Bipolar Disorders
January 13, 2023
Giovanni Martinotti, Bernardo Dell’osso, Giorgio Di Lorenzo et al.
72 citations
Esketamine nasal spray reduced depressive symptoms in people with treatment-resistant bipolar depression as effectively as in those with unipolar treatment-resistant depression, with no significant differences in response or remission rates after one and three months. The treatment also showed greater anxiety-reducing effects in the bipolar group. No treatment-emergent affective switch occurred, supporting the safety and tolerability of esketamine for bipolar treatment-resistant depression.
Annals of General Psychiatry
November 26, 2023
Giuseppe Maina, Marina Adami, Giuseppe Ascione et al.
56 citations
A Delphi panel of 60 Italian psychiatrists found wide variation in how treatment-resistant depression (TRD) is managed in Italy, highlighting a need for standardized strategies and treatments specifically approved for TRD. High consensus emerged on adding lithium or antipsychotics as augmentation therapies and on the need for long-term maintenance therapy. Esketamine nasal spray was identified as the best option for TRD patients, with agreement that it can be administered in a community outpatient setting given appropriate educational support for patients.
Current neuropharmacology
January 1, 2025
Gianluca Rosso, Giacomo d'Andrea, Stefano Barlati et al.
23 citations
Among patients with treatment-resistant depression who continued esketamine nasal spray for at least six months, 76.2% responded or achieved remission. Of those who had not responded by six months, a subset improved by twelve months. Side effects occurred in 71.8% of patients at six months, decreasing to 42% at twelve months; the most common were sedation and dissociation. Only two patients stopped treatment due to tolerability issues. The findings suggest esketamine is effective and safe for mid- to long-term treatment, with a novel observation of late clinical response in some patients. Results require confirmation in larger samples and longer observation periods.
Journal of Personalized Medicine
April 1, 2025
Marco Di, M. Pepe, G. D’andrea et al.
18 citations
Most patients with treatment-resistant depression reported positive experiences with esketamine nasal spray. In a survey of 236 outpatients, 88.4% reported enhanced quality of life. Satisfaction levels varied: 10.2% were unsatisfied, 19.1% partially satisfied, 44.4% satisfied, and 26.3% very satisfied. The most satisfied patients noted early improvements in depressed mood, suicidal thoughts, and restlessness, and reported functional gains across all domains. Artificial intelligence analysis of open-ended responses identified themes of personal growth and a desire for tailored treatment settings. Integrating patient-reported experiences may help personalize care and improve adherence.
Healthcare (Basel, Switzerland)
January 29, 2024
Valerio Ricci, Domenico De Berardis, Giuseppe Maina
16 citations
Third-generation antipsychotics (aripiprazole, cariprazine, brexpiprazole, and lurasidone) show promise for treating substance-induced psychosis, a condition triggered by substance misuse or withdrawal that features prominent hallucinations, delusions, mood disturbances, and cognitive issues. Substances such as cannabinoids, cocaine, amphetamines, and LSD are especially likely to induce psychosis. The review describes each drug's unique pharmacological properties and neurotransmitter interactions, suggesting they may address both psychotic symptoms and substance misuse. The authors call for more research on long-term effects and advocate combining medication with psychological treatments, emphasizing the complexity of managing substance-induced psychosis.
Psychopathology
January 1, 2024
Valerio Ricci, Giuseppe Maina, Giovanni Martinotti
11 citations
Dissociation in addiction involves a fragmented sense of self that extends beyond momentary experiences, creating a persistent discontinuity of identity. This process compresses an individual's vital space and freezes their perception of time, impairing emotion, sensation, and comprehension. The authors construct a framework through historical analysis and phenomenological perspective, exploring trauma and temporality to understand dissociative experiences in addiction.
Psychiatry International
October 15, 2024
Valerio Ricci, Giovanni Martinotti, Giuseppe Maina
9 citations
Substance-induced psychosis (SIP) is increasingly common, especially among adolescents and young adults using cannabis, cocaine, and novel psychoactive substances. This review examines how SIP differs from primary psychotic disorders by focusing on two key concepts: Gaëtan de Clérambault's "mental automatism," where involuntary thoughts and sensations feel alien to the self, and the "twilight state" of consciousness, marked by altered perception of space, time, and social interaction. These phenomena help explain how substance use triggers psychotic processes and how SIP can transition to persistent psychosis with frequent, potent use. The review advocates for a clinical–phenomenological approach to improve diagnosis and treatment.
