A phase III multisite randomised controlled trial to compare the efficacy of cannabidiol to placebo in the treatment of cannabis use disorder: the CBD-CUD study protocol.

BACKGROUND: Cannabis use disorder (CUD) is increasingly common and contributes to a range of health and social problems. Cannabidiol (CBD) is a non-intoxicating cannabinoid recognised for its anticonvulsant, anxiolytic and antipsychotic effects with no habit-forming qualities. Results from a Phase IIa randomised clinical trial suggest that treatment with CBD for four weeks reduced non-prescribed cannabis use in people with CUD. This study examines the efficacy, safety and quality of life of longer-term CBD treatment for patients with moderate-to-severe CUD. METHODS/DESIGN: A phase III multi-site, randomised, double-blinded, placebo controlled parallel design of a 12-week course of CBD to placebo, with follow-up at 24 weeks after enrolment. Two hundred and fifty adults with moderate-to-severe CUD (target 20% Aboriginal), with no significant medical, psychiatric or other substance use disorders from seven drug and alcohol clinics across NSW and VIC, Australia will be enrolled. Participants will be administered a daily dose of either 4 mL (100 mg/mL) of CBD or a placebo dispensed every 3-weeks. All participants will receive four-sessions of Cognitive Behavioural Therapy (CBT) based counselling. Primary endpoints are self-reported cannabis use days and analysis of cannabis metabolites in urine. Secondary endpoints include severity of CUD, withdrawal severity, cravings, quantity of use, motivation to stop and abstinence, medication safety, quality of life, physical/mental health, cognitive functioning, and patient treatment satisfaction. Qualitative research interviews will be conducted with Aboriginal participants to explore their perspectives on treatment. DISCUSSION: Current psychosocial and behavioural treatments for CUD indicate that over 80% of patients relapse within 1-6 months of treatment. Pharmacological treatments are highly effective with other substance use disorders but there are no approved pharmacological treatments for CUD. CBD is a promising candidate for CUD treatment due to its potential efficacy for this indication and excellent safety profile. The anxiolytic, antipsychotic and neuroprotective effects of CBD may have added benefits by reducing many of the mental health and cognitive impairments reported in people with regular cannabis use. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry: ACTRN12623000526673 (Registered 19 May 2023).

Measuring Objective and Subjective Sleep during Lisdexamfetamine Treatment of Acute Methamphetamine Withdrawal: A Feasibility Study.

INTRODUCTION: Sleep disturbance is common during methamphetamine (MA) use and withdrawal; however, the feasibility of combined subjective-objective measurement of sleep-wake has not been shown in this population. Actigraphy is a well-established, non-invasive measure of sleep-wake cycles with good concordance with polysomnography. This study aimed to investigate the feasibility and utility of using actigraphy and sleep diaries to investigate sleep during MA withdrawal. METHODS: We conducted a feasibility and utility study of actigraphy and sleep diaries during a clinical trial of lisdexamfetamine for MA withdrawal. Participants were inpatients for 7 days, wore an actigraph (Philips Actiwatch 2) and completed a modified Consensus Sleep Diary each morning. Participants were interviewed between days 3-5. RESULTS: Ten participants (mean age 37 years, 90% male) were enrolled. No participant removed the device prematurely. Participants interviewed (n = 8) reported that the actigraph was not difficult or distracting to wear or completion of daily sleep diary onerous. Actigraphic average daily sleep duration over 7 days was 568 min, sleep onset latency 22.4 min, wake after sleep onset (WASO) 75.2 min, and sleep efficiency 83.6%. Sleep diaries underreported daily sleep compared with actigraphy (sleep duration was 56 min (p = 0.008) and WASO 47 min (p < 0.001) less). Overall sleep quality was 4.4 on a nine-point Likert scale within the diary. CONCLUSIONS: Continuous actigraphy is feasible to measure sleep-wake in people withdrawing from MA, with low participant burden. We found important differences in self-reported and actigraphic sleep, which need to be explored in more detail.

Patient-Reported Outcomes During and After Hepatitis C Virus Direct-Acting Antiviral Treatment Among People Who Inject Drugs.

