Giovanni Martinotti

• MD, PhD, PhB, MAA
• Lecturer at University of Chieti-Pescara

Substance use and the emergence of Novel Psychoactive Substances (NPS) present a significant public health challenge and diagnostic dilemma, particularly in the context of psychosis. The increasing availability of psychoactive substances among youth has led to a rise in Substance Use Disorders (SUDs), with profound implications for mental health. T...

Xylazine, traditionally used as a veterinary sedative, has recently emerged as a new psychoactive substance, being typically ingested in combination with fentanyl derivatives and hence raising significant public health concerns. Despite its increasing prevalence, little is known about its molecular interactions with human neuroreceptors, specifical...

Background The widespread availability and accessibility of over-the-counter (OTC) medicines play a vital role in modern healthcare systems, enabling individuals to manage minor health concerns independently. However, certain OTC medications possess pharmacological properties that render them susceptible to misuse and abuse, including stimulants, l...

Background Childhood traumas have long been recognized as pivotal determinants in the progression and severity of depressive disorders, especially in treatment-resistant depression (TRD). These early life adversities can induce distinct neurostructural and functional alterations, potentially mediating the responsiveness to antidepressant therapies....

Background Alcohol/Substance Use Disorder (AUD/SUD) among schizophrenic patient represent a common and problematic co-occurrence, with a rate of comorbidity assessed between 40% and 70%, especially in young patients at the onset of their disorder (1-2). Comorbid patients are usually difficult to treat: they show a very low level of compliance, and...

Background Semaglutide is a medication used to treat type 2 diabetes and obesity, belonging to a class of drugs known as glucagon-like peptide-1 (GLP-1) receptor agonists [1]. GLP-1 is a hormone released in the intestine during the digestion of food helping to regulate blood sugar levels by stimulating the release of insulin. Semaglutide mimics the...

Background Repetitive transcranial magnetic stimulation (rTMS) is a promising neuromodulation technique for treating cocaine use disorders (CUDs) [1]. The brain-derived neurotrophic factor (BDNF) and its precursor proBDNF are critical neurotrophins altered in this disorder [2]. proBDNF is increased in patients in withdrawal and is positively relate...

Background Treatment-Resistant Depression (TRD) affects almost 30% of patients with Major Depressive Disorder (MDD) (1). Esketamine Nasal Spray (ESK-NS) has recently been approved for TRD in combination with a Serotonin Specific Reuptake Inhibitor/SSRI or a Serotonin-Norepinephrine Reuptake Inhibitor/SNRI. There is a lack of studies investigating t...

Background: Alcohol Use Disorders (AUD), affec-tive disorders, and personality disorders are among the most prevalent mental health conditions observed in individuals exhibiting suicidal behavior, encompassing both completed and attempted suicides. A robust association between AUD and suicidal behavior has been established through retrospective and...

Introduction/Objective Data on long-term treatment with Esketamine Nasal Spray (ESKNS) in real-world patients with treatment resistant depression (TRD) is scarce. The primary aim of the study is to evaluate the effectiveness and tolerability of ESK-NS treatment at 6 and 12-month follow-ups. Methods This is part of an observational, retrospective,...

Background Psychotic disorders, characterized by altered brain function, significantly impair reality perception. The neurodevelopmental hypothesis suggests these disorders originate from early brain development disruptions. Glial-derived neurotrophic factor (GDNF) is crucial for neuronal survival and differentiation, especially in dopaminergic neu...

Known as “designer drugs” or “legal highs,” new psychoactive substances (NPS), are a growing concern globally. These substances refer to synthetic or modified compounds designed, including synthetic cannabinoids, synthetic cathinones, synthetic opioids, and other compounds, mimicking the effects of traditional illicit drugs while avoiding legal res...

Background Methylphenidate (MPH), a central nervous system stimulant primarily prescribed for attention-deficit/hyperactivity disorder (ADHD), has seen increasing rates of misuse and abuse, particularly in patients with dual diagnosis (co-occurring psychiatric disorders and substance use disorders/SUDs). The heightened risk of dependence and advers...

Background Co-occurrence of substance use disorders is frequent in patients with mental health disorders is a condition known as “dual diagnosis”. The use of substances worsens the prognosis and lowers the quality of life of psychiatric patients. It also increases the risk of hospitalization and suicide rate. Objectives To assess the effects of ar...

