Publications by authors named "Jason M White"

107 Publications

Pholedrine is a marker of direct disposal of methamphetamine.

Sci Total Environ 2021 Aug 30;782:146839. Epub 2021 Mar 30.

Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide 5001, South Australia, Australia. Electronic address:

Consumption of methamphetamine has primarily been estimated in wastewater-based epidemiology by measuring the parent compound. However, this could lead to overestimation when methamphetamine is directly disposed into the sewer system. In this respect, it would be advantageous to measure a specific metabolite of methamphetamine instead. We identified 4-hydroxymethamphetamine (pholedrine) as a potential marker. Stability experiments were performed in both filtered and unfiltered wastewater. Correlations with relative loads in wastewater were used to establish its potential as a marker of direct disposal of methamphetamine, or even as a wastewater-based epidemiology biomarker of methamphetamine consumption. This study then investigated the use of pholedrine in combination with methamphetamine to better detect direct disposal events and its potential as a marker of methamphetamine consumption. Examples from both South Australia and New Zealand exemplify the use of pholedrine to identify potential instances of direct disposal of methamphetamine.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146839DOI Listing
August 2021

International snapshot of new psychoactive substance use: Case study of eight countries over the 2019/2020 new year period.

Water Res 2021 Apr 3;193:116891. Epub 2021 Feb 3.

Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide 5001, South Australia, Australia. Electronic address:

There is considerable concern around the use of new psychoactive substances (NPS), but still little is known about how much they are really consumed. Analysis by forensics laboratories of seized drugs and post-mortem samples as well as hospital emergency rooms are the first line of identifying both 'new' NPS and those that are most dangerous to the community. However, NPS are not necessarily all seized by law enforcement agencies and only substances that contribute to fatalities or serious afflictions are recorded in post-mortem and emergency room samples. To gain a better insight into which NPS are most prevalent within a community, complementary data sources are required. In this work, influent wastewater was analysed from 14 sites in eight countries for a variety of NPS. All samples were collected over the 2019/2020 New Year period, a time which is characterized by celebrations and parties and therefore a time when more NPS may be consumed. Samples were extracted in the country of origin following a validated protocol and shipped to Australia for final analysis using two different mass spectrometric strategies. In total, more than 200 were monitored of which 16 substances were found, with geographical differences seen. This case study is the most comprehensive wastewater analysis study ever carried out for the identification of NPS and provides a starting point for future, ongoing monitoring of these substances.
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http://dx.doi.org/10.1016/j.watres.2021.116891DOI Listing
April 2021

Application of catecholamine metabolites as endogenous population biomarkers for wastewater-based epidemiology.

Sci Total Environ 2021 Apr 14;763:142992. Epub 2020 Oct 14.

University of South Australia, Clinical and Health Sciences (CHS), Health and Biomedical Innovation, South Australia 5000, Australia. Electronic address:

Wastewater-based epidemiology studies use catchment populations to normalise chemical marker mass loads in 24-h composite wastewater samples. However, one of the biggest uncertainties within the field is the accuracy of the population used. A population marker in wastewater may significantly reduce the uncertainty. This study evaluated the catecholamine metabolites - homovanillic acid (HVA) and vanillylmandelic acid (VMA) - as potential population biomarkers. Influent wastewater 24-h composite samples were collected from 38 wastewater catchments from around Australia (representing ~33% of Australia's population), extracted and analysed by liquid chromatography tandem mass spectrometry. Measured mass loads were compared to population sizes determined by mapping catchment maps against high-resolution census data. Both biomarkers correlated with coefficient of determinations (r) of 0.908 and 0.922 for HVA and VMA, respectively. From the regression analysis, a slope (i.e. the daily per-capita excretion) of 1.241 and 1.067 mg.day.person was obtained for HVA and VMA, respectively. The mass load ratio between VMA:HVA were very similar to that reported in literature for urinary analysis among all catchments. Overall, this study provided further evidence that catecholamine metabolites are suitable candidates as population biomarkers for future studies.
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http://dx.doi.org/10.1016/j.scitotenv.2020.142992DOI Listing
April 2021

How the recreational stimulant market has changed: Case study in Adelaide, Australia 2016-2019.

Sci Total Environ 2021 Feb 24;757:143728. Epub 2020 Nov 24.

University of South Australia, UniSA: Clinical and Health Sciences, Health and Biomedical Innovation, Adelaide 5000, South Australia, Australia. Electronic address:

The human consumption of stimulant drugs is known to increase over festive periods. In this work, four illicit stimulants: 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), cocaine and methamphetamine and three new psychoactive substances (NPS): ethylone, mephedrone and N-ethylpentylone were monitored in influent wastewater over the Christmas-New Year period in South Australia from 2016 to 2019 using liquid chromatography-mass spectrometry. The differences in Christmas - New Year consumption between years were evaluated and daily mass loads were compared to the average for that year to determine drug levels over the festive period. Although MDMA, MDA and cocaine showed year-on-year increases, the use over the New Year period was far higher than over the rest of the year, consistent with recreational drug use. These were also the drugs that were used predominantly on weekends during the year. Methamphetamine, which does not have a pattern of predominant weekend use, and the NPS showed variable trends. These results suggest that during holiday periods there are increases in the use of a limited set of drugs only and these can be predicted from patterns of use during the non-holiday periods.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143728DOI Listing
February 2021

What is the drug of choice of young festivalgoers?

Drug Alcohol Depend 2020 11 28;216:108315. Epub 2020 Sep 28.

University of South Australia, UniSA: Clinical and Health Sciences, Health and Biomedical Innovation, Adelaide, SA 5000, Australia. Electronic address:

Background: Drug and alcohol consumption are commonplace at festivals including those aimed at younger attendees. However, there is little quantitative information about the extent of this consumption. This work investigates drug use at a school-leaver festival and how it compares to non-festival weeks.

Methods: Influent wastewater was collected over three consecutive weeks from a location where a school-leaver festival occurs. Multiple liquid chromatography-mass spectrometry methods were used to analyse the use of illicit drugs, pharmaceuticals with abuse potential, new psychoactive substances (NPS), alcohol and cannabis. A method for human neurotransmitter metabolites was also utilised to show the population change and allow the drugs found to be normalised to a population.

