Transitions to polysubstance use: Prospective cohort study of adolescents in Australia.

BACKGROUND AND AIMS: Adolescent polysubstance use has been associated with adverse social and health outcomes. Our aim was to measure rates and transitions to polysubstance use during adolescence and identify factors associated with initiation and discontinuation of polysubstance use. DESIGN: Prospective cohort study. Multistate Markov modelling was used to estimate rates and identify correlates of transitions between substance use states. SETTING AND PARTICIPANTS: Adolescent-parent dyads (n = 1927; adolescents in grade 7, age ≈13 years) were recruited from Australian schools during 2010/11 (Wave 1). Adolescents were surveyed annually until 2016/17 (n = 1503; age ≈19 years; Wave 7) and parents were surveyed annually until 2014/15 (Wave 5). MEASUREMENTS: Alcohol, tobacco, cannabis and 3,4-methylenedioxymethamphetamine (MDMA) use outcomes were collected at Waves 3-7. Potential confounders were collected at Waves 1-6 and consisted of sex, anxiety and depression symptoms and externalizing problems, parental monitoring, family conflict and cohesion, parental substance use and peer substance use. Covariates were age and family socioeconomic status. FINDINGS: Few adolescents engaged in polysubstance use at earlier waves (Wave 3: 5%; Wave 4: 8%), but proportions increased sharply across adolescence (Waves 5-7: 17%, 24%, 36%). Rates of transitioning to polysubstance use increased with age, with few (<9%) adolescents transitioning out. More externalizing problems (odds ratio [OR] = 1.10; 99.6% confidence interval [CI] = 1.07-1.14), parental heavy episodic drinking (OR = 1.22; 99.6% CI = 1.07-1.40), parental illicit substance use (OR = 3.56; 99.6% CI = 1.43-8.86), peer alcohol use (OR = 5.68; 99.6% CI = 1.59-20.50) and peer smoking (OR = 4.18; 99.6% CI = 1.95-8.81) were associated with transitioning to polysubstance use. CONCLUSIONS: Polysubstance use in Australia appears to be rare during early adolescence but more common in later adolescence with low rates of transitioning out. Externalizing problems and greater parental and peer substance use are risk factors for adolescent polysubstance use that may be suitable intervention targets.

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

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

Changes in illicit drug use and markets with the COVID-19 pandemic and associated restrictions: findings from the Ecstasy and Related Drugs Reporting System, 2016-20.

AIMS: To describe (i) self-reported changes in drug use and (ii) trends in price, perceived availability, and perceived purity of illicit drugs, among people who regularly use ecstasy/ 3,4-methylenedioxymethamphetamine (MDMA) and other illicit stimulants in Australia following COVID-19 and associated restrictions. DESIGN: Annual interviews with cross-sectional sentinel samples conducted face-to-face in 2016-19 and via video conferencing or telephone in 2020. Data were collected via an interviewer-administered structured questionnaire. SETTING: Australian capital cities. PARTICIPANTS: Australians aged 16 years or older who used ecstasy/MDMA and other illicit stimulants on a monthly or more frequent basis and resided in a capital city, recruited via social media and word-of-mouth (n ~ 800 each year). MEASUREMENTS: Key outcome measures were self-reported illicit drug market indicators (price, purity and availability) and, in 2020 only, perceived change in drug use (including alcohol and tobacco) since March 2020 and reasons for this change. FINDINGS: For most drugs, participants reported either no change or a reduction in their use since COVID-19 restrictions were introduced. Ecstasy/MDMA was the drug most frequently cited as reduced in use (n = 552, 70% of those reporting recent use), mainly due to reduced opportunities for socialization. While market indicators were largely stable across most drugs, the odds of perceiving MDMA capsules as 'high' in purity decreased compared with 2016-19 [adjusted odds ratio (aOR) = 0.72, 95% confidence interval (CI) = 0.53-0.99], as did perceiving them as 'easy' to obtain (aOR = 0.42, CI = 0.26-0.67). The odds of perceiving cocaine and methamphetamine crystal as 'easy' to obtain also decreased (aOR = 0.67, CI = 0.46-0.96 and aOR = 0.12, CI = 0.04-0.41, respectively). CONCLUSIONS: After COVID-19-related restrictions were introduced in Australia, use of ecstasy/MDMA, related stimulants and other licit and illicit drugs mainly appeared to remain stable or decrease, primarily due to impediments to socialization.

