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Background: Integrating molecular-targeted agents into combination chemotherapy is transformative for enhancing treatment outcomes in cancer. However, realizing the full potential of this approach requires a clear comprehension of the genetic dependencies underlying drug synergy. While the interactions between conventional chemotherapeutics are well-explored, the interplay of molecular-targeted agents with conventional chemotherapeutics remains a frontier in cancer treatment. Hence, we leveraged a powerful functional genomics approach to decode genomic dependencies that drive synergy in molecular-targeted agent/chemotherapeutic combinations in gastric adenocarcinoma, addressing a critical need in gastric cancer therapy. Methods: We screened pharmacological interactions between fifteen molecular-targeted agent/conventional chemotherapeutic pairs in gastric adenocarcinoma cells, and examined the genome-scale genetic dependencies of synergy integrating genome-wide CRISPR screening with the shRNA-based signature assay. We validated the synergy in cell death using fluorescence-based and lysis-dependent inference of cell death kinetics assay, and validated the genetic dependencies by single-gene knockout experiments. Results: Our combination screen identified SN-38/erlotinib as the drug pair with the strongest synergism. Functional genomics assays unveiled a genetic dependency signature of SN-38/erlotinib identical to SN-38. Remarkably, the enhanced cell death with improved kinetics induced by SN-38/erlotinib was attributed to erlotinib's off-target effect, inhibiting ABCG2, rather than its on-target effect on EGFR. Conclusion: In the era of precision medicine, where emphasis on primary drug targets prevails, our research challenges this paradigm by showcasing a robust synergy underpinned by an off-target dependency. Further dissection of the intricate genetic dependencies that underlie synergy can pave the way to developing more effective combination strategies in gastric cancer therapy. [ABSTRACT FROM AUTHOR]

Rationale: Cocaine use disorder (CUD) is a brain disorder for which there is no Food and Drug Administration-approved pharmacological treatment. Evidence suggests that glutamate and metabotropic glutamate receptor subtype 5 (mGlu5) play critical roles in synaptic plasticity, neuronal development, and psychiatric disorders. Objective: In the present study, we tested the hypothesis that the mGlu5 receptor is functionally involved in intravenous cocaine self-administration and assessed the effects of sex and cocaine exposure history. Methods: We used a preclinical model of CUD in rats that were allowed long access (LgA; 6 h/day) or short access (ShA; 1 h/day) to intravenous cocaine (750 µg/kg/infusion [0.1 ml]) self-administration. Rats received acute intraperitoneal or oral administration of the mGlu5 receptor negative allosteric modulator mavoglurant (1, 3, and 10 mg/kg) or vehicle. Results: Both intraperitoneal and oral mavoglurant administration dose-dependently reduced intravenous cocaine self-administration in the first hour and in the entire 6 h session in rats in the LgA group, with no effect on locomotion. In the ShA group, mavoglurant decreased locomotion but had no effects on cocaine self-administration. We did not observe significant sex × treatment interactions. Conclusions: These findings suggest that the mGlu5 receptor is involved in escalated cocaine self-administration. These findings support the development of clinical trials of mavoglurant to evaluate its potential therapeutic benefits for CUD. [ABSTRACT FROM AUTHOR]

Background: Rhinitis medicomentosa (RM) is a form of non-allergic rhinitis caused by the use of nasal decongestants for longer than the recommended duration. Because of this problem of use, addiction to the drug occurs in individuals. In our study, we aimed to evaluate the susceptibility of RM patients to substance addiction. Methods: The study was planned as a prospective, multicentric study between September 2022 and September 2023. Patients diagnosed with RM were included in the study. Beck depression scale, Drug use disorders identification test, Substance Abuse Proclivity Scale were applied to the patients participating in the study. The research data were analyzed electronically with SPSS program version 25. Results: The study included 86 patients with an average age of 31 years. The average duration of medication use was 22 months. Age, gender, duration of nasal congestion, duration of drug use and smoking were not independent predictors for depression and substance use tendency. Conclusion: The relationship between RM and addictive substances is not clear. The tendency to use drugs did not increase in RM patients. In the light of these data, we think that there is no need for a practice other than routine functioning in the use of drugs and similar substances that are likely to cause addiction in RM patients. [ABSTRACT FROM AUTHOR]

Persistent neurochemical and biological disturbances resulting from repeated cycles of drug reward, withdrawal, and relapse contribute to drug dependence. Methamphetamine (MA) is a psychostimulant with substantial abuse potential and neurotoxic effects, primarily affecting monoamine neurotransmitter systems in the brain. In this study, we aimed to explore the progression of drug dependence in rat models of MA self-administration, extinction, and reinstatement through targeted and non-targeted metabolomics analyses. Metabolic profiles were examined in rat plasma during the following phases: after 16 days of MA self-administration (Group M); after 16 days of self-administration followed by 14 days of extinction (Group MS); and after self-administration and extinction followed by a reinstatement injection of MA (Group MSM). Each group of MA self-administration, extinction, and reinstatement induces distinct changes in the metabolic pathways, particularly those related to the TCA cycle, arginine and proline metabolism, and arginine biosynthesis. Additionally, the downregulation of glycerophospholipids and sphingomyelins in Group MSM suggests their potential role in MA reinstatement. These alterations may signify the progressive deterioration of these metabolic pathways, possibly contributing to drug dependence following repeated cycles of drug reward, withdrawal, and relapse. These results provide valuable insights into the metabolic changes associated with MA use at various stages, potentially facilitating the discovery of early diagnostic biomarkers and therapeutic targets for MA use disorders. [ABSTRACT FROM AUTHOR]

Background: The number of persons using opioids has increased worldwide in the last decade, particularly the use of opioid analgesics in North America and Africa. In Germany, the prevalence of heroin addiction has remained relatively stable. Method: Narrative review of the literature. Results: Opioid-assisted maintenance treatment (OMT) with the established substances methadone, levomethadone, slow-release morphine and buprenorphine is recommended as the first-line treatment for heroin dependence. The OMT reduces the use of heroin, mortality and individual suffering and improves the quality of life and physical health. A diamorphine and heroine-assisted treatment is an option for people who do not benefit from conventional OMT. An alternative to the use of diamorphine could be treatment with hydromorphone hydrochloride. The regulations on carrying out maintenance treatment in the Controlled Substances Prescription Act and the guidelines of the Federal Medical Association in Germany have been loosened based on the experiences of the COVID-19 pandemic, for example with respect to take-home prescriptions. There is an ongoing intensive discussion on how to deal with the decreasing number of outpatient clinics offering OMT. Conclusion: The first-line treatment for opioid addiction is opioid-assisted substitution treatment, including diamorphine and heroin-assisted treatment. Long-acting depot medications and implants still play a subordinate role. [ABSTRACT FROM AUTHOR]

Rationale: Methamphetamine addiction is a persistent and intractable pathological learning and memory, whereas no approved therapeutics is available. However, few attentions have been paid to how associative learning participates in the formation of intractable memory related to drug addiction Objectives and methods: To investigate the role of associative learning in methamphetamine addiction and the underlying neurobiological mechanism, methamphetamine self-administration, oral sucrose self-administration, chemogenetic neuromanipulation, and fiber photometry in mice were performed in this study. Results: We reported that associative learning increased methamphetamine-induced self-administration, but not oral sucrose self-administration. In addition, the enhancement of methamphetamine-induced self-administration was independent of more methamphetamine consumption, and remained with higher drug-taking and motivation in the absence of visual cues, suggesting the direct effects of the associative learning that enhanced methamphetamine-induced self-administration. Moreover, chemogenetic inactivation of the secondary visual cortex (V2) reduced the enhancement of the drug-taking induced by associative learning but did not alter sucrose-taking. Further fiber photometry of V2 neurons demonstrated that methamphetamine-associative learning elicits V2 neuron excitation, and sucrose-associative learning elicits V2 neuron inhibition. Conclusions: Therefore, this study reveals the neurobiological mechanism of V2 excitability underlying how associative learning participates in the formation of intractable memory related to drug addiction, and gives evidence to support V2 as a promising target for stimulation therapy for methamphetamine addiction. [ABSTRACT FROM AUTHOR]

