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Anastasia Suraev,1– 3 Llewellyn Mills,4,5 Sarah V Abelev,1 Thomas R Arkell,6 Nicholas Lintzeris,4,5,* Iain S McGregor1– 3,* 1The University of Sydney, Lambert Initiative for Cannabinoid Therapeutics, Sydney, NSW, Australia; 2The University of Sydney, Faculty of Science, School of Psychology, Sydney, NSW, Australia; 3The University of Sydney, Brain and Mind Centre, Sydney, NSW, Australia; 4Drug and Alcohol Services, South East Sydney Local Health District, Sydney, NSW, Australia; 5Department of Addiction Medicine, Faculty Medicine and Health, University of Sydney, Sydney, NSW, Australia; 6Centre for Human Psychopharmacology, Swinburne University of Technology, Hawthorn, VIC, Australia*These authors contributed equally to this workCorrespondence: Iain S McGregor, The University of Sydney, Lambert Initiative for Cannabinoid Therapeutics, Level 6, Building M02F, 94 Mallett Street Camperdown, Sydney, NSW, 2050, Australia, Tel +612 9351 0883, Email iain.mcgregor@sydney.edu.auIntroduction: Sleep disorders are the third most common indication for the prescription of medical cannabis products in Australia, after pain and anxiety. While the use of cannabis for medical purposes is growing in Australia, underlying consumer behaviours and patterns of use, particularly around sleep disorders, are poorly understood.Methods: We conducted a subanalysis of the cross-sectional “Cannabis as Medicine Survey” 2020– 2021 (CAMS-20) (N = 1600), to explore the characteristics of a sample of Australians who were using prescribed and/or illicit medical cannabis to treat a self-reported sleep disorder.Results: When asked to specify up to seven different conditions they were treating with medical cannabis, a total of 1030 (64%) respondents [mean (SD) 44.9 (13.6) years] selected a sleep disorder, with “insomnia disorder” (85.5%), ‘sleep-related movement disorders’ (26%) and ‘sleep-related breathing disorders’ (11.1%) the most common subtypes. Only 165 (16.8%) respondents selected a self-reported sleep disorder as the main health condition being treated. Relative to other health conditions, use of medical cannabis for a self-reported sleep disorder was associated with younger age, increased likelihood of using both prescribed and illicit forms of medical cannabis, inhaled routes of administration, and THC-dominant products. Most respondents reported a reduction in the use of benzodiazepines and alcohol since starting medical cannabis. Binary logistic regression showed that respondents who predominantly used inhaled routes of administration, and concomitant use of medical cannabis for pain, mental health and/or substance use disorder, or a gastrointestinal disorder, were significantly more likely to also use medical cannabis to treat a self-reported sleep disorder.Conclusion: Overall, these results suggest that self-reported sleep disorders are often being treated with medical cannabis alongside other health conditions (often pain or a mental health disorder) and that use of inhaled methods, THC-dominant products, and illicit sources of medical cannabis are common among people with self-reported sleep disorders in Australia.Keywords: medical cannabis, THC, CBD, cannabinoid, insomnia, sleep disorders, survey

Amphetamine type substances (ATS) are commonly used by Australian alcohol and other drug service entrants. We describe demographic characteristics, patterns of ATS and other substance use, health and social conditions among clients entering New South Wales (NSW) public alcohol and other drug services.Retrospective cohort of 13,864 records across six health districts (2016-2019) for clients seeking substance use treatment. These districts service approximately 44% of the NSW population aged 15 years and over. Multivariate analysis was conducted on a subsample for whom full data were available (N = 9981). Data included NSW Minimum Data Set for drug and alcohol treatment services and Australian Treatment Outcomes Profile items.Over the preceding 4 weeks, 77% (n = 10,610) of clients (N = 13,864) reported no recent ATS use, 15% (n = 2109) reported 'low frequency' (1-12 days) and 8% (n = 1145) 'high frequency' (13-28 days) use. ATS use was most common among people attending for ATS or opioids as primary drug of concern. A multinomial regression (N = 9981) identified that clients reporting recent arrest (aOR 1.74, 95% CI 1.36, 2.24), higher cannabis use frequency (aOR 1.01, 95% CI 1.00, 1.02), lower opioid use frequency (aOR 0.98, 95% CI 0.97, 0.99) and poorer quality of life (aOR 0.91, 95% CI 0.86, 0.97) were more likely to report 'high frequency' rather than 'low frequency' ATS use.People who use ATS experience health and social issues that may require targeted responses. These should be integrated across all services, not only for clients with ATS as principal drug of concern.

Cannabinoid co-administration may enable reduced opioid doses for analgesia. This updated systematic review on the opioid-sparing effects of cannabinoids considered preclinical and clinical studies where the outcome was analgesia or opioid dose requirements. We searched Scopus, Cochrane Central Registry of Controlled Trials, Medline, and Embase (2016 onwards). Ninety-two studies met the search criteria including 15 ongoing trials. Meta-analysis of seven preclinical studies found the median effective dose (ED50) of morphine administered with delta-9-tetrahydrocannabinol was 3.5 times lower (95% CI 2.04, 6.03) than the ED50 of morphine alone. Six preclinical studies found no evidence of increased opioid abuse liability with cannabinoid administration. Of five healthy-volunteer experimental pain studies, two found increased pain, two found decreased pain and one found reduced pain bothersomeness with cannabinoid administration; three demonstrated that cannabinoid co-administration may increase opioid abuse liability. Three randomized controlled trials (RCTs) found no evidence of opioid-sparing effects of cannabinoids in acute pain. Meta-analysis of four RCTs in patients with cancer pain found no effect of cannabinoid administration on opioid dose (mean difference −3.8 mg, 95% CI −10.97, 3.37) or percentage change in pain scores (mean difference 1.84, 95% CI −2.05, 5.72); five studies found more adverse events with cannabinoids compared with placebo (risk ratio 1.13, 95% CI 1.03, 1.24). Of five controlled chronic non-cancer pain trials; one low-quality study with no control arm, and one single-dose study reported reduced pain scores with cannabinoids. Three RCTs found no treatment effect of dronabinol. Meta-analyses of observational studies found 39% reported opioid cessation (95% CI 0.15, 0.64, I2 95.5%, eight studies), and 85% reported reduction (95% CI 0.64, 0.99, I2 92.8%, seven studies). In summary, preclinical and observational studies demonstrate the potential opioid-sparing effects of cannabinoids in the context of analgesia, in contrast to higher-quality RCTs that did not provide evidence of opioid-sparing effects.

