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Introduction: Inducting buprenorphine from methadone has traditionally involved initial opioid withdrawal, with risk of mental state deterioration in patients with serious mental illness (SMI). Micro‐dosing of buprenorphine, with small incremental doses, is a novel off‐label approach to transitioning from methadone and does not require a period of methadone abstinence. Given the limited literature about buprenorphine microdosing, we aimed to evaluate the feasibility and safety of inducting buprenorphine in a series of patients on methadone with SMI. Methods: For this retrospective case series, we reviewed the records of 16 patients with SMI at a Melbourne addiction treatment centre, from January 2021 to July 2022, who transitioned via micro‐dosing, from high‐dose methadone (>30 mg) to buprenorphine and depot‐buprenorphine. Psychiatric diagnoses, mental state, other substance withdrawal, transfer success, transition time, opioid withdrawal symptoms and overall patient experience were collected via objective and subjective reporting. Results: Methadone to buprenorphine transfer was completed by 88% of patients. Mental health measures remained stable with the exception of mildly increased anxiety. Median transfer time was 6.5 days for inpatients, 9 days for mixed setting and 10 days for outpatients. Most patients (93%) rated their experience 'manageable' reporting mild withdrawal symptoms. One patient met study criteria for precipitated withdrawal. Discussion and Conclusions: This retrospective case series provides evidence that the use of a micro‐dosing buprenorphine induction for methadone to buprenorphine transitions, including to depot‐buprenorphine, has negligible risk, is tolerated by patients with SMI and is unlikely to precipitate an exacerbation of their mental illness. [ABSTRACT FROM AUTHOR]

Introduction: Despite recommendations for ambulatory withdrawal programs appearing in many contemporary alcohol and other drug treatment guidelines, to date there have been few studies exploring such programs from client and service stakeholder perspectives. The aim of this study was to explore both individual and service stakeholder perceptions of a nurse practitioner‐led ambulatory withdrawal service on the Gold Coast, Queensland, Australia. Methods: Data were obtained from three groups: clinicians with knowledge of the service (n = 6); relatives of clients who had used the service (n = 2); and clients who had used the service (n = 10) using a Qualitative Descriptive design. Saldaña's (Saldaña, The coding manual for qualitative researchers. 2013) structural coding framework was used to analyse and code data into themes, with the study reported in accordance with the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist (Tong et al. Int J Qual Health Care 2017;19:349–57). Results: Participants noted advantages of the nurse practitioner‐led ambulatory withdrawal service, including rapid availability of admission to the service and a person‐centred approach. Compared with other ambulatory withdrawal options, clients valued the ability to remain in their own environment, however participants suggested greater follow‐up after withdrawal, with the potential of a home visiting service for greater client engagement and treatment retention. Discussion and Conclusions: Findings provide evidence to suggest that nurse practitioner‐led ambulatory withdrawal services are an acceptable option for a proportion of clients who need rapid access to services when they wish to make changes to their alcohol and/or other drug use. Furthermore, they can provide person‐centred care for comorbid physical and mental ill health occurring in addition to psychosocial issues associated with alcohol and/or other drug use. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We sought to determine whether clonidine, a non-opioid α-2-adrenergic agonist, would effectively treat neonatal opioid withdrawal syndrome (NOWS). METHODS: This was an intention-to-treat randomized clinical trial. Enrollment criteria included prenatal opioid exposure, age ≤7 days, gestational age ≥35 weeks, no other medical condition, and need for pharmacotherapy. Primary outcomes were length of treatment and neurobehavioral performance. RESULTS: A total of 1107 patients were screened for enrollment (645 ineligible, 91 parents or staff unavailable, 216 declined, 155 consented). Of 155 infants, 120 required treatment and were randomized to receive oral clonidine (n = 60) at 1 µg/kg/dose or morphine (n = 60), 0.06 mg/kg/dose, every 3 hours. Infants with no improvement had their doses increased by 25% of the initial dose every 12 to 24 hours. Those without improvement by the fourth dose increase, received adjunct therapy. Length of treatment did not differ between morphine and clonidine, with median (95% confidence interval [CI]) days, respectively, of 15 (13-17) and 17 (15-19), P = .48. More clonidine-treated infants (45%) needed adjunct therapy versus 10% in the morphine group, adjusted odds ratio (95% CI) = 8.85 (2.87-27.31). After treatment completion, the NICU Network Neurobehavioral Scales summary scores did not differ between clonidine-treated and morphine-treated infants. CONCLUSIONS: Length of pharmacologic treatment and final neurobehavioral performance were not significantly different between the clonidine- and morphine-treated groups. Clonidine appears to be an effective non-opioid medication to treat NOWS. Future studies are needed to determine the optimal clonidine dosage for a quicker response and obviation of adjunct therapy. [ABSTRACT FROM AUTHOR]

Objective Results Conclusion A post‐marketing surveillance was conducted to evaluate the safety and efficacy of the buprenorphine transdermal patch under actual clinical practice.Of the 3017 patients included in the safety analysis, adverse drug reactions (ADRs) were observed in 1524 (50.5%), the most common being nausea, skin symptoms at the site of application, constipation, and vomiting. The incidences of respiratory depression and withdrawal symptoms were low, and no drug dependence was observed. Among the 2573 patients included in the efficacy analysis, the efficacy (≥2‐point improvement in the numerical rating scale) rate was 74.4%, which was significantly higher in older adults (≥65 y.o) than in younger adults. Discontinuation was mostly caused by ADRs during the early initiation phase.This study demonstrated the safety and efficacy of long‐term administration of buprenorphine transdermal patches, suggesting that pain control is possible over the long term if attention is paid to ADRs in the early stages of administration. [ABSTRACT FROM AUTHOR]

Objective: This systematic review and meta-analysis aimed to assess interventions to reduce opioid use for patients with chronic non-cancer pain (CNCP) versus usual care or active controls in primary care settings. Methods: In this registered study (PROSPERO: CRD42022338458), we searched MEDLINE, Embase PsycInfo, CINAHL, and Cochrane Library from inception to December 28th 2021, and updated on Dec 14th 2023 for randomized controlled trials (RCTs) and cohort studies with no restrictions. Methodological quality was assessed using the Cochrane Risk of Bias tool for RCTs and Newcastle Ottawa Scale for cohort studies. Primary outcomes included mean reduction in morphine equivalent daily dose (reported as mean differences [MDs] mg/day; 95% confidence intervals [95%CIs]) and/or opioid cessation proportion. Secondary outcomes were mean changes in pain severity (reported as standardized mean difference [SMDs]; 95%CIs) and (serious) adverse events. Meta-analyses were performed using random-effects models. Results: We identified 3,826 records, of which five RCTs (953 participants) and five cohort studies (901 participants) were included. Overall, opioid dosage was significantly reduced in intervention groups compared to controls (MD: -28.63 mg/day, 95%CI: -39.77 to -17.49; I2 = 31.25%; eight studies). Subgroup analyses revealed significant opioid dose reductions with mindfulness (MD: -29.36 mg/day 95%CI: -40.55 to -18.17; I2 = 0.00%; two trials) and CBT-based multimodalities (MD: -41.68 mg/day; 95%CI: -58.47 to -24.89; I2 = 0.00%; two cohort studies), respectively, compared to usual care. No significant differences were observed in opioid cessation (Odds ratio: 1.10, 95%CI: -0.48 to 2.67, I2 = 58.59%; two trials) or pain severity (SMD: -0.13, 95%CI: -0.37 to 0.11; I2 = 33.51%; three trials). Adverse events were infrequently examined, with withdrawal symptoms commonly reported. Conclusions: The studied interventions were effective in reducing opioid dosage for people with CNCP in primary care. They highlighted the importance of multidisciplinary collaboration. Large-scale RCTs measuring the long-term effects and cost of these interventions are needed before their implementation. [ABSTRACT FROM AUTHOR]

Currently, depression-induced suicide has emerged as the primary contributor to the worldwide burden of disability. However, the prevailing drug treatment not only suffers from delayed effectiveness and limited efficacy, but also there are withdrawal symptoms and rebound phenomenon. Consequently, there is an imperative to investigate safer and more efficient treatments to ameliorate the clinical manifestations of depression. At present, there is increased evidence that probiotics can improve the symptoms of depression, but the existing studies use many and mixed types of probiotics, and it is impossible to determine the specific efficacy of bifidobacteria in the treatment of depression. This review will systematically review the effects of bifidobacteria on the treatment effect of depression, Meta-analysis showed that Bifidobacterium-related preparations effectively improved depressive symptoms in patients with depression. This study represents the initial meta-analysis conducted on the use of bifidobacteria-related agents for treating depression. The objective was to determine the effect of bifidobacteria-related preparations on improving depressive symptoms. We found that Bifidobacterium and its related agents can effectively reduce depression scale scores in patients with depression, suggesting the need for further research into this potential strategy for the prevention and treatment of depression. [ABSTRACT FROM AUTHOR]