Introduction: Pain and disability management are crucial for a speedy recovery. Combining analgesics with different mechanisms of action provides greater pain relief with lower doses, promoting efficient multimodal analgesia. This study evaluated the efficacy and safety between two fixed-dose combinations (FDC): etoricoxib/tramadol compared to paracetamol/tramadol for the management of acute low back pain (LBP) in a 7-day treatment. Methods: We conducted a phase IIIb, prospective, randomized, and multicenter study in patients with acute LBP treated with etoricoxib 90 mg/tramadol 50 mg (one packet of granules diluted in 100 ml of water, once a day [QD], for 7 days) or paracetamol 975 mg/tramadol 112.5 mg (one tablet of 325 mg/37.5 mg, three times a day [TID], for 7 days) to assess the efficacy (in terms of pain and disability improvement) and safety. Results: One hundred and twenty-four patients were randomized to receive either etoricoxib/tramadol QD (n = 61) or paracetamol/tramadol TID (n = 63). From the magnitude of change in pain evaluations, differences were observed between the treatment groups at 3 [p = 0.054, CI 95% − 0.648 (− 0.010 to 1.306)] and 5 days (p = 0.041). The proportion of patients with a 30% reduction in Visual Analogue Scale (VAS) score was statistically significant when comparing the treatment groups on the third day of follow-up [p = 0.008, CI 95% 0.241 (0.061–0.421)]. An improvement in LBP's disability to perform activities of daily routine (Oswestry and Roland–Morris questionnaires) was observed in both treatment groups. A total of 79 adverse events (AEs) (38 [48.1%] with etoricoxib/tramadol and 41 [51.9%] with paracetamol/tramadol) were reported. The most frequent AEs were nausea (17.7%) and dizziness (16.4%). Conclusions: The results show the clinical benefits of etoricoxib/tramadol FDC, such as the sparing effect of tramadol dose per day, early therapeutic response rate compared with paracetamol/tramadol; which translates into faster pain relief, better adherence, less tramadol drug dependency, and a reduction of related AEs incidence. Trial registration: ClinicalTrials.gov identifier, NCT04968158. [ABSTRACT FROM AUTHOR]

Objectives: Naltrexone prophylaxis is a well-established treatment for opioid use disorder. Our study aimed to track patients on naltrexone and investigate the factors predictive of retention. Materials and methods: The study comprised 100 participants initiated on naltrexone, who underwent a 12-week follow-up. We analyzed a range of socio-demographic and clinical variables at 04 and 12 weeks to compare those who remained in treatment program with those who experienced relapse. Results: The results revealed a predominantly young, unmarried, male, rural-dwelling sample with heroin as the primary opioid. Intravenous use was common (75%), with 57% of the participants exhibiting positive serology results for infections by hepatitis C (HCV), hepatitis B (HBV), and/or human immunodeficiency virus (HIV), and a significant proportion initiating opioids before the age of 20 (31%). The retention rates at 04 and 12 weeks were 83% and 64%, respectively. Several socio-clinical factors including age of initiation of use, rural residence, and comorbid psychiatric illness significantly influenced retention at 04 and 12 weeks. Conclusion: The findings highlight the importance of tailored interventions that take into consideration the age, residence, socio-economic status, and psychiatric comorbidity to enhance retention rates. Identifying these factors can help improve the effectiveness of treatment programs and promote sustained recovery efforts. [ABSTRACT FROM AUTHOR]

This study aimed to identify factors for successful cross-sector collaboration with faith-based responses to the opioid epidemic in southern Appalachia. In-depth interviews were conducted with representatives from organizations responding to the opioid epidemic (N = 25) and persons who have experienced opioid dependency (N = 11). Stakeholders perceived that collaboration is hindered by stigma, poor communication, and conflicting medical and spiritual approaches to opioid dependency. Collaborations are facilitated by cultivating compassion and trust, sharing information along relational lines, and discerning shared commitments while respecting different approaches. The study concludes with theoretical and practical implications for both religious leaders and potential cross-sector collaborators. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are a novel type of non-coding RNAs. Despite the fact that the functional mechanisms of most circRNAs remain unknown, emerging evidence indicates that circRNAs could sponge microRNAs (miRNAs), bind to RNA binding proteins (RBP), and even be translated into protein. Recent research has demonstrated the crucial roles played by circRNAs in neuropsychiatric disorders. The medial prefrontal cortex (mPFC) is a crucial component of drug reward circuitry and exerts top-down control over cognitive functions. However, there is currently limited knowledge about the correlation between circRNAs and morphine-associated contextual memory in the mPFC. Here, we performed morphine-induced conditioned place preference (CPP) in mice and extracted mPFC tissue for RNA-sequencing. Our study represented the first attempt to identify differentially expressed circRNAs (DEcircRNAs) and mRNAs (DEmRNAs) in the mPFC after morphine-induced CPP. We identified 47 significantly up-regulated DEcircRNAs and 429 significantly up-regulated DEmRNAs, along with 74 significantly down-regulated DEcircRNAs and 391 significantly down-regulated DEmRNAs. Functional analysis revealed that both DEcircRNAs and DEmRNAs were closely associated with neuroplasticity. To further validate the DEcircRNAs, we conducted qRT-PCR, Sanger sequencing, and RNase R digestion assays. Additionally, using an integrated bioinformatics approach, we constructed ceRNA networks and identified critical circRNA/miRNA/mRNA axes that contributed to the development of morphine-associated contextual memory. In summary, our study provided novel insights into the role of circRNAs in drug-related memory, specifically from the perspective of ceRNAs. [ABSTRACT FROM AUTHOR]

Maladaptive metacognitive thoughts about sleep often precede incidences of sleep disturbances. While the relationship between sleep disturbances and khat dependence is known, no research has examined the function of metacognition as a potential mediator between khat dependency and sleep problems in polysubstance users. This study used a brief structured questionnaire to measure the sleep problems, the severity of khat dependence (SDS-khat), and a metacognition score on khat-chewing polysubstance users (n = 374, age = 26.95 ± 3.80 years). The association was determined using Baron and Kenny's mediation effect model. The average SDS-khat score was 6.66 ± 1.41, and the metacognition score was 26.40 ± 4.09. Severity of khat dependence showed significant negative correlation with metacognition (b = −.53, standard error (SE) =.15, p <.001), and metacognition showed significant negative correlation with complaints of sleep disturbances, sleep deficit-related daytime problems, and sleep deficit-related socio-occupational disturbances (b = −.17, SE =.03, p <.001), (b = −.19, SE =.03, p <.001), (b = −.12, SE =.05, p <.05) respectively. Polysubstance users with khat dependence and comorbid sleep disturbances were more likely to have poor metacognition. [ABSTRACT FROM AUTHOR]

Substance abuse among adolescents has become a growing issue throughout the world. The significance of research on this life period is based on the occurrence of neurobiological changes in adolescent brain which makes the individual more susceptible for risk-taking and impulsive behaviors. Alcohol and nicotine are among the most available drugs of abuse in adolescents. Prolonged consumption of nicotine and alcohol leads to drug dependence and withdrawal which induce various dysfunctions such as memory loss. Coenzyme Q10 (CoQ10) is known to improve learning and memory deficits induced by various pathological conditions such as Diabetes mellitus and Alzheimer's disease. In the present study we investigated whether CoQ10 treatment ameliorates memory loss following a nicotine-ethanol abstinence. Morris water maze and novel object recognition tests were done in male Wistar rats undergone nicotine-ethanol abstinence and the effect of CoQ10 was assessed on at behavioral and biochemical levels. Results indicated that nicotine-ethanol abstinence induces memory dysfunction which is associated with increased oxidative and inflammatory response, reduced cholinergic and neurotrophic function plus elevated Amyloid-B levels in hippocampi. CoQ10 treatment prevented memory deficits and biochemical alterations. Interestingly, this ameliorative effect of CoQ10 was found to be dose-dependent in most experiments and almost equipotential to that of bupropion and naloxone co-administration. CoQ10 treatment could effectively improve memory defects induced by nicotine-ethanol consumption through attenuation of oxidative damage, inflammation, amyloid-B level and enhancement of cholinergic and neurotrophic drive. Further studies are required to assess the unknown side effects and high dose tolerability of the drug in human subjects. [ABSTRACT FROM AUTHOR]

