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Objectives: The objective of this study was to compare and contrast the experiences of interdisciplinary attendees (spokes) and experts (hub members) from three Extension for Community Healthcare Outcomes (ECHO) programmes: hepatitis C, chronic pain and concurrent mental health and substance use disorders., Design: Prospective qualitative study., Setting: Single-centre in tertiary care., Participants: The team conducted 30 one-on-one interviews with spokes and 4 focus groups with hub members from three ECHO programmes., Analyses: Three analysts were involved to perform a reflexive thematic analysis., Results: Our results showed the benefits and limitations of the three ECHOs, varying according to specificities of targeted chronic conditions. Three overarching themes were identified from the data analysis: (1) perceived impacts of an interprofessional educational setting; (2) nature of disease and interprofessional interactions as determinants of clinical practice changes in diagnoses and treatments and (3) impacts on patient engagement and care pathways., Conclusions: The extent to which a chronic disease relies on a biopsychosocial approach, the degree of interdisciplinary care required and the simplicity/complexity of treatment algorithms influence perceived benefits and barriers to participating in ECHO programmes. These points raised by our study are important in the understanding of the successes and limitations of implementing an ECHO programme. They are essential as they provide key information for tailoring Project ECHO to the chronic disease it addresses., Competing Interests: Competing interests: GP received honoraria from Canopy Growth and research grant from Pfizer Canada for work unrelated to the present study. AT has a family member working for ViiV USA, a pharmaceutical company. Other members have no competing interest to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Amphetamine-type stimulants (ATSs) are related to significant harm worldwide, with limited effective pharmacological treatments for ATS use disorder (ATSUD). Modafinil has been explored as a potential treatment for ATSUD. This systematic review and meta-analysis (PROSPERO ID: CRD42023388487) aimed to evaluate the efficacy and safety of modafinil for the treatment of ATSUD., Methods: A comprehensive search of major indexing sources and trial registries, from inception to search date, was conducted on February 15, 2023, and updated on October 31, 2023. Eligible studies were randomized placebo-controlled trials (RCTs) of modafinil in individuals meeting the criteria for the Diagnostic and Statistical Manual of Mental Disorders, fourth and fifth editions, diagnoses of ATSUD. Eligible studies were assessed for risk of bias, using the Cochrane Risk of Bias tool. The primary outcome included the effect of modafinil on ATS use. Secondary outcomes included retention in treatment, ATS craving, treatment discontinuation due to adverse events (AEs), and serious AEs. Subgroup analysis by modafinil dose was conducted where appropriate. Risk ratio (RR) or Peto's odds ratio (OR) was calculated for the meta-analysis of dichotomous variables and standardized mean difference (SMD) was calculated for the random-effect meta-analysis of continuous variables., Results: Five RCTs ( N  = 451 participants) were included. Modafinil did not significantly impact ATS use (RR = 0.99; 95% CI, 0.97 to 1.02; p  = 0.655), retention in treatment (RR = 1.02; 95% CI, 0.91 to 1.14; p  = 0.799), ATS craving (SMD = -0.36; 95% CI, -1.19 to 0.47; p  = 0.398), or treatment discontinuation due to AEs (Peto's OR = 0.48; 95% CI, 0.20 to 1.14; p  = 0.100). These results were consistent across subgroup analyses. More episodes of serious AEs were reported in the modafinil group than in the placebo group, at higher doses (Peto's OR = 4.80; 95% CI, 1.18 to 19.56, p  = 0.029)., Conclusion: There is currently no evidence suggesting that modafinil has a statistically significant effect on efficacy outcomes in populations with ATSUD. Continued research into effective treatments and harm reduction strategies for ATSUD is essential., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: LE is a shareholder and employee of OneCare Inc., which is a biotechnology mental health company. OneCare Inc., biotechnologies’ work does not relate to the contents of the present article. DJA received study materials from Cardiol Therapeutics and Exka for clinical trials not related to the present article (2022–2024). The other authors have no potential conflicts to declare.

Objectives: Cannabis use is common in people with early-phase psychosis (EP) and is associated with worse treatment outcomes. Few targeted interventions for cannabis use behaviour in this population exist, most focusing on abstinence, none focusing on harm reduction. Many people with EP will not seek treatment for their cannabis use with current therapeutic options. Understanding preferences for cannabis-focused harm reduction interventions may be key to improving outcomes. This study aimed to determine preferences of young adults with EP who use cannabis for cannabis-focused harm reduction interventions., Methods: Eighty-nine young adults across Canada with EP interested in reducing cannabis-related harms were recruited. An online questionnaire combining conventional survey methodology and two unique discrete choice experiments (DCEs) was administered. One DCE focused on attributes of core harm reduction interventions (DCE 1) and the second on attributes of boosters (DCE 2). We analysed these using mixed ranked-ordered logistic regression models. Preference questions using conventional survey methodology were analysed using summary statistics., Results: Preferred characteristics for cannabis-focused harm reduction interventions (DCE 1) were: shorter sessions (60 min vs. 10 min, odds ratio (OR): 0.72; P  < 0.001); less frequent sessions (daily vs. monthly, OR: 0.68; P  < 0.001); shorter interventions (3 months vs. 1 month, OR: 0.80; P  < 0.01); technology-based interventions (vs. in-person, OR: 1.17; P  < 0.05). Preferences for post-intervention boosters (DCE 2) included opting into boosters (vs. opting out, OR: 3.53; P  < 0.001) and having shorter boosters (3 months vs. 1 month, OR: 0.79; P  < 0.01). Nearly half of the participants preferred to reduce cannabis use as a principal intervention goal (vs. using in less harmful ways or avoiding risky situations)., Conclusions: Further research is required to see if technology-based harm reduction interventions for cannabis featuring these preferences translate into greater engagement and improved outcomes in EP patients., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: BF has held research grants and contracts in the areas of substance use, health and policy from public funding and government-related agency (i.e., public-only) organizations and has consulted as a scientific expert with such entities in different countries. DJA received investigational products (2022-23) from Cardiol Therapeutics for a clinical trial funded by Quebec Ministry of Health and Social Services.