The article explores the use of extended-release buprenorphine (XR-BUP) as a treatment option for opioid use disorder (OUD) in the criminal-legal system. It highlights the benefits of XR-BUP, such as improved initiation and adherence to treatment, prolonged relief from withdrawal symptoms, and reduced stigma. The authors compare XR-BUP to other medications for OUD and discuss the challenges and considerations in implementing XR-BUP in carceral settings. The article emphasizes the importance of evidence-based decision-making and economic evaluations to ensure optimal use of resources in providing care for incarcerated individuals with OUD. Additionally, the text mentions ongoing research by the Justice Community Opioid Innovation Network (JCOIN) to evaluate the accessibility, implementation, effectiveness, and cost-effectiveness of medication for opioid use disorder (MOUD) in the criminal-legal system. The goal is to inform policy decisions and improve MOUD access and outcomes for incarcerated individuals. Continued funding and research are necessary to address ongoing issues and adapt to changing circumstances. [Extracted from the article]

Background and Objectives Methods Results Discussion and Conclusion Scientific Significance Amidst increasing opioid‐related overdoses in the USA, opioid use disorder (OUD) treatment has seen few novel treatments emerge. High‐potency synthetic opioids (HPSOs) have altered clinical approaches, prompting evaluation of existing medications for opioid use disorder (MOUD) and interest in slow‐release oral morphine (SROM) as another therapeutic option. Here we survey addiction specialists on the influence of HPSOs on clinical practice, views on current MOUD regulations, and openness to novel therapies such as SROM.Anonymous, online survey conducted at a national conference of addiction specialists (N = 91). Pearson χ2 tests and Fisher's exact tests to compare respondent characteristics.Approximately 89% of respondents (N = 91) acknowledge that HPSOs shifted addiction treatment in recent years, with 86% modifying their MOUD prescribing accordingly. Moreover, 84% report having patients who could benefit from other full opioid agonists beyond methadone for OUD management. Many report off‐label prescribing of full agonist opioids other than methadone for withdrawal symptoms or initiating MOUD. Eighty percent reported being in favor of incorporating SROM as a third‐line monotherapy for OUD.This sample of addiction specialists supports innovative alternatives for MOUD in the USA to combat the challenges posed by fentanyl and related HPSOs. Future work should further addiction specialists' opinions on barriers to OUD treatment and exploration of these international strategies in the USA.This appears to be the first study exploring addiction specialists' perspectives on regulatory barriers to OUD treatment and their willingness to uptake internationally adopted strategies such as SROM. [ABSTRACT FROM AUTHOR]

The study aimed to verify the effectiveness of a multi-activity training program in reducing smartphone addiction and improving sleep quality among primary school students. The main study sample consisted of 23 students from the fifth and sixth grades, aged between 10 and 12 years, with an average age of 11.04 years and a standard deviation of 0.706. This sample was divided into two equivalent groups: a control group (12 students) and an experimental group (11 students). The students were selected based on high levels of smartphone addiction (upper quartile) and low levels of sleep quality (lower quartile). The study tools included a smartphone addiction scale, a sleep quality scale for primary school students, and a multi-activity training program to reduce smartphone addiction for primary school students, all developed by the researchers. After applying the program, several results were obtained, the most important of which are: There were statistically significant differences at the 0.01 significance level between the mean ranks of the control and experimental groups in the post-measurement of the smartphone addiction scale and its sub-dimensions (daily life problems, excessive use, withdrawal symptoms) in favor of the control group, There were statistically significant differences at the 0.01 significance level between the mean ranks of the control and experimental groups in the post-measurement of the sleep quality scale and its sub-dimensions (healthy sleep indicators, stable and deep sleep, daily performance) in favor of the experimental group. There were statistically significant differences at the 0.01 significance level between the mean ranks of the experimental group in the pre- and postmeasurements of the total score of the smartphone addiction scale and its sub-dimensions in favor of the pre-measurement. There were statistically significant differences at the 0.01 significance level between the mean ranks of the experimental group in the pre- and post-measurements of the total score of the sleep quality scale and its sub-dimensions (healthy sleep indicators, stable and deep sleep, daily performance) in favor of the post-measurement. There were no statistically significant differences between the mean ranks of the experimental group in the post- and follow-up measurements for the sub-dimensions of excessive use and withdrawal symptoms. There were statistically significant differences at the 0.01 significance level in the post- and follow-up measurements of the total score of the smartphone addiction scale and the daily life problems dimension in favor of the follow-up measurement, but there were no statistically significant differences between the mean ranks of the experimental group in the post- and follow-up measurements on the sleep quality scale and its sub-dimensions. [ABSTRACT FROM AUTHOR]

A self-administered questionnaire for screening cigarette dependence was developed based on a set of 6335 Chinese adult smokers (termed the China Cigarette Dependence Test, CCDT). Both a 20-item version (CCDT-20) and a 7-item of the questionnaire (CCDT-7) were developed following 2-round of tests on their construct validity, test-retest reliability and internal consistency, covering seven dimensions (cigarettes per day, tolerance, withdrawal symptoms, craving, loss of control, regularity, and stereotypy). The results showed that the CCDT-20 and CCDT-7 scores were higher in daily smokers than in occasional smokers, and both were associated with self-rated nicotine dependence, exhaled carbon monoxide (CO), saliva cotinine, and DSM-V. The CCDT-20 and CCDT-7 scales were found to be easier to use by smokers in China and provided a more reliable measure of their cigarette dependence. [ABSTRACT FROM AUTHOR]

Introduction: Buprenorphine is used to treat opioid use disorder (OUD). However, therapy is often disrupted during acute pain episodes, and re-initiation is often deferred due to intolerable interruption in opioid analgesics. This case report describes a unique strategy for inducing buprenorphine without stopping opioid analgesics. Case: One patient with OUD and acute pain was initiated on buprenorphine using intravenous microdosing without precipitated withdrawal or pain exacerbation. Full agonist opioids were successfully weaned after discharge and the patient was linked with a community-based treatment program. Conclusion: This case describes use of intravenous buprenorphine to treat OUD and acute pain without adverse consequences. [ABSTRACT FROM AUTHOR]

According to the Centers for Disease Control and Prevention (CDC), 100,306 drug overdose deaths occurred in the US during a 12-month period ending in April 2021. Opioids were involved in 75% of these related deaths. Opioid Use Disorder (OUD) is a constantly evolving public health crisis with potentially lethal consequences. In 2017, 900 adolescents began to misuse opioids every day. Nearly 10% of high school seniors reported using opioids nonmedically. Additionally, the incidence for hospitalizations for adolescents among children 1-19 years of age increased nearly 2-fold from 1997 to 2012. This data emphasizes the dangers associated with the increasing accessibility of pharmaceutical and non-pharmaceutical opioids, particularly for adolescents. All three of the currently FDA approved medications for OUD have shown clear efficacy in decreasing all-cause mortality in adults. It is proposed that the same effects should be seen in adolescents but limited data is present. A recent study analyzed buprenorphine and naltrexone treatment amongst OUD in adolescents between 2001-2014; only 1 in 4 youth received any medication therapy within six months of diagnosis. Adolescents under 16 were the most likely to receive medications. However, even adolescents aged 17, for whom buprenorphine is FDA approved for, were less likely to receive therapy than adults over 18 years of age. The following case report aims to demonstrate how subcutaneous extended release buprenorphine treatment can be initiated effectively as an outpatient in an adolescent with OUD. It is critical that clinicians work to expand access to pharmacotherapy for adolescents struggling with OUD to ensure proper management and reduction of opioid-related overdoses. [ABSTRACT FROM AUTHOR]