Psychopathology
January 1, 2024
Valerio Ricci, Giuseppe Maina, Giovanni Martinotti
8 citations
The twilight state of consciousness involves a narrowed yet expanded awareness, marked by perceptual shifts in time and space. New psychoactive substances can induce this state by deconstructing core components of consciousness, potentially triggering exogenous psychosis. This paper uses a phenomenological approach to explore how these substances alter spatial and temporal perception during the twilight phase, highlighting an overlooked aspect of psychopathology.
Frontiers in psychiatry
January 1, 2025
Valerio Ricci, Maria Celeste Ciavarella, Carlotta Marrangone et al.
7 citations
Substance-induced psychoses (SIPs) triggered by novel psychoactive substances differ from endogenous psychoses like schizophrenia in three key ways: dissociation, mental automatism, and temporality. Dissociation in SIPs causes fragmentation of consciousness and identity detachment, distinct from the spaltung seen in schizophrenia. Mental automatism, as described by De Clerambault, appears early in SIPs with cognitive disruptions preceding delusions. Temporally, SIPs trap individuals in an eternal present, disconnected from past and future, unlike the fragmented temporality in schizophrenia. The paper argues that a phenomenological approach aids clinical differentiation and targeted interventions.
Journal of psychoactive drugs
January 8, 2025
Valerio Ricci, Domenico De Berardis, Sheikh Shoib et al.
4 citations
Frequent recreational ketamine use among young adults is linked to more psychotic-like experiences, such as unusual thoughts and perceptions. In ten participants aged 18–24 who used ketamine multiple times weekly, higher use frequency correlated with more such experiences, while other drugs like THC, MDMA, and alcohol did not significantly contribute. The findings suggest ketamine's action on NMDA receptors may produce symptoms resembling schizophrenia. The small sample and reliance on self-report limit the conclusions, and more research is needed to confirm causality and long-term effects.
Journal of Psychiatric Research
June 19, 2025
Valerio Ricci, Ilenia di Muzio, Mancusi Gianluca et al.
2 citations
Synthetic cannabinoid users experiencing first-episode psychosis show more severe positive psychotic symptoms, persistent aberrant salience, and limited recovery of alexithymia over six months compared to natural cannabis users and non-users. Dissociative symptoms are more prominent in both user groups, with synthetic cannabinoid users showing minimal improvement. Negative symptoms are higher in non-users but decrease across all groups. Alexithymia correlates with specific aberrant salience subscales, particularly Feelings of Increased Significance and Sense Sharpening. These findings indicate synthetic cannabinoids are associated with more severe and persistent psychotic symptoms and emotional dysregulation than natural cannabis.
Rivista di psichiatria
November 1, 2024
Valerio Ricci, Domenico de Berardis, Giovanni Martinotti et al.
2 citations
Abruptly stopping cannabis use can trigger psychotic symptoms in vulnerable individuals. An analysis of four patients seen between 2019 and 2023 describes psychotic features that emerged after sudden cannabis withdrawal. The report suggests that withdrawal, not only chronic use, may be a risk factor for precipitating psychosis, especially in susceptible patients. Clinicians should be aware of this potential risk.
Psychopathology
January 1, 2026
Valerio Ricci, Massimiliano Aragona, Giuseppe Maina et al.
1 citation
Hallucinations in schizophrenia, substance-induced psychosis (SIP), and substance-related persistent psychosis (PP) differ qualitatively. Schizophrenic hallucinations typically occur in clear consciousness with variable sensory vividness. SIP hallucinations arise in an oneiroid (dreamlike) state with increased vividness and multisensory integration. PP hallucinations occur in a twilight state of consciousness, often simpler but intrusive. These phenomenological differences provide a conceptual framework for more accurate diagnosis and treatment, especially in substance-related psychopathologies.
Psychiatry research
September 1, 2026
Valerio Ricci, Andrea Paggi, Giovanni Martinotti et al.
In patients with cannabis-induced first-episode psychosis, dissociative symptoms—especially depersonalization and derealization—are strong independent predictors of poor functional recovery over 24 months. Among 72 patients, three recovery trajectories emerged: Rapid Recovery (34.7%, GAF +29.1 points), Gradual Recovery (40.3%, GAF +15.7 points), and Persistent Impairment (25.0%, GAF +4.7 points). A symptom-function discrepancy occurred in 31.9% of patients, where psychotic symptoms improved but functioning did not; these patients had higher baseline dissociation scores (33.8 vs. 18.1). Dissociation mediated 35% of cannabis's negative effect on functional outcomes. A high-risk subgroup (22%) with elevated dissociation, depression, and continued cannabis use showed minimal improvement despite treatment. Routine dissociation assessment and targeted interventions may improve outcomes.
