Physical Dependence Research Articles

Abuse potential assessment of the dual orexin receptor antagonist daridorexant in rats.

Drugs that act on the central nervous system (CNS) and have sedative effects can lead to abuse in humans. New CNS-active drugs often require evaluation of their abuse potential in dedicated animal models before marketing approval. Daridorexant is a new dual orexin receptor antagonist (DORA) with sleep-promoting properties in animals and humans. It was approved in 2022 in the United States and Europe for the treatment of insomnia disorder. Nonclinical evaluation of abuse potential of daridorexant using three specific rat models assessing reinforcement, interoception, and withdrawal. Reinforcing effects of daridorexant were assessed in an operant rat model of intravenous drug self-administration. Similarity of interoceptive effects to those of the commonly used sleep medication zolpidem was tested in an operant drug discrimination task. Withdrawal signs indicative of physical dependence were evaluated upon sudden termination of chronic daridorexant treatment. Rat experiments were conducted at a dose range resulting in daridorexant plasma concentrations equaling or exceeding those achieved at the clinically recommended dose of 50 mg in humans. Daridorexant had no reinforcing effects, was dissimilar to zolpidem in the drug discrimination task, and did not induce any withdrawal-related signs upon treatment discontinuation that would be indicative of physical dependence. Daridorexant showed no signs of abuse or dependence potential in rats. Our data indicate that daridorexant, like other DORAs, has a low potential for abuse in humans.

Faktor – faktor yang Berhubungan dengan Kebersihan Gigi dan Mulut pada Lansia

The lack of oral hygiene become a problem for elderly. The main aims of this research is to analyze the related factors due to oral hygiene consists of age, sex, education degree, occupation, marital status, knowledge, motivation, physical dependence, culture, anxiety, economic of family and elderly. The design of this research were descriptive analytic and cross sectional. UPTD Puskesmas I Penebel was the location where this research was conducted. Purposes sampling technique was used with the total samples where 80 respondents. The results showed the significant correlation between oral hygiene and knowledge (p value 0,013, r = 0,277), motivation (p value 0,005, r = 0,311), physical dependence (p value 0,011, r = 0,285), economic of family and elderly (p value 0,0000, r = 0,400), anxiety (p value 0,0185, r = -0,265). There was no correlation between culture and oral hygiene (p value 0,187, r = -0,149). Based on this research, it is recomended that oral hygiene supposed to be clearly informed to elderly by elderly posyandu (integrated treatment) activities, and regularly oral hygiene checkup which is integrated in puskesmas (civic health Centre).

Effect of the interaction between brand attachment and physiological nicotine dependence on motivation to quit smoking

Our studyaimed to explore the effect of the interaction between brand attachment and nicotine dependence on the motivation to quit smoking. Contrary to our initial hypothesis, whichsuggestedthathighlevels of brand attachmentcombinedwithstrong nicotine dependencewouldlead to low motivation to quit smoking, ourresultsrevealed an unexpected trend. Participants lessattached to a specific cigarette brand wereactuallylessinclined to quit smoking, indicatingthatindividualswho are not stronglyattached to a specific cigarette brand maybesonicotine-dependentthat the type of cigarette itselfbecomesless important. Thus, theymaybelessmotivated to quit smoking. A comprehensiveunderstanding of thesemechanismswouldoftenrequire a multidimensionalapproach. This shouldbeinvestigated in future studies, integratingvarious variables to obtain a more holistic perspective of the phenomenon.

Emergency Admissions and the Prescribing of Buprenorphine, Methadone, and Psychotropic Medications in People with Sickle Cell Disease: An Analysis of National Insurance Claims

