Publications by authors named "Raimondo Bruno"

232 Publications

Profile and correlates of colorimetric reagent kit use among people who use ecstasy/MDMA and other illegal stimulants in Australia.

Int J Drug Policy 2021 Jul 7;97:103334. Epub 2021 Jul 7.

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia; School of Psychological Sciences, University of Tasmania, Hobart, Australia.

Background: Colorimetric reagent kits can provide information about the compounds present in drug samples. This study aimed to identify patterns and correlates of colorimetric reagent kit use, as well as behavioural outcomes of testing, amongst people who use illegal stimulants in a context that lacks permanent government-sanctioned drug checking services.

Methods: Australians residing in capital cities who reported regularly using ecstasy/MDMA and/or other illegal stimulants ≥monthly in the past six months were recruited via social media and word-of-mouth from April-July 2019 (N = 792). Participants were asked about testing the contents and/or purity of illegal drugs, and features of last colorimetric reagent kit use. Logistic regression identified correlates of last using a kit (referent: no use of drug checking technology to test drug contents/purity in the past year).

Results: Over one-third (36%) reported testing drug contents and/or purity; of this group, 86% had last used a colorimetric reagent kit. On the last occasion, 52% reported someone else had conducted testing; 58% said testing occurred <24 h before planned drug use; and 24% reported testing for quantity of a substance. Correlates of drug checking comprised: being younger, male, past six-month use of new psychoactive substances, accessing community-based health services for alcohol or other drug reasons, selling drugs for cash profit, obtaining information from peers who had tried the drug, and searching online for reports of the drug by stamp/appearance. The majority (84%) tested a substance they had been sold and/or given as MDMA; of these, 87% detected MDMA. Of those who expected and detected MDMA, 29% and 11% reported results to their peers and dealer, respectively.

Conclusion: People who use ecstasy/MDMA and/or other illegal stimulants seek out objective information about substance contents. In countries that lack permanent government-sanctioned drug checking services, it is important to acknowledge that people already engage in drug checking but with suboptimal technologies and without tailored specialist advice and education.
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http://dx.doi.org/10.1016/j.drugpo.2021.103334DOI Listing
July 2021

Determining clinical cutoff scores for the Australian Treatment Outcomes Profile psychological health, physical health and quality of life questions.

Drug Alcohol Rev 2021 Jun 29. Epub 2021 Jun 29.

Drug and Alcohol Services, South Eastern Sydney Local Health District, Sydney, Australia.

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.
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http://dx.doi.org/10.1111/dar.13346DOI Listing
June 2021

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.

Addiction 2021 Jun 22. Epub 2021 Jun 22.

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia.

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.
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http://dx.doi.org/10.1111/add.15620DOI Listing
June 2021

Cannabinoid polymorphisms interact with plasma endocannabinoid levels to predict fear extinction learning.

Depress Anxiety 2021 Jun 20. Epub 2021 Jun 20.

School of Psychological Sciences, University of Melbourne, Melbourne, Australia.

Background: The endocannabinoid system is gaining increasing attention as a favorable target for improving posttraumatic stress disorder (PTSD) treatments. Exposure therapy is the gold-standard treatment for PTSD, and fear extinction learning is a key concept underlying successful exposure.

Methods: This study examined the role of genetic endocannabinoid polymorphisms in a fear extinction paradigm with PTSD compared to healthy participants (N = 220). Participants provided saliva for genotyping, completed a fear conditioning and extinction task, with blood samples taken before and after the task (n = 57). Skin conductance was the outcome and was analyzed using mixed models.

Results: Results for cannabinoid receptor type 1 polymorphisms suggested that minor alleles of rs2180619 and rs1049353 were associated with poorer extinction learning in PTSD participants. The minor allele of the fatty acid amide hydrolase (FAAH) polymorphism rs324420 was associated with worse extinction in PTSD participants. Subanalysis of healthy participants (n = 57) showed the FAAH rs324420 genotype effect was dependent on plasma arachidonoyl ethanolamide (AEA) level, but not oleoylethanolamide or 2-arachidonoyl glycerol. Specifically, higher but not lower AEA levels in conjunction with the minor allele of FAAH rs324420 were associated with better extinction learning.

Conclusions: These findings provide translational evidence that cannabinoid receptor 1 and AEA are involved in extinction learning in humans. FAAH rs324420's effect on fear extinction is moderated by AEA plasma level in healthy controls. These findings imply that FAAH inhibitors may be effective for targeting anxiety in PTSD, but this effect needs to be explored further in clinical populations.
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http://dx.doi.org/10.1002/da.23170DOI Listing
June 2021

Alcohol use among young Australian adults in May-June 2020 during the COVID-19 pandemic: a prospective cohort study.

Addiction 2021 Jun 9. Epub 2021 Jun 9.

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia.

Aims: To estimate change in young people's alcohol consumption during COVID-19 restrictions in Australia in early-mid 2020, and test whether those changes were consistent by gender and level of consumption prior to the pandemic.

Design: Prospective longitudinal cohort.

Setting: Secondary schools in New South Wales, Tasmania and Western Australia.

