Vaping to quit smoking: Qualitative study of people receiving opioid agonist treatment.

INTRODUCTION: Most patients receiving opioid agonist treatment (OAT) smoke tobacco. Approved cessation interventions are less effective in this group than the wider population. We investigated how people on OAT experience nicotine vaping to quit smoking. METHODS: Patients on OAT randomised to the vaping arm of a smoking cessation trial were invited to participate in structured interviews incorporating broad pre-determined themes. A qualitative descriptive approach employing template analysis was used. Four authors coded transcripts, discussed discrepancies, modified the template using both inductive and deductive approaches. Authors made explicit their starting orientations and independent authors sought disconfirmatory data in a subsequent round of analysis. RESULTS: Four women and eight men (median age 44 years) participated, including four who identified as Aboriginal. Participants reported vaping as cheaper, more acceptable and less stigmatising than smoking but expressed concerns about ongoing accessibility due to the Australian prescription access model. Some found it technically challenging at first, but not more so than standard nicotine replacement therapies. Participants gave accounts of craving and withdrawal experiences, including supplementary use of nicotine patches, and compulsions to vape frequently and intensely, potentially indicating need for higher nicotine dosage. Participants generally reported that vaping helped them quit smoking, though some worried about swapping nicotine addictions. Others were glad to be using a lower-risk alternative. DISCUSSION AND CONCLUSIONS: This group reported varied experiences of nicotine vaping but were mainly optimistic that it could help them and others quit smoking. This was despite initial nicotine cravings and concerns about remaining addicted long-term.

Implementation of time-limited parenteral hydromorphone in people with treatment-resistant injecting opioid use disorder: a protocol for a single-site, uncontrolled, open-label study to assess feasibility, safety and cost.

INTRODUCTION: Supervised injectable opioid treatment (SIOT) is an evidence-based intervention targeting opioid-dependent people for whom existing treatments have been ineffective. This project will primarily assess the feasibility and the acceptability of time-limited SIOT using injectable hydromorphone delivered in an existing Australian public opioid treatment programme, with secondary outcomes of safety, cost, changes in drug use and other health outcomes. If feasible, the goal is to scale up the intervention to be more widely available in Australia. METHODS AND ANALYSIS: Between 20 and 30 participants will be offered two times per day hydromorphone to inject under direct observation, in addition to their current opioid agonist treatment (OAT), for up to 2 years. At the end of 2 years of supervised hydromorphone treatment, participants will be continued on standard OAT only. Informed consent will be obtained from all participants included in the study. This is a single-site, uncontrolled, open-label study where quantitative and qualitative interview data will be collected at baseline, 12 months and lastly at 3 months following their final hydromorphone dose. The main outcome measures are feasibility, as assessed by recruitment, retention and participation in treatment, and acceptability to participants, clinic staff and other stakeholders assessed by qualitative interviews. Secondary outcome measures of safety, as assessed by adverse events, and cost will also be assessed, as well as a range of other drug and health outcomes. ETHICS AND DISSEMINATION: This study received ethical approval from the St Vincent's Hospital Human Research Ethics Committee (2019/ETH00418). This will be the first study of time-limited SIOT in the Australian setting. All results will be submitted to peer-reviewed journals, scientific conferences and local practice meetings. A preliminary report on outcomes will also be presented to local health policy makers. A consumer and community forum will also be held to feedback results to a broader audience. TRIAL REGISTRATION NUMBER: ACTRN12621001729819.

Pilot study with randomised control of dual site theta burst transcranial magnetic stimulation (TMS) for methamphetamine use disorder: a protocol for the TARTAN study.