Background Although there have been efforts to address overdose risks and treatment gaps in general populations receiving opioids, there is has been little research examining potential drug-related poisoning risks in some of the highest-need and complex populations, including those with sickle cell disease (SCD). Chronic opioid medications are necessary and well-tolerated for the treatment of chronic pain, diffuse inflammation, chronic organ damage, and vaso-occlusive pain crises for people with SCD. Previous studies have found that patients with SCD are not more likely to develop addiction to opioids than the general population. However, amid the ongoing endemic of drug-related poisonings in the U.S., epidemiological data is scarce regarding the clinical characteristics of people who have SCD and physiologic opioid tolerance and dependence. There has been particularly limited work on the intersection of sociodemographic characteristics, substance use, and other mental health conditions in the SCD population. Concern has also been raised about the ongoing opioid epidemic contributing to increased stigma, and greater barriers to the management of acute and chronic pain in SCD. Studies have shown that preoccupation with opioid prescription monitoring hindered the ability of physicians to provide comprehensive SCD care. People with SCD often face more restrictive utilization management policies for opioids than peers with other forms of chronic pain (i.e., cancer-related pain). In order for us to develop better interventions for people with SCD, real-world data is urgently needed to describe the current treatment landscape and identify gaps in care for people with SCD and physiologic opioid dependence or tolerance. Using administrative claims data in the US, we aim to: 1) quantify the burden of hospitalization and emergency room admission for medication-related poisoning events, 2) describe the prevalence of opioid prescriptions, such as buprenorphine and methadone, in people with SCD and physiologic opioid dependence or misuse. Methods In this retrospective cohort study of people with physiologic opioid dependence or opioid use disorder (OUD), we analyzed ten years (1/2006-12/2016) of data from the Merative™ MarketScan® Commercial and Multi-State Medicaid Databases. The predictor variable was SCD (versus a comparator group of people with chronic pain) with diagnoses identified using ICD-9/10 codes. The outcome variables were 1) emergency admissions or hospitalization for non-fatal drug/medication-related poisoning events during enrollment, and 2) prescriptions for buprenorphine, methadone, and other opioids, identified via procedure codes and linked pharmacy records respectively. We used multivariable cox regression to estimate the relationship between SCD diagnosis and time until poisoning events. Multivariable poisson regression models were used to assess the relationship between SCD and buprenorphine, methadone, and other opioid prescriptions. Results Our overall cohort consisted of 25,448 people with ICD9-10 opioid dependence or misuse, including 313 with SCD and 25,135 with non-SCD chronic pain. In the SCD cohort, the median age was 30.8 years, and 82% were enrolled in Medicaid. Compared to the non-SCD chronic pain cohort, the SCD cohort had more hospitalizations or emergency admission for iatrogenic events (37.4% vs 9.8%, aHR=2.21[2.12-2.31]). With regards to medication receipt compared to peers with non-SCD chronic pain, the SCD cohort had a lower prevalence of buprenorphine prescriptions (8% vs 30.1%, aRR=0.20[0.18-0.21]) and a higher prevalence of methadone prescriptions for chronic pain (63.6% vs 6.8%, aRR=5.36[5.21-5.51]) and non-methadone/non-buprenorphine opioid prescriptions (80.5% vs 33.7%, aRR=2.20[2.15-2.25]). Conclusions We observed an elevated rate of emergency admission and/or hospitalization for drug/medication-related poisoning, as well as a significant burden of psychiatric comorbidity in a cohort of people with SCD and physiologic opioid dependence or OUD. The prescribing of potentially safer opioids, such as buprenorphine, was uncommon in the cohort. Further research is urgently needed to optimize opioid treatment strategies, combat stigma, and improve the comprehensive management of pain and co-occurring disorders in the SCD population.

Early Initiation of Ketamine Infusion for Pain Management in Pediatric BMT Patients with Mucositis

