Participant Fraud in Virtual Qualitative Substance Use Research: Recommendations and Considerations for Detection and Prevention Based on a Case Study.

Background: The COVID-19 pandemic has accelerated and amplified the use of virtual research methods. While online research has several advantages, it also provides greater opportunity for individuals to misrepresent their identities to fraudulently participate in research for financial gain. Participant deception and fraud have become a growing concern for virtual research. Reports of deception and preventative strategies have been discussed within online quantitative research, particularly survey studies. Though, there is a dearth of literature surrounding these issues pertaining to qualitative studies, particularly within substance use research. Results: In this commentary, we detail an unforeseen case study of several individuals who appeared to deliberately misrepresent their identities and information during participation in a virtual synchronous qualitative substance use study. Through our experiences, we offer strategies to detect and prevent participant deception and fraud, as well as challenges to consider when implementing these approaches. Conclusions: Without general awareness and protective measures, the integrity of virtual research methods remains vulnerable to inaccuracy. As online research continues to expand, it is essential to proactively design innovative solutions to safeguard future studies against increasingly sophisticated deception and fraud.

Characteristics, treatment patterns and retention with extended-release subcutaneous buprenorphine for opioid use disorder: A population-based cohort study in Ontario, Canada.

BACKGROUND: Uptake and retention for opioid agonist treatment (OAT) remains low. Novel extended-release formulations may improve OAT accessibility by reducing the frequency of healthcare visits. Our aim was to examine uptake, characteristics, treatment patterns and retention of individuals initiating extended-release subcutaneous buprenorphine (BUP-ER), a monthly injectable OAT. METHODS: We conducted a population-based cohort study among adults aged 18+ initiated on BUP-ER between February 3, 2020 and March 31, 2022 in Ontario, Canada. Using administrative health data, we defined continuous BUP-ER use based on repeat injections within a 56-day period and used Kaplan-Meier curves to estimate time on treatment. Among new BUP-ER recipients, we described individual and prescriber characteristics, healthcare utilization and treatment patterns. RESULTS: 2366 individuals initiated BUP-ER. The median time to BUP-ER discontinuation was 183 days (interquartile range: 66-428 days) and 52.0% of individuals were co-prescribed buprenorphine/naloxone at least once throughout the period of BUP-ER receipt. Among individuals who initiated on a dose of 300mg BUP-ER and had three or more injections, 18.8% continued to receive only 300mg doses (N=276 of 1470). Furthermore, 28.6% of those whose dose was reduced to 100mg (N=341 of 1194) had a subsequent dose increase to 300mg. CONCLUSIONS: On average, people initiating BUP-ER discontinue within the first 6 months of treatment. While BUP-ER is likely providing an important OAT option, the high occurrence of discontinuation, supplementation with buprenorphine/naloxone, and frequent dose increases suggest inadequacy of current dosing recommendations among a proportion of individuals.

Psychosocial and pharmacologic interventions for problematic methamphetamine use: Findings from a scoping review of the literature.

RATIONALE: Methamphetamine use and related harms have risen at alarming rates. While several psychosocial and pharmacologic interventions have been described in the literature, there is uncertainty regarding the best approach for the management of methamphetamine use disorder (MUD) and problematic methamphetamine use (PMU). We conducted a scoping review of recent systematic reviews (SR), clinical practice guidelines (CPG), and primary controlled studies of psychosocial and pharmacologic treatments for MUD/PMU. METHODS: Guided by an a priori protocol, electronic database search updates (e.g., MEDLINE, Embase) were performed in February 2022. Screening was performed following a two-stage process, leveraging artificial intelligence to increase efficiency of title and abstract screening. Studies involving individuals who use methamphetamine, including key subgroups (e.g. those with mental health comorbidities; adolescents/youths; gay, bisexual, and other men who have sex with men) were sought. We examined evidence related to methamphetamine use, relapse, use of other substances, risk behaviors, mental health, harms, and retention. Figures, tables and descriptive synthesis were used to present findings from the identified literature. RESULTS: We identified 2 SRs, one CPG, and 54 primary studies reported in 69 publications that met our eligibility criteria. Amongst SRs, one concluded that psychostimulants had no effect on methamphetamine abstinence or treatment retention while the other reported no effect of topiramate on cravings. The CPG strongly recommended psychosocial interventions as well as self-help and family support groups for post-acute management of methamphetamine-related disorders. Amongst primary studies, many interventions were assessed by only single studies; contingency management was the therapy most commonly associated with evidence of potential effectiveness, while bupropion and modafinil were analogously the most common pharmacologic interventions. Nearly all interventions showed signs of potential benefit on at least one methamphetamine-related outcome measure. DISCUSSION: This scoping review provides an overview of available interventions for the treatment of MUD/PMU. As most interventions were reported by a single study, the effectiveness of available interventions remains uncertain. Primary studies with longer durations of treatment and follow-up, larger sample sizes, and of special populations are required for conclusive recommendations of best approaches for the treatment of MUD/PMU.