Chloroform-based liquid-liquid extraction and LC-MS/MS quantification of endocannabinoids, cortisol and progesterone in human hair.

Understanding the role of endogenous cannabinoids (endocannabinoids) in disease is of increasing importance. However, tools to investigate endocannabinoid levels in humans are limited. In the current study, we report a simplified sample preparation method for quantifying endocannabinoids and steroid hormones in hair using liquid-liquid extraction combined with ultra performance liquid chromatography coupled to tandem mass spectrometry. The fully validated method is at least R2 = 0.99 linear between 5 and 1,000 pg/mg for each analyte and the detection limits are at or below 0.50 pg/mg for cortisol, progesterone, oleoylethanolamide, and arachidonoyl ethanolamide, and 2.65 pg/mg for 2-arachidonoyl glycerol. Sequential extraction of hair samples revealed that multiple extractions may be required for quantitative recovery of steroids. However endogenous cannabinoids were efficiently recovered using a single sample extraction. The method was applied to a psychosocial stress study where participants provided samples of both hair and saliva. Endogenous hair arachidonoyl ethanolamide levels were negatively associated with resting, but not stressed, salivary cortisol levels in healthy participants. This simplified method enables the detailed study of hormonal and endocannabinoids in human hair with high sensitivity.

A Systematic Review and Meta-Analysis of Cognitive Performance among People with Chronic Use of Opioids for Chronic Non-Cancer Pain.

OBJECTIVE: Opioids, often prescribed for chronic non-cancer pain, may adversely affect cognition. Research has not been synthesized in recent years, during which time academic interest has increased. This study presents meta-analyses on cognitive performance in people taking opioids for chronic non-cancer pain (CNCP). METHODS: We ran systematic literature searches in EMBASE, Medline, and PsycINFO. Eligible studies included people taking opioids for CNCP, an opioid-free group (i.e., case-control) or session (e.g., pre-post), and objective cognitive assessments. Using random-effects meta-analyses, we computed pooled effect sizes for differential task performance for each study design across five domains (motor performance, attention, working memory, executive functions, memory). RESULTS: Seventeen studies were included. Case-control studies covered three control types (healthy, CNCP, taper-off). Pre-post studies were grouped into five follow-ups (four to six and six to nine weeks; three, six, and 12 months). Effect sizes ranged from 0.02-0.62. Cases showed small magnitude impairments in attention and memory compared with healthy controls. Although limited by small sample sizes, there was no clear evidence of impairment in cases compared with opioid-free controls with CNCP. Cases showed some cognitive improvements from opioid-free baseline to follow-up. Effects were strongest for attention and working memory and were apparent from four weeks to six months follow-up. Other effects were small and nonsignificant. CONCLUSIONS: Opioid therapy for CNCP did not worsen cognitive performance and improved it for some domains. People who take opioids for CNCP may evidence deficits in attention and memory, but this is unlikely to translate to global impairment and likely relates to pain more so than opioids.

Clinical correlates and outcomes associated with pregabalin use among people prescribed opioids for chronic non-cancer pain: A five-year prospective cohort study.

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Pregabalin use was common, but for most people use was not associated with clinically meaningful improvements in pain or functioning.

Risk factors for indicators of opioid-related harms amongst people living with chronic non-cancer pain: Findings from a 5-year prospective cohort study.

