Search Results (89)

Background/Objectives: Cannabis use has a particularly high prevalence in individuals with psychotic disorders. Although cannabis use is generally associated with cognitive impairments in the general population, its impact on cognition in psychosis remains controversial. This study aimed to investigate the association between cannabis use and cognitive performance in a cohort of individuals affected by psychotic disorders. Methods: A total of 105 inpatients with psychotic disorders (mean age: 40.3 years; 34 females) were recruited from the University Hospital Center “Mother Teresa” in Tirana. Data collection included socio-demographic and clinical variables. Cognitive functioning was evaluated using the Montreal Cognitive Assessment (MoCA), while psychopathology was assessed with the Brief Negative Symptom Scale (BNSS), the Calgary Depression Scale for Schizophrenia (CDSS), the Psychotic Symptom Rating Scales (PSYRATS), and the Scale for the Assessment of Thought, Language, and Communication (TLC). Results: Cannabis users (CU) were more frequently male, younger, and exhibited an earlier onset of psychosis compared to non-users (No-CU). Importantly, CU demonstrated higher MoCA scores, with the most favorable outcomes observed among daily users. Conclusions: Contrary to the prevailing assumption that cannabis use exacerbates cognitive decline, our findings indicate an unexpected association between cannabis use and preserved cognitive functioning in psychosis. These results underscore the need to consider dosage, frequency, and cannabinoid composition (THC/CBD ratio) when interpreting cannabis-related cognitive outcomes in psychotic disorders. Full article

Ketamine (KET) administration protocols vary widely in their design, with acute, sub-chronic, and chronic dosing regimens used to induce psychotic-like behavior in rodent models. This review compares representative classic and contemporary studies employing differing KET administration protocols to model psychosis in laboratory rodents. Specifically, we have focused on the behavioral tasks and analytical methods used to validate KET-induced symptoms of psychosis-like and schizophrenia-like behaviors. While variability in behavioral tasks complicates direct comparisons across studies, these findings provide a framework for selecting dosing strategies aligned with specific research objectives. Acute KET protocols are particularly suited for addiction research or as a preliminary approach preceding longer-term studies. In contrast, protocols utilizing repeated or sub-chronic, or chronic administration of KET tend to yield more comprehensive models of psychosis-like behavior and are better suited for examining the associated enduring cognitive and neurobiological impairments. Administering KET intravenously or intraperitoneally at frequent intervals or with a bolus dose, may sustain higher levels of bioavailable KET, thereby producing a more robust and reliable psychosis-like phenotype, especially relevant for investigations of long-term cognitive and neurological dysfunction. Full article

Objective: To scope the available literature on antipsychotic treatment in substance-induced psychotic disorders, summarize evidence across substance categories, and highlight priorities for future research. Methods: This scoping review followed Arksey and O’Malley’s framework and PRISMA-ScR guidelines. A systematic search of PubMed, Scopus, Embase, PsycINFO, and Cochrane Library (January 1985–August 2025) identified studies examining antipsychotic treatment in cannabis-, stimulant-, and hallucinogen-induced psychoses. Two reviewers independently screened studies and extracted data using a standardized form. Given marked heterogeneity, findings were synthesized descriptively. Results: Seventeen studies met inclusion criteria: 3 randomized controlled trials (17.6%), 10 observational studies (58.8%), and 4 case series (23.5%). Most evidence involved cannabis-induced (n = 7) and methamphetamine-induced (n = 6) psychosis. Randomized trials showed comparable efficacy between risperidone and haloperidol for cannabis-induced psychosis, and between quetiapine and haloperidol for methamphetamine-induced psychosis. Case series suggested potential benefits of third-generation antipsychotics such as lurasidone and cariprazine. No controlled studies were identified for cocaine- or hallucinogen-induced psychoses. Conclusions: Evidence for antipsychotic treatment in substance-induced psychoses remains scarce and uneven. While conventional antipsychotics appear effective for cannabis- and methamphetamine-related presentations, other substances remain virtually unstudied. Substantial evidence gaps and limited methodological quality highlight urgent research needs. Full article