Physician and nurse practitioner perspectives of a modified Routine Opioid Outcome Monitoring (ROOM) Tool.

Introduction The Routine Opioid Outcome Monitoring (ROOM) Tool was developed for use in community pharmacies in Australia. It facilitates pharmacists' screening and brief interventions regarding an individual's opioid use for chronic pain. At our academic teaching hospital, the ROOM Tool was adapted to incorporate a communication tool that includes a pharmacist's assessment and recommendations for primary care providers. This modified ROOM Tool was implemented as part of usual care in our outpatient pharmacies; however, the value to primary care providers is unknown. Aim The aim of this study was to determine primary care provider perspectives on the modified ROOM Tool. Methods Focus groups were conducted with primary care providers from an Academic Family Health Team. The focus group encompassed topics related to the positive and negative aspects of the modified ROOM Tool in supporting the care of patients using opioids for chronic pain. Qualitative content analysis of transcripts was performed to identify themes. Results Three focus groups were conducted with a total of six participants. Four themes emerged: (i) Facilitators to using the tool, (ii) Barriers to using the tool, (iii) Recommendations for improvement, (iv) Impact of the tool on patient care and safety. Discussion The ROOM Tool paired with the communication tool supports collaboration between pharmacists and primary care providers. The communication tool standardises the approach for communicating the pharmacist's assessment and recommendations. Recommendations to refine this modified ROOM Tool may increase its utility to primary care providers and enhance the impact on patient care and safety.

Protocol for a qualitative study exploring the pharmacist's role in supporting postsecondary students with psychotropic medication management.

INTRODUCTION: Findings from the National College Health Assessment (2019) stated that anxiety and depression are the most prevalent diagnosed mental illnesses among Canadian postsecondary students with one-fifth of students self-reporting a lifetime diagnosis. Psychotropic medications can be an important component of a multifaceted approach to the management and treatment of mental illness and are the most commonly dispensed via community pharmacies. Community pharmacies provide an opportunity for pharmacists to have a prominent role in supporting patients' psychotropic medication management. However, there has been limited exploration of how pharmacists can address patients' psychotropic medication management needs, experiences and opportunities for improvements especially for emerging adults. METHODS AND ANALYSIS: This qualitative study will incorporate Thorne's approach to interpretative description. Purposeful snowball sampling will be used to identify students (18-25 years) taking psychotropic medication(s) to manage their mental health. Participants will be interviewed one on one using a semistructured interview guide virtually. Inductive thematic analysis is underway with data analysis being iterative and reflexive using NVivo. Information provided from the interviews will be reviewed and summarised into key themes. ETHICS AND DISSEMINATION: This study was approved by the University of Toronto Health Sciences Research Ethics Board (REB #43185). It is expected that there will be a very low risk for mild psychological and social harm for participants as they will have the ability to stop the interview at any time and will be aware of confidentiality. The results from this study will be used to create or adapt healthcare team services including the role of pharmacists within the healthcare ecosystem at the university and contribute to developing the next stage of research to evaluate feasibility and effectiveness of programmes at the university that help postsecondary students to manage psychotropic medication.

Assessing the impact of the slow-release oral morphine drug shortages in Ontario, Canada: A population-based time series analysis.

