Search Results (180)

Substance use during pregnancy is an increasingly important yet under-recognized threat to maternal and child health. This narrative review synthesizes the current evidence available on the epidemiology, pathophysiology, clinical management, and policy landscape of prenatal exposure to alcohol, tobacco, opioids, benzodiazepines, cocaine, cannabis, methamphetamines, and other synthetic drugs. All major psychoactive substances readily cross the placenta and can remain detectable in breast milk, leading to a shared cascade of obstetric complications (hypertensive disorders, placental abruption, pre-term labor), fetal consequences (growth restriction, structural malformations), and neonatal morbidities such as neonatal abstinence syndrome and sudden infant death. Mechanistically, trans-placental diffusion, oxidative stress, inflammatory signaling, and placental vascular dysfunction converge to disrupt critical neuro- and cardiovascular developmental windows. Early identification hinges on the combined use of validated screening questionnaires (4 P’s Plus, CRAFFT, T-ACE, AUDIT-C, TWEAK) and matrix-specific biomarkers (PEth, EtG, FAEE, CDT), while effective treatment requires integrated obstetric, addiction, and mental health services. Medication for opioid use disorders, particularly buprenorphine, alone or with naloxone, confers superior neonatal outcomes compared to methadone and underscores the value of harm-reducing non-punitive care models. Public-health strategies, such as Mexico’s “first 1 000 days” framework, wrap-around clinics, and home-visiting programs, demonstrate the potential of multisectoral interventions, but are hampered by structural inequities and punitive legislation that deter care-seeking. Research gaps persist in polysubstance exposure, culturally tailored therapies, and long-term neurodevelopmental trajectories. Multigenerational, omics-enabled cohorts, and digital longitudinal-care platforms represent promising avenues for closing these gaps and informing truly preventive perinatal health policies. Full article

A multimodal approach is recommended to optimize perioperative pain control in animals, although opioid use in horses remains limited due to the risks of central nervous system (CNS) stimulation and reduced intestinal motility. A group of 19 healthy, male, mixed-breed horses were divided into two groups and medicated with acepromazine (0.05 mg kg⁻¹) and detomidine (10 µg kg⁻¹), with methadone (0.05 mg kg⁻¹) (ADM) or saline (ADS) administered intravenously (IV). Physiological variables, intestinal motility, gastric distention, and facial pain (EQUUS-FAP) were evaluated one day before (DB), before the surgical procedure (BS), and at 1, 2, 4, 6, and 8 h (T1h–T8h) after administration (ADM-ADS). Results are presented as means with standard deviation or medians with an interquartile range. Analysis of variance, the Mann–Whitney, and Durbin tests were applied (p < 0.05). Intestinal motility was reduced at T1h and T2h, returning to baseline by T6h and T8h in both groups. Ultrasonographic examination revealed reduced motility, with less significant changes in the left ventral colon (LVC), right ventral colon (RVC), and cecum. Gastric dilatation was more pronounced in the ADM group at T1, 4, 6, and 8h. EQUUS-FAP scores were significantly lower in ADM at T2, 4, and 6h. ADM protocol may aid chemical restraint and analgesia without increasing hypomotility. 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/Objectives: The consumption of opioids is a public health problem that significantly affects quality of life. In Spain, 7585 people are enrolled in the Methadone Maintenance Programme (MMP), which is an effective intervention with a low adherence rate. In this study, factors associated with the quality of life of MMP users, especially perceived social support and treatment adherence, were analysed. We hypothesised that low levels of adherence and social support would be associated with poorer quality of life. Methods: This was a cross-sectional observational study with an analytical approach. Quality of life (WHOQoL-BREF), perceived social support (DUKE-UNC-11), and treatment adherence (MMAS-8) among MMP users were studied, and data on sociodemographic and clinical characteristics were collected through ad hoc questionnaires and a review of electronic medical records. Linear and logistic regression models were used. Results: A total of 70 individuals were included in this study. The mean age was 56.9 years, and 83% of the participants were male. The perceived quality of life was low in the four domains evaluated (range of 47.4–48.2). A total of 38.57% of the participants had low perceived social support. Treatment adherence was low or moderate in 77.1% of the participants. Greater perceived social support was associated with better quality of life in all domains (p < 0.05). Quality of social life was negatively associated with the use of nonbenzodiazepine neuroleptics and HIV status. Treatment adherence was lower in insulin therapy users. Conclusions: Social support is a key determinant of the quality of life of MMP users. Health policies should promote social support networks as a strategy to improve the well-being of this population. Full article