The International journal of social psychiatry
April 26, 2026
Valerio Ricci, Giovanni Martinotti, Giuseppe Maina
Distinguishing substance-induced psychotic disorders from primary psychotic disorders with substance use is diagnostically challenging. A systematic review of 36 studies covering over 80,000 individuals found that cannabis-induced psychosis typically involves prominent positive symptoms, preserved negative symptoms, and elevated affective and anxiety features, with 36% to 46% transitioning to schizophrenia spectrum disorders. Methamphetamine-induced psychosis ranges from simple persecutory delusions and tactile hallucinations in transient cases—with markedly elevated violence rates (75.6%)—to complex sensory disturbances in persistent cases. Despite substance-specific patterns, substantial overlap with primary disorders and poor diagnostic stability (25% to 39% of initial diagnoses converting to primary disorders) limit cross-sectional assessment. Superior antipsychotic response at lower doses may favor substance-induced etiology.
Frontiers in Psychiatry
January 30, 2025
Valerio Ricci, Alessandro Sarni, Giuseppe Maina
The relationship between substance use and psychosis has been debated for centuries. This paper examines substance-induced psychotic disorder (SIP) through the historical theories of Gaëtan de Clérambault and Karl Bonhoeffer. De Clérambault's concept of mental automatism describes involuntary intrusions into consciousness, such as unbidden thoughts or sensations, as the core mechanism of psychosis. Bonhoeffer's exogenous psychosis model emphasizes how external triggers like drugs interact with biological vulnerabilities to produce psychotic episodes. Together, these frameworks suggest that prolonged substance use can erode mental resilience, leading to chronic psychosis, and offer insights for diagnosis and treatment.
Frontiers in psychiatry
January 1, 2025
Valerio Ricci, Domenico De Berardis, Giovanni Martinotti et al.
Cannabis use, especially high-potency THC products, is consistently linked to elevated dissociative experiences in patients with first-episode psychosis. Users scored 11-13 points higher on the Dissociative Experiences Scale-II than non-users, and daily high-potency use tripled the odds of clinically significant dissociation (OR: 3.21). These dissociative symptoms, along with more severe anomalous self-experiences, predicted poorer functional outcomes at 12 months (GAF scores: 52 ± 14 vs. 67 ± 12). About 75% of patients showed reduced dissociation after stopping cannabis, suggesting potential reversibility. The evidence certainty was moderate for dissociation severity and low for self-disturbance outcomes.
Schizophrenia research
March 24, 2026
Valerio Ricci, Stefania Chiappini, Giovanni Martinotti et al.
Treatment response in substance-induced psychotic disorders is predicted by several factors with varying levels of evidence. Acute symptom onset within 24-48 hours of substance use predicts favorable treatment response, while prominent negative symptoms predict slower remission and higher transition to chronic psychotic disorders. Poor premorbid functioning and bimodal response patterns (rapid remission within 30 days versus poor outcomes thereafter) distinguish responders from non-responders. Early age of substance use onset, family history of psychotic disorders, abstinence achievement, and premorbid cognitive capacity may influence outcomes. Cannabis-induced and methamphetamine-induced psychosis warrant particular caution given higher persistence rates and psychiatric comorbidity.
The Journal of nervous and mental disease
September 1, 2024
Valerio Ricci, Giuseppe Maina, Gilberto Di Petta et al.
Substance-induced psychosis, especially from cannabis and cocaine, can transition to persistent psychosis, with cannabis posing a particularly high risk. Differences exist between substance-induced and primary psychotic disorders, and external factors play a key role. A phenomenological perspective describes this as a disruption in perception, altering time and space and causing hallucinations. The concept of a "twilight state" of consciousness helps explain the shift from substance use to psychosis, affecting spatiality, intersubjectivity, and temporality. This challenges standard diagnostic models and calls for a more nuanced understanding of how substances trigger psychotic experiences.
Frontiers in Psychiatry
January 8, 2024
V. Ricci, Ilenia di Muzio, F. Ceci et al.
Patients with first-episode psychosis who use synthetic cannabinoids (SPICE) experience more severe and persistent positive symptoms and less improvement in aberrant salience—the tendency to assign excessive meaning to neutral stimuli—compared with natural cannabis users and non-users. Non-users show better recovery in global functioning. Aberrant salience scores decline over six months in all groups, but SPICE-users start higher and improve less. Negative symptoms are most prominent among non-users. These findings may help clinicians tailor diagnosis and treatment for substance-induced versus non-substance-related psychosis.