Participants: Subsample of a cohort (n = 443) recruited in the first year of secondary school in 2010-11. Analysis data included three waves collected in September 2017-July 2018, September 2018-May 2019 and August 2019-January 2020), and in May-June 2020.

Measurements: The primary predictors were time, gender and level of consumption prior to the pandemic. Outcome variables, analysed by mixed-effects models, included frequency and typical quantity of alcohol consumption, binge drinking, peak consumption, alcohol-related harm and drinking contexts.

Findings: Overall consumption (frequency × quantity) during the restrictions declined by 17% [incidence rate ratio (IRR) = 0.83; 95% confidence interval (CI) = 0.73, 0.95] compared to February 2020, and there was a 35% decline in the rate of alcohol-related harms in the same period (IRR = 0.66; 95% CI = 0.54, 0.79). Changes in alcohol consumption were largely consistent by gender.

Conclusions: From a survey of secondary school students in Australia, there is evidence for a reduction in overall consumption and related harms during the COVID-19 restrictions.
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http://dx.doi.org/10.1111/add.15599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212116PMC
June 2021

Safety and tolerability of oral lisdexamfetamine in adults with methamphetamine dependence: a phase-2 dose-escalation study.

BMJ Open 2021 05 18;11(5):e044696. Epub 2021 May 18.

Drug and Alcohol Clinical Research and Improvement Network, C/O South East Sydney Local Health District, Sydney, New South Wales, Australia.

Objectives: To examine the safety of an agonist-type treatment, lisdexamfetamine (LDX), at 250 mg/day among adults with methamphetamine (MA) dependence.

Design: A dose-escalating, phase-2, open-label, single-group study of oral LDX at two Australian drug treatment services.

Setting: The study was conducted at two Australian stimulant use disorder treatment clinics.

Participants: There were 16 participants: at least 18 years old, MA dependent for at least the preceding 2 years using ICD-10 criteria, reporting use of MA on at least 14 of the preceding 28 days.

Interventions: Daily, supervised LDX of 100-250 mg, single-blinded to dose, ascending-descending regimen over 8 weeks (100-250 mg over 4 weeks; followed by 4-week dose reduction regimen, 250-100 mg). Participants were followed through to week 12.

Outcomes: Primary outcomes were safety, drug tolerability and regimen completion at the end of week 4. Participants were followed to week 12. Secondary outcomes included: change in MA use; craving; withdrawal; severity of dependence; risk behaviour; change in other substance use; medication acceptability; potential for non-prescription use; adherence and neurocognitive functioning.

Results: Fourteen of 16 participants (87.5%) completed escalation to 250 mg/day. Two participants withdrew from the trial in the first week: one relocated away from the study site, the other self-withdrew due to a possible, known side effect of LDX (agitation). There was one serious adverse event of suicidal ideation which resolved. All other adverse events were mild or moderate in severity and known side effects of LDX. No participant was withdrawn due to adverse events. MA use decreased from a median of 21 days (IQR: 16-23) to 13 days (IQR: 11-17) over the 4-week escalation period (p=0.013).

Conclusions: LDX at a dose of up to 250 mg/day was safe and well tolerated by study participants, warranting larger trials as a pharmacotherapy for MA dependence.

Trial Registration Number: ACTRN12615000391572.
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http://dx.doi.org/10.1136/bmjopen-2020-044696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137170PMC
May 2021

Changes in mental health and help-seeking among young Australian adults during the COVID-19 pandemic: a prospective cohort study.

Psychol Med 2021 May 10:1-9. Epub 2021 May 10.

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia.

Background: Young people may have elevated risk for poorer mental health during the coronavirus disease 2019 (COVID-19) pandemic, yet longitudinal studies documenting this impact are lacking. This study assessed changes in mental health and help-seeking since COVID-19 restrictions in young Australians, including gender differences.

Methods: Data were drawn from a recent subsample (n = 443; 60% female; Mage = 22.0) of a prospective cohort originally recruited in secondary school to complete annual surveys. The subsample completed an additional COVID-19 survey during COVID-19 restrictions (May-June 2020), which was compared to responses from their latest annual survey (August 2019-March 2020). Mixed effect models with time and gender as the primary predictors were conducted for: (i) scores on the Patient Health Questionnaire Depression 9-item (PHQ-9) and Generalised Anxiety Disorder 7-item (GAD-7) modules assessed before and during COVID-19 restrictions, and (ii) self-reported help-seeking from a health professional in February 2020, and the month preceding May-June 2020.

Results: Mean symptom scores increased from before to during COVID-19 restrictions on the PHQ-9 (coefficient: 1.29; 95% CI 0.72-1.86) and GAD-7 (0.78; 95% CI 0.26-1.31), but there was no increase in help-seeking over time (odds ratio 0.50; 95% CI 0.19-1.32). There was no evidence of differential changes by gender.

Conclusions: This study found increases in depression and anxiety symptoms but not greater help-seeking among young Australian adults during the first wave of the pandemic. Increasing availability and awareness of accessible treatment options and psychoeducation is critical, as well as further research into risk and protective factors to help target treatment to this vulnerable age group.
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http://dx.doi.org/10.1017/S0033291721001963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144825PMC
May 2021

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

J Pharm Biomed Anal 2021 Jul 27;201:114103. Epub 2021 Apr 27.