Opioid use disorder (OUD) is a chronic disease that remains difficult to treat, even with significant improvements in available medications. While current treatments work well for some, they often do not account for the unique needs of individual patients, leading to less-than-ideal results. Precision medicine offers a new path forward by tailoring treatments to fit each person’s genetic, psychological, and social needs. This review takes a close look at medications for OUD, including methadone, buprenorphine, and naltrexone, as well as long-acting options that may improve adherence and convenience. Beyond medications, the review highlights the importance of addressing mental health co-morbidities, trauma histories, and social factors like housing or support systems to create personalized care plans. The review also explores how emerging technologies, including artificial intelligence and digital health tools, can enhance how care is delivered. By identifying research gaps and challenges in implementing precision medicine into practice, this review emphasizes the potential to transform OUD treatment. A more individualized approach could improve outcomes, reduce relapse, and establish a new standard of care focused on recovery and patient well-being. Full article

Background/Objective: Fentanyl plays a pivotal role in the opioid epidemic, defined by four waves of overdose deaths. To analyse fentanyl research trends, examining its links to mental health, pharmaceutical development, healthcare, diseases, and pathophysiology within the broader social and health context of the time. Methods: To understand the evolution of scientific publications on fentanyl and its relationship to the opioid crisis, a search using Web of Science Core Collection and PubMed was conducted. A total of 53,670 documents were retrieved related to opioid scientific production, among which 1423 articles (3%) focused specifically on fentanyl. The 21,546 MeSH terms identified in these documents were analysed by publication year and specific fields: Psychiatry and Psychology, Chemicals and Drugs, Healthcare, Diseases, and Phenomena and Processes. R-statistical/FactoMineR libraries were used for the correspondence analysis. Results: In the first overdose death wave, research focused on improving therapies and reducing side effects. The second wave emphasised detoxification methods with naltrexone, methadone, and behavioural therapies. The third wave addressed psychological treatments and HIV-syringe-sharing prevention. The fourth wave prioritised less addictive analogues and understanding consumer profiles to combat the epidemic. Conclusions: Fentanyl research has evolved alongside real-world challenges, reinforcing the connection between patients’ needs, healthcare professionals’ roles, illicit users, policymakers, and the research community’s contributions to addressing both therapeutic use and its broader societal impact. These findings highlight the necessity for an interdisciplinary approach to scientific research integrating prevention, treatment, education, legal reform, and social support, emphasising the need for public health policies and collaborative research to mitigate its impact. Full article

Introduction: Methadone, a synthetic opioid used for opioid substitution therapy (OST), is typically associated with arrhythmias rather than direct myocardial depression. Neurological complications, especially with concurrent antipsychotic use, have also been reported. Acute left ventricular failure in young adults is uncommon and often linked to genetic or infectious causes. We present a rare case of reversible cardiogenic shock and cerebellar insult due to methadone toxicity. Case Presentation: A 37-year-old man with a history of drug abuse on OST with methadone (130 mg/day) was admitted to the ICU with hemodynamic instability, seizures, and focal neurological deficits. Diagnostic workup revealed low cardiac output syndrome and a right cerebellar insult, attributed to methadone toxicity. The patient received individualized catecholamine support. After 10 days in the ICU, he was transferred to a general ward for ongoing cardiac and neurological rehabilitation and discharged in stable condition seven days later. Conclusions: Methadone-induced reversible left ventricular failure, particularly when accompanied by cerebellar insult, is rare but potentially life-threatening. Early recognition and multidisciplinary management are essential for full recovery in such complex toxicological presentations. 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