Background: As many as 90% of children undergoing hematopoietic stem cell transplant (HSCT) will experience painful mucositis. The mainstay of treatment for these children has been opioid analgesia which can be associated with sedation and respiratory depression. Additionally, these children may experience heightened opioid tolerance and physiologic dependence contributing to lengthy admissions. Ketamine is an anesthetic and analgesic which has been used successfully in conjunction with opioids in the treatment of painful mucositis. This study aimed to reduce total opioid use per day by 10% and overall pain scores by 2 in pediatric patients with mucositis undergoing HSCT through initiation of ketamine at the same time as an opioid patient-controlled analgesia (PCA). Methods: Beginning April 2022, HSCT patients (both autologous and allogeneic) at Children's Hospital Colorado were started on ketamine infusion in conjunction with an opioid PCA for management of painful mucositis. Mucositis severity and duration, opioid consumption, pain and functional scores, time of initiation of ketamine therapy, ketamine side effects, and duration of PCA and ketamine therapy were recorded for a retrospective (April 2021- March 2022, n=6) and a prospective cohort (April 2022- April 2023, n=17). A 2-sample-T-test was used to calculate the difference in mean cumulative opioid use per day and the mean 24-hour average pain scores between the retrospective and prospective groups. Results: 71% of children in the prospective group underwent ketamine initiation alongside an opioid PCA. Patients in this group had a 46% reduction in mean cumulative opioid use per day (CI 1.265-2.318, p=0.000). Reduction in 24-hour pain scores between the retrospective and prospective groups was 1.18, failing to meet our goal of 2.0. However, there was still a statistically significant difference in mean scores (CI 0.499-1.860, p=0.001). Additionally, this intervention was tolerated well and only 1 patient (16%) was intolerant of ketamine side effects in the prospective cohort. Conclusions: Initiation of ketamine alongside an opioid PCA for the treatment of mucositis pain is safe and significantly reduces cumulative opioid exposure and 24-hour pain scores in children undergoing HSCT.

Revolutionizing orofacial pain management: the promising potential of stem cell therapy.

Orofacial pain remains a significant health issue in the United States. Pain originating from the orofacial region can be composed of a complex array of unique target tissue that contributes to the varying success of pain management. Long-term use of analgesic drugs includes adverse effects such as physical dependence, gastrointestinal bleeding, and incomplete efficacy. The use of mesenchymal stem cells for their pain relieving properties has garnered increased attention. In addition to the preclinical and clinical results showing stem cell analgesia in non-orofacial pain, studies have also shown promising results for orofacial pain treatment. Here we discuss the outcomes of mesenchymal stem cell treatment for pain and compare the properties of stem cells from different tissues of origin. We also discuss the mechanism underlying these analgesic/anti-nociceptive properties, including the role of immune cells and the endogenous opioid system. Lastly, advancements in the methods and procedures to treat patients experiencing orofacial pain with mesenchymal stem cells are also discussed.

Comparative Study of efficacy of various solvent systems in extraction of morphine from viscera

Morphine, the main alkaloid of opium, was first obtained from poppy seeds in 1805. It is a potent analgesic, though its use is limited due to tolerance, withdrawal, and the risk of abuse. Morphine is still routinely used today, though there are a number of semi-synthetic opioids of varying strength such as codeine, fentanyl, methadone, hydrocodone, hydromorphone, meperidine, and oxycodone. Morphine is used for the management of chronic, moderate to severe pain. Opioids, including morphine, are effective for the short term management of pain. Patients taking opioids long term may need to be monitored for the development of physical dependence, addiction disorder, and drug abuse.

Identification and Pharmacological Characterization of a Low-Liability Antinociceptive Bifunctional MOR/DOR Cyclic Peptide.

Peptide-based opioid ligands are important candidates for the development of novel, safer, and more effective analgesics to treat pain. To develop peptide-based safer analgesics, we synthesized a mixture-based cyclic pentapeptide library containing a total of 24,624 pentapeptides and screened the mixture-based library samples using a 55 °C warm water tail-withdrawal assay. Using this phenotypic screening approach, we deconvoluted the mixture-based samples to identify a novel cyclic peptide Tyr-[D-Lys-Dap(Ant)-Thr-Gly] (CycloAnt), which produced dose- and time-dependent antinociception with an ED50 (and 95% confidence interval) of 0.70 (0.52-0.97) mg/kg i.p. mediated by the mu-opioid receptor (MOR). Additionally, higher doses (≥3 mg/kg, i.p.) of CycloAnt antagonized delta-opioid receptors (DOR) for at least 3 h. Pharmacological characterization of CycloAnt showed the cyclic peptide did not reduce breathing rate in mice at doses up to 15 times the analgesic ED50 value, and produced dramatically less hyperlocomotion than the MOR agonist, morphine. While chronic administration of CycloAnt resulted in antinociceptive tolerance, it was without opioid-induced hyperalgesia and with significantly reduced signs of naloxone-precipitated withdrawal, which suggested reduced physical dependence compared to morphine. Collectively, the results suggest this dual MOR/DOR multifunctional ligand is an excellent lead for the development of peptide-based safer analgesics.

