Search Results (59)

Background/Objectives: Gabapentinoids are first-line treatments for neuropathic pain (NP); however, real-world evidence regarding their safety and effectiveness in complex clinical populations remains limited. This study aimed to evaluate the effectiveness and safety profile of gabapentinoid therapy in patients managed within a specialized pain relief institution. Methods: A retrospective cohort study (n = 109) was conducted (January 2024 to December 2024). Effectiveness was assessed via DN4 and VAS over one year. Time to improvement was analyzed using Kaplan–Meier curves. Results: The cohort (mean age 66.2 ± 15.3 years) presented 100% comorbidity and polypharmacy (66.1% opioids; 67.9% antidepressants). Although all patients showed improvement, only 35.8% achieved “maximal improvement.” Pregabalin demonstrated faster VAS reduction than gabapentin (p = 0.029), though long-term success was comparable (p = 0.30). Significantly, 100% of patients reported at least one adverse drug event (ADE), primarily somnolence (66.1%), though no serious ADEs occurred. Lower baseline pain scores were significant predictors of therapeutic success. Conclusions: Gabapentinoids are effective for long-term NP management; however, their use is consistently associated with non-serious ADEs. In specialized settings characterized by extensive CNS-active polypharmacy, proactive pharmacovigilance and multidisciplinary oversight are essential to balance analgesic effectiveness with medication safety. Full article

Background: Chronic pain, opioid use, and mental health disorders frequently co-occur in older adults, forming a complex and mutually reinforcing triad. Neurobiological ageing processes—such as neuroinflammation, dopaminergic decline, and impaired top-down regulation—may increase vulnerability to maladaptive coping strategies, including opioid misuse. This review aims to integrate neurobiological, affective, and clinical evidence to propose a unified neuropsychiatric framework for understanding the intersection between chronic pain, emotional distress, and opioid vulnerability in later life, while highlighting implications for integrated treatment and opioid stewardship. Methods: This structured narrative review synthesised interdisciplinary evidence from neuroscience, geriatric psychiatry, and pain medicine. The literature was thematically organised to examine shared neurobiological and psychosocial mechanisms underlying chronic pain, affective disorders, and opioid use disorder (OUD) in older adults, with attention to treatment strategies and stewardship principles. Results: Converging evidence suggests a neuroprogressive continuum linking chronic pain, emotional distress, opioid misuse, and cognitive decline. Key mechanisms include frontolimbic dysfunction, impaired reward processing, and chronic allostatic load. Therapeutic approaches that integrate analgesia with emotional regulation—such as buprenorphine, serotonin–noradrenaline reuptake inhibitors (SNRIs), and multimodal tapering strategies—may offer neuroprotective benefits. Effective opioid stewardship appears to require integrated functional, cognitive, and affective monitoring. Conclusions: Pain management in older adults may benefit from moving beyond symptom-focused approaches toward a neuropsychiatric model of care aimed at preserving homeostatic balance across sensory, emotional, and motivational domains. Within this framework, opioid therapy can be conceptualised as a potential means of functional and neuroaffective restoration, rather than solely as a strategy for risk reduction. Full article

Addiction poses a major global public health challenge. It is characterized by high prevalence, chronic relapse and limited efficacy of available pharmacotherapies across different substance use disorders. Increasing evidence demonstrates that incretin-based therapies directly modulate metabolic signaling pathways that intercross with central reward and motivational circuits, including hypothalamic-mesolimbic networks and dopaminergic neurotransmission. As a result, agents such as glucagon-like peptide 1 receptor agonists, originally developed for the treatment of type 2 diabetes and obesity, are now being actively investigated for their role in addiction treatment. This narrative review summarizes the current knowledge on the role of incretin-based therapies in the neurobiology of addiction. Evidence from preclinical models and human studies supports the potential therapeutic effect of glucagon-like peptide 1 receptor agonists in the treatment of alcohol use disorder, nicotine dependence, and the administration of other psychoactive substances, including psychostimulants, opioids, and cannabinoids. Preclinical studies consistently demonstrate that glucagon-like peptide 1 receptor agonists reduce substance intake, attenuate reward-related behaviors, and suppress relapse-like responding. So far, human evidence remains limited and is largely derived from observational studies. Preliminary research suggests potential reductions in substance use severity and overdose risk among individuals treated with incretin-based agents. While these findings highlight incretin signaling as a promising therapeutic option in addiction, the current evidence is insufficient to support their routine clinical use in the treatment of substance dependence. Therefore, further research is required to clarify underlying mechanisms and establish clinical efficacy. In particular, well-designed randomized controlled trials are needed to determine safety, tolerance and effectiveness of incretin-based therapies across different substance use disorders. Full article

