Psilocybin desynchronizes the human brain

Nature, Год журнала: 2024, Номер 632(8023), С. 131 - 138

Опубликована: Июль 17, 2024

Abstract A single dose of psilocybin, a psychedelic that acutely causes distortions space–time perception and ego dissolution, produces rapid persistent therapeutic effects in human clinical trials 1–4 . In animal models, psilocybin induces neuroplasticity cortex hippocampus 5–8 It remains unclear how brain network changes relate to subjective lasting psychedelics. Here we tracked individual-specific with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were before, during for 3 weeks after high-dose (25 mg) methylphenidate (40 mg), brought back an additional 6–12 months later. Psilocybin massively disrupted connectivity (FC) subcortex, causing more than threefold greater change methylphenidate. These FC driven by desynchronization across spatial scales (areal, global), which dissolved distinctions reducing correlations within anticorrelations between networks. Psilocybin-driven strongest the default mode network, is connected anterior thought create our sense space, time self. Individual differences strongly linked experience. Performing perceptual task reduced psilocybin-driven changes. caused decrease weeks. Persistent reduction hippocampal-default may represent neuroanatomical mechanistic correlate proplasticity

Язык: Английский

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Exploring mechanisms of psychedelic action using neuroimaging

Nature Mental Health, Год журнала: 2024, Номер 2(2), С. 141 - 153

Опубликована: Фев. 9, 2024

Язык: Английский

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Psychedelics and the ‘inner healer’: Myth or mechanism?

Journal of Psychopharmacology, Год журнала: 2024, Номер 38(5), С. 417 - 424

Опубликована: Апрель 12, 2024

Background: Reference to an intrinsic healing mechanism or ‘inner healer’ is commonplace amongst psychedelic drug-using cultures. The refers the belief that compounds, plants concoctions have intrinsically regenerative action on mind and brain, analogous mechanisms within physical body, for example, after sickness injury. Aims: Here, we sought test critique this idea by devising a single subjective rating item pertaining perceived healing’ effects. Methods: was issued 59 patients high (25 mg, n = 30) ‘placebo’ (1 29) dose of psilocybin in double-blind randomised controlled trial depression. Results: Inner healer scores were higher versus placebo ( t 3.88, p < 0.001). Within high-dose sub-sample only, inner predicted improved depressive symptomatology at 2 weeks post-dosing. Conclusions: principle activating via psychedelics scientifically nascent; however, study takes positivist pragmatic step forward, asking whether it warrants further examination.

Язык: Английский

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Deep CANALs: a deep learning approach to refining the canalization theory of psychopathology

Neuroscience of Consciousness, Год журнала: 2024, Номер 2024(1)

Опубликована: Янв. 1, 2024

Psychedelic therapy has seen a resurgence of interest in the last decade, with promising clinical outcomes for treatment variety psychopathologies. In response to this success, several theoretical models have been proposed account positive therapeutic effects psychedelics. One more prominent is "RElaxed Beliefs Under pSychedelics," which proposes that psychedelics act therapeutically by relaxing strength maladaptive high-level beliefs encoded brain. The recent "CANAL" model psychopathology builds on explanatory framework RElaxed pSychedelics proposing canalization (the development overly rigid belief landscapes) may be primary factor psychopathology. Here, we make use learning theory deep neural networks develop series refinements original CANAL model. Our contribution disambiguate two separate optimization landscapes underlying representation brain and describe unique pathologies can arise from each. Along each dimension, identify either too much or little canalization, implying construct does not simple linear correlation presentation expanded paradigm, demonstrate ability novel predictions regarding what aspects amenable psychedelic therapy, as well forms ultimately most beneficial given individual.

Язык: Английский

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A role for the serotonin 2A receptor in the expansion and functioning of human transmodal cortex

Brain, Год журнала: 2023, Номер 147(1), С. 56 - 80

Опубликована: Сен. 11, 2023

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 developmental driver potent modulator the macroscale functional organization human cerebral cortex. A wealth evidence indicates anatomical cortex follows a unimodal-to-transmodal gradient. Situated at apex processing hierarchy-where it plays central role in integrative processes underpinning complex, human-defining cognition-the transmodal has disproportionately expanded development evolution. Notably, adult especially rich 5-HT2AR expression recent suggests that, during early development, neural progenitor cells stimulates their proliferation-a critical process for evolutionarily-relevant cortical expansion. Drawing multimodal neuroimaging cross-species investigations, we argue by contributing to expansion being prevalent its hierarchy brain, major both functioning. Owing unique excitatory downstream cellular effects, neuronal agonism promotes neuroplasticity, learning cognitive psychological flexibility context-(hyper)sensitive manner with therapeutic potential. Overall, delineate dual 5-HT2ARs enabling modulation

Язык: Английский

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Neural Geometrodynamics, Complexity, and Plasticity: A Psychedelics Perspective