Restricting social networking site use for one week produces varied effects on mood but does not increase explicit or implicit desires to use SNSs: Findings from an ecological momentary assessment study.

Recent research on the addictive potential of modern technologies such as the internet, smartphones, or social networking sites (SNSs) has suggested that emotional and motivational changes associated with the sudden discontinuation of engagement with the technology mirror the aversive consequences seen when drug use is ceased abruptly. This has been observed even in moderate users and interpreted as a manifestation of withdrawal, an important marker of physical dependence in substance use disorders. On the other hand, a growing literature emphasises the positive effects of "digital detox" on mental health and well-being. Using a battery of affective and motivational measures, both explicit and implicit, the present study tracked the effects of a week of significantly reduced SNS use in moderate to heavy SNS users (N = 51). Our pre-registered analyses showed that the intervention elicited affective changes neither consistent with a general withdrawal syndrome (i.e., increased negative affect and cravings) nor with a general beneficial effect on well-being: While our data indicated some abstinence-related decreases of negative affect and boredom, they also showed a reduction of positive affect. These changes occurred regardless of problematic/addictive use behaviours. Importantly, restricting SNS use for one week had no effect on implicit measures of SNS use motivation (i.e., approach biases, time distortion and effort expenditure for SNS access) nor did it influence explicit cravings and SNS cue-reactivity. Together our findings suggest that restricting SNS use has nuanced and potentially offsetting effects on well-being. These could arise because use reduction may concurrently remove experiences that trigger negative emotions (e.g., upward social comparisons or Fear of Missing Out) but also those that elicit positive emotions (e.g., social approval). The hypothesised lack of a net effect on well-being would be consistent with our finding that voluntary reduction of SNS use does not mitigate or exacerbate SNS-related urges.

Amelioration of morphine withdrawal syndrome by systemic and intranasal administration of mesenchymal stem cell-derived secretome in preclinical models of morphine dependence.

Morphine is an opiate commonly used in the treatment of moderate to severe pain. However, prolonged administration can lead to physical dependence and strong withdrawal symptoms upon cessation of morphine use. These symptoms can include anxiety, irritability, increased heart rate, and muscle cramps, which strongly promote morphine use relapse. The morphine-induced increases in neuroinflammation, brain oxidative stress, and alteration of glutamate levels in the hippocampus and nucleus accumbens have been associated with morphine dependence and a higher severity of withdrawal symptoms. Due to its rich content in potent anti-inflammatory and antioxidant factors, secretome derived from human mesenchymal stem cells (hMSCs) is proposed as a preclinical therapeutic tool for the treatment of this complex neurological condition associated with neuroinflammation and brain oxidative stress. Two animal models of morphine dependence were used to evaluate the therapeutic efficacy of hMSC-derived secretome in reducing morphine withdrawal signs. In the first model, rats were implanted subcutaneously with mini-pumps which released morphine at a concentration of 10 mg/kg/day for seven days. Three days after pump implantation, animals were treated with a simultaneous intravenous and intranasal administration of hMSC-derived secretome or vehicle, and withdrawal signs were precipitated on day seven by i.p. naloxone administration. In this model, brain alterations associated with withdrawal were also analyzed before withdrawal precipitation. In the second animal model, rats voluntarily consuming morphine for three weeks were intravenously and intranasally treated with hMSC-derived secretome or vehicle, and withdrawal signs were induced by morphine deprivation. In both animal models secretome administration induced a significant reduction of withdrawal signs, as shown by a reduction in a combined withdrawal score. Secretome administration also promoted a reduction in morphine-induced neuroinflammation in the hippocampus and nucleus accumbens, while no changes were observed in extracellular glutamate levels in the nucleus accumbens. Data presented from two animal models of morphine dependence suggest that administration of secretome derived from hMSCs reduces the development of opioid withdrawal signs, which correlates with a reduction in neuroinflammation in the hippocampus and nucleus accumbens.

Effect of physical exercise on sleep quality in college students: Mediating role of smartphone use.