Background: Cannabidiol (CBD) has been proposed to have a therapeutic potential over a wide range of neuropsychiatric disorders, including substance use disorders. Pre-clinical evidence suggests that CBD can increase anandamide (AEA) plasma concentration, possibly mediating some of its therapeutic properties. Whether CBD exerts such an effect on AEA in individuals with cocaine use disorder (CUD) remains unknown. Aims: To explore the sustained effects of daily CBD administration on AEA plasma concentrations compared with placebo in CUD. Methods: We used data from a randomized, double-blind, placebo-controlled trial evaluating CBD's efficacy in CUD. Seventy-eight individuals were randomized to receive a daily oral dose of 800 mg CBD ( n = 40) or a placebo ( n = 38). Participants stayed in an inpatient detoxification setting for 10 days, after which they were followed in an outpatient setting for 12 weeks. AEA plasma concentration was measured at baseline and at 23-h post CBD ingestion on day 8 and week 4. A generalized estimating equation model was used to assess CBD's effects on AEA, and sensitivity analyses were computed using Bayesian linear regressions. Results: Sixty-four participants were included in the analysis. Similar mean AEA plasma concentrations in both treatment groups ( p = 0.357) were observed. At day 8, mean AEA plasma concentrations (± standard deviation) were 0.26 (± 0.07) ng/mL in the CBD group and 0.29 (± 0.08) ng/mL in the placebo group ( p = 0.832; Bayes factor [BF] = 0.190). At week 4, they were 0.27 (± 0.09) ng/mL in the CBD group and 0.30 (± 0.09) ng/mL in the placebo group ( p = 0.181; BF = 0.194). Conclusion: While not excluding any potential acute and short-term effect, daily CBD administration did not exert a sustained impact on AEA plasma concentrations in individuals with CUD compared with placebo. Registration: clinicaltrials.gov (NCT02559167).

Background: Cannabis use is highly prevalent in young people with first-episode psychosis (FEP). Most report cannabis use and are often diagnosed with a cannabis use disorder upon admission to specialized services for psychosis. Cannabis use in this population is associated with worse clinical and psychosocial outcomes, rendering it an important clinical target. Despite this, few cannabis-specific interventions have been developed for FEP and empirically evaluated through randomized controlled trials. Most evaluated interventions have targeted cannabis abstinence, with limited efficacy, but none have centered on harm reduction outcomes for people with FEP who use cannabis. Early intervention services (EIS), the standard of care for FEP, have not successfully addressed problematic cannabis use in people with FEP either. Clinical trials are needed to explore the potential of harm reduction strategies, although these should be preceded by robust pilot studies to establish optimal design and approaches., Objective: Recognizing the need for harm reduction strategies for individuals with FEP who use cannabis and based on research on patients' preferences supporting harm reduction interventions, we developed a mobile app-based cannabis harm reduction intervention for this population. This intervention is called Cannabis Harm-reducing Application to Manage Practices Safely (CHAMPS). Here, we describe the protocol for a multicenter, 2-arm, parallel group, randomized pilot trial evaluating the acceptability of CHAMPS for people with FEP who use cannabis and the feasibility of conducting a full-scale trial in this population using CHAMPS. The impact on key clinical outcomes will also be explored., Methods: This pilot trial aims to recruit 100 young people with FEP using cannabis from 6 Canadian EIS clinics. Participants will be randomized in a 1:1 ratio to CHAMPS+EIS or EIS-only. CHAMPS acceptability will be assessed using completion rates for the intervention arm. Trial feasibility will be assessed using a retention rate for randomized participants. Secondary outcomes will explore tendencies of change in the use of protective behavioral strategies and in motivation to change strategies. Exploratory outcomes include cannabis use-related problems, other substance use, the severity of dependence, psychotic symptoms, and health care service use., Results: Recruitment began in December 2021. Data collection and analysis are expected to be completed in early 2024. Study results describing CHAMPS acceptability and trial feasibility will then be submitted for publication in a peer-reviewed journal., Conclusions: CHAMPS uniquely combines evidence-based approaches, patient perspectives, and mobile health technology to support harm reduction in people with FEP who use cannabis. Attaining adequate acceptability and feasibility through this trial may justify further exploration of harm reduction tools, particularly within the context of conducting a larger-scale randomized controlled trial. This pilot trial has the potential to advance knowledge for researchers and clinicians regarding a feasible and user-acceptable research design in the cannabis and early psychosis fields., Trial Registration: ClinicalTrials.gov NCT04968275, https://clinicaltrials.gov/ct2/show/NCT04968275., International Registered Report Identifier (irrid): DERR1-10.2196/53094., (©Stephanie Coronado-Montoya, Amal Abdel-Baki, José Côté, David Crockford, Simon Dubreucq, Benedikt Fischer, Pamela Lachance-Touchette, Tania Lecomte, Sophie L'Heureux, Clairélaine Ouellet-Plamondon, Marc-André Roy, Ovidiu Tatar, Phillip Tibbo, Marie Villeneuve, Anne Wittevrongel, Didier Jutras-Aswad. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 18.12.2023.)

