ORCID Profile
0000-0001-6750-1078
Current Organisation
University of South Australia
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Publisher: Springer Science and Business Media LLC
Date: 05-1993
DOI: 10.1007/BF02245527
Abstract: Antimicrobial resistance within pets has gained worldwide attention due to pets close contact with humans. This report examined at the molecular level, the antimicrobial resistance mechanisms associated with kennel cough and cat flu. 1378 pets in total were assessed for signs of respiratory infection, and nasal and conjunctival swabs were collected across 76 diseased animals. Phenotypically, 27% of the isolates were characterized by multidrug resistance and possessed high levels of resistance rates to β-lactams. Phenotypic ESBLs/AmpCs production were identified within 40.5% and 24.3% of the isolates, respectively. Genotypically, ESBL- and AmpC-encoding genes were detected in 33.8% and 10.8% of the isolates, respectively, with bla
Publisher: Elsevier BV
Date: 08-2020
Publisher: Wiley
Date: 03-05-2011
DOI: 10.1111/J.1360-0443.2011.03399.X
Abstract: To improve our understanding of the pharmacology of 'ecstasy' in recreational environments in particular, to describe the composition of ecstasy pills, patterns of ecstasy use and the relationship between dose of 3,4-methylendioxymeth hetamine (MDMA) and resulting plasma concentrations. A naturalistic observational study of 56 experienced 'ecstasy' users in recreational settings in Australia. Drug use patterns (number of pills consumed, other drugs consumed). drug content of pills and resultant plasma concentrations of MDMA and related drugs were assessed by gas chromatography/mass spectrometry (GC/MS). Ecstasy pills generally contained MDMA, but this was often combined with other drugs such as 3,4-ethylendioxyethyl hetamine (MDEA) and meth hetamine. The dose of MDMA per pill ranged from 0 to 245 mg and users consumed from one-half to five pills, with the total dose consumed ranging up to 280 mg. Plasma concentrations of MDMA increased with number of pills consumed and cumulative MDMA dose. Use of larger numbers of pills was associated with extended exposure to the drug. MDMA is the major active drug in ecstasy pills, but there is a high degree of variation in doses. Use of multiple pills over the course of one session is common and results in a sustained increase in MDMA plasma concentrations over a number of hours. This is likely to lead to a much greater exposure of the brain to MDMA than would be predicted from controlled single-dose pharmacokinetic studies.
Publisher: Elsevier BV
Date: 08-2000
DOI: 10.1016/S0278-5846(00)00113-5
Abstract: 1. This study was prompted by recent deaths that have occurred after recreational administration of the substituted hetamine para-methoxy hetamine (PMA). Because relatively little is known regarding its mechanism(s) of action, its effects on physiological, behavioural and neurochemical parameters were compared with the well known effects of 3,4-methylenedioxymeth hetamine (MDMA). 2. Equivalent doses of PMA (5-20 mg/kg) produced greater hypothermia than MDMA at an ambient temperature of 20 degrees C. At 30 degrees C, PMA continued to evoke hypothermia except the highest dose where hyperthermia ensued. MDMA altered body temperature only at the highest dose where hyperthermia also resulted. 3. At both 20 and 30 degrees C, MDMA stimulated locomotor activity whereas PMA had modest effects and then, only at high doses. 4. In vivo chrono erometry was used to measure the effect of MDMA and PMA on release, and inhibition of uptake, of serotonin (5-HT) and dopamine (DA) in the dorsal striatum of anaesthetised rats. As expected, MDMA evoked release of DA and inhibited uptake of both DA and 5-HT. By contrast, PMA was a relatively weak releasing agent and did not inhibit DA uptake. However, PMA potently inhibited uptake of 5-HT. 5. Taken together these data suggest that the acute adverse effects of PMA are more likely to be associated with alterations in serotonergic rather than dopaminergic neurotransmission.
Publisher: Elsevier BV
Date: 04-2000
DOI: 10.1016/S0014-2999(00)00165-5
Abstract: Abecarnil is a non-benzodiazepine that possesses anxiolytic and anticonvulsant properties. Conflicting reports of tolerance and withdrawal signs following chronic abecarnil administration have emerged from animal studies using different species and different models of tolerance and dependence. This study used a radiotelemetric method to examine any emergence of tolerance and abstinence signs in the rat following long-term abecarnil administration. Hooded Wistar rats, n=6 per group, were administered either abecarnil (8 mg/kg/bidaily, i.p.) or vehicle for 24 days. Locomotor activity, body temperature and electromyographic (EMG) activity were measured daily immediately following abecarnil administration. Tolerance to the abecarnil-induced muscle relaxant effects and decreased locomotor activity developed within 21 days. Administration of the benzodiazepine antagonist flumazenil (25 mg/kg), 18 h after abecarnil cessation, precipitated abstinence signs that included decreases in body temperature, and large increases in locomotor activity and muscle tone. Moreover, continuous recording of these measures over the 4 days after flumazenil administration indicated a prolonged increase in daytime locomotor activity, suggestive of spontaneous withdrawal. These data support earlier findings that reported signs of tolerance during administration of abecarnil and abstinence signs following abecarnil cessation.
Publisher: SAGE Publications
Date: 25-02-2021
Abstract: Little is known on current practices and challenges associated with the legal trade of medicines controlled under international conventions in low-income countries. This qualitative survey involved semi-structured interviews of stakeholders engaged in the trade of controlled medicines at a global level or at a country level in 3 African countries (Uganda, Kenya, Democratic Republic of the Congo). Nine interviews were conducted, including 3 international wholesalers, 2 relief organizations, 2 procurement officers, and 2 regulatory officers. Additionally, 4 other participants provided written information. All participants consistently reported that the current process of procuring controlled medicines in compliance with international conventions was long and complex given the number of administrative steps required for obtaining export and import authorizations, which are mandatory for both narcotic and psychotropic medicines. It may be difficult or impossible to obtain import authorizations from some health authorities in low-income countries because of long delays, mistakes in forms, absence or shortage of staff, or when annual national estimates are exceeded. The complexities of the trade of controlled medicines directly contribute to the lack of access to essential controlled medicines, both narcotics and psychotropics, in low-income countries.
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.CLINPH.2019.02.005
Abstract: The study aim was to determine if use of illicit hetamines or ecstasy is associated with abnormal excitability of the corticomotoneuronal pathway and manipulation of novel objects with the hand. Three groups of adults aged 18-50 years were investigated: in iduals with a history of illicit hetamine use, in iduals 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. Resting MEP litude was larger in the hetamine 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 hetamine group (p = 0.020) but not the ecstasy group. History of illicit hetamine use, in particular meth hetamine, is associated with abnormal motor cortical and/or corticomotoneuronal excitability in males and abnormal manipulation of novel objects in both males and females. Abnormal excitability and hand function is evident months to years after cessation of illicit hetamine use.
Publisher: American Chemical Society (ACS)
Date: 08-12-2021
Publisher: Springer Science and Business Media LLC
Date: 18-06-2021
Publisher: Wiley
Date: 03-2000
DOI: 10.1046/J.1365-2923.2000.00488.X
Abstract: The objective of this study is to determine whether the presence of a drug and alcohol unit and comprehensive medical education have made a difference to the detection and management of alcohol-related problems in a general teaching hospital. Data were obtained from hospital case notes before and after the introduction of the drug and alcohol unit and medical education. S les of general admissions and admissions with an alcohol diagnosis were obtained. The outcome measures included alcohol history taking, quantification of alcohol consumption and management of alcohol dependence. It was found that for the general admission s le, interns were more likely to take an alcohol history, both in the accident and emergency (A&E) department and on the ward, in 1994 compared to 1988. The difference in the A&E department was statistically significant (P = 0.009). In the A&E department in 1994 there was a greater prevalence of alcohol history taking for male patients (odds ratio (OR) 10.09, 95% confidence interval (CI) 1.89 to 53.70, P = 0.007) compared with female patients (OR = 1.81, 95% CI 0.38 to 8.57, P = 0.045). There were no differences in alcohol history taking by interns in the s les of alcohol-related admissions. There were no statistically significant differences in the prevalence of documenting alcohol histories quantitatively in either s le. The use of alcohol withdrawal charts, ordering diazepam for alcohol withdrawal and ordering drugs which conformed to the hospital formulary all increased significantly by 1994. The prevalence of ordering thiamine and consulting the drug and alcohol unit both decreased slightly by 1994, but not significantly. Improvements have been found in the detection and management of alcohol use since the introduction of the Drug and Alcohol Unit and medical education, but there is still room for further improvement and particular areas where greater attention is needed are identified.
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.MIDW.2015.11.011
Abstract: to utilise qualitative data from investigation of the screening tool ASSIST Version 3.0 with pregnant women to help determine its appropriateness for this cohort, thus informing potential innovations to enhance the questionnaire׳s utility. pregnant women were co-administered the ASSIST Version 3.0 and three established substance use questionnaires (the T-ACE for alcohol, the Timeline FollowBack for cannabis and the Revised Fagerstrom Questionnaire for tobacco). antenatal clinics and the antenatal ward of the Women׳s and Children׳s Hospital, Adelaide, South Australia. 104 pregnant substance-users. as well as the quantitative date (reported elsewhere), rich qualitative data documenting participants' perspectives and experiences in antenatal care were thematically analysed. Women constantly reported friends and family urging them to stop use. Although care providers also advocated cessation or curtailment of use, this advice was reported as unpredictable, with only some providers strongly attuned to such recommendations. Some women voiced suggestions for the appropriate level of provider advice. While pregnancy was often reported as a motivator for changing substance-using behaviour, others reported continued attachment to use which was clearly linked to dependence. Those who reported successful control of use were in contrast to others who were more pragmatic, sceptical in relation to attributable harms, and disinterested in change. There were limited reports of experiences of discrimination directed to pregnant substance users. However, those instances were clearly linked with subsequent lack of honest discussions with care providers, resulting in an absence of appropriate support. current absence of universal screening for substance use has the potential for less than optimal consequences for both mother and baby. appropriate screening accompanied by honest, non-judgmental dialogue can guide the necessary interventions to achieve better outcomes. The recent development of the more concise and easier to administer ASSIST-LITE was partly informed by this investigation.
Publisher: Elsevier BV
Date: 10-2004
Publisher: Wiley
Date: 10-2020
DOI: 10.1111/ADD.15256
Abstract: 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. Longitudinal quantitative analysis of influent wastewater data for alcohol concentration. Adelaide, South Australia. Wastewater catchment area representative of 1.1 million inhabitants. Twenty‐four hour composite influent wastewater s les 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 s les 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. 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 s ling 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 s ling periods. April 2020 recorded the lowest alcohol consumption relative to April in previous years, dating back to 2016. 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.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2011
Publisher: Elsevier BV
Date: 04-2004
Publisher: Weston Medical Publishing
Date: 07-2019
Abstract: 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 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 s le, 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.
