Psychedelic drugs, including lysergic acid diethylamide (LSD) and other agonists of the serotonin 2A receptor (5HT2A-R), induce drastic changes in subjective experience, and provide a unique opportunity to study the neurobiological basis of consciousness. One of the most notable neurophysiological signatures of psychedelics, increased entropy in spontaneous neural activity, is thought to be of...
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....
High-level brain functions are widely believed to emerge from the orchestrated activity of multiple neural systems. However, lacking a formal definition and practical quantification of emergence for experimental data, neuroscientists have been unable to empirically test this long-standing conjecture. Here we investigate this fundamental question by leveraging a recently proposed framework known...
Recent findings suggesting the potential transdiagnostic efficacy of psychedelic-assisted therapy have fostered the need to deepen our understanding of psychedelic brain action. Functional neuroimaging investigations have found that psychedelics reduce the functional segregation of large-scale brain networks. However, beyond this general trend, findings have been largely inconsistent. We argue...
A topic of growing interest in computational neuroscience is the discovery of fundamental principles underlying global dynamics and the self-organization of the brain. In particular, the notion that the brain operates near criticality has gained considerable support, and recent work has shown that the dynamics of different brain states may be modeled by pairwise maximum entropy Ising models at...
Abstract Recent research has demonstrated the potential of psychedelic therapy for mental health care. However, the psychological experience underlying its therapeutic effects remains poorly understood. This paper proposes a framework that suggests psychedelics act as destabilizers, both psychologically and neurophysiologically. Drawing on the ‘entropic brain’ hypothesis and the ‘RElaxed...
This theoretical article revives a classical bridging construct, canalization, to describe a new model of a general factor of psychopathology. To achieve this, we have distinguished between two types of plasticity, an early one that we call 'TEMP' for 'Temperature or Entropy Mediated Plasticity', and another, we call 'canalization', which is close to Hebbian plasticity. These two forms of...
Background: Psilocybin is a serotonin type 2A (5-HT 2A ) receptor agonist and naturally occurring psychedelic. 5-HT 2A 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...
Schizophrenia and states induced by certain psychotomimetic drugs may share some physiological and phenomenological properties, but they differ in fundamental ways: one is a crippling chronic mental disease, while the others are temporary, pharmacologically-induced states presently being explored as treatments for mental illnesses. Building towards a deeper understanding of these different...
Background: A trial of psilocybin (COMP360) versus escitalopram for major depressive disorder (MDD) was reported as negative, as there was no significant difference in the primary outcome, mean change in the 16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS SR-16). However, analyses using three other depression scales (17-item Hamilton Depression Rating Scale [HAMD-17],...
Abstract Psychedelic drugs, including lysergic acid diethylamide (LSD) and other agonists of the serotonin 2A receptor (5HT2A-R), induce drastic changes in subjective experience, and provide a unique opportunity to study the neurobiological basis of consciousness. One of the most notable neurophysiological signatures of psychedelics, increased entropy in spontaneous neural activity, is thought...
s attention that there was a typo in the script used to calculate the differential entropy. Therefore, the reported entropy estimations are invalid and do not produce the expected increase in entropy when using
Background: The Relaxed Beliefs Under pSychedelics (REBUS) model proposes that serotonergic psychedelics decrease the precision weighting of neurobiologically-encoded beliefs, and offers a unified account of the acute and therapeutic action of psychedelics. Although REBUS has received some neuroscientific support, little research has examined its psychological validity. We conducted a...
Dynamic functional connectivity (dFC) in resting-state fMRI holds promise to deliver candidate biomarkers for clinical applications. However, the reliability and interpretability of dFC metrics remain contested. Despite a myriad of methodologies and resulting measures, few studies have combined metrics derived from different conceptualizations of brain functioning within the same analysis -...
Clinical research into serotonergic psychedelics is expanding rapidly, showing promising efficacy across myriad disorders. Resting-state functional magnetic resonance imaging (rs-fMRI) is a commonly used strategy to identify psychedelic-induced changes in neural pathways in clinical and healthy populations. Here we, a large group of psychedelic imaging researchers, review the 42 research...
The integrated information theory of consciousness (IIT) is divisive: while some believe it provides an unprecedentedly powerful approach to address the 'hard problem', others dismiss it on grounds that it is untestable. We argue that the appeal and applicability of IIT can be greatly widened if we distinguish two flavours of the theory: strong IIT, which identifies consciousness with specific...
Emergence is a profound subject that straddles many scientific disciplines, including the formation of galaxies and how consciousness arises from the collective activity of neurons. Despite the broad interest that exists on this concept, the study of emergence has suffered from a lack of formalisms that could be used to guide discussions and advance theories. Here, we summarize, elaborate on,...
The human brain entertains rich spatiotemporal dynamics, which are drastically reconfigured when consciousness is lost due to anaesthesia or disorders of consciousness (DOC). Here, we sought to identify the neurobiological mechanisms that explain how transient pharmacological intervention and chronic neuroanatomical injury can lead to common reconfigurations of neural activity. We developed and...
Introduction: As their name suggests, 'psychedelic' (mind-revealing) compounds are thought to catalyse processes of psychological insight; however, few satisfactory scales exist to sample this. This study sought to develop a new scale to measure psychological insight after a psychedelic experience: the Psychological Insight Scale (PIS). Methods: The PIS is a six- to seven-item questionnaire...
Can the use of psychedelic drugs induce lasting changes in metaphysical beliefs? While it is popularly believed that they can, this question has never been formally tested. Here we exploited a large sample derived from prospective online surveying to determine whether and how beliefs concerning the nature of reality, consciousness, and free-will, change after psychedelic use. Results revealed...
RATIONALE: Classic psychedelics are currently being studied as novel treatments for a range of psychiatric disorders. However, research on how psychedelics interact with other psychoactive substances remains scarce. OBJECTIVES: The current study aimed to explore the subjective effects of psychedelics when used alongside cannabis. METHODS: Participants (n = 321) completed a set of online surveys...
Abstract A central question in neuroscience concerns the relationship between consciousness and its physical substrate. Here, we argue that a richer characterization of consciousness can be obtained by viewing it as constituted of distinct information-theoretic elements. In other words, we propose a shift from quantification of consciousness—viewed as integrated information—to its...
Background: Recent years have seen a resurgence of research on the potential of psychedelic substances to treat addictive and mood disorders. Historically and contemporarily, psychedelic studies have emphasized the importance of contextual elements ('set and setting') in modulating acute drug effects, and ultimately, influencing long-term outcomes. Nevertheless, current small-scale clinical and...
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...
Psychedelic psychotherapy, therapy enhanced with psychedelic drugs such as LSD or psilocybin (the active ingredient of ‘magic mushrooms’), has been suggested to improve psychological well-being. For this reason, trials on psychedelic therapy for the treatment of depression, addiction and other conditions are ongoing. Recently, ‘microdosing’ – a way of administering psychedelics that involves...