Rationale: Methamphetamine (METH) exposure has toxicity in sperm epigenetic phenotype and increases the risk for developing addiction in their offspring. However, the underlying transgenerational mechanism remains unclear. Objectives: The current study aims to investigate the profiles of sperm epigenetic modifications in male METH-exposed mice (F0) and medial prefrontal cortex (mPFC) transcriptome in their male first-generation offspring (F1). Methods: METH-related male F0 and F1 mice model was established to investigate the effects of paternal METH exposure on reproductive functions and sperm DNA methylation in F0 and mPFC transcriptomic profile in F1. During adulthood, F1 was subjected to a conditioned place preference (CPP) test to evaluate sensitivity to METH. The gene levels were verified with qPCR. Results: METH exposure obviously altered F0 sperms DNA methylated profile and male F1 mPFC transcriptomic profile, many of which being related to neuronal system and brain development. In METH-sired male F1, subthreshold dose of METH administration effectively elicited CPP, along with more mPFC activation. After qPCR verification, Sort1 and Shank2 were at higher levels in F0 sperm and F1 mPFC. Conclusions: Our findings put new insights into paternal METH exposure-altered profiles of F0 sperm DNA methylation and male F1 mPFC transcriptomics. Several genes, such as Sort1 and Shank2, might be used as potential molecules for further research on the transgenerational vulnerability to drug addiction in offspring by paternal drug exposure. [ABSTRACT FROM AUTHOR]

Addiction is a leading cause of disease burden worldwide and remains a challenge in current neuroscience research. Drug-induced lasting changes in gene expression are mediated by transcriptional and epigenetic regulation in the brain and are thought to underlie behavioral adaptations. Emerging evidence implicates astrocytes in regulating drug-seeking behaviors and demonstrates robust transcriptional response to several substances of abuse. This review focuses on the astrocytic transcriptional and epigenetic mechanisms of drug action. [ABSTRACT FROM AUTHOR]

The prevention and treatment of addiction (moderate to severe substance use disorder—SUD) have remained challenging because of the dynamic and complex interactions between multiple biological and social determinants that shape SUD. The pharmacological landscape is ever changing and the use of multiple drugs is increasingly common, requiring an unraveling of pharmacological interactions to understand the effects. There are different stages in the trajectory from drug use to addiction that are characterized by distinct cognitive and emotional features. These are directed by different neurobiological processes that require identification and characterization including those that underlie the high co-morbidity with other disorders. Finally, there is substantial individual variability in the susceptibility to develop SUD because there are multiple determinants, including genetics, sex, developmental trajectories and times of drug exposures, and psychosocial and environmental factors including commercial determinants that influence drug availability. Elucidating how these factors interact to determine risk is essential for identifying the biobehavioral basis of addiction and developing prevention and treatment strategies. Basic research is tasked with addressing each of these challenges. The recent proliferation of technological advances that allow for genetic manipulation, visualization of molecular reactions and cellular activity in vivo, multiscale whole brain mapping across the life span, and the mining of massive data sets including multimodality human brain imaging are accelerating our ability to understand how the brain functions and how drugs influence it. Here, we highlight how the application of these tools to the study of addiction promises to illuminate its neurobiological basis and guide strategies for prevention and treatment. [ABSTRACT FROM AUTHOR]

Background: The extraordinary growth in women's incarceration over the past several decades has resulted in calls for expansion of research into their unique needs and experiences, including those related to pregnancy and perinatal care. However, while research into the health outcomes of women who are incarcerated while pregnant has grown, research on women's custodial and perinatal care patterns has remained nearly non-existent. Here, we sought to describe (1) the characteristics of the population of women who came to be incarcerated in a state prison system during pregnancy and (2) the characteristics of women's custodial and perinatal care patterns during and after incarceration. Methods: We conducted a retrospective chart review of the population of women who received perinatal care while incarcerated in the Arkansas state prison system over a 5-year period from June 2014 to May 2019. Electronic medical records and state prison records were merged to form our study population. Data were from 212 women (Mage = 28.4 years; 75.0% non-Latina White) with a singleton pregnancy who received at least one obstetric care visit while incarcerated. Results: Drug-related convictions were the most common crimes leading to women's incarceration while pregnant, and violent crime convictions were rare. Nearly half (43.4%) of women who gave birth in custody did so within 90 days of admission and the great majority (80.4%) released within 1-year of giving birth, including 13.3% who released within 30 days. Discussion: The frequency with which women who became incarcerated while pregnant released from prison either prior to or shortly after giving birth was a striking, novel finding of this study given the implications for perinatal care disruption among a high-risk population and the harms of forced separation from infants within hours of birth. Conclusions: Diversionary programs for pregnant women convicted of crimes, particularly in states without current access, are urgently needed and should be a priority for future policy work. [ABSTRACT FROM AUTHOR]

Although people with heroin addiction demonstrate impairment in delay discounting, no studies have explored the effects of drug-related cues on this impairment in this population. The present study aimed to examine the effects of suprathreshold and subthreshold drug-related cues on the level of delay discounting in individuals with heroin addiction. Study 1 recruited 37 male with heroin addiction and 34 male healthy individuals to complete an adapted version of the delay-discounting task. Drug-related or neutral cues of 500ms were presented before cross-selection was performed. Study 2 recruited 35 men with heroin addiction and 33 male healthy individuals who completed an adapted version of the delayed discounting task. Drug or neutral cues were presented for 33 ms with the addition of masked stimuli. The area under the curve values in the supra- and subthreshold drug-related cue conditions were significantly smaller than those in the neutral cue conditions in the group of participants with heroin addiction, but no such differences were found in the control group. This suggests that the level of delay discounting in people with heroin addiction is influenced by supra- and subthreshold drug-related cues, resulting in higher subjective discounting of delayed rewards. This finding may have clinical significance in the prevention of and intervention for heroin addiction. [ABSTRACT FROM AUTHOR]

Estrogen regulates a wide range of neuronal functions in the brain, such as dendritic spine formation, remodeling of synaptic plasticity, cognition, neurotransmission, and neurodevelopment. Estrogen interacts with intracellular estrogen receptors (ERs) and membrane-bound ERs to produce its effect via genomic and non-genomic pathways. Any alterations in these pathways affect the number, size, and shape of dendritic spines in neurons associated with psychiatric diseases. Increasing evidence suggests that estrogen fluctuation causes changes in dendritic spine density, morphology, and synapse numbers of excitatory and inhibitory neurons differently in males and females. In this review, we discuss the role of estrogen hormone in rodents and humans based on sex differences. First, we explain estrogen role in learning and memory and show that a high estrogen level alleviates the deficits in learning and memory. Secondly, we point out that estrogen produces a striking difference in emotional memories in men and women, which leads them to display sex-specific differences in underlying neuronal signaling. Lastly, we discuss that fluctuations in estrogen levels in men and women are related to neuropsychiatric disorders, including schizophrenia, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BPD), major depressive disorder (MDD), substance use disorder (SUD), and anxiety disorders. [ABSTRACT FROM AUTHOR]

