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Stefano L. Sensi

18 papers in the library · 521 citations · publishing 2021-2026

Papers

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Mechanistic insights toward dissociating therapeutic from psychedelic effects: bridging the gap between psychedelic research and mental health care

Translational Psychiatry June 24, 2026 Mauro Pettorruso, Giacomo D’andrea, Antonio Inserra et al.

Clinical trials investigating psychedelic compounds for depression and anxiety-related disorders are yielding promising preliminary results. Psychedelics produce profound alterations in brain function—such as suppression of the default mode network and thalamocortical dysregulation—leading to intense subjective experiences including ego dissolution and mystical-type states. While often...

REM sleep as a dummy-model of the world: A theoretical framework.

Progress in neurobiology June 19, 2026 Stefano T Censi, Alberto Granzotto, Stefano L. Sensi

Sleep remains a complex and only partially understood neurophysiological process, with current theories often fragmented across electrophysiological, metabolic, and phenomenological domains. In this paper, we propose an advanced and integrative framework that conceptualizes rapid eye movement (REM) sleep as a state in which the brain constructs a provisional dummy model of the external world....

A Shared Entropic Axis Spans States of Consciousness Across Pharmacological and Clinical Conditions

bioRxiv Preprint Server June 12, 2026 Dante Sebastián Galván Rial, Gabriel A. Della Bella, Lorina Naci et al. preprint

A general account of how diverse states of consciousness arise from brain activity requires a quantitative framework that generalises across them. The Entropic Brain Theory proposes that states of consciousness can be ordered along a single dimension defined by the entropy of spontaneous neural activity, but this prediction has not been tested across pharmacological and clinical perturbations...

Psychedelics and ketamine/esketamine in depressive disorders: biological mechanisms and associated neuroimaging and clinical changes.

Transl Psychiatry October 31, 2025 Giacomo D’andrea, Stefania Chiappini, Laura Ciavoni et al. 3 citations

Psychedelics and ketamine/esketamine in depressive disorders: biological mechanisms and associated neuroimaging and clinical changes.

Effectiveness of repeated Esketamine nasal spray administration on anhedonic symptoms in treatment-resistant bipolar and unipolar depression: A secondary analysis from the REAL-ESK study group.

Psychiatry Research July 26, 2025 Giacomo D’andrea, Clara Cavallotto, Mauro Pettorruso et al. 16 citations

INTRODUCTION Anhedonia, defined as the diminished ability to experience or anticipate pleasure, is a core symptom of major depressive disorder (MDD) and bipolar depression (BD), and associated with depression severity, suicidality and poor treatment outcomes. Conventional antidepressants demonstrate limited efficacy against anhedonia. Esketamine nasal spray (ESK-NS) - a novel NMDA receptor...

Xylazine as an emerging new psychoactive substance; focuses on both 5‐HT7 and κ‐opioid receptors' molecular interactions and isosteric replacement

Archiv der Pharmazie March 1, 2025 Giuseppe Floresta, Alberto Granzotto, Vincenzo Patamia et al. 12 citations

Abstract Xylazine, traditionally used as a veterinary sedative, has recently emerged as a new psychoactive substance, being typically ingested in combination with fentanyl derivatives and hence raising significant public health concerns. Despite its increasing prevalence, little is known about its molecular interactions with human neuroreceptors, specifically the serotonin 7 (5‐HT 7 R) and...

Exploring vortioxetine combination with intranasal esketamine: A feasible alternative to SSRI/SNRI? - Insights from the REAL-ESK study.

Journal of Affective Disorders December 15, 2024 Giacomo d'Andrea, Andrea Miuli, Mauro Pettorruso et al. 6 citations

Treatment-Resistant Depression (TRD) affects almost 30 % of patients with Major Depressive Disorder (MDD). Esketamine Nasal Spray (ESK-NS) has recently been approved for TRD in combination with a Serotonin Specific Reuptake Inhibitor/SSRI or a Serotonin-Norepinephrine Reuptake Inhibitor/SNRI. There is a lack of studies investigating the effectiveness and safety of ESK-NS in combination with...

The central role of the Thalamus in psychosis, lessons from neurodegenerative diseases and psychedelics.

Transl Psychiatry December 13, 2023 Marco Onofrj, Mirella Russo, Stefano Delli Pizzi et al. 42 citations

The PD-DLB psychosis complex found in Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB) includes hallucinations, Somatic Symptom/Functional Disorders, and delusions. These disorders exhibit similar presentation patterns and progression. Mechanisms at the root of these symptoms also share similarities with processes promoting altered states of consciousness found in Rapid Eye Movement...

LSD-induced changes in the functional connectivity of distinct thalamic nuclei.

Neuroimage December 1, 2023 Stefano Delli Pizzi, Piero Chiacchiaretta, Carlo Sestieri et al. 27 citations

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...