Central Science Laboratory, University of Tasmania, Australia.

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 R = 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.
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http://dx.doi.org/10.1016/j.jpba.2021.114103DOI Listing
July 2021

Pharmaceutical Opioid Use Patterns and Indicators of Extramedical Use and Harm in Adults With Chronic Noncancer Pain, 2012-2018.

JAMA Netw Open 2021 Apr 1;4(4):e213059. Epub 2021 Apr 1.

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia.

Importance: Despite concern about harms related to long-term prescribed opioid use among individuals with chronic noncancer pain (CNCP), no study has examined whether the same patients engage in a risky pattern of use consistently for the long term.

Objective: To examine the prevalence, incidence, persistence, and cessation of a range of opioid behaviors, indicators of extramedical use, and harm among individuals who are prescribed opioids.

Design, Setting, And Participants: This 5-year prospective cohort study in communities across Australia included 1514 adults who were prescribed opioids for CNCP. Data collection took place from August 2012 to December 2018, and data analysis took place from February to November 2020.

Exposure: Prescription opioid use.

Main Outcomes And Measures: High-dose opioid use (≥200 oral morphine equivalent [OME] mg/d); requesting an increase in opioid dose; requesting an early prescription renewal; tampering with opioid medication; diversion of medication to others; and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision opioid dependence. Cessation of opioid use was also assessed.

Results: Of the 1514 participants, 672 (44.39%) were men, the mean (SD) age was 58 (19) years, and 737 (48.68%) were unemployed. At each annual interview, approximately 1 in 8 people (10.98% [95% CI, 10.33%-11.63%] to 14.73% [95% CI, 13.98%-15.48%] at any given interview) were taking more than 200 OME mg/d; comparatively more had requested an increased dosage in the previous 3 months (8.46% [95% CI, 7.89%-9.03%] to 23.77% [95% CI, 22.82%-24.73%]); and fewer asked for an early prescription renewal (4.61% [95% CI, 4.19%-5.03%] to 13.97% [95% CI, 13.24%-14.70%]). In any given interview, between 3.06% (95% CI, 2.72%-3.40%) and 7.86% (95% CI, 7.31%-8.41%) of respondents reported tampering and between 0.47% (95% CI, 0.33%-0.60%) and 1.39% (95% CI, 1.16%-1.62%) reported diversion to others. Between 8.28% (95% CI, 7.71%-8.84%) and 13.06% (95% CI, 12.35%-13.77%) met criteria for opioid dependence at each interview. Opioid cessation increased across interviews, from year 1 (9.15% [95% CI, 8.55%-9.74%]) to year 5 (20.02% [19.14%-20.89%]). There was considerable incidence and cessation in all behaviors from 1 interview to the next: most who engaged in any of these behaviors only did so at only 1 interview. For pharmaceutical opioid dependence, between 55.26% (95% CI, 53.81%-56.71%) and 64.44% (95% CI, 62.87%-66.00%) of cases in 1 interview did not meet dependence criteria in the following interview.

Conclusions And Relevance: These findings suggest considerable fluidity in opioid use, extramedical behaviors, and opioid dependence among people with CNCP. This reinforces the need for reassessment of the effectiveness and safety of prescription opioid use over time.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.3059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035647PMC
April 2021

Trends and characteristics of extra-medical use of quetiapine among people who regularly inject drugs in Australia, 2011-2018.

Drug Alcohol Depend 2021 04 17;221:108636. Epub 2021 Feb 17.

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, 2052, Australia.

Background And Aims: There are ongoing concerns regarding the extra-medical use of quetiapine and related harms. We aimed to investigate trends in quetiapine use and extra-medical use among people who regularly inject drugs (PWID) in Australia between 2011-2018, and examine changes in the characteristics associated with extra-medical use of quetiapine, comparing those reporting use in 2011 and 2018.

Methods: This study examines eight years of survey data (2011-2018; n = 7,135 PWID) from Australia's Illicit Drug Reporting System. Linear regression was used to analyse trends over time, and multinomial logistic regression used to identify factors associated with extra-medical quetiapine use in 2011 and 2018.

Findings: The percentage of PWID reporting extra-medical quetiapine use decreased from 14.9 % in 2011 to 12.0 % in 2018; ranging between 10.5 %-15.8 % across years, and reported use was typically infrequent (less than once a month). In both 2011 and 2018, extra-medical quetiapine use was associated with use of benzodiazepines (2011 Adjusted Odds Ratio (AOR) 4.76, 95 % confidence interval (Cl) 2.31-9.82; 2018 AOR 3.10, 95 % Cl 1.84-5.23) and stimulants (2011 AOR 2.81, 95 % Cl 1.51-5.21; 2018 AOR 2.68, 95 % Cl 1.32-5.46) in the past six months.

