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Journal articleSingleton SP, Timmermann C, Luppi AI, et al., 2025,
Network control energy reductions under DMT relate to serotonin receptors, signal diversity, and subjective experience
, Communications Biology, Vol: 8Psychedelics 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 articleGreenway KT, Garel N, Dinh-Williams L-AL, et al., 2025,
The Music for Subanesthetic Infusions of Ketamine randomised clinical trial: ketamine as a psychedelic treatment for highly refractory depression
, The British Journal of Psychiatry, Pages: 1-9, ISSN: 0007-1250<jats:sec id="S0007125025001023_as1"> <jats:title>Background</jats:title> <jats:p>Ketamine exerts potent but transient antidepressant effects in treatment-resistant depression (TRD). Combinations of ketamine and psychotherapy have attracted interest, but no trial has investigated a psychedelic model of ketamine–psychotherapy for TRD to our knowledge.</jats:p> </jats:sec> <jats:sec id="S0007125025001023_as2"> <jats:title>Aims</jats:title> <jats:p>This secondary analysis of a randomised clinical trial (RCT) explores the therapeutic effects and experiential mechanisms of the Montreal Model of ketamine–psychotherapy for TRD, with or without music.</jats:p> </jats:sec> <jats:sec id="S0007125025001023_as3"> <jats:title>Method</jats:title> <jats:p>A two-centre, single-blinded, RCT conducted in Montreal, Canada, between January 2021 and August 2022 (NCT04701866). Participants received ketamine–psychotherapy for TRD – six subanaesthetic infusions over 4 weeks and psychological support – with either music or matched non-music support during ketamine doses, as per random group assignments. The primary therapeutic outcome was the Montgomery–Åsberg Depression Rating Scale, assessed by blinded raters. Psychedelic-like experiences, evaluated by the Mystical Experience Questionnaire and Emotional Breakthrough Inventory, and their session-by-session relationships with depression were explored with multilevel, time-lagged covariate models with autoregressive residuals.</jats:p> </jats:sec> <jats:sec id="S0007125025001023_as4"> <jats:title>Results</jats:title> <jats:p>Thirty-two participants with severe and highly comorbid TRD, including high rates of personality disorder and suicidality, received 181 ketamine infusions. Therapeuti
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Journal articleLynskey MT, Athanasiou-Fragkouli A, Schlag AK, et al., 2025,
Medicinal Cannabis Use Among People with Obsessive Compulsive Disorder: Changes in Quality of Life After Three Months
, Psychoactives, Vol: 4, Pages: 16-16<jats:p>Obsessive–compulsive disorder (OCD) has an estimated prevalence between 1 and 2.3%. Existing treatments may not be suitable or effective for all people with OCD, and there is increasing interest in whether these individuals may benefit from the use of cannabis-based medical products (CBMPs). We document the characteristics of 257 people reporting a diagnosis of OCD within Project T21, a study of medical cannabis patients, and examined whether the use of prescribed cannabinoids improves quality of life. Individuals with OCD were prescribed an average of 2.2 CBMPs, with most products classified as THC-dominant flowers (73.7%). Three months after initiating treatment, there were substantial improvements in quality of life (Cohen’s d = 0.48; 95% CI = 0.29–0.65), general health (Cohen’s d = 0.43; 95% CI = 0.26–0.61), mood/depression (Cohen’s d = 0.85; 95% CI = 0.65–1.04), and sleep (Cohen’s d = 0.61; 95% CI = 0.43–0.79). There was a corresponding reduction in anxiety symptoms among the subsample who completed the GAD-7 (Cohen’s d = 1.14; 95% CI = 0.84–1.44). Eight individuals (5.7%) reported a total of 14 adverse effects, with the majority of these (57%) being described as mild. Given emerging evidence that those with OCD can benefit from CBMPs, coupled with the increased availability of these unlicensed products internationally, there is a need for more research, including clinical trials, to identify those who may benefit most from the use of these medicines.</jats:p>
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Journal articleRoseby W, Kettner H, Roseman L, et al., 2025,
Enhanced meaning in life following psychedelic use: converging evidence from controlled and naturalistic studies
, Frontiers in Psychology, ISSN: 1664-1078 -
Journal articleWall MB, Demetriou L, Giribaldi B, et 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 articlePalacek 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>
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Journal articleTimmermann Slater CB, Sanders J, Reydellet D, et al., 2025,
Exploring 5-MeO-DMT as a pharmacological model for deconstructed consciousness
, Neuroscience of Consciousness, Vol: 2025, ISSN: 2057-21075-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.
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Journal articlePasquini L, Simon AJ, Gallen CL, et 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
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Journal articleHavenith MN, Leidenberger M, Brasanac J, et 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>
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Journal articleAgnorelli C, Spriggs M, Godfrey K, et al., 2025,
Neuroplasticity and Psychedelics: A comprehensive examination of classic and non-classic compounds in pre and clinical models.
, Neurosci Biobehav RevNeuroplasticity, 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.
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