Introduction: Standardised data collection processes allow for harmonisation and comparison of data across different studies and services. This project aimed to develop a ‘core dataset’ to serve as the default collection when designing future studies and evaluations, building upon data routinely collected in clinical Alcohol and Other Drug (AOD) settings in NSW, Australia. Methods: A working group was established, comprising clinicians, researchers, data managers, consumers from public sector and NGO AOD services in the NSW Drug and Alcohol Clinical Research and Improvement Network (DACRIN). A series of Delphi meetings occurred to reach consensus on the data items to be included in the core dataset for three domains: demographics, treatment activity, and substance use variables.Results: There were 20-40 attendees at each meeting. An initial consensus criterion of having received >70% of the vote was established. Given the difficulty in reaching consensus for most items, subsequently this was changed to eliminate items that received

Prescription opioid use disorder (pOUD) is an important sequela of long-term prescribed opioids for chronic pain. General practitioners (GPs) may not systematically diagnose or manage this; however, it is unclear why.This scoping review searched multiple databases to assess GPs' experience diagnosing and managing patients prescribed opioids for chronic pain who have developed pOUD.The 19 included articles report high levels of GP concern regarding opioid diversion, inappropriate use, abuse, misuse, diversion, dependence and addiction. Confidence screening and detecting pOUD is mixed, and few screen systematically. The most common response is declining to prescribe rather than diagnosing and managing pOUD.GPs experience high levels of conflict when considering potential pOUD in their patients with chronic pain prescribed opioids. Their experiences diagnosing and managing pOUD are not fully understood. Further theory-based research may help to understand this and assist future policy directions, programs and research priorities.

There is no effective treatment for methamphetamine withdrawal. This study aimed to determine the feasibility and safety of a tapering dose of lisdexamfetamine for the treatment of acute methamphetamine (MA) withdrawal.Open-label, single-arm pilot study, in an inpatient drug and alcohol withdrawal unit assessing a tapering dose of oral lisdexamfetamine dimesylate commencing at 250 mg once daily, reducing by 50 mg per day to 50 mg on Day 5. Measures were assessed daily (days 0-7) with 21-day telephone follow-up. Feasibility was measured by the time taken to enrol the sample. Safety was the number of adverse events (AEs) by system organ class. Retention was the proportion to complete treatment. Other measures included the Treatment Satisfaction Questionnaire for Medication (TSQM), the Amphetamine Withdrawal Questionnaire and craving (Visual Analogue Scale).Ten adults seeking inpatient treatment for MA withdrawal (9 male, median age 37.1 years [IQR 31.7-41.9]), diagnosed with MA use disorder were recruited. The trial was open for 126 days; enroling one participant every 12.6 days. Eight of ten participants completed treatment (Day 5). Two participants left treatment early. There were no treatment-related serious adverse events (SAEs). Forty-seven AEs were recorded, 17 (36%) of which were potentially causally related, all graded as mild severity. Acceptability of the study drug by TSQM was rated at 100% at treatment completion. Withdrawal severity and craving reduced through the admission.A tapering dose regimen of lisdexamfetamine was safe and feasible for the treatment of acute methamphetamine withdrawal in an inpatient setting.

The study aimed to culturally adapt the Australian Treatment Outcomes Profile (ATOP; Ryan et al., 2014) in the Greek context and to evaluate its psychometric properties in a sample of people in substitution treatment for opiate dependence. The Hellenic Treatment Outcomes Profile (HTOP) was initially validated through the process of clinician and patient focus groups that ensured its content and face validity, respectively. Inter-rater reliability and concurrent validity were satisfactory for all HTOP items. The HTOP is an extremely useful instrument that assesses the patients’ therapeutic course briefly and comprehensively. We expect it will contribute to a more targeted and individualized patient care, as well as to a better evaluation of our services, through standardizing the therapeutic outcomes monitoring.

BACKGROUND AND AIMS: Opioid agonist treatment is effective but resource intensive to administer safely in custodial settings, leading to significant under-treatment of opioid dependence in these settings world-wide. This study assessed the safety of subcutaneous slow-release depot buprenorphine in custody. SETTING: This is an open-label, non-randomized trial conducted in correctional centres in New South Wales, Australia. Sixty-seven men and women, aged ≥ 18 years of various security classifications with a diagnosis of moderate to severe DSM-5 opioid use disorder currently serving a custodial sentence of ≥ 6 months were recruited between November 2018 and July 2019. Patients not in opioid agonist treatment at recruitment commenced depot buprenorphine; patients already stable on oral methadone treatment were recruited to the comparison arm. INTERVENTION AND COMPARATOR: Depot buprenorphine (CAM2038 weekly for 4 weeks then monthly) and daily oral methadone. Safety was assessed by adverse event (AE) monitoring and physical examinations at every visit. Participants were administered a survey assessing self-reported diversion and substance use at baseline and weeks 4 and 16. FINDINGS: Retention in depot buprenorphine treatment was 92.3%. Ninety-four per cent of patients reported at least one adverse event, typically mild and transient. No diversion was identified. The prevalence of self-reported non-prescribed opioid use among depot buprenorphine patients decreased significantly between baseline (97%) and week 16 (12%, odds ratio = 0.0035, 95% confidence interval = 0.0007-0.018, P

