Cytochrome P450-2D6 activity in people with codeine use disorder.

Compound-analgesics containing codeine (CACC) have been a common source of codeine for people seeking opioid replacement therapy (ORT) for codeine use disorder (CUD). Our previous work demonstrated no relationship between pre-treatment CACC and ORT buprenorphine doses; we hypothesised that CYP2D6 activity would partially account for this disconnection. One hundred six participants with CUD were compared to a published population sample of 5408 Australian patients. Mean age of participants with CUD at treatment entry was 35 years, with mean 6.1 years duration of CUD. Mean codeine dose was 660 mg/day (range 40-2700 mg). Mean calculated CYP2D6 activity scores were significantly higher in the codeine group (CUD 1.65 + 0.63 vs. Gen pop 1.39 + 0.65, Wilcoxon W = 347,001, p < 0.001). Pre-treatment CACC dose weakly predicted sublingual buprenorphine doses overall; there was a stronger relationship within ultrarapid metabolisers. While normal and ultrarapid metabolisers of codeine were more likely to have a diagnosis of CUD, poor or intermediate CYP2D6 metaboliser status may protect against CUD.

Should psychiatrists support the availability of nicotine e-cigarettes in Australia?

OBJECTIVE: To examine the position statement of the Royal Australian and New Zealand College of Psychiatrists (RANZCP) regarding the availability of electronic cigarettes in Australia. CONCLUSION: There is limited evidence supporting the efficacy of nicotine e-cigarettes as an effective tobacco harm-reduction or cessation strategy for people with mental illness. The recommendations to increase their availability under regulation must be balanced with the physical and mental health risks of vapour inhalation and nicotine use, particularly for youth. Future recommendations by the RANZCP in relation to e-cigarettes must consider both the available evidence for harm reduction and the potential risks associated with youth e-cigarette use.

Craving Mediates Stress in Predicting Lapse During Alcohol Dependence Treatment.

BACKGROUND: Stress, craving, and depressed mood have all been implicated in alcohol use treatment lapses. Few studies have examined all 3 factors. Progress has been limited because of difficulties with craving assessment. The Alcohol Craving Experience Questionnaire (ACE) is a new measure of alcohol craving. It is both psychometrically sound and conceptually rigorous. This prospective study examines a stress-treatment response model that incorporates mediation by craving and moderation by depressed mood and pharmacotherapy. METHODS: Five hundred and thirty-nine consecutively treated alcohol-dependent patients voluntarily participated in an abstinence-based 12-week cognitive-behavioral therapy (CBT) program at a hospital alcohol and drug outpatient clinic. Measures of stress, craving, depressed mood, and alcohol dependence severity were administered prior to treatment. Treatment lapse and treatment dropout were assessed over the 12-week program duration. RESULTS: Patients reporting greater stress experienced stronger and more frequent cravings. Stronger alcohol craving predicted lapse, after controlling for dependence severity, stress, depression, and pharmacotherapy. Alcohol craving mediated stress to predict lapse. Depressed mood and anticraving medication were not significant moderators. CONCLUSIONS: Among treatment seeking, alcohol-dependent patients, craving mediated the relationship between stress and lapse. The effect was not moderated by depressed mood or anticraving medication.

The Quik Fix study: a randomised controlled trial of brief interventions for young people with alcohol-related injuries and illnesses accessing emergency department and crisis support care.

