Cannabis is the most widely used psychoactive substance subject to legal restriction worldwide, and one of its best-characterized acute effects is a distortion of the lived sense of time: users reliably report that time slows, fragments, or loses its ordinary continuity, an effect documented since the earliest controlled studies of marijuana intoxication and confirmed across decades of...
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...
Intranasal esketamine has been available for treatment-resistant depression (TRD) since 2019, but the trials that led to its approval answer only some of the questions prescribers face. About 97% of trial participants had failed only one or two antidepressant classes, and patients with bipolar disorder, psychosis, obsessive–compulsive disorder, four personality disorders, moderate-to-severe...
Abstract Background Treatment-resistant depression (TRD) represents a major clinical challenge and is associated with substantial symptom burden, functional impairment, and poor prognosis. Beyond traditional monoaminergic models, converging evidence indicates that dysfunction of the glutamatergic system plays a central role in the pathophysiology of TRD, contributing to impaired neuroplasticity...
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...
BACKGROUND Cannabis-induced psychosis presents complex sex-based disparities that challenge traditional epidemiological patterns. While males demonstrate higher cannabis use rates, emerging evidence reveals paradoxical vulnerability patterns where females may show heightened susceptibility to cannabis-related psychotic outcomes despite lower consumption rates. OBJECTIVE To map evidence for...
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...
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...
Borderline personality disorder (BPD) often occurs alongside treatment-resistant depression (TRD), but the impact of BPD on real-world outcomes with intranasal esketamine is unclear. Consecutive TRD outpatients initiating intranasal esketamine treatment at four Italian centres between 1 September 2024 and 30 September 2025 were enrolled in the study (n = 90): 45 with comorbid BPD and 45 without...
Esketamine has demonstrated efficacy in treatment-resistant depression (TRD), but medium-term real-world functional outcomes remain understudied. This study described 6-month depressive symptoms and functional trajectories during routine esketamine treatment, focusing on functional outcomes and remission correlates. In this prospective multicenter study, 60 patients with TRD initiating...
Suicidal ideation and deliberate self-harm are frequent and persistent in treatment-resistant depression (TRD), particularly when comorbid borderline personality disorder (BPD) is present. Real-world evidence on antisuicidal outcomes during intranasal esketamine in this population remains limited. In this multicentre prospective observational study, 90 outpatients with TRD received intranasal...
Functional recovery in cannabis-induced first-episode psychosis (FEP) remains incompletely understood. Dissociative symptoms, frequently associated with cannabis use, may represent a key but underexplored determinant of functional trajectories. This prospective cohort study followed 72 patients meeting DSM-5 criteria for cannabis-induced psychotic disorder over 24 months. Functional recovery...
Background and hypothesis Cannabis use initiation during adolescence has increased globally, raising concerns about neurodevelopmental consequences during this critical period when the brain undergoes extensive remodeling in cannabinoid receptor-rich regions. Study design This systematic review examines neurodevelopmental consequences of adolescent cannabis use, focusing on structural brain...
Distinguishing substance-induced psychotic disorders (SIPD) from primary psychotic disorders with concurrent substance use remains a critical diagnostic challenge for treatment planning and prognostic counseling. To systematically review the clinical phenomenology of SIPD, identify distinguishing symptom patterns, and examine relationships between phenomenology and outcomes. A systematic search...
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Background/Objectives: Esketamine-related dissociation is a transient, pharmacologically induced altered state that differs from the trait-like pathological dissociation typically observed in trauma-related conditions. While most studies have quantified these effects using the Clinician-Administered Dissociative States Scale (CADSS), patients' subjective phenomenology and meaning-making remain...
BACKGROUND Novel psychoactive substances (NPS) represent an evolving public health threat, yet evidence on their acute and long-term psychiatric consequences remains limited. OBJECTIVE To systematically review psychiatric and neurological consequences of NPS use across the full clinical spectrum, with primary focus on synthetic cannabinoids and related compounds, and to characterize...
Healthcare professionals encounter challenges in discerning endogenous and exogenous, drug-related, psychopathological phenomena. This study aimed to explore qualitative differences between hallucinations in schizophrenia and two forms of substance-related psychosis. These are substance-induced psychosis (SIP), which has an acute onset and is usually transient, and substance-related persistent...
Objective: To scope the available literature on antipsychotic treatment in substance-induced psychotic disorders, summarize evidence across substance categories, and highlight priorities for future research. Methods: This scoping review followed Arksey and O’Malley’s framework and PRISMA-ScR guidelines. A systematic search of PubMed, Scopus, Embase, PsycINFO, and Cochrane Library (January...
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,...
Purpose: Treatment-resistant depression (TRD) is a common phenomenon and a considerable clinical challenge; recently, esketamine in conjunction with an oral antidepressant (AD) has emerged as a potential treatment for TRD. Several studies have shown the efficacy of esketamine in improving depressive symptoms. This prospective study aims to explore the long-term effects of esketamine therapy on...
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...