Introduction: The Australian Treatment Outcomes Profile (ATOP) is a brief instrument that measures self-reported substance use, health, and wellbeing in the previous 28 days for people in alcohol and other drug treatment. Previous studies have established the concurrent validity, inter-rater, and test-retest reliability of the tool. The current study sought to identify recommended cutoff scores for ATOP items for psychological health, physical health and quality of life that identify clients reporting clinically significant problems warranting further assessment and/or intervention, compared to cutoffs used by 'gold-standard' measures for these domains. Methods: Clients attending for treatment for problems with opioid (n = 144) or alcohol use (n = 134) completed the ATOP and comparison standardised questionnaires (Kessler-10, Short Form Survey 12 and the Personal Wellbeing Index) with a researcher. Receiver operating characteristics analysis, along with clinician perspectives, were used to recommend cutoff scores for ATOP items indicative of clinically significant problems. Results: A cutoff score of 5 or less out of 10 was identified as an optimal pragmatic cutoff for ATOP items relating to psychological health, physical health and quality of life items with regards to balancing sensitivity, specificity, and application in a treatment setting. Discussion and conclusions: The recommended clinical cutoffs will support clinicians and treatment services to identify clients who require further assessment and follow up for their psychological health, physical health and quality of life. The current study provides further evidence for the utility of the ATOP for individual clinical review, service planning and research.

Objectives To review the currently available evidence on transfer strategies from methadone to sublingual buprenorphine used in clinical trials and observational studies of medication for opioid use disorder treatment, and to consider whether any strategies yield better clinical outcomes than others. Methods Six medical and public health databases were searched for articles and conference abstracts. The Cochrane Central Register of Controlled Trials and the World Health Organization International Clinical Trials Registry Platform were used to identify unpublished trial results. Records were dually screened, and data were extracted and checked independently. Results were summarized qualitatively and, when possible, analyzed quantitatively. Results Eighteen studies described transfer from methadone to buprenorphine. Transfer protocols were extremely varied. Most studies reported successful rates of transfer, even among studies involving transfer from high methadone doses, although lower pretransfer methadone dose was significantly associated with higher rate of successful transfer. Precipitated withdrawal was not reported frequently. A range of innovative approaches to transfer from methadone to buprenorphine remains untested. Conclusions Few studies have used designs that enable comparison of different approaches to transfer patients from methadone to buprenorphine. Most international clinical guidelines provide recommendations consistent with the available evidence. However, clinical guidelines should be perceived as providing "guidance" rather than "protocols," and clinicians and patients need to exercise judgment when attempting transfers.

Pregabalin has become widely used as an alternative to opioids in treating certain types of chronic non-cancer pain, but few studies have examined its clinical efficacy outside trials. We address this gap by examining the utilization, correlates and clinical outcomes of pregabalin use among an Australian community-based cohort of people prescribed opioids for chronic non-cancer pain. Through a five-year prospective cohort study (n = 1514) we examined associations between pregabalin use and pain severity and interference, mental health, opioid dose and past month use of ambulance and emergency department services. We used fixed-effects regression models to examine within-participant differences, and random-effects regression models to examine within and between participant differences in clinical outcomes. In an analysis of cases with complete data over five-years (n = 896), the prevalence of pregabalin use ranged from 16% at cohort entry to 29% at 36- and 48-months, and 46% reported pregabalin use at any time during the five years.. Pregabalin use was associated with greater pain severity and interference and greater use of high-risk opioid doses (>90 oral morphine equivalents/day). Pregabalin use was not associated with changes in mental health symptoms, ambulance, or emergency department attendance in the fixed or random effects models. Pregabalin use was common, but for most people use was not associated with clinically meaningful improvements in pain or functioning.

Buprenorphine is a partial opioid agonist commonly used to treat opioid dependence. The pharmacology of buprenorphine increases the risk of a precipitated opioid withdrawal when commencing patients on buprenorphine treatment, particularly when transferring from long acting opioids (e.g. methadone). There is little documented experience regarding the management of precipitated withdrawal. In our case, a patient developed a significant precipitated opioid withdrawal following buprenorphine administration, and was able to be successfully treated in hospital with further buprenorphine. This demonstrates that rapid increases in buprenorphine dose can be used as an effective treatment for buprenorphine‐induced precipitated opioid withdrawal. The use of buprenorphine to manage withdrawal then allows the individual to continue on this highly effective treatment.

Background and Aims The Australian Treatment Outcomes Profile (ATOP) is a brief instrument measuring recent substance use, risk profile and general health and wellbeing among clients attending alcohol and other drug (AoD) treatment services. This study evaluates the ATOP for concurrent validity, inter-rater and test–re-test reliability among alcohol and opioid treatment groups. Design For concurrent validity and inter-rater reliability, participants completed an ATOP with a clinician and an ATOP plus standardized questionnaires (time-line follow-back, Opiate Treatment Index, Kessler-10, 12-item Short Form Survey, World Health Organization Quality of Life-BREF, Personal Wellbeing Index) with a researcher within 3 days. For test–re-test reliability, participants completed two ATOPs with a researcher within a 3-day interval. Setting Outpatient AoD treatment centres in Australia. Participants For testing concurrent validity and inter-rater reliability, 278 participants were recruited by advertisements in waiting-rooms or clinician invitation during 2016 to 2018. A further 94 participants were recruited to examine test–re-test reliability. Measurements Statistical tests used for concurrent validity and test–re-test reliability were Pearson’s and Spearman’s rank order correlations for continuous variables, and Cohen’s κ for nominal variables. Inter-rater reliability was assessed using Krippendorf’s α. Findings Most Australian Treatment Outcomes Profile items returned excellent or moderate validity and reliability. For the main substances used—alcohol, cannabis and benzodiazepines—concurrent validity, inter-rater reliability and test–re-test reliability all reached excellent or good agreement (0.72–0.96). Psychological health, physical health and quality of life showed fair to strong agreement with their comparator scales (0.47–0.85). Conclusions The Australian Treatment Outcomes Profile is a validated and reliable instrument for assessing recent substance use and clinical risk, health and welfare among alcohol and opioid clients in alcohol and other drug treatment settings. Its ability to reliably measure complex constructs, such as psychological and physical health, against longer scales makes it suitable for integration into routine clinical care, enabling regular monitoring of patient outcomes and safety parameters.