BACKGROUND: Alcohol is a major preventable cause of injury, disability and death in young people. Large numbers of young people with alcohol-related injuries and medical conditions present to hospital emergency departments (EDs). Access to brief, efficacious, accessible and cost effective treatment is an international health priority within this age group. While there is growing evidence for the efficacy of brief motivational interviewing (MI) for reducing alcohol use in young people, there is significant scope to increase its impact, and determine if it is the most efficacious and cost effective type of brief intervention available. The efficacy of personality-targeted interventions (PIs) for alcohol misuse delivered individually to young people is yet to be determined or compared to MI, despite growing evidence for school-based PIs. This study protocol describes a randomized controlled trial comparing the efficacy and cost-effectiveness of telephone-delivered MI, PI and an Assessment Feedback/Information (AF/I) only control for reducing alcohol use and related harm in young people. METHODS/DESIGN: Participants will be 390 young people aged 16 to 25 years presenting to a crisis support service or ED with alcohol-related injuries and illnesses (including severe alcohol intoxication). This single blinded superiority trial randomized young people to (i) 2 sessions of MI; (ii) 2 sessions of a new PI or (iii) a 1 session AF/I only control. Participants are reassessed at 1, 3, 6 and 12 months on the primary outcomes of alcohol use and related problems and secondary outcomes of mental health symptoms, functioning, severity of problematic alcohol use, alcohol injuries, alcohol-related knowledge, coping self-efficacy to resist using alcohol, and cost effectiveness. DISCUSSION: This study will identify the most efficacious and cost-effective telephone-delivered brief intervention for reducing alcohol misuse and related problems in young people presenting to crisis support services or EDs. We expect efficacy will be greatest for PI, followed by MI, and then AF/I at 1, 3, 6 and 12 months on the primary and secondary outcome variables. Telephone-delivered brief interventions could provide a youth-friendly, accessible, efficacious, cost-effective and easily disseminated treatment for addressing the significant public health issue of alcohol misuse and related harm in young people. TRIAL REGISTRATION: This trial is registered with the Australian and New Zealand Clinical Trials Registry ACTRN12613000108718.

An Australian retrospective observational cohort comparison of the use of long-acting injectable buprenorphine products.

INTRODUCTION: In early 2019, Australia became the first jurisdiction to have two brands of long-acting injectable buprenorphine (LAI-B) products available. Previously published studies have mostly followed pre-planned dosing schedules and seldom compared use of both products. This study presents a retrospective analysis of the "real-world" dosing requirements of patients on LAI-B. METHOD: Five clinics provided data for patients commenced on LAI-B between 1 February 2019 and 30 June 2021 for buprenorphine doses and intervals between dosing. The study recorded basic demographic data including age, gender, and previous dose of transmucosal buprenorphine. The Local Institutional Ethics Committee provided approval. RESULTS: Over 3600 individual doses (59 % Buvidal® & 41 % Sublocade®) were administered to 340 individual patients (median age 40 years, 63 % male), with the longest duration in treatment of 856 days. Median estimated duration of a treatment episode was 16.5 months (95%CI: 14.3-19.1). Approximately 94 % transferred from transmucosal buprenorphine (median daily dose 16 mg, range 2-32 mg). Most common LAI-B doses were Sublocade® 100 mg (22.4 %) and Buvidal® Monthly 128 mg (21.5 %); Buvidal® Weekly 24 mg (0.8 %) was least used. 13 % transitioned between LAI-B products. Weekly dose intervals were a median 7 days and monthly doses were given a median of 28 days apart. Overall, 36 % discontinued LAI-B before the census date. DISCUSSIONS AND CONCLUSIONS: Most patients who started LAI-B remained in treatment, with similar rates in both products. A small, but appreciable number of people switched brands, suggesting that it remains important to have treatment options available.

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.

Telephone-based motivational interviewing enhanced with individualised personality-specific coping skills training for young people with alcohol-related injuries and illnesses accessing emergency or rest/recovery services: a randomized controlled trial (QuikFix).

