International Journal of Molecular Sciences
September 23, 2018
Domenico de Berardis, Michele Fornaro, Alessandro Valchera et al.
171 citations
Suicide remains difficult to predict despite advances in neuroscience. The World Health Organization reports one million suicide deaths annually, with one every 40 seconds. Recent genomic studies suggest genetics influence suicide risk. Combining genomic and clinical assessments has identified biomarkers for suicidal ideation involved in neural connectivity, mood, and immune response, including the mammalian target of rapamycin (mTOR) signaling pathway. This provides a neurobiological basis for drugs like ketamine, an NMDA antagonist, which has shown rapid antidepressant and anti-suicidal effects. This review examines preclinical and clinical evidence for ketamine's efficacy in treating suicidal ideation in mood disorders, addressing the neurobiological processes of suicide and potential therapeutics.
Frontiers in Psychiatry
November 20, 2017
Laura Orsolini, Gabriele Duccio Papanti, Domenico de Berardis et al.
99 citations
Hallucinogen-persisting perception disorder (HPPD) is a syndrome of prolonged or recurring perceptual symptoms resembling acute hallucinogen effects. It has been linked to LSD, cannabis, MDMA, psilocybin, mescaline, and psychostimulants, and more recently to novel psychoactive substances. Symptoms are mainly visual, including geometric pseudo-hallucinations, haloes, flashes of light, motion-perception deficits, afterimages, and micropsia, though depressive and thought disorders may co-occur. First described in 1954, HPPD was formally recognized as a syndrome in the DSM-IV-TR in 2000. Its neural substrates, risk factors, and causes remain largely unknown. This mini review surveys psychopathological bases, etiological hypotheses, and psychopharmacological approaches, including associations with novel substances, based on a literature search of PubMed/Medline, Google Scholar, and Scopus without time restrictions.
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.
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 Topics in Medicinal Chemistry
January 31, 2020
Domenico de Berardis, Carmine Tomasetti, Maurizio Pompili et al.
38 citations
Abnormalities in glutamatergic neurotransmission are hypothesized to play a role in mood disorders, prompting investigation of NMDA receptor modulators for Major Depressive Disorder (MDD). Intranasal esketamine, an NMDA receptor antagonist, has been developed for treatment-resistant depression (TRD) and for rapidly reducing depressive symptoms, including suicidal ideation, in MDD patients at imminent suicide risk. A systematic review of literature up to October 2019 found that intravenous esketamine elicits rapid and sustained antidepressant effects in refractory patients. Phase II studies showed intranasal esketamine had rapid onset and persistent efficacy in TRD and MDD patients at suicide risk, though phase III data had discrepancies.
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.
Frontiers in Psychiatry
May 22, 2018
Laura Orsolini, Michela Ciccarese, Duccio Papanti et al.
25 citations
A new 'psychedelic trend' has emerged, driven by psychonauts who consume a variety of novel psychoactive substances (NPS) from animals. This review identifies several species—including ants, amphibians, and fish—that possess psychoactive properties and are abused recreationally. Routes of administration vary by animal, substance, metabolism, toxicity, and cultural context. Online access to these animals is facilitated through tourism-related search terms such as 'frog trip' and 'religious trip.' The review combines online psychonaut reports with literature searches from PubMed/Medline and Google Scholar to provide an overview of commonly abused 'psychedelic animals.'
Current Neuropharmacology
October 20, 2025
Vassilis Martiadis, Fabiola Raffone, Danilo Atripaldi et al.
21 citations
A single dose of esketamine quickly reduced suicidal thoughts and depression in people with treatment-resistant depression. Preliminary evidence suggests that men and women may respond differently, indicating that personalized treatment approaches could improve results. More research is needed to confirm these gender differences, examine long-term effects, and understand the biological reasons behind them.
Psychiatry Research
July 26, 2025
G. D’andrea, C. Cavallotto, M. Pettorruso et al.
16 citations
Anhedonia, the reduced ability to experience pleasure, is a core symptom of both unipolar and bipolar depression that often responds poorly to standard antidepressants. In a real-world observational study of 253 treatment-resistant patients (199 with unipolar depression, 54 with bipolar depression), repeated doses of esketamine nasal spray added to ongoing medication significantly reduced anhedonia over three months. The effect was distinct from overall mood improvement. At three months, 51.92% of bipolar and 38% of unipolar patients showed at least a 50% reduction in anhedonia scores. Dropout rates were low (around 13–14%), and manic switches were rare. The findings suggest esketamine has a targeted, transdiagnostic anti-anhedonic effect.