Naloxone is a life-saving medication that reverses opioid overdose; naloxone can be provided on a 'take-home' basis so naloxone can be administered outside of the health-care setting. The Overdose Response and Take Home Naloxone (ORTHN) project established a model of care for take-home naloxone (THN) interventions across alcohol and other drug and harm reduction services in NSW, Australia. This paper evaluates the staff training and credentialing program, and examines staff attitudes and perspectives regarding the provision of THN interventions in these settings.Staff across seven services were trained through a 'train-the-trainer' credentialing model to deliver ORTHN, including naloxone supply. Staff were surveyed regarding their experience, attitudes and knowledge on THN prior to and after training, and after 6 months. At the 6 months follow up, staff were asked about the interventions they provided, barriers and enablers to uptake, and opinions regarding future rollout.A total of 204 staff were trained and credentialed to provide the ORTHN intervention. Most (60%) were nurses, followed by needle syringe program workers and allied health/counsellors (32%). Linear and logistic regression analyses indicated that the training program was associated with significant improvements in staff knowledge and attitudes towards overdose and THN; however, only attitudinal improvements were maintained over time. There were high rates of staff satisfaction with the ORTHN intervention and training.The ORTHN program is 'fit for purpose' for broad implementation in these settings. A number of potential barriers (e.g. time, medication and staffing costs) and enablers (e.g. peer engagement, regulatory framework for naloxone supply) in implementing THN interventions were identified.

Some evidence suggests that males and females may differ in their responses to acute cannabis effects, including subjective drug effects and behavioural effects, and cannabinoid pharmacokinetics. This is significant given current changes to cannabis-related policies and, in consequence, increased cannabis accessibility. The present study combines data from two randomized controlled trials to investigate possible differences among males (n = 21) and females (n = 19) in the acute effects of vaporized cannabis containing 13.75 mg Delta 9-tetrahydrocannabinol (THC), with and without cannabidiol (CBD; 13.75 mg). To control for differences in the timing of assessments, peak (or peak change from baseline) scores were calculated for a range of measures including subjective drug effects, cognitive performance, cardiovascular effects, and plasma concentrations of THC, CBD, and their respective primary metabolites. While THC elicited robust and significant changes in all but one outcome measure relative to placebo, relatively few sex differences were observed after controlling for BMI and plasma THC concentrations. Relative to females, males performed better overall on a divided attention task (DAT) and had higher peak plasma concentrations of 11-nor-9-carboxy-THC (11-COOH-THC). Males and females did not differ with respect to plasma concentrations of any other analyte, subjective drug effects, or cardiovascular measures. These data indicate an absence of systematic sex differences in acute cannabis effects given a moderate dose of vaporized cannabis. They do not preclude the possibility that sex differences may emerge with higher THC doses or with other commonly used routes of administration (e.g., orally administered oils or edibles).

Background and aims Not all people experiencing opioid dependence benefit from oral opioid agonist treatment. The aim of this study was to examine perceptions of (supervised) injectable opioid agonist treatment (iOAT) (described as ‘an opioid similar to heroin self‐injected at a clinic several times a day’) among people who regularly use opioids and determine how common iOAT eligibility criteria accord with interest in iOAT. Design Cross‐sectional survey Setting Sydney, Melbourne and Hobart, Australia. Participants A total of 344 people (63% male) who use opioids regularly and had ever injected opioids, interviewed December 2017–March 2018. The mean age of participants was 41.5 years [standard deviation (SD) = 8.5]. Measurements Primary outcome measures were interest in iOAT, factors associated with interest and the proportion of participants who would be eligible using common criteria from trials and guidelines. We examined willingness to travel for iOAT, medication preferences and perspectives on whom should receive iOAT. Findings Overall, 53% of participants (n = 182) believed that iOAT would be a good treatment option for them. Participants who believed that iOAT was a good treatment option for them were more likely to be male [adjusted odds ratio (aOR) = 1.76, 95% confidence interval (CI) = 1.10–2.82], have used heroin in the past month (aOR = 6.03, 95% CI = 2.86–12.71), currently regularly inject opioids (aOR = 1.84, 95% CI = 1.16–2.91) and have met ICD‐10 criteria for opioid dependence (aOR = 3.46, 95% CI = 1.65–7.24). Those interested in iOAT had commenced more treatment episodes (aOR =1.06, 95% CI = 1.00–1.12). Among those interested in iOAT (n = 182), 26% (n = 48) met common eligibility criteria for iOAT. Conclusions Interest in injectable opioid agonist treatment does not appear to be universal among people who regularly use opioids. Among study participants who expressed interest in injectable opioid agonist treatment, most did not meet common eligibility criteria.

Introduction and Aims: The Australian Treatment Outcomes Profile (ATOP) is a brief clinical tool measuring recent substance use, health and wellbeing among clients attending alcohol and other drug (AOD) treatment services. It has previously been assessed for concurrent validity and inter-rater reliability. In this study we examine whether it is suitable for administration over the telephone. Design and Methods: We recruited a sample of 107 AOD clients across public sector specialist AOD treatment services in New South Wales, Australia between 2016 and 2018. Participants had a mean age of 47 years and 46% were female. Participants completed a face-to-face ATOP and a phone ATOP with a researcher within 5 days. Comparisons between the two administration modes were undertaken using Spearman’s rank correlation coefficient for continuous or ordinal variables, and Cohen’s Kappa for nominal variables. Results. Among 107 participants, 59% were attending for alcohol treatment and 41% for opioid treatment. Most ATOP items (76%) reached above 0.7 (good) or 0.9 (excellent) agreement between face-to-face and telephone use. Discussion and Conclusions: Our findings suggest that the ATOP is a suitable instrument for telephone monitoring of recent substance use, health and social functioning among AOD clients. Its validation for remote use over the telephone will support staff to monitor clients’ risks and outcomes—of particular relevance in response to the COVID-19 pandemic in which services are increasingly relying on telework approaches to client monitoring.