Background: Cannabis use is the most prevalent among adolescents and young adults; frequent consumption is associated with cannabis use disorder (CUD) and psychosis, with a high prevalence (up to 50%) of CUD in individuals with first-episode psychosis (FEP). Early Intervention Services (EIS) for psychosis include face-to-face psychosocial interventions for CUD, because reducing or discontinuing cannabis use improves clinical and health care service use outcomes. However, multiple barriers (eg, staff availability and limited access to treatment) can hinder the implementation of these interventions. Mobile health (mHealth) interventions may help circumvent some of these barriers; however, to date, no study has evaluated the effects of mHealth psychological interventions for CUD in individuals with FEP., Objective: This study describes the protocol for a pilot randomized controlled trial using a novel mHealth psychological intervention (iCanChange [iCC]) to address CUD in young adults with FEP. iCC was developed based on clinical evidence showing that in individuals without psychosis, integrating the principles of cognitive behavioral therapy, motivational interviewing, and behavioral self-management approaches are effective in improving cannabis use-related outcomes., Methods: Consenting individuals (n=100) meeting the inclusion criteria (eg, aged 18-35 years with FEP and CUD) will be randomly allocated in a 1:1 ratio to the intervention (iCC+modified EIS) or control (EIS) group. The iCC is fully automatized and contains 21 modules that are completed over a 12-week period and 3 booster modules available during the 3-month follow-up period. Validated self-report measures will be taken via in-person assessments at baseline and at 6, 12 (end point), and 24 weeks (end of trial); iCC use data will be collected directly from the mobile app. Primary outcomes are intervention completion and trial retention rates, and secondary outcomes are cannabis use quantity, participant satisfaction, app use, and trial recruiting parameters. Exploratory outcomes include severity of psychotic symptoms and CUD severity. For primary outcomes, we will use the chi-square test using data collected at week 12. We will consider participation in iCC acceptable if ≥50% of the participants complete at least 11 out of 21 intervention modules and the trial feasible if attrition does not reach 50%. We will use analysis of covariance and mixed-effects models for secondary outcomes and generalized estimating equation multivariable analyses for exploratory outcomes., Results: Recruitment began in July 2022, and data collection is anticipated to be completed in July 2024. The main results are expected to be submitted for publication in 2024. We will engage patient partners and other stakeholders in creating a multifaceted knowledge translation plan to reach a diverse audience., Conclusions: If feasible, this study will provide essential data for a larger-scale efficacy trial of iCC on cannabis use outcomes in individuals with FEP and CUD., Trial Registration: ClinicalTrials.gov NCT05310981; https://www.clinicaltrials.gov/ct2/show/NCT05310981., International Registered Report Identifier (irrid): PRR1-10.2196/40817., (©Ovidiu Tatar, Amal Abdel-Baki, Anne Wittevrongel, Tania Lecomte, Jan Copeland, Pamela Lachance-Touchette, Stephanie Coronado-Montoya, José Côté, David Crockford, Simon Dubreucq, Sophie L'Heureux, Clairélaine Ouellet-Plamondon, Marc-André Roy, Philip G Tibbo, Marie Villeneuve, Didier Jutras-Aswad. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 25.11.2022.)

Objectives: Individuals with a cocaine use disorder (CUD) are more likely to present anxiety, which in turn negatively impacts substance use outcomes. Some evidence suggests that cannabidiol (CBD) presents anxiolytic properties and could be a treatment for substance use disorders. This study explores CBD's effect on stress biomarker (cortisol) and anxiety symptoms in people with CUD., Methods: Exploratory analyses were conducted using data from a randomized, double-blind, placebo-controlled trial evaluating CBD's efficacy to treat CUD. We randomized 78 individuals with CUD into receiving a daily oral dose up to 800 mg CBD (n = 40) or placebo (n = 38). The trial was divided into 2 phases: an inpatient detoxification lasting 10 days and an outpatient follow-up lasting 12 weeks. Anxiety symptoms and stress response were assessed using a visual analog scale, the Beck Anxiety Inventory, and cortisol levels at multiple time points throughout the study. We also measured anxiety after a stressful and a cocaine-cue scenarios. We used generalized estimating equations models and multiple linear regression to assess CBD's effects on anxiety and cortisol levels., Results: Both treatment groups had similar mean anxiety scores according to the Beck Anxiety Inventory ( P = 0.27) and the visual analog scale ( P = 0.18). CBD did not decrease anxiety after a stressful ( P = 0.14) and a cocaine ( P = 0.885) scenarios compared with placebo. No statistically significant group difference was found in cortisol levels ( P = 0.76)., Conclusions: We found no evidence for 800 mg of CBD to be more efficacious than placebo for modulating anxiety symptoms and cortisol levels in individuals with CUD., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 American Society of Addiction Medicine.)

Objective: To describe current approaches in treatment of opioid use disorder (OUD) within Canadian psychosocial outpatient, day, and residential addiction treatment programs, with an emphasis on the use of opioid agonist therapy (OAT)., Method: An online census survey was conducted in English and French of Canadian psychosocial addiction treatment programs ( N  = 214)., Results: Programs estimated that 25% of their clients have OUD. A slight majority of programs provide some type of specialized services to clients with OUD (58%), most frequently providing or facilitating access to OAT but also specialized counselling, case management, education, and harm reduction services.Most programs reported that they admitted clients on OAT (88%) and only a minority expected or encouraged clients to taper (14%) or discontinue (6%). Programs focusing on client abstinence as the treatment goal were more likely to expect or encourage tapering or discontinuation than programs that focus on helping clients achieve personal consumption goals. Of programs that did not currently facilitate OAT, 44% indicated that they would provide OAT, but lacked the necessary accreditation, physician support, or other resources. No philosophical objections to OAT were noted.OAT initiation was provided by 30% of programs, 23% referred to another service within their organization, and 29% referred to a service outside their organization. The remaining 18% did not facilitate OAT initiation at all, ranging from 0% in Quebec to 23% in the Prairies. Overdose response kits were provided by 86% of programs. The majority not providing kits indicated willingness if policy support and resources were provided (67%)., Conclusions: Overall, the results demonstrate that psychosocial programs provide some specialized services for OUD but desire further support specifically to provide OAT, including training, knowledge, and the expertise of individuals qualified to prescribe and dispense OAT. Many psychosocial treatment programs expressed a need for staff and resources for this purpose.

