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Background: While it is established that addictive doses of methamphetamine correlate with inflammation-mediated neurotoxic pathways, the extent of toxicity resulting from subchronic administration at lower doses remains uncertain. Objectives: This study aimed to investigate the subtle effects of daily subchronic methamphetamine (MA) administration on neuroinflammatory processes, cognitive dimensions, gene expression, and hippocampal morphology. Methods: The experimental study employed a longitudinal design with three groups (G1B, G2B, G3B) receiving methamphetamine (5 mg/kg, intraperitoneally, once daily) for 1, 2, or 3 weeks, respectively. Corresponding control groups (G1A, G2A, G3A) received 0.2 mL of normal saline. Spatial learning, novel object recognition, and passive avoidance tests were conducted to assess spatial, recognition, and fear avoidance memories. Hippocampal morphology was evaluated using Nissl staining, and the expressions of NLRP3, ASC, and caspase-1 genes were measured as markers of neuroinflammation. Results: Statistical analyses, including one-way and two-way ANOVA, showed that subchronic low-dose administration of MA led to significant activation of the inflammasome (NLRP3, ASC, and caspase-1), which may have resulted in pyramidal cell death in the hippocampus. The hippocampal structure in the CA1 region was completely disrupted. Spatial memory and passive avoidance learning were impaired in the MA groups, while recognition memory remained unaffected. Conclusions: The findings suggest that prolonged administration of 5 mg/kg of methamphetamine may be associated with significant inflammasome activation, pyramidal cell death, and mild cognitive decline. Contrary to previous evidence, even lower doses of methamphetamine taken over an extended period could be neurotoxic. [ABSTRACT FROM AUTHOR]

Introduction:Treatment of opioid use disorders (OUDs) via safe and effective approaches has been investigated for years. Methadone maintenance treatment (MMT) has been considered an effective therapy for opioid addiction. It has been observed that patients with genetic polymorphisms often show variability in the optimal drug dose requirement and treatment schedule. This study aimed to investigate the relationship between single nucleotide polymorphisms (SNPs) in the ATP-binding cassette subfamily B member-1 (ABCB1), the mu-opioid receptor (OPRM1), and cytochrome P450 (CYP) genes and methadone dose in patients undergoing MMT in Mazandaran Province, Iran. Methods: In a cross-sectional study, 216 male MMT patients (20 to 45 years old) who were involved in the treatment program for at least three months were randomly recruited from six MMT clinics in Mazandaran province between 2018 and 2020. Blood samples were taken, DNA was extracted, and SNPs of CYP2B6 (G516T, A785G), CYP2C19 (-3402C>T), CYP3A4 (-392A>G), OPRM (A118G), and ABCB1 (C3435T, G2677T, G2677A, and C1236T) genes were evaluated using polymerase chain reaction-restriction fragment length polymorphism (RFLP). Results: Our results showed no significant relationship between all the studied genotypes and methadone dose requirements. Conclusion: The present study, for the first time in the Mazandaran population, reported no significant correlations between methadone dose requirement and different SNPs in the ABCB1, OPRM1, and CYP genes in MMT patients, which is consistent with other studies conducted on the Iranian population. [ABSTRACT FROM AUTHOR]

Introduction: The opiate dosage adequacy scale (ODAS) is one of the most common assessment tools in studies on substance use disorders, which evaluates the “adequacy” of opiate medication doses in individuals recruited in maintenance approaches. There is no investigation on the Persian version of this questionnaire in Iran. This research validated a Persian version of the ODAS. Methods: The Persian version of the ODAS was translated and revised based on the original scale presented by González-Saiz et al. The psychometric characteristics of the ODAS were assessed via direct interviews. Three trained interviewers questioned 250 patients treated in methadone maintenance clinics in Mazandaran Province (Northern Iran) for more than three months. Internal consistency and factor analysis were conducted using SPSS software, version 24. Results: The internal consistency of ODAS was satisfactory (Cronbach’s α=0.81). Across all items, considerable inter-rater reliability was discovered (kappa values between 0.90 and 1). A four-component structure was produced by the factor analysis that accounted for 77.5% of the total variance. Cronbach’s α coefficients of the four components of Heroin craving and overmedication, Consumption, objective opiate withdrawal symptoms, and subjective opiate withdrawal symptoms were 0.84, 0.91, 0.83, and 0.74, respectively. Conclusion: The reliability and validity of the Persian version of the ODAS were satisfactory in a sample of methadone maintenance subjects. [ABSTRACT FROM AUTHOR]

Recently, mesenchymal stem/stromal cells (MSCs) transplantation has been introduced as a promising option to support cartilage structure and improve its function in preclinical models and patients suffering from osteoarthritis (OA). MSCs strongly provoke their preferred influence in vivo by inhibiting the inflammatory responses and applying immunomodulation by releasing anti‐inflammatory mediators such as transforming growth factor‐β and interleukin‐10. Such mediators downregulate fibroblast‐like synoviocytes growth and migration, leading to chondroprotection. Furthermore, improving the chondrocyte proliferation and extracellular matrix hemostasis in addition to the suppression of the matrix metalloproteinases activities can support cartilage tissue organization. In this light, various published results have demonstrated that MSCs therapy can considerably decrease pain and restore knee function in OA patients. In the current review, we have concentrated on recent advances in MSCs‐based therapeutics to elicit both chondrogenic and chondroprotective impacts in OA patients, focusing on the last decade in vivo results. [ABSTRACT FROM AUTHOR]