Drug Dependence Research Articles

Gene × environment effects and mediation involving adverse childhood events, mood and anxiety disorders, and substance dependence.

Adverse childhood events (ACEs) contribute to the development of mood and anxiety disorders and substance dependence. However, the extent to which these effects are direct or indirect and whether genetic risk moderates them is unclear. We examined associations among ACEs, mood/anxiety disorders and substance dependence in 12,668 individuals (44.9% female, 42.5% African American/Black, 42.1% European American/white). Using latent variables for each phenotype, we modelled direct and indirect associations of ACEs with substance dependence, mediated by mood/anxiety disorders (the forward or 'self-medication' model) and of ACEs with mood/anxiety disorders, mediated by substance dependence (the reverse or 'substance-induced' model). In a subsample, we tested polygenic scores for the substance dependence and mood/anxiety disorder factors as moderators in the mediation models. Although there were significant indirect paths in both directions, mediation by mood/anxiety disorders (the forward model) was greater than that by substance dependence (the reverse model). Greater genetic risk for substance use disorders was associated with a weaker direct association between ACEs and substance dependence in both ancestry groups (reflecting gene × environment interactions) and a weaker indirect association in European-ancestry individuals (reflecting moderated mediation). We found greater evidence that substance dependence reflects self-medication of mood/anxiety disorders than that mood/anxiety disorders are substance induced. Among individuals at higher genetic risk for substance dependence, ACEs were less associated with that outcome. Following exposure to ACEs, multiple pathways appear to underlie the associations between mood/anxiety disorders and substance dependence. Specification of these pathways could inform individually targeted prevention and treatment approaches.

INVESTIGATION OF THE ANALGESIC ACTIVITY OF NEW LIGANDS OF THE NMDA RECEPTOR COMPLEX

According to the Russian Society for the Study of Pain, 90% of patients seeking medical help experience pain, with 70% suffering from chronic pain [15, 16]. It should be acknowledged that the capabilities of traditional analgesic methods are limited, and the prescription of opioids is associated with an increase in complications, the development of tolerance, drug dependence, and an increase in the patient's hospital stay costs. Thus, the main directions for improving pain relief include the rational combination of analgesics with different mechanisms of action and the development of new effective and safe medicinal substances with analgesic activity. It is known that the activation of spinal cord NMDA receptors is a key factor in the pathogenesis of acute and chronic pain. Therefore, the use of existing NMDA antagonists in analgesic schemes, as well as the development of new compounds targeting the NMDA receptor complex, is of particular interest. New ligands of the glutamate NMDA receptor complex are derivatives of imidazole-4,5-dicarboxylic acid. The conformational rigidity of the molecules of imidazole-4,5-dicarboxylic acid derivatives allow for increased selectivity of interaction and reduced side effects. The aim of the study was to investigate the analgesic effect of new ligands of the glutamate NMDA receptor complex - derivatives of imidazole-4,5-dicarboxylic acid in mice using the tail-flick test and the formalin test. The tested compounds (IEM-303 and IEM-2044) were administered intraperitoneally at doses of 5, 10, 15, 20 mg/kg. Мetamizole was used as a comparison drug. The experiments demonstrated a significant dose-dependent analgesic effect of the tested compounds in experimental models of acute pain at doses of 5-20 mg/kg. In the groups receiving IEM-2044 and IEM-303, the tail-flick latency increased by 1.4-1.7 times compared to the control group. The analgesic activity of the tested compounds at doses of 10-20 mg/kg was comparable to the analgesic activity of metamizole, indicating the prospect of developing these agents and further searching for effective and safe analgesics among this pharmacological class.