Objectives: The link between cannabis use and psychotic symptoms or disorders is well known. However, the relation between cannabis withdrawal and psychotic symptoms is less studied. Methods: To our knowledge, this is the first publication of an observational systematic report of cannabis-induced psychotic disorder with onset during withdrawal. Here, we review patients presenting to a major emergency room in Montreal between January 2020 and September 2023 in a context of psychotic symptoms following cannabis cessation. Results: In total, seven male and one female patients presented at the peak of cannabis withdrawal with acute psychotic symptoms, representing less than 1% of all emergency service admissions. Conclusions: We discuss current knowledge regarding the endocannabinoid system and dopamine homeostasis to formulate hypotheses regarding these observations. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to estimate health state utility values (HSUVs) for the key health states found in opioid use disorder (OUD) cost-effectiveness models in the published literature. Methods: Data obtained from six trials representing 1,777 individuals with OUD. We implemented mapping algorithms to harmonize data from different measures of quality of life (the SF-12 Versions 1 and 2 and the EQ-5D-3 L). We performed a regression analysis to quantify the relationship between HSUVs and the following variables: days of extra-medical opioid use in the past 30 days, injecting behaviors, treatment with medications for OUD, HIV status, and age. A secondary analysis explored the impact of opioid withdrawal symptoms. Results: There were statistically significant reductions in HSUVs associated with extra-medical opioid use (-0.002 (95% CI [-0.003,-0.0001]) to -0.003 (95% CI [-0.005,-0.002]) per additional day of heroin or other opiate use, respectively), drug injecting compared to not injecting (-0.043 (95% CI [-0.079,-0.006])), HIV-positive diagnosis compared to no diagnosis (-0.074 (95% CI [-0.143,-0.005])), and age (-0.001 per year (95% CI [-0.003,-0.0002])). Parameters associated with medications for OUD treatment were not statistically significant after controlling for extra-medical opioid use (0.0131 (95% CI [-0.0479,0.0769])), in line with prior studies. The secondary analysis revealed that withdrawal symptoms are a fundamental driver of HSUVs, with predictions of 0.817 (95% CI [0.768, 0.858]), 0.705 (95% CI [0.607, 0.786]), and 0.367 (95% CI [0.180, 0.575]) for moderate, severe, and worst level of symptoms, respectively. Conclusion: We observed HSUVs for OUD that were higher than those from previous studies that had been conducted without input from people living with the condition. Plain English Summary: Thus far, health-related quality of life estimates for patients with opioid use disorder in the United States are limited, and importantly, they were not generated from studies among people living with the condition. This study extracted data from six clinical trials providing data among 1,777 people with opioid use disorder, made publicly available by the National Institutes of Health, to produce estimates of health-related quality of life. Our study found higher health-related quality of life estimates as compared to previous studies, modest impact of medications for opioid use disorder and strong impact of withdrawal symptoms on this outcome. These higher values among people with opioid use disorder might reflect the very negative perception of this condition among members of the general population (among whom these estimates have been generated previously). However, these relatively high estimates could also reflect an adaptation to the condition or a lack of awareness of associated-health damage in the context of dependence. The low number of observations providing data on medications for opioid use disorder led to high uncertainty around related estimates of health-related quality of life, but our findings could also reflect real experiences by patients in the absence of the positive effects of non-medication opioids, which deserve more attention in clinical practice. Our study suggests that systematically measuring withdrawal symptoms and representing these in health economic models might provide a more accurate representation of health-related quality of life among people with opioid use disorder and therefore of the impact and cost-effectiveness of interventions. Clinical trial registration details: The information reported here results from secondary analyses of data from clinical trials conducted by the National Institute on Drug Abuse (NIDA). Specifically, data from NIDA-CTN-0001 (NCT00032955 and 'Buprenorphine/Naloxone versus Clonidine for Inpatient Opiate Detoxification'), NIDA-CTN-0002 (NCT00032968 and 'Buprenorphine/Naloxone versus Clonidine for Outpatient Opiate Detoxification'), NIDA-CTN-0009 (NCT00067158 and 'Smoking Cessation Treatment with Transdermal Nicotine Replacement Therapy in Substance Abuse Rehabilitation Programs'), NIDA-CTN-0030 (NCT00316277 and 'A Two-Phase Randomized Controlled Clinical Trial of Buprenorphine/Naloxone Treatment Plus Individual Drug Counseling for Opioid Analgesic Dependence'), NIDA-CTN-0049 (NCT01612169 and 'Project HOPE - Hospital Visit as Opportunity for Prevention and Engagement for HIV-Infected Drug Users'), NIDA-CTN-0051 (NCT02032433 and 'Extended-Release Naltrexone vs. Buprenorphine for Opioid Treatment') were included. NIDA databases and information are available at (https://datashare.nida.nih.gov). Additional observational data was used to equate different measures of health-related quality of life onto the same scale using psychometric methods. These data included the National Health Measurement Study (which is available at https://www.disc.wisc.edu/) and the Household Component files for the Medical Expenditure Panel Survey (which is available at https://meps.ahrq.gov/mepsweb/). [ABSTRACT FROM AUTHOR]

Young adults are a high-risk population for developing smartphone addiction (SA), which bring about social issues. One theoretically and empirically supported proximal risk factor of SA is preference for smartphone-based internet applications (PSIA). However, most previous studies ignore gender difference and symptomatic heterogeneity of SA. Besides, many previous data analyses contain non-addicts, and the results derived might not be applicable to smartphone addicts. To bridging the gap, we used a symptom-level network analysis to assess gender differences in the links between preferences for 8 smartphone-based internet applications and 4 SA symptoms among young adults with high-level phone addiction (619 women and 415 men). The results showed that: (1) The relationship between the preference for video and the "loss of control" symptom was more pronounced in female addicts compared to their male counterparts. (2) Shopping app had stronger bridge centrality in women's smartphone applications-SA network, which was positively linked with more SA symptoms. (3) Our research identified marginal gender differences in smartphone addicts' psychological networks, with female addicts showing stronger links between social media/eBook preferences and withdrawal symptoms, and male addicts displaying a stronger connection between gaming/eBook and other smartphone activities. The study provides a visualized network association and network metrics for understanding the relationship between PSIA and SA. We propose adopting a selective processing hypothesis and an evolutionary psychology perspective to aid in understanding these gender differences. [ABSTRACT FROM AUTHOR]

Background: Untreated pain is a source of significant physical and psychosocial distress in patients with cancer. While guidelines for prescribing opioids have improved the treatment of cancer-related pain, all patients who take opioids are at risk for developing opioid-induced respiratory depression (OIRD). The current treatment for OIRD is naloxone although guidelines are highly variable on initial dose and indication. Patients with cancer on chronic opioids are at risk for increased suffering due to naloxone-induced opioid withdrawal and loss of pain control. Aim: A review of the evidence for the safety and benefits of using buprenorphine instead of naloxone for reversal of OIRD in patients prescribed chronic opioids for cancer-related pain. Methods: A realist review of the literature was completed following the RAMSES Framework. An iterative literature search of electronic databases was used to identify appropriate literature relating to buprenorphine and naloxone safety and use as reversal agents in OIRD. Results: While naloxone does reverse OIRD it does have the risk of pulmonary edema and research has consistently shown that naloxone is usually given for the wrong indications and/or at an inappropriate dose for patients on chronic opioids for cancer-related pain. Buprenorphine has been shown to safely reverse OIRD with less incidence and severity of withdrawal and uncontrolled pain when compared to naloxone. Conclusions: Because of the potential for decreased opioid withdrawal-associated symptoms, this review argues that buprenorphine warrants additional study and consideration to replace naloxone as the first-line rescue medication for patients with cancer on chronic opioids who experience OIRD. [ABSTRACT FROM AUTHOR]

Background: As cannabis legalization continues to spread across the United States, average Δ9-tetrahydrocannabinol concentrations in recreational products have significantly increased, and no prior study has evaluated effective treatments to reduce cannabis use among high potency cannabis users. Some research has found that the non-intoxicating cannabinoid cannabidiol reduces cannabis use and cannabis use disorder-related symptoms, such as affective disturbance and withdrawal. Results of these studies are promising but limited to synthetic or isolated forms of cannabidiol. Objective: Conduct a placebo-controlled randomized control trial comparing the effects of hemp-derived cannabidiol on reducing Δ9-tetrahydrocannabinol use in concentrate users with cannabis use disorder. Methods: Design. Double-blind, three-arm randomized placebo-controlled trial. Setting. University in the Denver-Boulder, CO, USA area. Study population. Community members who are heavy, stable cannabis concentrate users that meet criteria for at least moderate cannabis use disorder and are seeking to decrease or stop cannabis use. Data. Self-report demographics, substance use, and mental health characteristics, blood and urine based biomarkers and anthropometrics. Outcomes. Affective, physiological, and physical withdrawal symptoms, Δ9-tetrahydrocannabinol use. Analysis. Three-group ANOVAs and χ2 tests will be used to compare baseline variables between groups. Characteristics that differ between groups will be evaluated as potential covariates in subsequent analyses. A multilevel modeling framework will be used for primary outcome analysis to account for the repeated observations nested within participants over time. Pairwise post-hoc simple effects tests will be conducted to confirm patterns of differences. Trial registration: ClinicalTrials.gov NCT06107062. [ABSTRACT FROM AUTHOR]

Background: Understanding the interplay between psychopathology of alcohol withdrawal syndrome (AWS) in alcohol use disorder (AUD) patients may improve the effectiveness of relapse interventions for AUD. Network theory of mental disorders assumes that mental disorders persist not of a common functional disorder, but from a sustained feedback loop between symptoms, thereby explaining the persistence of AWS and the high relapse rate of AUD. The current study aims to establish a network of AWS, identify its core symptoms and find the bridges between the symptoms which are intervention target to relieve the AWS and break the self-maintaining cycle of AUD. Methods: Graphical lasso networkwere constructed using psychological symptoms of 553 AUD patients. Global network structure, centrality indices, cluster coefficient, and bridge symptom were used to identify the core symptoms of the AWS network and the transmission pathways between different symptom clusters. Results: The results revealed that: (1) AWS constitutes a stable symptom network with a stability coefficient (CS) of 0.21-0.75. (2) Anger (Strength = 1.52) and hostility (Strength = 0.84) emerged as the core symptom in the AWS network with the highest centrality and low clustering coefficient. (3) Hostility mediates aggression and anxiety; anger mediates aggression and impulsivity in AWS network respectively. Conclusions: Anger and hostility may be considered the best intervention targets for researching and treating AWS. Hostility and anxiety, anger and impulsiveness are independent but related dimensions, suggesting that different neurobiological bases may be involved in withdrawal symptoms, which play a similar role in withdrawal syndrome. [ABSTRACT FROM AUTHOR]

