Psychological Medicine
July 22, 2019
Fabrizio Schifano, Flavia Napoletano, Stefania Chiappini et al.
118 citations
A novel web-crawling tool called NPS.Finder® identified several thousand new psychoactive substances (NPS)—roughly four times more than European and international drug agencies report. Synthetic cannabinoids, new synthetic opioids, ketamine-like dissociatives, novel stimulants, novel psychedelics, and certain prescription and over-the-counter medicines were most commonly linked to psychopathological consequences. The rapid proliferation of recreational psychotropics poses a challenge for psychiatry because the pharmacodynamics and pharmacokinetics of many NPS remain poorly understood. Health and mental health professionals need up-to-date information on the range of NPS, their intake methods, sought-after effects, drug combinations, and associated medical and psychopathological risks.
Experimental neurology
May 1, 2021
Fabrizio Schifano, Stefania Chiappini, Andrea Miuli et al.
49 citations
Several new psychoactive substances (NPS) can trigger serotonin syndrome, a dangerous condition of excessive serotonin activity marked by altered mental status, neuromuscular effects, and autonomic hyperactivity. A systematic review of three retrospective studies, two case series, and five case reports identified implicated substances including psychedelic phenethylamines (2C-I, 25I-NBOMe, 5-IT) and synthetic cathinones (mephedrone, MDPV, methylone, butylone, NRG3, AMT, MXP), as well as the antidepressant bupropion when misused at high doses or combined with other serotonergic drugs. Most substances were taken orally, though nasal insufflation and sublingual administration occurred. Psychiatric history was negative for most subjects. Clinicians should recognize NPS risks and diagnostic challenges due to undetectability in routine drug screenings.
Frontiers in Psychiatry
November 20, 2019
Laura Orsolini, Stefania Chiappini, Duccio Papanti et al.
41 citations
The spread of novel psychoactive substances (NPS), especially among young people, raises concerns about psychosis linked to synthetic drugs. These 'new psychoses' differ clinically from classical psychosis. This mini-review synthesizes clinical and psychopathological features of NPS-induced psychoses and their treatment, based on a PubMed/Medline search for synthetic cannabinoids and cathinones. It contrasts classical psychoses with NPS-induced ones and offers therapeutic guidelines for clinicians in addiction psychiatry.
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.
Human psychopharmacology
May 1, 2020
Laura Orsolini, Stefania Chiappini, Duccio Papanti et al.
27 citations
Ayahuasca, a hallucinogenic plant preparation used in sacred ceremonies by indigenous Amazonian groups, may offer therapeutic benefits for mental health. Evidence from preclinical, observational, and experimental studies suggests it acts as a fast-acting and enduring antidepressant, emotional regulator, anxiolytic, and antiaddictive drug. It appears safe and well tolerated, with nausea and vomiting as the most common transient side effects. However, findings indicate it should not be used in bipolar or psychotic patients due to increased risk of manic switch or psychotic onset. Further research with randomized, double-blind, placebo-controlled trials and neuroimaging is needed to better evaluate its therapeutic potential in mental disorders.
Expert review of neurotherapeutics
April 1, 2025
Stefania Chiappini, Gaia Sampogna, Antonio Ventriglio et al.
17 citations
Depression involves a wide range of emotional, cognitive, and physical symptoms that disrupt daily life. Societal changes such as technological advances, economic pressures, climate change, and shifting cultural norms have altered how depression appears and is understood, leading to the identification of new depression subtypes. These include depression in adolescents and young adults, depression with social disconnection, depression with alcohol or substance use disorder, depression with gender dysphoria, and depression linked to stressful events and environmental factors. Managing these subtypes requires individualized treatment approaches. While SSRIs and SNRIs remain standard, atypical antidepressants like trazodone, ketamine, neuromodulation, and personalized psychotherapy offer hope for complex or treatment-resistant cases.
Pharmaceuticals (Basel, Switzerland)
March 31, 2024
Maria Pepe, Marco Di Nicola, Fabrizio Cocciolillo et al.
6 citations
The psychoactive substance 3-MeO-PCP, a type of NMDA receptor antagonist, can cause persistent psychotic symptoms and cognitive impairment. A literature review and case report describe a 29-year-old man who developed substance-induced psychotic disorder after small oral intakes over two weeks, culminating in a high dose. Psychometric tests, neuropsychological assessment, and brain PET-CT imaging revealed lasting effects. Identifying the clinical features and neural substrates of NPS-induced psychoses may help distinguish them from other psychotic disorders and guide tailored treatments.
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.
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.
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.