E. M. et al. · Neuropharmacology (2018)

LSD modulates effective connectivity and neural adaptation mechanisms in an auditory oddball paradigm

Timmermann, C., Spriggs, M. J., Kaelen, M. et al. · Neuropharmacology (2018)

Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor

Preller, K. H., Burt, J. B., Adkinson, B. et al. · eLife (2018)

Whole-brain multimodal neuroimaging model using serotonin receptor maps explains non-linear functional effects of LSD

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Awe: a putative mechanism underlying the effects of classic psychedelic-assisted psychotherapy

Hendricks, P. S. · International Review of Psychiatry (2018)

143 cited
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Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: a systematic review of systematic reviews

Dos Santos, R. G., Bouso, J. C., Hallak, J. E. · Expert Review of Clinical Pharmacology (2018)

191 cited
DMT models the near-death experience

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Psychedelics as anti-inflammatory agents

Flanagan, T. W., Nichols, C. D. · International Review of Psychiatry (2018)

N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function

Barker, S. · Frontiers in Neuroscience (2018)

The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act

Johnson, M. W., Griffiths, R. R., Hendricks, P. S. et al. · Neuropharmacology (2018)

Psilocybin modulates functional connectivity of the amygdala during emotional face discrimination

Grimm, O., Kraehenmann, R., Preller, K. H. et al. · European Neuropsychopharmacology (2018)

Dark Classics in Chemical Neuroscience: Mescaline

Cassels, B. K., Sáez-Briones, P. · ACS Chemical Neuroscience (2018)

Integrating Psychedelic Medicines and Psychiatry: Theory and Methods of a Model Clinic

Sloshower, J. A. · Plant Medicines Healing and Psychedelic Science (2018)

The Use of Salvia divinorum from a Mazatec Perspective

Maqueda, A. E. · Plant Medicines Healing and Psychedelic Science (2018)

Role of the 5-HT2A Receptor in Self- and Other-Initiated Social Interaction in Lysergic Acid Diethylamide-Induced States: A Pharmacological fMRI Study

Preller, K. H., Schilbach, L., Pokorny, T. et al. · Journal of Neuroscience (2018)

The entropic brain - revisited

Carhart-Harris, R. L. · Neuropharmacology (2018)

Unifying theories of psychedelic drug effects

Swanson, L. R. · Frontiers in Pharmacology (2018)

Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD)

Nichols, D. E. · ACS Chemical Neuroscience (2018)

Is LSD toxic?

Nichols, D. E., Grob, C. S. · Forensic Science International (2018)

The hidden therapist: evidence for a central role of music in psychedelic therapy

Kaelen, M., Giribaldi, B., Raine, J. et al. · Psychopharmacology (2018)

213 cited
The Experience Elicited by Hallucinogens Presents the Highest Similarity to Dreaming within a Large Database of Psychoactive Substance Reports

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Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression

Roseman, L., Nutt, D. J., Carhart-Harris, R. L. · Frontiers in Pharmacology (2018)

Psilocybin disrupts sensory and higher order cognitive processing but not pre-attentive cognitive processing-study on P300 and mismatch negativity in healthy volunteers

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Altered network hub connectivity after acute LSD administration

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Psychiatry & the psychedelic drugs. Past, present & future

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Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD

Atasoy, S., Leor, R., Kaelen, M. et al. · Scientific Reports (2017)

The serotonin hallucinogen 5-MeO-DMT alters cortico-thalamic activity in freely moving mice: Regionally-selective involvement of 5-HT1A and 5-HT2A receptors

Riga, M. S., Llad O-Pelfort, L., Artigas, F. et al. · Neuropharmacology (2017)

Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: similarities and differences in subjective experiences

Carbonaro, T. M., Hurwitz, E., Johnson, M. W. · Psychopharmacology (2017)

102 cited
Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms

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Acute LSD effects on response inhibition neural networks

Schmidt, A., Müller, F., Lenz, C. et al. · Psychological Medicine (2017)

Serotonin 2A receptor signaling underlies LSD-induced alteration of the neural response to dynamic changes in music

Barrett, F. S., Preller, K. H., Herdener, M. et al. · Cerebral Cortex (2017)

The Mechanisms of Psychedelic Visionary Experiences: Hypotheses from Evolutionary Psychology

Winkelman, M. J. · Frontiers in Neuroscience (2017)

Psychedelic Drugs in Biomedicine

Kyzar, E. J., Nichols, C. D., Gainetdinov, R. R. et al. · Trends in Pharmacological Sciences (2017)

Increased thalamic resting state connectivity as a core driver of LSD-induced hallucinations

Lenz, C., Dolder, P. C., Lang, U. E. et al. · Acta Psychiatrica Scandinavica (2017)