Background: Cocaine use disorder (CUD) is associated with various cognitive deficits that impede patients' functionality, prognosis and therapeutic outcomes. New pharmacological treatments for CUD that could improve cognition are needed., Objective: To explore whether cannabidiol (CBD) is superior to placebo to improve cognitive functioning in individuals with CUD., Methods: We conducted an exploratory analysis of a single site, randomized, double-blind, placebo-controlled trial evaluating CBD's efficacy in reducing craving, cocaine use and relapse in individuals with CUD. Seventy-eight individuals diagnosed with CUD were randomized to receive either CBD (800 mg) or placebo for 92 days. We used the Cambridge Neuropsychological Test Automated Battery (CANTAB) to assess inhibition (Stop Signal Task; SST), risky decision making (Cambridge Gambling Task; CGT) and visual memory (Pattern Recognition Memory; PRM). This assessment was made on day 1, day 7 and at week 6. We controlled for sex, severity of dependence and baseline cognitive scores in our generalized estimating equation models., Results: Both groups performed similarly on the PRM (correct answers: p = 0.080), SST (stop signal reaction time: p = 0.644) and CGT (quality of decision making: p = 0.994; deliberation time: p = 0.507; delay aversion: p = 0.968; risk taking: p = 0.914) tests., Conclusions: We found no evidence for 800 mg of CBD to be more efficacious than placebo for improving cognitive outcomes. Clinical trials evaluating pharmacological treatments for CUD should continue to be a research priority., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Cocaine use disorder (CUD) is a major public health issue associated with physical, social, and psychological problems. Excessive and repeated cocaine use induces oxidative stress leading to a systemic inflammatory response. Cannabidiol (CBD) has gained substantial interest for its anti-inflammatory properties, safety, and tolerability profile. However, CBD anti-inflammatory properties have yet to be confirmed in humans. This exploratory study is based on a single-site randomized controlled trial that enrolled participants with CUD between 18 and 65 years, randomized (1:1) to daily receive either CBD (800 mg) or placebo for 92 days. The trial was divided into a 10-day detoxification (phase I) followed by a 12-week outpatient follow-up (phase II). Blood samples were collected from 48 participants at baseline, day 8, week 4, and week 12 and were analyzed to determine monocytes and lymphocytes phenotypes, and concentrations of various inflammatory markers such as cytokines. We used generalized estimating equations to detect group differences. Participants treated with CBD had lower levels of interleukin-6 (p = 0.017), vascular endothelial growth factor (p = 0.032), intermediate monocytes CD14 + CD16 + (p = 0.024), and natural killer CD56 neg CD16 hi (p = 0.000) compared with participants receiving placebo. CD25 + CD4 + T cells were higher in the CBD group (p = 0.007). No significant group difference was observed for B lymphocytes. This study suggests that CBD may exert anti-inflammatory effects in individuals with CUD., (© 2021. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Background and Aims: Cocaine use disorder (CUD) is a significant public health concern for which no efficacious pharmacological interventions are available. Cannabidiol (CBD) has attracted considerable interest as a promising treatment for addiction. This study tested CBD efficacy for reducing craving and preventing relapse in people with CUD., Design: Single-site double-blind randomized controlled superiority trial comparing CBD with placebo., Setting and Participants: Centre Hospitalier de l'Université de Montréal, Canada. Seventy-eight adults (14 women) with moderate to severe CUD participated., Intervention: Participants were randomly assigned (1 : 1) by stratified blocks to daily 800 mg CBD (n = 40) or placebo (n = 38). They first underwent an inpatient detoxification phase lasting 10 days. Those who completed this phase entered a 12-week outpatient follow-up., Measurements: Primary outcomes were drug-cue-induced craving during detoxication and time-to-cocaine relapse during subsequent outpatient treatment., Findings: During drug-cue exposure, craving scores [mean ± standard deviation (SD)] increased from baseline by 4.69 (2.89) versus 3.21 (2.78) points, respectively, in CBD (n = 36) and placebo (n = 28) participants [confidence interval (CI) = -0.33 to 3.04; P = 0.069; Bayes factor = 0.498]. All but three participants relapsed to cocaine by week 12 with similar risk for CBD (n = 34) and placebo (n = 27) participants (hazard ratio = 1.20, CI = 0.65-2.20, P = 0.51; Bayes factor = 0.152). CBD treatment was well tolerated and associated mainly with diarrhoea., Conclusions: CBD did not reduce cocaine craving or relapse among people being treated for CUD., (© 2021 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: Up to 74 % of people with an opioid use disorder (OUD) will experience depression in their lifetime. Understanding and addressing the concept of preference for depression treatments and clinical trial designs may serve as an important milestone in enhancing treatment and research outcomes. Our goal is to evaluate preferences for depression treatments and clinical trial designs among individuals with an OUD and comorbid depression., Methods: We evaluated preferences for depression treatments and clinical trial designs using an online cross-sectional survey including a best-best discrete choice experiment. We recruited 165 participants from opioid agonist treatment clinics and community-based services in Calgary, Charlottetown, Edmonton, Halifax, Montreal, Ottawa, Quebec City, St. John's and Trois-Rivières, Canada., Results: Psychotherapy was the most accepted (80.0 %; CI: 73.9-86.1 %) and preferred (31.5 %; CI: 24.4-38.6 %) treatment. However, there was a high variability in acceptability and preferences of depression treatments. Significant predictors of choice for depression treatments were administration mode depending on session duration (p < 0.001), access mode (p < 0.001) and treatment duration (p < 0.001). Significant predictors of choice for clinical trial designs were allocation type (p = 0.008) and monetary compensation (p = 0.033). Participants preferred participating in research compared to non-participation (p < 0.001)., Conclusions: Accessibility and diversity of depression interventions, including psychotherapy, need to be enhanced in addiction services to ensure that all patients can receive their preferred treatment. Ensuring proper monetary compensation and comparing an intervention of interest with an active treatment might increase participation of depressed OUD patients in future clinical research initiative., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Extension for Community Healthcare Outcomes (Project ECHO©) is an innovative model for continuing professional development that uses videoconferencing technology to support and train general practitioners remotely. The model has been replicated to a variety of settings and locations for capacity building in healthcare professionals caring for patients with chronic and complex health conditions. Limited research has been conducted so far on the impact of ECHO in the field of concurrent mental health and substance use disorders (ie, concurrent disorders (CDs)). Therefore, this mixed methods study aims to develop a comprehensive understanding of an ECHO programme impact for CD management on nurses' competency development and clinical practice., Methods and Analysis: The proposed mixed methods study, based on a convergent parallel design, will be conducted in the province of Quebec, Canada, to collect, analyse and interpret quantitative (QUAN) and qualitative (QUAL) data from a specific ECHO Program on CDs. In the QUAN component, an observational prospective cohort study will be conducted over a 12-month period. All nurses who participated in the programme between 2018 and 2020 and who consent to research will be recruited to collect data on the extent of their learning and practice outcomes at three time points. Alongside the surveys, nurses will be invited to participate in individual semistructured interviews. In-depth QUAL data will be subjected to a thematic analysis and will assist in exploring how and in which conditions nurses developed and mobilised their competencies in clinical practice. A comparison-of-results strategy will be used in the final integration component of the study., Ethics and Dissemination: This study protocol was approved by the Ethics Committee of the Université de Montréal Hospital Center (#19.295) and the Université de Montréal Ethics Committee (CERSES-20-017 R). We aim to disseminate the findings through international academic conferences, international peer-reviewed journals and professional media., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Depression is the most common psychiatric comorbidity among people with opioid use disorders (OUDs). However, whether and how comorbid depression is associated with the outcomes of opioid agonist therapy (OAT) remains poorly understood. The objective of this review was to identify and describe the association between depression and main outcomes (opioid use and treatment retention) of methadone and buprenorphine treatment among people with OUDs. Methods: A literature review was conducted by searching five electronic databases (MEDLINE, PubMed, Embase, Evidence-Based Medicine Reviews [EBMR], and Cumulative Index of Nursing and Allied Health Literature [CINAHL] Complete) from January 1970 to April 2019. Two independent reviewers screened titles and abstracts of the identified records by using pre-established eligibility criteria. Next, full texts were reviewed and studies that met inclusion criteria were selected. Finally, a descriptive synthesis of extracted data was performed. Results: In total, 12,296 records were identified and 18 studies that met inclusion criteria were retained. Of these, six studies reported reduced opioid use and seven reported increased opioid use during methadone or buprenorphine treatment. In addition, three studies reported an increased retention rate and four documented a decreased retention rate during methadone or buprenorphine treatment. The remaining studies did not find any significant association between depression and opioid use or treatment retention. Overall, the evidence did not demonstrate a consistent association between depression and outcomes of methadone or buprenorphine treatment. Conclusions: Although the inconsistent nature of the current evidence prohibited us from drawing definitive conclusions, we posit that the presence of depression among OUDs patients may not always predict negative outcomes related to retention and drug use during the course of OAT. Particularly, the hypothesis that adequate treatment of depression can improve treatment retention is promising and is in line with the call for increased efforts to provide integrated care for comorbid mental health disorders and addiction. Future studies with rigorous methodology are essential to better characterize the complex interplay between depression, OAT, and OUDs.