Assessment of tobacco dependence is especially relevant in clinical settings, but different measures are used. The present study examines the predictive value of five tobacco dependence measures on abstinence at 6- and 12-month follow-ups in a sample of treatment-seeking smokers who had received a cognitive-behavioral intervention to quit smoking. A sample of 1108 treatment-seeking smokers was used. We assessed tobacco dependence with the Fagerstrom Test for Cigarette Dependence (FTCD), and the Nicotine Dependence Syndrome Scale short version (NDSS-S), as well as three measures derived from the FTCD: Heaviness of Smoking Index (HSI), the non-HSI items from the FTCD (non-HSI), Time to First Cigarette (TTFC). Regression models and the area under the receiver (AUC) operating characteristic curves were used to predict abstinence at 6- and 12-month follow-ups. Results showed that the FTCD, HSI, and TTFC were significant predictors of abstinence at 6- and 12-month follow-ups. AUC values were low for all measures, being highest for the HSI at both time points (0.63 and 0.62), followed by the FTCD (0.61 at both time points) and the TTFC (0.60 at both time points). Findings indicated that greater tobacco dependence is a significant predictor of a lower likelihood of long-term abstinence. Moreover, short tobacco dependence measures such as the HSI and the TTFC significantly predicted 6- and 12-month abstinence, similarly to the FTCD. Therefore, using a pragmatic criterion according to time availability would be useful when choosing the measures in clinical settings. [ABSTRACT FROM AUTHOR]

Abnormal genetic polymorphism of trace amine-associated receptor 1 (TAAR1) rs8192620 site has been confirmed to induce methamphetamine (MA) use and drug craving. However, the genetic susceptibility difference between MA addicts and heroin addicts is unknown. This study evaluated genetic heterogeneity of TAAR1 rs8192620 between MA and heroin addicts and elucidated whether rs8192620 genotypes associated with discrepancy in emotional impulsivity, which would help to instruct individualized treatment in addiction via acting on TAAR1 and evaluate risk of varied drug addiction. Participants consisting of gender-matched 63 MA and 71 heroin abusers were enrolled in the study. Due to mixed drug usage in some MA addicts, MA users were further subdivided into 41 only-MA (only MA taking) and 22 mixed-drug (Magu composed of about 20% MA and 70% caffeine) abusers. Via inter-individual single nucleotide polymorphism (SNP) analysis and two-sample t tests, respectively, the genotypic and Barratt Impulsiveness Scale-11 (BIS-11) scores differences between groups were completed. With following genotypic stratification, the differences in BIS-11 scores between groups were analyzed through two-sample t test. Individual SNP analysis showed significant differences in alleles distribution of rs8192620 between MA and heroin subjects (p = 0.019), even after Bonferroni correction. The TT homozygotes of rs8192620 dominated in MA participants, while C-containing genotypes in heroin (p = 0.026). There was no association of genotypes of TAAR1 rs8192620 with addicts' impulsivity. Our research indicates that the TAAR1 gene polymorphism might mediate the susceptibility discrepancy between MA and heroin abuse. [ABSTRACT FROM AUTHOR]

Alcohol and cocaine (COC) are commonly co-used drugs that cause addiction and have harmful effects. Their abuse may threaten the health of the abuser and public safety by causing serious accidents or crimes. The recidivism rate of drug-related crimes closely correlates with alcoholism. Several incidences of alcohol consumption in combination with drug abuse have been reported. Here, liquid chromatography tandem mass spectrometric method was developed to simultaneously analyze ethyl glucuronide (EtG), a metabolite of ethanol; COC; cocaethylene (CE), an alcohol-derived metabolite of COC; and benzoylecgonine (BZE), a major metabolite of COC, to determine the concurrent use of alcohol with COC. For pre-treatment, ultracentrifugation (5 min, 50,000 g) and mixed-mode anion exchange solid-phase extraction were used to increase the recovery of target compounds and minimize the matrix effect of hair. The lower limits of quantification were: 7 pg/mg (EtG), 2 pg/mg (COC), 10 pg/mg (CE), and 1 pg/mg (BZE). The correlation coefficient (r) of the calibration curve within the quantified range of target compounds was ≥ 0.9978. The intra- and inter-day accuracies were − 6.1–9.7% and − 9.3–8.3%, and intra- and inter-day precisions were 0.5–10.3% and 0.6–14.4%, respectively. The recovery, matrix effect, process efficiency, and autosampler stability were 89.2–104.8%, 81.6–105.4%, 81.5–107.1%, and 96.6–109.7%, respectively. The novel analytical method was validated with hair samples from individuals suspected of alcohol and COC use, and the method could distinguish between independent and concurrent use. Based on the findings, the analytical approach developed in this study is anticipated to be valuable in drug and alcohol dependence tests that require the simultaneous detection of alcohol and COC abuse. [ABSTRACT FROM AUTHOR]

Background and purpose: The use of the recreational drug gamma-hydroxybutyric acid (GHB) has increased over the past decade, concomitantly leading to a higher incidence of GHB use disorder. Evidence-based treatment interventions are hardly available and cognitive effects of long-term GHB use remain elusive. In order to study the development of GUD and the causal effects of chronic GHB consumption, a GHB self-administration model is required. Experimental approach: Long Evans rats had access to GHB in their home cage according to a two-bottle choice procedure for 3 months. Intoxication and withdrawal symptoms were assessed using an automated sensor-based setup for longitudinal behavioral monitoring. Rats were trained in an operant environment according to a fixed ratio (FR) 1, 2, and 4 schedule of reinforcement. Addiction-like behaviors were assessed through progressive ratio-, non-reinforced-, and quinine-adulterated operant tests. In addition, the novel object recognition test and elevated plus maze test were performed before and after GHB self-administration to assess memory performance and anxiety-like behavior, respectively. Key results: All rats consumed pharmacologically relevant levels of GHB in their home cage, and their intake remained stable over a period of 3 months. No clear withdrawal symptoms were observed following abstinence. Responding under operant conditions was characterized by strong inter-individual differences, where only a subset of rats showed high motivation for GHB, habitual GHB-seeking, and/or continued responding for GHB despite an aversive taste. Male rats showed a reduction in long-term memory performance 3 months after home-cage GHB self-administration. Anxiety-like behavior was not affected by GHB self-administration. Conclusion and implications: The GHB self-administration model was able to reflect individual susceptibility for addiction-like behavior. The reduction in long-term memory performance upon GHB self-administration calls for further research into the cognitive effects of chronic GHB use in humans. [ABSTRACT FROM AUTHOR]

The term "economon" (i:'ka.nə.muhn; plural: economa) is introduced here to describe an economic unit composed of two participants engaged in mutually reinforcing operant behavior. Economa are basic building blocks of transactional behavior that aggregate in social networks called economies. In a drug-addiction economon, operant behavior by one participant (the "supplier") provides an addictive drug as a reinforcer to the second participant (a "Person with Substance Use Disorder; PwSUD"). Reciprocal operant behavior by the PwSUD usually provides money as a reinforcer to the supplier. After defining the features of the drug-addiction economon, this article discusses its implications for (1) prevalence and virulence of drug addiction, (2) opportunities for drug-addiction research in general, (3) the "brain-disease model of addiction" in particular, and (4) factors that mitigate harm or promote risk of drug addiction. The economon model is intended to provide a novel perspective on the uniquely human disorder of drug addiction. [ABSTRACT FROM AUTHOR]

Substance craving may be triggered in people recovering from substance use disorder when listening to the same music genres they had listened to during active addiction. Given the limited research on this topic, this study examined how the combination of music and drugs facilitate addiction among people with active addiction and the role of music within this phenomenon. This phenomenological study included semi-structured interviews with 36 non-active addiction participants. Content analysis was employed to reveal themes and sub-themes regarding participants' views on the role and meaning of music during active addiction. Interview analysis revealed two main themes. The mutual enhancing effect theme relates to participants' utilization of music in service of the drug and vice versa. This mutual enhancing effect had an impact on sharpening sensory abilities and the mood participants wanted to amplify or evoke. The full addiction and music theme relates to a timepoint during active use, when music ceased to be relevant, and drugs dominated the entire experience. Participants reported down spiraling into their abuse, seeking seclusion and feeling lonelier and more depressed. The findings are discussed in light of theories in addiction and psychology of music. Rehabilitative implications are suggested. [ABSTRACT FROM AUTHOR]