Results: A total of 12 compounds were quantifiable: methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), alcohol, cannabis, cocaine, morphine, codeine, fentanyl, buprenorphine, oxycodone and nicotine. The NPS methylone was found solely over the festival weekend but at levels below the limit of quantification of the analytical method. The catecholamine metabolites vanillylmandelic acid (VMA) and homovanillic acid (HVA) were found over the entire three weeks, with identical trends - an increase over the festival weekend - indicating a population increase. HVA was used to normalise the drug mass loads to derive a population normalised mass load. Statistical differences using Hedges' g showed large changes in the use of MDMA and MDA over the festival week. Smaller increases were also seen for alcohol and cocaine.

Conclusions: The drugs of choice for the attendees of this school-leaver festival were MDMA and MDA.
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http://dx.doi.org/10.1016/j.drugalcdep.2020.108315DOI Listing
November 2020

Changes in alcohol consumption associated with social distancing and self-isolation policies triggered by COVID-19 in South Australia: a wastewater analysis study.

Addiction 2021 06 1;116(6):1600-1605. Epub 2020 Oct 1.

Clinical and Health Sciences, Health and Biomedical Innovation, University of South Australia, Adelaide, Australia.

Aim: To assess the effects of social distancing and social isolation policies triggered by COVID-19 on alcohol consumption using wastewater analysis in Adelaide, South Australia.

Design: Longitudinal quantitative analysis of influent wastewater data for alcohol concentration.

Setting: Adelaide, South Australia.

Participants: Wastewater catchment area representative of 1.1 million inhabitants.

Measurements: Twenty-four hour composite influent wastewater samples were collected from four wastewater treatment plants in Adelaide, South Australia for 7 consecutive days (Wednesday-Tuesday) every 2 months from April 2016-April 2020. The alcohol metabolite ethyl sulfate was measured in samples using chromatography-tandem mass spectrometry. Data were population-weighted adjusted with consumption expressed as standard drinks/day/1000 people. Weekly consumption and weekend to mid-week consumption ratios were analysed to identify changes in weekday alcohol use pattern.

Findings: Estimated weekend alcohol consumption was significantly lower (698 standard drinks/day/1000 people) after self-isolation measures were enforced in April 2020 compared with the preceding sampling period in February 2020 (1047 standard drinks/day/1000 people), P < 0.05. Weekend to midweek consumption ratio was 12% lower than the average ratio compared with all previous sampling periods. April 2020 recorded the lowest alcohol consumption relative to April in previous years, dating back to 2016.

Conclusions: Wastewater analysis suggests that introduction of social distancing and isolation policies triggered by COVID-19 in Adelaide, South Australia, was associated with a decrease in population-level weekend alcohol consumption.
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http://dx.doi.org/10.1111/add.15256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537161PMC
June 2021

Determination of prescribed and designer benzodiazepines and metabolites in influent wastewater.

Anal Methods 2020 07 6;12(28):3637-3644. Epub 2020 Jul 6.

University of South Australia, UniSA: Clinical and Health Sciences, Health and Biomedical Innovation, Adelaide 5000, South Australia, Australia.

Benzodiazepines are important prescription pharmaceuticals used to help in the treatment of anxiety and sleep disorders. However, they also have a strong potential for abuse. In this respect, illicit benzodiazepines, i.e. not prescribed in Australia and designer benzodiazepines, which are new compounds that are not legally prescribed in any jurisdiction, have emerged in the illicit Australian market in recent years. Designer benzodiazepines are a new class of new psychoactive substances (NPS) and are particularly dangerous due to limited toxicity information and propensity to be mistaken for conventional benzodiazepines, leading to severe side effects and potentially death. It is therefore important to assess the prevalence of the use of these compounds in the community. The current work presents a validated liquid chromatography-mass spectrometry method for 20 prescribed and designer benzodiazepines and metabolites: 7-amino nimetazepam, alpha-hydroxy alprazolam, alprazolam, clonazepam, delorazepam, deschloroetizolam, diazepam, diclazepam, etizolam, flubromazepam, flunitrazepam, lorazepam, lormetazepam, meclonazepam, midazolam, nimetazepam, nitrazepam, oxazepam, pyrazolam and temazepam. Quetiapine, a prescription sedative drug that has been diverted for non-medical use, was also validated. Limits of quantification were predominantly below 10 ng L, except for the ubiquitous oxazepam, quetiapine and temazepam, which were between 75-300 ng L. Stability, recovery and matrix effects were also examined. Finally, this method was applied to influent wastewater from South Australia, which showed the presence of many benzodiazepines including the NPS etizolam.
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http://dx.doi.org/10.1039/d0ay00560fDOI Listing
July 2020

The complexities associated with new psychoactive substances in influent wastewater: The case of 4-ethylmethcathinone.

Drug Test Anal 2020 Oct 20;12(10):1494-1500. Epub 2020 Jul 20.

UniSA: Clinical and Health Sciences, Health and Biomedical Innovation, University of South Australia, Adelaide, South Australia, Australia.

Consumption of new psychoactive substances (NPS) is an international problem for health, policing, forensic, and analytical laboratories. The transience of these substances in the community, combined with continual slight structural changes to evade legislation makes the elucidation of NPS an analytical challenge. This is amplified in a matrix as complex as wastewater. For that reason, suspect and non-target methodologies, employing high resolution mass spectrometry are the most appropriate current tool to facilitate the identification of new and existing compounds. In the current work, a qualitative screening method of influent wastewater using liquid chromatography-high resolution mass spectrometry showed a strong signal at m/z 192.1382 - identical to that of two NPS standards that were in our method (pentedrone and 4-methylethcathinone), and with identical fragment ions, but the retention times did not match. This work shows the methodology followed to identify this compound, highlighting the challenges of the identifying "new" compounds in influent wastewater.
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http://dx.doi.org/10.1002/dta.2890DOI Listing
October 2020

Anabasine-based measurement of cigarette consumption using wastewater analysis.

Drug Test Anal 2020 Sep 26;12(9):1393-1398. Epub 2020 Jun 26.

UniSA: Clinical and Health Sciences, Health and Biomedical Innovation, University of South Australia, South Australia, Australia.