Endogenous opioids, such as Endomorphin-2, are not typically associated with severe constipation, unlike pharmaceutical opioids, which induce opioid-induced constipation (OIC) by activating μ-opioid receptors in the gastrointestinal tract. In this study, we present a mathematical model, which integrates the serotonergic and opioid pathways, simulating the interaction between serotonin and opioid signaling within the enteric nervous system (ENS). The model explores the mechanisms underlying OIC, with a focus on the change in adenylyl cyclase (AC) activity, cAMP accumulation, and the distinct functionalities of Endomorphin-2 compared to commonly used pharmaceutical opioids. We study the effects of Morphine, Fentanyl, and Methadone and contrast them with Endomorphin-2. Our findings reveal that opioids do not perturb the signaling of serotonin, but only the activity of AC, suggesting that serotonin levels have no influence on improving opioid-induced constipation. Furthermore, this study reveals that the primary difference between endogenous and pharmaceutical opioids is their degradation rates. This finding shows that modulating opioid degradation rates significantly improves cAMP recovery. In conclusion, our insights steer towards exploring opioid degrading enzymes, localized to the gut, as a strategy for mitigating OIC. Full article

Buprenorphine has gained widespread popularity for use in rabbits, while much less is known about methadone. Our aim was to compare sedative, analgesic, and respiratory effects of methadone and buprenorphine as part of balanced anaesthesia. Forty-eight female New Zealand white rabbits undergoing calvaria defects were randomly equally assigned to receive either 0.03 mg kg⁻¹ of buprenorphine (group B) or 0.3 mg kg⁻¹ of methadone (group M) in combination with 15 mg kg⁻¹ of ketamine and 0.1 mg kg⁻¹ of dexmedetomidine SC. Fifteen minutes later, sedation was scored. A laryngeal mask was placed, and inhalational anaesthesia started. Rescue intraoperative analgesia was administered based on autonomic variations. Arterial blood gases were analysed intra- and postoperatively. Postoperative analgesia was administered if the Rabbit Grimace Scale (RbtGS) score was ≥4. The Mann–Whitney test, t-test, and relative risk followed by chi-square test were used to compare the treatment groups. Deeper sedation was observed in rabbits of group M than in those of group B. Rescue analgesia was administered intraoperatively to seven animals in group B and five in group M (p = 0.739) and postoperatively to three in group B and twelve in group M (p = 0.013). Rabbits of both groups showed short-term respiratory acidosis. RbtGS scores indicated better and longer analgesia in group B compared to group M. Full article

Background: Alcohol use disorder in the context of heroin addiction presents a significant challenge for clinicians, particularly in selecting the most appropriate pharmacological treatment. Methods: The present study aimed to retrospectively evaluate the efficacy of a six-month methadone maintenance (MM)/sodium oxybate (SMO) combination treatment in reducing ethanol intake among chronic alcohol-dependent patients with heroin use disorder (HUD). Specifically, we compared outcomes between those who continued SMO treatment after alcohol detoxification (MM/SMO-Maintained) and those who discontinued it (MM/SMO-Detoxified). Data were recruited using the ‘Pisa Addiction Database’ through a retrospective, naturalistic, cross-sectional comparative design involving a single patient assessment. Results: Our results indicate that treatment retention was higher in the MM/SMO-Maintained group. Conversely, discontinuing SMO treatment after alcohol detoxification was associated with a higher likelihood of dropout. At the endpoint, the MM/SMO-Maintained group showed significant improvement and was considered less severely ill. Conclusions: Long-term SMO treatment has proven to be well tolerated and effective in preventing relapse in individuals with both alcohol and HUD undergoing agonist opioid treatment. SMO may be considered the closest pharmacological option to substitution therapy for alcohol use disorder, and ongoing agonist opioid treatment should not preclude its co-administration. Full article