BACKGROUND: Slow-release oral morphine (SROM) is used to manage pain, and as opioid agonist treatment (OAT). Between 2017 and 2021 in Canada, several drug shortages occurred for Kadian© (SROM-24). The purpose of this study was to evaluate the impact of these shortages on people's ability to remain on this medication. METHODS: We conducted a retrospective population-based time series analysis of SROM-24 dispensed between January 1, 2014, and December 31, 2021, in Ontario, Canada. Using interventional autoregressive integrated moving average models (ARIMA) models, we evaluated the association between SROM-24 drug shortages and treatment discontinuation. Analyses were also stratified by the SROM-24 indication (pain or OAT). RESULTS: We identified 22,479 SROM-24 recipients, of which one-third (33.9%) were aged 65 or above and just over half (51.9%) were female. In our primary analysis of monthly SROM-24 discontinuation, we observed a significant sustained monthly increase following the shortages in November 2019 (+0.29%/month; 95% CI: 0.16%, 0.43%; p < .001) with significant sudden, temporary changes following the shortages in March 2020 (+2.00%; 95% CI: 0.95%, 3.05%; p < .001), July 2021 (+3.53%; 95% CI: 2.20%, 4.86%; p < .001), and August 2021 (+4.98%; 95% CI: 3.49%, 6.47%; p < .001). Similar results were observed in our stratified analyses, with sustained high rates of discontinuation among people accessing SROM-24 as OAT. CONCLUSIONS: The SROM-24 shortages resulted in significant treatment disruptions across all recipients. These findings have important implications for those with few treatment alternatives, including people using SROM-24 as OAT who are at risk of adverse outcomes following treatment disruptions.

Separate and combined effects of alcohol and cannabis on mood, subjective experience, cognition and psychomotor performance: A randomized trial.

Co-use of alcohol and cannabis is associated with increased frequency and intensity of use and related problems. This study examined acute effects of alcohol and cannabis on mood, subjective experience, cognition, and psychomotor performance. Twenty-eight healthy cannabis users aged 19-29 years with recent history of binge drinking completed this within-subjects, double-blind, double-dummy, placebo-controlled, randomized clinical trial. Participants received: placebo alcohol and placebo cannabis (<0.1% THC); alcohol (target breath alcohol content [BrAC] 80 mg/dL) and placebo cannabis; placebo alcohol and active cannabis (12.5% THC); and active alcohol and cannabis over four sessions. Profile of Mood States (POMS), Addiction Research Centre Inventory (ARCI), verbal free recall (VFR), Digit Symbol Substitution Test (DSST), Continuous Performance Test (CPT), and grooved pegboard (GPB) task were administered before and approximately 75 min after drinking alcohol (1 h after smoking cannabis ad libitum). Significant effects of condition were found for the POMS (Tension-Anxiety, Confusion) and ARCI (MBG, LSD, PCAG, Euphoria, Sedation), predominantly with greater increases emerging after cannabis or alcohol-cannabis combined relative to placebo. Significant effects were found for VFR (immediate total and delayed recall, percent retained), DSST (trials attempted, trials correct, reaction time), and GPB (non-dominant hand) predominantly with greater declines in performance after alcohol and alcohol-cannabis combined relative to placebo and/or cannabis. Cannabis appeared to affect mood and subjective experience, with minimal impact on cognitive performance. Alcohol appeared to impair cognitive and psychomotor performance, with minimal impact on mood and subjective experience. Acute effects of alcohol and cannabis combined were additive at most.

Duration of use and outcomes among people with opioid use disorder initiating methadone and buprenorphine in Ontario: a population-based propensity-score matched cohort study.

AIMS: To characterize comparative risks and benefits of methadone versus buprenorphine/naloxone in a contemporary cohort where the unregulated drug supply is dominated by fentanyl. DESIGN, SETTING AND PARTICIPANTS: Population-based propensity-score matched cohort study conducted in Ontario, Canada among people aged 18+ initiating opioid agonist therapy (OAT) for an opioid use disorder between October 2016 and December 2018 (n = 18 880). INTERVENTION: Initiation of methadone versus buprenorphine/naloxone. MEASUREMENTS: The primary outcome was opioid overdose (fatal and non-fatal) while on treatment, with secondary outcomes including opioid overdose (first 30 days of treatment), treatment discontinuation, health-care interactions related to treatment of opioid use disorder, receiving a weekly supply of take-home doses and opioid overdose within 30 days of treatment discontinuation. Outcomes were assessed over 1 year. FINDINGS: Overall, 7517 people initiating buprenorphine were matched to an equal number of methadone-treated individuals. Risk of opioid overdose while on treatment [hazard ratio (HR) = 0.50; 95% confidence interval (CI) = 0.37-0.68] or within the first 30 days of treatment (HR = 0.51, 95% CI = 0.31-0.85) was lower among buprenorphine recipients compared to methadone recipients. In secondary analyses, people initiating buprenorphine had a higher risk of treatment discontinuation within the first year (median time to discontinuation 104 versus 265 days, HR = 1.43, 95% CI = 1.37-1.49), had lower rates of health-care interactions for OUD (186.4 versus 254.3 per person-year; rate ratio = 0.73; 95% CI = 0.72-0.75), and a higher rate of receiving weekly take-home doses (HR = 2.33; 95% CI = 2.20-2.46). Overdose rates in the period following OAT discontinuation were higher than those observed while on treatment, but did not differ significantly by OAT type. CONCLUSIONS: Although treatment retention is higher among methadone recipients, overdose risk is also elevated compared to buprenorphine recipients. These findings demonstrate the benefits of any OAT on avoidance of overdose, particularly following treatment discontinuation and with the increasingly unpredictable drug supply in North America.