Community tobacco use can be monitored over time using wastewater-based epidemiological approaches by estimating the mass loads of nicotine and its metabolites, cotinine, or hydroxycotinine, in wastewater. However, due to the use of nicotine in smoking cessation products, other sources of nicotine contribute to cotinine and hydroxycotinine loads. The use of nicotine replacement therapies could vary in space and time and mask the true rates of tobacco consumption. Therefore, this work evaluated the content of tobacco specific markers, anatabine and anabasine, in cigarettes, in urine of smokers, and in wastewater. The results indicated that the anabasine content in both licit and illicit cigarettes in Australia is less variable than anatabine and is therefore considered a better measure of tobacco consumption. A study determining the excretion of tobacco-specific alkaloids of smoking and non-smoking volunteers gave an average urinary mass load of anabasine of 4.38 μg/L/person and a daily mass load of 1.13 μg/day/person. Finally, this was compared with the mass loads of anabasine from wastewater-based epidemiology data of 3 μg/day/person to estimate cigarette rates in a South Australian city: equivalent to 2.6 cigarettes/person/day. The rate of decline of cigarette use was greater when using anabasine as a measure of consumption compared with cotinine. This is the first study to estimate the rate of anabasine excretion, which can be used to estimate tobacco use independent of therapeutically prescribed nicotine.
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http://dx.doi.org/10.1002/dta.2874DOI Listing
September 2020

Towards an efficient method for the extraction and analysis of cannabinoids in wastewater.

Talanta 2020 Sep 18;217:121034. Epub 2020 Apr 18.

Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide, 5001, Australia. Electronic address:

Owing to the risks and dangers of xenobiotic cannabinoids (phyto and synthetic), studies are required to evaluate community consumption. The analysis of excreted cannabinoids in wastewater can provide information about community consumption for a defined catchment area. The recovery of cannabinoids from complex wastewater matrices is difficult due to the hydrophobic properties of these compounds. In this study, a liquid chromatography tandem mass spectrometry (LC-MS/MS) method was optimised for the recovery of 30 cannabinoids from wastewater, including the cannabis urinary biomarker 11-nor-9-carboxy-Δ-tetrahydrocannabinol (THC-COOH), cannabidiol (CBD), and a variety of different generational synthetic cannabinoids and metabolites. Method validation assessed criteria including linearity, selectivity, recovery, ion-suppression, filtration losses and matrix effect. Two sample preparation approaches-liquid-liquid extraction (LLE) and solid phase extraction (SPE)-were compared, with comparable limits of quantification between 0.001 and 0.5 µg L in wastewater. Filtration was found to reduce the recovery for many of the investigated cannabinoids, where up to 97% of analyte was lost. The method was applied to 15 different catchment areas across Australia to gauge the community use of the cannabinoids in this study. The cannabis biomarker THC-COOH was quantified at all locations, and cannabidiol was measured at eight catchment areas. Three synthetic cannabinoids were detected at the limit of detection: 5-fluoro APINACA, JWH-073 (4-hydroxypentyl), and MDMB-CHMICA.
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http://dx.doi.org/10.1016/j.talanta.2020.121034DOI Listing
September 2020

Determining changes in new psychoactive substance use in Australia by wastewater analysis.

Sci Total Environ 2020 Aug 7;731:139209. Epub 2020 May 7.

University of South Australia, UniSA: Clinical and Health Sciences, Health and Biomedical Innovation, Adelaide 5000, South Australia, Australia. Electronic address:

Measuring community consumption of new psychoactive substances (NPS) is notoriously difficult to assess by traditional means such as surveys and seizure data. Previously, we used the approach to demonstrate the prevalence of NPS on a national scale. In the current study we explored the temporal resolution for the analysis of NPS in wastewater from Australia. Samples covering all States and Territories in Australia and both metropolitan and regional areas and were collected bimonthly from October 2017-June 2018 and October 2019-February 2020. A qualitative screening method was applied, screening for 201 NPS. In total, 15 substances were found from a variety of classes of NPS. The most prevalent class was synthetic cathinones, with pentylone, N-ethylpentylone and ethylone found in all periods in at least one site in the earlier sampling period, as well as the amphetamine-like paramethoxyamphetamine (PMA). In the latter period, synthetic cathinones were also the most prevalent, including eutylone, marking the first time that this compound has been detected in wastewater. This study shows the application of wastewater analysis to detect outbreaks of NPS use and temporal differences among sites.
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http://dx.doi.org/10.1016/j.scitotenv.2020.139209DOI Listing
August 2020

Differential cardiovascular responses to cutaneous afferent subtypes in a nociceptive intersegmental spinal reflex.

Sci Rep 2019 12 13;9(1):19049. Epub 2019 Dec 13.

Departments of Neurology and Physiology, Emory University, Atlanta, GA, USA.

Electrical stimulation to segmental dorsal cutaneous nerves (DCNs) activates a nociceptive sensorimotor reflex and the same afferent stimulation also evokes blood pressure (BP) and heart rate (HR) responses in rats. To investigate the relationship between those cardiovascular responses and the activation of nociceptive afferents, we analyzed BP and HR responses to electrical stimulations at each DCN from T6 to L1 at 0.5 mA to activate A-fiber alone or 5 mA to activate both A- and C-fibers at different frequencies. Evoked cardiovascular responses showed a decrease and then an increase in BP and an increase and then a plateau in HR. Segmentally, both cardiovascular responses tended to be larger when evoked from the more rostral DCNs. Stimulation frequency had a larger effect on cardiovascular responses than the rostrocaudal level of the DCN input. Stimulation strength showed a large effect on BP changes dependent on C-fibers whereas HR changes were dependent on A-fibers. Additional A-fiber activation by stimulating up to 4 adjacent DCNs concurrently, but only at 0.5 mA, affected HR but not BP. These data support that cutaneous nociceptive afferent subtypes preferentially contribute to different cardiovascular responses, A-fibers to HR and C-fibers to BP, with temporal (stimulation frequency) and spatial (rostrocaudal level) dynamics.
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http://dx.doi.org/10.1038/s41598-019-54072-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911054PMC
December 2019

Central Plasticity of Cutaneous Afferents Is Associated with Nociceptive Hyperreflexia after Spinal Cord Injury in Rats.

Neural Plast 2019 19;2019:6147878. Epub 2019 Nov 19.

Departments of Neurology and Physiology, Emory University School of Medicine, Atlanta GA 30322, USA.