BACKGROUND: Transcranial magnetic stimulation (TMS) (including the theta burst stimulation (TBS) form of TMS used in this study) is a non-invasive means to stimulate nerve cells in superficial areas of the brain. In recent years, there has been a growth in the application of TMS to investigate the modulation of neural networks involved in substance use disorders. This study examines the feasibility of novel TMS protocols for the treatment of methamphetamine (MA) use disorder in an ambulatory drug and alcohol treatment setting. METHODS: Thirty participants meeting the criteria for moderate to severe MA use disorder will be recruited in community drug and alcohol treatment settings and randomised to receive active TMS or sham (control) intervention. The treatment is intermittent TBS (iTBS) applied to the left dorsolateral prefrontal cortex (DLPFC), then continuous TBS (cTBS) to the left orbitofrontal cortex (OFC). Twelve sessions are administered over 4 weeks with opt-in weekly standardized cognitive behaviour therapy (CBT) counselling and a neuroimaging sub-study offered to participants. Primary outcomes are feasibility measures including recruitment, retention and acceptability of the intervention. Secondary outcomes include monitoring of safety and preliminary efficacy data including changes in substance use, cravings (cue reactivity) and cognition (response inhibition). DISCUSSION: This study examines shorter TBS protocols of TMS for MA use disorder in real-world drug and alcohol outpatient settings where withdrawal and abstinence from MA, or other substances, are not eligibility requirements. TMS is a relatively affordable treatment and staff of ambulatory health settings can be trained to administer TMS. It is a potentially scalable and translatable treatment for existing drug and alcohol clinical settings. TMS has the potential to provide a much-needed adjuvant treatment to existing psychosocial interventions for MA use disorder. A limitation of this protocol is that the feasibility of follow-up is only examined at the end of treatment (4 weeks). TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12622000762752. Registered on May 27, 2022, and retrospectively registered (first participant enrolled) on May 23, 2022, with protocol version 7 on February 24, 2023.

Factors associated with experiencing stigma, discrimination, and negative health care treatment among people who inject drugs.

INTRODUCTION: Stigma has negative consequences for the health of people who inject drugs and people living with hepatitis C virus (HCV). This study evaluated factors associated with stigma related to injecting drug use (IDU) or HCV and those associated with being treated negatively by health workers. METHODS: ETHOS Engage is an observational cohort study of people who inject drugs attending drug treatment clinics and needle and syringe programs in Australia. Participants completed a questionnaire including IDU- and HCV-related stigma, and negative treatment by health workers. Logistic regression was used to identify factors associated with experiencing stigma and negative treatment in a cross-sectional sample. RESULTS: Of 1,211 participants, 31% were women, 64% had injected drugs in the previous month, and 65% had been diagnosed with HCV. IDU-related stigma was reported by 57% of participants and was associated with being a woman, higher than Year 10 education, homelessness, opioid agonist treatment, recent injecting, overdose history, hospitalisation for drug use, and unknown HCV status. HCV-related stigma was reported by 34% of participants diagnosed with HCV and was associated with being a woman, homelessness, receptive needle/syringe sharing, arrest for drug use/possession, and recent HCV testing. Negative treatment from health workers was reported by 45% of participants and was associated with being a woman, receptive needle/syringe sharing, hospitalisation for drug use, and arrest for drug use/possession. DISCUSSION AND CONCLUSIONS: Results highlight important intersections and disparities in stigmatising experiences among people who inject drugs. Considering these intersections can assist health services provide more inclusive care.

A qualitative study of using nicotine products for smoking cessation after discharge from residential drug and alcohol treatment in Australia.