Background: illegal drugs significantly contribute to global health issues, with health complications often occurring not only in regular users with Substance Use Disorders (SUDs) but also in first-time and occasional users. Methods: this study examines five clinical cases from a public hospital in Ibiza, Spain, where patients presented with acute...

Substance-induced psychosis (SIP) is an increasingly prevalent and complex condition that presents significant diagnostic and therapeutic challenges. With the rising use of novel psychoactive substances (NPSs) and potent traditional compounds like cannabis and cocaine, particularly among adolescents and young adults, understanding the mechanisms an...

Background: Piperazines, synthetic compounds known for their stimulant and hallucinogenic effects, have gained prominence among novel psychoactive substances (NPS) and are frequently associated with adverse psychiatric outcomes, including psychosis. Methods: A systematic review of the literature available up to 23 May 2024 was conducted, using the...

Despite the centrality of the diagnostic assessment in psychiatry, the diagnostic agreement among mental health practitioners often varies from poor to moderate. The potential of Large Language Models (LLMs; such as ChatGPT), among other approaches, has been studied to be used as standardized tools to support clinicians’ decision-making. The curren...

The psychopathological manifestations associated with substance use, including induced psychotic experiences , are increasingly relevant but not well-understood within the medical community. Novel psychoactive substances and potentiated old compounds like cannabis and cocaine have emerged as a global concern, especially among adolescents and young...

Treatment-Resistant Depression (TRD) poses a substantial health and economic challenge, persisting as a major concern despite decades of extensive research into novel treatment modalities. The considerable heterogeneity in TRD’s clinical manifestations and neurobiological bases has complicated efforts toward effective interventions. Recognizing the...

Instagram is the social network with the largest number of adolescent users in Italy; it is also the social network with the largest number of suicide‐related posts. Suicide is the third leading cause of death in Italy in the 15–19 age group. This study aims to describe Italian posts on Instagram related to suicide and to investigate whether there...

Glucagon-like peptide-1 (GLP-1) is involved in a range of central and peripheral pathways related to appetitive behavior. Hence, this study explored the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on substance and behavioral addictions, including alcohol, caffeine, nicotine, cannabis, psychostimulants, compulsive shopping, and...

Background Image and Performance-Enhancing Drugs (IPEDs) can enhance mental and physical capabilities and impact one’s overall health. Initially confined in sport environments, IPEDs use has become increasingly widespread in a high-performing society. The present study was aimed at profiling IPEDs use during the COVID-19 lockdown among an internati...

Background and objectives Schizophrenia is a chronic, complex mental health disorder requiring effective management to mitigate its broad personal and societal impacts. This narrative review assesses the efficacy, effectiveness, and side effects of third-generation antipsychotics (TGAs) like aripiprazole, brexpiprazole, and cariprazine, focusing on...

The widespread use of novel psychoactive substances (NPSs)-defined as new narcotic or psychotropic agents not classified under the Single Convention on Narcotic Drugs of 1961 or the Convention on Psychotropic Substances of 1971-poses a significant challenge to contemporary mental health paradigms due to their impact on psychiatric disorders. This s...

The role of dopamine in the pathophysiology of gambling disorder (GD) remains incompletely understood, with disparate research findings concerning presynaptic and postsynaptic structures and dopaminergic synthesis. The aim of this study was to investigate potential correlations between striatal dopamine transporter (DAT) lateralization and asymmetr...

Objective: The Psychological-Physical-Pain Visual Analogue Scale (PPP-VAS) was thought to probably help in identifying patients at risk of suicide. However, no data on its validity to measure psychological pain was available. Our main aim was to investigate the convergent validity of the PPP-VAS using two well-validated scales of psychological pain...

Background: Dual disorders (DDs) involve the coexistence of a substance use disorder (SUD) with another mental illness, often from the psychotic and affective categories. They are quite common in clinical practice and present significant challenges for both diagnosis and treatment. This study explores the effectiveness of brexpiprazole, a third-gen...

b> Background: The state of twilight consciousness is marked by a focused narrowing of awareness, maintaining vigilance and attention while simultaneously experiencing perceptual shifts in the surrounding environment. It is crucial to recognize that this twilight state represents not just a contraction but also an expansion of conscious experience....