Background: To promote parent-child reunification, family dependency drug courts (FDDCs) facilitate substance use disorder treatment for people whose children have been removed due to parental substance use. The COVID-19 pandemic disrupted FDDC operations, forcing FDDCs to quickly adapt to new circumstances. Although existing research has examined COVID-19 impacts on adult drug courts and civil dependency courts, studies have yet to examine the impact of COVID-19 on FDDCs specifically. Methods: To explore the impact of COVID-19 on FDDCs, we conducted 20 focus groups and 5 individual interviews with court team members from five Florida FDDCs between 2020 and 2022. Data were analyzed using iterative categorization. Results: Five overarching themes emerged. First, FDDCs adopted virtual technology during the pandemic and more flexible drug screening policies. Second, virtual technology was perceived as improving hearing attendance but decreasing client engagement. FDDC team members discussed a potential hybrid in-person/virtual hearing model after the pandemic. Third, COVID-19 negatively impacted parent-child visitation opportunities, limiting development of bonds between parents and children, and parent-child bonding is a key consideration during judicial reunification decisions. Fourth, COVID-19 negatively impacted the mental health of court team members and clients. Court team members adopted new informal roles, such as providing technical support and emotional counseling to clients, in addition to regular responsibilities, resulting in feeling overwhelmed and overworked. Court team members described clients as feeling more depressed and anxious, in part due to limited visitation opportunities with children, which decreased clients' motivation for substance use recovery. Fifth, COVID-19 decreased recruitment of potential clients into FDDCs. Conclusions: If FDDCs continue to rely on virtual hearings beyond the pandemic, they must develop practices for improving client engagement during virtual hearings. FDDCs should preemptively develop procedures for improving parent-child visitation during future public health crises, because limited visitation opportunities could weaken parent-child bonding and, ultimately, the likelihood of reunification. [ABSTRACT FROM AUTHOR]

Buprenorphine extended-release (ER) injection for subcutaneous use (Brixadi®; CAM2038; hereafter referred to as buprenorphine ER) is a useful addition to the treatment options for opioid use disorder (OUD). Brixadi® is formulated using FluidCrystal® injection depot technology, allowing for a low volume prefilled syringe and steady release of buprenorphine over one week or one month. In a pivotal phase 3 trial, weekly or monthly subcutaneous buprenorphine ER was non-inferior to daily sublingual buprenorphine/naloxone in terms of the proportion of opioid-negative urine samples and the responder rate. Based on the cumulative distribution function of the percentage of opioid-negative samples, superiority was demonstrated with subcutaneous buprenorphine ER compared with sublingual buprenorphine/naloxone. In the DEBUT trial, patients who received subcutaneous buprenorphine ER reported higher and more sustained treatment satisfaction than those who received sublingual buprenorphine. Real-world studies have also demonstrated high levels of satisfaction with buprenorphine ER in patients with opioid dependence. Buprenorphine ER was generally well tolerated, with a systemic safety profile similar to that of sublingual buprenorphine/naloxone. The most common treatment-emergent adverse events were injection-site reactions. Plain Language Summary: Opioid use disorder (OUD) is the long-term use of opioids that adversely affects physical and mental health. Treatment of OUD is based on psychosocial support and the use of opioid agonists to reduce illicit opioid use, craving, and HIV risk. The partial opioid agonist buprenorphine extended-release (ER) injection for subcutaneous use (Brixadi®; CAM2038; hereafter referred to as buprenorphine ER) is approved for patients with OUD who have started treatment with a single dose of a transmucosal buprenorphine product or who are already being treated with buprenorphine. The drug is released continuously over one week or one month. In a phase 3 trial in patients with OUD, weekly or monthly subcutaneous buprenorphine ER was not inferior to daily sublingual buprenorphine/naloxone in terms of a response to treatment (measured by urine drug screening and self-reporting of illicit opioid use). Buprenorphine ER was generally well tolerated. The most commonly reported adverse events were reactions at the injection site. Thus, weekly or monthly subcutaneous buprenorphine ER is a useful addition to the treatment options for OUD. [ABSTRACT FROM AUTHOR]

Research suggests that reducing rates of drug addiction requires a range of physical spaces where drug users and counselors can meet, build community, and work together. The efficacy of this 'social infrastructure,' however, depends not just on how its shared spaces facilitate access to social networks, but on how institutional rules and norms govern the social interaction that takes place in those spaces. I suggest that institutional norms nurture sobriety to the extent that the social arrangements they foster are (i) discretionary, since individuals trying to re-establish sobriety have heterogeneous social preferences; (ii) unconditional, since individuals' efforts to re-achieve sobriety frequently involve setbacks; and (iii) low-pressure, since individuals may find extraneous turmoil damaging to their renascent sobriety. To the extent that institutional norms facilitate contrary social arrangements, shared settings are liable to backfire—to undermine or at least fail to nurture sobriety—which I illustrate using the case of sobriety-oriented organizations in the Boston area. Critically, while the first two aspects are governed largely by intra-organizational norms, the third is governed by norms between multiple sobriety-oriented organizations. Upholding healthful local norms, then, demands commitment at both the organization and system levels. [ABSTRACT FROM AUTHOR]

The aim of this article is to revisit the multivariate causes of drug use. From the initial drive to experiment, to a progression towards dependence, this review endeavours to extrapolate the aetiology of causation. In doing so, prevalence of, and attitudes towards drug use are firstly examined. Influences on why people use illicit drugs are subsequently explored through the lens of established risk factors. Drug use and dependence are embedded within a complex interplay of invidual, genetic, cultural, and socio-economic components. By exploring the aetiology of drug use in a holistic sense, this will not only aid the therapeutic quality of intervention from clinicians, but enable the development of more comprehensive and tailored intervention plans in supporting recovery. [ABSTRACT FROM AUTHOR]

Technology transfer centers (TTCs) facilitate the movement of evidence-based practices in behavioral healthcare from theory to practice. One of the largest such networks is the Substance Abuse and Mental Health Services Administration's (SAMHSA) TTC Network. This brief report shares findings from an organizational network analysis (ONA) of the network conducted as part of an external evaluation. For non-supervisory TTCs (n = 36) across three focus areas (addiction, prevention, and mental health), the authors computed network density, harmonic closeness, and non-null dyadic reciprocity for five types of interactions (e.g., "collaborated in workgroups"), then, for each interaction type, used Welch's T-test to compare mean harmonic closeness of standalone TTC grantees versus multiple-TTC grantees. ONA identified potentially isolated regional TTCs as well as mismatches between some centers' desired scope and their network centrality and enabled investigation of broader questions around behavioral health support systems. The approach appears useful for evaluating TTCs and similar support networks. [ABSTRACT FROM AUTHOR]

A key tenet of critical health research is that individual symptoms must be considered in light of the social and political contexts that shape or, in some cases, produce them. Precisely how oppressive social forces give rise to individual symptoms, however, remains challenging to theorize. This article contributes to debates over the interpretation of symptoms through a close reading of the case of Leon, an African American man struggling with an addiction to crack cocaine. Leon presented a complex illness narrative in which his addiction was clearly a product of structural racism, but also the result of dynamics within his family. Drawing on critical reevaluations of Freud's concept of the dreamwork, I call attention to the surface elements of Leon's narrative—what I term the surface of the symptom—and to the formal mechanisms by which latent contents (such as the social, the political, and the personal) are transformed into the manifest form of his symptom. This formal mode of reading offers a productive way of approaching questions of demystification and interpretation, one that holds in tension the register of social causation with the singularities of individuals and their symptoms. [ABSTRACT FROM AUTHOR]