INTRODUCTION: Tobacco smoking is highly prevalent among alcohol and other drugs (AOD) service clients and, despite interest in quitting, abstinence is rarely sustained. Nicotine products may assist after discharge from residential treatment services, but little is known about client receptivity to them. This study examined AOD withdrawal service clients' experiences of two types of nicotine products for smoking cessation post-discharge, combination nicotine replacement therapy (cNRT) and nicotine vaping products (NVP). METHODS: We held semi-structured telephone interviews with 31 Australian AOD service clients in a clinical trial of a 12-week smoking cessation intervention using Quitline support plus cNRT or NVP delivered post-discharge from a smoke-free residential service. We asked about health and social factors, nicotine cravings, Quitline experience, and barriers and facilitators to cNRT or NVP, then thematically analysed data. RESULTS: cNRT and NVP were described by participants as feasible and acceptable for smoking cessation. For most participants, cost limited cNRT access post study, as did difficulty navigating NVP prescription access. Quitline support was valued, but not consistently used, with participants noting low assistance with NVP-facilitated cessation. Participants considered both cessation methods acceptable and socially supported, and sought information on decreasing nicotine use via NVP. DISCUSSION AND CONCLUSIONS: AOD service clients highly valued receiving cNRT or NVP with behavioural support for smoking reduction or abstinence. Both interventions were acceptable to service clients. Findings suggest a potential need to examine both whether NVP use should be permitted in this context, and guidance on the individual suitability of cNRT or NVP.

96-week retention in treatment with extended-release subcutaneous buprenorphine depot injections among people with opioid dependence: Extended follow-up after a single-arm trial.

BACKGROUND: The most recent formulation of buprenorphine treatment is extended-release depot injections (BUP-XR) that are administered subcutaneously by health care professionals. This study aimed to observe treatment outcomes of BUP-XR delivered in standard practice during a 96-week follow-up period in a community setting. METHODS: This study is an extension of the CoLAB study, a prospective single-arm, multicentre, open label trial (N=100, 7 sites in Australia) among people with opioid dependence who received monthly injections of BUP-XR to evaluate the retention in treatment. Participants were followed for 96 weeks, comprising 48 weeks of the CoLAB study followed by a 48-week extension. RESULTS: Of 100 participants at baseline, 47 were retained on BUP-XR at 96 weeks. The median time retained on monthly depot was 90 weeks. Heroin use (adjusted OR=0.19, P=0.012) in the month prior to baseline was associated with lower odds of retention on BUP-XR. Older age at first opioid use (adjusted OR= 1.08, P=0.009) and longer duration in OAT at baseline (adjusted OR= 1.12, P=0.001) were associated with increased retention. Prevalence of past four-weeks opioid use was estimated at 4% at 96 weeks of treatment (prevalence 0.04, 95%CI: 0.00-0.11) compared to 15% at baseline. Quality of life and medication treatment satisfaction improved over time for those retained in treatment. CONCLUSION: This is one of the few studies to describe long term (96 week) retention in treatment with BUP-XR in a community setting. It displayed retention rates with 47% of participants completing 96 weeks of treatment with BUP-XR. Patient reported outcomes suggest improvements in client wellbeing. FUNDING: Indivior.

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.

Participant experiences in a pilot study for methamphetamine withdrawal treatment: Implications for retention.

INTRODUCTION: There is little knowledge of the perspectives of people who use methamphetamine and have participated in clinical trials, and none for interventions not intended to address abstinence. A better understanding of these experiences could lead to more patient centred clinical trial design. This study seeks to understand the experiences of people who completed a clinical trial of lisdexamfetamine for the treatment of acute methamphetamine withdrawal. METHODS: Thematic analysis of open-ended, semi-structured interviews with eight people who participated in an inpatient clinical trial of lisdexamfetamine for acute methamphetamine withdrawal. Interviews were conducted between days 3 and 6 of admission to an inner-city Sydney hospital. RESULTS: Participants described how research procedures, the research setting, and the investigational product affected their experiences while enrolled in a clinical trial. Of particular importance to participants were transparent and low burden trial procedures, a welcoming trial environment, trusting relationships and effective communication, which were linked with the participants' subsequent decision to remain enrolled in the trial. DISCUSSION: The experiences of participants in this clinical trial can be distilled into four meta-themes: agency, caring-trust, safety, and communication. Participants spontaneously linked these experiences with a capacity to remain enrolled in the study. By considering the experiences of trial participants in clinical trial design, researchers can improve the experiences of future trial participants and facilitate their choice to remain enrolled in clinical trials.