BACKGROUND: The literature suggests patient characteristics and higher opioid doses and long-term duration are associated with problematic opioid behaviours but no one study has examined the role of all these factors simultaneously in a long-term prospective cohort study. METHODS: Five-year, community-based, prospective cohort of people prescribed opioids for chronic non-cancer pain (CNCP). Logistic mixed effect models with multiple imputation were used to address missing data. Oral morphine equivalent (OME) mg per day was categorised as: 0 mg OME/day, 1-49 mg OME/day (reference), 50-89 mg OME/day, 90-199 mg OME/day and 200mg+ OME/day. Patient risk factors included: age, gender, substance use, mental health history and pain-related factors. Main outcomes included: Prescribed Opioids Difficulties Scale (PODS), Opioid-Related Behaviours In Treatment (ORBIT) scale, and ICD-10 opioid dependence. Multiple confounders for problematic opioid behaviours were assessed. FINDINGS: Of 1,514 participants 44.4% were male (95%CI 41.9-46.9) and their mean age was 58 years (IQR 48-67). Participants had a mean duration of pain of 10 years (IQR 4.5-20.0) and had been taking strong opioids for a median of four years (IQR 1.0-10.0). At baseline, median OME/day was 73 (IQR 35-148). At 5-years, 85% were still taking strong opioids. PODS moderate-high scores reduced from 59.9% (95%CI 58.8-61.0) at baseline to 51.5% (95%CI 50.0-53.0) at 5-years. Around 9% met criteria for ICD-10 opioid dependence at each wave. In adjusted mixed effect models, the risk factors most consistently associated with problematic opioid use were: younger age, substance dependence, mental health histories and higher opioid doses. INTERPRETATION: Both patient risk factors and opioid dose are associated with problematic opioid use behaviours.

Cannabis use in patients 3 months after ceasing nabiximols for the treatment of cannabis dependence: Results from a placebo-controlled randomised trial.

INTRODUCTION AND AIMS: Previous studies suggest cannabinoid agonist treatment is effective in reducing cannabis use in dependent treatment seekers, however few studies have reported on post-treatment outcomes. We examine cannabis use outcomes 12 weeks after cessation of treatment from a randomised placebo-controlled trial of nabiximols for the treatment of cannabis dependence. METHOD: 128 participants received either nabiximols (n = 61) or placebo (n = 67) for 12 weeks, in combination with psychosocial interventions. Self-reported number of days of cannabis use in the previous 28 days was measured at baseline, 4, 8, and 12 weeks (end of treatment) and again at 24 weeks (3 months after treatment ceased). Urinalysis was used to confirm self-report data at Week 24 interview. RESULTS: A factorial mixed-effects model for repeated measures regression revealed that the nabiximols group used cannabis on 6.8 fewer days in the previous 28 days at week 12 (end of treatment) than the placebo group (p = 0.002, CI: 2.1,11.4), and 6.7 fewer days in the previous 28 days at the week-24 follow-up than the placebo group (p = 0.006, CI: 1.4,12.1). A significantly higher proportion of the nabiximols group (14/61; 23 %) than the placebo group (6/67; 9%) reported abstinence from cannabis in the previous 28 days at the week-24 research interview OR=3.0, CI: 1.1, 9.1; p=0.035, NNT=8, CI: 4, 71). DISCUSSIONS AND CONCLUSIONS: The benefits of treatment incorporating nabiximols with psychosocial interventions in reducing cannabis use appears to persist for up to 3 months after the cessation of treatment. A stepped care model of treatment is proposed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12616000103460) https://www.anzctr.org.au.

Simultaneous quantification of endocannabinoids, oleoylethanolamide and steroid hormones in human plasma and saliva.