To investigate the effect of physical exercise on sleep quality and the mediating effect of smartphone use behavior in college students. A cross-sectional study design was adopted. An online survey of 5,075 college students was conducted using the Physical Activity Rating Scale-3, the Pittsburgh Sleep Quality Index, and the Mobile Phone Addiction Tendency Scale. The sleep quality of college students was poor, and the proportion of college students with good sleep quality was 23.567%. A significant correlation existed between sleep quality and physical exercise (r = -0.159, P < 0.001) and mobile phone addiction (r = 0.355, P < 0.001). Physical exercise can predict sleep quality in college students (β = -0.011, P < 0.001). Smartphone use plays a part in mediating the process by which physical exercise affects sleep quality. Chinese college students have poor sleep quality. Physical exercise and smartphone use behavior are important factors affecting the sleep quality of college students. Physical exercise can directly predict the sleep quality of college students and can predict the sleep quality of college students through the mediating effect of smartphone use behavior.

Association of patient clinical and gut microbiota features with vancomycin-resistant enterococci environmental contamination in nursing homes: a retrospective observational study

Preventing transmission is crucial for reducing infections with multidrug-resistant organisms (MDROs) in nursing homes. To identify resident characteristics associated with MDRO spread, we investigated associations between patient characteristics and contamination of their proximate room surfaces with vancomycin-resistant enterococci (VRE). In this retrospective observational study, we used demographic and clinical data (including data on comorbidities, physical independence, catheter use within the past 30 days, and antibiotic exposure within the past 30 days) and surveillance cultures of patient body sites and room surfaces at enrolment and during weekly follow-up visits within the first month, and monthly thereafter (up to 6 months), in six US nursing homes collected in a previous clinical trial (September, 2016, to August, 2018). We did 16S rRNA gene sequencing on perirectal surveillance swabs to investigate the association between the gut microbiota and the culture status of participants and their rooms. We included 245 participants (mean age 72·5 years [SD 13·6]; 111 [45%] were men, 134 [55%] were women, 132 [54%] were non-Hispanic white, and 112 [46%] were African American). We collected 2802 participant samples and 5592 environmental samples. At baseline, VRE colonisation was present in 49 (20%) participants, with environmental surfaces being contaminated in 36 (73%) of these patients. Hand contamination among VRE-colonised participants was more common in those with environmental contamination compared with those without (50 [51%] of 99 vs seven [13%] of 55; p<0·0001). We found a correlation between hand contamination and both groin and perirectal colonisation and contamination of various high-touch room surfaces (Cohen's κ 0·43). We found participant microbiota composition to be associated with antibiotic receipt within the past 30 days (high-risk antibiotics p=0·011 and low-risk antibiotics p=0·0004) and participant VRE colonisation status, but not environmental contamination among VRE-colonised participants (participant only vs uncolonised p=0·071, both participant and environment vs uncolonised p=0·025, and participant only vs participant and environment p=0·29). Multivariable analysis to identify independent factors associated with VRE-colonised participants contaminating their environment identified antibiotic exposure (adjusted odds ratio 2·75 [95% CI 1·22-6·16]) and male sex (2·75 [1·24-6·08]) as being associated with increased risk of environmental contamination, and physical dependence as being associated with a reduced risk of environmental contamination (0·91 [0·83-0·99]). Our data support antibiotic use and interaction with proximal surfaces by physically independent nursing home residents as under-appreciated drivers of environmental contamination among VRE-colonised residents. Integrating resident hand-hygiene education and antimicrobial stewardship will strengthen efforts to reduce MDROs in nursing homes. US Centers for Disease Control and Prevention, National Institute of Health, Canadian Institutes of Health Research, and University of Michigan.

Zingerone Alleviates Morphine Tolerance and Dependence in Mice by Reducing Oxidative Stress-Mediated NLRP3 Inflammasome Activation.