Physical exercise may affect drug use by balancing neurohormonal system mechanisms. Cortisol and β-endorphin, associated with stress, mood, and pleasure feelings, can be affected by exercise and act as regulators of withdrawal symptoms associated with drug use during short-term abstinence. The present study investigated the effect of a supervised, two-month moderate-intensity aerobic exercise program on salivary cortisol and β-endorphin levels in patients with an opioid use disorder (OUD) and on a substitution treatment during a short-term, 24–36 h withdrawal phase from methadone/buprenorphine medication. Ninety opioid users (41 females) in methadone and buprenorphine substitution treatment were randomly divided into four groups: (a) buprenorphine exercise (BEX) (n = 26; age (mean ± SD): 41.9 ± 6.1 yrs), (b) buprenorphine control (BCON) (n = 25; age: 41.9 ± 5.6 yrs), (c) methadone exercise (MEX) (n = 20; age: 46.7 ± 6.6 yrs), and (d) methadone control (MCON) (n = 19; age: 46.1 ± 7.5 yrs). The exercise intervention groups (BEX and MEX) followed a training program on a treadmill for 20 min at 70% HRmax, 3 days/week for 8 weeks. The responses of cortisol and β-endorphin were measured before (t0) and immediately after an exercise session (t20) on different days (i.e., the 1st, 12th, and 24th session) corresponding to the beginning, middle, and end of the training program. A significant increase in β-endorphin levels was observed after the completion of the training intervention (24th exercise session) in both exercise groups (BEX before: 63.8 ± 33; BEX after: 185.6 ± 182.8 pg/mL; MEX before: 115 ± 211; MEX after: 262.3 ± 505.7 pg/mL), whereas β-endorphin was decreased in the control groups (BCON before: 34.7 ± 20.1; BCON after: 24.2 ± 8.8 pg/mL; MCON before: 129.7 ± 185.7; MCON after: 84.9 ± 104.3 pg/mL) (p < 0.05). Inversely, cortisol decreased in both exercise groups post-intervention (BEX before: 9.5 ± 5.9; BEX after: 2.8 ± 1.5 ng/mL; MEX before: 9.3 ± 6.6; MEX after: 3.1 ± 1.5 ng/mL) and increased in control groups (BCON before: 6.3 ± 2.5; BCON after: 10.1 ± 5.4 ng/mL; MCON before: 7.5 ± 3.2; MCON after: 12.5 ± 4.3 ng/mL) (p < 0.05). Moderate-intensity aerobic exercise can beneficially influence β-endorphin and cortisol levels in individuals undergoing treatment for OUD. By increasing endogenous opioid levels and reducing stress hormones, exercise emerges as a promising adjunctive strategy for alleviating withdrawal symptoms, enhancing emotional regulation, and potentially reducing the risk of relapse. The inverse relationship between β-endorphin and cortisol highlights the role of physical activity as a long-term modulator of neuroendocrine function in the context of substance use recovery. Future research should prioritize longitudinal studies extending beyond two months and involving larger, more diverse populations. Additionally, investigating the integration of exercise with non-pharmacological interventions—and its effects on relapse rates, mental health outcomes, and overall quality of life—would provide further insight into its therapeutic value in addiction recovery. Full article

To compare the use of postoperative analgesia for mastectomy, 44 dogs were randomly allocated to either the Splash treatment group (group A) or the Transverse Abdominis Plane block treatment group (TAP, group B). Following intramuscular (IM) premedication with pethidine (4 mg kg⁻¹) and acepromazine (0.01 mg kg⁻¹), anesthesia was induced with intravenous (IV) propofol and maintained with isoflurane by an anesthetist (DC) who was unaware of the treatment. In group A, ropivacaine 0.5% (2 mg kg⁻¹) was administered prior to surgical wound closure. In group B, ropivacaine 0.5% (0.8–1 mg kg⁻¹ per point) was administered by ultrasound-guided TAP block with two injection points per treated body side. At the end of the surgery, all dogs received pethidine (4 mg kg⁻¹ IM), meloxicam (0.2 mg kg⁻¹ IV), and acepromazine (0.005 mg kg⁻¹ IV). The animals’ pain was assessed by the anesthetist, who remained unaware of the treatment type used, via the Short Form of the Glasgow Composite Pain Scale. When the pain scores were ≥6, methadone (0.2 mg kg⁻¹ IV) and gabapentin (10 mg kg⁻¹ per oral) were started. When the pain score remained ≥ 6, ketamine (1 mg kg⁻¹ subcutaneously) was administered. The dogs in the TAP block group had lower postoperative pain scores 3–12 h after anesthesia administration was terminated and required significantly less rescue analgesia. Full article