Addiction is a serious public health problem, and the current pharmacotherapy is unable to prevent drug use reinstatement. Studies have focused on physical exercise as a promising coadjuvant treatment. Our research group recently showed beneficial neuroadaptations in the dopaminergic system related to amphetamine-relapse prevention involving physical exercise-induced endogenous opioid system activation (EXE-OS activation). In this context, additional mechanisms were explored to understand the exercise benefits on drug addiction. Male rats previously exposed to amphetamine (AMPH, 4.0 mg/kg) for 8 days were submitted to physical exercise for 5 weeks. EXE-OS activation was blocked by naloxone administration (0.3 mg/kg) 5 min before each physical exercise session. After the exercise protocol, the rats were re-exposed to AMPH for 3 days, and in sequence, euthanasia was performed and the VTA and NAc were dissected. In the VTA, our findings showed increased immunocontent of proBDNF, BDNF, and GDNF and decreased levels of AMPH-induced TrkB; therefore, EXE-OS activation increased all these markers and naloxone administration prevented this exercise-induced effect. In the NAc, the same molecular markers were also increased by AMPH and decreased by EXE-OS activation. In this study, we propose a close relation between EXE-OS activation beneficial influence and a consequent neuroadaptation on neurotrophins and dopaminergic system levels in the mesolimbic brain area, preventing the observed AMPH-relapse behavior. Our outcomes bring additional knowledge concerning addiction neurobiology understanding and show that EXE-OS activation may be a potential adjuvant tool in drug addiction therapy. [ABSTRACT FROM AUTHOR]

Current study aimed to compare the psychopathological profile of patients with chronic diseases using the BM-SCL-90-R in Malaysia. This was a cross-sectional study carried out in Kuala Lumpur and consisted of 648 individuals including heroin addiction patients, diabetes patients, and the healthy population. The majority of the subjects were Malay (79.2%) and Muslim (79.3%). The current finding found the rate of psychopathological symptoms among heroin addiction patients, diabetes patients, and the healthy people at 42% (95% CI: 36.5–49.7), 43.1% (95% CI: 35.5–48.5), and 14.7% (95% CI: 9.9–19.5), respectively. The rate of all psychopathological symptoms in heroin addiction patients and diabetes patients was significantly higher than the healthy group, except obsessive–compulsive which was lower in diabetes patients. The odds ratios for depression (OR = 0.61, 95% CI: 0.41–0.91) and obsessive–compulsive (OR = 0.21, 95% CI: 0.12–0.36) in diabetes patients were significantly lower than the heroin addiction patients, and the mean scores of phobic anxiety, paranoid, and psychotic in diabetes patients were significantly higher than heroin addiction patients. This study indicates that there is a significant difference between the psychopathological profiles of these chronic patients. This study highlights a need for further comparative studies focusing on the link between specific psychopathological symptoms and chronic diseases in Malaysia. [ABSTRACT FROM AUTHOR]

Opiate alkaloids and their synthetic derivatives are still widely used in pain management, drug addiction, and abuse. To avoid serious side effects, compounds with properly designed pharmacological profiles at the opioid receptor subtypes are long needed. Here a series of 17-N-substituted derivatives of normorphine and noroxymorphone analogues with five- and six-membered ring substituents have been synthesized for structure–activity study. Some compounds showed nanomolar affinity to MOR, DOR and KOR in in vitro competition binding experiments with selective agonists [3H]DAMGO, [3H]Ile5,6-deltorphin II and [3H]HS665, respectively. Pharmacological characterization of the compounds in G-protein signaling was determined by [35S]GTPγS binding assays. The normorphine analogues showed higher affinity to KOR compared to MOR and DOR, while most of the noroxymorphone derivatives did not bind to KOR. The presence of 14-OH substituent resulted in a shift in the pharmacological profiles in the agonist > partial agonist > antagonist direction compared to the parent compounds. A molecular docking-based in silico method was also applied to estimate the pharmacological profile of the compounds. Docking energies and the patterns of the interacting receptor atoms, obtained with experimentally determined active and inactive states of MOR, were used to explain the observed pharmacological features of the compounds. [ABSTRACT FROM AUTHOR]

Drug abuse has a high prevalence worldwide and causes many health-related disorders. There are limited human exposure studies on establishing lead exposure levels and their propensity for drug addiction. In the present study, blood samples were tested for lead (Pb) concentrations in illicit drug users together with the related symptoms in comparison with control group of non-drug users. The study was performed on 250 volunteers divided equally in four drug groups, namely, opioids, hashish, methadone, and methamphetamine, and one control group of non-drug users. Participants were recruited from drug addiction clinics and camps in Kashan city, Iran, who were using drugs continuously for more than 1 year. Control group was recruited from companions of the patients with no drug use history. In the investigated groups of drug users, the highest blood-lead level (BLL) concentrations were observed in the opioid group (mean 37.57 µg/dL) with almost 3.7 times higher than in the control group (mean 3.39 µg/dL). In the methamphetamine group, type of occupation had the significant association with BLL concentrations. The positive correlation was revealed in the opioid and methadone groups for BLL concentrations and the duration of drug usage. In the opioid group, the highest BLL concentrations were observed among users who used both methods of drug use: smoking and eating. Also, several behavioral and life-style factors were identified which influence the blood-lead concentration in the drug users. The results of our study revealed that the BLL concentrations in investigated drug users' groups were significantly higher than in the control group (P < 0.001). That can be related with the Pb contents in illicitly used drugs. Apart other adverse health effects, long-term illicit drug use might cause to lead poisoning. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to compare sex differences in the clinical manifestations related to dependence behaviors in medication-overuse headache (MOH). Methods: Consecutive patients with newly diagnosed chronic migraine (CM) with and without MOH based on the Third Edition of International Classification of Headache Disorders (ICHD-3) were enrolled prospectively from the headache clinic of a tertiary medical center. Demographics and clinical profiles were collected by using a questionnaire, which included current use of tobacco, alcohol, and caffeinated beverages, the Leeds Dependence Questionnaire (LDQ), the Severity of Dependence Scale (SDS), the Headache Impact Test-6 (HIT-6), and the Pittsburgh Sleep Quality Index (PSQI). Results: In total, 1419 CM patients (1135F/284 M, mean age 41.7 ± 13.9 years) were recruited, including 799 with MOH (640F/159 M, mean age 42.5 ± 13.2 years) (56.3%). Smoking was associated with an increased risk for MOH in men (odds ratio [OR] = 3.60 [95% confidence interval = 1.73–7.50], p = 0.001), but not in women (OR = 1.34 [0.88–2.04], p = 0.171) (p = 0.021 for interaction). Hypnotic use ≥ 3 days/week was a risk factor for MOH (OR = 2.55 [95% confidence interval = 2.00–3.24], p < 0.001), regardless of sex. By using receiver operating characteristics (ROC) curves, the cutoff scores of the LDQ for MOH were determined at 7 for women and 6 for men, and those for the SDS were 5 and 4, respectively (area under curve all ≥ 0.83). Among patients with MOH, the male sex was associated with a shorter latency between migraine onset and CM onset (12.9 ± 11.1 vs. 15.4 ± 11.5 years, p = 0.008), despite less average headache intensity (6.7 ± 1.9 vs. 7.2 ± 1.9, p = 0.005), functional impacts (HIT-6: 63.4 ± 8.3 vs. 65.1 ± 8.0, p = 0.009), and sleep disturbances (PSQI: 10.9 ± 4.4 vs. 12.2 ± 4.3, p = 0.001). Conclusions: The current study identified an association between smoking and MOH in men, as well as sex-specific cutoffs of the LDQ and the SDS, for MOH. MOH was characterized by a shorter latency between migraine onset and CM onset in men and a more severe phenotype in women. Sex should be considered as an important factor in the evaluation of MOH. [ABSTRACT FROM AUTHOR]