3-chloromethcathinone (3-CMC) is a synthetic cathinone that gained relevance, having been involved in a large number of seizures and poisoning reports. Despite this, literature currently lacks information on its pharmaco-toxicological effects. This study aims to investigate the acute sensorimotor and physiological effects of 3-CMC (0.1–30 mg/kg; i.p.) in male and female CD-1 mice and its effects (1 and 10 mg/kg) on Prepulse Inhibition (PPI). Furthermore, we describe a series of 3-CMC (or CMC)-related human intoxications (Italy, 2014–2025) registered by the PCC–National Toxicology Information Centre. Finally, we predicted the ADMET properties of 3-CMC compared to 2-CMC, 4-CMC, 2-MMC, and two 3-CMC metabolites. 3-CMC induced in mice locomotor stimulation in mice, relevant tachypnoea and hypothermia, sensorimotor, and PPI alterations were observed only at high doses, with minor sex differences. All intoxications were non-fatal and involved male patients showing psychomotor agitation, psychosis, aggressiveness, CNS depression, but also cardiac arrhythmias, thoracic pain, and tachypnea. N-dealkylation, N-hydroxylation, and phenyl hydroxylation were the main predicted reactions. Drug–drug interaction potential and cardiotoxicity were suggested for all compounds. This interdisciplinary study elucidates 3-CMC effects and its associated risks, opening new objectives for future studies on CMC compounds to provide critical information to clinicians and the toxicological field. Full article

Background: It has recently been proposed that the retina plays an important modulatory role in the control of motor function that is usually attributed exclusively to the function of the nigro-striatal dopamine (NSD) system. Indeed, it has been proposed further that Parkinson’s disease (PD) begins in and progresses from the retina and may be effectively treated from there. While previous intraocular work has employed intravitreal (IVIT) administration of toxins to induce experimental PD, the first study series reported here examines the effect of IVIT haloperidol on motor performance while the second study examines the effect of IVIT haloperidol on the unilateral rotation model of PD, both in a circadian context. Methods: Motor tests included open field performance and the latency to perform three motor tests after the IVIT injection of haloperidol with and without amphetamine pretreatment. In a second study, IVIT injections of the melatonin antagonist ML-23 or L-dopa were made after unilateral lesions of the NSD in rats that were placed in a rotometer examining spontaneous ipsilateral and contralateral turning. Results: IVIT haloperidol produced robust changes in several motor parameters during the light and dark phase of the LD cycle which were enhanced by amphetamine pretreatment. In the second study, while IVIT L-dopa had only a minor effect on spontaneous rotation during the light phase, IVIT haloperidol produced a robust effect upon ipsilateral turning. The reduction in spontaneous ipsilateral turning was seen after IVIT injections into the eye ipsilateral or contralateral to the hemisphere in which NSD destruction occurred. Reduced turning was seen during both the light and dark phases of the L/D cycle. Conclusions: These results illustrate that IVIT injections of DA and melatonin receptor antagonists can differentially alter motor function via the retina. This suggests that the retina may be a treatment target not only for PD but also for other DA- and melatonin-mediated disorders such as drug addiction, psychosis and schizophrenia. Full article

Background: Synthetic cannabinoid receptor agonists (SCRAs, commercially known as “Spice”) have become a leading cause of substance-induced psychosis worldwide. These compounds show strong associations not only with acute psychotic episodes but also, in a subset of patients, with persistent or relapsing psychotic disorders, patterns that raise concern about progression to schizophrenia. Yet clinicians still lack clear, evidence-based guidance, and the optimal management of SCRA-induced psychosis remains inadequately defined. Methods: We carried out a systematic search of PubMed, Scopus, and Web of Science on 2 April 2025, identifying 35 primary studies that together describe roughly 4600 clinical presentations (≈77% male; mean age: 24.7 years). Results: Across diverse settings a convergent three-step pharmacological strategy emerged. First, rapid tranquillization with parenteral benzodiazepines consistently controlled severe agitation and autonomic instability. Second, when florid psychosis persisted beyond 30–60 min, clinicians introduced a second-generation antipsychotic—most commonly olanzapine, risperidone, or aripiprazole—often at doses exceeding those used for primary psychoses. Third, for the minority of refractory or relapse-prone cases, escalation to long-acting injectable formulations or low-dose clozapine achieved symptom control, even at plasma levels below those required in treatment-resistant schizophrenia. Although the evidence base consists largely of uncontrolled clinical descriptions, across studies, a recurrent clinical pattern was observed: initial benzodiazepines for agitation, followed by antipsychotics when psychosis persisted and escalation to clozapine or long-acting injectables in refractory cases. This approach appears to be associated with symptom improvement, although the certainty of the evidence is low to very low. Conclusions. Prospective, comparative studies are urgently needed to refine dosing, directly compare antipsychotic classes, and evaluate emerging cannabinoid-modulating interventions. Full article