Endogenous cannabinoids are an increasingly intriguing target for biological research, given the changing legal status of medicinal cannabinoid-based products throughout the world. However, studying the endogenous cannabinoid system is a relatively new field, with few research teams attempting to develop quantitative methods for these important modulatory analytes in human matrices, other than blood. Here we develop and validate simultaneous methods for quantifying arachidonoyl-ethanolamide, 2-arachidonoyl glycerol, oleoylethanolamide, cortisol and progesterone in human plasma and saliva using liquid-liquid extraction combined with ultra-high performance liquid chromatography coupled to tandem mass spectrometry. The method was fully validated over the linear concentration range 1-20 ng/mL for each analyte in plasma (R2 = 0.98-0.99) and saliva (R2 = 0.99). We find that salivary endogenous cannabinoids and cortisol are acutely responsive to exercise, suggesting that targeting the saliva system may present a convenient way for future research of endogenous cannabinoids. This finding also encourages a broader understanding of the endogenous cannabinoid system during stress responses, and our method may consequently lead to a better understanding of the role of endogenous cannabinoids in peripheral tissues.

Validation of the Australian Treatment Outcomes Profile for use in clients with cannabis dependence.

INTRODUCTION AND AIMS: The Australian Treatment Outcomes Profile (ATOP) was developed as a clinical tool for monitoring the substance use, health and wellbeing of clients in alcohol and other drug treatment. This is the first psychometric validation of the ATOP in a cannabis-dependent treatment population. DESIGN AND METHODS: A total of 128 individuals with cannabis dependence enrolled in an outpatient randomised controlled trial were administered the ATOP and gold-standard health and wellbeing questionnaires once by clinicians and once by researchers at baseline. Concurrent validity was assessed by testing ATOP Psychological Health, Physical Health and Quality of Life questions against concurrently administered gold-standard questionnaires: the Short Form 36 Health Survey (SF-36), the 21-item Depression, Anxiety and Stress Scale (DASS-21) and the Sheehan Disability Scale (SDS). Interrater reliability was tested by comparing clinician-administered ATOP items at the medical screening interview to the same ATOP items administered by researchers at baseline. RESULTS: ATOP Psychological Health showed moderate to strong correlations with SF-36 Mental Components, SF-36 Mental Health and DASS-21 scores (r = 0.40-0.52) and ATOP Physical Health with SF-36 Physical Components and SF-36 General Health scores (r = 0.36-0.67). The ATOP Quality of Life scale showed moderate agreement with the SDS and six-dimensional health state short form scales (r = 0.38-0.40). ATOP substance use, employment, education and child care items showed good to excellent interrater reliability (Krippendorff's α = 0.62-0.81), and tobacco use, Psychological Health, Physical Health and Quality of Life showed fair to moderate interrater reliability (Krippendorff's α = 0.42-0.53). DISCUSSION AND CONCLUSIONS: The ATOP appears to be valid and reliable when tested in a population with cannabis-dependence, justifying its widespread use in clinical settings.

Development of a Brief Patient-Administered Screening Tool for Prescription Opioid Dependence for Primary Care Settings.

OBJECTIVE: To develop a short, patient-administered screening tool that will allow for earlier assessment of prescription opioid dependence (often referred to as addiction) in primary care settings. DESIGN AND SETTING: Cross-sectional analysis (N = 1,134) from the two-year time point of the Pain and Opioids IN Treatment (POINT) cohort was used in the scale development. SUBJECTS: Participants who completed two-year interviews in the POINT study, a prospective cohort study that followed people with chronic noncancer pain over a five-year period, and who were prescribed strong opioids for a minimum of six weeks at baseline. METHODS: An advisory committee provided advice on wording and content for screening in primary care settings. Univariate logistic regression identified individual items that were significantly associated with meeting ICD-11 criteria for prescription opioid dependence. Exploratory and confirmatory factor analysis (EFA and CFA) were conducted, and items were reduced to identify a small item set that were discriminative and shared a simple underlying structure. RESULTS: Sixty-four variables associated with ICD-11 criteria for prescription opioid dependence were initially identified. Four rounds of EFA were performed, resulting in five items remaining. CFA identified two possible four-item combinations, with the final combination chosen based on greater item endorsement and the results of goodness-of-fit indices. CONCLUSIONS: Addressing prescription opioid dependence is an important part of the global public health challenge surrounding rising opioid-related harm. This study addresses an important initial requisite step to develop a brief screening tool. Further studies are required to validate the tool in clinical settings.