Publisher: Elsevier BV
Date: 10-2003
DOI: 10.1016/S0376-8716(03)00190-X
Abstract: Slow-release oral morphine (SROM) has been proposed as an alternative maintenance pharmacotherapy to methadone for treatment of opioid dependence. However, the pharmacodynamics and pharmacokinetics of SROM have not been previously assessed in a methadone maintenance population. In 14 methadone maintenance patients reporting adequate (holders, n=7) or inadequate (non-holders, n=7) withdrawal suppression between doses, plasma drug concentrations and indices of opioid effect (withdrawal severity, pupil diameter, and respiratory rate) were determined across a 24 h inter-dosing interval on one occasion at steady-state for methadone and SROM (once-daily Kapanol) using an open-label, crossover design. Opioid effects were of a similar overall magnitude following dosing for each drug and showed an inverse association with plasma drug concentrations, which peaked later for morphine compared to (R)-methadone (6.5 +/- 2.3 h vs. 2.5 +/- 1.4 h, P<0.001). For methadone non-holders, the number of self-reported opioid withdrawal symptoms prior to dosing was less for SROM compared to methadone (3.4 +/- 2.6 vs. 9.0 +/- 3.2, P<0.01) for holders it was approximately equal (4.4 +/- 3.0 vs. 4.0 +/- 3.7, P<0.76). Maintenance doses were more strongly related to plasma drug concentrations for SROM compared to methadone and may thus be more predictive of therapeutic response for the former medication. Twelve of the 14 subjects preferred SROM to methadone (P=0.01). The pharmacodynamics and pharmacokinetics of SROM support its use as an alternative once-daily agonist option in the treatment of opioid dependence, particularly for patients responding poorly to methadone maintenance treatment.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Oxford University Press (OUP)
Date: 05-03-2019
DOI: 10.1093/PM/PNY025
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2013
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.SMRV.2017.01.005
Abstract: Medications that trigger sleepwalking may inadvertently put the patient at risk of injury to themselves and/or others, and contribute to poor treatment adherence. The aim of this study was to systematically review the literature to identify drugs that may increase the risk of sleepwalking. A search of CINAHL, EMBASE, PsycINFO, PubMed, and ScienceDirect was conducted with the keywords 'sleepwalking' OR 'somnambulism'. Of the original 83 sourced papers, 62 met the inclusion criteria and were subsequently included for review. Twenty-nine drugs, primarily in four classes-benzodiazepine receptor agonists and other gamma aminobutyric acid (GABA) modulators, antidepressants and other serotonergic agents, antipsychotics, and β-blockers-were identified as possible triggers for sleepwalking. The strongest evidence for medication-induced sleepwalking was for zolpidem and sodium oxybate. All other associations were based on case reports. This research highlights the importance of considering sleepwalking in risk profiles in clinical trials, particularly for drugs that enhance GABA activity at the GABA
Publisher: Elsevier BV
Date: 10-2021
Publisher: Public Library of Science (PLoS)
Date: 13-02-2013
Publisher: Wiley
Date: 23-09-2013
DOI: 10.1002/HUP.2351
Abstract: To investigate movement speed and rhythmicity in abstinent cannabis users, we hypothesized that abstinent cannabis users exhibit decreased maximal finger tapping frequency and increased variability of tapping compared with non-drug users. The study involved 10 healthy adult cannabis users and 10 age-matched and gender-matched controls with no history of illicit drug use. Subjects underwent a series of screening tests prior to participation. Subjects were then asked to tap a strain gauge as fast as possible with the index finger of their dominant hand (duration 5 s). The average intertap interval did not significantly differ between groups, but the coefficient of variation of the intertap interval was significantly greater in the cannabis group than in controls (p=0.011). The cannabis group also exhibited a slow tapping frequency at the beginning of the task. Rhythmicity of finger tapping is abnormal in in iduals with a history of cannabis use. The abnormality appears to be long lasting and adds to the list of functional changes present in abstinent cannabis users.
Publisher: Wiley
Date: 06-2006
DOI: 10.1111/J.1369-1600.2006.00014.X
Abstract: Knowledge of how methadone disposition may fluctuate during the course of maintenance treatment is presently limited. This study investigated long-term fluctuations in methadone pharmacokinetics in five methadone maintenance patients who participated in two 24-hour testing sessions separated by at least one year. Results indicated substantial fluctuations between sessions in dose-corrected average steady-state plasma (R)-methadone concentrations (Cav), ranging from a 51% decrease to a 466% increase. These fluctuations were not consistently associated with changes in methadone dose or self-reported withdrawal status. The plasma (S)-:(R)-methadone Cav ratio increased significantly (12%, P = 0.04) between the sessions, suggesting a different pattern of long-term change in the pharmacokinetics of each enantiomer over time. The pronounced and variable fluctuations in methadone disposition evident in these patients highlight the need for an in idualized approach to patient dosing and monitoring.
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.SCITOTENV.2018.09.348
Abstract: New Psychoactive Substances (NPS) are an ever-changing class of compounds designed to imitate the effects of current recreational drugs. Such a erse 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 s les using a suspect screening approach. Weekend s les 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.
Publisher: Elsevier
Date: 2023
Publisher: Elsevier BV
Date: 03-2009
DOI: 10.1016/J.JPAIN.2008.10.003
Abstract: This observational study aimed to determine whether pain sensitivity in patients with noncancer chronic pain, taking either methadone or morphine, is similar to patients maintained on methadone for dependence therapy, compared with a control group. Nociceptive thresholds were measured on a single occasion with von Frey hairs, electrical stimulation, and cold pressor tests. In all subjects receiving methadone or morphine, nociceptive testing occurred just before a scheduled dose. Cold pressor tolerance values in patients with noncancer, chronic pain, treated with morphine and methadone, were 18.1 +/- 2.6 seconds (mean +/- SEM) and 19.7 +/- 2.3 seconds, respectively in methadone-maintained subjects it was 18.9 +/- 1.9 seconds, with all values being significantly (P < .05) lower than opioid-naïve subjects (30.7 +/- 3.9 seconds). These results indicate that patients with chronic pain managed with opioids and methadone-maintained subjects are hyperalgesic when assessed by the cold pressor test but not by the electrical stimulation test. None of the groups exhibited allodynia as measured using the von Frey hairs. These results add to the growing body of evidence that chronic opioid exposure increases sensitivity to some types of pain. They also demonstrate that in humans, this hyperalgesia is not associated with allodynia. This article presents an observational study whereby the pain sensitivity of patients with chronic pain managed with opioids and opioid-maintained patients were compared with opioid-naïve patients. The results suggest that opioid use may contribute to an increase in the sensitivity to certain pain experimental stimuli.
Publisher: Wiley
Date: 26-02-2018
DOI: 10.1111/ADD.14157
Abstract: Tobacco and alcohol consumption remain priority public health issues world-wide. As participation in population-based surveys has fallen, it is increasingly challenging to estimate accurately the prevalence of alcohol and tobacco use. Wastewater-based epidemiology (WBE) is an alternative approach for estimating substance use at the population level that does not rely upon survey participation. This study examined spatio-temporal patterns in nicotine (a proxy for tobacco) and alcohol consumption in the Australian population via WBE. Daily wastewater s les (n = 164) were collected at 18 selected wastewater treatment plants across Australia, covering approximately 45% of the total population. Nicotine and alcohol metabolites in the s les were measured using liquid chromatography-tandem mass spectrometry. Daily consumption of nicotine and alcohol and its associated uncertainty were computed using Monte Carlo simulations. Nation-wide daily average and weekly consumption of these two substances were extrapolated using ordinary least squares and mixed-effect models. Nicotine and alcohol consumption was observed in all communities. Consumption of these substances in rural towns was three to four times higher than in urban communities. The spatial consumption pattern of these substances was consistent across the monitoring periods in 2014-15. Nicotine metabolites significantly reduced by 14-25% (P = 0.001-0.008) (2014-15) in some catchments. Alcohol consumption remained constant over the studied periods. Strong weekly consumption patterns were observed for alcohol but not nicotine. Nation-wide, the daily average consumption per person (aged 15-79 years) was estimated at approximately 2.5 cigarettes and 1.3-2.0 standard drinks (weekday-weekend) of alcohol. These estimates were close to the sale figure and apparent consumption, respectively. Wastewater-based epidemiology is a feasible method for objectively evaluating the geographic, temporal and weekly profiles of nicotine and alcohol consumption in different communities nationally.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2001
DOI: 10.1016/S0304-3959(00)00391-2
Abstract: Opioid substitution treatment for dependence may alter sensitivity to pain. Previous studies on pain sensitivity in methadone maintenance patients have yielded contradictory results. This study compared nociceptive responses between 16 patients on stable, once daily, doses of methadone and 16 matched control subjects. Two types of nociceptive stimuli were used: (1) electrical stimulation and (2) a cold pressor test. Two parameters were measured: detection for onset of pain, and pain tolerance. Methadone patients were tested over an inter-dosing period: at the time of trough plasma methadone concentration (0 h), and 3 h after their daily dose. Control subjects were tested twice 3 h apart. Blood s les were collected to determine plasma methadone concentration. In methadone patients, trough to peak increases in mean R-(-)- and S-(+)-methadone concentrations (118 and 138 ng/ml to 185 and 259 ng/ml, respectively) resulted in significant increases in pain detection and tolerance values for both nociceptive stimuli. Using electrical stimulation, methadone patients' pain tolerance values were lower than controls at 0 h, but higher than controls at 3 h no significant differences in pain detection values were found. For the cold pressor test, methadone patients detected pain significantly earlier than controls at 0 h, and were also substantially less pain tolerant than controls at both 0 and 3 h. There were no significant differences in pain detection values between the two groups at 3 h. Pain tolerance to pain detection ratios for methadone patients were significantly lower than controls for the cold pressor test at 0 and 3 h, and for electrical stimulation at 0 h only. In summary, the relative pain sensitivity of methadone maintenance patients is determined by the nature of the nociceptive stimulus (e.g. cold pressor test versus electrical stimulation), the plasma methadone concentration (trough versus peak plasma concentration), and whether thresholds are determined for detection of pain or pain tolerance. Although responding to changes in plasma methadone concentration, maintenance patients are markedly hyperalgesic to pain induced by the cold pressor test.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2004
Publisher: Elsevier BV
Date: 02-1999
DOI: 10.1016/S0014-2999(98)00984-4
Abstract: Morphine maintenance doses of 10 mg kg(-1) day(-1), 20 mg kg(-1) day(-1) and 30 mg kg(-1) day(-1) were administered to three groups of rats via miniosmotic pumps for 7 days to induce physical dependence. They were then allowed to undergo spontaneous withdrawal. Radiotelemetric blood pressure measurements showed that morphine increased systolic and diastolic blood pressure on the first day of morphine treatment and produced a dose dependent decrease in heart rate, systolic and diastolic blood pressure thereafter. After the peak depressive effect, development of tolerance to morphine was observed in systolic and diastolic blood pressure, but not in the heart rate. During spontaneous withdrawal, both systolic and diastolic blood pressure increased beyond pre-morphine levels for all doses and there was a rebound increase in heart rate at the 30 mg kg(-1) day(-1) dose. These results suggest that the improved sensitivity of telemetric measures combined with the use of minipumps for morphine treatment provide an animal model of spontaneous opioid withdrawal.
Publisher: Springer Science and Business Media LLC
Date: 06-12-2018
DOI: 10.1007/S00216-017-0747-2
Abstract: 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 s les including antidepressants (amitriptyline, dothiepin, doxepin), antipsychotics (amisulpride, clozapine), illicit drugs (cocaine, meth hetamine, hetamine, 3,4-methylenedioxymeth hetamine (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 (meth hetamine) 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 s ling combined with quantitative and qualitative analysis can deliver. Graphical abstract Temporal analysis of licit and illicit drugs in South Australia.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Wiley
Date: 25-03-2003
DOI: 10.1046/J.1360-0443.2003.00335.X
Abstract: To assess the efficacy of buprenorphine compared with methadone maintenance therapy for opioid dependence in a large s le using a flexible dosing regime and the marketed buprenorphine tablet. Patients were randomized to receive buprenorphine or methadone over a 13-week treatment period in a double-blind, double-dummy trial. Three methadone clinics in Australia. Four hundred and five opioid-dependent patients seeking treatment. Patients received buprenorphine or methadone as indicated clinically using a flexible dosage regime. During weeks 1-6, patients were dosed daily. From weeks 7-13, buprenorphine patients received double their week 6 dose on alternate days. Retention in treatment, and illicit opioid use as determined by urinalysis. Self-reported drug use, psychological functioning, HIV-risk behaviour, general health and subjective ratings were secondary outcomes. Intention-to-treat analyses revealed no significant difference in completion rates at 13 weeks. Methadone was superior to buprenorphine in time to termination over the 13-week period (Wald chi 2 = 4.371, df = 1, P = 0.037), but not separately for the single-day or alternate-day dosing phases. There were no significant between-group differences in morphine-positive urines, or in self-reported heroin or other illicit drug use. The majority (85%) of the buprenorphine patients transferred to alternate-day dosing were maintained in alternate-day dosing. Buprenorphine did not differ from methadone in its ability to suppress heroin use, but retained approximately 10% fewer patients. This poorer retention was due possibly to too-slow induction onto buprenorphine. For the majority of patients, buprenorphine can be administered on alternate days.