Conclusions: Slightly more than one in ten PWID reported extra-medical quetiapine use between 2011-2018. Overall, the frequency of extra-medical quetiapine use among PWID was low, however, individuals often engaged in polysubstance use that has the potential to cause other drug-related harms. Targeted harm-reduction interventions focused on polysubstance use are therefore warranted to reduce potential risks among this group.
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http://dx.doi.org/10.1016/j.drugalcdep.2021.108636DOI Listing
April 2021

Trends in cocaine use, markets and harms in Australia, 2003-2019.

Drug Alcohol Rev 2021 Feb 24. Epub 2021 Feb 24.

National Drug and Alcohol Research Centre, UNSW Sydney, Sydney, Australia.

Introduction: This paper aims to describe cocaine use, markets and harms in Australia from 2003 to 2019.

Methods: Outcome indicators comprised prevalence of use from triennial household surveys; patterns of use from annual surveys of sentinel samples who use stimulants; and cocaine-related seizures, arrests, hospitalisations, deaths and treatment episodes. Bayesian autoregressive time-series analyses were conducted to estimate trend over time: Model 1, no change; Model 2, constant rate of change; and Model 3, change over time differing in rate after one change point.

Results: Past-year population prevalence of use increased over time. The percentage reporting recent use in sentinel samples increased by 6.1% (95% credible interval [CrI ] 1.2%,16.9%; Model 3) per year from around 2017 (48%) until the end of the series (2019: 67%). There was a constant annual increase in number of seizures (count ratio: 1.1, CrI 1.1,1.2) and arrests (1.2, CrI 1.1,1.2), and percentage reporting cocaine as easy to obtain in the sentinel samples (percent increase 1.2%, CrI 0.5%,1.8%; Model 2). Cocaine-related hospitalisation rate increased from 5.1 to 15.6 per 100 000 people from around 2011-2012 to 2017-2018: an annual increase of 1.3 per 100 000 people (CrI 0.8,1.8; Model 3). While the death rate was low (0.23 cocaine-related deaths per 100 000 people in 2018; Model 2), treatment episodes increased from 3.2 to 5.9 per 100 000 people from around 2016-2017 to 2017-2018: an annual increase of 2.9 per 100 000 people (CrI 1.6,3.7; Model 3).

Discussion And Conclusions: Cocaine use, availability and harm have increased, concentrated in recent years, and accompanied by increased treatment engagement.
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http://dx.doi.org/10.1111/dar.13252DOI Listing
February 2021

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

Pain Med 2021 04;22(4):979-993

School of Psychological Sciences, University of Tasmania, Tasmania, Australia.

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.
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http://dx.doi.org/10.1093/pm/pnab005DOI Listing
April 2021

Trajectories of alcohol-induced blackouts in adolescence: early risk factors and alcohol use disorder outcomes in early adulthood.

Addiction 2021 Aug 1;116(8):2039-2048. Epub 2021 Feb 1.

National Drug and Alcohol Research Centre, University of New South Wales, Australia.

Background And Aims: Experience of alcohol-induced memory blackouts in adolescence may be an important risk factor for later harms. This longitudinal study (i) modelled trajectories of alcohol-related blackouts throughout adolescence, (ii) explored early-adolescent predictors of blackout trajectories and (iii) examined the association between blackout trajectories and alcohol use disorder (AUD) symptoms.

Design: Longitudinal study in which data from six annual surveys of a longitudinal cohort of Australian adolescents were used to model latent class growth trajectories of blackouts, adjusting for alcohol consumption frequency and typical quantity. Regression models were used to determine whether parent, child and peer factors at baseline (mean age = 12.9) predicted profiles of blackout trajectory membership and whether blackout trajectories predicted meeting criteria for AUD in early adulthood (mean age = 19.8).

Setting And Participants: Australian adolescents (n = 1821; mean age = 13.9-18.8 years).

Measurements: Alcohol-related blackouts, alcohol consumption frequency, typical consumption quantity and DSM-5 AUD in early adulthood were all self-reported.

Findings: We identified a three-class solution: delayed alcohol initiation, rare blackouts (n = 701; 38.5%); early initiation, rare blackouts (n = 869; 47.7%); and early initiation, increasing blackouts (n = 251; 13.8%). Female sex was associated with increased risk of early initiation, increasing blackouts relative to delayed initiation, rare blackouts [relative risk ratio (RRR) = 3.90; 99.5% confidence interval (CI) = 1.96, 7.76] and relative to early initiation, rare blackouts (RRR = 2.89; 99.5% CI = 1.42, 5.87). Early initiation, rare blackouts [odds ratio (OR) = 1.96; 99.5% CI = 1.17, 3.29] and early initiation, increasing blackouts (OR = 4.93; 99.5% CI = 2.32, 10.48) were each associated with increased odds of meeting criteria for AUD in early adulthood relative to delayed initiation, rare blackouts. Early initiation, increasing blackouts was associated with increased odds of meeting criteria for AUD in early adulthood relative to early initiation, rare blackouts (OR = 2.51; 99.5% CI = 1.18, 5.38).

Conclusions: Females in Australia appear to be at higher risk of adolescent alcohol-related blackouts independent of alcohol consumption levels and age of initiation. Alcohol-related blackouts may be associated with later alcohol use disorder.
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http://dx.doi.org/10.1111/add.15415DOI Listing
August 2021

Endocannabinoid reactivity to acute stress: Investigation of the relationship between salivary and plasma levels.