Background: Dual disorders (DD) entail the coexistence of a substance use disorder (SUD) and another mental health condition, often within psychotic and affective disorders. This study aims to evaluate lurasidone, an innovative atypical antipsychotic, in individuals diagnosed with schizophrenia spectrum disorder and concurrent comorbidities of alco...

There is only limited epidemiological information on Orthorexia Nervosa; the aim of the present study is, therefore, to assess the prevalence of ON in a population of young adults and to identify possible specific features and eventual psychopatological dimensions. 1317 participants (732 females and 585 males; mean age 22.36 yrs) completed a batter...

New Psychoactive Substances (NPS) are modifying the drug scenario worldwide and have become a public health concern because of their toxicological profiles and their harmful physical/psychological effects. 3-Methoxy-Phencyclidine (3-MeO-PCP), a non-competitive antagonist of glutamate N-methyl-D-aspartate (NMDA) receptors, belongs to the phencyclidi...

Introduction: Intravenous ketamine (KET-IV) and intranasal esketamine (ESK-NS) are effective in the acute treatment of Treatment-Resistant Depression (TRD). Studies comparing KET-IV and ESK-NS concerning their action, safety, and tolerability are currently lacking.Materials and methods: We combined patients' data from two unipolar TRD cohorts that...

Major depressive disorder (MDD) is prevalent and disabling among older adults. Standing on its tolerability profile, vortioxetine might be a promising alternative to selective serotonin reuptake inhibitors (SSRIs) in such a vulnerable population. We conducted a randomised, assessor- and statistician-blinded, superiority trial including older adult...

Adolescence is marked by increased susceptibility to trauma-related disorders and substance and behavioral addictions (SBAs). Complex post-traumatic stress disorder (cPTSD) is a newly recognized condition characterized by specific features in addition to those of classic PTSD and is often associated with SBAs. This study adopted a psychopathology n...

The connections between sexual abuse and abuse of alcohol or drugs are varied and bidirectional, with most sexual assaults involving substance consumption by the perpetrator, the victim, or both [1].

Background: Dual disorders (DD) involve the coexistence of substance use disorder (SUD) with another mental illness, often from psychotic and affective categories. This study explores the ef-fectiveness of brexpiprazole, a third-generation antipsychotic, in individuals diagnosed with schizophrenia spectrum disorder (DSM-V) and comorbid AUD/SUD (DSM...

Background Natural Cannabis (NC) and Synthetic Cannabinoids (SCs) use can increase the risk and exacerbate the course of psychotic disorders. These could be influenced by the Aberrant Salience (AS) construct. It refers to an excess of attribution of meaning to stimuli that are otherwise regarded as neutral, thereby transform them into adverse, dang...

Brain-derived neurotrophic factor (BDNF) and its precursor, proBDNF, are known to significantly contribute to brain homeostasis, neuroplasticity, and neuronal remodeling. Although these neurotrophins are thought to have opposing roles, both play a critical part in shaping long-lasting behavioral changes following substance use. In this context, our...

Background A better characterization of educational processes during psychiatry training is needed, both to foster personal resilience and occupational proficiency. Methods An adequate coverage of medical residents at the national level was reached (41.86% of the total reference population, 29 out of 36 training centers—80.55%). Controls were recru...

Background: Cannabis is the most used recreational drug worldwide. Its use can increase the risk of developing psychotic disorders and exacerbate their course. However, little is known about the relationship between psychosis and withdrawal and the literature is still scarce. Case presentation: In this study, based on an analysis of 4 patients r...

Purpose/background: Based on a population-pharmacokinetic model, the European Medicines Agency has recently approved a simplified starting strategy of aripiprazole once a month (AOM), injectable and long-acting antipsychotic, with two 400 mg injections and a single oral 20 mg dose of aripiprazole, administered on the same day, instead of 1 injecti...

The role of the thalamus in mediating the effects of lysergic acid diethylamide (LSD) was recently proposed in a model of communication and corroborated by imaging studies. However, a detailed analysis of LSD effects on nuclei-resolved thalamocortical connectivity is still missing. Here, in a group of healthy volunteers, we evaluated whether LSD in...

This case report was conducted by searching for the following keywords on PubMed: High Functioning Autism, Autism Spectrum Disorder, cariprazine, aripiprazole, partial agonist antipsychotic, DRD2/DRD3. High Functioning Autism (HFA) is a neurodevelopmental disorder characterized by the core symptoms of autism spectrum disorder (ASD) with average int...