Background: Postoperative pain levels and opioid requirements vary considerably, even among patients undergoing similar surgical interventions. The pupillary pain index—a pupillometry-derived measure of nociception-antinociception balance—may help individualize postoperative analgesia. We therefore tested the hypothesis that a pupillary pain index-guided opioid titration at the end of surgery reduces postoperative pain and opioid consumption compared with standard care. Methods: At the end of surgery, a portable infrared pupilometer was used to measure pupillary dilation reflex during stepwise tetanic stimulation (10–60 mA), generating a pupillary pain index score. Adult patients undergoing elective ear-nose-throat surgery under general anesthesia were randomized to pupillary pain index-guided opioid therapy or standard care. Opioid administration in the pupillary pain index group followed predefined pupillary pain index cutoffs; in the control group, analgesia was managed per routine practice. Postoperative opioid consumption and pain—assessed using a numerical rating scale (NRS, 0–10)—were recorded every 30 min for 2 h in the post-anesthesia care unit. Linear models with covariates including remifentanil, weight, nose surgery, and sex were calculated to compare outcomes between groups. Results: Mean (±SD) opioid consumption during the first 2 postoperative hours was 4.9 ± 4.3 mg in the pupillary pain index-guided group and 6.5 ± 4.3 mg in the control group (adjusted p = 0.12). Mean pain scores were 2.0 ± 1.1 and 2.6 ± 1.4, respectively (adjusted p = 0.10). Conclusions: Pupillary pain index-guided analgesia resulted in a nearly 25% reduction in opioid consumption and lower pain scores, although not statistically significant. This suggests that PPI-guided analgesia is not inferior to standard care in terms of pain management. Full article

Background: Emotional dysregulation and impulsivity represent key risk factors for adverse trajectories in adults with ADHD and are frequently observed among patients with opioid use disorder (OUD). Levomethadone, the R-enantiomer of methadone, provides more stable dopaminergic modulation than the racemic formulation and may improve emotional control. The primary objective was to examine emotional, clinical, and substance use changes after the switch to levomethadone and to determine whether these trajectories differed according to ADHD screening status. This study evaluated emotional, clinical, and behavioral outcomes—including substance use—after transitioning from racemic methadone to levomethadone maintenance therapy, focusing on the moderating role of ADHD symptoms and dose escalation. Methods: Eighty-three OUD patients in methadone maintenance were assessed at baseline, T1 (mean = 2.13 months, SD = 0.65), and T2 (mean = 6.20 months, SD = 0.91). Emotional dysregulation (RIPOST), clinical severity (Clinical Global Impression), and days of substance use were analyzed using Linear Mixed Models (participants with ≥1 valid follow-up). ADHD symptoms (Adult ADHD Self-Report Scale DSM-5) were evaluated with Wilcoxon signed-rank tests. Dose escalation (↑levomethadone) was defined as ≥1 increase during follow-up and was only included in the mixed models. Substance use analyses were restricted to baseline active users. Results: Emotional impulsivity significantly decreased over time only in participants screening positive for ADHD symptoms (ASRS ≥ 14), independent of dose escalation. Emotional instability also declined but across the full cohort. CGI scores improved in all participants. Substance use patterns showed a modest overall improvement, with reductions most evident for sedatives and alcohol. The findings indicate a specific effect of levomethadone on affective regulation and clinical stabilization, particularly in individuals with impulsivity traits. Conclusions: Levomethadone maintenance appears to improve emotional regulation and global functioning beyond dose-related effects, supporting its potential value in complex OUD patients with clinically relevant ADHD symptomatology. Combined treatment with levomethadone and methylphenidate may further enhance executive control and craving regulation in this population. Full article