Electrical stimulations of dorsal cutaneous nerves (DCNs) at each lumbothoracic spinal level produce the bilateral cutaneus trunci muscle (CTM) reflex responses which consist of two temporal components: an early and late responses purportedly mediated by A and C fibers, respectively. We have previously reported central projections of DCN A and C fibers and demonstrated that different projection patterns of those afferent types contributed to the somatotopic organization of CTM reflex responses. Unilateral hemisection spinal cord injury (SCI) was made at T10 spinal segments to investigate the plasticity of early and late CTM responses 6 weeks after injury. Both early and late responses were drastically increased in response to both ipsi- and contralateral DCN stimulations both above (T6 and T8) and below (T12 and L1) the levels of injury demonstrating that nociceptive hyperreflexia developed at 6 weeks following hemisection SCI. We also found that DCN A and C fibers centrally sprouted, expanded their projection areas, and increased synaptic terminations in both T7 and T13, which correlated with the size of hemisection injury. These data demonstrate that central sprouting of cutaneous afferents away from the site of injury is closely associated with enhanced responses of intraspinal signal processing potentially contributing to nociceptive hyperreflexia following SCI.
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http://dx.doi.org/10.1155/2019/6147878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885787PMC
July 2020

Determination of 21 synthetic cathinones, phenethylamines, amphetamines and opioids in influent wastewater using liquid chromatography coupled to tandem mass spectrometry.

Talanta 2020 Feb 18;208:120479. Epub 2019 Oct 18.

School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, 5000, Australia. Electronic address:

Human consumption of illicit novel psychoactive substances (NPS) is a continuing problem. New derivatives are constantly appearing, circumventing national and international laws. The use of these compounds tend to be sporadic and many are consumed as mixtures, meaning very low amounts of each are detectable at any one time. The analysis of excreted NPS in wastewater provides information on community prevalence. A wastewater-based epidemiology approach has been applied in the current study for the quantification of 21 NPS. These include three phenethylamines (25B-NBOMe, 25C-NBOMe, 25I-NBOMe), ten synthetic cathinones (3-ethylmethcathinone (3-EMC), 3-methylbuphedrone, 3-methylmethcathinone (3-MMC), 4-fluoromethcathinone (4-FMC), 4-methylbuphedrone, 4-methylethcathinone (4-MEC), buphedrone, butylone, N-ethylpentylone and pentylone), five synthetic opioid analgesics (AH-7921, butyryl fentanyl, furanyl fentanyl, U-47700 and valeryl fentanyl) as well as the synthetic amphetamine 4-fluoroamphemtaine (4-FA), ketamine analogue methoxetamine and methiopropamine. Limits of detection were between 0.01 and 0.5 ng/L and limits of quantification were between 0.05 and 1 ng/L. The method was applied to wastewater samples from South Australia collected over the Christmas-New Year period when recreational drug use tends to be high. Seven NPS (butylone, butyryl fentanyl, furanyl fentanyl, methoxetamine, N-ethylpentylone, pentylone and valeryl fentanyl) were found, with N-ethylpentylone showing the highest mass loads at 36 mg/day/1000 inhabitants.
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http://dx.doi.org/10.1016/j.talanta.2019.120479DOI Listing
February 2020

A sensitive analytical method for the measurement of neurotransmitter metabolites as potential population biomarkers in wastewater.

J Chromatogr A 2020 Feb 14;1612:460623. Epub 2019 Oct 14.

School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5000, Australia.

Wastewater-based epidemiology is a growing research field which provides valuable information on community drug use and chemical exposure. One parameter critical to estimations of drug use is the catchment area population. A population biomarker could be used to provide this information. This study evaluated the analytical suitability of three endogenous biomarkers of human activity: the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) which has previously been proposed and two further candidates, the catecholamine metabolites vanillylmandelic acid (VMA) and homovanillic acid (HVA). An analytical method involving derivatization was developed and validated for two candidates, 5-HIAA and HVA by liquid chromatography - mass spectrometry. The best performance was obtained for VMA as the underivatized analyte. The derivatized extracts produced a 100 times better sensitivity. The three neurotransmitter metabolites were evaluated as population biomarkers in wastewater samples. All were stable in sample, not lost upon filtration and showed stable inter-day mass loads over seven days for a metropolitan wastewater treatment plant. When applied to a small community during a festival period, mass loads of both HVA and VMA reflected the increase in the catchment population, whilst 5-HIAA proved to be more variable.
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http://dx.doi.org/10.1016/j.chroma.2019.460623DOI Listing
February 2020

Measuring opioid dependence in chronic pain patients: A comparison between addiction clinic and pain clinic patient populations.

J Opioid Manag 2019 Jul/Aug;15(4):285-293

Senior Lecturer in Addiction Studies, Adelaide Medical School, University of Adelaide, South Australia, Australia.

Objective: To compare dependence characteristics between patients with chronic pain treated within an addiction medicine setting with those attending specialist pain clinics.

Setting And Patients: Forty patients with chronic non-cancer pain taking opioid analgesics for >1 year were recruited from university-affiliated, tertiary teaching hospital clinics; 20 from an addiction medicine clinic (addiction clinic group) and 20 from specialist pain clinics (pain clinic group).

Design And Main Outcome Measures: Data regarding demographics, past and current substance use, pain history and current daily opioid intake were collected. Patients completed three questionnaires: the Severity of Opioid Dependence Questionnaire, Leeds Dependence Questionnaire, and Pain Disability Index. A novel "Opioid Problem Checklist score" assessing drug-related problems was also determined for each patient.

Results: The addiction clinic group were younger, more likely to have experienced drug overdose and had a shorter duration of chronic pain. No significant differences in dependence questionnaire scores were found between groups. However, higher Pain Disability Index scores and higher Opioid Problem Checklist scores (indicating more drug-related problems) were found for the addiction clinic group.

Conclusions: Some degree of dependence was present across both addiction and pain clinic groups, supporting the notion a state of dependence can be identified among chronic pain patients taking opioids long term. Aberrant behaviors were not common in the pain clinic sample, suggesting these patients are unlikely to meet Diagnostic and Statistical Manual of Mental Disorders-V criteria for Substance Use Disorder. However, opioid dependence carries significant risks for relapse, chronicity, morbidity and mortality, warranting specific medical management. Management of such risks should be considered routine care in chronic pain patients taking opioids long term.
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http://dx.doi.org/10.5055/jom.2019.0514DOI Listing
October 2019

Prevalence of self-reported movement dysfunction among young adults with a history of ecstasy and methamphetamine use.