Validity of severity of dependence scale-Indonesia in patients with drug and alcohol dependence

A quick and self-administrative screening tool to detect dependence on various substances is vital in the early detection of multiple substance dependence. This study aimed to validate the severity of the dependence scale Indonesian version (SDS-Ina) in a sample of clinically diagnosed substance-related disorder subjects. The study was an observational study and rapid assessment of suspected patients with drug and alcohol dependence in an outpatient psychiatric unit in Yogyakarta, Indonesia. The translated severity of dependence scale-Indonesia (SDS-Ina) questionnaire was given out to 65 subjects through an online form. The content validity of the translated SDS was assessed with Aiken’s V, and concurrent validity was analyzed in comparison to the Diagnostic of Statistical and Manual Mental Disorder IV (DSM-IV) diagnosis criteria with Pearson correlation coefficient and factor validity through principal component analysis (PCA). Reliability was assessed using Cronbach’s Alpha and test-retest reliability. Aiken’s V index concluded that our content validity was valid (all>0.75). A Pearson correlation coefficient of=0.93 (P<0.001), PCA of all items ≥0.60 further validates the SDS-Ina. Internal reliability of Cronbach’s Alpha 0.907 and test-retest reliability (intraclass correlation coefficient (ICC): all≥0.75). In conclusion, the translated SDS is a valid and reliable tool to measure the psychological dependence of Indonesian subjects involved in this study.

Parent-child conflict: A risk factor for substance abuse among adolescents

Parent-child conflict: A risk factor for substance abuse among adolescents

Parental Influence on Smoking Behavior in Teenagers

Adolescence is a problematic and difficult period because it often gives rise to several problems that are difficult to overcome, such as drug and cigarette dependence. The proportion of smoking among teenagers aged less than 15 years is greater than among those aged above because teenagers tend to have a greater curiosity, so they are more likely to smoke than adults. Parents are one of the factors causing smoking behavior in teenagers, because parents are figures for their children, so if parents smoke, teenagers tend to imitate their parents' behavior. Parents who smoke significantly increase teenagers' tendency to smoke by 1.397 times compared to teenagers whose parents are not smokers. Smoking has a huge negative impact on teenagers. Knowing how much influence parents have on adolescent smoking behavior. This research uses quantitative methods, and analytical descriptive design with a cross-sectional approach. The research population was teenagers with smoking behavior, totaling 83 respondents. The sampling technique uses purposive sampling. The questionnaire used was created by researchers from modifications from various sources. There is a significant relationship between parental influence and smoking behavior in adolescents. With an OR of 2,824, this means that parents have a 2,824 times chance of causing smoking behavior in teenagers. There is a need to educate parents not to smoke at home and in front of their children.

Tramadol consumption as edgework: intersections of pleasures and risks in the accounts of Nigerian youths

ABSTRACT This study explores the complex interplay of pleasures and risks in young people’s tramadol consumption. It draws from semi-structured interviews with 39 male youths in two cities in Nigeria, and thematic analysis using edgework as a theoretical approach. Data highlight how high-risk tramadol consumption (e.g. heavy and frequent consumption, cocktails), motivated by a desire for pleasure and fun, served as a response to boredom and drudgery in daily life. Tramadol consumption opened up new horizons of affective, experiential and social possibilities, enabling young people to experience self-reflexivity and agency in widespread precarity. Data also captured lived experiences of risks and harms associated with tramadol consumption as well as situated strategies for working the edge of high-risk consumption. These strategies had limited effectiveness due to drug dependence and the structural drivers of high-risk consumption. Findings evidence a need to rethink drug harm reduction for marginalized youth. Specifically, they indicate a need to merge structural-level interventions (e.g. better job opportunities and drug treatment services) with individual strategies (such as dose reduction and occasional consumption). Interventions that address the social and structural drivers of high-risk consumption could help to create an ‘enabling environment’ for young people to practice harm reduction.

Coming Up…

The annual meeting of the College on Problems of Drug Dependence (CPDD) will be held June 15‐19 in Montreal. For more information, go to https://cpdd.org/

Establishing Geriatric Opiate Use Patterns in Trauma.