Introduction: Methadone is an opioid-sparing opioid and it is increasingly used in children undergoing surgery due to its beneficial effects on postoperative pain scores, decreased opioid requirements, and fewer adverse effects compared to other opioids. Intraoperative methadone is not well studied in pediatric cardiac surgery. We hypothesized that intraoperative methadone-based analgesia would provide comparable effectiveness in pain management to non-methadone-based analgesia, including caudal morphine, following pediatric cardiac surgery. Methods: We conducted a retrospective cohort study of 287 children undergoing cardiac surgery using single institutional electronic health records with Society of Thoracic Surgeons database outcomes. Patients were administered intravenous opioids plus caudal morphine (≤6 years) or intravenous opioids in the non-methadone group versus intravenous methadone (two 0.1 mg/kg doses given intraoperatively) with or without additional intraoperative opioids. The primary outcome was postoperative opioid use in morphine milligram equivalents (MME)/kg. Results: This study included 287 pediatric cardiac surgical patients with a mean age of 3.8 years, 59% male, and 72% White. Among 287 patients, 67 (23%) received intraoperative methadone. Unadjusted analysis showed the methadone group had lower postoperative opioid use on the day of surgery (median = 0.3 vs. 0.5 MME/kg, p = 0.005). Adjusted analyses showed there were no significant differences in postoperative opioid use, average pain, maximum pain, antiemetic use, reintubation, and use of naloxone between methadone and non-methadone groups. Hospital length of stay was 2.62 times longer (95% CI: [1.55, 4.41] p < 0.001) in the methadone group vs non-methadone group, but this was only shown in the younger children (≤6 years), who also had higher max pain scores in the methadone group. All outcomes were similar between analgesia groups in older children (>6 years). Conclusions: Intraoperative methadone-based analgesia had comparable effectiveness in postoperative opioid use, pain, and antiemetic use compared to non-methadone-based intraoperative pain management for pediatric cardiac surgery. Large prospective studies of perioperative methadone are needed to examine methadone’s analgesic benefits in children undergoing cardiac surgery. Full article

Background/Objectives: Methadone maintenance treatment (MMT) is widely used in opioid use disorder (OUD). Its efficacy is influenced by its metabolism, primarily mediated by Cytochrome P450 (CYP450) enzymes in the liver. Genetic polymorphisms in CYP450 genes and other factors, such as age, sex, and concomitant treatments, contribute to interindividual variability in methadone response. This article addresses the relevance of pharmacokinetic biomarkers in methadone metabolism and its impact on treatment outcomes in European populations over the past 25 years. Methods: A systematic review was conducted using four databases (PsycINFO, PubMed, Scopus, and Web of Science) for studies published between 2000 and 2024 following the PRISMA 2020 guidelines (CRD42025641373 in PROSPERO). Two independent reviewers screened and assessed the study quality using NHLBI tools. Discrepancies were solved through consensus. Relevant data including sample size, genetic biomarkers, and key findings were extracted for each study. Data were synthesized and described in detail. Results: Fourteen studies on pharmacogenetic biomarkers influencing methadone metabolism in European populations were analyzed, encompassing a total of 3180 subjects. CYP2B6*6 was identified as a key variant associated with increased (S)-methadone plasma levels, potentially leading to cardiac complications, while the role of other pharmacokinetic genes, including ABCB1 and CYP2D6, was inconclusive. Conclusions: Genetic polymorphisms significantly influence methadone metabolism, with the CYP2B6*6 allele playing a key role in (S)-methadone metabolism and associated with cardiac risks. Pharmacogenetic studies integrating co-mediation—the principal cause of phenoconversion—as a potential variable alongside gender differences and encompassing adequate sample sizes could improve outcomes and establish the basis for personalized medicine of MMT. Full article