Biol Psychol 2021 02 15;159:108022. Epub 2021 Jan 15.

School of Psychology, University of Tasmania, Australia.

The endogenous cannabinoid (eCB) system has been shown in animal models to regulate the initiation and termination of central nervous responses to stress. In human studies, the role of peripherally measured eCBs is much less clear and the effect in salivary eCBs has not been studied. In this study, we use a novel method to quantify cortisol and eCBs arachidonoyl ethanolamide (AEA) and 2-arachidonoyl glycerol (2-AG) in human saliva, as well as in plasma samples. Forty-five females and 32 males completed a mixed physiological/psychosocial stress-induction study where saliva, and blood samples in males, were collected at baseline, immediately following, 30-minutes following, and 45-minutes following stress induction. Cortisol significantly increased after stress, but there were sex differences in the cortisol response to stress, with females having higher cortisol after stress compared to males. There was a significant increase in salivary levels of 2-AG immediately following stress induction, but no effect of AEA. Salivary AEA was higher in males compared to females. Surprisingly, there was no effect of stress on plasma AEA or 2-AG levels in the male cohort, though small effect sizes for 2-AG were observed, which is consistent with most other human literature. This study is the first to show that the eCB system is active in human saliva and is responsive to acute stress, possibly as part of the sympathetic nervous system response.
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http://dx.doi.org/10.1016/j.biopsycho.2021.108022DOI Listing
February 2021

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

Br J Clin Pharmacol 2020 Dec 28. Epub 2020 Dec 28.

National Drug and Alcohol Research Centre, UNSW, Sydney, Australia.

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.
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http://dx.doi.org/10.1111/bcp.14715DOI Listing
December 2020

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

EClinicalMedicine 2020 Nov 16;28:100592. Epub 2020 Oct 16.

National Drug and Alcohol Research Centre, UNSW, Sydney, Australia.

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.
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http://dx.doi.org/10.1016/j.eclinm.2020.100592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700907PMC
November 2020

Assessing the concurrent validity, inter-rater reliability and test-re-test reliability of the Australian Treatment Outcomes Profile (ATOP) in alcohol and opioid treatment populations.

Addiction 2021 05 4;116(5):1245-1255. Epub 2021 Jan 4.

Sydney School of Medicine (Central Clinical School), Faculty of Medicine and Health, The University of Sydney, NSW, Australia.

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.
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http://dx.doi.org/10.1111/add.15331DOI Listing
May 2021

Combining transdermal and breath alcohol assessments, real-time drink logs and retrospective self-reports to measure alcohol consumption and intoxication across a multi-day music festival.

Drug Alcohol Rev 2020 Nov 10. Epub 2020 Nov 10.

School of Psychological Sciences, University of Tasmania, Hobart, Australia.

Introduction And Aims: Comprehensively investigating alcohol-related behaviours in the context of a dynamic multi-day alcohol-licensed event is important for understanding and minimising patron risk. We aimed to assess the measurement utility of implementing a multi-dimensional alcohol assessment battery using biometric data collection, real-time drink logs and retrospective self-report measures over the course of a 4-day music festival.

Methods: Fourteen adults participated (n = 7 male, mean age 21.9 years). Breath and transdermal alcohol concentration (BrAC and TAC, respectively) were measured using breathalysers and transdermal alcohol bracelets. A real-time drink log was completed via smartphones on initiating each drink, and a retrospective questionnaire was administered up to twice daily throughout the event (6 timepoints total).

Results: While almost all participants (92.9%) logged significantly fewer drinks in real-time than they retrospectively reported via the twice-daily questionnaires, logs provided important contextual information including the types of drinks consumed and drinking intensity. Compared to BrAC, TAC provided a better understanding of the time course of intoxication, indicating highest alcohol consumption outside of static BrAC assessment windows. However, BrAC provided a better assessment of present state: all participants were 0.00% BrAC at departure despite over two-fifths (42.9%) of the sample's last TAC reading exceeding 0.00%.

Conclusions: As standalone assessments, each method possessed limitations. As a combined battery, they were successfully administered simultaneously, resulting in a more comprehensive overview of alcohol consumption/intoxication over the prolonged drinking session. However, the marked burden of simultaneous administration should be considered, and measures should be chosen judiciously based on research needs.
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November 2020

Validity and Reliability of the Computer-Administered Routine Opioid Outcome Monitoring (ROOM) Tool.

Pain Med 2020 12;21(12):3645-3654

Monash Addiction Research Centre, Monash University Peninsula Campus, Frankston, Victoria, Australia.

Objective: The Routine Opioid Outcome Monitoring (ROOM) tool measures outcomes with opioids using an established framework which includes domains such as pain, mood, opioid use disorder, alcohol use, and constipation. This study aims to validate and establish the test-retest reliability of the computer-administered ROOM tool.

Design And Setting: Cross-sectional analysis of an online sample.

Subjects: Participants comprised those with chronic noncancer pain who regularly used prescription opioids.