Drug Alcohol Depend 2019 12 27;205:107595. Epub 2019 Sep 27.

School of Pharmacy and Medical Sciences, University of South Australia, GPO Box 2471, Adelaide, SA, 5001, Australia. Electronic address:

Background: Illicit stimulant use is associated with long-lasting changes in movement and movement-related brain regions. The aim of our study was to investigate the prevalence of movement dysfunction in this population. We hypothesized that prevalence of self-reported movement dysfunction is higher among stimulant users than non-stimulant users.

Methods: Three groups of adults completed a survey containing questions about demographics, health, drug use, and movement. The groups consisted of ecstasy users with no history of methamphetamine use (ecstasy group, n = 190, 20 ± 3 yrs.), methamphetamine users (methamphetamine group, n = 331, 23 ± 5 yrs.), and non-stimulant users (control group, n = 228, 25 ± 8 yrs.). Movement data was analyzed with logistic regression.

Results: In the unadjusted logistic regression model, group had a significant effect on fine hand control, tremor, and voice/speech questions, but not on other movement domain questions. The prevalence of tremor and abnormal fine hand control was significantly higher in the ecstasy and methamphetamine groups than in the control group (p < 0.018), and changes in voice/speech was more prevalent in the ecstasy group than in the control group (p = 0.015). Age and use of cannabis and hallucinogens were confounding variables. However, inspection of chi-square tables suggests that the effect of these parameters on the movement data is likely to be minor.

Conclusions: The prevalence of self-reported tremor and changes in fine hand control and voice/speech is significantly higher in stimulant users than in non-stimulant users. Inclusion of these common and noticeable changes in body function may aid public health campaigns that target prevention or harm minimization.
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http://dx.doi.org/10.1016/j.drugalcdep.2019.107595DOI Listing
December 2019

Temporal and spatial dynamics of spinal sensorimotor processing in an intersegmental cutaneous nociceptive reflex.

J Neurophysiol 2019 08 5;122(2):616-631. Epub 2019 Jun 5.

Department of Physiology, Emory University, Atlanta, Georgia.

The cutaneus trunci muscle (CTM) reflex produces a skin "shrug" in response to pinch on a rat's back through a three-part neural circuit: ) A-fiber and C-fiber afferents in segmental dorsal cutaneous nerves (DCNs) from lumbar to cervical levels, ) ascending propriospinal interneurons, and ) the CTM motoneuron pool located at the cervicothoracic junction. We recorded neurograms from a CTM nerve branch in response to electrical stimulation. The pulse trains were delivered at multiple DCNs (T-L), on both sides of the midline, at two stimulus strengths (0.5 or 5 mA, to activate Aδ fibers or Aδ and C fibers, respectively) and four stimulation frequencies (1, 2, 5, or 10 Hz) for 20 s. We quantified both the temporal dynamics (i.e., latency, sensitization, habituation, and frequency dependence) and the spatial dynamics (spinal level) of the reflex. The evoked responses were time-windowed into Early, Mid, Late, and Ongoing phases, of which the Mid phase, between the Early (Aδ fiber mediated) and Late (C fiber mediated) phases, has not been previously identified. All phases of the response varied with stimulus strength, frequency, history, and DCN level/side stimulated. In addition, we observed nociceptive characteristics like C fiber-mediated sensitization (wind-up) and habituation. Finally, the range of latencies in the ipsilateral responses were not very large rostrocaudally, suggesting a myelinated neural path within the ipsilateral spinal cord for at least the A fiber-mediated Early-phase response. Overall, these results demonstrate that the CTM reflex shares the temporal dynamics in other nociceptive reflexes and exhibits spatial (segmental and lateral) dynamics not seen in those reflexes. We have physiologically studied an intersegmental reflex exploring detailed temporal, stimulus strength-based, stimulation history-dependent, lateral and segmental quantification of the reflex responses to cutaneous nociceptive stimulations. We found several physiological features in this reflex pathway, e.g., wind-up, latency changes, and somatotopic differences. These physiological observations allow us to understand how the anatomy of this reflex may be organized. We have also identified a new phase of this reflex, termed the "mid" response.
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http://dx.doi.org/10.1152/jn.00146.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734403PMC
August 2019

Simultaneous determination of 24 opioids, stimulants and new psychoactive substances in wastewater.

MethodsX 2019 19;6:953-960. Epub 2019 Apr 19.

School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, 5000, Australia.

Wastewater-based epidemiology has become a reputable means to estimate drug consumption within a community. However, these methods typically focus solely on illicit drugs or a single chemical family, with multi-class methods out of favour due to the increased analytical challenges. •A sensitive liquid chromatography - mass spectrometry method was developed for the simultaneous determination of 24 opioids, stimulants and new psychoactive substances in influent wastewater.•Filtered wastewater samples, preserved with sodium metabisulfite, were pretreated and 1000 times concentrated using off-line solid phase extraction.•The method was optimised and fully validated for all compounds, with limits of quantification between 0.2 and 300 ng/L.
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http://dx.doi.org/10.1016/j.mex.2019.04.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500910PMC
April 2019

Use of illicit amphetamines is associated with long-lasting changes in hand circuitry and control.

Clin Neurophysiol 2019 05 26;130(5):655-665. Epub 2019 Feb 26.

School of Pharmacy and Medical Sciences, University of South Australia, GPO Box 2471, Adelaide, SA 5001, Australia. Electronic address:

Objective: The study aim was to determine if use of illicit amphetamines or ecstasy is associated with abnormal excitability of the corticomotoneuronal pathway and manipulation of novel objects with the hand.

Methods: Three groups of adults aged 18-50 years were investigated: individuals with a history of illicit amphetamine use, individuals with a history of ecstasy use but minimal use of other stimulants, and non-drug users. Transcranial magnetic stimulation was delivered to the motor cortex and the electromyographic response (motor evoked potential; MEP) was recorded from a contralateral hand muscle. Participants also gripped and lifted a novel experimental object consisting of two strain gauges and an accelerometer.

Results: Resting MEP amplitude was larger in the amphetamine group (6M, 6F) than the non-drug and ecstasy groups (p < 0.005) in males but not females. Overestimation of grip force during manipulation of a novel object was observed in the amphetamine group (p = 0.020) but not the ecstasy group.