OBJECTIVES: People who inject drugs (PWID) are at a high risk of hepatitis C virus (HCV) infection. HCV cure is associated with improved patient-reported outcomes (PROs), but there are little data among PWID. This study aimed to assess the change in PROs during and after HCV direct-acting antiviral (DAA) treatment. METHODS: This analysis used data from 2 clinical trials of DAA treatment in PWID. PROs assessed included health-related quality of life, social functioning, psychological distress, housing, and employment. Generalized estimating equations and group-based trajectory modeling were used to assess changes in PROs over time. RESULTS: No significant changes in the 3-level version of EQ-5D scores, EQ visual analogue scale scores, social functioning, psychological distress, and housing were observed over the 108-week study period. There was a significant increase in the proportion of participants employed (18% [95% confidence interval (CI) 12%-23%] at baseline to 28% [95% CI 19%-36%] at the end of the study). Participants were more likely to be employed at 24 weeks and 108 weeks after commencing treatment. Having stable housing increased the odds of being employed (odds ratio 1.70; 95% CI 1.00-2.90). The group-based trajectory modeling demonstrated that most outcomes remained stable during and after DAA treatment. CONCLUSIONS: Although no significant improvement was identified in health-related quality of life after HCV DAA treatment, there was a modest but significant increase in employment during study follow-up. The study findings support the need for multifaceted models of HCV care for PWID addressing a range of issues beyond HCV treatment to improve quality of life.

Substance use, socio-demographic characteristics, and self-rated health of people seeking alcohol and other drug treatment in New South Wales: baseline findings from a cohort study.

OBJECTIVE: To investigate the demographic characteristics, substance use, and self-rated health of people entering treatment in New South Wales public health services for alcohol, amphetamine-type stimulants, cannabis, cocaine, or opioids use, by principal drug of concern. DESIGN: Baseline findings of a cohort study; analysis of data in patient electronic medical records and NSW minimum data set for drug and alcohol treatment services. SETTING, PARTICIPANTS: People completing initial Australian Treatment Outcomes Profile (ATOP) assessments on entry to publicly funded alcohol and other drug treatment services in six NSW local health districts/networks, 1 July 2016 - 30 June 2019. MAIN OUTCOME MEASURES: Socio-demographic characteristics, and substance use and self-rated health (psychological, physical, quality of life) during preceding 28 days, by principal drug of concern. RESULTS: Of 14 087 people included in our analysis, the principal drug of concern was alcohol for 6051 people (43%), opioids for 3158 (22%), amphetamine-type stimulants for 2534 (18%), cannabis for 2098 (15%), and cocaine for 246 (2%). Most people commencing treatment were male (9373, 66.5%), aged 20-39 years (7846, 50.4%), and were born in Australia (10 934, 86.7%). Polysubstance use was frequently reported, particularly by people for whom opioids or amphetamine-type stimulants were the principal drugs of concern. Large proportions used tobacco daily (53-82%, by principal drug of concern group) and reported poor psychological health (47-59%), poor physical health (32-44%), or poor quality of life (43-52%). CONCLUSIONS: The prevalence of social disadvantage and poor health is high among people seeking assistance with alcohol, amphetamine-type stimulants, cannabis, cocaine, or opioids use problems. Given the differences in these characteristics by principal drug of concern, health services should collect comprehensive patient information during assessment to facilitate more holistic, tailored, and person-centred care.

Practice change intervention to improve antenatal care addressing alcohol consumption during pregnancy: a randomised stepped-wedge controlled trial.

BACKGROUND: Clinical guideline recommendations for addressing alcohol consumption during pregnancy are sub-optimally implemented and limited evidence exists to inform practice improvements. The aim of this study was to estimate the effectiveness of a practice change intervention in improving the provision of antenatal care addressing alcohol consumption during pregnancy in public maternity services. METHODS: A randomised stepped-wedge controlled trial was undertaken with all public maternity services in three sectors (one urban, two regional/rural) of a single local health district in New South Wales, Australia. All antenatal care providers were subject to a seven-month multi-strategy intervention to support the introduction of a recommended model of care. For 35 months (July 2017 - May 2020) outcome data were collected from randomly selected women post an initial, 27-28 weeks and 35-36 weeks gestation antenatal visit. Logistic regression models assessed intervention effectiveness. RESULTS: Five thousand six hundred ninety-four interviews/online questionnaires were completed by pregnant women. The intervention was effective in increasing women's reported receipt of: assessment of alcohol consumption (OR: 2.63; 95% CI: 2.26-3.05; p < 0.001), advice not to consume alcohol during pregnancy and of potential risks (OR: 2.07; 95% CI: 1.78-2.41; p < 0.001), complete care relevant to alcohol risk level (advice and referral) (OR: 2.10; 95% CI: 1.80-2.44; p < 0.001) and all guideline elements relevant to alcohol risk level (assessment, advice and referral) (OR: 2.32; 95% CI: 1.94-2.76; p < 0.001). Greater intervention effects were found at the 27-28 and 35-36 weeks gestation visits compared with the initial antenatal visit. No differences by sector were found. Almost all women (98.8%) reported that the model of care was acceptable. CONCLUSIONS: The practice change intervention improved the provision of antenatal care addressing alcohol consumption during pregnancy in public maternity services. Future research could explore the characteristics of pregnant women and maternity services associated with intervention effectiveness as well as the sustainment of care practices over time to inform the need for, and development of, further tailored practice change support. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (Registration number: ACTRN12617000882325; Registration date: 16/06/2017) https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372985&isReview=true.

