Publications

Journal article

Singleton SP, Timmermann C, Luppi AI, Eckernäs E, Roseman L, Carhart-Harris RL, Kuceyeski Aet al., 2025,

Network control energy reductions under DMT relate to serotonin receptors, signal diversity, and subjective experience

, Communications Biology, Vol: 8

Psychedelics offer a profound window into the human brain through their robust effects on perception, subjective experience, and brain activity patterns. The serotonergic psychedelic N,N-dimethyltryptamine (DMT) induces a profoundly immersive altered state of consciousness lasting under 20 min, allowing the entire experience to be captured during a single functional magnetic resonance imaging (fMRI) scan. Using network control theory, we map energy trajectories of 14 individuals undergoing fMRI during DMT and placebo. We find that global control energy is reduced after DMT injection compared to placebo. Longitudinal trajectories of global control energy correlate with longitudinal trajectories of electroencephalography (EEG) signal diversity (a measure of entropy) and subjective drug intensity ratings. At the regional level, spatial patterns of DMT’s effects on these metrics correlate with serotonin 2a receptor density from positron emission tomography (PET) data. Using receptor distribution and pharmacokinetic information, we recapitulate DMT’s effects on global control energy trajectories, demonstrating control models can predict pharmacological effects on brain dynamics.

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Journal article

Wall MB, Demetriou L, Giribaldi B, Roseman L, Ertl N, Erritzoe D, Nutt DJ, Carhart-Harris RLet al., 2025,

Reduced Brain Responsiveness to Emotional Stimuli With Escitalopram But Not Psilocybin Therapy for Depression

, American Journal of Psychiatry, Vol: 182, Pages: 569-582, ISSN: 0002-953X

Journal article

Palacek K, Carhart-Harris R, Fabiano N, 2025,

The salience network is functionally twice as large in depression: The first depression biomarker?

, Genomic Psychiatry, Pages: 1-3, ISSN: 2997-254X

<jats:p><jats:bold>This commentary examines recent findings demonstrating that individuals with depression exhibit a functionally expanded salience network compared to non-depressed controls. Neuroimaging data reveals this network expansion predates symptom onset and remains stable regardless of symptom severity or treatment interventions. The authors propose this distinctive neural signature as a potential biomarker for depression risk, enabling earlier identification and intervention. They discuss three potential mechanisms underlying this expansion: compensatory network changes, genetic predisposition, and relative expansion secondary to atrophy in other brain regions. The commentary emphasizes the need to conceptualize depression as a disorder of neural connectivity rather than isolated neurotransmitter imbalances, with implications for developing targeted therapeutic approaches.</jats:bold></jats:p>

Journal article

Timmermann Slater CB, Sanders J, Reydellet D, Barba T, Luan L, Soto Angona O, Ona G, Allocca G, Smith C, Daily Z, Mason N, Kloft-Heller L, Kuchar M, Janeckova L, Palenicek T, Erritzoe D, Ramaekers J, Carhart-Harris R, Uthaug Met al., 2025,

Exploring 5-MeO-DMT as a pharmacological model for deconstructed consciousness

, Neuroscience of Consciousness, Vol: 2025, ISSN: 2057-2107

5-MeO-DMT is a short-acting psychedelic that is anecdotally reported to induce a radical disruption of the self and a paradoxical quality of aroused, waking awareness that is nevertheless devoid of any specific perceptual contents. Here, we conducted an exploratory observational study of the phenomenological and neuronal effects of this compound. We collected micro-phenomenological interviews, psychometric questionnaires, and electroencephalography (EEG) in naturalistic ceremonial settings where 5-MeO-DMT was ingested. Results revealed that the 5-MeO-DMT experience followed a dynamic progression that—only in the most extreme cases—manifested as a complete absence of self-experience and other phenomenal content with preserved awareness. Furthermore, visual imagery, bodily self-disruption, narrative self-disruption, and reduced phenomenal distinctions occurred in a variable fashion. EEG analyses revealed the 5-MeO-DMT experience was characterised by (global) alpha and (posterior) beta power reductions, implying a mode of brain functioning where top-down models are inhibited. Our preliminary phenomenological findings confirm the potential utility of 5-MeO-DMT as a pharmacological model for deconstructed consciousness while noting the limitations of employing retrospective questionnaires for this purpose. Considering the exploratory nature of this study and its limitations inherent to its naturalistic nature, further research employing real-time experience sampling and phenomenologically trained participants in controlled environments could expand our findings to meaningfully inform the potential of this tool for the scientific study of consciousness.