Publisher: Wiley
Date: 11-2000
DOI: 10.1046/J.1365-2125.2000.00272.X
Abstract: To investigate the steady-state pharmacokinetics of (R)- and (S)-methadone in a methadone maintenance population. Eighteen patients recruited from a public methadone maintenance program underwent an interdosing interval pharmacokinetic study. Plasma and urine s les were collected and analysed for methadone and its major metabolite (EDDP) using stereoselective h.p.l.c. Methadone plasma protein binding was examined using ultrafiltration, and plasma alpha1-acid glycoprotein concentrations were quantified by radial immunoassay. (R)-methadone had a significantly (P < 0.05) greater unbound fraction (mean 173%) and total renal clearance (182%) compared with (S)-methadone, while maximum measured plasma concentrations (83%) and apparent partial clearance of methadone to EDDP (76%) were significantly (P < 0.001) lower. When protein binding was considered (R)-methadone plasma clearance of the unbound fraction (59%) and apparent partial intrinsic clearance to EDDP (44%) were significantly (P < 0.01) lower than for (S)-methadone, while AUCtau_¿u¿ss (167%) was significantly (P 0.2) differences between the methadone enantiomers for AUCtauss, steady-state plasma clearance, trough plasma concentrations and unbound renal clearance. Patients excreted significantly (P < 0.0001) more (R)-methadone and (S)-EDDP than the corresponding enantiomers. Considerable interin idual variability was observed for the pharmacokinetic parameters, with coefficients of variation of up to 70%. Steady-state pharmacokinetics of unbound methadone are stereoselective, and there is large interin idual variability consistent with CYP3A4 mediated metabolism to the major metabolite EDDP the variability did not obscure a significant dose-plasma concentration relationship. Stereoselective differences in the pharmacokinetics of methadone may have important implications for pharmacokinetic-pharmacodynamic modelling but is unlikely to be important for therapeutic drug monitoring of methadone, in the setting of opioid dependence.
Publisher: Elsevier BV
Date: 08-2021
Publisher: Elsevier BV
Date: 12-2001
DOI: 10.1016/S0024-3205(01)01485-0
Abstract: The present study examined the effect of the gamma-aminobutyric acidB (GABA(B)) receptor agonist, baclofen on naloxone-induced withdrawal signs in morphine-dependent rats and modification by the antagonist, 3-aminopropyl-cyclohexylmethylphosphinic acid (CGP 46381). Morphine was administered via mini-osmotic pumps for 7 days to induce physical dependence. Baclofen (20 mg kg(-1)) decreased stereotyped head movements, chewing, chatter, ptosis and body weight loss, induced by naloxone (10 mg kg(-1)) in morphine-dependent rats. CGP 46381 (20 mg kg(-1)) reversed the effects exerted by baclofen on stereotyped head movements, ptosis, and weight loss and partially reversed the effect of baclofen on chewing. It can be concluded that baclofen has some potential in the treatment of opioid withdrawal and that GABA(B) receptors may be implicated in such a withdrawal.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Elsevier BV
Date: 07-2011
DOI: 10.1016/J.FORSCIINT.2011.01.037
Abstract: Accurate information on drug use in communities is essential if health, social and economic harms associated with illicit drug use are to be addressed efficiently. In most countries population drug use is estimated indirectly via surveys, medical presentations and police and custom seizures. All of these methods have at least some problems due to bias, small s les and/or long time delays between collecting the information and analysing the results. Recently the direct quantification of drug residues in wastewater has shown promise as a means of monitoring drug use in defined geographical areas. In this study we measured 3,4-methylenedioxymeth hetamine (MDMA), meth hetamine and benzoylecgonine in sewage inflows in metropolitan and regional areas of Australia and compared these data with published European data. Cocaine use was small compared to European cities (p<0.001) but was compensated for by much greater consumption of meth hetamine (p<0.001) and MDMA (p<0.05). MDMA was more popular in regional areas (p<0.05) whereas meth hetamine and cocaine were mainly consumed in the city (p<0.05). Greater than 5-fold increases in MDMA use were detected on weekends (p<0.001). This approach has the potential to improve our understanding of drug use in populations and should be further developed to improve prevention and treatment programs.
Publisher: Elsevier BV
Date: 09-2004
Publisher: Elsevier BV
Date: 11-2020
Publisher: Wiley
Date: 06-2003
Publisher: Wiley
Date: 27-10-2004
Publisher: Elsevier BV
Date: 2022
Publisher: Informa Healthcare
Date: 13-12-2007
Abstract: The use of opioids outside of medical practice is a significant health problem with important social and political implications. Although treatment of opioid dependence is traditionally focused on heroin users, there is increasing recognition that a large number of people become dependent through the use of prescription opioids. The necessity for long-term treatment has also been increasingly recognised. At present, there are several pharmacotherapies available for maintenance treatment, including drugs that are full agonists at the opioid receptor (e.g., methadone, slow-release oral morphine), a partial agonist (buprenorphine) and an opioid antagonist (naltrexone). This review examines the existing strategies, highlights problems associated with their use and discusses the opportunities for new treatment approaches, particularly the use of long-acting formulations.
Publisher: Wiley
Date: 08-07-2006
DOI: 10.1080/10550490600754374
Abstract: Methadone maintenance is associated with hyperalgesia and elevated mood disturbance-effects opposite to those induced by acute opioid administration, which may undermine outcomes during substitution therapy. This study examined the impact of switching between methadone and slow-release morphine on pain sensitivity and mood status in 14 methadone maintenance patients using an open-label crossover design. Pain responses were nearly identical for each drug. Patients reporting inadequate withdrawal suppression on methadone showed greater mood stability when transferred to morphine, but overall mood disturbance levels did not differ between drugs. Hyperalgesia and mood disturbance cannot be resolved by changing from methadone to morphine maintenance.
Publisher: Informa UK Limited
Date: 04-2012
DOI: 10.2147/PGPM.S29272
Publisher: Elsevier BV
Date: 26-01-2004
DOI: 10.1016/J.EJPHAR.2003.11.025
Abstract: Illicit and therapeutic opioid administration can result in overdose due to opioid-induced respiratory depression. Research investigating the respiratory depressant effects of opioids has been limited due to difficulties associated with acquiring long-term respiratory data. This study examined the novel use of radiotelemetry to measure respiratory rate, heart rate, locomotor activity and blood pressure in rats treated chronically with methadone. Over 4 days of treatment, respiratory rate decreased, but partial tolerance appeared to develop during active (night) periods. Decreased heart rate was observed during the night periods and tolerance appeared to develop to this effect. Activity and blood pressure did not change with treatment. The effects of naloxone hydrochloride and naloxone methiodide administration on the methadone-treated rats were also examined and both antagonists increased respiratory rate and heart rate, with only naloxone hydrochloride producing significant increases in activity. Radiotelemetry offers a means of evaluating drug effects on respiratory rate continually in ambulatory, unstressed animals.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2012
Publisher: Wiley
Date: 21-04-2004
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.NTT.2009.09.001
Abstract: This study compared the neurological development of 4 month old infants exposed to buprenorphine or methadone during pregnancy to that of a control group of non-exposed infants. Participants were 30 buprenorphine-maintained women, 22 methadone-maintained women and 33 non opioid-dependent controls, and their infants. Women were enrolled during pregnancy as part of an open-label non-randomised flexible-dosing longitudinal study. Groups were matched for maternal age, parity, gravida, and tobacco and alcohol use. Infant neurological development was assessed by measuring latency of pattern reversal visual evoked potentials (VEP). One-way between groups analyses of variance (ANOVA) were conducted to test the statistical significance of differences between the mean latencies of the peak response to two different sized checkerboard patterns (48' and 69' of retinal arc). Infants prenatally exposed to methadone had significantly prolonged latencies, compared with infants in the control group and infants prenatally exposed to buprenorphine, in response to checks of 48' and 69'. VEP latencies of infants prenatally exposed to buprenorphine did not differ significantly from controls for either check size. After adjustment for covariates, prenatal exposure to methadone remained a significant predictor of VEP response to checks of 48', but not 69'. Maternal self-reported used of marijuana during pregnancy made a significant unique contribution to the variance in P1 latencies for both check sizes. Data from this controlled, non-randomised study suggest that buprenorphine may confer an advantage over methadone as a maintenance drug during pregnancy in terms of infant neural development at 4 months of age.
Publisher: Elsevier BV
Date: 25-01-2010
DOI: 10.1016/J.EJPHAR.2009.09.056
Abstract: Methadone used for opioid dependence therapy is associated with increased pain sensitivity. This study aimed to investigate whether methadone administration lowers nociceptive threshold in adult male Sprague-Dawley (SD) rats, and if this threshold could be altered by the NMDA receptor antagonist memantine. Rats were implanted with osmotic pumps delivering 1mg/kg/day methadone (n=6), or saline placebo (n=6) (0.51 microl/h). A separate cohort of rats received either methadone 1mg/kg/day (n=8) or methadone 1mg/kg/day with 20mg/kg/day memantine (n=8). Nociception was measured by the Hargreave's paw withdrawal test. Baseline nociception was measured on day 0 prior to osmotic pump implantation and was measured daily for the following 21 days. Osmotic pumps were removed following nociceptive testing on day 14. Methadone only treated rats had a mean paw withdrawal latency significantly lower than the corresponding values for saline on days 8, 9, 10, 11, 12, 14, and 17 (P 0.05). Paw withdrawal latency of rats treated with methadone co-administered with memantine did not differ significantly compared to methadone only (P>0.05). This demonstrates that methadone induces hyperalgesia in the SD rat yet this hyperalgesia resolves following discontinuation of methadone administration. Furthermore, memantine does not alter the development of methadone-induced hyperalgesia.
Publisher: Elsevier BV
Date: 06-2000
DOI: 10.1016/S0091-3057(00)00176-3
Abstract: Radiotelemetry was utilized to compare zolpidem and lorazepam tolerance and withdrawal in rats. Locomotor activity, electromyographic activity (EMG), and body temperatures were used to assess the acute drug effects, and as measures of tolerance and withdrawal. Lorazepam, zolpidem, or vehicle was administered for 12 days, and data were recorded daily, immediately, after treatment. Data were also recorded immediately after flumazenil (25 mg/kg, IP) precipitated withdrawal and during 4 days of spontaneous withdrawal. Complete tolerance to the acute effects of lorazepam administration developed within 7 days of treatment and both flumazenil-precipitated and spontaneous withdrawal were observed. In contrast, there was no tolerance to the sedative actions of zolpidem administration after 12 days, but complete tolerance to the hypothermic and muscle relaxant effects was apparent after 8 days of treatment. Despite the presence of tolerance, no evidence of either spontaneous or flumazenil-induced withdrawal was recorded in these rats. In conclusion, this model suggests that as a sedative zolpidem has significant advantages over the classic benzodiazepines.
Publisher: Oxford University Press (OUP)
Date: 09-03-2023
DOI: 10.1093/NTR/NTAC275
Abstract: Mixed findings have been reported about the impact of the COVID-19 pandemic on smoking behavior in different populations. In this study, we aimed to quantify changes in smoking prevalence through the proxy of nicotine consumption in the Australian population from 2017 to 2020 inclusive. Estimates of nicotine consumption between 2017 and 2020 were retrieved from a national wastewater monitoring program that covers up to 50% of the Australian population. National sales data for nicotine replacement therapy (NRT) products from 2017 to 2020 were also acquired. Linear regression and pairwise comparison were conducted to identify data trends and to test differences between time periods. The average consumption of nicotine in Australia decreased between 2017 and 2019 but increased in 2020. Estimated consumption in the first half of 2020 was significantly higher (~30%) than the previous period. Sales of NRT products increased gradually from 2017 to 2020 although sales in the first half of the year were consistently lower than in the second half. Total nicotine consumption increased in Australia during the early stage of the pandemic in 2020. Increased nicotine consumption may be due to people managing higher stress levels, such as from loneliness due to control measures, and also greater opportunities to smoke/vape while working from home and during lockdowns in the early stage of the pandemic. Tobacco and nicotine consumption have been decreasing in Australia but the COVID-19 pandemic may have temporarily disrupted this trend. In 2020, the higher impacts of lockdowns and working from home arrangements may have led to a temporary reversal of the previous downward trend in smoking during the early stage of the pandemic.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.SCITOTENV.2013.11.075
Abstract: Wastewater analysis has the potential to provide objective information on community drug use. Introducing a population biomarker (PB) in the s le analysis may significantly reduce errors in the back-calculation associated with population estimation and wastewater volume measurement. A number of potential PBs have been suggested but no systematic evaluation has been conducted so far. This study evaluated the eligibility of the previously suggested PB candidates (creatinine, cholesterol, coprostanol and cotinine) as well as three new ones (cortisol, androstenedione and 5-hydroxyindoleacetic acid (5-HIAA)) using five criteria. We assessed the quantification method, affinity to particulate matter and stability of candidates in wastewater, as well as the constancy of inter-day excretion and correlation between excretion and census population. All PB candidates were quantifiable in wastewater. Cholesterol and coprostanol were eliminated from further consideration due to affinity to particulate matters in the wastewater. Creatinine, cortisol and androstenedione were disqualified for stability reasons. On a population scale, both cotinine and 5-HIAA were excreted (RSD=8.01 ± 1.13% and 10.20 ± 0.89%, respectively) at a constant rate and concentrations of each correlated well with the census population (r=0.9809 and 0.9442, respectively). Overall, both cotinine and 5-HIAA are eligible PBs, but the neurotransmitter metabolite 5-HIAA may be more suitable for international comparisons.