Alcohol consumption is an important risk factor for illness, disability, and mortality. Alcohol withdrawal symptoms have a significant health concern for individuals with alcohol dependence. This study aims to investigate the prevalence of withdrawal symptoms and liver function test abnormalities in this population and also to identify the factors associated with the severity of withdrawal symptoms. This cross-sectional study was conducted at a tertiary care facility involving 100 patients seeking treatment for alcohol dependence. Data collection included structured interviews and assessments using standardized scales and biochemical tests. Descriptive statistics, t-tests, and chi-square tests were employed to analyse the data. Individuals exhibiting mild/moderate alcohol withdrawal symptoms in this study displayed several distinctive features. They were more likely to have attained at least a high school education, their average alcohol consumption was notably lower, Importantly, their blood parameters, including RBC count, platelet count, total bilirubin levels, and liver enzyme levels (AST and ALT), generally exhibited fewer deviations from normal ranges. Family history of alcohol dependence and nicotine dependence was common among the participants. This research highlights the need for a holistic approach to address alcohol dependence, taking into consideration sociodemographic factors, clinical markers, and the diverse nature of this condition. The findings provide important insights for healthcare professionals to identify individuals at higher risk and guide treatment decisions. [ABSTRACT FROM AUTHOR]

Background: Relapsing seizures following discontinuation of antiseizure drugs (ASDs) has been the focus of several researches in recent years. This research aimed to identify the predictive factors of seizure recurrence after anti-seizure drugs withdrawal among epileptic patients who had achieved two years seizures remission. Methods: A total of 60 epileptic patients who had achieved two years seizures remission and began ASDs withdrawal were followed prospectively for one year. The patients were divided into two groups; patients with and without relapsed seizures. Clinical and demographic details were recorded. National Hospital Seizure Severity Scale (NHS3) was used to assess theseverity of epilepsy. Regular Electroencephalogram (EEG) monitoring was done. Anxiety and depressive symptoms were assessed by using generalized anxiety disorder 7 (GAD7) and Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) scales respectively. Results: Risk of post-withdrawal relapsed seizures increased with; history of status epilepticus (p=0.002), focal seizures (p=0.005), late remission of initial epileptic seizures (p=0.002), delay of ASD therapy (p<0.001), Poly-therapy (p<0.001), post-withdrawal epileptiform EEG (p<0.001), high NHS3, GAD7, NDDI-E scores (p<0.001) Conclusions: Risk of relapsing seizures after ASDs withdrawal during the first year was 60%. The decision to withdraw ASDs necessitates individual evaluation of each case with accurate assessment of risk factors associating with relapsed seizures. [ABSTRACT FROM AUTHOR]

Loperamide is an over‐the‐counter peripheral mu‐opioid agonist commonly used to manage diarrhoea. When taken in an excessive dose, loperamide's penetration of the central nervous system increases, leading to euphoria, respiratory depression and other opioid effects. A health warning was released in the United States in 2016 with increased reports of excessive loperamide use leading to cardiac conduction abnormalities such as ventricular tachycardia, prolonged QTc and Torsades des Pointes. The growing number of cases is likely due to the increased restrictions on other opioids. Loperamide use disorder has been managed effectively in the United States and the United Kingdom using buprenorphine. In Australia, there have been recent opioid restrictions limiting easy access to opioids. We describe the case of a 28‐year‐old male who was admitted to hospital on multiple occasions with symptoms relating to loperamide use disorder. Buprenorphine was used to manage withdrawal symptoms in the hospital and maintain abstinence from loperamide in the community through an opioid agonist treatment program. To our knowledge, this is the first case study to describe the successful management of loperamide use disorder with buprenorphine within Australia. Our findings suggest that buprenorphine can be used to manage patients with loperamide associated withdrawal and help them remain abstinent upon discharge. Extramedical use of over‐the‐counter opioid medication may be becoming an emerging trend in Australia, and increased monitoring is warranted to prevent detrimental health outcomes. [ABSTRACT FROM AUTHOR]

Cannabis use and cannabis use disorders have taken on a new social significance as a result of partial legalization. In 2021 a total of 4.5 million adults (8.8%) in Germany used the drug. The number of users as well as problematic use have risen in the last decade. Cannabis products with a high delta-9-tetrahydrocannabinol (THC) content and their regular use lead to changes in cannabinoid receptor distribution in the brain and to modifications in the structure and functionality of relevant neuronal networks. The consequences of cannabinoid use are particularly in the psychological functioning and can include intoxication, harmful use, dependence with withdrawal symptoms and cannabis-induced mental disorders. Changes in the diagnostics between ICD-10 and ICD-11 are presented. Interdisciplinary S3 guidelines on cannabis-related disorders are currently being developed and will be finalized shortly. [ABSTRACT FROM AUTHOR]

Introduction: In recent years, pregabalin has received growing attention due to its abuse liability. The aim of this study was to further characterize patterns of pregabalin users from substance abuse treatment facilities and detect changes in users profile over the study period. Methods: The data source was the Observation des Produits Psychotropes Illicites ou Détournés de leur Utilisation Médicamenteuse (OPPIDUM) program, an annual, repeated, cross-sectional, nationwide, multicenter survey that collects consumption data from patients with substance use disorders. First, we described the characteristics of pregabalin users and their consumption patterns. We compared these data between 2008 and 2018 (P1) and 2019 and 2022 (P2). Second, we conducted a multiple correspondence analysis to identify profiles of users. Results: From 2008 to 2022, 291 pregabalin users (0.37% of all users) from 116 substance abuse treatment facilities were identified. The number of pregabalin users was lower than 15 per year in P1 (n = 89) and between 40 and 60 per year in P2 (n = 202). The number of users who reported pregabalin as the first substance leading to dependence increased significantly in P2 compared with P1 (p < 0.005). When comparing P2 with P1, there was a significant increase in precarity (p < 0.001), users in prison (p = 0.002), withdrawal symptoms (p < 0.001), dependence (p < 0.001), use of higher dose of pregabalin (p = 0.029), and acquisition by deal/street market (p < 0.001). The multiple correspondence analysis allowed for the identification of distinct profiles of pregabalin users: (i) a cluster with mainly users from P1, who presented a simple use of pregabalin, and were older (> 45 years), were involved in opioid agonist treatment (OAT), and obtained pregabalin legally; and (ii) a cluster with mainly users from P2, who presented pregabalin dependence, and were younger (< 26 years), reported pregabalin as the first substance leading to dependence, used doses higher than the market authorization, were in severe precarity, and were in prison. Conclusions: These data showed that the profile of pregabalin users has changed in the last years. Pregabalin use disorders also affect users without history of addiction. [ABSTRACT FROM AUTHOR]

The incidence of substance use and behavioral addictions continues to increase throughout the world. The Global Burden of Disease Study shows a growing impact in disability-adjusted life years due to substance use. Substance use impacts families, communities, health care, and legal systems; yet, the vast majority of individuals with substance use disorders do not seek treatment. Within the United States, new legislation has attempted to increase the availability of buprenorphine, but the impact of substance use continues. Although medications and group support therapy have been the mainstay of treatment for substance use, lifestyle medicine offers a valuable adjunct therapy that may help strengthen substance use recovery through healthy neuroplastic changes. [ABSTRACT FROM AUTHOR]

Currently, systemic glucocorticoids are taken by about 1–3% of the general population, up to 1.8% long-term. Moreover, about 50% of patients taking these drugs orally develop glucocorticoid-induced adrenal insufficiency (GIAI) after their withdrawal. Despite this scale of the problem and the length of time the issue has been studied, there are currently no standard algorithms for reducing the dose or discontinuing glucocorticoids. The evidence base on this issue has been performed on relatively few clinical studies, which are extremely heterogeneous with respect to the populations studied, designs, regimens of glucocorticoid use, and diagnostic approaches to adrenal insufficiency. Thus, the weight of evidence on this issue remains inadequate, resulting in each institution having its own approach to dose reduction and discontinuation of glucocorticoids, or no approach at all. This article summarizes current information about GIAI, allowing for improved approaches to dose reduction or discontinuation of glucocorticoids. Improving the management tactics of patients who have been receiving glucocorticoids for a long time will lead to a reduction in the risk of complications of GIAI, including life-threatening ones, as well as to a significant improvement in the quality of life of patients.