Substance-induced psychosis is a recognized clinical entity, commonly linked to cannabinoids, stimulants, hallucinogens, alcohol, and polysubstance use. These agents may provoke transient or persistent psychotic symptoms during intoxication or withdrawal. Opioids, however, constitute a noteworthy exception: psychosis is rarely observed during opioid intoxication, and emerging data suggest that opioid agonists might even exert antipsychotic-like effects. This article examines the paradoxical interaction between opioids and psychosis, with attention to clinical reports of psychotic symptoms arising following abrupt discontinuation of methadone or buprenorphine. In numerous cases, symptoms resolved swiftly after reintroduction of the opioid agonist, implying a neuromodulatory role. Opioids, unlike other substances of abuse, seem to lack intrinsic psychotogenic effects and may influence dopaminergic activity via kappa-opioid receptor antagonism and endorphinergic mechanisms. This challenges standard models of substance-induced psychosis and calls for a refined understanding of opioid pharmacodynamics in psychiatric contexts. In psychotic presentations among polysubstance users who also use opioids, restoring opioid agonist therapy should be prioritized, with antipsychotics reserved as second-line options—preferably agents with favorable receptor profiles. Where opioids are not involved, antipsychotics remain first-line, but should be applied judiciously, with efforts to taper when clinically appropriate. Full article

Background: Anabolic–androgenic steroids (AASs) are commonly used for performance enhancement but have been linked to significant neurobiological consequences. This review explores the impact of AASs on neurochemical pathways, cognitive function, and psychiatric disorders, highlighting their potential neurotoxicity. Methods: A narrative review of current literature was conducted to examine AASs-induced alterations in neurotransmitter systems, structural and functional brain changes, and associated psychiatric conditions. The interplay between AASs use and other substances was also considered. Results: Chronic AASs exposure affects serotonin and dopamine systems, contributing to mood disorders, aggression, and cognitive deficits. Structural and functional changes in the prefrontal cortex and limbic regions suggest long-term neurotoxicity. AASs use is associated with increased risks of depression, anxiety, and psychosis, potentially driven by hormonal dysregulation and neuroinflammation. Co-occurring substance use exacerbates neurocognitive impairments and behavioral disturbances. Discussion: While evidence supports the link between AASs use and neurotoxicity, gaps remain in understanding the precise mechanisms and long-term effects. Identifying biomarkers of brain damage and developing targeted interventions are crucial for mitigating risks. Increased awareness among medical professionals and policymakers is essential to address AASs-related neuropsychiatric consequences. Conclusions: AASs abuse poses significant risks to brain health, necessitating further research and prevention efforts. Evidence-based strategies are needed to educate the public, enhance early detection, and develop effective interventions to reduce the neuropsychiatric burden of AASs use. Full article

Background: Cataract is the leading cause of severe, non-traumatic vision loss worldwide, leading to multiple adverse outcomes in mental health, including depression, anxiety, and cognitive decline; however, the relationship to psychotic symptoms remains unclear. While congenital vision loss appears protective against psychosis, acquired vision loss or acute deprivation are inducing psychotic symptoms. Methods: This study of 200 consecutive cataract patients, with severe vision loss, compares Paranoid Ideation and Psychoticism symptoms pre surgery, measured with the SCL-90-R scale, to those symptoms that persisted two months post-surgery. Results: The results confirm the hypothesis that cataract surgery is associated with a reduction in those symptoms (Wilcoxon Z = 5.425, p < 0.001 for Paranoid Ideation and Wilcoxon Z = 6.478, p < 0.001 for Psychoticism). Higher improvement in those variables was associated with higher improvement in visual acuity while controlling for age, gender and stressful life events during the past six months. Conclusions: Those results point to the importance of addressing loss of visual function especially in patients with pre-existing psychotic symptoms or signs of cognitive decline. Full article