Background: High-risk injection behaviors are associated with high prevalence of mental health problems among people who inject drugs (PWID). However, whether the use of mental health services is associated with lower risk of sharing injection material remains undetermined. This study aims to examine the association between mental health service utilisation and receptive sharing risk, and determine the potential modifying effect of psychological distress on this association., Methods: Participants answered an interviewer-administered questionnaire at 3-month intervals gathering information on sociodemographic characteristics, substance use and related behaviors, services utilisation and significant mental health markers. Relationship between the use of mental health services and receptive sharing was modeled using the generalized estimating equation (GEE), controlling for age at baseline, gender, and other potential confounders. Psychological distress was estimated using the Kessler Psychological Distress Scale (K10). Effect modification was investigated by adding an interaction term in the univariate GEE analysis., Results: 358 participants contributed to 2537 visits (median age 40.3, 82% male). Mental health service utilisation was reported in 631 visits (25%), receptive sharing in 321 visits (13%) and severe psychological distress in 359 visits (14%). In multivariate GEE analyses, a significant association was identified between receptive sharing and the use of mental health services (aOR = 0.69; 95% CI = 0.50-0.94). We found no evidence of effect modification by psychological distress., Conclusion: Among PWID, mental health service utilisation was associated with lower likelihood of receptive sharing, regardless of level of psychological distress. These findings should be taken into account when designing harm reduction strategies for this population., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Depression is one of the most prevalent psychiatric disorders among opioid-dependent individuals. Clinical trials testing selective serotonin reuptake inhibitors among depressed patients on methadone maintenance therapy (MMT) failed to show efficacy, whereas those on tricyclic antidepressants produced mixed results with potential for cardiotoxicity. Desvenlafaxine (DESV) is a SNRI with minimal cardiotoxicity and drug interactions. This study sought to assess feasibility and tolerability of using DESV in depressed patients on MMT. A total of 18 depressed individuals on MMT received DESV (50-100 mg/day) for 8 weeks. Participants were assessed for the following: (a) Safety of DESV using Systematic Assessment for Treatment Emergent Events-GI, ECG [corrected Q-T (QTc) interval measurement] and methadone serum levels; (b) depressive symptoms using Montgomery-Äsberg Depression Rating Scale (MADRS); and (c) other outcomes including anxiety, suicidality, craving, substance use, quality of life, and other depression scales. Registration number on ClinicalTrials.gov is NCT02200406. Among participants who completed the study, MADRS scores significantly decreased at week 8 compared with baseline. Responders and remitters on MADRS at week 8 were 61 and 50%, respectively. There was no significant change in [corrected Q-T (QTc) interval measurement] between baseline and week 4. DESV was well tolerated and associated with improvement of depressive symptoms. DESV may be a promising contender to treat depression in individuals on MMT and deserves further exploration in a randomized double-blinded clinical trial.

Laboratory rodents provided chronic unlimited access to running wheels display increased neurogenesis in the hippocampal dentate gyrus. In addition, recent studies indicate that such an access to wheels stimulates dendritic arborization in newly formed neurons. However, (i) the presence of the running wheel in the housing environment might also bear intrinsic influences on the number and shape of new neurons and (ii) the dendritic arborization of new neurons might be insensitive to moderate daily running activity (i.e., several hours). In keeping with these uncertainties, we have examined neurogenesis and dendritic arborization in newly formed granular cells in adult C57Bl/6N male mice housed for 3 weeks under standard conditions, with a locked wheel, with a running wheel set free 3 h/day, or with a running wheel set permanently free. The results indicate that the presence of a blocked wheel in the home cage increased cell proliferation, but not the number of new neurons while running increased in a duration-dependent manner the number of newborn neurons, as assessed by DCX labeling. Morphological analyses of the dendritic tree of newborn neurons, as identified by BrdU-DCX co-staining, revealed that although the presence of the wheel stimulated their dendritic architecture, the amplitude of this effect was lower than that elicited by running activity, and was found to be running duration-dependent., (© 2015 Wiley Periodicals, Inc.)

