Background: Ketamine, a dissociative anaesthetic and non-competitive NMDA receptor antagonist, has legitimate medical applications. However, rising illicit use across the United Kingdom (UK) has been accompanied by growing reports of toxicity, dependence, and deaths. These have led to renewed policy discussions. Rationale and Aim: Previous national studies have reported ketamine-related deaths elsewhere in the UK, but not in Scotland. This study examined all Scottish deaths (2013-2024) where ketamine was implicated, to provide a comprehensive evidence base for UK-wide policy discussions. Methods: Data were derived from anonymised National Records of Scotland records. All cases where ketamine was implicated in death were identified. Descriptive and comparative analyses were undertaken by year, sex, age, manner, and substances co-implicated. Results: Eighty-eight deaths were identified (≈0.5% of cases), with a steady increase over time. Most decedents were male (81.8%); mean age was 35 years. Most (84%) were accidental and involved polysubstance use—typically opioids (58%), stimulants (55%), benzodiazepines (48%), gabapentinoids (25%), and alcohol (22%). Acute drug use was the principal cause of death in 85% of cases. Discussion: The marked upward trend parallels that observed elsewhere in the UK. Polysubstance involvement, especially combinations of ketamine with opioids or benzodiazepines, substantially increases fatal risk through additive central nervous system depression. These findings reinforce the need for clearer public health messaging, targeted harm-reduction interventions, and careful monitoring of misuse, prescribing and diversion trends. Conclusions: Scottish ketamine-related deaths increased twentyfold in a decade. Most are preventable, highlighting the need for continued targeted education, intervention, and epidemiological monitoring.

Background: Migraine is a highly prevalent neurological disorder. Conventional therapies may be limited by side effects and suboptimal efficacy. Cannabidiol (CBD) has emerged as a potential alternative therapy with a more favorable safety profile. Methods: In this 12-week prospective observational cohort study, we evaluated the safety, feasibility, and preliminary efficacy of two full-spectrum CBD-rich oils—industrial and artisanal—for chronic migraine in 40 individuals that began self-medicating with either oil (N = 20 per group), provided through an existing initiative by an industrial company and a patient association. The oil was titrated individually to reach a target dose of 100 mg/day of CBD. Assessments were conducted using the Migraine Disability Assessment Questionnaire (MIDAS), Headache Impact Test (HIT-6), Mini Sleep Questionnaire (MSQ), and the World Health Organization Quality of Life—5-item version (WHOQOL-5). Results: Both formulations led to improvements in migraine-related disability, headache impact, quality of life, quality of sleep, and subjective well-being. Adverse events occurred at similar rates across groups. Conclusions: In sum, full-spectrum CBD-rich oil—both industrial and artisanal—appears effective in reducing migraine burden in individuals with chronic migraine, while maintaining an acceptable side effects profile. These findings support the need for randomized controlled trials to determine the lowest and most effective regimens, and cannabinoid compositions.