Background: Due to the high prevalence of severe infections, antibiotics are frequently administered in anaesthesia and intensive care units. Despite their therapeutic efficacy, several antibiotics exhibit neurotoxic potential, resulting in central and peripheral neurological complications in patients. This review aims to summarise the current evidence on antibiotic-induced neurotoxicity, particularly in critical care settings. Methods: A comprehensive literature analysis was performed to assess the neurotoxic profiles, underlying mechanisms, and clinical manifestations associated with different antibiotic classes, including beta-lactams, fluoroquinolones, macrolides, aminoglycosides, and others. Results: Beta-lactam antibiotics (especially cephalosporins and carbapenems) are strongly associated with seizures, encephalopathy, and EEG abnormalities, mainly through GABAergic inhibition and mitochondrial dysfunction. Fluoroquinolones and macrolides can cause psychosis, insomnia, and neuropathy via NMDA activation and oxidative stress. Linezolid carries the risk of serotonin syndrome and optic neuropathy, while glycopeptides and aminoglycosides are primarily associated with ototoxicity. Risk factors include advanced age, renal or hepatic impairment, and high serum drug levels. Conclusions: The neurotoxic potential of antibiotics is a critical but under-recognised aspect of pharmacotherapy in intensive care. Improved awareness, pharmacovigilance, dose adjustment, and drug monitoring are crucial for mitigating adverse neurological effects. Full article

Background: The effective management of psychotic and bipolar disorders in tertiary care can improve patient outcomes, yet the role of clinical pharmacists in optimising psychotropic medication use remains underexplored in South Africa. This study aims to investigate the role and interventions of clinical pharmacists in managing psychotic and bipolar disorders within a tertiary hospital in South Africa. Methods: A quantitative, descriptive study was conducted among 60 adult patients admitted to the psychiatric and internal medicine wards diagnosed with psychotic and/or bipolar disorder. A previously validated, standardised pharmaceutical care form was utilised for a purposive sample of inpatient files. Medication-related problems were identified, and appropriate interventions were suggested. Prescriptions were also assessed for adherence to treatment guidelines, including the South African Standard Treatment Guidelines, the American Psychiatric Association guidelines, and the National Institute for Health and Care Excellence guidelines. Results: The study included 60 patients (37 females) with a mean age of 37 years. Diagnoses included schizophrenia (28.8%), bipolar disorder (27.5%), and stimulant-induced psychosis (19.3%). Sixty-two medication-related problems were identified, leading to 77 proposed interventions, of which 65 were implemented. Among the prescriptions, 75% (n = 45) adhered to the South African Standard Treatment guidelines, 76% (n = 46) adhered to the NICE guidelines, and 71% (n = 43) adhered to the APA guidelines. Conclusions: Clinical pharmacists identified a number of medication-related problems in patients with psychotic and bipolar disorders, and their proposed interventions were largely accepted. The findings highlight the pharmacist’s role in optimising medication therapy and adherence to guidelines, suggesting that improved treatment monitoring is necessary in this setting. Full article

Poria cocos extract attenuates MK-801-induced hyperactivity via RhoA/ROCK1 pathway modulation in mice. Background/Objectives: Poria cocos (P. cocos), a traditional East Asian medicinal mushroom, serves as a medicine and nutritional supplement, has been used to improve sleep and mood. Its bioactive compounds may regulate calcium signaling and Rho family proteins, which are linked to cytoskeletal remodeling and psychiatric symptoms. This study investigated the effects of P. cocos ethanol extract (PCEE) on Rho signaling, cytoskeleton dynamics, and behavior in MK-801-treated cells and mice. Methods: PCEE components were analyzed using HPLC. IMR-32 and Neuro2A cells were treated with MK-801 and PCEE to assess changes in F-actin (via fluorescence staining), cell migration (wound healing and Transwell assays), and Rho signaling proteins (by immunoblotting). In vivo, C57BL/6 mice received MK-801 to induce hyperactivity, followed by PCEE treatment. RhoA/ROCK1 pathway protein levels in the prefrontal cortex were analyzed. Results: PCEE reversed MK-801-induced inhibition of cell migration, F-actin disruption, and dysregulation of Rho-related proteins (RhoGDI1, RhoA, CDC42, Rac1, ROCK1, MLC2, PFN1). In mice, PCEE significantly reduced MK-801-induced hyperactivity and normalized RhoA/ROCK1 signaling in the brain. Conclusion: PCEE modulates cytoskeletal dynamics by regulating RhoA/ROCK1 signaling and attenuates MK-801-induced behavioral and molecular changes, suggesting its therapeutic potential for psychosis with fewer adverse effects. Full article