Impact of changes in opioid funding and clinical policies on rapid tapering of opioids in Ontario, Canada.

ABSTRACT: Reports have emerged of abrupt tapering among recipients of long-term prescription opioids to conform new prescribing guidelines. We conducted a population-based, repeated cross-sectional time-series study among very high-dose (≥200 MME) opioid recipients in Ontario, Canada, to examine changes in the monthly prevalence of rapid tapering from 2014 to 2018, defined as recipients experiencing either a ≥50% reduction in daily doses or abrupt discontinuation sustained for 30 days. Interventional autoregressive integrated moving average models were used to test for significant changes following key guidelines and drug policies and programs. A sensitivity analysis examined rapid tapering sustained for 90 days. The monthly prevalence of rapid tapering events was stable from January 2014 to September 2016 (average monthly prevalence: 1.4%) but increased from 1.4% in October 2016 to 1.8% in April 2017 (P = 0.001), coincident with Ontario's Fentanyl Patch-for-Patch Return Program implementation. Transient spikes in the prevalence of rapid tapering also occurred 2 months after Ontario's delisting of publicly funded high-strength opioids and the release of updated Canadian Opioid Prescribing Guideline for Chronic Pain, reaching 2.3% in March 2017 and July 2017, respectively. However, this prevalence decreased to 1.2% in December 2018 (P < 0.0001). Although the prevalence of abrupt opioid discontinuation was lower, similar trends were observed. Our sensitivity analysis examining long-lasting rapid tapering found similar trends but lower prevalence, with no changes in complete discontinuation. These temporary increases in rapid tapering events highlight the need for improved communication and evidence-based resources for prescribers to minimize negative consequences of evolving policies and guidelines.

The role of pharmacists in opioid stewardship: A scoping review.

BACKGROUND: The opioid epidemic is an international public health concern. Pharmacists are in a strategic position to promote and implement effective opioid stewardship due to both their central role on health care teams and frequent interaction with patients. Despite this integral role, pharmacists do not have harmonized scopes of practice in opioid stewardship. OBJECTIVES: This scoping review was conducted to identify and critically review the role of pharmacists in opioid stewardship and identify future areas of study. METHODS: The scoping review was conducted according to the methodological framework proposed by Arksey and O'Malley, which was further modified by the Joanna Briggs Institute. Six databases were searched for original, peer-reviewed research; PubMed (MEDLINE), Ovid Embase, Ovid International Pharmaceutical Abstracts, Scopus, Cochrane Library, and APA PsycInfo. RESULTS: In 92% of the included studies (n = 77), opioid stewardship interventions led by either a pharmacist or in an interdisciplinary team resulted in improvements in at least one outcome measure, with education and medication therapy adjustments being the most predominant activities. Other areas supported by evidence include community stakeholder education, policy and guideline setting, and risk assessment. CONCLUSION: This scoping review provides valuable insight into the various roles pharmacists can have in opioid stewardship. The findings from this review identified opioid stewardship activities that can make significant contributions towards reducing the impact of the opioid crisis. This review informs future research and has the potential to influence pharmacy practice on a national and international scale.

Predictors of and reasons for early discharge from inpatient withdrawal management settings: A scoping review.