The global opioid crisis necessitates innovative non-pharmacological interventions for pain management and addiction recovery. This comprehensive narrative review synthesizes evidence from approximately 75 studies supporting manual therapy’s modulation of endogenous opioid systems and explores potential applications in addiction treatment. Manual therapy interventions, including massage and joint manipulation, demonstrate significant neurochemical effects, with controlled studies showing 16% increases in plasma β-endorphin levels (p = 0.025) persisting approximately one hour following treatment. These effects appear mediated through periaqueductal gray-rostral ventromedial medulla descending pathways, with naloxone reversibility studies confirming opioid-mediated mechanisms. The endogenous opioid system undergoes profound dysregulation during addiction, creating therapeutic opportunities for interventions capable of stimulating natural opioid release without exogenous substances. Clinical applications in addiction recovery may include withdrawal symptom management, craving reduction, and restoration of dysregulated reward pathways. Manual therapy’s demonstrated safety profile, accessibility, and compatibility with existing treatment modalities position it as an ideal complementary intervention for comprehensive addiction programs. However, significant methodological limitations in existing studies necessitate cautious interpretation. Rigorous randomized controlled trials specifically examining manual therapy’s effects in addiction recovery populations represent the highest research priority. Manual therapy as an endogenous opioid modulator represents a promising frontier in addiction medicine but warrants rigorous scientific investigation before potential clinical integration into evidence-based treatment protocols. Full article

Background and Objectives: Ultrasound (US)-guided peripheral regional anesthesia (pRA) is gaining increasing importance in emergency medicine as an effective, low-ridsk alternative to general anesthesia (GA), procedural sedation (PS), or opioid therapy. By enabling rapid, direct pain management in the emergency department (ED), pRA can help preserve scarce surgical and anesthetic resources and, in some cases, avoid inpatient admissions. The aim of this study was to analyze the indications, techniques, and clinical impact of pRA in the orthopedic-focused ED of an affiliated hospital. Materials and Methods: All pRA and PS procedures performed over a six-year period were retrospectively reviewed among 35,443 orthopedic-trauma emergency patients. pRA was carried out under US guidance with standardized monitoring. Diagnoses, block techniques, effectiveness, and complications were analyzed descriptively. Results: A total of 1292 patients (3.7%) underwent either pRA (n = 1117; 3.2%) or PS (n = 175; 0.5%). pRA was performed in 22% of cases for interventions such as reductions or extensive wound management. In 78%, pRA was applied for analgesia, for example, in the diagnostic work-up and treatment of non-immediately operable fractures, lumbago, or arthralgia. The most common pRA techniques were brachial plexus blocks (54%) and femoral nerve blocks (25%). Fascial plane blocks (6.1%) and paravertebral blocks (1.5%) were rarely used. PS was performed in 175 of 1292 patients (13%), although pRA would have been feasible in 159 of these cases. No complications of pRA were observed, and GA could routinely be avoided. Conclusions: US-guided pRA proved to be an effective and safe alternative to PS, GA, or systemic analgesia for selected indications, allowing immediate treatment without the need for operative capacities. To ensure safe application, these techniques should be an integral part of the training curriculum for ED personnel. Full article