Intranasal esketamine as tool for rapid cycling bipolar disorder: A case report of successful mood stabilization

Psychiatry Research Case Reports October 18, 2023 Giacomo D’andrea, Ornella di Marco, Francesco Maria Semeraro et al. 1 citation

Rapid Cyclic Bipolar Disorder (RCBD) is a debilitating condition that manifests as four or more episodes of depression, mania, or hypomania in a span of one year, with depression being the predominant event. RCBD is prevalent among individuals diagnosed with bipolar disorder and is associated with elevated suicide risk, prolonged disease duration, unfavorable clinical outcomes, and cognitive...

Predicting outcome with Intranasal Esketamine treatment: A machine-learning, three-month study in Treatment-Resistant Depression (ESK-LEARNING)

Psychiatry Research July 29, 2023 Mauro Pettorruso, Roberto Guidotti, Giacomo D’andrea et al. 56 citations

Treatment-resistant depression (TRD) represents a severe clinical condition with high social and economic costs. Esketamine Nasal Spray (ESK-NS) has recently been approved for TRD by EMA and FDA, but data about predictors of response are still lacking. Thus, a tool that can predict the individual patients' probability of response to ESK-NS is needed. This study investigates sociodemographic and...

Investigating the Effectiveness and Tolerability of Intranasal Esketamine Among Older Adults With Treatment-Resistant Depression (TRD): A Post-hoc Analysis from the REAL-ESK Study Group

American Journal of Geriatric Psychiatry July 8, 2023 Giacomo D’andrea, Stefania Chiappini, Roger S McIntyre et al. 36 citations

INTRODUCTION: Treatment-resistant depression (TRD) is a serious and debilitating psychiatric disorder that frequently affects older patients. Esketamine nasal spray (ESK-NS) has recently been approved as a treatment for TRD, with multiple studies establishing its efficacy and tolerability. However, the real-world effectiveness, tolerability, and safety of this treatment in older adults is still...

Spatial Correspondence of LSD-Induced Variations on Brain Functioning at Rest With Serotonin Receptor Expression.

Biological psychiatry. Cognitive neuroscience and neuroimaging July 1, 2023 Stefano Delli Pizzi, Piero Chiacchiaretta, Carlo Sestieri et al. 18 citations

Lysergic acid diethylamide (LSD) is an atypical psychedelic compound that exerts its effects through pleiotropic actions, mainly involving 1A/2A serotoninergic (5-HT) receptor subtypes. However, the mechanisms by which LSD promotes a reorganization of the brain's functional activity and connectivity are still partially unknown. Our study analyzed resting-state functional magnetic resonance...

In vivo mapping of pharmacologically induced functional reorganization onto the human brain’s neurotransmitter landscape

Science Advances June 14, 2023 Leor Roseman, Christopher Timmermann, Daniel Golkowski et al. 65 citations

To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain’s rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically induced macroscale functional reorganization, by relating the regional distribution of 19 neurotransmitter receptors and transporters...

Esketamine in treatment-resistant depression patients comorbid with substance-use disorder: A viewpoint on its safety and effectiveness in a subsample of patients from the REAL-ESK study

European Neuropsychopharmacology May 4, 2023 Stefania Chiappini, Giacomo D’andrea, Sergio De Filippis et al. 48 citations

Esketamine, the S-enantiomer of ketamine, has recently emerged as a therapy for treatment-resistant depression (TRD), showing both rapid antidepressant action and good efficacy and high safety. It is also indicated for the acute short-term treatment of psychiatric emergency due to major depressive disorder (MDD) and for depressive symptoms in adults with MDD with acute suicidal...

Treating bipolar depression with esketamine: Safety and effectiveness data from a naturalistic multicentric study on esketamine in bipolar versus unipolar treatment‐resistant depression

Bipolar Disorders January 13, 2023 Giovanni Martinotti, Bernardo Dell’osso, Giorgio Di Lorenzo et al. 72 citations

BACKGROUND: Bipolar depression accounts for most of the disease duration in type I and type II bipolar disorder (BD), with few treatment options, often poorly tolerated. Many individuals do not respond to first-line therapeutic options, resulting in treatment-resistant bipolar depression (B-TRD). Esketamine, the S-enantiomer of ketamine, has recently been approved for treatment-resistant...

Mapping Pharmacologically-induced Functional Reorganisation onto the Brain’s Neurotransmitter Landscape

bioRxiv (Cold Spring Harbor Laboratory) July 13, 2022 Andrea I. Luppi, Justine Y. Hansen, Ram Adapa et al. 5 citations preprint

Abstract To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain’s rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically-induced macroscale functional reorganisation, by relating the regional distribution of 19 neurotransmitter receptors and...

Therapeutic Potentials of Ketamine and Esketamine in Obsessive–Compulsive Disorder (OCD), Substance Use Disorders (SUD) and Eating Disorders (ED): A Review of the Current Literature

Brain Sciences June 27, 2021 Giovanni Martinotti, Stefania Chiappini, Mauro Pettorruso et al. 114 citations

The obsessive-compulsive spectrum refers to disorders drawn from several diagnostic categories that share core features related to obsessive-compulsive disorder (OCD), such as obsessive thoughts, compulsive behaviors and anxiety. Disorders that include these features can be grouped according to the focus of the symptoms, e.g., bodily preoccupation (i.e., eating disorders, ED) or impulse control...