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Laura Murphy,1 Karen Ng,2 Pearl Isaac,3 Jaris Swidrovich,4 Maria Zhang,3,5 Beth A Sproule3,5 1Department of Pharmacy, University Health Network, Toronto, ON, Canada; 2Toronto Academic Pain Medicine Institute, Toronto, ON, Canada; 3Pharmacy Department, Centre for Addiction and Mental Health, Toronto, ON, Canada; 4College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada; 5Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, CanadaCorrespondence: Beth A SprouleCentre for Addiction and Mental Health (CAMH), 1025 Queen Street West, Toronto, ON, M6J 1H4, CanadaTel +1-416-535-8501 x35601Fax +1-416-583-1277Email beth.sproule@camh.caAbstract: 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.Keywords: chronic pain, pharmacist, patient-centered care, stigma

Laura Murphy,1,2 Karen WK Ng,1 Victoria CH Su,3 Sarah Woodworth-Giroux,4 Todd S Levy,1 Beth A Sproule,2,5 Andrea D Furlan1,6 1University Health Network, Toronto, ON, Canada; 2Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada; 3St Paul's Hospital, Lower Mainland Pharmacy Services, Vancouver, BC, Canada; 4Windsor Regional Hospital, Windsor, ON, Canada; 5Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; 6Institute for Work and Health, Toronto, ON, Canada Abstract: This paper provides an overview of research, guidelines, and clinical considerations for the use of medications for chronic pain in the management of patients with an alcohol use disorder. A review of the literature identified randomized controlled trials, epidemiological cohort studies, consensus guidelines, and one systematic review and meta-analysis. Where gaps in the literature existed, clinical experience of the authors is included. Use of nonopioid medications should be given priority and may offer a more favorable risk profile as well as benefits beyond pain management, such as improvement in anxiety, depression, or insomnia. Pregabalin and gabapentin have additional benefits to decrease alcohol cravings or time to relapse after a period of abstinence from alcohol. Drug interactions between selected analgesics and alcohol, disulfiram, or naltrexone require careful consideration. Keywords: chronic pain, alcohol use disorder, opioids

Objectives: The purpose of this study was to examine sex-stratified independent predictors of patient-initiated discharge from an inpatient withdrawal management service and to determine whether those predictors differed by sex., Methods: This study compared people who had self-initiated versus planned discharges and used sex-stratified generalized estimating equations models to identify independent predictors of patient-initiated discharge. Predictors examined included age, ethnicity, substance of concern, tobacco use, mental health comorbidities, day of discharge, referral source, children, and social assistance funds., Results: Among females, there were 722 discharges, 116 of which were patient initiated. Among females, increasing age was associated with lower odds of patient-initiated discharge ( OR = 0.97, 95% CI [0.95, 0.98]). Racialized females were nearly 2 times more likely to experience patient-initiated discharge compared with White females ( OR = 1.8, 95% CI [1.09, 3.00]). Compared with weekdays, weekends were associated with over 4 times the odds of patient-initiated discharge ( OR = 4.77, 95% CI [2.66, 8.56]). Having one or more mental health comorbidities was associated with lower odds of patient-initiated discharge compared with having no mental health comorbidities ( OR = 0.51, 95% CI [0.32, 0.82]). Among males, there were 1,244 discharges, 185 of which were patient initiated. Among males, increasing age was associated with decreased odds of patient-initiated discharge ( OR = 0.97, 95% CI [0.95, 0.98]). Compared with weekdays, weekends were associated with nearly 15 times the odds of patient-initiated discharge ( OR = 14.9, 95% CI [9.11, 24.3])., Conclusions: Males and females have shared and unique predictors of patient-initiated discharge. Future studies should continue to examine the influence of sex and gender on engagement with addictions care., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article., (Copyright © 2024 International Nurses Society on Addictions.)

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.

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., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: BH has previously received honoraria from Eversana Inc for provision of methodologic advice related to the conduct of systematic reviews. All other authors have no conflicts to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Hersi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.

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., Competing Interests: Declarations of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (© 2022 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., (© 2021 Australasian Professional Society on Alcohol and other Drugs.)

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., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

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).