Conclusions: History of illicit amphetamine use, in particular methamphetamine, is associated with abnormal motor cortical and/or corticomotoneuronal excitability in males and abnormal manipulation of novel objects in both males and females.

Significance: Abnormal excitability and hand function is evident months to years after cessation of illicit amphetamine use.
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http://dx.doi.org/10.1016/j.clinph.2019.02.005DOI Listing
May 2019

LC-HRMS suspect screening to show spatial patterns of New Psychoactive Substances use in Australia.

Sci Total Environ 2019 Feb 28;650(Pt 2):2181-2187. Epub 2018 Sep 28.

School of Pharmacy and Medical Sciences, University of South Australia, Adelaide 5001, Australia. Electronic address:

New Psychoactive Substances (NPS) are an ever-changing class of compounds designed to imitate the effects of current recreational drugs. Such a diverse market is difficult to assess by traditional means, while collected information can become obsolete before it is available. Wastewater-based epidemiology is one technique which can capture information on where and when NPS appear at the community level. The aim of this study was to identify NPS in wastewater samples using a suspect screening approach. Weekend samples were collected from 50 wastewater treatment plants from Australian capital cities and regional areas across all eight States and Territories and screened against a database containing almost 200 NPS. A total of 22 different NPS were found across all regional and metropolitan wastewater treatment plants. Results showed that the most detected compounds were of the cathinone class, with both Alpha-PVP and methcathinone found in every region. In addition, five different synthetic cannabinoids were detected, at least once in half of the regions analysed. Herein, we report the first comprehensive nationwide analysis of NPS and show the utility of liquid chromatography-high resolution mass spectrometry screening for delivering spatial information of the NPS being consumed in communities.
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http://dx.doi.org/10.1016/j.scitotenv.2018.09.348DOI Listing
February 2019

Investigating the appearance of new psychoactive substances in South Australia using wastewater and forensic data.

Drug Test Anal 2019 Feb 12;11(2):250-256. Epub 2018 Sep 12.

School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, 5001, Australia.

New psychoactive substances (NPS) have increased in use and popularity worldwide. Wastewater analysis has been successfully applied to evaluate illicit drugs use within a population. However, for NPS, such an approach may be limited due to low doses of NPS combined with their ever-changing composition and usage. The dynamic nature of the NPS market means use may be opportunistic, infrequent, and with few users. Hence, the use of complementary information sources is recommended to improve the knowledge on NPS consumption. The aim of this study was to investigate the changing landscape of NPS use on a community scale by combining wastewater analysis and forensic toxicology. Forensic analysis provided specific information on NPS prevalence in post-mortem blood samples in Adelaide, South Australia over five years, while wastewater analysis showed community use over the same period. A qualitative liquid chromatography--high resolution mass spectrometry method was initially used to screen the wastewater samples. A total of 24 NPS were found: 6 in wastewater only, 13 in forensic post-mortem toxicology samples only, and 5 in both. As these results showed the presence of NPS, a targeted method was subsequently employed to quantify levels of these NPS in wastewater. Temporal trends were found in wastewater with distinct tendencies for synthetic cathinones visible over the period studied.
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http://dx.doi.org/10.1002/dta.2484DOI Listing
February 2019

Investigating the correlation between wastewater analysis and roadside drug testing in South Australia.

Drug Alcohol Depend 2018 06 10;187:123-126. Epub 2018 Apr 10.

School of Pharmacy and Medical Sciences, University of South Australia, GPO Box 2471, Adelaide, SA 5001, Australia. Electronic address:

Background: The societal impact of drug use is well known. An example is when drug-intoxicated drivers increase the burden on policing and healthcare services.

Methods: This work presents the correlation of wastewater analysis (using UHPLC-MS/MS) and positive roadside drug testing results for methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and cannabis from December 2011-December 2016 in South Australia.

Results: Methamphetamine and MDMA showed similar trends between the data sources with matching increases and decreases, respectively. Cannabis was relatively steady based on wastewater analysis, but the roadside drug testing data started to diverge in the final part of the measurement period.

Conclusions: The ability to triangulate data as shown here validates both wastewater analysis and roadside drug testing. This suggests that changes in overall population drug use revealed by WWA is consistent and proportional with changes in drug-driving behaviours. The results show that, at higher levels of drug use as measured by wastewater analysis, there is an increase in drug driving in the community and therefore more strain on health services and police.
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http://dx.doi.org/10.1016/j.drugalcdep.2018.02.030DOI Listing
June 2018

Buprenorphine Maintenance Subjects Are Hyperalgesic and Have No Antinociceptive Response to a Very High Morphine Dose.

Pain Med 2019 01;20(1):119-128

Discipline of Pharmacology, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia.

Objective: Acute pain management in opioid-dependent persons is complicated because of tolerance and opioid-induced hyperalgesia. Very high doses of morphine are ineffective in overcoming opioid-induced hyperalgesia and providing antinociception to methadone-maintained patients in an experimental setting. Whether the same occurs in buprenorphine-maintained subjects is unknown.

Design: Randomized double-blind placebo-controlled. Subjects were tested on two occasions, at least five days apart, once with intravenous morphine and once with intravenous saline. Subjects were tested at about the time of putative trough plasma buprenorphine concentrations.

Setting: Ambulatory.

Subjects: Twelve buprenorphine-maintained subjects: once daily sublingual dose (range = 2-22 mg); no dose change for 1.5-12 months. Ten healthy controls.

Methods: Intravenous morphine bolus and infusions administered over two hours to achieve two separate pseudo-steady-state plasma concentrations one hour apart. Pain tolerance was assessed by application of nociceptive stimuli (cold pressor [seconds] and electrical stimulation [volts]). Ten blood samples were collected for assay of plasma morphine, buprenorphine, and norbuprenorphine concentrations until three hours after the end of the last infusion; pain tolerance and respiration rate were measured to coincide with blood sampling times.