ISSUES: Early discharges, also known as 'against medical advice' discharges, frequently occur in inpatient withdrawal management settings and can result in negative outcomes for patients. The purpose of this scoping review is to identify what is known about predictors of and reasons for the early discharge among adults accessing inpatient withdrawal management settings. APPROACH: MEDLINE, CINAHL, PsycINFO, ASSIA and EMBASE were searched, resulting in 2587 articles for screening. Title and abstract screening and full-text review were completed by two independent reviewers. Results were synthesised in quantitative and qualitative formats. KEY FINDINGS: Sixty-two studies were included in this scoping review. All studies focused on predictors of early discharge, except one which only described reasons for the early discharge. Forty-eight percent of studies involved retrospective review of health records data. The most frequently examined variables were demographics. Variables related to the treatment setting, such as referral source and treatment received, were examined less frequently but were more consistently associated with early discharge compared to demographics. Only six studies described patient reasons for the early discharge, which were retrieved via clinical documentation. The most common reasons for early discharge were dissatisfaction with treatment and family issues. IMPLICATIONS AND CONCLUSIONS: Most demographic variables do not consistently predict early discharge, and reasons for early discharge are not well understood. Future studies should focus on the predictive value of non-patient-level variables, or conduct analyses to account for predictors of early discharge among different subgroups of people (e.g. by gender or ethnicity). Qualitative research exploring patient perspectives is needed.

Pharmacists as Personalized Medicine Experts (PRIME): Experiences Implementing Pharmacist-Led Pharmacogenomic Testing in Primary Care Practices.

Research exploring the integration of pharmacogenomics (PGx) testing by pharmacists into their primary care practices (including community pharmacies) has focused on the "external" factors that impact practice implementation. In this study, additional "internal" factors, related to the capabilities, opportunities, and motivations of pharmacists that influence their ability to implement PGx testing, were analyzed. Semi-structured interview data from the Pharmacists as Personalized Medicine Experts (PRIME) study, which examined the barriers and facilitators to implementing PGx testing by pharmacists into primary care practice, were analyzed. Through thematic analysis, using the theoretical domains framework (TDF) domains as deductive codes, the authors identified the most relevant TDF domains and applied the behavioural change wheel (BCW) to generate intervention types to aid in the implementation of PGx testing. Pharmacists described how their professional identities, practice environments, self-confidence, and beliefs in the benefits of PGx impacted their ability to provide a PGx-testing service. Potential interventions to improve the implementation of the PGx service included preparing pharmacists for managing an increased patient load, helping pharmacists navigate the software and technology requirements associated with the PGx service, and streamlining workflows and documentation requirements. As interest in the wide-scale implementation of PGx testing through community pharmacies grows, additional strategies need to address the "internal" factors that influence the ability of pharmacists to integrate testing into their practices.

Sex differences in the acute pharmacological and subjective effects of smoked cannabis combined with alcohol in young adults.

Objective: The prevalence of co-use of alcohol and cannabis is increasing, particularly among young adults. Sex differences in the effects of alcohol alone and cannabis alone have been observed in animals and humans. However, sex differences in the acute pharmacological effects of cannabis combined with alcohol have not yet been studied. In young adults, aged 19-29 years, we aimed to examine sex differences following an intoxicating dose of alcohol (target 0.08% breath alcohol content) combined with a moderate dose of cannabis (12.5% Δ9-tetrahydrocannabinol; THC) using an ad libitum smoking procedure. Method: Using a within-subjects design, 28 regular cannabis users (16 males; 12 females) received in random order: (a) placebo alcohol and placebo cannabis, (b) active alcohol and placebo cannabis, (c) placebo alcohol and active cannabis, and (d) active alcohol and active cannabis. Blood samples for THC were collected and measures of vital signs, subjective drug effects, and cognition were collected. Results: In the alcohol-cannabis combined condition, females smoked significantly less of the cannabis cigarette compared to males (p < .001), although both sexes smoked similar amounts in the other conditions. There was minimal evidence that females and males differed in THC blood concentrations, vitals, subjective effects, or cognitive measures. Conclusions: In the alcohol-cannabis combined condition, females experienced the same acute pharmacological and subjective effects of alcohol and cannabis as males, after smoking less cannabis, which has potential implications for informing education and policy. Further research is warranted on sex differences in cannabis pharmacology, as well as the combined effects of alcohol and cannabis. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The Role of the Pharmacist in the Care of Patients with Chronic Pain.

Pharmacists across the healthcare continuum are well positioned to collaborate with patients to effectively manage their chronic pain. Evidence supports positive outcomes when pharmacists undertake these roles; however, there are barriers preventing uptake across the profession. This paper aims to expand awareness of the breadth of these roles, including pharmaceutical care provision, interprofessional collaboration, pain and medication education, support for patients in self-management and acceptance of responsibility to be culturally responsive and decrease stigma. Pharmacists are accessible healthcare professionals and can improve the care of patients with chronic pain.