Publisher: Informa UK Limited
Date: 04-2012
DOI: 10.2147/JPR.S27738
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.FORSCIINT.2013.06.007
Abstract: A decline in 3,4-methylenedioxy-N-methyl hetamine (MDMA) use in Adelaide, Australia from 2009 to 2010 was confirmed by us previously. Reports suggested that the shortage in MDMA supply was associated with an increased prevalence of other synthetic stimulants, but quantitative measurements were unavailable. To obtain objective data on the community use of synthetic stimulants, we collected wastewater s les from multiple treatment plants in Adelaide, Australia from 2009 to 2011 and analysed them using solid-phase extraction/liquid chromatography/tandem mass spectrometry (SPE-LC-MS/MS), targeting MDMA and some of the most reported synthetic cathinones and piperazines. Data were temporally compared. MDMA and six other synthetic stimulants were detected and quantified in wastewater s les. While MDMA level decreased markedly from 2009 to 2010 and remained low in 2011, localized increased use of mephedrone, methylone, methylenedioxypyrovalerone (MDPV), benzylpiperazine (BZP), 3-trifluoromethylphenylpiperazine (TFMPP), but not methcathinone, was observed in 2010 and 2011. This suggested that the decline in MDMA use was associated with an increase in the use of a number of other synthetic stimulants. However, the lag time from the decrease in MDMA to the increase in use of a number of these stimulants, together with the highly regionalized use of all synthetic stimulants except methcathinone indicates that there was no direct population wide substitution in response to the reduction in MDMA.
Publisher: Elsevier BV
Date: 03-1995
DOI: 10.1016/0306-3623(94)00175-M
Abstract: 1. While GABAB antagonists have been examined in vitro, very few have been tested in vivo. A range of GABAB antagonists were tested against baclofen-induced muscle relaxation and hypothermia. 2. The GABAB antagonists exhibited a range of in vivo activity profiles. 3. CGP 35348 showed clear antagonist effects, while BPBA and 4-ABPA appeared to have agonist properties. 4. Phaclofen, 2-hydroxysaclofen, 3-APPA and 9G seemed to have little effect in this system at the doses tested. 5. Differences between in vivo and in vitro activity could be explained by differences in blood-brain barrier permeability, or possible differences in affinities for the sub-classes of GABAB receptors.
Publisher: Elsevier BV
Date: 04-2001
DOI: 10.1016/S0028-3908(00)00196-9
Abstract: The present study used a radiotelemetric method to compare the muscle relaxant, hypothermic and locomotor depressant actions of the imidazopyridine zolpidem, with those of the benzodiazepines lorazepam and diazepam. Rats, n=7 per group, were ided into 3 dose-dependent treatment groups (highest, middle, and lowest). Each rat within a treatment group received a single dose of diazepam, lorazepam, zolpidem and vehicle. All three drugs induced dose-dependent decreases in body temperature, locomotor activity and electromyographic (EMG) activity. Administration of zolpidem (5 and 10 mg/kg) resulted in maximal decrements in locomotor activity that were comparable to those elicited by both diazepam (10 and 20 mg/kg) and lorazepam (12.5 and 25 mg/kg). Zolpidem (10 mg/kg) decreased EMG activity levels to approximately 45% of vehicle treated controls a value similar to that induced by diazepam (2.5 mg/kg). These data suggest that the imidazopyridine zolpidem has a similar profile of acute effects in comparison to the benzodiazepines diazepam and lorazepam. However, the relative magnitude of the effects differed, with zolpidem producing less hypothermia and muscle relaxation than the two benzodiazepines.
Publisher: Elsevier BV
Date: 05-1997
DOI: 10.1016/S0091-3057(96)00166-9
Abstract: Spontaneously hypertensive rats (SHRs) rats have been reported to have decreased sensitivity to pain, but as yet a mechanism has not been identified. This study investigated the effects of subcutaneous and intracerebroventricular (ICV) infusions of angiotensin II on blood pressure, locomotor activity, and tailflick and hot plate latencies in the Wistar-Kyoto (WKY) and outbred Wistar rat. Peripheral but not central administration of angiotensin II (567 micrograms/kg/day) increased hot plate latencies in WKY and Wistar rats to a level equivalent to that observed in the SHR. Peripheral administration of norepinephrine (50 and 100 mg/kg/day) to WKYs increased blood pressure but had no effect on hotplate latency. ICV administration of losartan (1 & 3 mg/kg/day) to SHRs had no effect on blood pressure or nociception. The results indicate that angiotensin II has a role in the altered pain perception observed in the SHR and that its site of action is peripheral.
Publisher: Springer Science and Business Media LLC
Date: 06-1999
Publisher: Elsevier BV
Date: 1994
DOI: 10.1016/0376-8716(94)90131-7
Abstract: The injecting behaviour and risky needle use of a s le of 193 methadone maintenance clients was investigated. The majority of the s le (n = 116) reported injecting one or more drugs in the month prior to data collection. Compared with non-injectors, the injectors were slightly younger, had been on the methadone program for a shorter period of time, had lower methadone doses and more severe drug and legal problems. The injecting sub-group was examined in more detail by comparing those subjects whose injecting practices conformed to guidelines on minimizing risk of HIV transmission with those who, in the preceding month, made at least one injection contravening these guidelines and thus placed themselves at risk of contracting HIV. A greater proportion of these risky injectors were unemployed. Importantly, risky injectors had lesser knowledge of means of preventing the spread of HIV than safe injectors. It is concluded that the reduction of HIV transmission could be enhanced by improvements in methadone programs, particularly ensuring adequate dosing and high retention rates. Further, there is a need to improve knowledge with regard to what are safe and what are risky injecting practices and needle/syringe cleaning methods.
Publisher: AMPCo
Date: 07-2017
DOI: 10.5694/MJA17.00137
Publisher: Wiley
Date: 29-11-2023
DOI: 10.1111/ADD.16083
Abstract: From 1 February 2018, codeine was rescheduled from an over‐the‐counter (OTC) to a prescription‐only medicine in Australia. We used wastewater‐based epidemiology to measure changes in population codeine consumption before and after rescheduling. We analysed 3703 wastewater s les from 48 wastewater treatment plants, taken between August 2016 and August 2019. Our s les represented 10.6 million people, 45% of the Australian population in state capitals and regional areas in each state or territory. Codeine concentrations were determined by liquid chromatography–tandem mass spectrometry and converted to per‐capita consumption estimates using the site daily wastewater volume, catchment populations and codeine excretion kinetics. Average per‐capita consumption of codeine decreased by 37% nationally immediately after the rescheduling in February 2018 [95% confidence interval (CI) = 35.3–39.4%] and substantially in all states between 24 and 51% (95% CI = 22.4–27.0% and 41.8–59.4%). The decrease was sustained at the lower level to August 2019. Locations with least pharmacy access decreased by 51% (95% CI = 41.7–61.7%), a greater decrease than 37% observed for those with greater pharmacy access (95% CI = 35.1–39.4%). Regional areas decreased by a smaller margin to cities (32 versus 38%, 95% CI = 30.2–34.1% versus 34.9–40.4%, respectively) from a base per‐capita usage approximately 40% higher than cities. Wastewater analysis shows that codeine consumption in Australia decreased by approximately 37% following its rescheduling as a prescription‐only medicine in 2018. Wastewater‐based epidemiology can be used to evaluate changes in population pharmaceutical consumption in responses to changes in drug scheduling.
Publisher: Elsevier BV
Date: 11-2023
Publisher: Elsevier
Date: 2017
Publisher: Elsevier BV
Date: 04-2003
DOI: 10.1016/S0376-8716(02)00322-8
Abstract: In maintenance patients methadone has been shown to produce considerable changes in opioid effects and withdrawal over the dosing interval. As a partial agonist buprenorphine may be expected to produce smaller changes, but the nature and magnitude of these changes have only been described for single doses. In the present study opioid effects and withdrawal were described in patients maintained on buprenorphine. Twenty four opioid dependent subjects were administered 16 mg buprenorphine tablets sublingually for 10 days. On day 10 plasma s les were collected and physiological, subjective and observer-rated measures collected pre-dose and at 14 time points during the dosing interval. No significant respiratory depression was observed. Consistent with the partial agonist properties of buprenorphine, other physiological and subjective changes were also of small magnitude. However, even at a once daily dose of 16 mg some patients experienced significant opioid withdrawal that was maximal at the end of the dosing interval. Buprenorphine maintenance should be associated with a high level of safety and a low level of disruption caused by changing opioid effects over the dosing interval, but some patients may require high doses or other strategies to completely suppress withdrawal.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2006
DOI: 10.1016/J.PAIN.2005.11.005
Abstract: Opioid dependent patients require higher than normal doses of opioid analgesics. However, this regimen has not been formally tested. This study utilised a double-blind placebo-controlled design to examine antinociceptive responses to saline and pseudo-steady-state plasma morphine concentrations (173+/-11 (mean+/-SEM), range 106-305 ng/ml) in 18 methadone participants in three stable, once daily methadone dose ranges 11-45 mg (n=6), 46-80 mg (n=6), 81-115 mg (n=6) and 10 controls. Testing commenced approximately 20 h after the maintenance dose with the next dose given 1h after morphine cessation. Nociceptive stimuli (cold pressor (seconds) and electrical stimulation (volts)) were used to measure pain detection threshold and pain tolerance. Blood s les were analysed by HPLC for plasma morphine and R-(-)-methadone concentrations. Methadone participants were hyperalgesic to cold pressor pain. High plasma morphine concentrations failed to significantly change cold pressor and electrical stimulation pain tolerance for methadone patients, but in controls, morphine significantly (P<0.05) increased mean pain tolerance to cold pressor by 59+/-29% (range -17% to 311%) and electrical stimulation by 19+/-6% (range 0% to 58%). Morphine significantly (P<0.05) decreased respiration rates by 12+/-3% (range -29% to 8%) in methadone subjects. On saline days, rising methadone concentrations significantly (P<0.01) increased cold pressor pain detection threshold by 32+/-6% (range 1-81%) and cold pressor pain tolerance by 23+/-6% (range -32% to 56%). Methadone maintained patients are hyperalgesic and cross-tolerant to the antinociceptive effects of very high plasma morphine concentrations. While even higher morphine doses may achieve some pain relief, this may be at the cost of unacceptable respiratory depression.
Publisher: Elsevier BV
Date: 09-2016
Publisher: Wiley
Date: 11-2012
DOI: 10.1111/J.1360-0443.2011.03634.X
Abstract: Opioids have been implicated in emotion regulation. Opioid users report decreased negative emotional response, but there has been no formal study on the effect of opioid administration on emotional reactivity. The aim of this study was to investigate the effect of methadone on emotional reactivity in methadone-maintained patients. Velten's mood induction procedures were used to induce elative and depressive emotional reactions in the subjects. Each group was administered both induction procedures at 0 hour and 3 hours (corresponding with trough and peak plasma methadone concentrations in methadone subjects). A drug treatment clinic with an out-patient methadone maintenance treatment programme. Twenty-one subjects currently on methadone maintenance treatment and 21 controls with no history of opioid dependence. Emotional reactivity was measured using mood visual analogue scales. At 0 hour, methadone and control subjects showed similar elation (methadone 13.2 ± 3.1 mean ± standard error of the mean [SEM], control 14.4 ± 3.7) and depression reactivity (methadone 23.6 ± 5.0, control 25.1 ± 5.0). However, at 3 hours repeated measures showed that methadone subjects had significantly decreased depression reactivity (methadone 18.5 ± 4.6, control 36.7 ± 5.7 P = 0.021) and elation reactivity (methadone 4.4 ± 1.9, control 19.0 ± 2.4) compared to controls. Opioid addicts on methadone maintenance appear to be less reactive to mood induction at times of peak plasma methadone concentration than non-addict controls this suggests that methadone blunts both elative and depressive emotional reactivity.
