Abstract 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...
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...
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...
Abstract Psychedelic substances are increasingly recognized for their potential to catalyse transformative shifts in worldviews. Central to these transformations are states of awe, a self-transcendent, epistemic emotion. This mixed-methods study explored how awe during psychedelic trips relates to lasting changes in boundaries between self and world, and epistemic shifts that follow...
Setting up a psychedelic study can be a long, arduous, and kafkaesque process. This rapidly-developing field poses several unique challenges for researchers, necessitating a range of considerations that have not yet been standardised. Many of the complexities inherent to psychedelic research also challenge existing assumptions around, for example, approaches to psychiatric prescribing, the...
bioRxivMarch 24, 2025Kenneth Shinozuka, Mattia Rosso, Clayton R. Coleman et al.3 citations
preprint
Abstract Lysergic acid diethylamide (LSD) and other psychedelic substances profoundly alter human consciousness. While several studies have demonstrated changes in brain function and connectivity associated with psychedelics, we still have a limited understanding of how LSD reshapes brain networks operating across different frequency bands. In this study, we applied the recently developed...
Abstract Major Depressive Disorder (MDD) is typically characterized by altered linear functional connectivity (FC) across large-scale brain networks. Yet, it is unclear whether similar alterations are observed when nonlinear FC is examined. This study investigated how antidepressant treatment (i.e., psilocybin and escitalopram) modulates both linear FC and nonlinear FC in individuals with MDD....
Psychedelics are serotonergic drugs that profoundly alter consciousness, yet their neural mechanisms are not fully understood. A popular theory, RElaxed Beliefs Under pSychedelics (REBUS), posits that psychedelics flatten the hierarchy of information flow in the brain. Here, we investigate hierarchy based on the imbalance between sending and receiving brain signals, as determined by directed...
Abstract The relationship between the default mode network (DMN) and task-positive networks, such as the frontoparietal control network (FPCN), is a prominent feature of functional connectivity (FC) in the human brain. This relationship is primarily anticorrelated at rest in healthy brains and is disrupted in altered states of consciousness. Although the DMN and FPCN seem to perform distinct...
Psychedelics are hallucinogenic drugs that have the potential to treat depression, post-traumatic stress disorder, and other psychiatric conditions. The dominant paradigm in contemporary psychedelic-assisted therapy is non-directive; that is, participants undergo the psychedelic treatment with minimal external guidance from therapists. However, the clinical outcomes of psychedelic therapy could...
Abstract Background Psychedelic substances exhibit complex interactions with the ‘set and setting’ of use, i.e., the internal state of the user and the external environment in which a psychedelic experience takes place. Despite the known importance of these contextual variables, psychedelic research has suffered from methodological weaknesses in reporting extra-pharmacological factors and from...
Abstract Psilocybin has been shown to induce fast and sustained improvements in mental well-being across various populations, yet its long-term mechanisms of action are not fully understood. Initial evidence suggests that longitudinal functional and structural brain changes implicate fronto-striatal-thalamic (FST) circuitry, a broad system involved in goal-directed behavior and motivational...
Aspects of the acute experience induced by the serotonergic psychedelic psilocybin predict symptomatic relief in multiple psychiatric disorders and improved well-being in healthy participants, but whether these therapeutic effects are immediate or are based on memories of the experience is unclear. To examine this, we co-administered psilocybin (25 mg) with the amnestic benzodiazepine midazolam...
OBJECTIVE: Affective symptoms such as anxiety, low mood, and loneliness are prevalent and highly debilitating symptoms among older adults (OA). Serotonergic psychedelics are currently investigated as novel interventions for affective disorders, yet little is known regarding their effects in OA. We investigated the mental health effects and psychological mechanisms of guided psychedelic group...
This interview explores the intimate relationship between language and consciousness, drawing insights from aphasia phenomenology, psychedelic experiences, and neuroscientific theories. Jeremy I. Skipper, a cognitive neuroscientist, argues that language is not merely a tool for reporting conscious experiences but plays a generative role in shaping and sustaining consciousness itself. He...
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...
Affective symptoms such as anxiety, low mood, and loneliness are prevalent and highly debilitating symptoms among older adults (OA). Serotonergic psychedelics are novel experimental interventions for affective disorders, yet little is known regarding their effects in OA. Using a prospective cohort design, we identified 62 OA (age ≥ 60 years) and 62 matched younger adults (YA) who completed...
Abstract The mechanisms by which Psilocybin Therapy (PT) improves depression remain an important object of study, with scientists actively exploring acute psychological experiences and neurobiological processes as candidates. In a phase 2, double-blind, randomized, active comparator controlled trial involving patients with moderate-to-severe major depressive disorder, we investigated whether...
Recent findings have shown that psychedelics reliably enhance brain entropy (understood as neural signal diversity), and this effect has been associated with both acute and long-term psychological outcomes, such as personality changes. These findings are particularly intriguing, given that a decrease of brain entropy is a robust indicator of loss of consciousness (e.g., from wakefulness to...
Abstract Do psychedelics affect sexual functioning postacutely? Anecdotal and qualitative evidence suggests they do, but this has never been formally tested. While sexual functioning and satisfaction are generally regarded as an important aspect of human wellbeing, sexual dysfunction is a common symptom of mental health disorders. It is also a common side effect of selective serotonin reuptake...
Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanisms are not currently known. Here, we leveraged the differential outcome in responders and non-responders to psilocybin (10 and 25 mg, 7 days apart) therapy for depression-to gain new insights into regions and networks implicated in the restoration of healthy brain dynamics. We used large-scale brain...
Integrating independent but converging lines of research on brain function and neurodevelopment across scales, this article proposes that serotonin 2A receptor (5-HT2AR) signalling 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...
The role of the thalamus in mediating the effects of lysergic acid diethylamide (LSD) was recently proposed in a model of communication and corroborated by imaging studies. However, a detailed analysis of LSD effects on nuclei-resolved thalamocortical connectivity is still missing. Here, in a group of healthy volunteers, we evaluated whether LSD intake alters the thalamocortical coupling in a...
Abstract The human brain is a complex system, whose activity exhibits flexible and continuous reorganisation 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...