Background Treatment-resistant depression (TRD) is defined by the European Medicines Agency as a lack of clinically meaningful improvement after treatment, with at least two different antidepressants. Individual, familiar, and socio-economic burden of TRD is huge. Given the lack of clear guidelines, the large variability of TRD approaches across di...

Post-traumatic stress disorder (PTSD) is a debilitating mental health disorder that causes significant dysfunction in individuals. Currently, there are many approved pharmacotherapy and psychotherapy treatment options for PTSD, but unfortunately, half of the patients do not respond to traditional therapies. In this article, we review clinical trial...

The term “dissociation” encompasses a wide array of symptoms and phenomena, all sharing the common characteristic of involving altered states of consciousness where an individual temporarily loses the sense of continuity of their own identity. In the context of addiction pathology, however, the dissociative paradigm remains a topic of ongoing debat...

Background: Autistic symptoms represent a frequent feature in people with schizophrenia spectrum disorders (SSD), with a significant impact on clinical, cognitive and functional outcomes. However, the prevalence and the cognitive and functional correlates of autistic symptoms in unaffected first-degree relatives of people with SSD remain to be asse...

The emergence of glucagon-like peptide-1 receptor agonists (GLP-1 RAs; semaglutide and others) now promises effective, non-invasive treatment of obesity for individuals with and without diabetes. Social media platforms’ users started promoting semaglutide/Ozempic as a weight-loss treatment, and the associated increase in demand has contributed to a...

Proof of correlation between psychotic spectrum disorders and suicide are found in literature, as well as between cannabis use disorder (CUD) and suicide and between CUD and schizophrenia. The study population of the selected papers consists of subjects diagnosed with schizophrenia spectrum or cannabis or SCs induced psychosis. Our objective is to...

Introduction: The challenges posed by treatment-resistant schizophrenia and depressive symptoms have led to ongoing difficulties despite the availability of antipsychotics and antidepressants. This review addresses the potential of amisulpride analogs, particularly SEP-4199, in addressing these challenges through enhanced efficacy and reduced side...

Rapid Cyclic Bipolar Disorder (RCBD) is a debilitating condition that manifests as four or more episodes of depression, mania, or hypomania in a span of one year, with depression being the predominant event. RCBD is prevalent among individuals diagnosed with bipolar disorder and is associated with elevated suicide risk, prolonged disease duration,...

Recent media reports commented about a possible antidiabetics’ misuse issue related to molecules promoted as a weight-loss treatment in non-obese people. We evaluated here available pharmacovigilance misuse/abuse signals related to semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, in comparison to other GLP-1 receptor agonists (albiglutide;...

Background: The association between cannabis use and positive symptoms in schizophrenia spectrum disorders is well documented, especially via meta-analyses. Yet, findings are inconsistent regarding negative symptoms, while other dimensions such as disorganization, depression, and excitement, have not been investigated. In addition, meta-analyses us...

Background: The association between cannabis use and positive symptoms in schizophrenia spectrum disorders is well documented, especially via meta-analyses. Yet, findings are inconsistent regarding negative symptoms, while other dimensions such as disorganization, depression, and excitement, have not been investigated. In addition, meta-analyses us...

Introduction and Aim Psychotic and mood disorders are associated with significant functional impairment, premature mortality, physical morbidity, and great social and economic burden. The aim of this study is to evaluate the effectiveness of psychosocial, psychological, and rehabilitative interventions implemented in an Italian psychiatric inpatien...

Background: Cannabis is the most widely used illicit substance. Numerous scientific evidence confirm the strong association between cannabis and psychosis. Exposure to cannabis can induce the development of psychosis and schizophrenia in vulnerable individuals. However, the neurobiological processes underlying this relationship are unknown. Neurot...

Post-traumatic stress disorder (PTSD) is a debilitating mental health disorder that causes significant dysfunction in individuals. Currently, there are many approved Pharmacotherapy and Psychotherapy treatment options for PTSD, but unfortunately, half of the patients do not respond to traditional therapies. In this article, we reviewed clinical tri...