Correlates of indicators of potential extra-medical opioid use in people prescribed opioids for chronic non-cancer pain.

INTRODUCTION AND AIMS: The opioid-related behaviours in treatment (ORBIT) scale are a measure of recent indicators of potential extra-medical opioid use. Indicators of potential extra-medical opioid use are divergent practices among people prescribed opioids that may place them at risk of harm. This study aimed to examine the correlates of indicators of potential extra-medical opioid use in people prescribed opioids for chronic non-cancer pain (CNCP). DESIGN AND METHODS: The Pain and Opioids IN Treatment (POINT) study is a prospective cohort study of people prescribed opioids for CNCP in Australia. People prescribed opioids solely for opioid dependence were excluded. This cross-sectional study utilised logistic regression to determine the characteristics associated with reporting any indicators of potential extra-medical opioid use. RESULTS: Of the 1505 participants, 38% reported at least one indicator of potential extra-medical opioid use, most commonly asking for an increase in prescribed opioid dose (21%) and early prescription renewal (12%). Indicators of potential extra-medical opioid use were associated with younger age (adjusted odds ratio [AOR] = 0.98; 95% confidence interval [CI] = 0.92, 0.99), male sex (AOR = 1.53; 95% CI = 1.15, 2.04), lifetime pharmaceutical opioid use disorder (AOR = 1.87; 95% CI = 1.31, 2.66) and lifetime illicit drug use disorder (AOR = 1.72; 95% CI = 1.18, 2.52). DISCUSSION AND CONCLUSIONS: Over one-third of the POINT cohort reported one or more indicators of potential extra-medical opioid use. Lifetime substance use disorders were associated these divergent practices, highlighting the importance of clinical monitoring and patient education for this patient group. Longitudinal studies are needed to investigate whether indicators of potential extra-medical opioid use predict opioid use disorders in this population.

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.

Antidepressant Use Among People Prescribed Opioids for Chronic Noncancer Pain.

OBJECTIVE: Although depression and chronic pain often coexist, few studies have examined antidepressant use among people with pain. This study examines the prevalence and characteristics associated with antidepressant use among people prescribed opioids for chronic noncancer pain (CNCP). DESIGN: Baseline data from a prospective cohort study. SETTING: Australian community. SUBJECTS: A total of 1166 people prescribed opioids for CNCP. METHODS: Baseline data collection consisted of a self-completed seven-day medication diary and telephone interview to collect information on sociodemographic characteristics and mental/physical health using validated questionnaires. Logistic regression was used to examine characteristics associated with antidepressant use, reporting adjusted odds ratios (AORs) and 95% confidence intervals (CIs). RESULTS: Of the 1166 participants, 668 (57.3%) were female, and the median (interquartile range) age was 59 (49-68) years. About half the cohort (N = 637, 54.6%) used antidepressants. Of these, 329 (51.7%) reported moderate to severe depression. Amitriptyline was the most commonly used antidepressant (17.3%). Factors independently associated with antidepressant use were being female (AOR = 1.47, 95% CI = 1.13-1.92), more years lived in pain (AOR = 1.01, 95% CI = 1.00-1.02), and use of nonopioid analgesics (AOR = 1.34, 95% CI = 1.01-1.78), benzodiazepines and related drugs (AOR = 1.84, 95% CI = 1.36-2.49), antiepileptics (AOR = 1.86, 95% CI = 1.38-2.51), and antipsychotics (AOR = 2.15, 95% CI = 1.22-3.77). CONCLUSIONS: Antidepressant use is common among people with CNCP prescribed opioids. Those using antidepressants were more likely to use other psychotropic medicines concurrently, highlighting that they are a high-risk population requiring comprehensive assessment to optimize outcomes and reduce potential harms from polypharmacy.