Background: Chronic post-surgical pain (CPSP) is a phenomenon that negatively influences patients’ quality of life and well-being. By definition, CPSP is a pain in the surgical area of injury that develops or increases after the operation and persists beyond the healing process. One of the populations that is especially vulnerable to CPSP is patients undergoing bariatric surgery, as obesity, chronic inflammation, pre-existing chronic pain, and severe postoperative pain are its risk factors. Therefore, we conducted a cross-sectional study assessing the prevalence of CPSP in patients undergoing laparoscopic sleeve gastrectomy (LSG). We also aimed to explore the potential influence of the promising opioid-free anesthesia (OFA) technique, assess if the CPSP after LSG had a potential neuropathic component, and additionally, determine whether the bariatric surgery altered chronic pain in this patient population. Methods: The study was registered on 11 November 2024, at ClinicalTrials.gov (NCT06686875). A cross-sectional study using e-survey.io was conducted among the patients who underwent LSG 3 months to 5 years earlier. Clinical data were retrieved from the hospital database. Results: Of the 135 patients who responded to our e-survey, 4.4% (n = 6, 95% CI 0.9–8%) reported CPSP. None of them had a PAIN DETECT score above 19, which would indicate a neuropathic component. Of the 32 patients who had pre-existing chronic pain, 31 reported a reduction in its intensity, and of the 16 patients on chronic opioid treatment, 10 discontinued opioid therapy. In a subgroup analysis, there was no significant difference in the prevalence of CPSP and long-term opioid therapy between the patients who had OFA and standard anesthesia (p > 0.05). Conclusions: The main finding of our study is that a minor, yet significant, portion of patients who underwent LSG develop CPSP, and OFA does not alter the risk. LSG appears to reduce pre-existing chronic pain and opioid use. Full article

Background/Objectives: Diabetic neuropathy (DN) is a prevalent complication of diabetes mellitus, affecting up to 50% of long-term patients and causing significant pain, reduced quality of life, and healthcare burden. Conventional treatments, including anticonvulsants, antidepressants, and opioids, offer limited efficacy and are associated with adverse effects. Emerging evidence suggests that cannabis, acting via the endocannabinoid system, may provide analgesic and neuroprotective benefits. This study evaluates the long-term effects of inhaled cannabis as adjunctive therapy for refractory painful DN. Inhaled cannabis exhibits rapid onset pharmacokinetics (within minutes, lasting 2–4 h) due to pulmonary absorption, targeting CB1 and CB2 receptors to modulate pain and inflammation. Methods: In this prospective, observational study, 52 patients with confirmed painful DN, unresponsive to at least three prior analgesics plus non-pharmacological interventions, were recruited from a single clinic. Following a 1-month washout, patients initiated inhaled medical-grade cannabis (20% THC, <1% CBD), titrated individually. Assessments occurred at baseline and annually for 5 years, including the Brief Pain Inventory (BPI) for pain severity and interference; the degree of pain relief; Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) score; HbA1c; and medication usage. Statistical analyses used repeated-measures ANOVA, Kruskal–Wallis tests, Welch’s t-tests, and Pearson’s correlations via Analyze-it for Excel. Results: Of 52 patients (mean age 45.3 ± 17.8 years; 71.2% male; diabetes duration 23.3 ± 17.8 years), 50 completed follow-up visits. Significant reductions occurred in BPI pain severity (9.0 ± 0.8 to 2.0 ± 0.7, p < 0.001), interference (7.5 ± 1.7 to 2.2 ± 0.9, p < 0.001), LANSS score (19.4 ± 3.8 to 10.2 ± 6.4, p < 0.001), and HbA1c (9.77% ± 1.50 to 7.79% ± 1.51, p < 0.001). Analgesic use decreased markedly (e.g., morphine equivalents: 66.8 ± 49.2 mg to 4.5 ± 9.6 mg). Cannabis dose correlated positively with pain relief (r = 0.74, p < 0.001) and negatively with narcotic use (r = −0.43, p < 0.001) and pain interference (r = −0.43, p < 0.001). No serious adverse events were reported; mild side effects (e.g., dry mouth or euphoria) occurred in 15.4% of patients. Conclusions: Inhaled cannabis showed sustained pain relief, improved glycemic control, and opioid-sparing effects in refractory DN over 5 years, with a favorable safety profile. These findings are associative due to the observational design, and randomized controlled trials (RCTs) are needed to confirm efficacy and determine optimal usage, addressing limitations such as single-center bias and small sample size (n = 52). Future studies incorporating biomarker analysis (e.g., endocannabinoid levels) could elucidate mechanisms and enhance precision in cannabis therapy. Full article