Opioid addiction and the opioid overdose epidemic are becoming more serious, and the development of therapeutic agents is essential for the pharmacological treatment of substance use disorders. The κ-opioid receptor (KOP) is a member of the opioid receptor system that has been gaining attention as a promising molecular target for the treatment of numerous human disorders, including pain, depression, anxiety, and drug addiction. Here, we biologically and pharmacologically evaluated a novel azepane-derived ligand, NP-5497-KA, as a selective KOP agonist. NP-5497-KA had 1000-fold higher selectivity for the KOP over the μ-opioid receptor (MOP), which was higher than nalfurafine (KOP/MOP: 65-fold), and acted as a selective KOP full agonist in the 3′,5′-cyclic adenosine monophosphate assay. The oral administration of NP-5497-KA (1–10 mg/kg) dose-dependently suppressed morphine-induced conditioned place preference in C57BL/6 J mice, and its effects were comparable to an intraperitoneal injection of nalfurafine (1–10 μg/kg). Nalfurafine (10 μg/kg) significantly inhibited rotarod performance, whereas NP-5497-KA (10 mg/kg) exerted no effect on rotarod performance. These results indicate that NP-5497-KA may be a novel option for the treatment of opioid use disorder with fewer side effects. [ABSTRACT FROM AUTHOR]

This study was a secondary analysis of baseline data from a clinical trial of an intensive group-based smoking cessation treatment for people with HIV (PWH) who smoke. It examined the cross-sectional relationship between perceived ethnic discrimination (PED) and cigarette smoking variables (i.e., nicotine dependence, motivation to quit smoking, self-efficacy to quit smoking) among PWH and explored whether depressive symptoms mediated the relationship between PED and smoking variables. Participants (N = 442; Mage = 50.6; 52.8% Male; 56.3% Black, non-Hispanic; 6.3% White, non-Hispanic; 13.3% Hispanic; 87.7% unemployed; 81.6% single) completed measures of demographics, cigarette smoking, depressive symptoms, and PED. Greater PED was related to lower self-efficacy to quit smoking, greater perceived stress, and greater depressive symptoms. In addition, depressive symptoms mediated the relationship between PED and two cigarette smoking variables (i.e., nicotine dependence, self-efficacy to quit smoking). Findings highlight the need for smoking interventions to target PED, self-efficacy, and depressive symptoms to improve smoking cessation variables among PWH. [ABSTRACT FROM AUTHOR]

The co-occurrence of substance use disorders (SUD) and other mental disorders (OMD) is assumed to be high, but the details are uncertain in Spain. The objective of the present study was to know the prevalence of this comorbidity, as well as the pharmacological treatment, both in specific addiction treatment networks and in mental health networks, with a gender perspective. Observational, multicenter study, with a randomized sample, of patients under treatment for SUD or OMD in Spain (N = 1783). A specific questionnaire, collecting sociodemographic and clinical variables, diagnosed SUD and OMD, and prescribed psychotropic drugs, was completed by treating clinicians. Differences between females and males were searched. A high prevalence of OMD was found in those patients treated for their SUD (71%), and also of diagnoses of SUD (59%) in people treated for OMD. Significant relationships between addiction to certain substances and specific mental disorders were found (with no main differences between women and men). The treatments for OMD were very common in the addiction treatment networks, but that of SUDs in those patients treated in the mental health networks was less than expected. A high prescription of benzodiazepines was found. Women were less frequently diagnosed with cannabis, opioid, and especially cocaine use disorders, and they had fewer psychotic disorders and more affective, anxiety, sleep, and eating disorders, with the rest being the same, including personality disorders. Women had fewer treatments with agonists and more with antagonists, and more prescriptions of anxiolytics and antidepressants. This study provides preliminary information on the coexistence in routine clinical practice of addictive disorders and other mental disorders in Spain, and on the treatment provided, and shows differences in prevalence and clinical characteristics, and especially in treatment approaches between women and men. Thus, should be useful to adapt the treatment response with greater precision, and with a gender perspective. [ABSTRACT FROM AUTHOR]

The chemical analysis of dental hard tissues can provide information on previous drug use due to the deposition of drugs into this tissue. For the interpretation of analytical results in, e.g., postmortem toxicology or regarding archeological samples, the influence of drug dosing, consumption frequency, duration of intake and type of drug on analyte concentrations in teeth has to be characterized. To approximate these correlations, in vitro models were applied to investigate the time dependency of drug deposition via and against pulp pressure (perfusion studies) and the concentration dependency of drug deposition via oral cavity (incubation study) as well as the influence of de- and remineralization (pH cycling) on the incorporation of drugs in bovine dentin pellets. Some of the drugs of abuse most relevant in forensic case work (amphetamines, opiates, cocaine and benzoylecgonine) were applied. Concentrations in dentin samples were analyzed by liquid chromatography–tandem mass spectrometry (LC–MS/MS) after pulverization and extraction via ultrasonication with methanol. The studies showed that drug deposition in dentin likely depends on the physicochemical properties of the drug molecules as well as on the duration of contact with drugs via the blood stream and on drug concentrations present in the oral cavity. Higher drug concentrations in teeth can result from a more frequent or longer drug use. In addition, intake of higher doses or oral/inhalative consumption can also be expected to lead to higher drug concentrations. These findings can be helpful for the interpretation of postmortem cases. [ABSTRACT FROM AUTHOR]

Drug overdose deaths continue to increase in the United States for all major drug categories. Over the past two decades the total number of overdose fatalities has increased more than fivefold; since 2013 the surge in overdose rates is primarily driven by fentanyl and methamphetamines. Different drug categories and factors such as age, gender, and ethnicity are associated with different overdose mortality characteristics that may also change in time. For example, the average age at death from a drug overdose has decreased from 1940 to 1990 while the overall mortality rate has steadily increased. To provide insight into the population-level dynamics of drug overdose mortality, we develop an age-structured model for drug addiction. Using an augmented ensemble Kalman filter (EnKF), we show through a simple example how our model can be combined with synthetic observation data to estimate mortality rate and an age-distribution parameter. Finally, we use an EnKF to combine our model with observation data on overdose fatalities in the United States from 1999 to 2020 to forecast the evolution of overdose trends and estimate model parameters. [ABSTRACT FROM AUTHOR]

Scholarship on negative social ties typically portrays them as distinct liabilities and optimal candidates for excision from social networks. I argue that this premise is based on a short-sighted understanding of what it means for social ties to be negative. In particular, negativity as a trait of social ties has multiple dimensions, such that ties can be negative in a relatively objective sense (that is, they can pose risk to network egos by virtue of some quality or qualities) with or without being negative in a relatively subjective sense (that is, feeling taxing to egos). To disentangle these two dimensions, I report on a case study of network ties among residents of Sycamore, a leased-housing program for young adults trying to overcome drug addictions. I describe how residents universally understood certain ties—ties to individuals who were addicted to drugs or otherwise had drugs in their possession—as risks to their sobriety, but found only some of those ties taxing. In fact, some risky ties seemed beneficial to residents by displaying nonjudgmental attitudes in the wake of residents' setbacks, reminding residents of their lowest points, and supplying residents with chances to practice self-restraint and advantageous decision making. The findings show how people can know that certain ties pose risks to their well-being but feel that the ties are good for them. Broadly, the article encourages greater attention to the multidimensional nature of ties' negativity and highlights the unexpected roles putatively negative ties play in individuals' lives. [ABSTRACT FROM AUTHOR]