Morphine (MPH) is widely used for pain management; however, long-term MPH therapy results in antinociceptive tolerance and physical dependence, limiting its clinical use. Zingerone (ZIN) is a natural phenolic compound with neuroprotective effects. We investigated the effects of single and repeated doses of ZIN on MPH-induced tolerance, dependence, and underlying biochemical mechanisms. After a dose-response experiment, tolerance was developed to MPH (10mg/kg, i.p.) for seven days. In the single-dose study, ZIN was administered on day seven. In the repeated-dose study, ZIN was administered for seven days. Naloxone (5mg/kg, i.p., 120min after MPH) was injected to assess withdrawal signs on day seven. The levels of thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), total thiol (TT), and glutathione peroxidase (GPx) were measured in the prefrontal cortex. The protein levels of interleukin-1 beta (IL-1β) and NLRP3-ASC-Caspase-1 axis were assessed by ELISA and Western blotting, respectively. Results showed that ZIN (100mg/kg) had no antinociceptive activity, and subsequent experiments were performed at this dose. Repeated ZIN reversed MPH antinociceptive tolerance, whereas single ZIN did not. Single and repeated ZIN attenuated naloxone-induced jumping. In addition, repeated ZIN significantly inhibited weight loss. Repeated ZIN suppressed the MPH-induced increase in TBARS, NO, IL-1β, NLRP3, ASC, and Caspase-1. It also inhibited MPH-induced TT and GPx reduction. In contrast, single ZIN had no effect. Findings suggest that ZIN reduces MPH-induced tolerance and dependence by suppressing oxidative stress and NLRP3 inflammasome activation. This study provides a novel therapeutic approach to reduce the side effects of MPH.

Evaluation of Low-dose Buprenorphine Initiation With Buprenorphine Buccal Films in Hospitalized Patients: A Retrospective Cohort Study.

Low-dose buprenorphine initiation (LDBI) strategies to transition patients from full opioid agonists to buprenorphine have previously been described using sublingual films, intravenous solution, transdermal patches, and, more recently, buccal films. The objective of this study was to describe the effectiveness of LDBI using novel titration schedules with buccal films. This is a retrospective cohort study of hospitalized patients with opioid use disorder (OUD) or physiologic dependence to opioids who underwent LDBI with buprenorphine buccal films at NYU Langone Health. Two LDBI protocols were evaluated, including a short titration schedule over 4 days and a long schedule over 7 days. The primary outcomes of interest included LDBI completion rates and incidence of opioid withdrawal. Forty-two patients underwent 46 LDBIs at NYU Langone Health between October 2020 and April 2022. The cohort comprised patients with OUD (57%), chronic pain with OUD (33%), and chronic pain without OUD (10%). Indications for LDBI most commonly included co-occurring pain precluding discontinuation of full opioid agonists (72%), prior history of precipitated withdrawal (30%), and methadone use (23%). The overall completion rate of LDBI was 78%. Withdrawal was encountered in 33% of patients; however, only 2 patients required LDBI discontinuation as a result. On multivariate analysis, a diagnosis of OUD was independently associated with withdrawal during LDBI. Buprenorphine buccal films can successfully be used off-label to facilitate LDBI in the hospital setting. We present 4- and 7-day titration protocols, which were well-tolerated, and provide practical considerations for use.

A qualitative study of chronic pain and opioid use: The impact of restrictive prescribing.

To explore the continuum of pain and addiction for patients with chronic pain (CP) who used opioids during a time of restrictive opioid prescribing in West Virginia. This qualitative descriptive study used a content analysis of semistructured interviews. Themes were identified through a reflective, iterative coding process. Consolidated criteria for reporting qualitative research guidelines were followed. West Virginia. Twenty people who used opioids to treat a CP condition, 10 pharmacists, 10 primary care providers, and 10 specialists. Semistructured interviews. To better understand the impact of restrictive prescribing measures on people who used opioids for CP. Patients initiated opioids for acute, painful conditions and described how long-term use led to physical dependence and, for some, opioid use disorder. Restrictive opioid prescribing laws led to care interruptions and decreased access and availability of prescribed opioid pain medication, driving some patients to seek illicit drugs. Economic considerations influenced drug use as the price of purchasing prescription opioids on the street went up, making heroin a cheaper alternative. Patients who transitioned to buprenorphine/naloxone as a treatment for pain or opioid use disorder viewed it as a positive change and a "life saver." Opioid use for CP is complex and multifaceted. The continuum of pain and opioid use disorder can begin with a prescription for acute pain and continue for the treatment of CP. Patients described how continued opioid use was not to "get high" but for pain control to improve their quality of life, continue to work, and be productive. For those who experience physical dependence on opioids, access to treatment is vital to recovery and pain management. Without individualized managed care, people confronted with a sudden interruption in prescription opioids may turn to illicit drugs to mitigate symptoms of opioid withdrawal and physical dependence.