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Rationale: Animal studies have found robust sex differences in the pharmacokinetics and pharmacodynamics of Δ 9 -tetrahydrocannabinol (THC). However, the human evidence remains equivocal, despite findings that women may experience more severe consequences of cannabis use than men., Objectives: The objective of this secondary analysis was to examine sex differences in THC pharmacokinetics and in acute subjective, physiological, and cognitive effects of smoked cannabis in a sample of regular cannabis users (use 1-4 days per week) aged 19-25 years., Methods: Ninety-one healthy young adults were randomized to receive active (12.5% THC; 17 females, 43 males) or placebo (< 0.1% THC; 9 females, 21 males) cannabis using a 2:1 allocation ratio. Blood samples to quantify concentrations of THC, 11-OH-THC, and 11-Nor-carboxy-THC (THC-COOH), as well as measures of subjective drug effects, vital signs, and cognition were collected over a period of 6 h following ad libitum smoking of a 750-mg cannabis cigarette., Results: Females smoked less of the cannabis cigarette than males (p = 0.008) and had a lower peak concentration of THC and THC-COOH than males (p ≤ 0.01). Blood THC concentrations remained lower in females even when adjusting for differences in estimated dose of THC inhaled. There was very little evidence of sex differences in visual analog scale (VAS) ratings of subjective drug effects, mood, heart rate, blood pressure, or cognitive effects of cannabis., Conclusions: Females experienced the same acute effects of smoked cannabis as males at a lower observed dose, highlighting the need for more research on sex differences in the pharmacology of THC, especially when administered by routes in which titrating to the desired effect is more difficult (e.g., cannabis edibles).

Background: The Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain (COG) was developed in response to increasing rates of opioid-related hospital visits and deaths in Canada, and uncertain benefits of opioids for chronic non-cancer pain (CNCP). Following publication, we developed a list of evaluable outcomes to assess the impact of this guideline on practice and patient outcomes., Methods: A working group at the National Pain Centre at McMaster University used a modified Delphi process to construct a list of clinical and patient outcomes important in assessing the uptake and application of the COG. An advisory group then reviewed this list to determine the relevance and feasibility of each outcome, and identified potential data sources. This feedback was reviewed by the National Faculty for the Guideline, and a National Advisory Group that included the creators of the COG, resulting in the final list of 5 priority outcomes., Results: Five outcomes were judged clinically important and feasible to measure: 1) Effects of opioids for CNCP on quality of life, 2) Assessment of patient's risk of addiction before starting opioid therapy, 3) Monitoring patients on opioid therapy for aberrant drug-related behaviour, 4) Mortality rates associated with prescription opioid overdose and 5) Use of treatment agreements with patients before initiating opioid therapy for CNCP. Data sources for these outcomes included patient's medical charts, e-Opioid Manager, prescription monitoring programs and administrative databases., Conclusion: Measuring the impact of best practice guidelines is infrequently done. Future research should consider capturing the five outcomes identified in this study to evaluate the impact of the COG in promoting evidence-based use of opioids for CNCP.