BACKGROUND AND AIMS: Recent meta-analyses of motivational interviewing (MI) for reducing risky alcohol use in young people have reported modest effects. Few studies have targeted individual patient factors to increase MI effectiveness. This study determined if MI enhanced with individualised personality-specific coping skills training (QuikFix) was more efficacious than standard MI or an assessment feedback/information (AF/I) control among young people with alcohol-related injuries or illnesses. DESIGN AND SETTING: Single-centre, single-blind, three-group superiority randomized controlled trial with 1-, 3-, 6- and 12-months follow-ups. Telephone intervention, Brisbane, Australia. PARTICIPANTS: A total of 398 young people (16-25 years; M age = 20.30 years, SD = 2.12; 54% female) with alcohol-related injuries and/or illnesses were recruited from an emergency department (ED) or rest/recovery service (RRS). MEASURES: The primary outcome was total standard (10 g ethanol) drinks in the past month (Timeline Follow back [TLFB]) at 12 months (primary time point). Secondary outcomes were total drinking days and standard drinks per drinking day (TLFB) in the past month and the frequency of alcohol-related problems in the past 3 months (Rutgers Alcohol Problem Index). INTERVENTIONS: Young people were randomized to two sessions of QuikFix enhanced with individualised personality-specific coping skills training (n = 132), two sessions of MI (n = 136) or one session of AF/I (n = 130), all delivered by telehealth. FINDINGS: QuikFix resulted in greater reductions (all P < 0.0017) in the primary outcome of total standard drinks (M = 19.50, CI 99.75% = [11.31, 27.68]) than both MI (M = 32.61, CI 99.75% = [24.82, 40.40]; Cohen's D = 0.40) and AF/I (M = 34.12, CI 99.75% = [26.59, 41.65]; D = 0.45) at 12 months (retention n = 324/398, 81%). QuikFix had greater reductions on drinking days (M = 3.16, CI 99.75% = [2.37, 3.96]) than both MI (M = 4.53, CI 99.75% = [3.57, 5.48];D = 0.38) and AF/I (M = 4.69, CI 99.75% = [3.73, 5.65];D = 0.42) and fewer drinks per drinking day (M = 5.02, CI 99.75% = [3.71, 6.33]) than AF/I (M = 7.15, CI 99.75% = [5.93, 8.38;D = 0.47) at 12 months. CONCLUSIONS: Young people with alcohol-related injuries and/or illnesses who attended ED and rest/recovery services and received an individualised personality-specific coping skills training intervention (QuikFix) had greater reductions in the amount of alcohol consumed at 12 months compared with those who received motivational interviewing or an assessment feedback/information intervention.

The Australian drug harms ranking study.

BACKGROUND/AIM: The aim of the current study was to review drug harms as they occur in Australia using the Multi-criteria Decision Analysis (MCDA) methodology adopted in earlier studies in other jurisdictions. METHOD: A facilitated workshop with 25 experts from across Australia, was held to score 22 drugs on 16 criteria: 9 related to harms that a drug produces in the individual and 7 to harms to others. Participants were guided by facilitators through the methodology and principles of MCDA. In open discussion, each drug was scored on each criterion. The criteria were then weighted using a process of swing weighting. Scoring was captured in MCDA software tool. RESULTS: MCDA modelling showed the most harmful substances to users were fentanyls (part score 50), heroin (part score 45) and crystal methamphetamine (part score 42). The most harmful substances to others were alcohol (part score 41), crystal methamphetamine (part score 24) and cigarettes/tobacco (part score 14). Overall, alcohol was the most harmful drug when harm to users and harm to others was combined. A supplementary analysis took into consideration the prevalence of each substance in Australia. Alcohol was again ranked the most harmful substance overall, followed by cigarettes, crystal methamphetamine, cannabis, heroin and pharmaceutical opioids. CONCLUSIONS: The results of this study make an important contribution to the emerging international picture of drug harms. They highlight the persistent and pervasive harms caused by alcohol. Policy implications and recommendations are discussed. Policies to reduce harm from alcohol and methamphetamine should be a priority.

A transdiagnostic dimensional approach towards a neuropsychological assessment for addiction: an international Delphi consensus study.