Effect of cannabis use in people with chronic non-cancer pain prescribed opioids: findings from a 4-year prospective cohort study.

BACKGROUND: Interest in the use of cannabis and cannabinoids to treat chronic non-cancer pain is increasing, because of their potential to reduce opioid dose requirements. We aimed to investigate cannabis use in people living with chronic non-cancer pain who had been prescribed opioids, including their reasons for use and perceived effectiveness of cannabis; associations between amount of cannabis use and pain, mental health, and opioid use; the effect of cannabis use on pain severity and interference over time; and potential opioid-sparing effects of cannabis. METHODS: The Pain and Opioids IN Treatment study is a prospective, national, observational cohort of people with chronic non-cancer pain prescribed opioids. Participants were recruited through community pharmacies across Australia, completed baseline interviews, and were followed up with phone interviews or self-complete questionnaires yearly for 4 years. Recruitment took place from August 13, 2012, to April 8, 2014. Participants were asked about lifetime and past year chronic pain conditions, duration of chronic non-cancer pain, pain self-efficacy, whether pain was neuropathic, lifetime and past 12-month cannabis use, number of days cannabis was used in the past month, and current depression and generalised anxiety disorder. We also estimated daily oral morphine equivalent doses of opioids. We used logistic regression to investigate cross-sectional associations with frequency of cannabis use, and lagged mixed-effects models to examine temporal associations between cannabis use and outcomes. FINDINGS: 1514 participants completed the baseline interview and were included in the study from Aug 20, 2012, to April 14, 2014. Cannabis use was common, and by 4-year follow-up, 295 (24%) participants had used cannabis for pain. Interest in using cannabis for pain increased from 364 (33%) participants (at baseline) to 723 (60%) participants (at 4 years). At 4-year follow-up, compared with people with no cannabis use, we found that participants who used cannabis had a greater pain severity score (risk ratio 1·14, 95% CI 1·01-1·29, for less frequent cannabis use; and 1·17, 1·03-1·32, for daily or near-daily cannabis use), greater pain interference score (1·21, 1·09-1·35; and 1·14, 1·03-1·26), lower pain self-efficacy scores (0·97, 0·96-1·00; and 0·98, 0·96-1·00), and greater generalised anxiety disorder severity scores (1·07, 1·03-1·12; and 1·10, 1·06-1·15). We found no evidence of a temporal relationship between cannabis use and pain severity or pain interference, and no evidence that cannabis use reduced prescribed opioid use or increased rates of opioid discontinuation. INTERPRETATION: Cannabis use was common in people with chronic non-cancer pain who had been prescribed opioids, but we found no evidence that cannabis use improved patient outcomes. People who used cannabis had greater pain and lower self-efficacy in managing pain, and there was no evidence that cannabis use reduced pain severity or interference or exerted an opioid-sparing effect. As cannabis use for medicinal purposes increases globally, it is important that large well designed clinical trials, which include people with complex comorbidities, are conducted to determine the efficacy of cannabis for chronic non-cancer pain. FUNDING: National Health and Medical Research Council and the Australian Government.

Adherence to the Caffeine Intake Guideline during Pregnancy and Birth Outcomes: A Prospective Cohort Study.