Background: Synthetic cathinones and cannabinoids have emerged as significant public health concerns, particularly in pediatric populations. Marketed under deceptive names such as “bath salts” and “K2/Spice”, these substances pose unique challenges due to their accessibility, potency, and unpredictable effects. This narrative review synthesizes evidence on the toxicological effects of synthetic cathinones and cannabinoids in pediatric patients, emphasizing clinical presentations, management challenges, and public health implications. Methods: A structured narrative review was conducted using PubMed and Scopus databases to identify peer-reviewed studies published between January 2010 and September 2024. The selected articles focus on neuropsychiatric, systemic, and management outcomes associated with these substances in individuals aged 0–18 years. Results: Five studies demonstrate that synthetic cathinones frequently cause seizures, sympathomimetic toxidrome (tachycardia, hypertension), and neuropsychiatric effects like paranoia and catatonia. Seven studies show synthetic cannabinoids induce psychosis, respiratory depression requiring ventilation in 12% of cases, and cardiovascular complications like myocardial ischemia. One study highlighted severe outcomes in pediatric accidental exposures, emphasizing the unpredictable and life-threatening effects of these substances, often exacerbated by co-ingestion with alcohol or THC. Conclusions: Pediatric exposure to synthetic cathinones and cannabinoids results in severe and unpredictable toxicological effects, necessitating tailored clinical management strategies and enhanced diagnostic capabilities. Public health measures, including stringent regulatory controls, targeted education initiatives, and robust surveillance systems, are critical to mitigating these risks. A multidisciplinary approach is essential to safeguard vulnerable pediatric populations from the escalating dangers posed by synthetic drugs, and future research must address the long-term impacts and mechanisms of toxicity. Full article

Schizophrenia (SZ), a complex psychiatric disorder of neurodevelopment, is characterised by a range of symptoms, including hallucinations, delusions, social isolation and cognitive deterioration. One of the hypotheses that underlie SZ is related to inflammatory events which could be partly responsible for symptoms. However, it is unknown how inflammatory molecules can contribute to cognitive decline in SZ. This review summarises and exposes the possible contribution of the imbalance between pro-inflammatory and anti-inflammatory interleukins like IL-1beta, IL-4 and TNFalfa among others on cognitive impairment. We discuss how this inflammatory imbalance affects microglia and astrocytes inducing the disruption of the blood–brain barrier (BBB) in SZ, which could impact the prefrontal cortex or associative areas involved in executive functions such as planning and working tasks. We also highlight that inflammatory molecules generated by intestinal microbiota alterations, due to dysfunctional microbial colonisers or the use of some anti-psychotics, could impact the central nervous system. Finally, the question arises as to whether it is possible to modulate or correct the inflammatory imbalance that characterises SZ, and if an immunomodulatory strategy can be incorporated into conventional clinical treatments, either alone or in complement, to be applied in specific phases, such as prodromal or in the first-episode psychosis. Full article

Background/Objectives: Antipsychotic medicines are used to treat several psychological disorders and some symptoms caused by dementia and schizophrenia. Haloperidol (Hal) is a typical antipsychotic usually used to treat psychosis; however, its use causes motor or extrapyramidal symptoms (EPS) such as catalepsy. Hal blocks the function of presynaptic D2 receptors on cholinergic interneurons, leading to the release of acetylcholine (ACh), which is hydrolyzed by the enzyme acetylcholinesterase (AChE). Methods: This study was designed to investigate the Hal-inhibitory effects on AChE activity in regions representative of the cholinergic system of mice and potential associations between cataleptic effects generated by Hal using therapeutic doses and their inhibitory effects on AChE. Results: The distribution of the AChE activity in the different regions of the brain followed the order striatum > hippocampus > (prefrontal cortex/hypothalamus/ cerebellum) > brainstem > septo-hippocampal system. In ex vivo assays, Hal inhibited AChE activity obtained from homogenate tissue of the striatum, hippocampus, and septo-hippocampal system in a concentration-dependent manner. The inhibitory concentration of 50% of enzyme activity (IC₅₀) indicated that the septo-hippocampal system required a higher concentration of Hal (IC₅₀ = 202.5 µmol·L⁻¹) to inhibit AChE activity compared to the striatum (IC₅₀ = 162.5 µmol·L⁻¹) and hippocampus (IC₅₀ = 145 µmol·L⁻¹). In in vivo assays, male Swiss mice treated with concentrations of Hal higher than 0.1 mg·kg⁻¹ induced cataleptic effects. Positive correlations with Spearman’s correlation were observed only between the lack of cataleptic effect and the decreased AChE activity of the hippocampus in the mice treated with 0.01 mg·kg⁻¹ of Hal but not in the striatum and septo-hippocampal system. Conclusions: Our results suggest that Hal could increase cholinergic effects via AChE inhibition, in addition to its dopamine antagonist effect, as an alternative approach to the treatment of behavioral disturbances associated with dementia. Full article