Introduction: Chronic low-back pain (CLBP) is a leading cause of disability, often requiring opioid therapy when conservative treatments fail. Transdermal buprenorphine and oral oxycodone/naloxone are commonly used, but their comparative effectiveness and safety remain underexplored. Materials and Methods: In this retrospective cohort study, 173 patients with CLBP treated at our center between June 2022 and May 2024 were analyzed. Group A (n = 88) received transdermal buprenorphine (5–15 μg/h), while Group B (n = 85) was treated with oral oxycodone/naloxone (10/5–20/10 mg/day). Treatment lasted four weeks, with dose titration after one week if pain was uncontrolled. Pain intensity (VAS), functional status (ODI), rescue medication use, and adverse effects were assessed at baseline and during follow-up. Results: Both groups showed significant reductions in VAS and ODI scores. Buprenorphine led to a greater functional improvement (ODI reduction p = 0.04) and a trend toward greater pain reduction (VAS p = 0.08). Rescue drug use was significantly lower in Group A (53.4%) compared to Group B (78.8%, p = 0.003). Adverse events were more frequent in the oxycodone group, particularly nausea and constipation. Conclusions: Transdermal buprenorphine provided comparable or superior analgesia with better tolerability and reduced reliance on rescue medication. It represents a safer, effective alternative for CLBP management in routine clinical practice. Full article

Background: Chronic Recurrent Multifocal Osteomyelitis (CRMO) is a rare auto-inflammatory condition affecting the growing skeleton. The standard first-line treatment of high-dose NSAIDs (non-steroidal anti-inflammatory drugs) is adequate only in a subset of patients. The American College of Rheumatology Consensus Guidelines suggest considering bisphosphonates in a certain category of patients based on evidence from a handful of case series reporting the outcome of pamidronate use. Aims: The aim of this study was to report the efficacy and safety of bisphosphonate, predominantly zoledronate, use in CRMO. Methods: A retrospective cohort study of children with CRMO receiving bisphosphonates was conducted between January 2008 and September 2023 at a single tertiary referral centre. We described the baseline characteristics; clinical indication, regimen and response to bisphosphonate treatment; changes in bone mineral density (BMD) and spine remodelling on dual-energy X-ray absorptiometry (DXA) scans; and safety data. Results: During the study period, 64 (72%, n = 46 females) patients with CRMO with a median age at diagnosis of 10 years (range: 3 to 16 years) were identified. Approximately 31% (n = 20) received either pamidronate (n = 2) or zoledronate (n = 14) or both (n = 4) due to changes in local protocols. The most frequent indications for bisphosphonate use were refractory pain [55%, n = 11/20], pain + spine involvement [35% (n = 7/20)] and spine involvement only [10% (n = 2)]. Prior to bisphosphonate therapy, 100% took regular NSAIDs (n = 19/19), 21% (n = 4/19) used opioids, 47% (n = 9/19) received oral steroid courses, and 10% (n = 2/19) received methotrexate. The median age at bisphosphonate treatment initiation was 12 years (range 6–18 years), and the duration of treatment was 2 years (range: 6 months to 5 years). Improvement in pain was reported by 88% of patients (n= 15/17, 1 was excluded as they had not started treatment yet). All non-responders (n = 2/17;) to bisphosphonate therapy were later recognised clinically to have pain amplification syndrome and were referred to the chronic pain multi-disciplinary team. This correlated to the complete treatment de-escalation of opioids (n = 3/3; 1 was excluded as they had not yet started treatment), steroids (n = 8/8) and methotrexate (n = 2/2). NSAIDs were discontinued in 44% of patients (n = 7 of 16; 1 was excluded due to missing data, and 3 were excluded due to NSAID intolerance). The median first-year increase in the LS BMAD (lumbar spine bone mineral apparent density) Z-score was +1.35, and that in the TBLH BMD (total body less head bone mineral density) Z-score was +0.7 (n = 11). Subsequently, median average annual increases in the LS BMAD Z-score of +0.65 and in the TBLH BMD Z-score of +0.45 (n = 5) were recorded. Around 30% of patients (n = 6) required treatment modification (dose reduction, frequency reduction or cessation) due to a rapid escalation in BMD. There were no fractures documented due to raised BMD. Evidence of spine remodelling on DXA vertebral fracture assessment was seen in 38% of patients with spinal lesions (n = 3 of 8). There was no radiological evidence of improvement in any vertebra plana lesion. First-phase reactions (pyrexia) were reported universally in patients who received bisphosphonates, but none were significant requiring hospitalisation. Conclusions: Similar to pamidronate, zoledronate with an advantageous dosing regimen is well tolerated and effective in improving pain and enabling the de-escalation of adjunctive therapy in CRMO. This is the first report tracking changes in BMD and spinal remodelling in response to zoledronate in CRMO patients. Spinal remodelling is minimal in vertebra plana lesions. Bone density monitoring and personalisation of the bisphosphonate dose and regimen are strongly recommended to avoid overtreatment. Full article