Several studies have indicated that animal models of exercise, such as voluntary wheel running, might be endowed with anxiolytic properties. Using the light/dark test of unconditioned anxiety, we have reported that one confounding factor in the estimation of wheel running impacts on anxiety might be the housing condition of the sedentary controls. The present mouse study analyzed whether the aforementioned observation in the light/dark test (i) could be repeated in the elevated plus-maze and social interaction tests of unconditioned anxiety, (ii) extended to conditioned anxiety, as assessed during cued fear recall tests, and (iii) required unlimited daily access to the running wheel. Housing with a locked wheel or with a free wheel that allowed limited or unlimited running activity triggered anxiolysis in the light/dark test, but not in the elevated plus-maze test, compared to standard housing. In the social interaction test, the duration, but not the number, of social contacts was increased in mice provided unlimited (but not limited) access to a wheel, compared to standard housing or housing with a locked wheel. Lastly, freezing responses to a cue during fear recall tests indicated that the reduction in freezing observed in mice provided limited or unlimited access to the wheels was fully accounted for by housing with a wheel. Besides confirming that the housing condition of the sedentary controls might bias the estimation of the effects of wheel running on anxiety, this study further shows that this estimation is dependent on the test used to assess anxiety., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: To assess the effect of duloxetine on ADHD in adults., Method: In a 6-week double-blind trial, 30 adults with ADHD received placebo or duloxetine 60 mg daily. The Conners' Adult ADHD Rating Scale (CAARS) and the Clinical Global Impression Scales (CGI) were used to assess symptom severity and clinical improvement. The Hamilton Anxiety Rating Scale (HARS) and the Hamilton Depression Rating Scale (HDRS) were used to measure the effect on anxiety and depressive symptoms., Results: The Duloxetine group showed lower score on CGI-Severity at Week 6 (3.00 vs. 4.07 for placebo, p < .001), greater improvement on CGI-Improvement (2.89 vs. 4.00 at Week 6, p < .001), and greater decreases on five of eight subscales of the CAARS. There was no treatment group effect on HDRS or HARS scores., Conclusion: Duloxetine may be a therapeutic option for adults with ADHD, but further studies are required to replicate these findings in larger samples.

Background: We have shown that the endogenous stimulation of cannabinoid type-1 (CB₁) receptors is a prerequisite for voluntary running in mice, but the precise mechanisms through which the endocannabinoid system exerts a tonic control on running performance remain unknown., Methods: We analyzed the respective impacts of constitutive/conditional CB₁ receptor mutations and of CB₁ receptor blockade on wheel-running performance. We then assessed the consequences of ventral tegmental area (VTA) CB₁ receptor blockade on the wheel-running performances of wildtype (gamma-aminobutyric acid [GABA]-CB₁⁺/⁺) and mutant (GABA-CB₁⁻/⁻) mice for CB₁ receptors in brain GABA neurons. Using in vivo electrophysiology, the consequences of wheel running on VTA dopamine (DA) neuronal activity were examined in GABA-CB₁⁺/⁺ and GABA-CB₁⁻/⁻ mice., Results: Conditional deletion of CB₁ receptors from brain GABA neurons, but not from several other neuronal populations or from astrocytes, decreased wheel-running performance in mice. The inhibitory consequences of either the systemic or the intra-VTA administration of CB1 receptor antagonists on running behavior were abolished in GABA-CB₁⁻/⁻ mice. The absence of CB1 receptors from GABAergic neurons led to a depression of VTA DA neuronal activity after acute/repeated wheel running., Conclusions: This study provides evidence that CB₁ receptors on VTA GABAergic terminals exert a permissive control on rodent voluntary running performance. Furthermore, it is shown that CB₁ receptors located on GABAergic neurons impede negative consequences of voluntary exercise on VTA DA neuronal activity. These results position the endocannabinoid control of inhibitory transmission as a prerequisite for wheel-running performance in mice., (Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

The endocannabinoid system (ECS) tightly controls emotional responses to acute aversive stimuli. Repeated stress alters ECS activity but the role played by the ECS in the emotional consequences of repeated stress has not been investigated in detail. This study used social defeat stress, together with pharmacology and genetics to examine the role of cannabinoid type-1 (CB(1)) receptors on repeated stress-induced emotional alterations. Seven daily social defeat sessions increased water (but not food) intake, sucrose preference, anxiety, cued fear expression, and adrenal weight in C57BL/6N mice. The first and the last social stress sessions triggered immediate brain region-dependent changes in the concentrations of the principal endocannabinoids anandamide and 2-arachidonoylglycerol. Pretreatment before each of the seven stress sessions with the CB(1) receptor antagonist rimonabant prolonged freezing responses of stressed mice during cued fear recall tests. Repeated social stress abolished the increased fear expression displayed by constitutive CB(1) receptor-deficient mice. The use of mutant mice lacking CB(1) receptors from cortical glutamatergic neurons or from GABAergic neurons indicated that it is the absence of the former CB(1) receptor population that is responsible for the fear responses in socially stressed CB(1) mutant mice. In addition, stress-induced hypolocomotor reactivity was amplified by the absence of CB(1) receptors from GABAergic neurons. Mutant mice lacking CB(1) receptors from serotonergic neurons displayed a higher anxiety but decreased cued fear expression than their wild-type controls. These mutant mice failed to show social stress-elicited increased sucrose preference. This study shows that (i) release of endocannabinoids during stress exposure impedes stress-elicited amplification of cued fear behavior, (ii) social stress opposes the increased fear expression and delayed between-session extinction because of the absence of CB(1) receptors from cortical glutamatergic neurons, and (iii) CB(1) receptors on central serotonergic neurons are involved in the sweet consumption response to repeated stress.