Journal article

Pasquini L, Simon AJ, Gallen CL, Kettner H, Roseman L, Gazzaley A, Carhart-Harris RL, Timmermann Cet al., 2025,

Dynamic medial parietal and hippocampal deactivations under DMT relate to sympathetic output and altered sense of time, space, and the self

, Imaging Neuroscience, Vol: 3

<jats:title>Abstract</jats:title> <jats:p>N,N-Dimethyltryptamine (DMT) is a serotonergic psychedelic, known to rapidly induce short-lasting alterations in conscious experience, characterized by a profound and immersive sense of physical transcendence alongside rich and vivid auditory distortions and visual imagery. Multimodal neuroimaging data paired with dynamic analysis techniques offer a valuable approach for identifying unique signatures of brain activity—and linked autonomic physiology—naturally unfolding during the altered state of consciousness induced by DMT. We leveraged simultaneous fMRI and EKG data acquired in 14 healthy volunteers prior to, during, and after intravenous administration of DMT, and, separately, placebo. fMRI data were preprocessed to derive individual dynamic activity matrices, reflecting the similarity of brain activity in time, and community detection algorithms were applied on these matrices to identify brain activity substates; EKG data were used to derive continuous heart rate. We identified a brain substate occurring immediately after DMT injection, characterized by hippocampal and medial parietal deactivations and increased superior temporal lobe activity under DMT. Deactivations in the hippocampus and medial parietal cortex correlated with alterations in the usual sense of time, space, and self-referential processes, reflecting a deconstruction of essential features of ordinary consciousness. Superior lobe activations, instead, correlated with audio/visual hallucinations and experience of “entities”, reflecting the emergence of altered sensory experiences under DMT. Finally, increased heart rate under DMT correlated positively with hippocampus/medial parietal deactivation and the experience of “entities”, and negatively with altered self-referential processes. These results suggest a chain of influence linking sympathetic regulation to hippocampal and medial parie

Journal article

Havenith MN, Leidenberger M, Brasanac J, Corvacho M, Carmo Figueiredo I, Schwarz L, Uthaug M, Rakusa S, Bernardic M, Vasquez-Mock L, Pérez Rosal S, Carhart-Harris R, Gold SM, Jungaberle H, Jungaberle Aet al., 2025,

Decreased CO2 saturation during circular breathwork supports emergence of altered states of consciousness

, Communications Psychology, Vol: 3

<jats:title>Abstract</jats:title> <jats:p>Altered states of consciousness (ASCs), induced e.g. during psychedelic-assisted therapy, show potential to treat prevalent mental health disorders like depression and posttraumatic stress disorder. However, access to such treatments is restricted by legal, medical, and financial barriers. Circular breathwork may present a non-pharmacological and hence more accessible alternative to engage similar therapeutic processes. Scientific studies of breathwork are only just emerging and its physiological and psychological mechanisms are largely unknown. Here, we track physiological and experiential dynamics throughout a breathwork session, comparing two forms of breathwork: Holotropic and Conscious-Connected breathwork. We show that a reduction in end-tidal CO<jats:sub>2</jats:sub> pressure due to deliberate hyperventilation is significantly correlated to ASC onset (<jats:italic>r</jats:italic> = -0.46; <jats:italic>p</jats:italic> < 0.001). Based on standard questionnaires (MEQ-30 and 11-DASC), the ASCs evoked by breathwork resembled those produced by psychedelics across several experiential domains such as ego dissolution, and their depth predicted psychological and physiological follow-on effects, including improved well-being and reduced depressive symptoms. Further analysis showed that different breathwork approaches produced highly similar outcomes. Our findings identify physiological boundary conditions for ASCs to arise in a non-pharmacological context, shedding light on the functional mechanisms of breathwork as well as its potential as a psychotherapeutic tool.</jats:p>

Journal article

Agnorelli C, Spriggs M, Godfrey K, Sawicka G, Bohl B, Douglass H, Fagiolini A, Parastoo H, Carhart-Harris R, Nutt D, Erritzoe Det al., 2025,

Neuroplasticity and Psychedelics: A comprehensive examination of classic and non-classic compounds in pre and clinical models.

, Neurosci Biobehav Rev

Neuroplasticity, the ability of the nervous system to adapt throughout an organism's lifespan, offers potential as both a biomarker and treatment target for neuropsychiatric conditions. Psychedelics, a burgeoning category of drugs, are increasingly prominent in psychiatric research, prompting inquiries into their mechanisms of action. Distinguishing themselves from traditional medications, psychedelics demonstrate rapid and enduring therapeutic effects after a single or few administrations, believed to stem from their neuroplasticity-enhancing properties. This review examines how classic psychedelics (e.g., LSD, psilocybin, N,N-DMT) and non-classic psychedelics (e.g., ketamine, MDMA) influence neuroplasticity. Drawing from preclinical and clinical studies, we explore the molecular, structural, and functional changes triggered by these agents. Animal studies suggest psychedelics induce heightened sensitivity of the nervous system to environmental stimuli (meta-plasticity), re-opening developmental windows for long-term structural changes (hyper-plasticity), with implications for mood and behavior. Translating these findings to humans faces challenges due to limitations in current imaging techniques. Nonetheless, promising new directions for human research are emerging, including the employment of novel positron-emission tomography (PET) radioligands, non-invasive brain stimulation methods, and multimodal approaches. By elucidating the interplay between psychedelics and neuroplasticity, this review informs the development of targeted interventions for neuropsychiatric disorders and advances understanding of psychedelics' therapeutic potential. "And one finds oneself, to put it all in perspective, in a situation where fifty different onomatopoeias, simultaneous, contradictory, and each constantly changing, would be the most faithful expression of it." Henri Michaux, Misérable Miracle, 1956.