Publisher: Elsevier BV
Date: 09-1999
DOI: 10.1016/S0091-3057(99)00116-1
Abstract: Ingestion of MDMA ("ecstasy") by humans can cause acute toxicity manifested by hyperthermia and death. Demethylenation of MDMA is catalyzed by cytochrome P-450 2D6 (CYP2D6) and cytochrome P-450 2D1 (CYP2D1) in humans and rats, respectively, and is polymorphically expressed. It has been proposed that CYP2D6 deficiency may account for the unexplained toxicity of MDMA. The female Dark Agouti rat is deficient in CYP2D1, and serves as a model for the human poor metabolizer. We investigated thermogenic and locomotor actions of MDMA in adult female Sprague-Dawley (CYP2D1 replete) and Dark Agouti rats. MDMA (2, 5, and 10 mg/kg) and saline were injected subcutaneously at ambient temperatures of 22 and 31 degrees C. There was no difference in core temperature responses between the two rat strains. Hypothermia occurred in the first 30 min and temperature elevation thereafter. MDMA increased locomotor activity in Sprague-Dawley but not in Dark Agouti rats. However, MDMA had pronounced lethal effects at 31 degrees C ambient in the Dark Agouti rats only. We conclude that the poor metaboliser phenotype may predispose to lethality, but the mechanism is as yet unknown.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2011
Publisher: Elsevier BV
Date: 06-2008
DOI: 10.1016/J.JSAT.2007.05.007
Abstract: Testing of a new scale, the Amphetamine Cessation Symptom Assessment (ACSA), in a s le of treatment-seeking hetamine users (N = 133) showed satisfactory reliability, while factor analysis identified three components explaining 64.7% of the variance in scores. Scores were inversely related to subjective general well-being (r = -.33, p < .01) and directly related to the Beck Depression Inventory (r = .59, p < .01). There were positive relationships between the ACSA and measures of hetamine dependence (r = .36, p < .01) and the intensity of recent hetamine use (r = .24, p < .01). The ACSA discriminated between "low-dose" and "high-dose" users, indicating discriminant validity. In inpatients (n = 63), ACSA scores declined significantly over time, while higher scores in inpatient treatment dropouts indicated predictive validity. The ACSA showed satisfactory reliability and validity, with a three-factor solution providing the best fit to the data. The ACSA could play an important role in providing clinical outcome data, particularly in outcome evaluation of new treatment protocols.
Publisher: Wiley
Date: 04-2000
DOI: 10.1046/J.1365-2923.2000.00493.X
Abstract: New medical graduates lack clinical skills in assessing and managing patients seeking drugs of dependence. This study compares the effectiveness of three different clinical skills training methods, with similar content, which were developed to teach these skills to senior medical students. A preliminary survey indicated that common problems seen by primary care practitioners included both new and previously known patients seeking either benzodiazepines or opiates. The common content of the teaching was determined from this survey. A didactic small group tutorial (DT), a video-based tutorial (VBT) using professional actors, and a computer-aided instruction package using digitized video (CAI) were developed with this common content, and trialled with undergraduate medical students over 2 years in a parallel-group design. Outcome was assessed by student feedback, performance on a case-based written examination and by a structured evaluation of interviews with simulated patients requesting drugs. Comparison was also made between methods on the basis of knowledge tests. No difference was seen in written examination and simulated patient outcomes between the three groups. However, the VBT was thought by the students to be preferable to other methods. The estimated development costs of CAI were higher, but total costs over a 6-year period were lower than for the DT and VBT. The results suggest that clinical skills can be taught equally effectively through several different methods. Collaboration between institutions in the development of widely applicable CAI tools should be an efficient and economical mode of teaching with a wide range of applications.
Publisher: Public Library of Science (PLoS)
Date: 18-12-2012
Publisher: Cambridge University Press (CUP)
Date: 02-04-2012
DOI: 10.1017/S2040174412000190
Abstract: This study aimed to determine if morphine is effective in ameliorating Neonatal Abstinence Syndrome (NAS) symptoms to non-opioid-exposed control levels in methadone- and buprenorphine-exposed infants. A prospective, non-randomized comparison study with flexible dosing was undertaken in a large teaching maternity hospital in Australia. Twenty-five infants in the groups of buprenorphine-, methadone- and control non-opioid-exposed infants were compared (total n = 75 infants). Oral morphine sulphate (1 mg/ml) was administered every 4 h to opioid agonist-exposed infants. Modified Finnegan Withdrawal Scale (MFWS) scores determined dosing: score of 8–10: 0.5 mg/kg/day, 11–13: 0.7 mg/kg/day and 14+: 0.9 mg/kg/day. Withdrawal score, amount of morphine administered and length of hospital stay, were used to assess NAS over a 4-week follow-up period. No controls achieved a score higher than 7 on the MFWS. There was no significant difference in the percentage of infants requiring treatment between methadone (60%) and buprenorphine (48%) infants. For treated infants, significantly ( P 0.01) more morphine was administered to methadone (40.07 ± 3.95 mg) compared with buprenorphine infants (22.77 ± 4.29 mg) to attempt to control NAS. Following treatment initiation, significantly more ( P 0.01) methadone (87%) compared with buprenorphine infants (42%) continued to exceed scoring thresholds for morphine treatment requirement, and non-opioid-exposed control infant scores. For treated infants, there was no significant difference in length of hospital stay between methadone and buprenorphine infants. Morphine treatment was not entirely effective in ameliorating NAS to non-opioid-exposed control symptom levels in methadone or buprenorphine infants. The regimen may be less effective in methadone compared with buprenorphine infants.
Publisher: Wiley
Date: 11-11-2010
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.CHROMA.2019.460623
Abstract: 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 s les. All were stable in s le, 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.
Publisher: Elsevier BV
Date: 02-1995
DOI: 10.1016/0024-3205(95)00043-6
Abstract: This study investigated the effects of captopril, hydralazine and losartan on the locomotor activity, tailflick and hot plate latencies in spontaneously hypertensive rats (SHR) and their genetic controls the Wistar-Kyoto rat (WKY). The increased hot plate latencies normally exhibited by the spontaneously hypertensive rat were reduced or abolished by captopril (95 mg/kg/day p.o.) and losartan (18 mg/kg/day p.o.) treatment, but were unaffected by hydralazine (19 mg/kg/day p.o.). There were no observable effects of any of the drugs on tailflick latencies or locomotor activity. The results highlight a potential role for angiotensin II in analgesia that is independent of blood pressure change.
Publisher: Springer Science and Business Media LLC
Date: 17-11-2001
Abstract: d-Amphetamine is known to have effects on heart rate, body temperature and locomotor activity. However, it is not known if GABAB receptor stimulation modifies these actions of d- hetamine. Using telemetry recordings, this study examined the interactions between the GABAB receptor agonist baclofen and d- hetamine, on heart rate responses, body temperature and locomotor activity, and whether these effects could be blocked by the GABAB receptor antagonist SCH 50911. Rats were prepared with telemetry implants, which allowed continuous monitoring of heart rate, core temperature and spontaneous locomotor activity. Drugs were subsequently administered subcutaneously to the animals for simultaneous recording over a period of 180 min. d-Amphetamine alone (0.3, 1.0 and 3.0 mg/kg) produced a dose-related increase in heart rate, but was without any effect on body temperature, whilst at 1.0 mg/kg, it significantly increased locomotor activity. Baclofen increased heart rate without affecting locomotor activity, and, at the highest dose of 10.0 mg/kg, it induced a significant reduction in body temperature. Graded doses of baclofen (3.0-10.0 mg/kg), when co-administered with d- hetamine (1.0 mg/kg), did not modify the d- hetamine-induced increase in heart rate, but the combination produced significant reductions of body temperature. The latter was only partially reversed by the GABAB receptor antagonist SCH 50911 (10.0 mg/kg). By contrast, the increase in locomotor activity by d- hetamine was markedly blocked by baclofen in a dose-related manner, and this effect was abolished by SCH 50911 (10.0 mg/kg). SCH 50911 alone at doses of 3.0, 6.0 and 10.0 mg/kg had no effect on temperature or locomotor activity. Heart rate was increased significantly, but the magnitude of change was small. The results of the present study suggest that stimulation of GABAB receptors by baclofen completely blocks the locomotor stimulatory effects of d- hetamine. Baclofen did not significantly modify the increase in heart rate produced by d- hetamine and decreased body temperature, both alone and in combination with d- hetamine. GABAB receptor ligands may well have potential as pharmacotherapies in the treatment of hetamine abuse and dependence.
Publisher: Wiley
Date: 15-07-2005
DOI: 10.1111/J.1360-0443.2005.01160.X
Abstract: To characterize the natural history of meth hetamine withdrawal during the first 3 weeks of abstinence. Cross-sectional study with comparison group. Setting A substance use treatment facility in Chiang Mai Province, Thailand. The s le comprised 21 in-patients undergoing treatment for meth hetamine dependence. Nine age- and sex-matched non-dependent in iduals provided comparison data. Instruments including: the Amphetamine Withdrawal Questionnaire, a modified version of the Cocaine Selective Severity Assessment, Clinical Global Impression scale and the St Mary's Hospital Sleep Questionnaire were completed daily for the first 3 weeks of abstinence. Meth hetamine withdrawal severity declined from a high initial peak within 24 hours of the last use of hetamines reducing to near control levels by the end of the first week of abstinence (the acute phase). The acute phase of hetamine withdrawal was characterized by increased sleeping and eating, a cluster of depression-related symptoms and less severely, anxiety and craving-related symptoms. Following the acute withdrawal phase most withdrawal symptoms remained stable and at low levels for the remaining 2 weeks of abstinence. This study has provided evidence of a meth hetamine withdrawal syndrome that can be categorized into two phases, the acute phase lasting 7-10 days during which overall symptom severity declined in a linear pattern from a high initial peak, and a subacute phase lasting at least a further 2 weeks.
Publisher: Wiley
Date: 27-06-2014
DOI: 10.1111/DDI.12234
Abstract: Over the past twelve years the number of papers that explore the impacts of climate change on bio ersity in the conservation literature has grown on average by 20% annually. By categorising these papers on their primary research questions, we show that the vast majority of these articles (88.6%) focus only on those impacts that arise directly as a result of climate change, ignoring the potentially significant indirect threats that arise from human adaptation responses. This pattern has remained fairly consistent throughout the review period (2000–2012), with a trend towards more articles considering both direct and indirect impacts towards the end of the period. We also find a bias in the time‐frames considered by published articles that project future impacts of climate change on bio ersity, with more than three‐quarters (77.9%) of papers only considering impacts after 2031, and almost half (49.1%) only considering impacts after 2051. This focus on long‐term, direct impacts creates a mismatch, not only with the life‐cycles of species and timescales of many ecological processes, but also with most management and policy timelines and the short‐term nature of human decision making processes. The focus on studying the long‐term, direct impacts of climate change on bio ersity is likely a function of the lack of availability of climate projections on shorter temporal scales a perception that short‐term impacts will be minor and, insufficient integration with the social and political sciences. While the direct impact of changes in mean climatic conditions will significantly change the biosphere by the end of the century, near term changes in seasonality and extreme events coupled with human adaptation responses are likely to have substantial impacts much sooner, threatening the survival of species and ecosystems. It is therefore essential that we balance our research efforts to facilitate a better understanding of these more imminent threats.
