Preprints.org
Kainat Riaz, Sejal Suneel, Mohammad Hamza Bin Abdul Malik et al.
1 citation
preprint
Half of patients with post-traumatic stress disorder (PTSD) do not respond to standard pharmacotherapy or psychotherapy. A review of six phase II randomized controlled trials indicates that MDMA-assisted psychotherapy can reduce PTSD symptoms, even in treatment-resistant cases, by increasing neurohormones such as dopamine, serotonin, norepinephrine, and oxytocin and by modulating brain regions involved in fear and anxiety. The FDA has granted MDMA-assisted psychotherapy a "Breakthrough Therapy" designation. Further research is needed to determine whether the benefits outweigh the risks and whether this approach can be integrated into existing treatment options.
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.
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.
Translational Psychiatry
June 24, 2026
Mauro Pettorruso, Giacomo D’andrea, Antonio Inserra et al.
Emerging clinical and preclinical evidence suggests that the therapeutic benefits of psychedelics for depression and anxiety may be separable from their consciousness-altering effects. Psychedelics produce profound brain changes, including suppression of the default mode network, leading to intense subjective experiences such as ego dissolution. These effects require extensive preparation and integration, exclude individuals with certain psychiatric vulnerabilities, and raise scalability concerns. Pharmacological strategies like serotonin 2A receptor antagonism and development of biased psychedelic analogues might retain therapeutic efficacy without psychedelic experiences. Preclinical data indicate that downstream molecular and network-level mechanisms could mediate therapeutic effects independently of subjective states. Confirming this dissociation could enable more scalable, accessible treatments for broader psychiatric populations.
Psychiatry research
June 16, 2026
Filippo Mazzoni, Fabiola Raffone, Arianna De Ciechi et al.
Among 90 outpatients with treatment-resistant depression, half also had borderline personality disorder (BPD). Depressive symptoms, measured by the MADRS scale, improved substantially over six months of intranasal esketamine treatment. The BPD group showed faster early improvement, and from one month onward had higher response rates (≥50% reduction in symptoms). Remission rates at six months were similar between groups (48.9% with BPD vs. 57.8% without). Anxiety and impulsivity decreased across the whole sample, and cognitive function did not worsen. No serious adverse events or dropouts occurred. Comorbid BPD did not hinder the overall remission outcome.
European psychiatry : the journal of the Association of European Psychiatrists
June 10, 2026
Riccardo Guglielmo, Miriam Olivola, Alberto Inuggi et al.
Over six months of routine esketamine treatment for treatment-resistant depression, depressive symptoms and daily functioning both improved progressively. By month six, 78.3% of patients showed a symptomatic response and 46.7% reached symptomatic remission, while 78.3% showed a functional response but only 33.3% achieved functional remission. Functional remission accumulated more slowly than symptomatic remission, with cumulative rates of 5% at one month, 15% at three months, and 33.3% at six months. Higher baseline disability and more previous antidepressant trials were linked to lower odds of functional remission at six months. The findings suggest that functional improvement follows a distinct trajectory from symptom improvement and should be monitored separately in treatment-resistant depression.
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.
Clinical Neuropsychopharmacology and Addiction
April 17, 2026
Antonio Inserra, Francesca Zoratto, Mauro Pettorruso et al.
No Summary
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.
The International Journal of Neuropsychopharmacology
August 1, 2025
Giovanni Martinotti, Clara Cavallotto, G D’andrea et al.
Psilocybin, a psychedelic compound that acts on serotonin receptors, shows promise for treatment-resistant depression, with remission rates up to 70% in some studies. The antidepressant and psychedelic effects may be separable, with the latter linked to 5-HT2A receptors. By co-administering the 5-HT2A antagonist ketanserin, psilocybin's hallucinogenic effects can be minimized, reducing bias from the mystical experience and improving clinical feasibility. A proposed study will randomly assign 68 treatment-resistant depression patients to receive either non-psychedelic psilocybin (two 25 mg doses, preceded by ketanserin) or accelerated repetitive transcranial magnetic stimulation (arTMS). Outcomes will be compared at day 60 using psychometric tests, EEG, and fMRI.
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.