Introduction: There is evidence that providers often overprescribe opiates in the postoperative period. Despite an ever-growing geriatric population, there is little research detailing current opiate usage in older patients after trauma. This population presents a unique set of challenges for pain management and prescription drug dependence due to sensitivity, a narrow therapeutic window, and high rates of pre-existing polypharmacy.Objective: Assess the use of narcotics in geriatric trauma patients with various injury patterns to establish a reference point for future intervention for reduction in narcotic dependence.Methods: We created a database of trauma patients' age ≥65 years admitted to a single level 1 trauma center in the Southeastern United States during the 2019 calendar year. Information gathered included patient factors, injury patterns, operative intervention, pain medications prescribed during hospitalization and at discharge, total and average daily morphine milligram equivalents (MME) inpatient and outpatient, and requests/prescriptions for narcotics at follow-up.Results: In 2019, there were 475 patients aged ≥65 admitted to our level 1 trauma center for acute traumatic injuries. 219 of those patients required operative intervention. Average total inpatient MME for this cohort was 169.0 with average daily MME of 22.89. The average total prescribed MME upon discharge was 79.27. There were 29 patients documented to request narcotic prescription refill at time of clinic follow-up, 27 of whom were prescribed a narcotic medication at follow-up.Conclusion: This dataset establishes a reference point for opiate use in geriatric trauma patients to facilitate further research for mitigation of risk in this population.

Identification of Key Hypolipidemic Components and Exploration of the Potential Mechanism of Total Flavonoids from Rosa sterilis Based on Network Pharmacology, Molecular Docking, and Zebrafish Experiment.

Hyperlipidemia is a prevalent chronic metabolic disease that severely affects human health. Currently, commonly used clinical therapeutic drugs are prone to drug dependence and toxic side effects. Dietary intervention for treating chronic metabolic diseases has received widespread attention. Rosa sterilis is a characteristic fruit tree in China whose fruits are rich in flavonoids, which have been shown to have a therapeutic effect on hyperlipidemia; however, their exact molecular mechanism of action remains unclear. Therefore, this study aimed to investigate the therapeutic effects of R. sterilis total flavonoid extract (RS) on hyperlipidemia and its possible mechanisms. A hyperlipidemic zebrafish model was established using egg yolk powder and then treated with RS to observe changes in the integral optical density in the tail vessels. Network pharmacology and molecular docking were used to investigate the potential mechanism of action of RS for the treatment of hyperlipidemia. The results showed that RS exhibited favorable hypolipidemic effects on zebrafish in the concentration range of 3.0-30.0 μg/mL in a dose-dependent manner. Topological and molecular docking analyses identified HSP90AA1, PPARA, and MMP9 as key targets for hypolipidemic effects, which were exerted mainly through lipolytic regulation of adipocytes and lipids; pathway analysis revealed enrichment in atherosclerosis, chemical carcinogenic-receptor activation pathways in cancers, and proteoglycans in prostate cancer and other cancers. Mover, chinensinaphthol possessed higher content and better target binding ability, which suggested that chinensinaphthol might be an important component of RS with hypolipidemic active function. These findings provide a direction for further research on RS interventions for the treatment of hyperlipidemia.

Electrochemical, Real-Time Monitoring of Hydrogen Peroxide in Drosophila (Fruit Fly) Intestines Using a Carbon Fiber Microelectrode (CFME) Modified with Platinum Nanoparticles (PtNPs)

Inflammatory bowel disease (IBD) is a serious global health problem, mainly manifested as chronic progressive gastrointestinal inflammation, which damages the gastrointestinal mucosa and affects the life of human beings. This disease is difficult to eradicate, prone to recurrent attacks, has a potential cancer risk and includes Crohn’s disease (CD) and ulcerative colitis (UC). Unfortunately, the available drugs serve to induce remission but may result in adverse reactions and drug dependence. However, in the case of inflammation-related diseases, it is possible to assess and measure the severity of the disease and the impact of treatment by monitoring the levels of hydrogen peroxide (H2O2). Moreover, in-situ detection is of great significance as it represents the inflammatory site. In this study, a carbon fiber microelectrode modified by platinum nanoparticles was prepared and used to monitor H2O2 in intestine of an UC Drosophila model established by dextran sodium sulfate. The results show that the electrochemical biosensor provides sensitive, real-time determination of H2O2 in vivo, which provides a new methodological basis for studying the occurrence and development of UC and drug screening.