Publisher: Elsevier BV
Date: 05-2002
DOI: 10.1016/S0376-8716(02)00007-8
Abstract: Studies of relative LAAM-methadone preference have indicated that a significant proportion of patients prefer levo-alpha-acetylmethadol (LAAM). The present study was designed to determine whether this preference is associated with better treatment outcomes. Sixty-two stable methadone patients participated in a randomised crossover clinical trial. They received LAAM (alternate days) and methadone (daily) for 3 months each, followed by a further 6-month period during which they were free to choose between the drugs. LAAM maintenance was associated with a lower rate of heroin use than methadone maintenance based on analysis of morphine concentration in hair and equivalent health outcomes. The majority of subjects showed a preference for LAAM (n=27, 69.2%) rather than methadone (n=12, 30.8%). The main reasons given for the LAAM preference were that it produced less withdrawal (39.3%), fewer side effects (28.5%), less craving for heroin (17.9%), and entailed fewer pick-up days (14.3%). Those who chose LAAM had lower levels of heroin use during LAAM maintenance, significantly better outcomes on two sub-scales of the SF-36 (Vitality and Mental Health), and reported that they felt more normal and that they were 'held' better when on LAAM. For those who chose methadone, there were no differences in outcomes between the LAAM and methadone maintenance periods. Preference for LAAM is associated with treatment outcomes as good or better than those with methadone.
Publisher: Elsevier BV
Date: 05-2023
Publisher: SAGE Publications
Date: 08-2008
DOI: 10.1080/08897070802218554
Abstract: Meth hetamine dependence is a serious public health problem worldwide for which there are no approved pharmacological treatments. Psychotherapy is still the mainstay of treatment however, relapse rates are high. The search for effective pharmacological treatment has intensified in the last decade. This review will highlight progress in pharmacological interventions to treat meth hetamine dependence as well as explore new pharmacological targets. Published data from clinical trials for stimulant addiction were searched using PubMed and summarized, as well as highlights from a recent symposium on meth hetamine pharmacotherapy presented at the ISAM 2006 meeting, including interim analysis data from an ongoing D- hetamine study in Australia. Early pilot data are encouraging for administering D- hetamine and methylphenidate as treatment for heavy hetamine users. Abilify at 15 mg/day dose increased hetamine use in an outpatient pilot study. Sertraline, ondansetron, baclofen, tyrosine, and imipramine were ineffective in proof-of-concept studies. Development of pharmacotherapy for meth hetamine dependence is still in an early stage. Data suggesting D- hetamine and methylphenidate as effective pharmacotherapy for meth hetamine addiction will need to be confirmed by larger trials. Preclinical data suggest that use of GVG, CB1 antagonist, and lobeline are also promising therapeutic strategies.
Publisher: Elsevier BV
Date: 10-09-2003
DOI: 10.1016/S0376-8716(03)00169-8
Abstract: This article presents the cost-effectiveness results of a randomised controlled trial conducted in two Australian cities. The trial was designed to assess the safety, efficacy and cost-effectiveness of buprenorphine versus methadone in the management of opioid dependence. The trial utilised a flexible dosing regime that was tailored to the clinical need of the patients, with high maximum doses, using the marketed formulation, under double-blind conditions. A total of 405 subjects were randomised to a treatment at one of three specialist outpatient drug treatment centres in Adelaide and Sydney, Australia. The perspective of the cost-effectiveness analysis was that of the service provider and included costs relevant to the provision of treatment. The primary outcome measure used in the economic analysis was change in heroin-free days from baseline to the sixth month of treatment. Treatment with methadone was found to be both less expensive and more effective than treatment with buprenorphine, which suggests methadone dominates buprenorphine. However, statistical testing found that the observed difference between the cost-effectiveness of methadone and buprenorphine treatments was not statistically significant. The results of this study provide useful policy information on the costs and outcomes associated with the use of methadone and buprenorphine and indicate that buprenorphine provides a viable alternative to methadone in the treatment of opioid dependence.
Publisher: SAGE Publications
Date: 04-2010
DOI: 10.1080/08897071003641578
Abstract: Acceptance and Commitment Therapy (ACT) incorporates developments in behavior therapy, holds promise but has not been evaluated for meth hetamine use disorders. The objective of this study was to test whether ACT would increase treatment attendance and reduce meth hetamine use and related harms compared to cognitive behavior therapy (CBT). One hundred and four treatment-seeking adults with meth hetamine abuse or dependence were randomly assigned to receive 12 weekly 60-minute in idual sessions of ACT or CBT. Attrition was 70% at 12 weeks and 86% at 24 weeks postentry. Per intention-to-treat analysis, there were no significant differences between the treatment groups in treatment attendance (median 3 sessions), and meth hetamine-related outcomes however, meth hetamine use (toxicology-assessed and self-reported), negative consequences, and dependence severity significantly improved over time in both groups. Although ACT did not improve treatment outcomes or attendance compared to CBT, it may be a viable alternative to CBT for meth hetamine use disorders. Future rigorous research in this area seems warranted.
Publisher: Wiley
Date: 03-09-2004
Publisher: Wiley
Date: 12-05-2004
Publisher: Elsevier BV
Date: 11-1997
DOI: 10.1016/S1056-8719(97)00081-6
Abstract: We examined the influence of procedures used in blood pressure measurement on blood pressure and the effects of antihypertensive agents. Subjects were spontaneously hypertensive rats (SHR) and their Wistar/Kyoto (WKY) controls. Blood pressure was recorded by telemetry. Twenty-four h baseline pressure were measured, and the effect of minor handling on blood pressure and heart rate was examined. The influence of restraint such as is used for tail-cuff blood pressures was examined. The effects of three different antihypertensive drugs was also examined in the SHR. In the home-cage environment, the SHRs showed higher systolic blood pressures, but had similar hypertensive responses to minor handling as the WKYs. Both strains had elevated heart rate and blood pressure when restrained in the manner used for tail-cuff readings. The antihypertensive effects of captopril and losartan in the SHR were unchanged when the animals were restrained but the hypotensive effect of hydralazine was greater. These results confirm that significant changes in heart rate and blood pressure can occur as a result of the minor procedures frequently used in blood pressure recording in both SHR and WKY rats. This suggests that telemetry may have significant advantages as a method for continuous blood pressure monitoring. The pharmacological profile of antihypertensive drugs may well be different in animals where telemetry is employed and are not subject to the stresses involved in previous methods of monitoring blood pressure.
Publisher: Elsevier BV
Date: 08-2022
DOI: 10.1016/J.SCITOTENV.2022.155696
Abstract: Methcathinone is a prevalent Novel Psychoactive Substance (NPS) used illicitly in some countries. Routine analysis of wastewater s led from catchments in South Australia has shown a consistent low-level presence of the compound, inconsistent with NPS use. This raised the question was the occurrence due to regular use as a drug of choice or was it an artefact being produced from other sources in the sewer system? NPS consumption is generally sporadic and would therefore point to the origin of methcathinone in wastewater being due to in-sewer oxidation of its legal precursor, pseudoephedrine. The present study tested this hypothesis by comparing the levels of pseudoephedrine and methcathinone in wastewater s les collected bimonthly from 8 catchment sites in South Australia. Laboratory experiments exposing pseudoephedrine to common household oxidizing agents (hypochlorite and percarbonate) were also performed and the production of methcathinone was demonstrated and monitored. The results of this study showed that the level of pseudoephedrine and methcathinone measured in wastewater followed a similar pattern. However, there were periods when the levels of each compound erged. Laboratory experiments showed that when exposed to various oxidizing agents, pseudoephedrine is oxidised to non-stoichiometric quantities of methcathinone. Although the use of methcathinone as a drug of choice remains possible, the results of this study indicate that the low and persistent level of methcathinone found in wastewater may arise in part from the oxidation of pseudoephedrine in the sewer system.
Publisher: Wiley
Date: 22-07-2015
DOI: 10.1002/DTA.1842
Abstract: Wastewater analysis, the chemical analysis of municipal sewage, is fast becoming the technique of choice to monitor changes in community consumption of a range of compounds over time. Currently wastewater analyses which estimate tobacco consumption focus on the major alkaloid nicotine and its urinary metabolite, cotinine. As nicotine is also present in replacement therapies such as nicotine gum and patches, this analysis is not specific and hence does not truly reflect the harmful consumption of tobacco. Two alkaloids - anabasine and anatabine - which are specific to dried tobacco, were assessed as biomarkers for tobacco consumption in wastewater, together with nicotine and cotinine. Consequently, solid phase extraction (SPE) and liquid chromatography-mass spectrometry (LC-MS) methods for the detection of anabasine, anatabine, nicotine, and cotinine in municipal wastewater were validated. All compounds were detected in wastewater extracts and found to have satisfactory recovery, accuracy, precision, and stability in wastewater. Daily flow volume and catchment population of the wastewater facility were used to estimate normalized consumption figures of mg/day/1000 people for composite s les collected over one week, in an application of the method. Anabasine and anatabine were found to be suitable wastewater biomarkers of tobacco and can be used to assess tobacco consumption of communities via wastewater analysis. Application of this methodology can be used to collect temporal consumption data which could be used to determine the efficacy of tobacco reduction strategies. Copyright © 2015 John Wiley & Sons, Ltd.
Publisher: Elsevier BV
Date: 07-2009
DOI: 10.1016/J.DRUGALCDEP.2009.03.008
Abstract: Buprenorphine, a mu-opioid receptor partial agonist, has been shown to be safe and effective for treatment of opioid dependence. A novel implantable formulation of buprenorphine (Probuphine), using a polymer matrix sustained-release technology, has been developed to offer treatment for opioid dependence while minimizing risks of patient noncompliance and illicit ersion. The goal of the current study was to conduct an initial, open-label, evaluation of the safety, pharmacokinetics, and efficacy of two doses of Probuphine in subjects with opioid dependence maintained on sublingual buprenorphine. Two doses of Probuphine were evaluated in 12 heroin-dependent volunteers switched from daily sublingual buprenorphine dosing to either two or four Probuphine implants based upon their buprenorphine daily maintenance dose of 8 mg or 16 mg respectively, and were monitored for 6 months. Probuphine implants provided continuous steady state delivery of buprenorphine until their removal at 6 months. Withdrawal symptoms and craving remained low throughout the 6 months. For the 12 subjects, an average of 59% of urines were opioid-negative across the 6 month treatment period. Injection site reactions were present in half of patients, but none were serious. No safety concerns were evident. These results suggest that Probuphine implants offer significant promise for enhancing delivery of effective opioid substitution treatment while minimizing risk for abuse of medication.
Publisher: Wiley
Date: 28-10-2008
Publisher: Wiley
Date: 20-07-2020
DOI: 10.1002/DTA.2890
Publisher: Wiley
Date: 10-2008
DOI: 10.1016/J.EJPAIN.2007.12.012
Abstract: The treatment of acute pain in patients maintained on methadone is difficult due to increased pain sensitivity (hyperalgesia) and cross-tolerance to other opioids. This study aimed to investigate whether remifentanil elicits antinociception in methadone-maintained subjects in a dose-dependent manner. Eight chronic methadone-maintained subjects attended the testing session approximately 20 h after their normal methadone dose (range 50-110 mgday(-1)). Following a 20 min saline infusion, subjects were administered intravenous remifentanil in seven increasing doses ranging from 0.5 to 3.5 microgkg(-1)min(-1), each for 2 0min. Testing was performed in the last 10 min of each infusion. The testing measures included nociception, as measured by the cold pressor test, withdrawal using the subjective opiate withdrawal scale (SOWS), and subjective opioid effects using the morphine-benzedrine group scale (MBG). Results showed dose-dependent increase in cold pressor tolerance time from baseline of 15.6+/-3.5 (mean+/-SEM)s up to 77.3+/-24.7s during this dosing protocol. During the infusion typical mu-opioid receptor agonist side effects were observed, but with no withdrawal. Methadone-maintained patients demonstrate significant tolerance to remifentanil and may require opioid doses 20-30 higher than required for the treatment of acute pain in opioid-naïve patients.