BACKGROUND: The US National Institutes of Mental Health Research Domain Criteria (RDoC) seek to stimulate research into biologically validated neuropsychological dimensions across mental illness symptoms and diagnoses. The RDoC framework comprises 39 functional constructs designed to be revised and refined, with the overall goal of improving diagnostic validity and treatments. This study aimed to reach a consensus among experts in the addiction field on the 'primary' RDoC constructs most relevant to substance and behavioural addictions. METHODS: Forty-four addiction experts were recruited from Australia, Asia, Europe and the Americas. The Delphi technique was used to determine a consensus as to the degree of importance of each construct in understanding the essential dimensions underpinning addictive behaviours. Expert opinions were canvassed online over three rounds (97% completion rate), with each consecutive round offering feedback for experts to review their opinions. RESULTS: Seven constructs were endorsed by ≥ 80% of experts as 'primary' to the understanding of addictive behaviour: five from the Positive Valence System (reward valuation, expectancy, action selection, reward learning, habit); one from the Cognitive Control System (response selection/inhibition); and one expert-initiated construct (compulsivity). These constructs were rated to be related differentially to stages of the addiction cycle, with some linked more closely to addiction onset and others more to chronicity. Experts agreed that these neuropsychological dimensions apply across a range of addictions. CONCLUSIONS: The study offers a novel and neuropsychologically informed theoretical framework, as well as a cogent step forward to test transdiagnostic concepts in addiction research, with direct implications for assessment, diagnosis, staging of disorder, and treatment.

Reduced thalamic grey matter volume in opioid dependence is influenced by degree of alcohol use: a voxel-based morphometry study.

The aim of this study was to make a comparison of brain structure between a group of opioid-dependent subjects and healthy controls. We report the results of an ;optimized' voxel-based morphometry study on a sample of nine opioid-dependent subjects with no comorbid substance misuse disorders versus 21 healthy controls. We found a significant reduction in grey matter volume of the thalamus after controlling for age and total grey matter volume. Regression analysis of substance use variables in the opioid-dependent sample shows that only level of alcohol use negatively predicts grey matter volume for this region of difference. We suggest that level of nondependent alcohol use could influence reduced thalamic grey matter volume in opioid-dependent subjects.

A qualitative study of patients' knowledge and views of about oral health and acceptability of related intervention in an Australian inpatient alcohol and drug treatment facility.

Social factors, health behaviours and the direct effects of substances contribute to the poor oral health and restricted access to dental services experienced by people who are dependent on drugs and/or alcohol. Admission for inpatient withdrawal management provides an opportunity for intervention to promote oral health but to be effective it must be acceptable to patients. To support intervention design, we examined patients' views about oral health, practices and treatment access, and appropriateness of health-promoting intervention in this context. Given paucity of knowledge in the area we employed a qualitative approach, data were collected in semi-structured interviews with inpatients of a public specialist alcohol and drug unit in Australia in September 2014. Analysis employed the framework approach. All 14 participants wanted 'good teeth' but few diligently attended to oral healthcare; most sought assistance only in emergencies. Participants' knowledge of services was limited and practical and affective barriers hindered access. With none recalling attention to oral health during admission, support was strong for incorporation of oral health in inpatient assessments. Participants wanted information about the impact of substances on oral health and oral hygiene practices provided in various formats, and facilitated referral to non-judgemental, affordable treatment. Patients regarded promotion of oral health in the inpatient context as important, relevant and acceptable. Support should respect the different knowledge, practices and motivations for oral health and recovery, of patients. Addressing practical and affective barriers to dental services will require collaboration between drug and alcohol and dental services, and this should be the focus of further research.

Human functional neuroimaging connectivity research in dependence.

Functional and effective connectivity are relatively new techniques in the analysis of functional neuroimaging studies in humans. They have previously been used in studies of 'normal' psychological and neurological processes such as vision before gradually transferring into use in pathological disease states such as schizophrenia. These techniques are now beginning to extend into the field of substance misuse and dependence. So far, most functional neuroimaging studies in this field have shown consistent patterns of activation in several brain regions, and theories are emerging based upon these and animal models. Studies of brain connectivity can now begin to help further unravel the tangle of disparate brain regions and their connections that underpin the psychopharmacological processes of dependence.