Effect of family intervention on relapse rate of Chinese patients with alcohol-dependent.

This study explored the impact of a family intervention on the relapse rate of Chinese patients with alcohol dependence. A total of 151 male patients with alcohol dependence who were discharged from the Substance Dependence Department of the Wenzhou Seventh People's Hospital from January to December 2020 were selected. They were divided into the control (n = 73) and experimental (n = 78) groups. Patients in both groups received routine alcohol cessation treatment. Moreover, patients in the experimental group were followed up by a professional psychiatrist to carry out individual family intervention. The Family Function Rating Scale (FAD), a Self-made general information questionnaire, and the Chinese version of the Family Intimacy and Adaptability Scale (FACESI-CV) were performed. Re-drinking rate and readmission rate were assessed. Family intervention could reduce relapse rate (31, 39.74%) and rehospitalization (27, 34.62%) compared with the control group. After family training, FAD factor scores were improved in the experiment group in comparison with the control group. Family training improved communication (18.2 ± 3.7), role (20.8 ± 2.5), emotional response (10.8 ± 1.8), emotional involvement (13.7 ± 1.2), behavioral control (19.8 ± 1.2), and overall functionality (23.5 ± 2.1) in the experiment group in comparison with the control group. After family training, intimacy (70.5 ± 8.7) and adaptability (64.1 ± 6.9) in the experiment group was higher than in the control group. After family intervention, Michigan Alcohol Dependence Scale (MAST) (9.21 ± 0.68) and Short-Form 36 (SF-36) (80.32 ± 4.47) in the experiment group were higher than the control group. Family intervention for families of patients with alcohol dependence can improve their family function, increase their family intimacy and adaptability, and reduce the rate of relapse.

GC-NPD analysis of topiramate in capillary dried plasma: assessing chemical dependency pharmacotherapy

GC-NPD analysis of topiramate in capillary dried plasma: assessing chemical dependency pharmacotherapy

Oral administration of coenzyme Q10 ameliorates memory impairment induced by nicotine-ethanol abstinence through restoration of biochemical changes in male rat hippocampal tissues

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.

Methylphenidate Versus Placebo for Treating Fatigue in Patients With Advanced Cancer: Randomized, Double-Blind, Multicenter, Placebo-Controlled Trial.

To compare effects and side effects of 6 weeks of individually dose-titrated methylphenidate or placebo on fatigue in palliative care patients with advanced cancer. This is a randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients had advanced incurable cancer and fatigue >3/10. Principal exclusions were hypertension; psychiatric, cardiovascular, cerebrovascular, renal, liver, or blood disorders; substance dependency; and epilepsy. Patients were randomly assigned 1:1 methylphenidate or placebo starting at 5 mg twice daily. Dose of methylphenidate/placebo was titrated once per week, over 6 weeks, up to a maximum of 20 mg three times daily. Trial ended at 10 weeks. Primary outcome was the difference in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scores between groups at 6 ± 2 weeks. Secondary outcomes included adverse effects, quality of life, and mood. One hundred sixty-two patients (73 men; mean, 65.8; standard deviation [SD], 10.3 years) were randomly assigned, and three were excluded from analysis. Seventy-seven were allocated placebo (baseline FACIT-F = 22 [SD, 10]); 82 were allocated methylphenidate (FACIT-F = 20 [SD, 9]). After 6 ± 2 weeks, FACIT-F scores were 1.97 points (95% CI, -0.95 to 4.90; P = .186) higher (better) on methylphenidate than placebo. Across 10 weeks of the study, FACIT-F was nominally higher in the methylphenidate group versus placebo (Diff, 2.20 [95% CI, 0.39 to 4.01]), but this did not reach the minimally clinically important difference (5-points). At 6 weeks, there were no differences between groups in quality-of-life or symptom domains except for depression scores (nominally reduced in the methylphenidate group: Diff, -1.35 [95% CI, -2.41 to -0.30]). There were no differences in mortality or serious adverse events. After 6 ± 2 weeks of treatment, methylphenidate was not superior to placebo for treating fatigue in advanced cancer. Methylphenidate was safe and well-tolerated.