Background Stimulant drugs are second only to cannabis as the most widely used class of illicit drug globally, accounting for 68 million past-year consumers. Dependence on amphetamines (AMPH) or methamphetamine (MA) is a growing global concern. Yet, there is no established pharmacotherapy for AMPH/MA dependence. A comprehensive assessment of the research literature on pharmacotherapy for AMPH/MA dependence may inform treatment guidelines and future research directions. Methods We systematically reviewed the peer-reviewed literature via the electronic databases PubMed, EMBASE, CINAHL and SCOPUS for randomised controlled trials reported in the English language examining a pharmacological treatment for AMPH/MA dependence or use disorder. We included all studies published to 19 June 2019. The selected studies were evaluated for design; methodology; inclusion and exclusion criteria; sample size; pharmacological and (if included) psychosocial interventions; length of follow-up and follow-up schedules; outcome variables and measures; results; overall conclusions and risk of bias. Outcome measures were any reported impact of treatment related to AMPH/MA use. Results Our search returned 43 studies that met our criteria, collectively enrolling 4065 participants and reporting on 23 individual pharmacotherapies, alone or in combination. Disparate outcomes and measures (n = 55 for the primary outcomes) across studies did not allow for meta-analyses. Some studies demonstrated mixed or weak positive signals (often in defined populations, e.g. men who have sex with men), with some variation in efficacy signals dependent on baseline frequency of AMPH/MA use. The most consistent positive findings have been demonstrated with stimulant agonist treatment (dexamphetamine and methylphenidate), naltrexone and topiramate. Less consistent benefits have been shown with the antidepressants bupropion and mirtazapine, the glutamatergic agent riluzole and the corticotropin releasing factor (CRF-1) antagonist pexacerfont; whilst in general, antidepressant medications (e.g. selective serotonin reuptake inhibitors [SSRIs], tricyclic antidepressants [TCAs]) have not been effective in reducing AMPH/MA use. Conclusions No pharmacotherapy yielded convincing results for the treatment of AMPH/MA dependence; mostly studies were underpowered and had low treatment completion rates. However, there were positive signals from several agents that warrant further investigation in larger scale studies; agonist therapies show promise. Common outcome measures should include change in use days. Future research must address the heterogeneity of AMPH/MA dependence (e.g. coexisting conditions, severity of disorder, differences between MA and AMPH dependence) and the role of psychosocial intervention. Electronic supplementary material The online version of this article (10.1007/s40263-020-00711-x) contains supplementary material, which is available to authorized users.

Alcohol and other drug (AOD) use is common in Australia with significant health and community impacts. General practitioners (GP) often see people with AOD use; however, there is little research to understand how specialist AOD services could assist GPs in the management of patients with AOD issues.Thirty-five GPs working in general practice in a metropolitan area in Sydney in New South Wales, Australia, participated in one of three focus groups. The groups were recorded, transcribed and thematically analysed.The five themes raised by participants were: GP personal agency and interest in AOD issues; GP education and training gaps; improving pathways between GP and specialist AOD services; easier access to AOD specialist advice; and improving access to collaborative care for patients with complex AOD presentations. Participants requested education on screening, assessing, managing AOD issues, focused on alcohol, stimulants and high-risk prescription medicines. They suggested better referral processes, discharge summaries and care planning for complex presentations. Participants wanted easy access to specialist advice and suggested collaborative care assisted by experienced AOD liaison nurses.Australia has several existing programs; online referral pathways and specialist phone advice, that address some of the issues raised. Unfortunately, many participants were not aware of these. GP education must be supported by multiple processes, including durable referral pathways, ready access to local specialist advice, clear communication (including patient attendance and a treatment plan), care planning and written summaries.

Prior research has examined the prevalence and correlates of cannabis use disorder (CUD) in people who use cannabis; however, these are poorly described for people using cannabis for medical reasons.Data came from a 2018 to 2019 online, anonymous, cross-sectional survey of Australians reporting using either illicit or licit cannabis for medical reasons within the past year. Included were questions on demographics, current and lifetime patterns of cannabis use, clinical conditions for which medical cannabis was used, and individual criteria for CUD and cannabis withdrawal syndrome. Bayesian Horseshoe logistic regression models were used to identify covariates associated with meeting CUD DSM-5 conditions for any-CUD (≥2/11 criteria) and moderate-severe-CUD (≥4/11).A total of 905 participants were included in the analysis. The majority (98%) used illicit cannabis products. Criteria for any-CUD criteria were met by 290 (32.0%), and 117 (12.9%) met criteria for moderate-severe-CUD. Tolerance (21%) and withdrawal (35%) were the most commonly met criteria. Correlates with the strongest association with CUD were inhaled route of administration [odds ratio (OR) = 2.96, 95% credible interval 1.11, 7.06], frequency of cannabis use (OR = 1.24, 1.11-1.35), proportion of cannabis for medical reasons (OR = 0.83, 0.74, 0.94), frequency of tobacco use (OR = 1.10, 1.03, 1.17), age (OR = 0.75, 0.64, 0.90) and pain as main clinical indication (OR = 0.58, 0.36, 1.00).Prevalence of CUD in medical cannabis users appears comparable to 'recreational' users, with many similar correlates. CUD was associated with using cannabis to treat mental health rather than pain conditions and inhaled over other routes of administration.

Although most unintentional opioid deaths in Australia are attributed to pharmaceutical opioids, take-home naloxone (THN) programmes have to date predominantly targeted people using illicit opioids in drug treatment and harm reduction settings. We sought to examine the feasibility of delivering THN brief interventions (THN-BIs) with intranasal naloxone in EDs.This pilot feasibility study was conducted across three major metropolitan EDs in Sydney and Melbourne. ED staff were surveyed about their perspectives regarding THN before completing a 30-min training programme in THN-BI delivery. Patients presenting with opioid overdose or considered high risk for future overdose were eligible to receive the THN-BI. Staff survey responses were compared between hospitals and provider types using one-way analysis of variances. Patient demographic and clinical characteristics were extracted from medical records and compared between hospitals and overdose type using Fisher's exact test and one-way analysis of variances.One hundred and twenty-two ED staff completed the survey. One hundred and ten (90.2%) agreed that EDs should provide THN-BIs, whereas 23 (19.2%) identified time constraints and 17 (12.9%) felt uncomfortable discussing overdose with patients. Fifty-seven patients received the THN-BI, with the majority (n = 50, 87.7%) having presented following opioid overdose. The median age was 44 years and 40 (71.4%) were men. Two-thirds of the overdoses (n = 31, 66.0%) were attributed to heroin with one-third (n = 16, 34%) being attributed to pharmaceutical opioids.ED-based delivery of THN-BIs can reach a wide range of individuals at-risk of overdose. The present study supports the feasibility of THN interventions in EDs and underscores the importance of addressing implementation barriers including staff training.