Background and Clinical Significance: Cocaine use disorder (CUD) is characterized by recurrent, cue-triggered and intrusive urges to use cocaine (craving), compulsive drug-seeking despite adverse consequences, and impaired control over intake, often co-occurring with excess weight and hedonic overeating. A dual-target rationale supports the fixed-dose naltrexone–bupropion (NB) combination: μ-opioid receptor (MOR) antagonism may mitigate opioid-facilitated mesolimbic reinforcement, while bupropion’s catecholaminergic effects and POMC activation support satiety and weight loss. Case Presentation: We describe a case study from an Italian outpatient setting of a 35-year-old man with a 10-year history of CUD, multiple failed detoxifications, and class I obesity (body mass index [BMI] 31 kg/m²) who initiated fixed-dose NB and was followed for 12 weeks under routine care. NB was associated with progressive attenuation of cue-reactive cocaine craving and improved appetite control, alongside clinically meaningful weight reduction, without psychiatric destabilization or emergent safety concerns; medication adherence remained stable. The patient maintained abstinence throughout follow-up and reported improved psychosocial functioning. Quantitatively, CCQ-B scores decreased from 7.2 at baseline to 2.1 at Week 12 (≈70% reduction), while BMI decreased from 31.0 to 25.5 kg/m² (≈−17.7%), with clinically meaningful weight loss and stable adherence. Conclusions: This case study supports the mechanistic rationale that dual NB therapy can simultaneously attenuate cocaine craving and facilitate weight control, addressing two clinically relevant targets in CUD. Although evidence for NB in CUD remains limited and mixed across stimulant populations, this observation highlights a plausible, testable therapeutic hypothesis that integrates mesolimbic and hypothalamic pathways and may inform the design of controlled trials in patients with co-occurring CUD and obesity. Full article

Background: Pain is a multifaceted and debilitating symptom in patients with gastrointestinal cancer, especially those undergoing surgical resection followed by chemotherapy. The interplay between inflammatory, neuropathic, and psychosocial components often renders conventional analgesia insufficient. Psychobiotics—probiotic strains with neuroactive properties—have recently emerged as potential modulators of pain perception through neuroimmune and gut–brain axis pathways. Methods: This post hoc analysis is based on the ProDeCa randomized, placebo-controlled trial, which originally aimed to assess the psychotropic effects of a four-strain psychobiotic formulation in postoperative gastrointestinal cancer patients receiving chemotherapy. In the current analysis, we evaluated changes in pain perception among non-depressed and depressed participants, who received either psychobiotics or placebo, along with standard analgesic regimes. Pain was assessed at baseline, after a month of treatment, and at follow-up, 2 months thereafter, using the Short-Form McGill Pain Questionnaire (SF-MPQ), capturing both sensory and affective components, as well as with the Present Pain Intensity and the VAS scores. Results: Psychobiotic-treated participants—particularly the non-depressed ones—exhibited a significant reduction in both quantitative and qualitative pain indices over time compared with placebo-treated ones. Improvements were noted in total pain rating index scores, sensory and affective subscales, and present pain intensity. These effects were sustained up to 2 months after intervention. In contrast, placebo groups demonstrated worsening in pain scores, probably influenced by ongoing chemotherapy and disease progression. The analgesic effect was less pronounced but still observable in the subgroup with symptoms of depression. Conclusions: Adjunctive psychobiotic therapy appears to beneficially modulate pain perception in gastrointestinal oncology patients receiving chemotherapy, with the most pronounced effects being in non-depressed individuals. These findings suggest psychobiotics as a promising non-opioid add-on for comprehensive cancer pain management and support further investigation in larger pain-targeted trials. Full article