The aims of this study were to identify: (i) the proportion of women exceeding the caffeine intake guideline (>200 mg/day) during each trimester, accounting for point of pregnancy awareness; (ii) guideline adherence trajectories across pregnancy; (iii) maternal characteristics associated with trajectories; and (iv) association between adherence and growth restriction birth outcomes. Typical and maximal intake per consumption day for the first trimester (T1; pre- and post-pregnancy awareness), second (T2), and third trimester (T3) were recorded for a prospective cohort of pregnant Australian women with singleton births (n = 1232). Birth outcomes were birth weight, small for gestational age, and head circumference. For each period, participants were classified as abstinent, within (≤200 mg), or in excess (>200 mg). Latent class growth analyses identified guideline adherence trajectories; regression analyses identified associations between adherence in each trimester and birth outcomes. The percentage of participants who reported caffeine use declined between T1 pre- and post-pregnancy awareness (89% to 68%), and increased in T2 and T3 (79% and 80%). Trajectories were: 'low consumption' (22%): low probability of any use; 'within-guideline' (70%): high probability of guideline adherence; and 'decreasing heavy use' (8%): decreasing probability of excess use. The latter two groups were more likely to report alcohol and tobacco use, and less likely to report planning pregnancy and fertility problems. Exceeding the guideline T1 pre-pregnancy awareness was associated with lower birth weight after covariate control (b = -143.16, p = 0.011). Overall, high caffeine intake pre-pregnancy awareness occurs amongst a significant minority of women, and continued excess use post-pregnancy awareness is more common where pregnancy is unplanned. Excess caffeine consumption pre-pregnancy awareness may increase the risk for lower birth weight. Increasing awareness of the guideline in pregnancy and preconception health care may be warranted.

Measuring spatial and temporal trends of nicotine and alcohol consumption in Australia using wastewater-based epidemiology.

BACKGROUND AND AIMS: Tobacco and alcohol consumption remain priority public health issues world-wide. As participation in population-based surveys has fallen, it is increasingly challenging to estimate accurately the prevalence of alcohol and tobacco use. Wastewater-based epidemiology (WBE) is an alternative approach for estimating substance use at the population level that does not rely upon survey participation. This study examined spatio-temporal patterns in nicotine (a proxy for tobacco) and alcohol consumption in the Australian population via WBE. METHODS: Daily wastewater samples (n = 164) were collected at 18 selected wastewater treatment plants across Australia, covering approximately 45% of the total population. Nicotine and alcohol metabolites in the samples were measured using liquid chromatography-tandem mass spectrometry. Daily consumption of nicotine and alcohol and its associated uncertainty were computed using Monte Carlo simulations. Nation-wide daily average and weekly consumption of these two substances were extrapolated using ordinary least squares and mixed-effect models. FINDINGS: Nicotine and alcohol consumption was observed in all communities. Consumption of these substances in rural towns was three to four times higher than in urban communities. The spatial consumption pattern of these substances was consistent across the monitoring periods in 2014-15. Nicotine metabolites significantly reduced by 14-25% (P = 0.001-0.008) (2014-15) in some catchments. Alcohol consumption remained constant over the studied periods. Strong weekly consumption patterns were observed for alcohol but not nicotine. Nation-wide, the daily average consumption per person (aged 15-79 years) was estimated at approximately 2.5 cigarettes and 1.3-2.0 standard drinks (weekday-weekend) of alcohol. These estimates were close to the sale figure and apparent consumption, respectively. CONCLUSIONS: Wastewater-based epidemiology is a feasible method for objectively evaluating the geographic, temporal and weekly profiles of nicotine and alcohol consumption in different communities nationally.

Perception of intoxication in a field study of the night-time economy: Blood alcohol concentration, patron characteristics, and event-level predictors.

OBJECTIVE: Determine the relationship of subjective intoxication to blood alcohol concentration (BAC) and examine whether patron and event-level characteristics modify the relationship of BAC to subjective intoxication. METHODS: An in-situ systematic random sample of alcohol consumers attending night-time entertainment districts between 10pm and 3am on Friday and Saturday nights in five Australian cities completed a brief interview (n=4628). Participants reported age, sex, and pre-drinking, energy drink, tobacco, illicit stimulant and other illicit drug use that night, and their subjective intoxication and BAC were assessed. RESULTS: Male and female drinkers displayed equally low sensitivity to the impact of alcohol consumption when self-assessing their intoxication (BAC only explained 19% of variance). The marginal effect of BAC was not constant. At low BAC, participants were somewhat sensitive to increases in alcohol consumption, but at higher BAC levels that modest sensitivity dissipated (actual BAC had less impact on self-assessed intoxication). The slope ultimately leveled out to be non-responsive to additional alcohol intake. Staying out late, pre-drinking, and being young introduced biases resulting in higher self-assessed intoxication regardless of actual BAC. Further, both energy drinks and stimulant use modified the association between BAC and perceived intoxication, resulting in more compressed changes in self-assessment as BAC varies up or down, indicating less ability to perceive differences in BAC level. CONCLUSIONS: The ability of intoxicated patrons to detect further intoxication is impaired. Co-consumption of energy drinks and/or stimulant drugs is associated with impaired intoxication judgment, creating an additional challenge for the responsible service and consumption of alcohol.