Alcohol-related emergency department injury presentations in Queensland adolescents and young adults over a 13-year period.

INTRODUCTION AND AIMS: The rate of alcohol-related emergency department (ED) presentations in young people has increased dramatically in recent decades. Injuries are the most common type of youth alcohol-related ED presentation, yet little is known about these injuries in young people. This paper describes the characteristics of alcohol-related ED injury presentations in young people over a 13-year period and determines if they differ by gender and/or age group (adolescents: 12-17 years; young adults: 18-24 years). DESIGN AND METHOD: The Queensland Injury Surveillance Unit (QISU) database collects injury surveillance data at triage in participating EDs throughout Queensland, Australia. A total of 4667 cases of alcohol-related injuries in young people (aged 12-24 years) were identified in the QISU database between January 1999 and December 2011, using an injury surveillance code and nursing triage text-based search strategy. RESULTS: Overall, young people accounted for 38% of all QISU alcohol-related ED injury presentations in patients aged 12 years or over. The majority of young adults presented with injuries due to violence and falls, whereas adolescents presented due to self-harm or intoxication without other injury. Males presented with injuries due to violence, whereas females presented with alcohol-related self-harm and intoxication. DISCUSSION AND CONCLUSIONS: There is a need for more effective ways of identifying the degree of alcohol involvement in injuries among young people presenting to EDs.

Brain imaging studies in human addicts.

Addiction provides fertile ground for the application of the tools of functional neuroimaging. They can be divided into studies of neural activity and neurotransmitter function. Using the former, both opiates and stimulants cause a global decrease in brain metabolism. Against this background, acute doses have still been shown to produce relative increases in brain activation in specific regions, e.g., anterior cingulate, thalamus, and amygdala. These are also regions frequently found with cue-exposure paradigms. Our own work on cue-exposure has shown that heroin-related stimuli provoke activation of the anterior cingulate and orbitofrontal regions. Brain metabolism has also been shown to increase in drug withdrawal from alcohol and cocaine. Neurotransmitter studies have shown that in alcohol dependence, GABA(A)-benzodiazepine (GABA-BDZ) receptors are reduced in a number of brain regions and suggest that there may be 'capacity within the system' in some benzodiazepine functions, but tolerance to others, e.g., time asleep. Finally, 11C-Ro15-4513 offers new opportunities for imaging the GABA-BDZ system.

Dependent heroin use and associated risky behaviour: the role of rash impulsiveness and reward sensitivity.

Impulsive temperament has long been considered as a risk factor for substance use disorders (SUD). Considering the heterogeneity of impulsivity, a biologically-based 2-factor model incorporating reward sensitivity and rash impulsiveness facets, has been proposed. Here we report how these two facets of impulsiveness could be associated with different aspects of dependent heroin use and associated risky behaviour. Two hundred and ninety three dependent heroin users and 232 non-users were assessed on reward sensitivity, rash impulsivity, and the related trait of punishment sensitivity. After adjusting for multiple comparisons, heroin users were found to be more rash-impulsive and reward-sensitive than non-users (p<0.001). Within users, rash impulsivity was associated with high risk behaviour including escalating heroin consumption, injecting heroin use, hazardous drinking, low treatment-seeking and risky sexual behaviour. Reward sensitivity was uniquely associated with early onset of drug use. While greater impulsivity is a common trait in drug users compared with non-users, the use of a 2-factor model of impulsivity provides additional information regarding specific aspects of drug initiation and maintenance that can be targeted in the prevention and treatment of heroin dependence.

Screening for alcohol and drug use in pregnancy.