Background and clinical significance: Acute reduction in vigilance is a frequent reason for emergency department admissions, especially among the elderly. While intracranial causes or infections with fluid depletion are often responsible, there remain cases where imaging, laboratory tests, and clinical examination fail to provide a clear diagnosis. Case presentation: A 91-year-old woman was presented to the emergency department with recurrent episodes of somnolence to deep coma. On admission, her vital signs were stable, and cerebral CT imaging revealed no intracranial pathology. Laboratory analyses, including blood gas measurements, were unremarkable. Empirical treatment for possible intoxications with benzodiazepines or opioids using flumazenil and naloxone had no effect. An Addison’s crisis was considered but excluded following methylprednisolone administration without improvement in consciousness. Eventually, an isolated elevation of serum ammonia was identified as the cause of the reduced vigilance. Further investigation linked the hyperammonemia to abnormal intestinal bacterial colonization, likely due to a prior ureteroenterostomy. There was no evidence of liver dysfunction, thus classifying the condition as non-hepatic hyperammonemia. Therapy was initiated with rifaximin, supported by aggressive laxative regimens. Ammonia levels and vital parameters were closely monitored. The patient’s condition improved gradually, with serum ammonia levels returning to normal and cognitive function fully restored. Conclusions: This case highlights an uncommon cause of coma due to non-hepatic hyperammonemia in the absence of liver disease, emphasizing the diagnostic challenge when standard evaluations are inconclusive. It underscores the need for broad differential thinking in emergency settings and the importance of considering rare metabolic disturbances as potential causes of altered mental status. Full article

Background and aims: Opioid maintenance therapy (OMT) is the first-line treatment for opioid use disorder (OUD), reducing opioid use and mortality while improving physical and mental health. However, concomitant substance use remains common, with cannabis being the most frequently used substance. This study assessed the prevalence and clinical correlates of cannabis use in OMT patients, as well as individual motivations. Methods: In this cross-sectional, single-center study, 128 OUD patients (96 male, 32 female) receiving OMT were assessed using standardized questionnaires: the Marijuana Smoking History Questionnaire (MSHQ), Cannabis Problems Questionnaire (CPQ) and the Severity of Dependence Scale (SDS). Cannabis users and non-users were compared regarding type (methadone vs. buprenorphine) and dosage of maintenance medication. Results: Cannabis use was reported by 41% of patients, 73% met criteria for cannabis dependence, 30% of the full sample. Of the patients, 85% reported cannabis-related legal issues. Common reasons for use included recreational motives (mood change, enhancement) and reduction in cravings for other substances. Cannabis dependence was significantly more common in patients receiving buprenorphine than methadone. Higher methadone doses were also associated with increased cannabis use. These results suggest a clinically relevant pattern. Conclusions: Cannabis use is highly prevalent and appears to be influenced by type and dosage of substitution medication. These findings highlight a complex interaction between opioid treatment and cannabis use, possibly involving behavioral coping or regulatory processes. Further longitudinal and placebo-controlled trials are needed to investigate the clinical and pharmacological interactions between cannabis and OMT, including effects on craving, withdrawal, and overall treatment outcomes. Full article