Coming Up…

The annual meeting of the College on Problems of Drug Dependence (CPDD) will be held June 15‐19 in Montreal. For more information, go to https://cpdd.org/

Developing practical strategies to reduce addiction-related stigma and discrimination in public addiction treatment centers: a mixed-methods study protocol

BackgroundPeople with substance use disorders (SUDs) have restricted engagement with health-care facilities and describe repeated experiences of stigma, discrimination, and mistreatment when receiving care at health-care and public addiction treatment centers (PATCs). The purpose of the current study is to design practical cultural-based strategies to reduce addiction-related stigma and discrimination at PATCs.Methods/designThe present study will use a mixed-methods design with an explanatory sequential approach. Phase 1 of the study will combine a cluster sampling technique combined with a cross-sectional survey of Patients with Substance Use Disorders (SUDs) in Mazandaran, Iran. A total of three hundred and sixty individuals with SUDs will be selected to assess their experiences of stigma and factors predicting stigma. Phase 2 will involve qualitative study aimed at exploring participants’ perceptions regarding the aspects and determinants of their stigma experience. The participants will include two groups: people with SUDs and staff/health-care providers at PATCs. Participants for Phase 2 will be purposively sampled from those involved in Phase 1.Qualitative data will be collected using in-depth semi-structured interviews and focus group discussions and analyzed using content analysis with a conventional approach. Phase 3 will focus on the development of new strategies to reduce the experiences of stigma among people with SUDs at PATCs. These strategies will be formulated based on the findings derived from the qualitative and quantitative data obtained in Phases 1 and 2, a comprehensive review of the literature, and expert opinions gathered using the nominal group technique.DiscussionThis is one of the few studies conducted within the domain of stigma pertaining to individuals who use drugs within the context of Iranian culture employing a mixed-methods approach, this study aims to develop culturally sensitive strategies to reduce such problems from the perspective of Iranian people who use drugs. It is anticipated that the study will yield evidence-based insights and provide practical strategies to reduce the stigma and discrimination experienced by people who use drugs at PATCs. Such outcomes are important for informing policymaking and designing healthcare interventions tailored to the needs of individuals grappling with substance dependency.

Evaluating the effectiveness of a mobile app-based self-guided psychological interventions to reduce relapse in substance use disorder: protocol for a randomized controlled trial.

Substance Use Disorder (SUD) persists as a significant public health challenge worldwide, with an estimated prevalence of approximately 10-15% across the global populace. This condition is characterized by a notably high risk of lapses and relapses, even subsequent to treatment interventions. Mobile health interventions, owing to their widespread accessibility, emerge as a promising approach to diminish the risk of relapse post-treatment and to broaden the scope of care, especially in regions with a scarcity of trained medical professionals. This study is designed to assess the effectiveness of mobile interventions in mitigating cravings and preventing lapses among individuals diagnosed with SUD. Employing a two-armed, randomized controlled trial framework, the study will evaluate a self-administered psychological intervention delivered through a mobile application, Nałogometr 2.0. Over a period of three months, participants will engage with intervention modules that primarily incorporate mindfulness techniques and Cognitive Behavioral Therapy (CBT) principles. Ecological Momentary Assessment (EMA) will be utilized to gather longitudinal data on a range of variables that are indicative of craving intensity and the risk of lapse. In addition to this, a monthly-administered battery of questionnaires will be employed to gauge the severity of substance dependence, as well as to measure levels of anxiety, depression, and overall life satisfaction. Results will be submitted for publication in peer-reviewed journals. https://clinicaltrials.gov/, identifier [NCT05730504].