Despite recent approval of pharmaceutical-grade cannabis products for the treatment of childhood epilepsy, some families continue to use artisanal cannabis products as a way to manage seizures in their children. However, such products are typically of unknown composition and quality, and may therefore pose an unpredictable health risk to the child. In the present analysis, 78 samples of cannabis products collected (as part of a previous study) from families of children with epilepsy (average age 8.8 ± 4.6 years) were analyzed for heavy metals (arsenic, cadmium, lead, and mercury), residual solvents (panel of 19 solvents) and pesticides (panel of 57 pesticides). Due to small sample volumes obtained, only a subset of samples was used in each analysis. Results showed that no cannabis sample exceeded the toxicity limits for heavy metals (n = 51 samples tested). Of the 58 cannabis samples tested for residual solvents, 17 (29%) contained concentrations of ethanol or isopropanol above the generally accepted limit of 5000 parts per million. With the volumes consumed, it was thought unlikely that children were consuming hazardous amounts of residual solvents, although this could not be ruled out in every case. Most samples (n = 31 samples tested) yielded inconclusive results for the pesticides, although one sample contained concentrations of bifenthrin that were 4.9 times higher than the acceptable limit. Overall, these results highlight the need for improved access to quality-assured cannabis products and the education of doctors, patients, and artisanal manufacturers around the contaminant exposure risk in unregulated cannabis products.

Background Opioid agonist treatment (OAT) is an effective intervention for opioid dependence. Extended-release buprenorphine injections (BUP-XR) may have additional potential benefits over sublingual buprenorphine. This single-arm trial evaluated outcomes among people receiving 48 weeks of BUP-XR in diverse community healthcare settings in Australia, permitting examination of outcomes when BUP-XR is delivered in standard practice. Methods Participants were recruited from a network of specialist public drug treatment services, primary care and some private practices in three states. Following a minimum 7 days on 8–32 mg of sublingual buprenorphine (±naloxone), participants received monthly subcutaneous BUP-XR injections administered by a healthcare practitioner and completed monthly research interviews. The primary endpoint was retention in treatment at 48 weeks. Findings Participants (n = 100) were 28% women, mean age 44 years with a long history of OAT (median 5.8 years); heroin was the most common opioid of concern (58%). Treatment retention at 24 and 48 weeks was 86% and 75%, respectively. Participants with past-month injecting drug use (OR 0.23; 95%CI: 0.09–0.61) or heroin use (OR 0.23; 95%CI: 0.08–0.65) at baseline had lower odds of being retained in treatment to 48 weeks. Reductions in multiple forms of extra-medical drug use were observed. Improvements in quality of life, participation in employment, and treatment satisfaction measures were also observed. Interpretation This real-world implementation study of BUP-XR demonstrated high retention and treatment satisfaction. This study provides important additional data on the uptake and experience of clients, with relevance for policy makers, health service planners, administrators, and practitioners. Funding Indivior. Trial registration ClinicalTrials.gov Identifier: NCT03809143

Introduction Despite decreasing consumption by general populations, use of synthetic cannabinoid receptor agonists (SCRAs) persists in some marginalised groups, including those who use other substances. This article explores SCRA consumption in an Australian cannabis treatment sample, comparing those who report ever using SCRAs with those who have never used SCRAs. Methods A questionnaire orally administered in person to a convenience sample of 154 cannabis treatment service clients from New South Wales, Australia (71% male, median age 35) collected information regarding cannabis and SCRA use including motivations, effects and health-related consequences of use, demographics, other substance use and overall health. Demographic profiles and between-group differences were explored. McNemar tests compared effects of SCRA and cannabis. Logistic regression analysis determined predictors of SCRA use. Results Half (53%) reported lifetime SCRA use; 20% reported previous-month use. The SCRA + cannabis group displayed greater polysubstance use and psychological distress. Reduced dependence on cannabis but higher levels of other substance use may predict SCRA use. Although curiosity motivated initial SCRA consumption, perceived psychoactive strength drove continued use. SCRAs appear to induce more negative side-effects than cannabis. Of the SCRA + cannabis group, 27% sought medical assistance for SCRA use. Most (90%) preferred cannabis to SCRAs, citing superior safety, effects and consistency of cannabis. Conclusions Among clients seeking treatment for cannabis use, SCRA use was relatively common, although not a preferred substance. Hazardous substance use and poor mental health characterised SCRA consumers, highlighting the need for continued monitoring by researchers and treatment providers of SCRA consumption in populations who use substances.