Purpose: The primary objective was to assess the performance benefits of caffeine (CAF) supplementation in habitual users. Importantly, this investigation was designed to account for the potential confounding effects of CAF withdrawal (CAFW), which are inherent and common in previous work. Methods: Ten CAF-consuming (394 [146] mg·d−1) recreational cyclists (age 39.1 [14.9] y; maximum oxygen consumption 54.2 [6.2] mL·kg–1·min–1) completed four 10-km time trials (TTs) on a cycle ergometer. On each trial day, 8 hours before reporting to the laboratory, subjects consumed 1.5 mg·kg–1 CAF to prevent withdrawal (no withdrawal [N]) or a placebo (PLA; withdrawal [W]). Then, 1 hour prior to exercise, they received either 6 mg·kg–1 CAF or PLA. These protocols were repeated 4 times, employing all combinations of N/W and CAF/PLA. Results: CAFW did not impair TT power output (PLAW vs PLANP =.13). However, preexercise CAF only improved TT performance when compared to PLA in the W condition (CAFN vs PLAWP =.008, CAFW vs PLAWP =.04), not when W was mitigated (PLAN vs CAFNP =.33). Conclusions: These data indicate that preexercise CAF only improves recreational cycling performance when compared to bouts preceded by CAF abstinence, suggesting that habitual users may not benefit from 6 mg·kg–1 of CAF and that previous work may have overstated the value of CAF supplementation for habitual users. Future work should examine higher doses of CAF for habitual users. [ABSTRACT FROM AUTHOR]

Background: Many people with opioid use disorder who stand to benefit from buprenorphine treatment are unwilling to initiate it due to experience with or fear of both spontaneous and buprenorphine-precipitated opioid withdrawal (BPOW). An effective means of minimizing withdrawal symptoms would reduce patient apprehensiveness, lowering the barrier to buprenorphine initiation. Ketamine, approved by the FDA as a dissociative anesthetic, completely resolved BPOW in case reports when infused at a sub-anesthetic dose range in which dissociative symptoms are common. However, most patients attempt buprenorphine initiation in the outpatient setting where altered mental status is undesirable. We explored the potential of short-term use of ketamine, self-administered sublingually at a lower, sub-dissociative dose to assist ambulatory patients undergoing transition to buprenorphine from fentanyl and methadone. Methods: Patients prescribed ketamine were either (1) seeking transition to buprenorphine from illicit fentanyl and highly apprehensive of BPOW or (2) undergoing transition to buprenorphine from illicit fentanyl or methadone and experiencing BPOW. We prescribed 4–8 doses of sublingual ketamine 16 mg (each dose bioequivalent to 3–6% of an anesthetic dose), monitored patients daily or near-daily, and adjusted buprenorphine and ketamine dosing based on patient response and prescriber experience. Results: Over a period of 14 months, 37 patients were prescribed ketamine. Buprenorphine initiation was completed by 16 patients, representing 43% of the 37 patients prescribed ketamine, and 67% of the 24 who reported trying it. Of the last 12 patients who completed buprenorphine initiation, 11 (92%) achieved 30-day retention in treatment. Most of the patients who tried ketamine reported reduction or elimination of spontaneous opioid withdrawal symptoms. Some patients reported avoidance of severe BPOW when used prophylactically or as treatment of established BPOW. We developed a ketamine protocol that allowed four of the last patients to complete buprenorphine initiation over four days reporting only mild withdrawal symptoms. Two patients described cognitive changes from ketamine at a dose that exceeded the effective dose range for the other patients. Conclusions: Ketamine at a sub-dissociative dose allowed completion of buprenorphine initiation in the outpatient setting in the majority of patients who reported trying it. Further research is warranted to confirm these results and develop reliable protocols for a range of treatment settings. [ABSTRACT FROM AUTHOR]

Background: Although social determinants of health (SDoH) have increasingly been understood as clinically important factors in the onset, maintenance, and relapse of substance use behavior, little research has evaluated neighborhood vigilance in terms of smoking. Objectives: The present investigation sought to evaluate the role of neighborhood vigilance in terms of smoking abstinence expectancies (i.e., perceived consequences of refraining from smoking, including negative mood, somatic symptoms, harmful consequences, and positive consequences) and severity of problems when trying to quit among adults who smoke. Results: Participants included 93 treatment-seeking people who smoke (45.2 years of age and 29% identified as female). Results: indicated that greater levels of neighborhood vigilance were associated with negative mood and harmful consequences abstinence expectancies. No effect was evident for somatic symptom abstinence expectancies after Bonferroni correction. Conclusions: As expected, neighborhood vigilance was not predictive of positive abstinence expectancies, offering explanatory specificity. Neighborhood vigilance was also associated with more severe problems when trying to quit smoking. The current findings suggest neighborhood vigilance represents an important contextual factor involved in certain negative beliefs about abstinence and challenges in quitting. [ABSTRACT FROM AUTHOR]

Many drastic actions are taken by cocaine users for the sake of experiencing high levels of dopamine, which depends on iron for its synthesis. Dopamine depletion and iron deficiency are also involved in the symptoms of restless leg syndrome (RLS). The intersecting biochemical pathways of cocaine use, iron deficiency, and RLS have not been adequately investigated. This case report reveals the successful treatment of a patient experiencing these conditions. A 63-year-old male with a history of cocaine use disorder, insomnia, and RLS sought emergency care for suicidality. Upon admission, he was also found to be iron deficient. He revealed that his RLS worsened when he attempted to abstain from cocaine. He also used alcohol to sustain the effects of cocaine when the cost of cocaine was too high. During hospitalization, his mood, cravings, and RLS were resolved with adjunctive iron supplementation, as well as treatment with 300 mg of Wellbutrin (bupropion hydroxychloride). If iron deficiency is present, the replenishment of the adequate dopaminergic receptor density and function via supplementation may play an essential role in the prevention of cocaine use and the cessation of cocaine withdrawal symptoms. Further research is warranted to validate these findings and to investigate the implications of iron supplementation in addiction medicine. [ABSTRACT FROM AUTHOR]

The problem of drug abuse is one of the most important scourges of society in our modern era, as its spread increases day after day in many countries of the world, and what makes matters worse is the emergence of new types of drugs whose chemical composition and source are unknown. There are many types of drugs, all of which pose serious health risks, the most important of which is addiction, which is represented by many behavioral and physiological phenomena and practices that develop upon repeated use of these narcotic substances. Mostly, it leads to a strong and urgent desire and need for continuous consumption and dependence on it in daily life, despite the harmful consequences that the addict suffers from, as well as the appearance of its withdrawal symptoms. Drugs include many types, some of which are extracted naturally from plants and some of which are chemically manufactured in laboratories. Without exception, all of them pose a real danger to physical and psychological health and may often lead to death. Narcotic substances are divided according to several factors, including their effect. On humans, the severity of addiction to it, as well as its chemical composition, etc. Plants produce a wide range of secondary metabolites as a defense as they strive to survive. These secondary metabolites include many alkaloids, most of which are used as narcotic substances. These chemicals often serve to deter plant-harming herbivores or to protect against pathogens and bush damage near plant roots, as well as to mitigate the effects of plantharming radiation. Interestingly, many of these chemical compounds have the ability to interact with the human body in specific ways, from organ failure and death to reactions that lead to useful and life-saving medications. [ABSTRACT FROM AUTHOR]

Introduction: Research indicates that take-home naloxone (THN) is saving lives across rural Appalachia, but whether it also results in treatment for opioid use disorders (OUDs) remains unclear. This study involves a detailed qualitative analysis of interviews with 16 individuals who had overdosed on opioids 61 times to understand why a THN intervention does not routinely lead to OUD treatment. Methods: This study builds upon a one-year (2018) qualitative study on community responses to opioid overdose fatalities in four adjacent rural counties in Western Pennsylvania. Using a semi-structured interview guide, 16 individuals who had experienced one or more overdoses were interviewed. Using NVivo, the transcribed audio-recorded interviews were coded, and a thematic analysis of the coded text was conducted. Findings: Findings reveal that of the 29 overdoses that included a THN intervention, only eight resulted in treatment. The analysis derives five individual-level barriers to treatment: (1) opioid dependence, (2) denial/readiness, (3) opioid withdrawal fears, (4) incarceration concerns, and (5) stigma and shame. These barriers impeded treatment, even though all the interviewees knew of treatment programs, how to access them, and in some cases had undergone treatment previously. Discussion and Conclusion: findings indicate that there is evidence that the five barriers make entering treatment after a THN intervention challenging and seemingly insurmountable at times. Recommendations based on the findings include increasing efforts to reduce stigma of OUDs in the community, including self-stigma resulting from misusing opioids, increasing informational efforts about Good Samaritan Laws, and increasing familiarity with medication-assisted treatments for OUDS. [ABSTRACT FROM AUTHOR]

