Brain Sciences
June 27, 2021
Giovanni Martinotti, Stefania Chiappini, Mauro Pettorruso et al.
114 citations
Ketamine and esketamine, N-methyl-D-aspartate receptor antagonists, show promise for treating obsessive-compulsive disorder (OCD), eating disorders, and substance use disorders, which share features like obsessive thoughts and compulsive behaviors. A review of literature up to April 2021, following PRISMA guidelines, found that while small studies indicate remarkable results for treatment-resistant depression, PTSD, and OCD, solid evidence for benefits in OCD spectrum and addiction is still lacking. The use is supported by glutamatergic neurotransmission dysregulation. Preliminary data are optimistic, but further studies are needed to clarify unknowns and long-term effectiveness.
Current Neuropharmacology
October 20, 2022
Alessio Mosca, Stefania Chiappini, Andrea Miuli et al.
30 citations
Ibogaine and noribogaine, psychedelic substances from plants of the Apocynaceae family, show some efficacy in treating substance use disorders, particularly opiate detoxification. However, their use carries concerning risks of cardiotoxicity and mortality. A meta-analysis of side effects found a significant risk of developing headaches after treatment. The evidence, drawn from case reports, randomized controlled trials, open-label studies, surveys, and observational studies, remains unclear on overall efficacy and toxicity. Further research is needed to evaluate therapeutic benefits and safety.
Current Neuropharmacology
January 14, 2021
Stefania Chiappini, Andrea Miuli, Alessio Mosca et al.
19 citations
Benzydamine, an over-the-counter anti-inflammatory drug, is being diverted and used recreationally at high dosages (500–1500 mg) for its hallucinogenic properties. A systematic review of eleven articles from 1997–2019, including case reports, surveys, and case series, along with analysis of European adverse drug reaction reports from 2005–2020, found three reported abuse cases. The findings suggest healthcare professionals should be aware of potential misuse and that emergency physicians should consider benzydamine abuse when patients present with psychotic symptoms.
Neuroscience & Biobehavioral Reviews
October 19, 2025
Alessio Mosca, Gianluca Mancusi, Stefania Chiappini et al.
6 citations
Synthetic cannabinoids are the novel psychoactive substances most strongly associated with acute psychosis and, in some cases, persistent or relapsing psychotic disorders. Some cases show symptoms overlapping with schizophrenia, suggesting a possible risk of transition to chronic illness. Synthetic cathinones and phenethylamines are also linked to psychotic manifestations including thought disturbances and perceptual abnormalities. While many psychotic episodes are transient, a notable proportion evolve into persistent states, indicating that these substances may unmask latent vulnerabilities or directly contribute to chronic psychotic disorders. Clinicians should systematically assess NPS use in first-episode psychosis patients.
Psychiatry International
September 20, 2024
Alessio Mosca, Stefania Chiappini, Andrea Miuli et al.
5 citations
Piperazines, synthetic compounds with stimulant and hallucinogenic effects, are linked to acute psychotic episodes. A systematic review of 4 studies found that piperazine abuse frequently triggers symptoms such as paranoia, auditory, and visual hallucinations. The compounds' complex polyreceptor action may explain these effects, similar to other novel psychoactive substances. Recovery is common after cessation and treatment, but data on long-term outcomes are limited. Further research into piperazine abuse and specific treatment protocols for substance-induced psychosis is needed.
Transl Psychiatry
October 31, 2025
Giacomo D’andrea, Stefania Chiappini, Laura Ciavoni et al.
3 citations
Psychedelics and ketamine/esketamine show promise for treating depressive disorders by inducing rapid and sustained antidepressant effects. The review examines their biological mechanisms, including modulation of glutamate and serotonin systems, promotion of neuroplasticity, and changes in brain connectivity and network function. Neuroimaging studies reveal alterations in default mode network, fronto-limbic connectivity, and thalamic activity. Clinical changes are associated with these brain alterations, though the precise relationships remain under investigation. The work synthesizes current evidence on how these compounds produce observable brain changes and symptom improvement, highlighting the need for further research to clarify mechanisms and optimize therapeutic applications.
Current Neuropharmacology
February 20, 2025
Alessio Mosca, Stefania Chiappini, Gianluca Mancusi et al.
3 citations
Abusing certain over-the-counter medications can trigger psychotic symptoms such as paranoia, hallucinations, and thought disorders. Antihistamines, dextromethorphan, and other OTC drugs are implicated. Dextromethorphan misuse is especially linked to chronic psychosis, while other substances more often cause acute substance-induced psychosis. The review analyzed 46 relevant studies from an initial pool of 2,677 articles, highlighting the need for greater awareness and interventions to address OTC drug misuse and its psychiatric consequences.