OBJECTIVE: this study examined the clinical utility and precision of routine screening for alcohol and other drug use among women attending a public antenatal service. STUDY DESIGN: a survey of clients and audit of clinical charts. PARTICIPANTS AND SETTING: clients attending an antenatal clinic of a large tertiary hospital in Queensland, Australia, from October to December 2009. MEASUREMENTS AND FINDINGS: data were collected from two sources. First, 32 women who reported use of alcohol or other drugs during pregnancy at initial screening were then asked to complete a full substance use survey. Second, data were collected from charts of 349 new clients who attended the antenatal clinic during the study period. Both sensitivity (86%, 67%) and positive predictive value (100%, 92%) for alcohol and other drug use respectively, were high. Only 15% of surveyed women were uncomfortable about being screened for substance use in pregnancy, yet the chart audit revealed poor staff compliance. During the study period, 25% of clients were either not screened adequately or not at all. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTISE: despite recommended universal screening in pregnancy and the apparent acceptance by our participants, alcohol and other drug (A&OD) screening in the antenatal setting remains problematic. Investigation into the reasons behind, and ways to overcome, the low screening rate could improve health outcomes for mothers and children in this at-risk group. Targeted education and training for midwives may form part of the solution as these clinicians have a key role in implementing prevention and early intervention strategies.

Prevalence of malnutrition and nutritional risk factors in patients undergoing alcohol and drug treatment.

OBJECTIVE: Chronic substance abuse is recognized to affect nutritional status and is associated with nutrient deficiencies and malnutrition. This study aimed to identify the prevalence of malnutrition and nutritional risk factors using a spread of measurements in patients undergoing alcohol and drug treatment. METHODS: Sixty-seven patients (48 male, 19 female) admitted to a public hospital detoxification unit participated: 49 were alcohol dependent (73%) and the remaining were opiate, benzodiazepine, and/or amphetamine dependent. Nutritional status was assessed by the Subjective Global Assessment. An appetite questionnaire (Simplified Nutritional Appetite Questionnaire), a diet-quality questionnaire (Australian Recommended Food Score), and blood biochemistry and hematologic tests were also applied. RESULTS: The prevalence of mild/moderate malnutrition was 24% according to the Subjective Global Assessment. Weight and body mass index were associated with nutritional status (P < 0.05). Appetite and diet quality were poor overall, with 88% of all participants requiring advice and guidance. Blood markers showed that 50% of all subjects were deficient in iron or vitamins (low vitamin A levels in 21%, low iron levels in 18%, low-range potassium in 12%, and low vitamin C levels in 8%). CONCLUSION: The prevalence of malnutrition in this patient population is likely to underestimate the prevalence of nutritional risk factors and micronutrient undernutrition. Multiple tools assessing nutritional status, appetite, diet quality, and blood test results have different advantages and can further identify the specific needs and appropriateness of nutritional education in patients during treatment for drug and alcohol use.

Brain opioid receptor binding in early abstinence from alcohol dependence and relationship to craving: an [11C]diprenorphine PET study.

The importance of the opioid receptor system in substance dependence is increasingly recognised. We used PET with the non-selective tracer [11C]diprenorphine to examine opioid receptor binding in early abstinence from alcohol dependence and the relationship to craving. We recruited 11 alcohol dependent patients and 13 controls. Subjects underwent one [11C]diprenorphine PET scan in early abstinence from dependent alcohol use (approximately 2 weeks) and 2 months later if continuously abstinent. Global and regional [11C]diprenorphine volumes of distribution (VD) were increased in alcohol dependent patients compared with controls but did not reach significance. We demonstrated a correlation between global and regional [11C]diprenorphine VD and craving in alcohol dependent patients which persisted in the anterior cingulate cortex into extended abstinence. This confirms previous work showing increased opioid receptor availability in early abstinence from substances of abuse and correlation with craving suggesting that the opioid system plays a fundamental role in this phase of addiction.