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.
Diseases
November 3, 2023
Kainat Riaz, Sejal Suneel, Mohammad Hamza Bin Abdul Malik et al.
16 citations
Half of patients with post-traumatic stress disorder (PTSD) do not respond to traditional therapies. A review of six phase II randomized controlled trials indicates that MDMA-assisted psychotherapy can reduce PTSD symptoms even in treatment-resistant cases. MDMA appears to work 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 how it might fit into existing PTSD treatment options.
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.
Alpha psychiatry
April 1, 2025
Francisco López-Muñoz, Pilar D'Ocón, Alejandro Romero et al.
3 citations
Most new antidepressants, including SSRIs, SNRIs, and other modern classes, were developed through rational, targeted design rather than chance. Only moclobemide and ketamine involved serendipity: moclobemide's antidepressant effect was discovered after chance observation of MAO inhibition during antihyperlipidemic research, and ketamine's antidepressant properties emerged from illicit use observations, not its original development as an anesthetic. The majority follow a type IV pattern where serendipity played no role.
European Psychiatry
March 1, 2016
Laura Orsolini, Alessandro Valchera, Duccio Papanti et al.
3 citations
Hallucinogen Persisting Perception Disorder (HPPD) is a syndrome marked by prolonged or recurring perceptual symptoms similar to acute hallucinogen effects, associated with substances like LSD, cannabis, MDMA, psilocybin, and mescaline. Symptoms mainly involve visual disturbances such as geometric pseudo-hallucinations, halos, flashes of light, motion-perception deficits, afterimages, and micropsy, though depressive and thought disorders may co-occur. First described in 1954, HPPD was formally established as a syndrome in the DSM-IV-TR in 2000. The neuronal substrate, risk factors, etiology, and pathogenesis remain unknown and under investigation. This critical review covers psychopathological bases, etiological hypotheses, and psychopharmacological approaches, presenting a case report and offering practical clinical recommendations.
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.
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.
Clinical Neuropsychopharmacology and Addiction
June 25, 2026
Luca Persico, Giacomo D’andrea, Clara Cavallotto et al.
Intranasal esketamine substantially reduced depression severity in 210 patients with treatment-resistant depression treated in routine clinical practice. Depression scores improved markedly over three months, and men showed a modest advantage over women by the end of treatment, with lower depression ratings and higher rates of response and remission. Among patients under 65 years, sex differences were small and not statistically significant; among those 65 and older, men appeared to benefit more numerically, but this difference did not hold up after statistical correction and remains uncertain. Discontinuation rates and safety outcomes were similar between sexes. The authors call for future studies to examine hormonal, vascular, inflammatory, and other factors that might explain the observed sex differences.
Preprints.org
April 29, 2026
Stefano Marini, Domenico de Berardis
preprint
Psychedelic drugs, both natural and synthetic, act on serotonin receptors and may enhance cognition, brain connectivity, neuroplasticity, and neuronal regeneration. Autism spectrum disorder involves social communication difficulties and repetitive behaviors, with no approved drugs for core symptoms. Current treatments for co-occurring conditions often have uncertain efficacy and tolerability. This review reports studies indicating that psychedelics could be therapeutically useful for some autism-related symptoms, suggesting a potential role in treatment.
Mental Wellness
April 21, 2026
Mohsen Khosravi, Domenico de Berardis, Massimo Tusconi
A systematic review and meta-analysis of 13 clinical trials with 606 participants found no statistically significant overall antidepressant effect of psilocybin-assisted psychotherapy for major depressive disorder and treatment-resistant depression. The pooled standardized mean difference was -0.79 with a 95% confidence interval from -3.98 to 2.40, and extreme heterogeneity across studies was observed. The type of control group accounted for most of the variation between studies, with waitlist and low-dose comparators exaggerating effect sizes. Session frequency moderated outcomes, with 2 to 5 sessions yielding larger effects and more intensive protocols reducing benefit. Psilocybin's antidepressant efficacy appears highly context-dependent rather than universally robust.
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.