Background: Although driving under the influence of cannabis is increasingly common among young adults, little is known about residual effects on driver behavior. This study examined acute and residual effects of smoked cannabis on simulated driving performance of young cannabis users., Methods: In this double-blind, placebo-controlled, parallel-group randomized clinical trial, cannabis users (1-4 days/week) aged 19-25 years were randomized with a 2:1 allocation ratio to receive active (12.5% THC) or placebo (0.009% THC) cannabis in a single 750 mg cigarette. A median split (based on whole-blood THC concentrations at the time of driving) was used to divide the active group into low and high THC groups. Our primary outcome was simulated driving performance, assessed 30 min and 24 and 48 h after smoking. Secondary outcomes included blood THC concentrations, subjective drug effects, and heart rate., Results: Ninety-six participants were randomized, and 91 were included in the final analysis (30 high THC, 31 low THC, 30 placebo). Mean speed (but not lateral control) significantly differed between groups 30 min after smoking cannabis (p ≤ 0.02); low and high THC groups decreased their speed compared to placebo. Heart rate, VAS drug effect and drug high increased significantly immediately after smoking cannabis and declined steadily after that. There was little evidence of residual effects in any of the measures., Conclusion: Acutely, cannabis caused decreased speed, increased heart rate, and increases in VAS drug effect and drug high. There was no evidence of residual effects on these measures over the two days following cannabis administration., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Opioid use disorder is a major health concern in North America. Currently, buprenorphine is one of the most common pharmacological interventions used to treat opioid use disorder. Despite increasing prevalence of opioid use disorder among females, little is known about sex considerations in relation to treatment with buprenorphine., Methods: CINAHL, PsycINFO, EMBASE, PubMed/MEDLINE and Cochrane Central were searched for randomized controlled trials examining buprenorphine maintenance versus other medication-assisted treatment, placebo, or withdrawal management to determine if there were any sex differences in treatment outcomes reported., Results: This review included 25 studies and found that only 52% included information related to sex differences in treatment outcomes or discussed any sex considerations in their studies. Of the 6,466 patients represented by these studies, only 26% were female. Of the studies conducting sex-specific analyses, seven studies examined treatment retention, five examined opioid use, two examined other substance use and one examined sexual risk behaviours. However, due to mixed findings, small sample sizes, and inability to conduct meta-analyses, no conclusive statements can be made about sex differences in these outcomes. None of the studies described sex differences in quality of life, legal involvement or mental and physical health., Conclusions: Low numbers of females have been included in randomized controlled trials examining buprenorphine compared to males. While sex differences in treatment outcomes were identified in this review, further research is needed in order to add to these findings. Future studies should include greater numbers of female participants and conduct sex-specific analyses., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Competing Interests: Statement of Conflicting Interests:None of the authors have conflicts of interest to disclose.

Competing Interests: Declaration of Conflicting Interests:The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Competing Interests: Declaration of Conflicting Interests:D. Buna is a member of the Advisory Board, OTC Pain Relievers, Johnson & Johnson Inc. No other author has a conflict of interest to disclose.

Background: Funders now frequently require that sex and gender be considered in research programmes, but provide little guidance about how this can be accomplished, especially in large research programmes. The purpose of this study is to present and evaluate a model for promoting sex- and gender-based analysis (SGBA) in a large health service research programme, the Ontario Pharmacy Evidence Network (OPEN)., Methods: A mixed method study incorporating (1) team members' critical reflection, (2) surveys (n = 37) and interviews (n = 23) at programme midpoint, and (3) an end-of-study survey in 2016 with OPEN research project teams (n = 6)., Results: Incorporating gender and vulnerable populations (GVP) as a cross-cutting theme, with a dedicated team and resources to promote GVP research across the programme, was effective and well received. Team members felt their knowledge was improved, and the programme produced several sex- and gender-related research outputs. Not all resources were well used, however, and better communication of the purposes and roles of the team could increase effectiveness., Conclusions: The experience of OPEN suggests that dedicating resources for sex and gender research can be effective in promoting SGBA research, but that research programmes should also focus on communicating the importance of SGBA to their members.

The treatment of chronic pain consumes a significant share of primary care. Community and family health team pharmacists frequently see patients with chronic pain, thus have the opportunity to improve their care. To assess the knowledge, perceptions, and attitudes of Ontario pharmacists, we invited 5,324 Ontario pharmacists, to participate in an online survey we developed using Qualtrics. The 31-question survey gathered demographic information, assessed pharmacists' knowledge of three chronic pain conditions; chronic lower back pain (CLBP, eight true/false statements); chronic headache disorder (CHD, eight true/false statements) and painful diabetic neuropathy (PDN, seven true/false statements), and their attitudes toward and perceptions of patients with these conditions, and knowledge, attitudes, and perceptions of opioids in pain management. We received 688 responses (12.9%) and 392 pharmacists completed the survey. The mean age of respondents was 48.5 years and 48.5% were male. More than 50% of respondents were in practice for more than 20 years and 58.7% worked 25-40 hours per week. The mean knowledge scores were 4.5/8, 5.5/8, and 5.3/8 for CBLP, CHD, and PDN respectively. While 95% of respondents were aware of the increasing death rates due to opioid use, only half were familiar with the Canadian guideline for safe opioid prescribing for non-cancer use. Responses were compared based on gender, time in practice and location of practice. Pharmacists with more than ten years of experience scored significantly higher than those with less experience. Fewer differences were found in comparisons of gender and location of practice. Safe and effective care of chronic pain patients, particularly with opioids, will require additional pharmacist education.