A Review on Chittodvega w.s.r to Generalized Anxiety Disorder and its Management

With the advent of modern science, human life has become much faster and more stressful. Psychiatric disorders are therefore expanding today, A wide range of psychiatric conditions have been described in Ayurveda. Ayurveda follows psychosomatic approach of health. Chittodvega is a Manasavikara mentioned by Charaka which is considered as a perfect word for highlighting the status of anxiety, Generalized Anxiety Disorder. Chittodvega can exists as a separate disease or can be an etiological factor for other psychic and psychosomatic diseases. Generalized anxiety disorder (GAD) is a mental health disorder that produces fear worry and a constant feeling of being overwhelmed. This on-going worry and tension may be accompanied by physical symptoms, such as restlessness, feeling on edge or easily fatigued, difficulty concentrating, muscle tension or problems sleeping. Being an alarming disease, it requires effective management. In recent years several synthetic drugs have been introduced for the treatment of anxiety disorders. Clinical trials have shown that anxiolytic drugs alone have limited long term efficacy and one cannot avoid major side effects such as drug dependence, drug resistance, sedation etc. Ayurveda follows psychosomatic approach of health. Acharya Charaka explains three types of therapies of physical and mental disorders Daivavyapasraya, Yuktivyapasrya, Satvajaya Chikitsa. So the present study deals with systemic review of Chittodvega from all the classics of Ayurveda and its management.

Review of Metabolic Syndrome (Santarpana Janya Vyadhi) and its Management by Virechana Karma and Vyoshadi Saktu

Ayurveda, considered the oldest form of healthcare globally, aligns individuals with the inherent principles of nature to maintain overall well-being by harmonizing body, mind, and spirit. In the contemporary age of rapid modernization and hectic lifestyles, people lead busy and stressful lives, marked by a growing consumption of high-calorie fast food. The prevalence of sedentary habits contributes to an increase in total body fat and cholesterol. It leads to health issues such as hypertension, heart diseases, hyperlipidemia, and truncal obesity. Metabolic syndrome (MetS) is a disorder of energy and storage containing of risk factor for various complications such as Type 2 diabetes mellitus and cardio vascular disease. Being an alarming disease, it requires effective management. In recent years several synthetic drugs have been introduced for the treatment of metabolic syndrome. Clinical trials have shown that antihypertensive, antidiabetic, antilipidemic drugs alone have limited long term efficacy and one cannot avoid major side effects such as drug dependence, drug resistance, sedation etc. Ayurvedic medicine provides a range of measures. In Ayurvedic literature, Acharya Charaka has mentioned group of diseases which arises due to over intake of heavy meals and sedentary life style collectively called as Santarpana Janya Vyadhi which can be symptomatically co-related with metabolic syndrome. Acharya Charaka has specified treatment methods involving substances (Dravyabhuta Chikitsa) and non-substances (Adravyabhuta Chikitsa) for conditions caused by over-nourishment, such as Vaman, Virechana, Raktmokshana, Vyayama (exercise), Dhooma(fumigation), Swedana(sudation), and Rooksha Anna Sewana (intake of dry substances). This paper aims to review metabolic syndrome in Ayurveda and its corresponding management strategies.

Navigating college campuses: The impact of stress on mental health and substance use in the post COVID-19 era

The college years are one of excitement and often thought of as a dream like setting of growth, creativity, and independence. This exciting time can be marred by the onset or exacerbation of mental health conditions, alcohol, and/or drug dependence. This writing looks to explore the world of college mental health and the changes the provisions of this type of care has undergone during and after the COVID-19 pandemic. We look at the staggering rates of diagnosed mental health diagnoses and mental health related symptoms that may undermine a student's ability to meet their full growth and academic potential. We look to explore different health settings where college age students are accessing care and how that care is being delivered (e.g. community vs on-campus, telehealth vs in-person). We also aim to highlight specific mental health conditions (e.g. anxiety, depression, suicidality, PTSD) and specific student stressors (e.g. participating in athletics, socioeconomic pressures) to underscore the message that the mental health of college age students is an area that needs continued study and engagement of all parties involved in student development and well-being.