Long-lasting subjective effects of LSD in normal subjects

Schmid, Y., Liechti, M. E. · Psychopharmacology (2017)

Psychedelic pleasures: An affective understanding of the joys of tripping

Bøhling, F. · International Journal of Drug Policy (2017)

Serotonin and brain function: a tale of two receptors

Carhart-Harris, R. L., Nutt, D. J. · Journal of Psychopharmacology (2017)

Dreams and psychedelics: neurophenomenological comparison and therapeutic implications

Kraehenmann, R. · Current Neuropharmacology (2017)

68 cited
Shannon entropy of brain functional complex networks under the influence of the psychedelic Ayahuasca

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Psychedelic drug use in healthy individuals: A review of benefits, costs, and implications for drug policy

Elsey, J. W. B. · Drug Science Policy and Law (2017)

A Single Dose of LSD Does Not Alter Gene Expression of the Serotonin 2A Receptor Gene (HTR2A) or Early Growth Response Genes (EGR1-3) in Healthy Subjects

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11 cited
Effects of LSD on music-evoked brain activity

Kaelen, M., Lorenz, R., Barrett, F. S. et al. · Biorxiv (2017)

Patients’ accounts of increased “Connectedness” and “Acceptance” after psilocybin for treatment-resistant depression

Watts, R., Day, C. M., Krzanowski, J. et al. · Journal of Humanistic Psychology (2017)

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Looking for the Self: Phenomenology, Neurophysiology and Philosophical Significance of Drug-induced Ego Dissolution

Millière, R. · Frontiers in Human Neuroscience (2017)

Modern clinical research on LSD

Liechti, M. E. · Neuropsychopharmacology (2017)

Psychedelics, personality and political perspectives

Nour, M. R., Evans, J., Carhart-Harris, R. L. · Journal of Psychoactive Drugs (2017)

164 cited
The therapeutic potential of psychedelic drugs: past, present, and future

Carhart-Harris, R. L., Goodwin, G. M. · Neuropsychopharmacology (2017)

Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin

Schartner, M., Carhart-Harris, R. L., Barrett, A. B. et al. · Scientific Reports (2017)

19 cited
The psychological and human brain effects of music in combination with psychedelic drugs

Kaelen, M. · Imperial College London (2017)

Psychedelics and the science of self-experience

Nour, M. R., Carhart-Harris, R. L. · British Journal of Psychiatry (2017)

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Dolder, P. C., Schmid, Y., Steuer, A. E. et al. · Clinical Pharmacokinetics (2017)

5-HT2A Agonists: A Novel Therapy for Functional Neurological Disorders?

Bryson, A., Carter, O., Norman, T. et al. · International Journal of Neuropsychopharmacology (2017)

18 cited
Tripping up addiction: the use of psychedelic drugs in the treatment of problematic drug and alcohol use

Morgan, C. J. A., McAndrew, A., Stevens, T. et al. · Current Opinion in Behavioral Sciences (2017)

An online survey of tobacco smoking cessation associated with naturalistic psychedelic use

Johnson, M. W., Garcia-Romeu, A., Johnson, P. S. et al. · Journal of Psychopharmacology (2017)

117 cited
Crystal Structure of an LSD-Bound Human Serotonin Receptor

Wacker, D., Wang, S., Mccorvy, J. D. et al. · Cell (2017)

Perception is in the Details: A Predictive Coding Account of the Psychedelic Phenomenon

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Classical hallucinogens and neuroimaging: A systematic review of human studies: hallucinogens and neuroimaging

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Psychedelics in the treatment of unipolar mood disorders: a systematic review

Rucker, J., Young, A. H., Jelen, L. A. et al. · Journal of Psychopharmacology (2016)

Psychedelics as Medicines: An Emerging New Paradigm

Nichols, C. D., Nichols, D. E., Johnson, M. W. · Clinical Pharmacology and Therapeutics (2016)

Possible role of biochemiluminescent photons for lysergic acid diethylamide (LSD)-induced phosphenes and visual hallucinations

Kapócs, G., Scholkmann, F., Salari, V. et al. · Reviews In The Neuroscience (2016)

Alterations of consciousness and mystical-type experiences after acute LSD in humans

Liechti, M. E., Dolder, P. C., Schmid, Y. · Psychopharmacology (2016)

190 cited
Treating Addiction: Perspectives from EEG and Imaging Studies on Psychedelics

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A Model for the Application of Target-Controlled Intravenous Infusion for a Prolonged Immersive DMT Psychedelic Experience

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29 cited
Ego-dissolution and psychedelics: validation of the ego-dissolution inventory (EDI)

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LSD alters eyes-closed functional connectivity within the early visual cortex in a retinotopic fashion

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Neural correlates of the LSD experience revealed... — Research Summary & Context | Blossom