Summary of recommendations and levels of evidence Chapter 2: Screening and assessment for unhealthy alcohol use Screening Screening for unhealthy alcohol use and appropriate interventions should be implemented in general practice (Level A), hospitals (Level B), emergency departments and community health and welfare settings (Level C). Quantity–frequency measures can detect consumption that exceeds levels in the current Australian guidelines (Level B). The Alcohol Use Disorders Identification Test (AUDIT) is the most effective screening tool and is recommended for use in primary care and hospital settings. For screening in the general community, the AUDIT-C is a suitable alternative (Level A). Indirect biological markers should be used as an adjunct to screening (Level A), and direct measures of alcohol in breath and/or blood can be useful markers of recent use (Level B). Assessment Assessment should include evaluation of alcohol use and its effects, physical examination, clinical investigations and collateral history taking (Level C). Assessment for alcohol-related physical problems, mental health problems and social support should be undertaken routinely (GPP). Where there are concerns regarding the safety of the patient or others, specialist consultation is recommended (Level C). Assessment should lead to a clear, mutually acceptable treatment plan which specifies interventions to meet the patient’s needs (Level D). Sustained abstinence is the optimal outcome for most patients with alcohol dependence (Level C). Chapter 3: Caring for and managing patients with alcohol problems: interventions, treatments, relapse prevention, aftercare, and long term follow-up Brief interventions Brief motivational interviewing interventions are more effective than no treatment for people who consume alcohol at risky levels (Level A). Their effectiveness compared with standard care or alternative psychosocial interventions varies by treatment setting. They are most effective in primary care settings (Level A). Psychosocial interventions Cognitive behaviour therapy should be a first-line psychosocial intervention for alcohol dependence. Its clinical benefit is enhanced when it is combined with pharmacotherapy for alcohol dependence or an additional psychosocial intervention (eg, motivational interviewing) (Level A). Motivational interviewing is effective in the short term and in patients with less severe alcohol dependence (Level A). Residential rehabilitation may be of benefit to patients who have moderate-to-severe alcohol dependence and require a structured residential treatment setting (Level D). Alcohol withdrawal management Most cases of withdrawal can be managed in an ambulatory setting with appropriate support (Level B). Tapering diazepam regimens (Level A) with daily staged supply from a pharmacy or clinic are recommended (GPP). Pharmacotherapies for alcohol dependence Acamprosate is recommended to help maintain abstinence from alcohol (Level A). Naltrexone is recommended for prevention of relapse to heavy drinking (Level A). Disulfiram is only recommended in close supervision settings where patients are motivated for abstinence (Level A). Some evidence for off-label therapies baclofen and topiramate exists, but their side effect profiles are complex and neither should be a first-line medication (Level B). Peer support programs Peer-led support programs such as Alcoholics Anonymous and SMART Recovery are effective at maintaining abstinence or reductions in drinking (Level A). Relapse prevention, aftercare and long-term follow-up Return to problematic drinking is common and aftercare should focus on addressing factors that contribute to relapse (GPP). A harm-minimisation approach should be considered for patients who are unable to reduce their drinking (GPP). Chapter 4: Providing appropriate treatment and care to people with alcohol problems: a summary for key specific populations Gender-specific issues Screen women and men for domestic abuse (Level C). Consider child protection assessments for caregivers with alcohol use disorder (GPP). Explore contraceptive options with women of reproductive age who regularly consume alcohol (Level B). Pregnant and breastfeeding women Advise pregnant and breastfeeding women that there is no safe level of alcohol consumption (Level B). Pregnant women who are alcohol dependent should be admitted to hospital for treatment in an appropriate maternity unit that has an addiction specialist (GPP). Young people Perform a comprehensive HEEADSSS assessment for young people with alcohol problems (Level B). Treatment should focus on tangible benefits of reducing drinking through psychotherapy and engagement of family and peer networks (Level B). Aboriginal and Torres Strait Islander peoples Collaborate with Aboriginal or Torres Strait Islander health workers, organisations and communities, and seek guidance on patient engagement approaches (GPP). Use validated screening tools and consider integrated mainstream and Aboriginal or Torres Strait Islander-specific approaches to care (Level B). Culturally and linguistically diverse groups Use an appropriate method, such as the “teach-back” technique, to assess the need for language and health literacy support (Level C). Engage with culture-specific agencies as this can improve treatment access and success (Level C). Sexually diverse and gender diverse populations Be mindful that sexually diverse and gender diverse populations experience lower levels of satisfaction, connection and treatment completion (Level C). Seek to incorporate LGBTQ-specific treatment and agencies (Level C). Older people All new patients aged over 50 years should be screened for harmful alcohol use (Level D). Consider alcohol as a possible cause for older patients presenting with unexplained physical or psychological symptoms (Level D). Consider shorter acting benzodiazepines for withdrawal management (Level D). Cognitive impairment Cognitive impairment may impair engagement with treatment (Level A). Perform cognitive screening for patients who have alcohol problems and refer them for neuropsychological assessment if significant impairment is suspected (Level A). Summary of key recommendations and levels of evidence Chapter 5: Understanding and managing comorbidities for people with alcohol problems: polydrug use and dependence, co-occurring mental disorders, and physical comorbidities Polydrug use and dependence Active alcohol use disorder, including dependence, significantly increases the risk of overdose associated with the administration of opioid drugs. Specialist advice is recommended before treatment of people dependent on both alcohol and opioid drugs (GPP). Older patients requiring management of alcohol withdrawal should have their use of pharmaceutical medications reviewed, given the prevalence of polypharmacy in this age group (GPP). Smoking cessation can be undertaken in patients with alcohol dependence and/or polydrug use problems; some evidence suggests varenicline may help support reduction of both tobacco and alcohol consumption (Level C). Co-occurring mental disorders More intensive interventions are needed for people with comorbid conditions, as this population tends to have more severe problems and carries a worse prognosis than those with single pathology (GPP). The Kessler Psychological Distress Scale (K10 or K6) is recommended for screening for comorbid mental disorders in people presenting for alcohol use disorders (Level A). People with alcohol use disorder and comorbid mental disorders should be offered treatment for both disorders; care should be taken to coordinate intervention (Level C). Physical comorbidities Patients should be advised that alcohol use has no beneficial health effects. There is no clear risk-free threshold for alcohol intake. The safe dose for alcohol intake is dependent on many factors such as underlying liver disease, comorbidities, age and sex (Level A). In patients with alcohol use disorder, early recognition of the risk for liver cirrhosis is critical. Patients with cirrhosis should abstain from alcohol and should be offered referral to a hepatologist for liver disease management and to an addiction physician for management of alcohol use disorder (Level A). Alcohol abstinence reduces the risk of cancer and improves outcomes after a diagnosis of cancer (Level A).