Progress Towards Elimination of Hepatitis C Infection Among People Who Inject Drugs in Australia: The ETHOS Engage Study.

BACKGROUND: Evaluating progress towards hepatitis C virus (HCV) elimination is critical. This study estimated prevalence of current HCV infection and HCV treatment uptake among people who inject drugs (PWID) in Australia. METHODS: The Enhancing Treatment of Hepatitis C in Opioid Substitution Settings Engage is an observational study of PWID attending drug treatment clinics and needle and syringe programs (NSPs). Participants completed a questionnaire including self-reported treatment history and underwent point-of-care HCV RNA testing (Xpert HCV Viral Load Fingerstick; Cepheid). RESULTS: Between May 2018 and September 2019, 1443 participants were enrolled (64% injected drugs in the last month, 74% receiving opioid agonist therapy [OAT]). HCV infection status was uninfected (28%), spontaneous clearance (16%), treatment-induced clearance (32%), and current infection (24%). Current HCV was more likely among people who were homeless (adjusted odds ratio, 1.47; 95% confidence interval, 1.00-2.16), incarcerated in the previous year (2.04; 1.38-3.02), and those injecting drugs daily or more (2.26; 1.43-2.42). Among those with previous chronic or current HCV, 66% (n = 520/788) reported HCV treatment. In adjusted analysis, HCV treatment was lower among females (.68; .48-.95), participants who were homeless (.59; .38-.96), and those injecting daily or more (.51; .31-.89). People aged ≥45 years (1.46; 1.06-2.01) and people receiving OAT (2.62; 1.52-4.51) were more likely to report HCV treatment. CONCLUSIONS: Unrestricted direct-acting antiviral therapy access in Australia has yielded high treatment uptake among PWID attending drug treatment and NSPs, with a marked decline in HCV prevalence. To achieve elimination, PWID with greater marginalization may require additional support and tailored strategies to enhance treatment.

Reinfection Following Successful Direct-acting Antiviral Therapy for Hepatitis C Virus Infection Among People Who Inject Drugs.

BACKGROUND: The aim of this analysis was to calculate the incidence of hepatitis C virus (HCV) reinfection and associated factors among 2 clinical trials of HCV direct-acting antiviral treatment in people with recent injecting drug use or currently receiving opioid agonist therapy (OAT). METHODS: Participants who achieved an end-of-treatment response in 2 clinical trials of people with recent injecting drug use or currently receiving OAT (SIMPLIFY and D3FEAT) enrolled between March 2016 and February 2017 in 8 countries were assessed for HCV reinfection, confirmed by viral sequencing. Incidence was calculated using person-time of observation and associated factors were assessed using Cox proportional hazard models. RESULTS: Seventy-three percent of the population at risk of reinfection (n = 177; median age, 48 years; 73% male) reported ongoing injecting drug use. Total follow-up time at risk was 254 person-years (median, 1.8 years; range, 0.2-2.8 years). Eight cases of reinfection were confirmed for an incidence of 3.1/100 person-years (95% confidence interval [CI], 1.6-6.3) overall and 17.9/100 person-years (95% CI, 5.8-55.6) among those who reported sharing needles/syringes. Younger age and needle/syringe sharing were associated with HCV reinfection. CONCLUSIONS: These data demonstrate the need for ongoing monitoring and improved strategies to prevent HCV reinfection following successful treatment among people with ongoing injecting drug use to achieve HCV elimination. CLINICAL TRIALS REGISTRATION: NCT02336139 and NCT02498015.

Unmet need for postpartum long-acting reversible contraception in women with substance use disorders and/or socioeconomic disadvantage.

