Public and patient interest in psychedelic-assisted psychotherapy is increasing, but people seeking access to psychedelic trials may be more clinically heterogeneous than the populations these trials can enrol. We conducted a cross-sectional descriptive analysis of previously unreported aggregate telephone-screening data from the coordinating site of PRIDE, an ongoing Italian multicentre phase...
While psychedelic experiences are often reported as positive, adverse psychological reactions can occur. We present the case of a 19-year-old Caucasian male who presented to the ER with suicidal thoughts after taking lysergic acid diethylamide (LSD) alone. He was diagnosed with anxious state associated with panic attacks, and suicidal thoughts without ideation or behaviors. He was admitted to...
Treatment-resistant depression (TRD) is a heterogeneous condition in which symptoms such as anhedonia, rumination, and anxiety contribute to persistent disability. Esketamine nasal spray (ESK-NS), accelerated repetitive transcranial magnetic stimulation (arTMS), and adjunctive brexpiprazole represent novel therapeutic options with distinct mechanisms, though their domain-specific effects in...
INTRODUCTION: Ketamine, initially developed as an anesthetic and now increasingly prescribed for treatment-resistant depression, is also widely misused in recreational contexts. Chronic ketamine use, often leading to dependence, has been associated with severe physical complications, including ulcerative cystitis and gastrointestinal dysfunction, as well as cognitive, affective, and psychotic...
Background: Intranasal esketamine (ESK-NS) is an effective treatment for treatment-resistant depression (TRD), but whether antidepressant outcomes differ by sex and age remains insufficiently explored. Methods: This secondary analysis of the REAL-ESK study included 210 patients with TRD treated with ESK-NS in routine clinical practice and assessed at baseline (T0), one month (T1), and three...
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...
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Scientific ReportsMarch 27, 2026Gianmauro Palombelli, Valentina Zecca, Marta Boffa et al.1 citation
Major depressive disorder is highly prevalent and disabling, and many patients do not respond to standard therapies, resulting in treatment-resistant depression (TRD). Progress in TRD requires preclinical models with poor response to conventional treatments. The Wistar-Kyoto rat exposed to chronic mild stress (WKY/CMS) offers a robust paradigm: it shows limited responsiveness to standard...
Disturbances of the minimal self, or anomalous self-experiences (ASEs), are increasingly regarded as a core feature of primary psychotic disorders (PPDs). However, it remains unclear whether similar self-disorders are present in substance-induced psychosis (SIP), a condition that often mimics PPDs in its early stages. The study aims to compare ASEs between PPD and SIP using the EASE interview,...
BACKGROUND: Over the past ten years, several psychedelic compounds, including tryptamines like lysergic acid diethylamide/LSD, psilocybin, ayahuasca, and dimethyltryptamine/DMT, have been tested in clinical trials for a range of psychiatric conditions, such as anxiety and depression. While these compounds are relatively available for treatment, ketamine and its S(+) enantiomer, esketamine, are...
Novel psychoactive substances (NPS) are increasingly used by young individuals for their psychoactive effects and have been frequently associated with the emergence of psychotic symptoms and schizophrenia spectrum disorders. However, it remains unclear whether NPS use directly increases the risk of psychosis onset or whether individuals with a predisposition to psychosis are more likely to...
Introduction: Treatment-Resistant Depression (TRD) affects approximately 30–50% of patients with Major Depressive Disorder (MDD) who fail to respond to at least two adequate antidepressant trials. This condition presents substantial clinical and functional challenges, and no universally accepted treatment algorithm currently exists. Emerging therapeutic strategies, particularly glutamatergic...
Background: Synthetic cannabinoid receptor agonists (SCRAs, commercially known as "Spice") have become a leading cause of substance-induced psychosis worldwide. These compounds show strong associations not only with acute psychotic episodes but also, in a subset of patients, with persistent or relapsing psychotic disorders, patterns that raise concern about progression to schizophrenia. Yet...
Depression is a prevalent and heterogeneous disorder with significant personal and social consequences. The rise of treatment-resistant depression (TRD) challenges traditional approaches and underscores the need for a broader neurobiological perspective. When monoaminergic modulation proves insufficient, clinical guidelines increasingly turn to non-monoaminergic interventions such as...
Abstract Background Among the innovative treatments investigated for depression, psilocybin appears to play an extremely promising role, with several studies showing remission rates up to 70% in patients with treatment-resistant depression (TRD) treated with protocols involving a single or double dose administration [1,2]. Psilocybin is a psychedelic compound belonging to the tryptamine class,...
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...
AIMS: This study aimed to investigate the differences in psychotic symptomatology, dissociative symptoms, alexithymia, and aberrant salience among three groups: non-cannabis users (NU), natural cannabis users (NC), and synthetic cannabinoid users (SCs). The study also explored the patterns of alexithymia and its associations with other psychopathological dimensions in these populations....
Background. Treatment-resistant depression (TRD) is a prevalent, high-burden disorder. Esketamine nasal spray (ESK-NS) has been approved for, T.R.D.; and efficacy has been observed in both clinical trials and real-world studies. However, observations integrating patients’ perspective on this treatment are limited. This multicentric Italian study explored experiences with ESK-NS in TRD patients,...
The phenomenology of depression is characterized by a wide array of emotional, cognitive, and physical symptoms that significantly disrupt an individual's life. Societal changes, driven by technological advancements, economic pressures, environmental concerns including climate change, and shifting cultural norms, have influenced how depression manifests and is understood. These developments...
BACKGROUND: The widespread availability and accessibility of over-the-counter (OTC) medicines play a vital role in modern healthcare systems, enabling individuals to manage minor health concerns independently. However, certain OTC medications possess pharmacological properties that render them susceptible to misuse and abuse, including stimulants, laxatives, sedatives, and opiate-containing...
Abstract Background Treatment-Resistant Depression (TRD) affects almost 30% of patients with Major Depressive Disorder (MDD) (1). 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...
Data on long-term treatment with Esketamine Nasal Spray (ESKNS) in real-world patients with treatment resistant depression (TRD) is scarce. The primary aim of the study is to evaluate the effectiveness and tolerability of ESK-NS treatment at 6 and 12-month follow-ups. This is part of an observational, retrospective, multicentric Italian study (REAL-ESK study). Subjects for the present study...
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...
Background: Piperazines, synthetic compounds known for their stimulant and hallucinogenic effects, have gained prominence among novel psychoactive substances (NPS) and are frequently associated with adverse psychiatric outcomes, including psychosis. Methods: A systematic review of the literature available up to 23 May 2024 was conducted, using the PubMed, Scopus, and Web of Science databases,...
Background Natural Cannabis (NC) and Synthetic Cannabinoids (SCs) use can increase the risk and exacerbate the course of psychotic disorders. These could be influenced by the Aberrant Salience (AS) construct. It refers to an excess of attribution of meaning to stimuli that are otherwise regarded as neutral, thereby transform them into adverse, dangerous, or mysterious entities. This leads the...