Results: Cold pressor responses (seconds): baseline: control 34 ± 6 vs buprenorphine 17 ± 2 (P = 0.009); morphine infusion-end: control 52 ± 11(P = 0.04), buprenorphine 17 ± 2 (P > 0.5); electrical stimulation responses (volts): baseline: control 65 ± 6 vs buprenorphine 53 ± 5 (P = 0.13); infusion-end: control 74 ± 5 (P = 0.007), buprenorphine 53 ± 5 (P > 0.98). Respiratory rate (breaths per minute): baseline: control 17 vs buprenorphine 14 (P = 0.03); infusion-end: control 15 (P = 0.09), buprenorphine 12 (P < 0.01). Infusion-end plasma morphine concentrations (ng/mL): control 23 ± 1, buprenorphine 136 ± 10.

Conclusions: Buprenorphine subjects, compared with controls, were hyperalgesic (cold pressor test), did not experience antinociception, despite high plasma morphine concentrations, and experienced respiratory depression. Clinical implications are discussed.
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http://dx.doi.org/10.1093/pm/pny025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329438PMC
January 2019

Effects of strategic early-morning caffeine gum administration on association between salivary alpha-amylase and neurobehavioural performance during 50 h of sleep deprivation.

Accid Anal Prev 2019 May 7;126:160-172. Epub 2018 May 7.

School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, AUS.

Self-assessment is the most common method for monitoring performance and safety in the workplace. However, discrepancies between subjective and objective measures have increased interest in physiological assessment of performance. In a double-blind placebo-controlled study, 23 healthy adults were randomly assigned to either a placebo (n = 11; 5 F, 6 M) or caffeine condition (n = 12; 4 F, 8 M) while undergoing 50 h (i.e. two days) of total sleep deprivation. In previous work, higher salivary alpha-amylase (sAA) levels were associated with improved psychomotor vigilance and simulated driving performance in the placebo condition. In this follow-up article, the effects of strategic caffeine administration on the previously reported diurnal profiles of sAA and performance, and the association between sAA and neurobehavioural performance were investigated. Participants were given a 10 h baseline sleep opportunity (monitored via standard polysomnography techniques) prior to undergoing sleep deprivation (total sleep time: placebo = 8.83 ± 0.48 h; caffeine = 9.01 ± 0.48 h). During sleep deprivation, caffeine gum (200 mg) was administered at 01:00 h, 03:00 h, 05:00 h, and 07:00 h to participants in the caffeine condition (n = 12). This strategic administration of caffeine gum (200 mg) has been shown to be effective at maintaining cognitive performance during extended wakefulness. Saliva samples were collected, and psychomotor vigilance and simulated driving performance assessed at three-hour intervals throughout wakefulness. Caffeine effects on diurnal variability were compared with previously reported findings in the placebo condition (n = 11). The impact of caffeine on the circadian profile of sAA coincided with changes in neurobehavioural performance. Higher sAA levels were associated with improved performance on the psychomotor vigilance test during the first 24 h of wakefulness in the caffeine condition. However, only the association between sAA and response speed (i.e. reciprocal-transform of mean reaction time) was consistent across both days of sleep deprivation. The association between sAA and driving performance was not consistent across both days of sleep deprivation. Results show that the relationship between sAA and reciprocal-transform of mean reaction time on the psychomotor vigilance test persisted in the presence of caffeine, however the association was relatively weaker as compared with the placebo condition.
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http://dx.doi.org/10.1016/j.aap.2018.01.026DOI Listing
May 2019

Upper limb function in children with attention-deficit/hyperactivity disorder (ADHD).

J Neural Transm (Vienna) 2018 04 12;125(4):713-726. Epub 2017 Dec 12.

School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, University of South Australia, GPO Box 2471, Adelaide, SA, 5001, Australia.

Upper limb function was investigated in children with ADHD using objective methods. We hypothesised that children with ADHD exhibit abnormal dexterity, force application during manipulation of a novel object, and movement rhythmicity. Two groups of age- and gender-matched children were investigated: 35 typically developing children (controls, 10.5 ± 0.4 years, 32M-3F) and 29 children (11.5 ± 0.5 years, 27M-2F) with formally diagnosed ADHD according to DSM-IV-TR criteria. Participants underwent a series of screening tests and tests of upper limb function while "off" medication. Objective quantification of upper limb function involved measurement of force during a grip and lift task, maximal finger tapping task, and maximal pinch grip. Acceleration at the index finger was also measured during rest, flexion and extension, and a postural task to quantify tremor. The Movement Assessment Battery for Children-2 (MABC-2) was also administered. Significant between-group differences were observed in movement rhythmicity, manipulation of a novel object, and performance of the MABC-2 dexterity and aiming and catching components. Children with ADHD lifted a novel object using a lower grip force (P = 0.036), and held the object with a more variable grip force (P = 0.003), than controls. Rhythmicity of finger tapping (P = 0.008) and performance on the dexterity (P = 0.007) and aiming and catching (P = 0.042) components of the MABC-2 were also significantly poorer in the ADHD group than controls. Movement speed, maximum pinch grip strength, and tremor were unaffected. The results of the study show for the first time that ADHD is associated with deficits in multiple, but not all domains of upper limb function.
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http://dx.doi.org/10.1007/s00702-017-1822-8DOI Listing
April 2018

Qualitative and quantitative temporal analysis of licit and illicit drugs in wastewater in Australia using liquid chromatography coupled to mass spectrometry.

Anal Bioanal Chem 2018 Jan 6;410(2):529-542. Epub 2017 Dec 6.

School of Pharmacy and Medical Sciences, University of South Australia, GPO Box 2471, Adelaide, South Australia, 5001, Australia.

The combination of qualitative and quantitative bimonthly analysis of pharmaceuticals and illicit drugs using liquid chromatography coupled to mass spectrometry is presented. A liquid chromatography-quadrupole time of flight instrument equipped with Sequential Window Acquisition of all THeoretical fragment-ion spectra (SWATH) was used to qualitatively screen 346 compounds in influent wastewater from two wastewater treatment plants in South Australia over a 14-month period. A total of 100 compounds were confirmed and/or detected using this strategy, with 61 confirmed in all samples including antidepressants (amitriptyline, dothiepin, doxepin), antipsychotics (amisulpride, clozapine), illicit drugs (cocaine, methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA)), and known drug adulterants (lidocaine and tetramisole). A subset of these compounds was also included in a quantitative method, analyzed on a liquid chromatography-triple quadrupole mass spectrometer. The use of illicit stimulants (methamphetamine) showed a clear decrease, levels of opioid analgesics (morphine and methadone) remained relatively stable, while the use of new psychoactive substances (methylenedioxypyrovalerone (MDPV) and Alpha PVP) varied with no visible trend. This work demonstrates the value that high-frequency sampling combined with quantitative and qualitative analysis can deliver. Graphical abstract Temporal analysis of licit and illicit drugs in South Australia.
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http://dx.doi.org/10.1007/s00216-017-0747-2DOI Listing
January 2018

Wastewater analysis shows a large decrease in oxycodone use in Adelaide.