Methods: Participants self-completed the online ROOM tool along with other validated measures (validation questionnaire), and those who were agreeable also completed the online test-retest questionnaire approximately two weeks later. Subcomponents of the ROOM tool (i.e., pain, mood, alcohol use, opioid use disorder, and constipation) were validated against longer measures of the same construct using Pearson correlation coefficients. Intraclass correlation coefficients were used to assess the stability of the ROOM tool over time.

Results: A total of 324 participants completed the validation questionnaire, of whom 260 also completed the test-retest questionnaire. The opioid use disorder domain showed good sensitivity (73.6) and specificity (75.8) against the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, any opioid use disorder. All ROOM components showed moderate correlation (r = 0.55-0.73) with their longer counterparts. Test-retest reliability was fair (0.58-0.75), indicating that responses were relatively stable over time. Reliability did vary, however, based on the components being measured and how certain tools were scored.

Conclusion: The computer-administered ROOM tool is a valid approach for brief monitoring of outcomes with prescribed opioids in primary care settings and appears to be acceptable to people who are using prescribed opioids for chronic pain.
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http://dx.doi.org/10.1093/pm/pnaa297DOI Listing
December 2020

Perceptions of injectable opioid agonist treatment (iOAT) among people who regularly use opioids in Australia: findings from a cross-sectional study in three Australian cities.

Addiction 2021 06 23;116(6):1482-1494. Epub 2020 Nov 23.

National Drug and Alcohol Research Centre, UNSW Sydney, Sydney, Australia.

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.
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http://dx.doi.org/10.1111/add.15297DOI Listing
June 2021

Dopamine, endocannabinoids and their interaction in fear extinction and negative affect in PTSD.

Prog Neuropsychopharmacol Biol Psychiatry 2021 03 28;105:110118. Epub 2020 Sep 28.

School of Psychological Sciences, University of Melbourne, Australia.

There currently exist few frameworks for common neurobiology between reexperiencing and negative cognitions and mood symptoms of PTSD. Adopting a dopaminergic framework for PTSD unites many aspects of unique symptom clusters, and this approach also links PTSD symptomology to common comorbidities with a common neurobiological deficiency. Here we review the dopamine literature and incorporate it with a growing field of research that describes both the contribution of endocannabinoids to fear extinction and PTSD, as well as the interactions between dopaminergic and endocannabinoid systems underlying this disorder. Based on current evidence, we outline an early, preliminary model that links re-experiencing and negative cognitions and mood in PTSD by invoking the interaction between endocannabinoid and dopaminergic signalling in the brain. These interactions between PTSD, dopamine and endocannabinoids may have implications for future therapies for treatment-resistant and comorbid PTSD patients.
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http://dx.doi.org/10.1016/j.pnpbp.2020.110118DOI Listing
March 2021

Adolescent Alcohol Use Trajectories: Risk Factors and Adult Outcomes.

Pediatrics 2020 10 23;146(4). Epub 2020 Sep 23.

National Drug and Alcohol Research Centre, University of New South Wales Sydney, Sydney, New South Wales, Australia.

Objectives: Adolescents often display heterogenous trajectories of alcohol use. Initiation and escalation of drinking may be important predictors of later harms, including alcohol use disorder (AUD). Previous conceptualizations of these trajectories lacked adjustment for known confounders of adolescent drinking, which we aimed to address by modeling dynamic changes in drinking throughout adolescence while adjusting for covariates.

Methods: Survey data from a longitudinal cohort of Australian adolescents ( = 1813) were used to model latent class alcohol use trajectories over 5 annual follow-ups (mean age = 13.9 until 17.8 years). Regression models were used to determine whether child, parent, and peer factors at baseline (mean age = 12.9 years) predicted trajectory membership and whether trajectories predicted self-reported symptoms of AUD at the final follow-up (mean age = 18.8 years).

Results: We identified 4 classes: abstaining ( = 352); late-onset moderate drinking ( = 503); early-onset moderate drinking ( = 663); and early-onset heavy drinking ( = 295). Having more alcohol-specific household rules reduced risk of early-onset heavy drinking compared with late-onset moderate drinking (relative risk ratio: 0.31; 99.5% confidence interval [CI]: 0.11-0.83), whereas having more substance-using peers increased this risk (relative risk ratio: 3.43; 99.5% CI: 2.10-5.62). Early-onset heavy drinking increased odds of meeting criteria for AUD in early adulthood (odds ratio: 7.68; 99.5% CI: 2.41-24.47).

Conclusions: Our study provides evidence that parenting factors and peer influences in early adolescence should be considered to reduce risk of later alcohol-related harm. Early initiation and heavy alcohol use throughout adolescence are associated with increased risk of alcohol-related harm compared with recommended maximum levels of consumption (late-onset, moderate drinking).
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http://dx.doi.org/10.1542/peds.2020-0440DOI Listing
October 2020

Profile and correlates of injecting-related injuries and diseases among people who inject drugs in Australia.

Drug Alcohol Depend 2020 11 29;216:108267. Epub 2020 Aug 29.

National Drug and Alcohol Research Centre, 22-32 King st. Randwick, University of New South Wales Sydney, Sydney, Australia.