The role of pharmacists in opioid stewardship: Protocol.

BACKGROUND: The opioid crisis is a worldwide public health concern. In North America, evidence suggests that the increase in opioid prescriptions correlates with the observed increase in opioid-related mortality and morbidity. Pharmacists are in a strategic position to promote effective opioid stewardship as they have a central role on healthcare teams. However, in many contexts, pharmacists do not have a harmonized scope of practice and no standardized opioid stewardship approach has been implemented. OBJECTIVES: A scoping review will be conducted to identify and summarize evidence on the role of pharmacists in opioid stewardship and identify areas for future study. METHODS: The scoping review will be conducted according to the methodological framework proposed by Arksey and O'Malley, which was further modified by the Joanna Briggs Institute. Six databases will be searched which include PubMed, Embase, International Pharmaceutical Abstracts, Scopus, Cochrane Library, and APA PsycInfo. PROJECT IMPACT: The findings of this review will identify opioid stewardship activities that can contribute towards reducing the impact of the opioid crisis. Additionally, it will provide foundational strategies to promote policy level change and foster a harmonized scope of practice. This review has the potential to inform future research, impact pharmacy practice, and drive policy change.

Exploring the use of extended release opioids at shortened dosing intervals in people with chronic pain and high risk medication or substance use.

Background Critical attention to rational opioid prescribing has emerged from the opioid epidemic in North America. Individuals with chronic pain are prescribed extended release opioids in an effort to maintain stable drug levels and for more convenient dosing, though evidence to support improvements in pain or function is lacking. It has been observed that extended release opioid products are used at intervals shorter than recommended by product monographs. The need for shortened intervals has been linked with potential inter-patient variability in pharmacokinetics, among other rationale. Implications of shortened dosing intervals for extended release opioids have not been systematically studied. Objective The aim of this study was to characterize the use of extended release opioid formulations at shortened dosing intervals in a population of patients with chronic pain and high risk for opioid-related harms. Setting This study took place in the Interprofessional Pain and Addiction Recovery Clinic, a specialty ambulatory clinic at the Centre for Addiction and Mental Health in Toronto, Canada for adults with chronic pain and a diagnosis or suspicion of substance use disorder. Method This was a retrospective cross-sectional study. Data were collected from records of patients with assessments completed in the years 2012-2017 (n = 210). Main outcome measure Proportion of patients using extended release opioids at shortened intervals. Results Sixty-one percent of individuals using extended release opioids (n = 78) were using them at shortened intervals. This use was associated with a higher daily morphine equivalent dose (533 mg vs 236 mg, p < 0.01), use of oxycodone extended release products (50% vs. 27%, p < 0.01), a longer duration of opioid therapy (8.9 vs. 6.8 years, p = 0.03) and a diagnosis of chronic neuropathic pain (63% vs. 39%, p < 0.01), with no differences in reported pain intensities, compared with use at standard intervals. Conclusion The use of extended release opioids at shortened intervals was associated with increased daily morphine equivalent doses, thus an increased risk of opioid-related mortality. It is unlikely that of those using extended release opioids, the high proportion of use at shortened intervals is the result of inter-patient differences in metabolism alone. Further study is warranted to explore the underlying drivers and implications for people with chronic pain.

Evaluating comparative effectiveness of psychosocial interventions adjunctive to opioid agonist therapy for opioid use disorder: A systematic review with network meta-analyses.