Background: Sexually transmitted disease (STD) cases are rising in the USA, especially among sexual and gender minorities, despite the availability of numerous STD prevention programs. We examined the differences in STD prevalence among sexual and gender minority subgroups with major depressive episode symptoms and substance use dependence. Methods: We combined 2017, 2018, and 2019 National Survey on Drug Use and Health (NSDUH) public-use data on adults (N = 127,584) to conduct weighted multivariable logistic regression and margins analyses. Results: Approximately 2.05% of the population reported having STDs. The population that had major depressive episode symptoms (AOR = 1.70, 95% CI = 1.46, 1.99), alcohol use dependence (AOR = 1.79, 95% CI = 1.49, 2.16), illicit drug use other than marijuana use dependence (AOR = 2.25, 95% CI = 1.73, 2.92), or marijuana use dependence (AOR = 1.90, 95% CI = 1.57, 2.31) had higher odds of contracting STDs compared to their counterparts. Lesbian/gay (AOR = 2.81, 95% CI = 2.24, 3.54) and bisexual (AOR = 1.95, 95% CI = 1.60, 2.37) individuals had higher odds of contracting STDs. Lesbians/gays with major depressive episode symptoms, alcohol use dependence, or illicit drug use other than marijuana use dependence had the highest probability of having STDs, compared to bisexuals and heterosexuals with major depressive episode symptoms, alcohol use, or illicit drug use other than marijuana use dependence. Bisexuals with marijuana use dependence had the highest probability of STD contraction compared to their lesbian/gay and heterosexual counterparts. Within each sexual identity subgroup, the probability of having STDs was higher for individuals with major depressive episode symptoms, or dependence on alcohol use, illicit drug use other than marijuana use, or marijuana use compared to their counterparts. Conclusion: Major depressive episode symptoms, substance use dependence, and sexual and gender minority status had higher risks for STD diagnosis, particularly for sexual and gender minorities with major depressive episode symptoms or substance use dependence. Tailored interventions based on major depressive episode symptoms and substance use dependence may reduce the prevalence of STD, especially among sexual and gender minorities. [ABSTRACT FROM AUTHOR]

Copyright of AIDS & Behavior is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Arterial hypertension, cigarette smoking, excessive alcohol abuse and drug addiction such as cocaine all are known risk factors for aneurysmal subarachnoid hemorrhage (SAH). However, there is little information on whether tramadol addiction should also be considered as a risk factor for SAH. The purpose of this study was to investigate the prevalence and the impact of tramadol addiction on the symptomatology of intracranial aneurysmal SAH. We recruited 237 cases with acute aneurysmal ASH with a mean age of 52.3 ± 11.8 ranging from 17 to 86 years old. Results: There were 124 males and 113 females; 43 cases had a history of tramadol addiction (18.1%). Tramadol addicts were significantly younger, more likely to be male (97.7%), and more commonly associated with seizure onset compared with non-addicts. Multiple aneurysms, wide neck, and sizable aneurysms were significantly more common in tramadol than non-tramadol addicts as were dissecting aneurysms. There is a high association of acute aneurysmal SAH with tramadol addiction, especially in young patients. Conclusions: Tramadol addiction might be regarded as modifiable risk factor of aneurysmal ASH and tramadol addicts had a worse presentation than non-tramadol addicts. If this finding is proved, it will be of great importance in managing patients with ruptured and un-ruptured intracranial aneurysms. Tramadol is available over-counter in some countries, more studies are needed. [ABSTRACT FROM AUTHOR]

Cancer pain remains a significant problem worldwide. It is often undertreated and presents in about half of cancer patients. Although several guidelines and pharmacological interventions for cancer pain management (CPM) exist, inadequate assessment and undertreatment of cancer pain are well-documented globally, especially in developing countries, including Libya. Perceptions, cultural and religious beliefs of healthcare professionals (HCP), patients, and caregivers about cancer pain and opioids are reported as barriers to CPM globally. This qualitative descriptive study aimed to explore Libyan HCPs', patients', and caregivers' views and religious beliefs about CPM and involved semi-structured interviews with 36 participants: 18 Libyan cancer patients, 6 caregivers, and 12 Libyan HCPs. Thematic analysis was used to analyse the data. Patients, caregivers, and newly qualified HCPs were concerned about poor tolerance and drug addiction. HCPs perceived a lack of policies and guidelines, pain rating scales, and professional education and training as CPM barriers. Some patients were unable to pay for medicines if they faced financial difficulties. Instead, patients and caregivers emphasised religious and cultural beliefs for managing cancer pain, including the use of the Qur'an and cautery. Our results suggest that religious and cultural beliefs, lack of knowledge and training in CPM among HCPs, and economic and Libyan healthcare system-related factors negatively affect CPM in Libya. [ABSTRACT FROM AUTHOR]

Gambling disorder is a common and problematic behavioral disorder associated with depression, substance abuse, domestic violence, bankruptcy, and high suicide rates. In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), pathological gambling was renamed "gambling disorder" and moved to the Substance-Related and Addiction Disorders chapter to acknowledge that research suggests that pathological gambling and alcohol and drug addiction are related. Therefore, this paper provides a systematic review of risk factors for gambling disorder. Systematic searches of EBSCO, PubMed, and Web of Science identified 33 records that met study inclusion criteria. A revised study acknowledges as risk factors for developing/maintaining a gambling disorder being a single young male, or married for less than 5 years, living alone, having a poor education, and struggling financially. [ABSTRACT FROM AUTHOR]

Objectives: Social behavior, a set of motivating activities critical for survival, is disturbed in cholestasis conditions and many substance abusers as well as psychiatric disorders. The documented loss of social interest in cholestatic patients may be associated with depressive symptoms. Interestingly, the endogenous opioid system is involved in the modulation of depression. Methods in this research: , we assessed the effect of cholestasis and drug dependence on social and depression behaviors using the Three-Chamber Paradigm Test, Forced Swim Test (FST), and Tail Suspension Test (TST) as well as Open Field Test (OFT) in male NMRI mice. Results: The results indicated that alone administration of morphine and tramadol, as well as co-administration of them, increased social motivation and novelty but decreased depression in bile duct ligated mice. Whereas, alone administration of naloxone (a µ-opioid receptor antagonist) and co-administration of it along with morphine and tramadol decreased social motivation and novelty while enhanced depression in the sham-operated and bile duct ligated mice. These administrations of drugs did not change locomotor activity compared to the control group. Conclusion: In conclusion, it appears that (i) both cholestasis and drug dependence impaired social motivation behavior, as well as induced depression-like behavior in the bile duct, ligated mice, (ii) alone administration of morphine and tramadol as well as co-treatment of them may protect against cholestasis and drug dependence induced abnormal behaviors, (iii) µ-opioid receptors play an important role in modulation of social motivation and depression behaviors in mice. [ABSTRACT FROM AUTHOR]

Copyright of Sozial Extra is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The rise in nonmedical opioid overdoses over the last two decades necessitates improved detection technologies. Manual opioid screening exams can exhibit excellent sensitivity for identifying the risk of opioid misuse but can be time-consuming. Algorithms can help doctors identify at-risk people. In the past, electronic health record (EHR)–based neural networks outperformed Drug Abuse Manual Screenings in sparse studies; however, recent data shows that it may perform as well or less than manual screenings. Herein, a discussion of several different manual screenings and recommendations is contained, along with suggestions for practice. A multi-algorithm approach using EHR yielded strong predictive values of opioid use disorder (OUD) over a large sample size. A POR (Proove Opiate Risk) algorithm provided a high sensitivity for categorizing the risk of opioid abuse within a small sample size. All established screening methods and algorithms reflected high sensitivity and positive predictive values. Neural networks based on EHR also showed significant effectiveness when corroborated with Drug Abuse Manual Screenings. This review highlights the potential of algorithms for reducing provider costs and improving the quality of care by identifying nonmedical opioid use (NMOU) and OUD. These tools can be combined with traditional clinical interviewing, and neural networks can be further refined while expanding EHR. [ABSTRACT FROM AUTHOR]

This study aims to explore the mechanism of psychological capital's influence on relapse tendency of drug addicts under the COVID-19, and construct a moderated mediation model. 977 individuals with drug addiction who come from a mandatory drug rehabilitation center in China completed the Chinese versions of Psychological capital Questionnaire, the Relapse Tendency Questionnaire,the Coping Style Questionnarie and the Life History Strategy Scale.The results showed that(1) there was a significant negative correlation between psychological capital and relapse tendency;(2)positive coping style mediated the relationship between psychological capital and relapse tendency;(3) life history strategy is an important moderator between psychological capital and positive coping style.These findings help us to better understand the impact of psychological capital and positive coping style on relapse tendency. [ABSTRACT FROM AUTHOR]