Introduction: People who inject drugs (PWID) commonly experience harms related to their injecting, many of which are consequences of modifiable drug use practices. There is currently a gap in our understanding of how certain injecting-related injuries and diseases (IRID) cluster together, and socio-demographic and drug use characteristics associated with more complex clinical profiles.

Method: Surveys were conducted with 902 Australian PWID in 2019. Participants provided information regarding their drug use, and past month experience of the following IRID: artery injection, nerve damage, skin and soft tissue infection, thrombophlebitis, deep vein thrombosis, endocarditis, septic arthritis, osteomyelitis, and septicaemia. We performed a latent class analysis, grouping participants based on reported IRID and ran a class-weighted regression analysis to determine variables associated with class-membership.

Results: One-third (34 %) of the sample reported any IRID. A 3-class model identified: 1) no IRID (73 %), moderate IRID (21 %), and 3) high IRID (6%) clusters. Re-using one`s own needles was associated with belonging to the high IRID versus moderate IRID class (ARRR = 2.38; 95 % CI = 1.04-5.48). Other factors, including daily injecting and past 6-month mental health problems were associated with belonging to moderate and high IRID classes versus no IRID class.

Conclusion: A meaningful proportion of PWID reported highly complex IRID presentations distinguished by the presence of thrombophlebitis and associated with greater re-use of needles. Increasing needle and syringe coverage remains critical in addressing the harms associated with injecting drug use and expanding the capacity of low-threshold services to address less severe presentations might aid in reducing IRID amongst PWID.
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http://dx.doi.org/10.1016/j.drugalcdep.2020.108267DOI Listing
November 2020

Parental supply of sips and whole drinks of alcohol to adolescents and associations with binge drinking and alcohol-related harms: A prospective cohort study.

Drug Alcohol Depend 2020 10 5;215:108204. Epub 2020 Aug 5.

National Drug & Alcohol Research Centre, Faculty of Medicine, UNSW Sydney, NSW, 2052, Australia; School of Psychology, University of Tasmania, Hobart, TAS, 7000, Australia.

Background: Parents frequently supply alcohol to their children, often only sips. We investigated whether supply of sips and whole drinks, from parents and other sources, are differentially associated with subsequent drinking outcomes.

Methods: A cohort of 1910 adolescents (mean age 12.9yrs) were surveyed annually over seven years from 2010-11. We examined prospective, adjusted associations between the quantity of supply from parental and non-parental sources in the preceding 12 months and five outcomes in the subsequent year, over several consecutive years: binge drinking; alcohol-related harms; symptoms of alcohol abuse, dependence and alcohol use disorder (AUD).

Results: In early waves, most parental supply comprised sips, while supply of whole drinks increased in later waves. Among those not receiving alcohol from other sources, parental supply of sips was associated with increased odds of binge drinking (OR: 1.85; 99.5 % CI: 1.17-2.91) and alcohol-related harms (OR: 1.70; 99.5 % CI: 1.20-2.42), but not with reporting symptoms of alcohol abuse, dependence or AUD, compared with no supply. Relative to no supply, supply of sips from other sources was associated with increased odds of binge drinking (OR: 2.04; 99.5 % CI: 1.14-3.67) only. Compared with supply of sips, supply of whole drinks by parents or others had higher odds of binge drinking, alcohol-related harms, symptoms of dependence and of AUD. Secondary analysis demonstrated that supply of larger quantities was associated with an increased risk of all outcomes.

Conclusion: Parental provision of sips is associated with increased risks and the supply of greater quantities was associated with an increasing risk of adverse outcomes.

Clinical Trial Registration: ClinicalTrials.gov (NCT02280551).
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October 2020

Validation of the OWLS, a Screening Tool for Measuring Prescription Opioid Use Disorder in Primary Care.

Pain Med 2020 11;21(11):2757-2764

Monash Addiction Research Centre, Monash University Peninsula Campus, Frankston, Victoria, Australia.

Objective: The OWLS is a screening tool for prescription opioid use disorder designed for use in primary care. This study aimed to confirm the optimal wording, scoring methods, and cutoff for the OWLS.

Design And Setting: Cross-sectional analysis of an online sample.

Subjects: Participants comprised those with chronic noncancer pain who regularly used prescription opioids.

Methods: Eligible participants self-completed an online version of the OWLS prescription opioid use disorder screening tool and the Composite International Diagnostic Interview Substance Abuse module. Receiver operating characteristics were calculated for three scoring methods for the OWLS, and these were compared with DSM-5 classification of any use disorder and moderate to severe opioid use disorder.

Results: Among the sample (N = 324), utilizing scoring method (i) (i.e., positive endorsement ≥ response option "a little bit") and a cutoff of 3 increased the percentage of correctly classified participants, with concurrent increases in specificity and decreases in false discovery rate, and false positive rate.

Conclusion: OWLS utilizing scoring method (i) with a cutoff of 3 was shown to be the optimal version and scoring method of this tool. This represents a time-efficient, simple scoring method, allowing for quick and accurate screening for opioid use disorder to occur.
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http://dx.doi.org/10.1093/pm/pnaa275DOI Listing
November 2020

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

Drug Alcohol Depend 2020 10 1;215:108220. Epub 2020 Aug 1.