Clinical Neuropsychopharmacology and Addiction
September 25, 2025
Stefania Chiappini, Clara Cavallotto, Andrea Miuli et al.
2 citations
About 30–50% of patients with major depression do not respond to two or more antidepressant trials, a condition called treatment-resistant depression (TRD). A narrative review of 60 studies found that glutamatergic agents such as intravenous ketamine and intranasal esketamine consistently produce rapid and clinically meaningful reductions in depressive symptoms. Augmentation with atypical antipsychotics also helps partial responders. Psychedelic-assisted therapies show sustained antidepressant benefits and affect biomarkers like BDNF and inflammatory markers. The findings suggest a shift toward personalized, mechanism-driven treatments for TRD, with ketamine and esketamine offering rapid relief for acute high-risk cases and psychedelics remaining experimental but promising as adjunctive options.
Brain Sci
September 17, 2025
Alessio Mosca, Stefania Chiappini, Andrea Miuli et al.
1 citation
Synthetic cannabinoids can cause psychosis that is often severe and difficult to treat. This systematic review examined published case reports and case series to identify effective treatment strategies. The review found that benzodiazepines and antipsychotics are commonly used, but many patients require intensive care and prolonged hospitalization. No single treatment protocol emerged as clearly superior, and outcomes varied widely, with some patients recovering fully while others experienced persistent psychotic symptoms. The authors suggest that early recognition and aggressive management may improve outcomes, but more research is needed to establish standardized treatment guidelines.
The International Journal of Neuropsychopharmacology
February 1, 2025
Clara Cavallotto, Giacomo D’andrea, Andrea Miuli et al.
1 citation
In patients with treatment-resistant depression, combining the antidepressant vortioxetine with esketamine nasal spray was as effective as the standard combination of an SSRI or SNRI with esketamine in reducing depressive symptoms over three months. The vortioxetine combination showed a larger effect in reducing emotional blunting and was linked to fewer treatment-emergent side effects, including dissociative symptoms. These findings suggest vortioxetine plus esketamine may be a valuable alternative, though larger randomized trials are needed to confirm the results.
Journal of Substance Use and Addiction Treatment
July 1, 2026
Alessio Mosca, Stefania Chiappini, Andrea Miuli et al.
Management of ketamine misuse relies on supportive care, psychotherapy, and off-label medications, but robust evidence is lacking. A systematic review of 73 studies found that approaches include symptomatic medical care, psychotherapeutic interventions such as motivational interviewing and cognitive-behavioral therapy, and pharmacological treatments including benzodiazepines, SSRIs, naltrexone, lamotrigine, and gabapentinoids, with varying effectiveness. Multidisciplinary strategies addressing both psychiatric and somatic complications, such as 'K-bladder' and 'K-cramps', are essential. High relapse rates and limited follow-up weaken the evidence, and there is an urgent need for controlled studies and standardized treatment protocols.
Clinical Neuropsychopharmacology and Addiction
March 10, 2026
Filippo Maria Ferro, Alessio Mosca
Substance-induced psychoses may help uncover mechanisms behind psychotic disorders and clarify the phenomenological specifics of schizophrenia. Some patients do not fully recover after an episode, suggesting persistent psychotic trajectories distinct from both acute substance-induced psychosis and primary psychotic disorders. The concept of Substance-Related Exogenous Psychosis positions exogenous psychoses as related to, but not identical with, schizophrenia. Drawing on classical psychopathology and recent self-disorder research, substance-induced psychoses can serve as heuristic models for exploring psychosis genesis. Comparisons using the EASE interview show similarities but also differences: substance-induced psychoses involve more superficial, transient self-alterations, while schizophrenia involves deeper, structurally embedded disturbances. This framework aims to guide future longitudinal studies.
Annals of general psychiatry
November 25, 2025
Luisa De Risio, Alessio Mosca, Arianna Pasino et al.
Anomalous self-experiences (ASEs), disturbances in the sense of a minimal self, are considered a core feature of primary psychotic disorders (PPDs) like schizophrenia, but it was unclear whether they also occur in substance-induced psychosis (SIP). This study compared ASEs in 27 clinically stable patients with schizophrenia spectrum disorders (SSD, mean age ~27) and 27 with SIP (mean age ~28) using the EASE interview. Total ASE scores did not differ between groups. However, SIP patients showed significantly higher disturbances in self-world boundary (Domain 4), while SSD patients trended higher in self-awareness and presence (Domain 2) and existential reorientation (Domain 5). These findings suggest ASEs are not exclusive to primary psychoses and challenge the assumption that self-disorders are unique to endogenous psychosis.