Journal article

Coleman CR, Shinozuka K, Tromm R, Dipasquale O, Kaelen M, Roseman L, Muthukumaraswamy S, Nutt DJ, Barnett L, Carhart-Harris Ret al., 2025,

The Role of the Dorsolateral Prefrontal Cortex in Ego Dissolution and Emotional Arousal During the Psychedelic State

, Human Brain Mapping, Vol: 46, ISSN: 1065-9471

Lysergic acid diethylamide (LSD) is a classic serotonergic psychedelic that induces a profoundly altered conscious state. In conjunction with psychological support, it is currently being explored as a treatment for generalized anxiety disorder and depression. The dorsolateral prefrontal cortex (DLPFC) is a brain region that is known to be involved in mood regulation and disorders; hypofunction in the left DLPFC is associated with depression. This study investigated the role of the DLPFC in the psycho-emotional effects of LSD with functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) data of healthy human participants during the acute LSD experience. In the fMRI data, we measured the correlation between changes in resting-state functional connectivity (RSFC) of the DLPFC and post-scan subjective ratings of positive mood, emotional arousal, and ego dissolution. We found significant, positive correlations between ego dissolution and functional connectivity between the left & right DLPFC, thalamus, and a higher-order visual area, the fusiform face area (FFA). Additionally, emotional arousal was significantly associated with increased connectivity between the right DLPFC, intraparietal sulcus (IPS), and the salience network (SN). A confirmational “reverse” analysis, in which the outputs of the original RSFC analysis were used as input seeds, substantiated the role of the right DLPFC and the aforementioned regions in both ego dissolution and emotional arousal. Subsequently, we measured the effects of LSD on directed functional connectivity in MEG data that was source-localized to the input and output regions of both the original and reverse analyses. The Granger causality (GC) analysis revealed that LSD increased information flow between two nodes of the ‘ego dissolution network’, the thalamus and the DLPFC, in the theta band, substantiating the hypothesis that disruptions in thalamic gating underlie the experience of eg

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Journal article

Zhou K, de Wied D, Carhart-Harris RL, Kettner Het al., 2025,

Prediction of hallucinogen persisting perception disorder and thought disturbance symptoms following psychedelic use

, PNAS Nexus, Vol: 4

Interest in using psychedelic drugs to treat psychiatric disorders is growing rapidly. While modern controlled clinical trials show a favorable safety and efficacy profile, it remains unclear if the risk of side effects would increase with broader use in more heterogeneous populations. To address this, we investigated the frequency and baseline predictors of delusional ideation, magical thinking, and “hallucinogen persisting perception disorder” (HPPD)-related symptoms following psychedelic use in a self-selected naturalistic sample. Using a prospective cohort study, symptoms were assessed in (N=654) participants at one week before a planned psychedelic experience, and at two and four weeks afterward. Across the sample, delusional ideation was found to be reduced one month after psychedelic use (P<0.001) with no changes detected in magical thinking. These findings were in seeming opposition to positive correlations between lifetime psychedelic use at baseline with magical thinking (rs=0.12, P=0.003) and delusional ideation (rs=0.11, P=0.01), suggesting that schizotypal traits, instead of being caused by, may merely correlate with psychedelic use. Importantly, over 30% of the sample reported HPPD-type effects at the 4-week endpoint, although rarely perceived as distressing (< 1% of the population). Younger age, female gender, history of a psychiatric diagnosis and baseline trait absorption predicted the occurrence of HPPD-like effects. This is in line with prior studies showing a high prevalence of HPPD-like symptoms in psychedelic users, which, however, appear to remain at a subclinical severity in most cases, explaining the comparatively lower prevalence of HPPD diagnoses.

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Journal article

Roseman L, 2025,

A reflection on paradigmatic tensions within the FDA advisory committee for MDMA-assisted therapy.

, J Psychopharmacol, Vol: 39, Pages: 313-315

The recent rejection of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy by the U.S. Food and Drug Administration (FDA) is a dramatic moment in the re-emergence of psychedelic research. In this perspective, I argue that it represents a case study for paradigmatic tensions within psychopharmacology. The regulatory system is still influenced by a paradigm that sees the therapeutic effects of drugs as primarily biological, and context is noise to control for. An emergent paradigm considers the therapeutic effects of drugs as interactive with context. Psychedelics are the anomaly that questions the dominant paradigm, mainly due to the determination of psychedelic researchers that the medicines are drugs with psychotherapy. While some of the critique offered by the FDA towards MAPS/Lykos's studies is crucial, much of it is related to the experiential and psychotherapeutic elements - which the FDA claims not to regulate. This leads to some paradoxes within the regulatory procedure, which hint at a need for a shift in how psychedelic-assisted therapy is regulated and researched. Both regulators and researchers will need to find ways to accommodate each other in service of a successful integration of a new paradigm in which drugs and psychotherapy interact.

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