Buprenorphine is a medication that is used to treat opioid use disorder by reducing withdrawal symptoms and cravings for opioids. Patients with poor adherence are at higher risk of relapse and overdose. Providers often test adherence through urine testing but are not aware of simulated adherence, where patients may directly add buprenorphine to the urine samples. As of now, there exists no literature on the simulated adherence practices for patients who stayed in the treatment for more than three months This study is a cross-sectional analysis of simulated adherence through urine toxicology results of 3950 patients undergoing buprenorphine/naloxone treatment. Simulated adherence was measured by the ratio of norbuprenorphine and buprenorphine <0.02 in the urine sample. Descriptive statistics as well as multivariate analysis was conducted to examine the relationship between patient information and outcomes. Out of 3950 patients, 411 (10.4%) had a history of one or more simulated adherence. On average, patients with multiple simulated adherences had 48.1% of their tests simulated, while on the contrary, patients with a single occurrence of simulated adherence had 17.6% of their tests simulated. Weekly testing and visit number of over 15 were associated with a higher likelihood of simulated adherence. The study demonstrates that simulated adherence is a recurring phenomenon among buprenorphine/naloxone treatment patients regardless of the duration in the treatment. Utilization of quantitative urine toxicology to identify simulated adherence will enable healthcare providers to formulate a more precise and effective treatment plan tailored to support individual patient needs. [ABSTRACT FROM AUTHOR]

Methadone maintenance treatment is effective for managing opioid use disorder, but it can have many adverse effects that result in dose reduction. Patients often report persistent withdrawal symptoms after the dose reduction, which can decrease their adherence to treatment and increase the risk for relapse. Acupuncture has been recognized as an appropriate nonpharmacologic treatment for substance dependence. This multicenter, randomized, sham-controlled trial assessed the efficacy of acupuncture versus sham acupuncture on methadone dose reduction. Visual Abstract. Effect of Acupuncture for Methadone Reduction: Methadone maintenance treatment is effective for managing opioid use disorder, but it can have many adverse effects that result in dose reduction. Patients often report persistent withdrawal symptoms after the dose reduction, which can decrease their adherence to treatment and increase the risk for relapse. Acupuncture has been recognized as an appropriate nonpharmacologic treatment for substance dependence. This multicenter, randomized, sham-controlled trial assessed the efficacy of acupuncture versus sham acupuncture on methadone dose reduction. Background: Methadone maintenance treatment (MMT) is effective for managing opioid use disorder, but adverse effects mean that optimal therapy occurs with the lowest dose that controls opioid craving. Objective: To assess the efficacy of acupuncture versus sham acupuncture on methadone dose reduction. Design: Multicenter, 2-group, randomized, sham-controlled trial. (Chinese Clinical Trial Registry: ChiCTR2200058123) Setting: 6 MMT clinics in China. Participants: Adults aged 65 years or younger with opioid use disorder who attended clinic daily and had been using MMT for at least 6 weeks. Intervention: Acupuncture or sham acupuncture 3 times a week for 8 weeks. Measurements: The 2 primary outcomes were the proportion of participants who achieved a reduction in methadone dose of 20% or more compared with baseline and opioid craving, which was measured by the change from baseline on a 100-mm visual analogue scale (VAS). Results: Of 118 eligible participants, 60 were randomly assigned to acupuncture and 58 were randomly assigned to sham acupuncture (2 did not receive acupuncture). At week 8, more patients reduced their methadone dose 20% or more with acupuncture than with sham acupuncture (37 [62%] vs. 16 [29%]; risk difference, 32% [97.5% CI, 13% to 52%]; P  < 0.001). In addition, acupuncture was more effective in decreasing opioid craving than sham acupuncture with a mean difference of −11.7 mm VAS (CI, −18.7 to −4.8 mm; P  < 0.001). No serious adverse events occurred. There were no notable differences between study groups when participants were asked which type of acupuncture they received. Limitation: Fixed acupuncture protocol limited personalization and only 12 weeks of follow-up after stopping acupuncture. Conclusion: Eight weeks of acupuncture were superior to sham acupuncture in reducing methadone dose and decreasing opioid craving. Primary Funding Source: National Natural Science Foundation of China. [ABSTRACT FROM AUTHOR]

Rationale/Objectives: Targeting cannabinoid receptor type 1 (CB1R) has shown promise for treating opioid withdrawal symptoms. This study aimed to investigate the efficacy of a specific CB1R negative allosteric modulator (NAM), Org27569, in reducing both naloxone-precipitated and protracted withdrawal symptoms in oxycodone-dependent mice. Methods: Mice received escalating doses of oxycodone (9–33 mg/kg IP) or saline twice daily for 9 days, followed by a final dose of oxycodone (33 mg/kg) or saline in the morning of day 9. In one cohort, the impact of Org27569 (3, 10, and 30 mg/kg) on naloxone (10 mg/kg IP) precipitated withdrawal symptoms was assessed. In another cohort, Org27569 (3 mg/kg) effects on the acquisition of conditioned place aversion to naloxone (0.6 mg/kg) precipitated opioid withdrawal, on behaviour following a 7–9-day abstinence period, and on naloxone (0.6 mg/kg) precipitated withdrawal-induced escape behaviour in a novel assay were assessed. Results: Although Org27569 decreased opioid withdrawal-induced jumping at doses of 10 and 30 mg/kg, these effects were confounded by reduced locomotion. At all doses tested, Org27569 had a modest inhibitory effect on gastrointestinal motility. At the lower dose of 3 mg/kg, which was not confounded by locomotor effects, Org27569 did not impact naloxone-precipitated withdrawal-induced jumping, acquisition of oxycodone withdrawal-induced conditioned place aversion, or naloxone-precipitated withdrawal-induced escape behaviour in a novel assay. A clear protracted opioid withdrawal phenotype was not observed in assays of anxiety-like or social behaviour. Conclusions: Org27569 effects on negative affective-like symptoms were confounded by locomotor effects and effects on gastrointestinal motility were not opioid withdrawal specific. Further studies are needed in a model that produces a more pronounced protracted withdrawal syndrome. [ABSTRACT FROM AUTHOR]

The present study aimed to examine the differential association between (i) harmonious and obsessive forms of passion for exercise (HP and OP, respectively) and (ii) specific exercise dependence symptoms. Self-reported cross-sectional data from 618 Spanish regular exercisers aged from 18 to 36 years (Mage = 21.15, SDage = 2.78, 39.80% females) were analysed using multiple-indicators-multiple-causes (MIMIC) models with a maximum-likelihood robust (MLR) estimation method. In these analyses, gender, age, perceived health status, exercise frequency, risk of eating disorders, and depressive symptoms were considered as potential confounding variables. The results showed that HP contributed to explaining significant proportions of variance in three specific exercise dependence symptoms (time, tolerance, and continuance), while OP contributed to explaining significant proportions of variance across the full range of exercise dependence symptoms. The variance explained by the regression models ranged from 23.50% (for withdrawal symptoms) to 54.70% (for time symptoms). These findings support the differential nature of the potential causal relationships between the autonomous and controlled processes of behavioural internalisation inherent to HP and OP, respectively, for exercise and specific exercise dependence symptoms. The controlled behavioural internalisation processes characterising OP (i.e., those involving exercise engagement under contingencies not necessarily endorsed by the individual) may be particularly maladaptive according to their specific and positive relationship with the full range of exercise dependence symptoms. [ABSTRACT FROM AUTHOR]

Phenibut, a GABAB receptor agonist, has surged in popularity due to its nootropic and anxiolytic effects. Despite not being FDA approved, it is accessible online due to its marketing as a dietary supplement, leading to unregulated distribution. Increasing reports have highlighted the risks of addiction and severe withdrawal symptoms associated with phenibut use. This case report explores the management of phenibut withdrawal in an outpatient setting using a baclofen taper. The slow taper was complicated by various withdrawal symptoms, and the patient was ultimately stabilized on lorazepam, baclofen, gabapentin, and clonidine after 5‐months time. This case is unique, as it also highlights challenges in tapering off baclofen following phenibut detoxification. The study underscores the need for further research on the pharmacological management of phenibut withdrawal, emphasizing the importance of raising awareness about phenibut's dangers and associated clinical presentations. [ABSTRACT FROM AUTHOR]

The Canadian Journal of Pain's "Book of Abstracts" delves into various aspects of pain management, such as addressing anti-Indigenous racism in healthcare, exploring pain sensitization mechanisms, and understanding placebo effects. The abstracts touch on genetics in cannabinoid metabolism, optogenetics in pain therapy, and the importance of patient perspectives in chronic pain care. The symposiums emphasize a patient-centric approach, the impact of psychological factors on pain perception, and the potential of mindfulness programs in chronic pain management. Experts at the Chronic Pain Symposium will discuss sex differences in receptor expression, risk trajectories linked to medication use, and cognitive factors influencing pain experiences, among other topics. [Extracted from the article]