Publisher: Elsevier BV
Date: 03-2006
DOI: 10.1016/J.ADDBEH.2005.05.016
Abstract: This economic evaluation was part of the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD) project. Data from four trials of heroin detoxification methods, involving 365 participants, were pooled to enable a comprehensive comparison of the cost-effectiveness of five inpatient and outpatient detoxification methods. This study took the perspective of the treatment provider in assessing resource use and costs. Two short-term outcome measures were used-achievement of an initial 7-day period of abstinence, and entry into ongoing post-detoxification treatment. The mean costs of the various detoxification methods ranged widely, from AUD 491 dollars(buprenorphine-based outpatient) to AUD 605 dollars for conventional outpatient AUD 1404 dollars for conventional inpatient AUD 1990 dollars for rapid detoxification under sedation and to AUD 2689 dollars for anaesthesia per episode. An incremental cost-effectiveness analysis was carried out using conventional outpatient detoxification as the base comparator. The buprenorphine-based outpatient detoxification method was found to be the most cost-effective method overall, and rapid opioid detoxification under sedation was the most cost-effective inpatient method.
Publisher: American Psychological Association (APA)
Date: 06-2017
DOI: 10.1037/PHA0000114
Abstract: Tolerance to the psychomotor impairing effects of opioid drugs is expected to develop with repeated dosing, but may be incomplete. The relationship between plasma opioid concentration and psychomotor function in opioid-dependent patients was examined to determine whether impairment was more likely at the time of highest plasma drug concentration. Sixteen patients participating in a cross-over trial comparing methadone and LAAM completed a tracking task (OSPAT) 11 times over the dosing-interval for methadone (24-hrs) and LAAM (48-hrs). Venous blood was collected for the quantification of plasma (R)-(-)-methadone, LAAM, and nor-LAAM concentrations. The Digit Symbol Substitution Test (DSST) and Trail-Making Test were administered at the time of peak plasma concentration. Ten healthy controls (HCs) also participated. OSPAT scores (obtained for 15 patients) fluctuated significantly across the dosing-interval for both drugs and were lower in patients than HCs at the times of peak concentrations of (R)-(-)-methadone (1 hr: (mean difference 95% CI) (2.13 0.18-4.08) 2 hrs: (2.38 0.48-4.28) postdosing) and LAAM (2 hrs: (1.81 0.09-3.53), and 4 hrs (1.90: 0.9-3.71) postdosing). Within-participant analysis of the peak-change from baseline for OSPAT scores found that 10 of the 15 patients could be categorized as impaired on methadone and 9 on LAAM. No HCs were impaired. Patients performed worse on the DSST and Trails-A than HCs, but not on Trails-B. Results suggest that some patients receiving opioids long term may exhibit impairment at the time of highest plasma drug concentration. These patients should be made aware that their ability to undertake complex tasks may be affected. (PsycINFO Database Record
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.PARKRELDIS.2016.02.019
Abstract: The sonographic appearance of the substantia nigra is abnormally bright and enlarged (hyperechogenic) in young adults with a history of illicit stimulant use. The abnormality is a risk factor for Parkinson's disease. The aim of the current study was to identify the type of illicit stimulant drug associated with substantia nigra hyperechogenicity and to determine if in iduals with a history of illicit stimulant use exhibit clinical signs of parkinsonism. We hypothesised that use of hetamines (primarily meth hetamine) is associated with substantia nigra hyperechogenicity and clinical signs of parkinsonism. The area of echogenic signal in the substantia nigra was measured in abstinent human hetamine users (n = 27 33 ± 8 years) and in three control groups comprising a) 'ecstasy' users (n = 19 23 ± 3 years), b) cannabis users (n = 30 26 ± 8 years), and c) non-drug users (n = 37 25 ± 7 years). A subset of subjects (n = 55) also underwent a neurological examination comprising the third and fifth part of the Unified Parkinson's Disease Rating Scale. Area of substantia nigra echogenicity was significantly larger in the hetamine group (0.276 ± 0.080 cm(2)) than in the control groups (0.200 ± 0.075, 0.190 ± 0.049, 0.191 ± 0.055 cm(2), respectively P < 0.002). The score on the clinical rating scale was also significantly higher in the hetamine group (8.4 ± 8.1) than in pooled controls (3.3 ± 2.8 P = 0.002). Illicit use of hetamines is associated with abnormal substantia nigra morphology and subtle clinical signs of parkinsonism. The results support epidemiological findings linking use of hetamines, particularly meth hetamine, with increased risk of developing Parkinson's disease later in life.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2001
DOI: 10.1097/00004714-200102000-00014
Abstract: Although methadone maintenance is designed to stabilize opioid-dependent patients, some experience significant withdrawal in the latter part of the 24-hour interdosing interval. This study was designed to determine the mood changes that maybe associated with such withdrawal. Eighteen methadone patients, nine of whom experienced significant withdrawal, were tested over a single interdosing interval. During this time, 13 blood s les were collected to measure plasma racemic methadone concentrations, and the Profile of Mood States (POMS) was administered on 11 of these occasions. The POMS was also administered on 11 occasions over 24 hours to 10 drug-free healthy controls. In comparison with controls, methadone patients showed increased anger, depression, tension, confusion, and fatigue, as well as decreased vigor. For all scales, maximal differences from controls occurred at times of trough methadone concentration and minimal differences around the time of peak concentration. Changes in mood over the interdosing interval were more exaggerated in the nine patients who experienced significant withdrawal compared with those who did not. The composite Total Mood Disturbance (TMD) scores were calculated for each subject at each time point. The sigmoid Emax model was used to relate plasma concentrations to these data and to calculate the slope factor (N). This model could be fitted for 14 of the 18 patients with a mean +/- SEM slope factor of 2.2 +/- 0.5. TMD score was also shown to be inversely related to the rate of decline in methadone concentration from peak to trough. These results show that significant mood changes occur in response to changes in methadone concentration, and these are more pronounced in those who experience withdrawal. The concentration-effect relationships suggest that relatively small changes in plasma concentration will result in significant mood change. Differences in the degree of mood change between those who do and do not experience significant withdrawal may be explained by variation in the rate of decline in plasma concentration from peak to trough.
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.TALANTA.2019.120479
Abstract: 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 hetamine 4-fluoro hemtaine (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 s les 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.
Publisher: Wiley
Date: 17-01-2013
Publisher: BMJ
Date: 07-2018
DOI: 10.1136/BMJOPEN-2017-020723
Abstract: Meth hetamine dependence is a growing public health concern. There is currently no pharmacotherapy approved for meth hetamine dependence. Lisdexamfetamine (LDX) dimesylate, used in the treatment of attention-deficit hyperactivity disorder and binge eating disorder, has potential as an agonist therapy for meth hetamine dependence, and possible benefits of reduced risk of aberrant use due to its novel formulation. A double-blind randomised controlled trial will be used to evaluate the efficacy of LDX in reducing meth hetamine use. The target s le is 180 participants with meth hetamine dependence of ≥2 years, using ≥14 days out of the previous 28, who have previously attempted but not responded to treatment for meth hetamine use. Participants will be randomly assigned to receive either a 15-week intervention consisting of induction (1 week of 150 mg LDX or placebo), maintenance (12 weeks of 250 mg LDX or placebo) and reduction (1 week of 150 mg LDX or placebo and 1 week of 50 mg LDX or placebo). All participants will be given access to four sessions of cognitive–behavioural therapy as treatment as usual and receive a 4-week follow-up appointment. The primary outcomes are efficacy (change from baseline in days of meth hetamine use by self-report for the last 28 days at week 13 and urinalyses confirmation of meth hetamine use) and safety (treatment-related adverse events). Secondary outcomes are total number of days of self-report meth hetamine use over the 12-week active treatment, longest period of abstinence during treatment period, percentage of achieving ≥21 days abstinence, craving, withdrawal, dependence, retention, bloodborne virus transmission risk behaviour, criminal behaviour, as well measures of abuse liability, physical and mental health, other substance use, cognitive performance, psychosocial functioning, treatment retention and satisfaction. Additionally, the study will assess the cost-effectiveness of LDX relative to the placebo control. The study has been approved by the Human Research Ethics Committee of St. Vincent’s Hospital, Sydney, Australia (HREC/16/SVH/222). Contact the corresponding author for the full trial protocol. ACTRN12617000657325 Pre-results.
Publisher: Elsevier BV
Date: 08-2001
DOI: 10.1016/S0014-2999(01)01185-2
Abstract: The role of metabolic polymorphism in the development of physical dependence to codeine was assessed in cytochrome P450 2D2 (CYP2D2) deficient Dark Agouti and CYP2D2 intact Sprague-Dawley rats by assessment of the severity of naloxone precipitated withdrawal after codeine and morphine administration. Plasma morphine concentrations after codeine were significantly higher (P<0.01) in Sprague-Dawley than in Dark Agouti rats with metabolic ratios of 0.71 +/- 0.27 and 0.07 +/- 0.04, respectively. Withdrawal after codeine resulted in significantly greater hypothermia (3.5-4 degrees C, P<0.0001) in Sprague-Dawley animals compared to the other groups. Body weight loss was similar for all groups ranging from 6.2 +/- 0.4 to 8.2 +/- 0.6 g. When strain and treatment data were combined, a relationship between body temperature and plasma morphine concentration could be described by the inverse Hill equation (r(2)=0.76, EC(50)=556 +/- 121 ng/ml, n=2.9 +/- 1.5). These data indicate that dependence and withdrawal after codeine administration are dependent on its bioconversion to morphine.
Publisher: Public Library of Science (PLoS)
Date: 29-12-2014
Publisher: Wiley
Date: 27-07-2005
Publisher: Wiley
Date: 09-01-2008
DOI: 10.1111/J.1360-0443.2007.02090.X
Abstract: To (i) examine the predictors of mortality in a randomized study of methadone versus buprenorphine maintenance treatment (ii) compare the survival experience of the randomized subject groups and (iii) describe the causes of death. Ten-year longitudinal follow-up of mortality among participants in a randomized trial of methadone versus buprenorphine maintenance treatment. Recruitment through three clinics for a randomized trial of buprenorphine versus methadone maintenance. A total of 405 heroin-dependent (DSM-IV) participants aged 18 years and above who consented to participate in original study. Baseline data from original randomized study dates and causes of death through data linkage with Births, Deaths and Marriages registries and longitudinal treatment exposure via State health departments. Predictors of mortality examined through survival analysis. There was an overall mortality rate of 8.84 deaths per 1000 person-years of follow-up and causes of death were comparable with the literature. Increased exposure to episodes of opioid treatment longer than 7 days reduced the risk of mortality there was no differential mortality among methadone versus buprenorphine participants. More dependent, heavier users of heroin at baseline had a lower risk of death, and also higher exposure to opioid treatment. Older participants randomized to buprenorphine treatment had significantly improved survival. Aboriginal or Torres Strait Islander participants had a higher risk of death. Increased exposure to opioid maintenance treatment reduces the risk of death in opioid-dependent people. There was no differential reduction between buprenorphine and methadone. Previous studies suggesting differential effects may have been affected by biases in patient selection.
Publisher: Wiley
Date: 03-2011
DOI: 10.1016/J.EJPAIN.2010.07.009
Abstract: Previous reports have demonstrated greater antinociception following administration of a buprenorphine/naloxone combination compared to buprenorphine alone among healthy volunteers. The aim of the current investigation was to determine whether buprenorphine antinociception could be enhanced with the addition of ultra-low dose naltrexone, using a range of dose ratios. A repeated-measures, double-blind, cross-over trial was undertaken with 10 healthy participants. The effects of each buprenorphine:naltrexone ratio (100:1, 133:1, 166:1, and 200:1) on cold pressor tolerance time and respiration were compared to the effects of buprenorphine only. The 166:1 ratio was associated with significantly greater tolerance time to cold pressor pain than buprenorphine alone. Minimal respiratory depression and few adverse events were observed in all conditions. These findings suggest that, as previously described with naloxone, the addition of ultra-low dose naltrexone can enhance the antinociceptive effect of buprenorphine in humans. This potentiation is dose-ratio dependent and occurs without a concomitant increase in adverse effects.