Associations between alcohol consumption and cardio-metabolic risk factors in young adults.

Introduction The benefits of alcohol consumption for cardiovascular and metabolic health may have been overstated due to inappropriate comparisons with abstainers and inadequate control for confounding factors including physical activity and mental health. We examined alcohol consumption and cardio-metabolic health in a cohort of young Australian adults overcoming these limitations. Methods Cross-sectional data of a cohort of 2200 participants (age range 25-36 years) from the 2004-06 Childhood Determinants of Adult Health were used. Alcohol consumption was assessed from questionnaire and cardio-metabolic risk factors were measured in clinics. Linear and log binomial regression were used to examine total alcohol consumption (categories: none 0 g/day; light >0-10 g/day [reference]; moderate >10-20 g/day; heavy >20-30 g/day; very heavy >30 g/day) against dichotomous metabolic syndrome and its components: waist circumference, triglycerides, high-density lipoprotein cholesterol, blood pressure and glucose. Covariates included socio-demographics, smoking, diet, physical activity, fitness, depression and anxiety. Results Of the 2220 participants (48% males, mean (standard deviation) age 29.5 (2.5) years), most were classified in the 'light drinking' group (54.2%), less were in the 'non-drinking' (13.2%), 'heavy' (5.2%) or 'very heavy' (5.5%) drinking groups. Only moderate drinking was associated with a significantly lower prevalence of metabolic syndrome (prevalence ratio = 0.64, p < 0.05) compared with light drinking. Higher levels of alcohol consumption were associated with higher high-density lipoprotein cholesterol (ß = 0.05, ptrend < 0.001). Very heavy compared to light drinkers had higher systolic (ß = 3.01 mm Hg, p < 0.01) and diastolic (ß = 2.07 mm Hg, p < 0.05) blood pressure. Conclusion Moderate alcohol consumption was associated with a lower prevalence of MetS, and more favourable levels of lipids but not glucose or blood pressure even when compared to light consumption and with account for a range of confounding factors.

A review of caffeine use as a risk or protective factor for women's health and pregnancy.

PURPOSE OF REVIEW: To provide a narrative synthesis of recently published studies on caffeine use as a risk or protective factor for health outcomes, with a focus on women's health and pregnancy. RECENT FINDINGS: Based on predominantly observational studies, moderate caffeine intake has been shown to be a protective factor for liver cancer, certain bowel conditions, colorectal cancer, skin cancer, and regular menstrual cycle function. However, heavy consumption is a risk factor for osteoporosis, urinary incontinence, and poorer birth and child developmental outcomes. Residual confounding and issues surrounding retrospective self-reported intake are cited as key limitations in the majority of these studies. Moderate caffeine intake has been associated with lower risk of cardiovascular disease and metabolic syndrome; however, recent genetic epidemiology studies provide no evidence for a causal relationship. SUMMARY: Greater inclusion of female participants in studies, and analysis of sex differences in the relationship between caffeine intake and certain health conditions, is necessary. The current literature suggests caffeine's role as a risk or protective factor differs across health conditions. Often, there are plausible biological mechanisms for this relationship. However, a continued precautionary stance is recommended until direct causal pathways are established. Review of recently published studies does not suggest that current intake guidelines for adults and for pregnant woman need to be modified.