Entropy, Год журнала: 2024, Номер 26(1), С. 90 - 90

Опубликована: Янв. 22, 2024

We explore the intersection of neural dynamics and effects psychedelics in light distinct timescales a framework integrating concepts from dynamics, complexity, plasticity. call this geometrodynamics for its parallels with general relativity’s description interplay spacetime matter. The geometry trajectories within dynamical landscape “fast time” are shaped by structure differential equation connectivity parameters, which themselves evolve over “slow driven state-dependent state-independent plasticity mechanisms. Finally, adjustment processes (metaplasticity) takes place an “ultraslow” time scale. Psychedelics flatten landscape, leading to heightened entropy complexity as observed neuroimaging modeling studies linking increases disruption functional integration. highlight relationship between criticality, fast synaptic Pathological, rigid, or “canalized” result ultrastable confined repertoire, allowing slower plastic changes consolidate them further. However, under influence psychedelics, destabilizing emergence complex leads more fluid adaptable state process that is amplified plasticity-enhancing psychedelics. This shift manifests acute systemic increase disorder possibly longer-lasting affecting both short-term long-term processes. Our offers holistic perspective on these substances their potential impacts function.

Язык: Английский

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The potential of 5‐methoxy‐N,N‐dimethyltryptamine in the treatment of alcohol use disorder: A first look at therapeutic mechanisms of action

Addiction Biology, Год журнала: 2024, Номер 29(4)

Опубликована: Апрель 1, 2024

Abstract Alcohol use disorder (AUD) remains one of the most prevalent psychiatric disorders worldwide with high economic costs. Current treatment options show modest efficacy and relapse rates are high. Furthermore, there increases in gap few new medications have been approved past 20 years. Recently, psychedelic‐assisted therapy psilocybin lysergic acid diethylamide has garnered significant attention AUD. Yet, they require amounts therapist input due to prolonged subjective effects (~4–12 h) leading costs impeding implementation. Accordingly, is an increasing interest rapid short‐acting psychedelic 5‐methoxy‐ N,N ‐dimethyltryptamine (5‐MeO‐DMT). This paper offers a first look at potential therapeutic mechanisms for AUD by reviewing current literature on 5‐MeO‐DMT. Primarily, 5‐MeO‐DMT able induce mystical experiences ego‐dissolution together psychological flexibility mindfulness. could decrease symptoms through alleviation mood‐related comorbidities consistent negative reinforcement self‐medication paradigms. In addition, preliminary evidence indicates that modulates neural oscillations might subserve (increases gamma ), mindfulness theta reorganization executive control networks coherence across frequencies) improve emotion regulation inhibition. Finally, animal studies characterized neuroplasticity, anti‐inflammation, 5‐HT 2A receptor agonism, downregulation metabotropic glutamate 5 clinical implications comorbidities. The concludes several recommendations future research establish purported action.

Язык: Английский

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Transient destabilization of whole brain dynamics induced by N,N-Dimethyltryptamine (DMT)

Communications Biology, Год журнала: 2025, Номер 8(1)

Опубликована: Март 11, 2025

Abstract The transition towards the brain state induced by psychedelic drugs is frequently neglected in favor of a static description their acute effects. We use time-dependent whole-brain model to reproduce large-scale dynamics measured with fMRI from 15 volunteers under 20 mg intravenous N,N-Dimethyltryptamine (DMT), short-acting psychedelic. To capture its transient effects, we parametrize proximity global bifurcation using pharmacokinetic equation. Simulated perturbations reveal heightened reactivity concentrated fronto-parietal regions and visual cortices, correlated serotonin 5HT2a receptor density, primary target psychedelics. These advances suggest mechanism explain key features also predicts that temporal evolution these aligns pharmacokinetics. Our results contribute understanding how psychedelics introduce where minimal can achieve maximal effect, shedding light on short episodes may extend an overarching influence over time.

Язык: Английский

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

Human Brain Mapping, Год журнала: 2025, Номер 46(5)

Опубликована: Апрель 1, 2025

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

Язык: Английский

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Neurophysiological correlates of ketamine-induced dissociative state in bipolar disorder: insights from real-world clinical settings

Molecular Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 14, 2025

Abstract Ketamine, a dissociative compound, shows promise in treating mood disorders, including treatment-resistant depression (TRD) and bipolar disorder (BD). Despite its therapeutic potential, the neurophysiological mechanisms underlying ketamine’s effects are not fully understood. This study explored acute changes induced by subanesthetic doses of ketamine BD patients with using electroencephalography (EEG) biomarkers. A cohort 30 (F = 12) inpatients TRD undergoing treatment was included study. EEG recordings were performed during one infusions ranging from 0.5 to 1 mg/kg, subjective evaluated Clinician-Administered Dissociative States Scale (CADSS). Both rhythmic arrhythmic features extrapolated signal. Patients who exhibited clinical response within week classified as early responders (ER), whereas those responded later categorized late (LR). Ketamine reduced low-frequency spectral power density while increasing gamma oscillatory power. Additionally, flattened slope spectra, indicating altered scale-free dynamics. also increased brain signal entropy, particularly high-frequency bands. Notably, LR greater compared ER, suggesting endophenotypic differences sensitivity. These findings provide valuable insights into depression, highlighting utility biomarkers for assessing real-world settings. Understanding neural correlates may contribute personalized approaches improved management disorders.

Язык: Английский

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