Med J Aust 2017 07;207(2):88

University of South Australia, Adelaide, SA.

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http://dx.doi.org/10.5694/mja17.00137DOI Listing
July 2017

History of cannabis use is associated with altered gait.

Drug Alcohol Depend 2017 09 21;178:215-222. Epub 2017 Jun 21.

School of Health Sciences and Sansom Institute for Health Research, University of South Australia, Adelaide, SA 5000, Australia. Electronic address:

Background: Despite evidence that cannabinoid receptors are located in movement-related brain regions (e.g., basal ganglia, cerebral cortex, and cerebellum), and that chronic cannabis use is associated with structural and functional brain changes, little is known about the long-term effect of cannabis use on human movement. The aim of the current study was to investigate balance and walking gait in adults with a history of cannabis use. We hypothesised that cannabis use is associated with subtle changes in gait and balance that are insufficient in magnitude for detection in a clinical setting.

Methods: Cannabis users (n=22, 24±6years) and non-drug using controls (n=22, 25±8years) completed screening tests, a gait and balance test (with a motion capture system and in-built force platforms), and a clinical neurological examination of movement.

Results: Compared to controls, cannabis users exhibited significantly greater peak angular velocity of the knee (396±30 versus 426±50°/second, P=0.039), greater peak elbow flexion (53±12 versus 57±7°, P=0.038) and elbow range of motion (33±13 versus 36±10°, P=0.044), and reduced shoulder flexion (41±19 versus 26±16°, P=0.007) during walking gait. However, balance and neurological parameters did not significantly differ between the groups.

Conclusions: The results suggest that history of cannabis use is associated with long-lasting changes in open-chain elements of walking gait, but the magnitude of change is not clinically detectable. Further research is required to investigate if the subtle gait changes observed in this population become more apparent with aging and increased cannabis use.
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http://dx.doi.org/10.1016/j.drugalcdep.2017.05.017DOI Listing
September 2017

Opioid antagonists with minimal sedation for opioid withdrawal.

Cochrane Database Syst Rev 2017 05 29;5:CD002021. Epub 2017 May 29.

School of Pharmacy and Medical Sciences, University of South Australia, GPO Box 2471, Adelaide, Australia, SA 5001.

Background: Managed withdrawal is a necessary step prior to drug-free treatment or as the endpoint of long-term substitution treatment.

Objectives: To assess the effects of opioid antagonists plus minimal sedation for opioid withdrawal. Comparators were placebo as well as more established approaches to detoxification, such as tapered doses of methadone, adrenergic agonists, buprenorphine and symptomatic medications.

Search Methods: We updated our searches of the following databases to December 2016: CENTRAL, MEDLINE, Embase, PsycINFO and Web of Science. We also searched two trials registers and checked the reference lists of included studies for further references to relevant studies.

Selection Criteria: We included randomised and quasi-randomised controlled clinical trials along with prospective controlled cohort studies comparing opioid antagonists plus minimal sedation versus other approaches or different opioid antagonist regimens for withdrawal in opioid-dependent participants.

Data Collection And Analysis: We used standard methodological procedures expected by Cochrane.

Main Results: Ten studies (6 randomised controlled trials and 4 prospective cohort studies, involving 955 participants) met the inclusion criteria for the review. We considered 7 of the 10 studies to be at high risk of bias in at least one of the domains we assessed.Nine studies compared an opioid antagonist-adrenergic agonist combination versus a treatment regimen based primarily on an alpha-adrenergic agonist (clonidine or lofexidine). Other comparisons (placebo, tapered doses of methadone, buprenorphine) made by included studies were too diverse for any meaningful analysis. This review therefore focuses on the nine studies comparing an opioid antagonist (naltrexone or naloxone) plus clonidine or lofexidine versus treatment primarily based on clonidine or lofexidine.Five studies took place in an inpatient setting, two studies were in outpatients with day care, two used day care only for the first day of opioid antagonist administration, and one study described the setting as outpatient without indicating the level of care provided.The included studies were heterogeneous in terms of the type of opioid antagonist treatment regimen, the comparator, the outcome measures assessed, and the means of assessing outcomes. As a result, the validity of any estimates of overall effect is doubtful, therefore we did not calculate pooled results for any of the analyses.The quality of the evidence for treatment with an opioid antagonist-adrenergic agonist combination versus an alpha-adrenergic agonist is very low. Two studies reported data on peak withdrawal severity, and four studies reported data on the average severity over the period of withdrawal. Peak withdrawal induced by opioid antagonists in combination with an adrenergic agonist appears to be more severe than withdrawal managed with clonidine or lofexidine alone, but the average severity over the withdrawal period is less. In some situations antagonist-induced withdrawal may be associated with significantly higher rates of treatment completion compared to withdrawal managed with adrenergic agonists. However, this result was not consistent across studies, and the extent of any benefit is highly uncertain.We could not extract any data on the occurrence of adverse events, but two studies reported delirium or confusion following the first dose of naltrexone. Delirium may be more likely with higher initial doses and with naltrexone rather than naloxone (which has a shorter half-life), but we could not confirm this from the available evidence.Insufficient data were available to make any conclusions on the best duration of treatment.

Authors' Conclusions: Using opioid antagonists plus alpha-adrenergic agonists is a feasible approach for managing opioid withdrawal. However, it is unclear whether this approach reduces the duration of withdrawal or facilitates transfer to naltrexone treatment to a greater extent than withdrawal managed primarily with an adrenergic agonist.A high level of monitoring and support is desirable for several hours following administration of opioid antagonists because of the possibility of vomiting, diarrhoea and delirium.Using opioid antagonists to induce and accelerate opioid withdrawal is not currently an active area of research or clinical practice, and the research community should give greater priority to investigating approaches, such as those based on buprenorphine, that facilitate the transition to sustained-release preparations of naltrexone.
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http://dx.doi.org/10.1002/14651858.CD002021.pub4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481395PMC
May 2017