Cognitive impairment has been associated with poor real-world functioning in patients with Schizophrenia. Previous studies have shown that pharmacological treatment with anticholinergic properties may contribute to cognitive impairment in Schizophrenia. We investigated the effect of the anticholinergic burden (ACB) on brain activity, cognition, and...

Background: Different craving typologies (i.e., reward, relief, obsessive) have been identified in alcohol use disorder (AUD) but have been less investigated in specific populations like AUD patients with polysubstance use (PSU). The role of dysfunctional personality traits and reward pathways has been reported in both AUD and PSU. We hypothesized...

Recent media reports commented about a possible issue of the misuse of antidiabetics related to molecules promoted as a weight-loss treatment in non-obese people. We evaluated here available pharmacovigilance misuse/abuse signals related to semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, in comparison to other GLP-1 receptor agonists (albi...

Introduction: Treatment-resistant depression (TRD) is a serious and debilitating psychiatric disorder that frequently affects older patients. Esketamine nasal spray (ESK-NS) has recently been approved as a treatment for TRD, with multiple studies establishing its efficacy and tolerability. However, the real-world effectiveness, tolerability, and sa...

Treatment-resistant depression (TRD) represents a severe clinical condition with high social and economic costs. Esketamine Nasal Spray (ESK-NS) has recently been approved for TRD by EMA and FDA, but data about predictors of response are still lacking. Thus, a tool that can predict the individual patients’ probability of response to ESK-NS is neede...

Purpose This paper aims to investigate the role of aripiprazole once monthly as a maintenance treatment in a sample of patients with schizophrenia comorbid with alcohol and substance use disorder (AUD/SUD). Design/methodology/approach A sample of 24 Italian adult patients has been recruited and treated with aripiprazole once monthly after clinical...

Recent media reports commented about a possible antidiabetics’ misuse issue related to molecules promoted as a weight-loss treatment in non-obese people. We here evaluated available pharmacovigilance misuse/abuse signals related to semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, in comparison to other GLP-1 receptor agonists (albiglutide;...

Introduction: Internet gaming disorder (IGD) is an emerging condition within the field of behavioural addictions. IGD has been demonstrated to be highly comorbid with many other mental health disorders. Among these, substance use has been associated with IGD, and there are underlying similarities between behavioural addictions and substance use di...

Objective: Peripartum depression is defined as the onset of depressive symptoms during pregnancy or within 12 months postpartum and affects 11.9% of women. Currently, its treatment often involves psychotherapy and antidepressants, though only one medication has been specifically approved to treat it. In this context, novel, safe non-pharmacologica...

Repetitive Transcranial Magnetic Stimulation (rTMS) has been approved by the FDA as an effective intervention for Treatment-Resistant Depression (TRD). However, there is little evidence about maintenance protocol necessity. The aim of this systematic review is to identify, characterize, and evaluate the current maintenance TMS protocols for MDD and...

Evidence on long-acting antipsychotics (LAIs) in unselected populations with severe mental illness is scant. In this mirror-image study, we compared multiple clinical outcomes 1 year before and after a first LAI prescription in adults with severe mental illness, describing clinical trajectories of LAI continuers and discontinuers. We compared LAI c...

Abstract: Esketamine, the S-enantiomer of ketamine, has recently emerged as a therapy for treatment- resistant depression (TRD), showing both rapid antidepressant action and good efficacy and high safety. It is also indicated for the acute short-term treatment of psychiatric emergency due to major depressive disorder (MDD) and for depressive sympto...

In a society that strives for appearance, fitness is increasingly viewed as a means to reach a certain aesthetic ideal, rather than a way to improve health and physical performance. Every day millions of posts appear on social media promoting a visual representation of apparently fit, healthy and 'perfect' bodies. Combining personal accounts, clini...

Lorcaserin is a 3-benzazepine that binds 5-HT2C serotonin receptors in the hypothalamus, where it mediates lack of hunger and/or satiety, and in the ventral tegmental area, the site of origin of the mesolimbic and mesocortical dopaminergic projections, which mediate pleasure and reward. The drug has been first developed for the treatment of obesity...

In recent years, some neurologists reconsidered their approach to Medically Unexplained Symptoms and proposed Functional Neurologic Disorders (FND) as a new entity, claiming that neurology could offer alternative treatment options to the psychotherapies provided in psychiatry settings. FNDs, for this purpose, should include only the disorders liste...