This study has investigated the role of hypothalamic and amygdalar type-1 cannabinoid (CB1) receptors in the emotional and neuroendocrine responses to stress. To do so, we used the Cre/loxP system to generate conditional mutant mice lacking the CB1 gene in neurons expressing the transcription factor single-minded 1 (Sim1). This choice was dictated by former evidence for Sim1-Cre transgenic mice bearing Cre activity in all areas expressing Sim1, which chiefly includes the hypothalamus (especially the paraventricular nucleus, the supraoptic nucleus, and the posterior hypothalamus) and the mediobasal amygdala. Genomic DNA analyses in Sim1-CB1(-/-) mice indicated that the CB1 allele was excised from the hypothalamus and the amygdala, but not from the cortex, the striatum, the thalamus, the nucleus accumbens, the brainstem, the hippocampus, the pituitary gland, and the spinal cord. Double-fluorescent in situ hybridization experiments further indicated that Sim1-CB1(-/-) mice displayed a weaker CB1 receptor mRNA expression in the paraventricular nucleus of the hypothalamus and the mediobasal part of the amygdala, compared to wild-type animals. Individually housed Sim1-CB1(-/-) mice and their Sim1-CB1(+/+) littermates were exposed to anxiety and fear memory tests under basal conditions as well as after acute/repeated social stress. A principal component analysis of the behaviors of Sim1-CB1(-/-) and Sim1-CB1(+/+) mice in anxiety tests (open field, elevated plus-maze, and light/dark box) revealed that CB1 receptors from Sim1-expressing neurons exert tonic, albeit opposite, controls of locomotor and anxiety reactivity to novel environments. No difference between genotypes was observed during the recall of contextual fear conditioning or during active avoidance learning. Sim1-CB1(-/-), but not Sim1-CB1(+/+), mice proved sensitive to an acute social stress as this procedure reverted the increased ambulation in the center of the open field. The stimulatory influence of repeated social stress on body and adrenal weights, water intake, and sucrose preference was similar in the two genotypes. On the other hand, repeated social stress abolished the decrease in cued-fear conditioned expression that was observed in Sim1-CB1(-/-) mice, compared to Sim1-CB1(+/+) mice. This study suggests that CB1 receptors located on Sim1-expressing neurons exert a tonic control on locomotor reactivity, unconditioned anxiety, and cued-fear expression under basal conditions as well as after acute or repeated stress., (Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)

The prevalence of patients diagnosed with both a psychiatric and an addiction disorder is considerable. Like many other large urban centers, Montreal harbors many of these socially marginalized individuals. In spite of a wide range of resources for the treatment of each condition taken singly, there has been until recently an alarming dearth of programs aimed at providing integrated treatment models. In recent years, the CHUM has endeavored to implement such a program in order to address the multiple needs of a population often rendered vulnerable in many respects. In this article, the authors address the magnitude of this "dual diagnosis" problem, existing intervention models and the obstacles faced by this population in terms of access to health care ; they describe the steps leading to the establishment of an Addiction Psychiatric Unit at the CHUM and the challenges arising from the creation of a multidisciplinary integrated treatment model in an urban setting.

In this article, the authors discuss the difficulties and opportunities of psychiatric training in an urban setting. Based on the example of Montréal, they ponder the interest and the relevance of this contextual framework for the training of future psychiatrists and other mental health professionals, regardless of the nature and location of their practice after their residency. The authors examine the advantages of this teaching environment and how to overcome its limits.

The atypical antipsychotic, quetiapine, is frequently prescribed on-label and off-label for the treatment of a variety of psychiatric disorders. As quetiapine has variable affinity for dozens of receptors, its clinical effects should also show a large variation as a function of dose and diagnostic category. This study attempts to elucidate the dose-response and comparative efficacy and tolerability (metabolic data) of quetiapine across psychiatric disorders. A systematic search was carried out in the electronic databases, PubMed and EMBASE, using the keywords 'quetiapine' and 'placebo'. Both monotherapy and add-on studies were included. A total of 41 studies were identified. In unipolar and bipolar depression, studies consistently found quetiapine to be effective versus placebo, at doses of approximately 150-300 and 300-600 mg per day, respectively. In bipolar mania, they consistently found quetiapine to be effective at doses of approximately 600 mg per day. In acute exacerbation of schizophrenia, the majority of studies found quetiapine to be effective at doses of approximately 600 mg per day; however, a few large studies found no difference versus placebo. In contrast, studies consistently found quetiapine to be more effective than placebo for stable schizophrenia. In obsessive-compulsive disorder, studies did not consistently find quetiapine to be effective at doses of approximately 300 mg per day. However, studies may have underestimated the efficacy of quetiapine for obsessive-compulsive disorder due to concomitant administration of antidepressants and the utilization of treatment-refractory patients. In generalized anxiety disorder, studies consistently found quetiapine to be effective at doses of approximately 150 mg per day. Finally, analysis of metabolic tolerability data suggests that even low doses of quetiapine may lead to increase in weight and triglycerides across psychiatric disorders. Interestingly, however, quetiapine-induced elevations in low-density lipoprotein and total cholesterol seem to be restricted to schizophrenia patients.

An overview of the literature on the emotional impacts of wheel running reveals contradictory findings. Among the hypotheses underlying such a discrepancy, that related to the different housing conditions of the controls, i.e., standard housing without any object or housing with blocked running wheels, merits attention. We addressed this point in C57Bl/6N mice by examining the consequences of chronic wheel running on anxiety, context fear recall, and behavioral despair compared either to standard control housing or to housing with blocked wheels. Compared to standard housing, wheel running proved anxiolytic while facilitating fear memory. On the other hand, wheel running increased behavioral despair but influenced neither anxiety nor fear memory when compared to housing with blocked wheels. This study suggests that investigations aimed at measuring the emotional consequences of wheel running should take into consideration the housing conditions of the controls to which are compared the runners., (Copyright © 2010 Wiley-Liss, Inc.)