The role of loneliness and learning burnout in the regulation of physical exercise on internet addiction in Chinese college students

ObjectiveTo explore the mediating effects of physical exercise on internet addiction in Chinese college students and to reveal the mediating effects of loneliness and learning burnout on physical exercise and internet addiction.Methods1238 Chinese college students were investigated by physical exercise scale, loneliness scale, learning burnout scale, and internet addiction scale. The SPSS 27.0 was used to conduct a correlation analysis of the data and AMOS21.0 was used to establish a structural equation model to investigate the mediation effect.ResultsPhysical exercise could directly negatively predict the internet addiction of college students. Loneliness and learning burnout partially mediate the relationship between physical exercise and internet addiction, and the mediating pathways included “physical exercise-loneliness-internet addiction”, “physical exercise-learning burnout-internet addiction”, and “physical exercise-loneliness-learning burnout-internet addiction”, accounting for 9.38%, 15.63% and 21.88% of the total effect, respectively. In the chain mediation effect, it was mainly the loneliness and sub-dimensions of learning burnout (low mood, misbehavior) that were at play.ConclusionPhysical exercise not only directly affects internet addiction of college students but also indirectly affects internet addiction through the independent mediating effect of loneliness and learning burnout and the chain mediating effect of “loneliness-learning burnout”.

Withdrawal from 3-Fluoroethamphetamine induces hyperactivity and depression-like behaviors in male mice.

3-Fluoroethamphetamine (3-FEA) belongs to the amphetamine class of stimulant drugs and functions as a releasing agent for the monoamine neurotransmitters norepinephrine, dopamine, and serotonin. 3-FEA acts on the central nervous system and elicits physical and mental side effects, such as euphoria, increased heart rate, and excitement. However, little is known about the withdrawal symptoms and behavioral changes induced by 3-FEA administration. This study aimed to evaluate the short-term consequences of 3-FEA administration (twice a day, 7 days, i.p.; 1 and 10 mg/kg) in C57BL/6J mice (male, 7 weeks old) at three behavioral levels following 1-4 days of withdrawal. The evaluation included (1) withdrawal score, (2) hyperactivity (open field [OF], elevated plus maze [EPM], and cliff avoidance [CA] test), and (3) depression-like behavior (forced-swim test). In the withdrawal score test, withdrawal behavior increased in all 3-FEA groups at 16 and 40 h after withdrawal. In the OF, EPM, and CA tests, the 3-FEA administration group showed significant changes in terms of hyperactivity. In addition, in the forced-swim test, both the 1 mg/kg and 10 mg/kg 3-FEA groups showed increased immobility time. These findings indicate that 3-FEA administration may lead to physical dependence, demonstrated by the withdrawal score increase and significant changes in hyperactivity and depression-like behavior following repeated administration and drug cessation. In conclusion, this study reveals the adverse consequences of 3-FEA administration and highlights the need for awareness raising and regulatory action to control the use of this new psychoactive substance.

Using Latent Profile Analysis to Examine Cannabis Use Contexts: Associations with Use, Consequences, and Protective Behaviors

Objective College students represent a large portion of the population, and report high rates of cannabis use and related negative outcomes, including interpersonal problems, risky behaviors, or physical dependency. The contexts in which students use cannabis (e.g., at a party, when feeling down or depressed, after a fight with a loved one) likely affect their risk of experiencing consequences. We aimed to discern profiles of cannabis use contexts and compare profiles on use frequency, consequences, and the use of cannabis protective behavioral strategies (PBS). Method College students were surveyed regarding their cannabis use contexts, frequency, consequences, and PBS use (n = 265; female = 72.8%). We used Latent Profile Analysis to identify patterns of cannabis use contexts and auxiliary testing to compare profiles on use frequency, consequences, and PBS use. Results Our examination revealed three latent profiles of cannabis use. The Social Use Profile was associated with use in predominantly social/uplifting contexts. The Physical & Emotional Pain Profile was also associated with use in these contexts but was defined by additional use in response to pain. The All Contexts Profile was associated with frequent use in all contexts, including those that were least endorsed by the other profiles. Profiles differed in cannabis use frequency, PBS use, and the number of consequences experienced, such that profiles were more likely to be associated with more frequent cannabis use, higher risk of experiencing use-consequences, and using fewer PBS as the number of use contexts increased across the profiles. Conclusions The contexts in which people use cannabis are associated with cannabis risk and protection. Prevention and intervention efforts may benefit from considering contexts of cannabis use.