BACKGROUND: In Australia, it is estimated that 30% of pregnancies are unintended and 25% of pregnancies end in abortion. Unintended pregnancy can be particularly problematic for women with substance use disorders (SUD) and/or socioeconomic disadvantage. Long-acting reversible contraception (LARC) including progestogen implants and intrauterine devices (IUD) are safe, affordable and extremely effective in decreasing rates of unintended pregnancy, yet are currently underutilised in Australia. AIMS: To determine the current rate of unintended pregnancy, contraception counselling and postpartum LARC use in women who attend an antenatal clinic for SUD and/or socioeconomic disadvantage in pregnancy. We hypothesise that there is an unmet need for contraception in this population. MATERIALS AND METHODS: We conducted a retrospective audit of women who birthed in a tertiary hospital in 2018 with SUD and/or additional social support needs. We recorded the rate of unintended pregnancy, the occurrence of antenatal and postpartum contraception counselling and the rate of immediate postpartum LARC uptake through review of our electronic medical database. RESULTS: Of the 210 women in our study population, we identified a high proportion of unintended pregnancies (64%), a low rate of antenatal (11%) and postpartum (35%) contraception counselling, and a low uptake of immediate postpartum LARC use (3.3%), confirming an unmet need for contraception. CONCLUSIONS: Further intervention is required to enhance the access to immediate postpartum LARC and reduce the risk and health burden of unintended pregnancy.

Implementation of a Multi-Modal Training Program for the Management of Comorbid Mental Disorders in Drug and Alcohol Settings: Pathways to Comorbidity Care (PCC).

OBJECTIVES: We aimed to evaluate the impact of the Pathways to Comorbidity Care (PCC) training program for alcohol and other drugs (AOD) clinicians to improve the management of comorbidity. METHODS: A controlled before-and-after study using PCC training was conducted across 6 matched sites in Australia including 35 clinicians. Controls received standard workplace training. PCC training included seminar presentations, workshops conducted by local "clinical champions," individual clinical supervision, and access to an online information portal. We examined (a) identification (screening, assessment) and treatment (treatment, referral) of comorbidity in practice (N = 10 clinical files per clinician), (b) self-efficacy, knowledge, and attitudes of clinicians. RESULTS: Significant improvements were observed in the PCC group but not the control sites with regards to the rate of clinical files showing identification of comorbidity (+50% v -12% change from baseline, respectively; [X2 (1, N = 340) = 35.29, p = .01] with only a trend for improvements in the rate of files demonstrating treatment of comorbidity [X2 (1, N = 340) = 10.45, p = .06]. There were significant improvements in the PCC relative to the control group for clinician self-efficacy, F(1,33) = 6.40, p = .02 and knowledge and attitudes of comorbidity monitoring, F(1,33) = 8.745, p = .01. CONCLUSIONS: The PCC training package may help improve identification of comorbidity, self-efficacy, and attitudes toward screening and monitoring of comorbidity in drug and alcohol settings.

The provision of preventive care for modifiable health risk behaviours by clinicians within substance use treatment settings: A systematic review.

People who use substances have a high prevalence of other modifiable health risk behaviours such as tobacco smoking which contribute to an increased mortality and morbidity. Preventive care can reduce the prevalence of such behaviours and is recommended by clinical practice guidelines. This review describes the prevalence of preventive care delivery by substance use treatment healthcare providers and examines differences by treatment setting. Five databases were searched for studies published between 2005 and 2017. Eligible studies reported levels of preventive care (assessment, brief advice and/or referral/follow-up) in substance use treatment services for tobacco smoking, nutrition or physical activity. Two reviewers independently conducted article screening, data extraction and methodological quality assessment. Sixteen studies were included and all except one investigated care provision for tobacco smoking only. Four studies reported care levels as a proportion and 12 studies reported care as a score-based mean. Client-reported receipt of smoking cessation care ranged from: 79-90% for assessment; 15-79% for brief advice; 0-30% for referral/follow-up. Meta-regression analyses of 12 studies found clinician-reported preventative care for tobacco smoking was more frequently reported in studies assessing care occurring across multiple substance use treatment settings, compared to studies reporting provision in inpatient only. This review indicated that, compared to smoking cessation care, little is known about the level of preventive care for nutrition or physical activity. Overall, the delivery of smoking cessation care reported was sub-optimal. High levels of assessment relative to brief advice and low levels of referral to ongoing assistance were indicated.