Varenicline tartrate is a smoking cessation aid that works by blocking nicotine receptors in the brain. It helps reduce cravings and withdrawal symptoms and helps you quit smoking. The study aimed to formulate and characterize varenicline tartrate orodispersible tablets using the synthetic disintegrants crospovidone and croscarmellose sodium in different ratios and directly compressible microcrystalline cellulose as diluent, and mannitol to improve mouthfeel using the direct compression method. A total of 13 varenicline orodispersible tablets are formulated and subsequently evaluated for pre-compression and post-compression physicochemical parameters such as angle of repose, Carr index, Hausner ratio, hardness, thickness, mass variation, drug content, friability, wetting time, disintegration time, dispersion time and water absorption ratio. Optimization was performed with percentage of crospovidone (X1 or A) and croscarmellose sodium (X2 or B) as independent variables, while disintegration time (Y1) and wetting time (Y2) were selected as dependent variables using the central composite design of Design-Expert® DX 12. Optimized formulations showed 99.68 % drug release in 60 min while the cumulative percentage drug release of pure drug was only 56.84 %. Finally, it was concluded that dissolution rate and bioavailability are improved with varenicline tartrate orodispersible tablets. [ABSTRACT FROM AUTHOR]

OBJECTIVE A risk stratified sedation weaning protocol improved patient outcomes in a pediatric intensive care unit (PICU). We sought to determine the protocol effect on medication costs. METHODS This was a retrospective observational cohort study in an academic tertiary care children’s hospital PICU (2018–2020) comparing the cost when weaning benzodiazepine, alpha agonist, and/or opioid infusions in intubated children <18 years of age. RESULTS There were 84 total sedation weaning instances (pre-protocol n = 41 and post-protocol n = 41); 2 patients had 2 encounters, 1 in each phase. The total cost (in 2022 United States Dollars) of sedation weaning was $400,328.87 ($15,994.44/kg) pre-protocol compared with $170,458.85 ($11,227.52/kg) post-protocol. The median cost of sedation wean per patient for pre-protocol patients was $3197.42 (IQR: $322.66–$12,643.29) and post-protocol patients was $1851.44 (IQR: $425.05–$5355.85; p = 0.275). A linear regression model estimated the expected cost of sedation wean for post-protocol patients to be $5173.20 lower than for pre-protocol patients of the same weight and overall drug risk (p = 0.036). The proportion of withdrawal symptoms in the pre-protocol patients (16%) was not significantly different from the proportion in the post-protocol patients (14%; p = 0.435). CONCLUSIONS Implementation of a PICU sedation weaning protocol in a single-center conferred cost benefit without negatively impacting patient outcomes. A larger multicenter study would provide insight to the applicability to PICUs in varied settings with differing patient populations. [ABSTRACT FROM AUTHOR]

Heavy substance use (SU) and substance use disorders (SUD) have complex etiologies and often severe consequences. Certain personality traits have been associated with an increased risk for SU(D), but far less is known about personality changes related to SU(D). This review aims to synthesize the existing literature on this research question. A systematic literature search was conducted from November 2022 to February 2023 in PubMed, EbscoHost, and Web of Science. Peer-reviewed original papers on SU(D)-related personality changes were included. Of 55 included studies, 38 were observational population-based studies and 17 were intervention studies. Overall, personality and SU measures, samples, study designs, and statistical approaches were highly heterogenous. In observational studies, higher SU was most consistently related to increases in impulsivity-related traits and (less so) neuroticism, while interventions in the context of SU(D) were mostly associated with increases in conscientiousness and self-efficacy and lasting decreases in neuroticism. Findings for traits related to extraversion, openness, conscientiousness, and agreeableness were mixed and depended on SU measure and age. Studies on bidirectional associations suggest that personality and SU(D) both influence each other over time. Due to their strong association with SU(D), impulsivity-related traits may be important target points for interventions. Future work may investigate the mechanisms underlying personality changes related to SU(D), distinguishing substance-specific effects from general SU(D)-related processes like withdrawal, craving, and loss of control. Furthermore, more research is needed to examine whether SU(D)-related personality changes vary by developmental stage and clinical features (e.g. initial use, onset, remission, and relapse). [ABSTRACT FROM AUTHOR]

Safe chemicals for drug withdrawal can be extracted from natural sources. This study investigates the effects of clonidine and Thymbra spicata extract (TSE) on mice suffering from morphine withdrawal syndrome. Thymol, which is the active constituent in TSE, was also tested. A total of 90 mice were divided into nine groups. Group 1 was the control group, while Group 2 was given only morphine, and Group 3 received morphine and 0.2 mg/kg of clonidine. Groups 4–6 were given morphine along with 100, 200, and 300 mg/kg of TSE, respectively. Groups 7–9 received morphine plus 30, 60, and 90 mg/kg of Thymol, respectively, for 7 days. An oral naloxone challenge of 3 mg/kg was used to induce withdrawal syndrome in all groups. Improvement of liver enzyme levels (aspartate aminotransferase, alkaline phosphatase, and alanine transaminase) (p <.01) and behavioral responses (frequencies of jumping, frequencies of two‐legged standing, Straub tail reaction) (p <.01) were significantly observed in the groups receiving TSE and Thymol (Groups 4–9) compared to Group 2. Additionally, antioxidant activity in these groups was improved compared to Group 2. Nitric oxide significantly decreased in Groups 4 and 6 compared to Groups 2 and 3 (p <.01). Superoxide dismutase increased dramatically in Groups 5, 8, and 9 compared to Groups 2 and 3 (p <.01). Groups 5–9 were significantly different from Group 2 in terms of malondialdehyde levels (p <.01). Certain doses of TSE and Thymol were found to alleviate the narcotics withdrawal symptoms. This similar effect to clonidine can pave the way for their administration in humans. Significance statement: Thymbra spicata extracts and Thymol may lessen narcotic drug withdrawal symptoms in specific dosages. Coadministration of T. spicata extract with morphine reduced the symptom severity of morphine withdrawal syndrome induced by naloxone. T. spicata extract and Thymol increase superoxide dismutase in morphine withdrawal groups. Thymol dramatically lowered the levels of alanine transaminase, aspartate aminotransferase, alkaline phosphatase activity, and total bilirubin. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To elicit expert consensus on quality indicators for the hospital-based care of opioidexposed infants. METHODS: We used the ExpertLens online platform to conduct a 3-round modified Delphi panel. Expert panelists included health care providers, parents in recovery, quality experts, and public health experts. We identified 49 candidate quality indicators from a literature review and environmental scan. A total of 32 experts rated the importance and feasibility of the indicators using a 9-point Likert scale (Round 1), reviewed and discussed the initial ratings (round 2), and revised their original ratings (Round 3). Numeric scores corresponded with descriptive ratings of "low" (1-3), "uncertain" (4-6), or "high" (7-9). We measured consensus using the RAND/UCLA Appropriateness Method. RESULTS: Candidate quality indicators assessed structures, processes, and outcomes in multiple domains of clinical care. After the final round, 36 indicators were rated "high" on importance and feasibility. Experts had strong consensus on the importance of quality indicators to assess universal screening of pregnant people for substance use disorder, hospital staff training, standardized assessment for neonatal opioid withdrawal syndrome, nonpharmacologic interventions, and transitions of care. For indicators focused on processes and outcomes, experts saw feasibility as dependent on the information routinely documented in electronic medical records or billing records. To present a more complete picture of hospital quality, experts suggested development of composite measures that summarize quality across multiple indicators. CONCLUSIONS: A panel of experts reached consensus on a range of quality indicators for hospitalbased care of opioid-exposed infants, with potential for use in national benchmarking, intervention studies, or hospital performance measurement. [ABSTRACT FROM AUTHOR]

Previous research has indicated that various factors, such as psychological distress, distress intolerance, anhedonia, impulsivity and smoking metacognitions, have been individually linked to the urge to smoke, withdrawal symptoms and dependence. However, these factors have not been collectively examined to determine whether smoking metacognitions independently and significantly contribute to these outcomes. Therefore, the aim of this study was to investigate the impact of distress intolerance, anhedonia, impulsivity and smoking metacognitions on the urge to smoke, withdrawal symptoms and dependency in men who are dependent on smoking. A total of 300 smoking‐dependent men completed psychological scales and smoking‐related measures. The findings of the study indicated that positive metacognitions about emotion regulation significantly predicted the urge to smoke, even when accounting for other significant predictors such as the number of daily cigarettes smoked, psychological distress, anhedonia and impulsivity. Furthermore, positive metacognitions about cognitive regulation were found to be a significant predictor of withdrawal symptoms, independent of other significant predictors such as psychological distress and the urge to smoke. Smoking dependence was predicted by negative metacognitions about uncontrollability beyond other significant predictors, including the number of daily cigarettes smoked and distress intolerance. These results highlight the role of metacognitions about smoking in both short‐ and long‐term clinical outcomes related to smoking. Consequently, addressing such beliefs during treatment for smoking dependence should be an important therapeutic goal. [ABSTRACT FROM AUTHOR]