Cultural adaptation and validation of the Arabic version of the short 12-item stroke-specific quality of life scale.

Given the excessive length and inconsistent validity of the existing long stroke-specific quality of life (SS-QOL) scales, there is a need to validate a shorter measuring tool. The aim of this study was to validate the Arabic version of the short 12-item SS-QOL (SS-QOL-12-AR) and examine its validity measures and psychometric properties. Additionally, the study aimed to assess the QOL after stroke and identify the sociodemographic and clinical factors that influence it in Lebanon. A cross-sectional study was conducted. The SS-QOL-12-AR structure was validated, and its reliability and internal consistency were assessed. The scale's specificity and sensitivity were evaluated and then compared with those of other SS-QOL scales. The correlation between each item and the overall scale were examined, and its convergent validity was evaluated. A total of 172 stroke survivors were included. The SS-QOL-12-AR structure was validated with a solution of two factors, with a Kaiser-Meyer-Olkin measure of sampling adequacy of 0.850 and a significant Bartlett's test of sphericity (p < 0.001). The Cronbach's alpha of the scale was 0.917. According to ROC curve analysis, the optimal cut-off point for distinguishing between lower and better QOL was 32.50. At this cut-off, the sensitivity and specificity were 70.0% and 71.2%, respectively. The area under the curve was 0.779 (95% CI 0.704-0.855, p < 0.001). The SS-QOL-12-AR demonstrated a strong and highly significant correlation with existing versions of the SS-QOL, confirming its convergent validity. 61.6% of stroke survivors had a lower QOL, which was significantly associated with poor stroke prognosis, increased physical dependence, current smoking, and alcohol abstinence. The SS-QOL-12-AR exhibits strong validity and reliability, demonstrating excellent psychometric properties. The scale holds potential for application in clinical practice and research settings, enabling the measurement of stroke-related consequences and evaluation of management outcomes.

Validation of a Computationally Efficient Model of the Mu-Opioid Receptor

The mu-opioid receptor (MOR) is a transmembrane protein and the primary target for pain-modulating drugs. Opioid drugs come with detrimental side-effects such as physical dependence and addiction. However, recent studies show that understanding structural properties and dynamics of MOR may aid in the design of opioid drugs with reduced side-effects. Molecular dynamics simulations allow researchers to study changes in protein conformation at an atomistic level. However, modeling systems including MOR embedded in a lipid bilayer can be computationally expensive. This study evaluates a modeling approach that uses harmonic restraints on the transmembrane regions of MOR to model the rigidity of the lipid bilayer without explicitly simulating lipid molecules, reducing the number of atoms in the simulation. The proposed model allows MOR to be simulated 49% faster than a simulation explicitly including the lipid bilayer. To assess the accuracy of the proposed model, simulations were performed of MOR in a lipid bilayer, the free MOR in water and MOR in water with harmonic restraints applied to all transmembrane residues using NAMD 3.0 alpha and the CHARMM36 force field. Dynamic properties of MOR were shown to be different in each system, with the free MOR having a higher root mean square deviation (RMSD) than MOR with an explicitly modeled lipid bilayer. The systems with harmonic restraint constants of 0.001 kcal/mol/Å2 applied to the transmembrane residues had RMSD values comparable to those in an explicitly modeled lipid bilayer. This study demonstrates that using restraints on the transmembrane residues of MOR is a feasible way of modeling the ligand-free receptor with reduced computational costs. This model could allow the dynamics of MOR in a lipid bilayer environment to be studied more efficiently. KEYWORDS: Molecular Dynamics; Atomistic Simulations; Computational Modeling; Mu-Opioid Receptor; G-Protein Coupled Receptor; Lipid Bilayer, Opioid, Transmembrane Protein