Drug and Alcohol Services, South East Sydney Local Health District, NSW, Australia; Division Addiction Medicine, Faculty Medicine and Health, University of Sydney, NSW, Australia; National Health and Medical Research Council, Clinical Trials Centre, Faculty Medicine and Public Health, University of Sydney, NSW, Australia.

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.
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http://dx.doi.org/10.1016/j.drugalcdep.2020.108220DOI Listing
October 2020

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

J Chromatogr B Analyt Technol Biomed Life Sci 2020 Sep 20;1152:122252. Epub 2020 Jun 20.

Central Science Laboratory, University of Tasmania, Australia.

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 (R = 0.98-0.99) and saliva (R = 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.
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September 2020

Patterns and correlates of prescribed and non-prescribed pregabalin use among a sample of people who inject drugs in Australia.

Drug Alcohol Rev 2020 07 17;39(5):568-574. Epub 2020 Jun 17.

National Drug and Alcohol Research Centre, UNSW Sydney, Sydney, Australia.

Introduction And Aims: Pregabalin is a gamma-aminobutyric acid analogue registered and subsidised for the treatment of neuropathic pain in Australia. Despite pre-clinical evidence of low abuse potential, there are increasing reports of extramedical use and overdose deaths involving pregabalin. This study aimed to describe patterns of pregabalin use among an Australian sample of people who inject drugs (PWID) and identify sociodemographic, substance use and mental/physical health correlates of prescribed and non-prescribed use.

Design And Methods: Data were obtained from the 2018 Illicit Drug Reporting System, comprising a cross-sectional sample of 905 PWID recruited from Australian capital cities. Multinomial logistic regression was used to identify correlates of past 6-month prescribed and non-prescribed pregabalin use.

Results: One-quarter (25%) of participants reported any past 6-month pregabalin use, with 10% reporting prescribed use and 15% non-prescribed use. Past 6-month use of prescribed benzodiazepines and non-prescribed pharmaceutical opioids were associated with both prescribed and non-prescribed pregabalin use compared to no recent pregabalin use. Pain/discomfort on the day of interview was significantly associated with prescribed pregabalin use. Recent use of non-prescribed benzodiazepines and illicit stimulants and past year non-fatal overdose were significantly associated with non-prescribed pregabalin use (compared to no recent pregabalin use).

Discussion And Conclusions: Pregabalin use was relatively common among an Australian sample of PWID. Benzodiazepine and pharmaceutical opioid use were positively correlated with both prescribed and non-prescribed pregabalin use, suggesting that education campaigns regarding the risks of harm associated with concomitant use of these substances are warranted (targeting both health professionals and consumers).
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http://dx.doi.org/10.1111/dar.13083DOI Listing
July 2020

What predicts pharmacists' engagement with opioid-outcome screening? Secondary analysis from an implementation study in community pharmacy.

Int J Clin Pharm 2021 Apr 12;43(2):420-429. Epub 2020 Jun 12.

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia.

Background Pharmacists have a key role to play in identifying and responding to emerging clinical problems with prescribed opioids. A pilot study in Australia examined the implementation of screening and brief intervention (Routine Opioid Outcome Monitoring [ROOM]) to identify and respond to opioid-related problems in community pharmacies. In this implementation study, the rate of screening varied considerably between pharmacies. Objective The aim of this study was to examine pharmacist characteristics associated with implementation of ROOM. Setting Community pharmacies in Victoria and New South Wales, Australia. Methods We implemented a validated computer-facilitated screening (ROOM), combined with brief intervention for opioid-related problems based on a widely accepted framework for monitoring outcomes. In this analysis, we examined the correlates of ROOM completion for individual pharmacists. Negative binomial regression was used to identify baseline predictors of greater screening, with the number of ROOM screens as the dependent (outcome) variable and pharmacist demographics, knowledge, confidence and comfort responding to prescription opioids problems, and attitudes towards evidence based practice examined as independent (predictor) variables. Main outcome measure Number of screens completed by an individual pharmacist as reported in follow-up surveys by pharmacist. Results Fewer years of practice was associated with a greater number of screenings conducted. On average, each additional decade of practice was associated with a 31% (95% CI 0%, 53%) reduction in the number of screenings undertaken by pharmacists. A multivariable analysis revealed that each additional decade practicing, lower knowledge of naloxone and lower confidence in identifying unmanaged pain were all independently associated with reduced engagement in screening after controlling for other variables. Conclusion Findings from this pilot study identified potential barriers to implementing opioid outcome monitoring. Further studies could test different groups of community pharmacists' experience of different barriers when implementing monitoring outcomes with prescribed opioids, to inform future implementation and clinical practice.
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http://dx.doi.org/10.1007/s11096-020-01074-5DOI Listing
April 2021

Assessing the validity of the Australian Treatment Outcomes Profile for telephone administration in drug health treatment populations.

Drug Alcohol Rev 2020 07 12;39(5):441-446. Epub 2020 May 12.

Sydney School of Medicine (Central Clinical School), Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.

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.
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http://dx.doi.org/10.1111/dar.13088DOI Listing
July 2020