Background: Assessing the relative value of cocaine and how it changes with chronic drug use represents a long-standing goal in addiction research. Surprisingly, recent experiments in rats--by far the most frequently used animal model in this field--suggest that the value of cocaine is lower than previously thought., Methodology/principal Findings: Here we report a series of choice experiments that better define the relative position of cocaine on the value ladder of rats (i.e., preference rank-ordering of different rewards). Rats were allowed to choose either taking cocaine or drinking water sweetened with saccharin--a nondrug alternative that is not biologically essential. By systematically varying the cost and concentration of sweet water, we found that cocaine is low on the value ladder of the large majority of rats, near the lowest concentrations of sweet water. In addition, a retrospective analysis of all experiments over the past 5 years revealed that no matter how heavy was past cocaine use most rats readily give up cocaine use in favor of the nondrug alternative. Only a minority, fewer than 15% at the heaviest level of past cocaine use, continued to take cocaine, even when hungry and offered a natural sugar that could relieve their need of calories., Conclusions/significance: This pattern of results (cocaine abstinence in most rats; cocaine preference in few rats) maps well onto the epidemiology of human cocaine addiction and suggests that only a minority of rats would be vulnerable to cocaine addiction while the large majority would be resilient despite extensive drug use. Resilience to drug addiction has long been suspected in humans but could not be firmly established, mostly because it is difficult to control retrospectively for differences in drug self-exposure and/or availability in human drug users. This conclusion has important implications for preclinical research on the neurobiology of cocaine addiction and for future medication development.

Chronic voluntary wheel-running activity has been reported to hypersensitise central CB1 receptors in mice. On the other hand, pharmacological findings suggest that the CB1 receptor could be involved in wheel-running behaviour and in running-induced neurogenesis in the hippocampus. We analysed wheel-running behaviour for 6 weeks and measured its consequences on hippocampal neurogenesis in CB1 knockout (CB1(-/-)) animals, compared to wild-type (CB1(+/+)) littermates. Because wheel running has been shown to affect locomotor reactivity in novel environments, memory for aversive events and depression-like behaviours, we also assessed these behaviours in control and running CB1(+/+) and CB1(-/-) mice. When compared with running CB1(+/+) mice, the distance covered weekly by CB1(-/-) mice was decreased by 30-40%, an observation accounted for by decreased time spent and maximal velocity on the wheels. Analyses of running distances with respect to the light/dark cycle revealed that mutant covered less distance throughout both the inactive and the active phases of that cycle. Locomotion in an activity cage, exploration in an open field, and immobility time in the forced swim test proved insensitive to chronic wheel running in either genotype. Wheel running, per se, did not influence the expression and extinction of cued fear memory but counteracted in a time-dependent manner the deficiency of extinction measured in CB1(-/-) mice. Hippocampal neurogenesis, assessed by doublecortin labelling of immature neurons in the dentate gyrus, was lowered by 40% in control CB1(-/-) mice, compared to control CB1(+/+) mice. Although CB1(-/-) mice ran less than their wild-type littermates, the 6-week running protocol increased neurogenesis to similar extents (37-39%) in both genotypes. This study suggests that mouse CB1 receptors control wheel running but not its neurogenic consequences in the hippocampus., (Copyright 2010 Elsevier Inc. All rights reserved.)

Aims: The aim of our study was to evaluate the possibility of identifying the fetal RhD status in maternal plasma using conventional hemi nested PCR analysis., Subjects and Methods: After informed written consent, 20 mL of peripheral blood were collected in 99 D-negative pregnant women either at an amniocentesis for prenatal diagnosis or at a prenatal checkup. Fetal DNA extracted from 400 microL of maternal plasma was analyzed by two different operators with a hemi-nested PCR extending an area of the RhD gene exon 10. The results were compared to the fetal RhD status obtained by PCR amniotic fluid analysis or blood analysis of newborns after delivery. The influence of mother's and baby's phenotype were also studied., Results: Among the 99 D-negative pregnant women, all Caucasian, 47 were in their second trimester and 52 in their third trimester (mean: 27.20 weeks of gestation +/-8.25). Sixty-nine fetuses were D-positive and thirty D-negative. The sensitivity and specificity of our technique were respectively 100% and 86.7% and 15% of discordant results were observed between the two operators. Four false positives were observed. According to maternal phenotype, a fetal unexpressed RHD gene was suspected in only one case because of a particular fetal phenotype (ddCcEe)., Conclusion: A conventional hemi nested PCR analysis of maternal plasma could be used for accurate fetal RhD status. However this procedure is difficult to apply for routine analysis because of the importance of anti-contamination measures required to obtain good results. Real time quantitative PCR analysis on fetal DNA is more suitable. Whatever the operating procedure used, polymorphism of RhD gene may follow in either false negative from presence of rearranged gene or false positive from occasional presence of a non functional RHD gene.

The authors report the case of a 55-year-old woman with prolapse presenting a differential diagnosis of urinary incontinence: a peritoneo-vaginal fistula with serous discharge in a patient with ascites and a history of hysterectomy. The only cases of peritoneo-vaginal fistula reported in the literature were discovered during extra-uterine pregnancy after hysterectomy.

Myotonic dystrophy is a rare disease (1/8000), that is rarely associated with pregnancy, due to the fact that parents carrying the disease often encounter hypogonadism. Myotonic dystrophy is a neuro-endocrinian 'heredo-degenerative' dystrophy, with dominant autosomic transmission. Its association with pregnancy can lead to several problems. The myotony is often aggravated which leads to obstetrical complications turning into fetal loss, premature term delivery, hydrops, in-utero death, difficulties in expulsion, haemorrhage during delivery and/or anaesthetic accidents. The following signs during the pregnancy can diagnose fetal damage: presence of a hydrops, rare active fetal movements, and low fetal cardiac rhythm. They signify serious fetal damage leading to a diagnosis of myotonic dystrophy. Personal and family antecedents as well as an important hypotony and respiratory distress discovered in the new born are equally evocative elements. In congenital cases (6-30% of the time) the prognosis of the child is pessimistic. For all of the above elements, transmission is of maternal origin. The diagnosis of the congenital form is difficult because the disease is often unknown by the mother. The appearance of molecular tools permits a diagnosis to be formed much more rapidly in a new-born suspected to carry the illness of neonatal Steinert. Two observations illustrate this pathology. The occurrence of congenital myotonic dystrophy in a new-born allows us to diagnose the disease within the mother.