Background: Brexpiprazole, a third-generation antipsychotic with partial dopamine D2/D3 and serotonin 5-HT1A agonist properties, has emerged as a promising therapeutic option for patients with schizophrenia, including those with comorbid substance use disorders (SUDs). Managing psychosis in the presence of substance use represents a major clinical challenge, often associated with poorer outcomes, reduced adherence, and increased relapse risk. Methods: This narrative review(non-systematic) synthesizes evidence from randomized controlled trials, observational real-world studies, and expert consensus reports published between 2020 and 2026. The literature was examined to evaluate the pharmacological mechanisms, clinical efficacy, safety, and practical use of brexpiprazole in psychotic disorders, with particular attention to populations with comorbid substance use disorders. As a narrative review, this work does not employ systematic search protocols or quality appraisal tools; findings should be interpreted with this methodological limitation in mind. Results: Available evidence suggests that brexpiprazole can meaningfully reduce both positive and negative symptoms of psychosis, while also demonstrating beneficial effects on substance craving and functional outcomes in patients with dual diagnoses. Across randomized and real-world studies, brexpiprazole shows a favorable tolerability profile, characterized by minimal activation, low sedation, reduced risk of extrapyramidal symptoms, and limited cardiometabolic burden. These properties support its use in complex clinical populations requiring long-term treatment and polypharmacological management. Clinical Implications and Decision-Making: Based on the available evidence, brexpiprazole may be particularly suitable for: (1) patients with prominent negative symptoms requiring improvement in motivation and social functioning; (2) individuals with comorbid substance use disorders, particularly stimulant use, where dopaminergic modulation may address both psychotic symptoms and craving; (3) patients who have experienced significant metabolic or motor side effects with other antipsychotics; (4) individuals requiring cognitive preservation or enhancement. However, clinicians should consider that most evidence derives from relatively short-term studies with selected populations, and long-term real-world effectiveness data remain limited. Treatment decisions should be individualized based on symptom profile, comorbidity burden, prior medication responses, and patient preferences. Conclusions: Brexpiprazole represents a clinically valuable option for the management of psychosis, particularly in patients with comorbid substance use disorders. Its balanced pharmacological profile, combined with consistent efficacy and good tolerability, supports its role in integrated, long-term treatment strategies for complex and dual-diagnosis populations.

Background: Patients affected by schizophrenia often experience a poor quality of life. Antipsychotics currently used reduce treatment compliance because of their side effects and their high non-responder rate. Antipsychotic polytherapy, also with Long-acting injectables (LAI) formulation, may increase the efficacy in refractory and non-compliant patients. This systematic review examines the coadministration of clozapine and aripiprazole LAI, studying its efficacy, tolerability and side-effects. Methods: The research was conducted on 6 August 2025, using PubMed, Scopus and Web of Science. The query search tool used was “aripiprazole AND clozapine AND (Long acting OR injectable OR LAI OR combination)”. Only original papers written in English were considered; animal research, in vitro experiments, also studies not specifying the formulation of aripiprazole were excluded. Results: Our research produced 1637 records. Removing repeated, not written in English and off topic articles, six papers were selected for qualitative synthesis. Conclusions: Available evidence on the combined use of clozapine and long-acting injectable aripiprazole is limited and largely derived from small observational studies. The reviewed reports describe recurring clinical observations suggesting that this strategy may be applicable in selected patients with treatment-resistant schizophrenia, particularly in the presence of poor adherence or clozapine-related tolerability concerns. Reported outcomes include symptom stabilization, improved adherence, and possible benefits on residual symptoms and clozapine-related adverse effects. Nonetheless, the low certainty of the evidence prevents firm conclusions regarding efficacy and safety, highlighting the need for further prospective controlled studies.

Substance-induced psychoses (SIP) may offer a useful vantage point for exploring mechanisms underlying psychotic disorders and for examining the phenomenological specificities of schizophrenia. Clinical observations suggest that a clinically relevant subset of patients does not fully recover after an episode of substance-induced psychosis, raising the hypothesis of more persistent psychotic trajectories that may differ from both acute SIP and primary psychotic disorders (PPD). In this context, the proposal of Substance-Related Exogenous Psychosis (SREP) situates exogenous psychoses as conditions related to, yet not fully overlapping with, schizophrenia. Drawing on the tradition of classical psychopathology, from Bonhoeffer’s exogenous model to the concept of lysergic psychoma, and integrating it with recent research on self-disorders, the hypothesis emerges that substance-induced psychoses may function as heuristic phenomenological models useful for exploring the genesis of psychotic phenomena. Examination of ipseity through the EASE interview suggest similarities between SIP and PPD, but also significant differences: SIP are characterized by more superficial and transient alterations of the self, whereas schizophrenia involves deeper and structurally embedded disturbances. From this perspective, the phenomenological comparison of schizophrenia, SIP, and SREP may help delineate with greater precision which dimensions of self-experience are compromised across these psychotic conditions. This conceptual framework is intended as a hypothesis-generating perspective, which may guide future longitudinal studies integrating phenomenology and substance-related mechanisms to refine the boundaries between acute SIP, persistent SIP/SREP trajectories, and schizophrenia spectrum disorders.