Misuse of prescription and non-prescription stimulants and related overdose deaths represent a growing public health crisis that warrants immediate intervention. We examined 100 posts and their respective comments from a public, recovery-oriented Reddit community in January 2021 to explore content related to DSM-V stimulant use disorder symptoms, access and barriers to recovery, and peer support. Using inductive and deductive methods, a codebook was developed with the following primary themes: 1) DSM-V Symptoms and Risk Factors, 2) Stigma/Shame, 3) Seeking Advice or Information, 4) Supportive or Unsupportive Comments. In 37% of posts community members reported taking high doses and engaging in prolonged misuse of stimulants. Nearly half of posts in the sample (46%) were seeking advice for recovery, but 42% noted fear of withdrawal symptoms or a loss of productivity (18%) as barriers to abstinence or a reduction in use. Concerns related to stigma, shame, hiding use from others (30%), and comorbid mental health conditions (34%) were also noted. Social media content analysis allows for insight into information about lived experiences of individuals struggling with substance use disorders. Future online interventions should address recovery barriers related to stigma and shame as well as fears associated with the physical and psychological impact of quitting stimulant misuse. [ABSTRACT FROM AUTHOR]

Background and Objectives: While inpatient withdrawal management/acute stabilization can improve outcomes for individuals with opioid use disorder (OUD), patients often leave treatment early due to mood, tension, and cravings associated with opioid withdrawal. The aim of this study was to evaluate the feasibility and preliminary effectiveness of a novel virtual reality (VR) based intervention; 3D Therapy Thrive (3DTT). Methods: Subjects with OUD (N = 32) were recruited from a community acute stabilization program and received up to two sessions of 3DTT. They completed questionnaires related to their overall satisfaction with the experience and side effects; as well as those related to mood, tension, and cravings. Results: There were no reported side effects and the majority of subjects (94%) reported high satisfaction with the experience. Out of 62 patients approached, 33 patients agreed to participate (53%) 33 patients completed one, and 17 of these patients (52%) completed both sessions of 3DTT, with 19 participants (58%) completing their treatment protocols. Compared to baseline, 3DTT participants reported significant reductions in depression, tension, and cravings (p's < 0.001). Discussion and Conclusions: This pilot study supports the feasibility and preliminary effectiveness of 3DTT for improving outcomes for inpatients with OUD. Future randomized controlled trials are necessary to evaluate the efficacy of 3DTT for improving retention, reducing cravings, and improving mood and tension. Scientific Significance: This is the first study to evaluate the feasibility of a psychologically informed VR intervention in inpatients with OUD. [ABSTRACT FROM AUTHOR]

Rationale: Medications are urgently needed to treat symptoms of drug withdrawal and mitigate dysphoria and psychiatric comorbidities that drive opioid abuse and relapse. ITI-333 is a novel molecule in development for treatment of substance use disorders, psychiatric comorbidities, and pain. Objective: Characterize the preclinical profile of ITI-333 using pharmacological, behavioral, and physiological assays. Methods: Cell-based assays were used to measure receptor binding and intrinsic efficacy of ITI-333; animal models were employed to assess effects on opioid reinstatement, precipitated oxycodone withdrawal, and drug abuse liability. Results: In vitro, ITI-333 is a potent 5-HT2A receptor antagonist (Ki = 8 nM) and a biased, partial agonist at μ-opioid (MOP) receptors (Ki = 11 nM; lacking β-arrestin agonism) with lesser antagonist activity at adrenergic α1A (Ki = 28 nM) and dopamine D1 (Ki = 50 nM) receptors. In vivo, ITI-333 blocks 5-HT2A receptor-mediated head twitch and MOP receptor-mediated effects on motor hyperactivity in mice. ITI-333 alone is a naloxone-sensitive analgesic (mice) which suppresses somatic signs of naloxone-precipitated oxycodone withdrawal (mice) and heroin cue-induced reinstatement responding without apparent tolerance or physical dependence after chronic dosing (rats). ITI-333 did not acutely impair gastrointestinal or pulmonary function (rats) and was not intravenously self-administered by heroin-maintained rats or rhesus monkeys. Conclusions: ITI-333 acts as a potent 5-HT2A receptor antagonist, as well a biased MOP receptor partial agonist with low intrinsic efficacy. ITI-333 mitigates opioid withdrawal/reinstatement, supporting its potential utility as a treatment for OUD. [ABSTRACT FROM AUTHOR]

This article considers what it might mean to do the moral work of grieving during an opioid epidemic. Becoming callous, bitter, or resentful are harms we can suffer to our characters when grieving losses, especially at epidemic scale. This article suggests how appreciating beauty can play roles in grieving that could help mitigate these harms. [ABSTRACT FROM AUTHOR]

Severe opioid withdrawal, risk of patient-initiated discharge, and some inpatients' use of unregulated substances prompt clinical and ethical questions considered in this commentary on a case. Short-acting opioids can be used to manage inpatients' pain and opioid use disorder (OUD) withdrawal symptoms. Including evidence-based interventions--such as naloxone kits, substance use equipment, and supervised consumption--in some inpatients' care plans may make those patients safer and reduce their risk of death. These and other strategies align with clinicians' ethical duties to minimize harms and maximize benefits for inpatients with OUD. [ABSTRACT FROM AUTHOR]

Introduction: Alcohol use disorder (AUD) is commonly associated with anxiety disorders and enhanced stress-sensitivity; symptoms that can worsen during withdrawal to perpetuate continued alcohol use. Alcohol increases neuroimmune activity in the brain. Our recent evidence indicates that alcohol directly modulates neuroimmune function in the central amygdala (CeA), a key brain region regulating anxiety and alcohol intake, to alter neurotransmitter signaling. We hypothesized that cannabinoids, such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), which are thought to reduce neuroinflammation and anxiety, may have potential utility to alleviate alcohol withdrawal-induced stress-sensitivity and anxiety-like behaviors via modulation of CeA neuroimmune function. Methods: We tested the effects of CBD and CBD:THC (3:1 ratio) on anxiety-like behaviors and neuroimmune function in the CeA of mice undergoing acute (4-h) and short-term (24-h) withdrawal from chronic intermittent alcohol vapor exposure (CIE). We further examined the impact of CBD and CBD:THC on alcohol withdrawal behaviors in the presence of an additional stressor. Results: We found that CBD and 3:1 CBD:THC increased anxiety-like behaviors at 4-h withdrawal. At 24-h withdrawal, CBD alone reduced anxiety-like behaviors while CBD:THC had mixed effects, showing increased center time indicating reduced anxiety-like behaviors, but increased immobility time that may indicate increased anxiety-like behaviors. These mixed effects may be due to altered metabolism of CBD and THC during alcohol withdrawal. Immunohistochemical analysis showed decreased S100β and Iba1 cell counts in the CeA at 4-h withdrawal, but not at 24-h withdrawal, with CBD and CBD:THC reversing alcohol withdrawal effects.. Discussion: These results suggest that the use of cannabinoids during alcohol withdrawal may lead to exacerbated anxiety depending on timing of use, which may be related to neuroimmune cell function in the CeA. [ABSTRACT FROM AUTHOR]

Background: Morphine withdrawal syndrome is often treated with chemical drugs; however, these drugs can have concerning side effects. Some natural substances might offer safer alternatives for managing withdrawal symptoms. The neuroprotective activity of the adenosine A1 receptor (A1R) in the central nervous system (CNS) has been mentioned before. As a novel natural agent, Japanese sake yeast is enriched with adenosine analogs. Objectives: As the first report, the present study was designed to evaluate the effects of the Japanese sake yeast supplement against the excitatory signs of morphine withdrawal syndrome in mice. Methods: Mice were treated orally (gavage) with sake yeast at doses of 100, 200, and 300 mg kg-1 once daily for a week. Furthermore, during the last 3 days of receiving sake yeast, the animals were made physically dependent on morphine by being given twice-daily subcutaneous injections of increasing doses of morphine (30 - 90 mg/kg) for 3 consecutive days. The withdrawal syndrome was induced in animals through the intraperitoneal (i.p.) administration of naloxone (3 mg kg-1) or was elicited spontaneously. After the examination of withdrawal signs, the animals were decapitated, and their brains were prepared for histopathology. Results: Sake yeast alleviated the intensity of ptosis, piloerection, diarrhea, irritability, and tremor during the two withdrawal syndrome protocols (P < 0.05) and diminished the number of jumping in naloxone-induced withdrawal syndrome (P < 0.01). The withdrawal symptom-lowering effect of sake yeast was reversed by the i.p. injection of an A1R-selective antagonist, 8-cyclopentyltheophylline (10 mg kg-1), and maintained following the i.p. injection of ZM241385 (15 mg kg-1), a selective adenosine A2AR antagonist. Furthermore, histopathological findings demonstrated that sake yeast at doses of 200 and 300 mg kg-1 inhibited the CA1 hippocampal neuronal damage induced by withdrawal syndrome (P < 0.05). Conclusions: Sake yeast suppresses the morphine withdrawal syndrome via the activation of A1R. [ABSTRACT FROM AUTHOR]