Point-of-collection testing (POCT) for Δ9 -tetrahydrocannabinol (THC) in oral fluid is increasingly used to detect driving under the influence of cannabis (DUIC). However, previous studies have questioned the reliability and accuracy of two commonly used POCT devices, the Securetec DrugWipe® 5s (DW5s) and Dräger DrugTest® 5000 (DT5000). In the current placebo controlled, double-blind, crossover study we used LC-MS/MS to accurately quantify cannabinoid concentrations in the oral fluid of fourteen participants at various timepoints (10, 60, 120 and 180 mins) following vaporization of 125 mg of THC-dominant (11% THC; 80% sensitivity, specificity and accuracy. Accuracy was lowest at 60 min, when THC concentrations were often close to the screening cut-off (10 ng/mL). POCT devices can be useful tools in detecting recent cannabis use; however, limitations should be noted, and confirmatory LC-MS/MS quantification of results is strongly advisable.

Background Buprenorphine is widely used in the treatment of opioid use disorder and pain management. Little is known about the analgesic effects of high-dose sublingual buprenorphine, particularly in doses of >8 mg. The aim of this study was to examine the effect of ascending doses of buprenorphine upon acute pain measures in patients stabilized on buprenorphine as treatment for opioid dependence. Methods The pilot study (n = 7) was a randomised, controlled, double-blind, double-dummy, within-subject crossover study examining cold-pressor threshold and tolerance testing under different buprenorphine dose conditions. Each participant attended three sessions to test the analgesic effect of buprenorphine in their usual dose (100%), 150% and 200% of their usual daily dose. Results No significant effects of increased dose were seen on experimental pain measures. Expected physiological effects on pupil size and pulse were observed with increasing dose. No effect of buprenorphine condition was seen on subjective ratings of drug strength, or self-reported sedation, though lower ratings drug liking were seen with 150% and 200% conditions, and lower ratings of ‘bad effects’ and intoxication were reported with the 200% buprenorphine dose condition. No safety concerns with the 150 and 200% buprenorphine dose condition were observed. Discussion This pilot study suggests that a ceiling effect on analgesia may be observed in people maintained on buprenorphine, though larger studies may confirm this finding. Clinical Trial Number: ACTRN12614001038684.

ObjectiveThe study objective was to identify the analgesic efficacy of three different pharmacological strategies in patients receiving methadone or buprenorphine as opioid agonist treatment (OAT). The three pharmacological approaches, a) increasing maintenance methadone/buprenorphine dose by 30%, b) adding oxycodone, or c) adding a single dose of gabapentin, were compared with a control condition of the participant’s usual OAT dose.DesignA randomized, controlled, double-blinded, double-dummy, within-subject crossover study.SubjectsNine participants on stable doses of methadone and eight participants on stable doses of buprenorphine were recruited.SettingAn outpatient opioid treatment clinic in inner city Sydney, Australia.MethodsThe cold pressor tolerance test was used to examine experimental pain threshold and tolerance. Ratings of subjective drug effects and safety measures (physiological and cognitive) were assessed.ResultsThere was no difference in the primary outcome measures of pain thresholds or tolerance between the conditions examined. Interindividual variability was evident. Differences in some subjective measures were identified, including lower pain recall, lower “bad effects,” and higher global satisfaction in the additional methadone condition. In the buprenorphine arm, increased drug liking and “bad effects” were detected with oxycodone administration, while increased subjective intoxication was identified with gabapentin.ConclusionsThere was no evidence of an objective improvement in analgesia with any condition compared with control. Further research is required to optimize pain management strategies in this population.

Policies to address opioid-related harms include strategies to reduce opioid prescribing for new and ongoing pain management. Concerns have been raised that people with chronic non-cancer pain (CNCP) may be adversely affected by prescribing restrictions, and by involuntary tapering and cessation of opioids. We describe self-reported challenges obtaining prescription opioids among people prescribed opioids long-term for CNCP and explore associations with participant and treatment characteristics.This cross-sectional study analysed data from a longitudinal cohort study of Australians prescribed restricted opioids for CNCP. In 2018, 861 participants who took part in Year 5 follow-up and who also reported past 12-month opioid use were asked about challenges obtaining opioid prescriptions, including prescriber access-related difficulties obtaining prescriptions or having opioids tapered or ceased involuntarily. Associations between challenges and demographics, treatment characteristics including daily opioid dose as oral morphine equivalent milligrams (OME mg/day), substance use disorder (SUD), and opioid dependence were assessed.Overall, 285 (31%) participants reported at least one challenge, predominantly prescriber access-related difficulties (n=177/285; 62%). Prescriber access-related difficulties were associated with younger age (adjustedOR 0.94 per year increase, 95%CI 0.93-0.96), and past 12-month pharmaceutical opioid dependence (adjustedOR 2.25, 95%CI 1.33-3.80). Involuntary opioid tapering or cessation was reported by 73 participants (26% of those reporting challenges) and was associated with lifetime SUD diagnosis (adjustedOR 2.15, 95%CI 1.15-3.90), and opioid doses of ≥200 OME mg/day (adjustedOR 2.41, 95%CI 1.18-4.88).One-third of participants with CNCP reported experiencing challenges obtaining prescriptions for opioids or having their opioid medicines involuntarily reduced. Given increasing restrictions to opioid access, it is important that strategies to reduce opioid-related harms are balanced against the current treatment needs of people prescribed opioids long-term for CNCP.

The mainstay of treatment for opioid use disorder are medications, methadone (a full opioid agonist), or buprenorphine (a partial opioid agonist), in conjunction with psychosocial interventions. Both treatments are effective but safety, efficacy, and patient preference can lead to a decision to change from one treatment to the other. Transfer from buprenorphine to methadone is not clinically challenging; however, changing from methadone to buprenorphine is more complex. Published reports describe varied approaches to manage this transfer to both minimize patient symptoms associated with withdrawal from methadone and reduce risk of precipitating withdrawal symptoms with introduction of the partial agonist buprenorphine [Lintzeris et al. J Addict Med. 2020; in press]. There is no single approach for methadone to buprenorphine that is superior to others and no approach that is suitable for all case presentations. This case conference describes three different approaches to achieve a successful methadone to buprenorphine transfer and provides commentary on how the case may be managed based on published transfer "strategies."