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...
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...
Psychiatry InternationalSeptember 10, 2026Tommaso Barlattani, Giorgio Sernia, Chiara D’Amelio et al.
Background: Evidence for repeated intranasal esketamine in obsessive–compulsive disorder (OCD) remains preliminary, particularly when OCD co-occurs with treatment-resistant depression (TRD). Methods: We report a 58-year-old woman treated with intranasal esketamine in routine clinical care for TRD; change in obsessive–compulsive symptoms was followed as a secondary observational outcome. Her...
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...
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...
Introduction Treatment-resistant depression (TRD) is a severe condition associated with high suicide risk and limited response to conventional antidepressants. Intranasal esketamine has shown rapid efficacy in reducing depressive symptoms and suicidal ideation. Objectives This observational study assessed the real-world effectiveness of esketamine in reducing suicidal ideation, self-harm...
Psychedelic drugs are serotonergic hallucinogens that can be divided into two types: naturally occurring (psilocybin, psilocin, and N,N-dimethyltryptamine) and synthetic (LSD, MDMA, 2,5-dimethoxy-4-iodoamphetamine, and ketamine). Psychedelics generally work on 5-hydroxytryptamine receptors and might be useful in cognitive enhancement, brain connectivity, neuroplasticity, and neuronal...
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...
This systematic review and meta-analysis synthesized data from 13 clinical trials (n=606) evaluating psilocybin-assisted psychotherapy for major depressive disorder and treatment-resistant depression. Despite early enthusiasm, the pooled standardized mean difference (-0.79, 95% confidence interval: -3.98 to 2.40, p=0.63) revealed no statistically significant overall antidepressant effect, with...
BACKGROUND: Treatment-resistant depression (TRD) affects approximately one-third of patients with major depressive disorder and represents a critical clinical challenge. Esketamine (S-ketamine, Spravato), approved by FDA and EMA since 2019, and psychedelic-assisted therapies (psilocybin, MDMA) share a pharmacological feature unique among approved psychiatric treatments: they induce altered...
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...
Esketamine rapidly improved suicidality and depression in TRD, with preliminary evidence suggesting gender-specific responses, and highlighting the importance of tailored interventions to maximize outcomes. Further research is needed to confirm these differences, explore the long-term effects, and understand the underlying mechanisms.
AbstractBackground and ObjectivesCannabis use is associated with psychotic disorder onset and exacerbation. This study examines how continued cannabis use affects depressive symptoms, psychotic symptoms, and suicidal behaviors following cannabis‐induced first‐episode psychosis (FEP).MethodsSixty‐five participants (aged 16–50 years) with FEP were recruited from psychiatric inpatient facilities...
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...
Given their great importance, as one of the most prescribed types of therapeutic drugs worldwide, we have analyzed the role of serendipity in the discovery of new antidepressants, ranging from selective serotonin reuptake inhibitors to more contemporary developments. We carried out a historical analysis of the discovery of new antidepressants, resorting to the original articles published on...
This study explores the psychotic-like experiences (PLEs) associated with recreational ketamine use among young adults. Ketamine, initially introduced as an anesthetic, is now widely used recreationally for its dissociative effects, raising concerns about its impact on mental health. Ten participants aged 18-24, who used ketamine recreationally multiple times a week, were assessed using the...
Cannabis use represents a significant environmental risk factor for psychotic disorders, with emerging evidence suggesting complex interactions between cannabinoid exposure, dissociative experiences, and fundamental disturbances of self-experience (self-disorders) in early psychosis. This systematic review examines the phenomenological and neurobiological relationships among dissociation,...
BACKGROUND: Cannabis is the most used recreational drug worldwide. Its use can increase the risk of developing psychotic disorders and exacerbate their course. However, little is known about the relationship between psychosis and withdrawal and the literature is still scarce. CASE PRESENTATION: In this study, based on an analysis of 4 patients referred to our mental health department and...
Background: Cannabis is the most widely used illicit substance. Numerous scientific evidence confirm the strong association between cannabis and psychosis. Exposure to cannabis can induce the development of psychosis and schizophrenia in vulnerable individuals. However, the neurobiological processes underlying this relationship are unknown. Neurotrophins are a class of proteins that serve as...
This narrative review explores the efficacy and tolerability of third-generation antipsychotics (TGAs)-aripiprazole, cariprazine, brexpiprazole, and lurasidone-for the management of substance-induced psychosis (SIP). SIP is a psychiatric condition triggered by substance misuse or withdrawal, characterized by unique features distinct from those of primary psychotic disorders. These distinctive...
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...
Abstract Background Treatment-resistant depression (TRD) is defined by the European Medicines Agency as a lack of clinically meaningful improvement after treatment, with at least two different antidepressants. Individual, familiar, and socio-economic burden of TRD is huge. Given the lack of clear guidelines, the large variability of TRD approaches across different countries and the availability...
Post-traumatic stress disorder (PTSD) is a debilitating mental health disorder that causes significant dysfunction in individuals. Currently, there are many approved pharmacotherapy and psychotherapy treatment options for PTSD, but unfortunately, half of the patients do not respond to traditional therapies. In this article, we review clinical trials and research on...
BACKGROUND: The Duration of Untreated Psychosis (DUP) is the time between the first-episode psychosis (FEP) and the initiation of antipsychotic treatment. It is an important predictor of several disease-related outcomes in psychotic disorders. The aim of this manuscript is investigating the influence of cannabis on the DUP and its clinical correlates. METHODS: During years 2014-2019, sixty-two...
Ayahuasca is a hallucinogenic plant preparation, traditionally consumed in sacred ceremonies by indigenous North-Westerner Amazonian countries like Colombia, Peru, Brazil, and Ecuador. It is fundamental to carefully balance benefits/risks related to the ayahuasca intake, both during ceremonies and experimental settings. The aim is at evaluating and comparing the potential therapeutic benefits...