BACKGROUND: Guidelines recommend that individuals with opioid use disorder (OUD) receive pharmacological and psychosocial interventions; however, the most appropriate psychosocial intervention is not known. In collaboration with people with lived experience, clinicians, and policy makers, we sought to assess the relative benefits of psychosocial interventions as an adjunct to opioid agonist therapy (OAT) among persons with OUD. METHODS: A review protocol was registered a priori (CRD42018090761), and a comprehensive search for randomized controlled trials (RCT) was conducted from database inception to June 2020 in MEDLINE, Embase, PsycINFO and the Cochrane Central Register of Controlled Trials. Established methods for study selection and data extraction were used. Primary outcomes were treatment retention and opioid use (measured by urinalysis for opioid use and opioid abstinence outcomes). Odds ratios were estimated using network meta-analyses (NMA) as appropriate based on available evidence, and in remaining cases alternative approaches to synthesis were used. RESULTS: Seventy-two RCTs met the inclusion criteria. Risk of bias evaluations commonly identified study limitations and poor reporting with regard to methods used for allocation concealment and selective outcome reporting. Due to inconsistency in reporting of outcome measures, only 48 RCTs (20 unique interventions, 5,404 participants) were included for NMA of treatment retention, where statistically significant differences were found when psychosocial interventions were used as an adjunct to OAT as compared to OAT-only. The addition of rewards-based interventions such as contingency management (alone or with community reinforcement approach) to OAT was superior to OAT-only. Few statistically significant differences between psychosocial interventions were identified among any other pairwise comparisons. Heterogeneity in reporting formats precluded an NMA for opioid use. A structured synthesis was undertaken for the remaining outcomes which included opioid use (n = 18 studies) and opioid abstinence (n = 35 studies), where the majority of studies found no significant difference between OAT plus psychosocial interventions as compared to OAT-only. CONCLUSIONS: This systematic review offers a comprehensive synthesis of the available evidence and the limitations of current trials of psychosocial interventions applied as an adjunct to OAT for OUD. Clinicians and health services may wish to consider integrating contingency management in addition to OAT for OUD in their settings to improve treatment retention. Aside from treatment retention, few differences were consistently found between psychosocial interventions adjunctive to OAT and OAT-only. There is a need for high-quality RCTs to establish more definitive conclusions. TRIAL REGISTRATION: PROSPERO registration CRD42018090761.

Understanding the effects of chronic benzodiazepine use in depression: a focus on neuropharmacology.

Benzodiazepines are frequently prescribed on an ongoing basis to individuals with depression, mainly to alleviate anxiety or insomnia, despite current guideline recommendations that continuous use should not exceed 4 weeks. Currently, there are no efficacy trials published beyond 8 weeks. Several antidepressant trials demonstrate that the concomitant use of a benzodiazepine is associated with poorer depressive outcomes and functional status; however, it is unclear why this is the case. Patients with depression receiving a benzodiazepine may reflect a more ill or high anxiety group, although even within anxiety disorders, the use of a benzodiazepine is associated with poorer outcomes. The neuroadaptive consequences of long-term benzodiazepine use may be a factor underlying these findings. Chronic benzodiazepine use results in decreased gamma-aminobutyric acid and monoaminergic function, as well as interference with neurogenesis, which are all purported to play a role in antidepressant efficacy. This review will discuss the oppositional neuropharmacological interactions between chronic benzodiazepine use and antidepressant mechanism of action, which could result in reduced antidepressant efficacy and function in depression.

Acute and residual mood and cognitive performance of young adults following smoked cannabis.

OBJECTIVES: To examine acute and residual mood and cognitive performance in young adult regular cannabis users following smoked cannabis. METHODS: Ninety-one healthy young adults completed this double-blind, placebo-controlled, parallel-groups study. Participants were randomized to receive active (12.5% THC) or placebo cannabis with a 2:1 allocation ratio, and mood [Profile of Mood States (POMS)] and cognitive performance [Hopkins Verbal Learning Test - Revised (HVLT-R), Digit Symbol Substitution Test (DSST), Continuous Performance Test (CPT), grooved pegboard (GPB)] were assessed before and 1, 24, and 48 (h) after smoking cannabis ad libitum. High and Low THC groups were based on blood THC concentrations. RESULTS: One hour after smoking cannabis, compared to Placebo, in both the High and Low THC groups, there were increases in POMS Arousal and Positive Mood, and in the High THC group only, increases in Confusion, Friendliness, and Elation, and a decrease in Fatigue. Increases in Friendliness and Elation in the High THC group remained significant for 24 h. The only significant acute effect of cannabis on cognition was a decrease in the percent of words retained in the HVLT-R in the High THC group compared to Placebo (mean difference = 15.8%, 95% CI = 3.6-28.0%, p = 0.006). Unexpectedly, compared to Placebo, both the High and Low THC groups improved in DSST performance at 48 h (p ≤ 0.016). CONCLUSIONS: Under the present experimental conditions, in young regular cannabis users, smoking cannabis ad libitum had significant effects on mood, some of which persisted 24 h later, yet minimal effects on cognition, and no evidence of residual cognitive impairment.