CNS Spectrums
June 25, 2020
Giovanni Martinotti, Luisa de Risio, Chiara Vannini et al.
102 citations
About 25% of first-episode psychoses are substance-induced. The DSM-5 definition assumes symptoms are transient and disappear after sustained abstinence, but this does not account for persistent cases. A new diagnostic framework is needed to differentiate comorbid conditions from substance-related psychoses. The authors propose a novel clinical entity called substance-related exogenous psychosis (SREP), covering both transient and persistent psychoses linked to substance use. SREP is distinct from schizophrenia, characterized by altered consciousness, persecutory delusions, visual and cenesthetic hallucinations, impulsivity, psychomotor agitation, affective and negative symptoms, a pervasive feeling of unreality, and intact insight. Delusions are secondary to abnormal perception from a 'sensorialization' of the world. Longitudinal studies are needed to validate this category.
Psychiatry Research
July 29, 2023
Mauro Pettorruso, Roberto Guidotti, Giacomo D’andrea et al.
56 citations
Machine learning models predicted which patients with treatment-resistant depression would respond to esketamine nasal spray. In a retrospective study of 149 patients, three random forest classifiers achieved 68.53% accuracy for response at one month and 66.26% at three months, and 68.60% accuracy for remission at three months. Features such as severe anhedonia, anxious distress, mixed symptoms, and bipolarity positively predicted response and remission, while benzodiazepine use and depression severity were linked to delayed responses. The findings suggest machine learning may aid personalized treatment decisions for treatment-resistant depression.
Psychiatry Research
August 18, 2025
Ilenia Rosa, L. Padula, Francesco Semeraro et al.
2 citations
Treatment-resistant depression (TRD) challenges standard approaches, prompting a shift toward non-monoaminergic interventions like neuromodulation and glutamatergic agents. This narrative review examines the endocannabinoid system (ECS) as a potential common pathway for these treatments. Evidence indicates that repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT) increase endocannabinoids anandamide and 2-arachidonoylglycerol, correlating with clinical improvement. Ketamine and esketamine modulate CB1 receptors, while psilocybin restores 2-AG and enhances CB1 expression in mood-related brain regions. These findings suggest ECS modulation may unify diverse antidepressant mechanisms in TRD, offering a promising target for novel therapies.
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.