Publisher: Elsevier BV
Date: 02-2008
DOI: 10.1016/J.FORSCIINT.2007.05.011
Abstract: Calculation of a blood alcohol concentration (BAC) at the time of an offence by forward or back-extrapolation, using population average values for ethanol pharmacokinetic parameters or a single estimate of in idual specific parameters, ignores the possibility of inter- and intra-subject variability. In order to estimate inter- and intra-subject variability in the elimination rate and absorption rate, BAC was measured over time in 12 male volunteers on 4 occasions. Subjects received 0.44 g kg(-1) body weight of ethanol on the first study day, and 0.70 g kg(-1) body weight on subsequent study days 1, 11 and 12 weeks later, to enable comparisons in variability over short and long time periods and when the same or different doses were administered. Evidence of both inter- and intra-subject variability was found, with inter-subject variability substantially smaller than intra-subject variability when the dose varied. Forensically important differences in pharmacokinetic parameters were observed within in iduals between occasions. These findings could have an important impact on medico-legal issues related to ethanol pharmacokinetics.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0AY00560F
Abstract: With illicit and designer benzodiazepines becoming more prevalent in the community, this work presents the validation and application of an analytical method for prescribed benzodiazepines and metabolites in wastewater.
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.ADDBEH.2012.05.022
Abstract: Positive effects of ecstasy on mood and self-esteem due to increased synaptic serotonin levels may indicate a potential antidepressant-like action. This effect may be more prominent in subjects with a pre-existing mood disturbance who may use ecstasy more frequently as a 'self-medication'. This study compared depressive symptoms and the immediate effects of ecstasy on mood in subjects with (WP) and without (NP) a predisposition to depression. Current ecstasy users were assessed using the profile of mood states (POMS) and beck depression inventory (BDI) when drug-free, and during social gathering, when 20 subjects voluntarily consumed ecstasy (ecstasy group) and 20 abstained from ecstasy (control group). Predisposition to depression was determined using the Brief Symptom Inventory. During social gathering, POMS and BDI were administered 60 min after ecstasy consumption, or at matched time for controls. 3,4-Methylenedioxymeth hetamine (MDMA) exposure was confirmed using saliva s les collected 60 min after pill ingestion. There was no difference in ecstasy use patterns between the groups. When drug-free, the WP subjects had greater mood disturbance and depressive symptoms than the NP group (POMS: NP 5.85±1.63, WP 14.5±2.81, p<0.05, BDI: NP 4.9±0.86, WP 11.2±1.65, p<0.01). During social gathering, WP subjects who consumed ecstasy reported a significant decrease in depressive symptoms (F(1,35)=5.47, p<0.05). A decrease in depressive symptoms was observed in subjects predisposed to depression. This antidepressant-like action of MDMA may contribute to its use, particularly among people with an existing or latent depressive disorder.
Publisher: Springer Science and Business Media LLC
Date: 13-06-2008
Abstract: Animal studies have demonstrated that co-administration of an ultra-low-dose opioid antagonist with an opioid agonist may result in enhanced analgesia. Investigation of this effect in humans has been limited and produced inconsistent findings, with previous reports suggesting that dose ratio may be critical to analgesic potentiation. The aim of the current investigation was to determine whether buprenorphine analgesia could be enhanced with the addition of ultra-low-dose naloxone among healthy volunteers, using a range of dose ratios. Tolerance to cold pressor pain was significantly greater with the combination of buprenorphine and naloxone compared to buprenorphine alone, and this effect was dose ratio dependent. Importantly, this enhanced analgesia occurred without an increase in adverse effects indeed at some ratios, respiratory depression was attenuated. These findings demonstrate that the addition of ultra-low-dose naloxone can enhance the analgesic effect of buprenorphine in humans without a concurrent increase in side effects.
Publisher: Wiley
Date: 03-2010
DOI: 10.1111/J.1465-3362.2009.00133.X
Abstract: This study is to test the acceptability of a single-session 'check-up' intervention for psychostimulant users and document participants' subsequent progress in reducing psychostimulant use and related harms. The design was pre-experimental single-group repeated measures. Eighty participants received the Psychostimulant Check-Up, with 62% completing a 3 month follow up. Participants were predominantly young adult meth hetamine users. The majority indicated that the Check-Up answered their questions, increased their awareness of services, and they would recommend it to their friends. At follow up, there was a significant reduction in self-reported meth hetamine use, the number of self-reported psychostimulant-related negative consequences experienced in the previous month and rates of injecting: 62% self-reported at least a 1 g reduction in meth hetamine use. The intervention was well accepted and the majority of those who received it subsequently made meaningful reductions in psychostimulant use and related harm. The intervention offers sufficient promise to warrant a randomised trial to establish whether improvements were specific to the intervention.
Publisher: Cambridge University Press (CUP)
Date: 28-05-2012
DOI: 10.1017/S2040174412000372
Abstract: The World Health Organization has identified substance use in the top 20 risk factors for ill health. Risks in pregnancy are compounded, with risk to the woman's health, to pregnancy progression and on both the foetus and the newborn. Intrauterine exposure can result in negative influences on offspring development, sometimes into adulthood. With effectively two patients, there is a clear need for antenatal screening. Biomarker reliability is limited and research efforts have been directed to self-report tools, often attempting to address potential lack of veracity if women feel guilty about substance use and worried about possible stigmatization. Tools, which assume the behaviour, are likely to elicit more honest responses querying pre-pregnancy use would likely have the same effect. Although veracity is heightened if substance use questions are embedded within health and social functioning questionnaires, such tools may be too lengthy clinically. It has been proposed that screening only for alcohol and tobacco, with focus on the month pre-pregnancy, could enable identification of all other substances. Alternatively, the Revised Fagerstrom Questionnaire could be used initially, tobacco being highly indicative of substance use generally. The ASSIST V.3.0 is readily administered and covers all substances, although the pregnancy ‘risk level’ cut-off for tobacco is not established. Alcohol tools – the 4Ps , TLFB and ‘drug’ CAGE ( with E: query of use to avoid withdrawal ) – have been studied with other substances and could be used. General psychosocial distress and mental ill-health often co-exist with substance use and identification of substance use needs to become legitimate practice for obstetric clinicians.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2009
Publisher: Springer Science and Business Media LLC
Date: 28-09-2006
Abstract: The increasing use of (+/-) 3,4-methylenedioxymeth hetamine (MDMA) in the setting of large dance parties ('raves') and clubs has been the source of some concern, because of potential acute adverse events, and because animal studies suggest that MDMA has the potential to damage brain serotonin (5-HT) neurons. However, it is not yet known whether MDMA, as used in the setting of dance parties, leads to plasma levels of MDMA that are associated with toxicity to 5-HT neurons in animals. The present study sought to address this question. Plasma MDMA concentrations, vital signs, and a variety of blood and urine measures were obtained prior to, and hours after, in iduals attended a dance party. After the dance party, subjects were without clinical complaints, had measurable amounts of residual MDMA in plasma, and nearly half of the subjects also tested positive for meth hetamine, another hetamine analog that has been shown to have 5-HT neurotoxic potential in animals. Plasma concentrations of MDMA did not correlate with self-reported use of 'ecstasy' and, in some subjects, overlapped with those that have been associated with 5-HT neurotoxicity in non-human primates. Additional subjects were likely to have had similar concentrations while at the dance party, when one considers the reported time of drug ingestion and the plasma half-life of MDMA in humans. Hematological and biochemical analyses were generally unremarkable. Moderate increases in blood pressure, heart rate and body temperature were observed in the subjects with the highest MDMA plasma concentrations. These findings are consistent with epidemiological findings that most people who use MDMA at dance parties do not develop serious clinical complications, and suggest that some of these in iduals may be at risk for developing MDMA-induced toxicity to brain serotonin neurons.
Publisher: Wiley
Date: 12-09-2019
DOI: 10.1002/DTA.2484
Abstract: 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 s les 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 s les. A total of 24 NPS were found: 6 in wastewater only, 13 in forensic post-mortem toxicology s les 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.
Publisher: Wiley
Date: 06-2008
Publisher: Wiley
Date: 1996
Publisher: Elsevier BV
Date: 12-2022
DOI: 10.1016/J.SCITOTENV.2022.158061
Abstract: Wastewater-based epidemiology is a tool incorporating biomarker analysis that can be used to monitor the health status of a population. Indicators of health include endogenous oxidative stress biomarkers and hormones, or exogenous such as alcohol and nicotine. 8-Iso-prostaglandin F
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.AAP.2018.01.026
Abstract: 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 s les 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.
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1016/J.DRUGALCDEP.2018.02.030
Abstract: The societal impact of drug use is well known. An ex le is when drug-intoxicated drivers increase the burden on policing and healthcare services. This work presents the correlation of wastewater analysis (using UHPLC-MS/MS) and positive roadside drug testing results for meth hetamine, 3,4-methylenedioxymeth hetamine (MDMA) and cannabis from December 2011-December 2016 in South Australia. Meth hetamine 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 erge in the final part of the measurement period. 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.
Publisher: Wiley
Date: 10-1999
Abstract: Opioid receptor antagonists have long been used in the diagnosis of opioid dependence and in the treatment of both opioid overdose and addiction. More recently they have been used in rapid opioid detoxification, a technique which has generated much ethical and scientific controversy. Because of this, the present review aims to integrate and summarize the current state of knowledge on adaptational changes to opioid systems as a result of antagonist administration. It is generally accepted that chronic treatment with an opioid antagonist results in opioid receptor upregulation. However, the mechanism(s) underlying this resultant opioid supersensitivity remain unresolved. In addition, there is not yet consensus regarding whether changes in opioid receptor number are directly responsible for the functional changes observed after chronic opioid antagonist treatment. Moreover, changes in opioid receptor number and sensitivity to opioid agonists and antagonists after chronic opioid antagonist treatment are dependent on dosing regimes as well as the kinetic properties of the antagonist itself. The role of these variables is appraised critically given the implication that an opioid antagonist can enhance functional responses. For ex le, such responses are an important consideration in the use of opioids because of possible adverse outcomes, such as overdose, after cessation of administration. Based on the literature discussed in this review it is concluded that caution is essential in the use of opioid antagonists for rapid opioid detoxification.
Publisher: Elsevier
Date: 2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2006
Publisher: Elsevier BV
Date: 11-2019
Publisher: Wiley
Date: 09-10-2013
DOI: 10.1002/DTA.1428
Abstract: Wastewater analysis has the potential to provide objective and timely data on population drug consumption, but some crucial factors such as pre-analysis drug loss during s le storage and filtration could affect the accuracy and reliability of the method, and these uncertainties have yet to be fully assessed. This study was designed to evaluate analyte stability in wastewater stored under different conditions with the aim of optimizing the s le storage procedures for future studies. It also investigated whether there is significant analyte loss during filtration before s le extraction and storage after that. The studied substances and metabolites were: cotinine, cocaine and its metabolite benzoylecgonine, phenethylamines hetamine, meth hetamine, 3,4-methylenedioxy hetamine (MDA), 3,4-methylenedioxymeth hetamine (MDMA), opioids including codeine, methadone, 6-monoacetylmorphine (MAM) and morphine. In most situations, storing s les at 4 °C is sufficient to stabilize analytes for at least 2 weeks, and refrigeration is unnecessary during s le transportation within 3 days. However, additional measures need to be taken if unstable analytes such as cocaine and MAM are to be analyzed. No significant analyte loss was observed in the filtration process or in reconstituted extract stored at 4 °C or -20 °C for 2 weeks. By choosing stable analytes and proper storage conditions, wastewater analysis has the potential to provide accurate data for estimation of community drug use.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Elsevier BV
Date: 2019
Publisher: Public Library of Science (PLoS)
Date: 29-11-2012
Publisher: Elsevier BV
Date: 10-2008
DOI: 10.1016/J.JSAT.2007.12.003
Abstract: The safety and tolerability of modafinil (400 mg/day, n = 14) and mirtazapine (60 mg/day, n = 13) in inpatient meth hetamine withdrawal treatment were compared to a historical comparison group receiving treatment as usual (pericyazine, 2.5-10 mg/day, n = 22). Modafinil and mirtazapine were well tolerated, producing minimal positive subjective effects and no discontinuation effects in this open-label study. Side effects were mild and transient. Aches and pains were most commonly reported by participants receiving mirtazapine, whereas headache was reported by modafinil-treated participants. Modafinil-treated participants had a milder withdrawal syndrome as measured by the Amphetamine Cessation Symptom Assessment and less sleep disturbance in comparison to mirtazapine. Pericyazine was associated with a more severe withdrawal syndrome in comparison to mirtazapine and modafinil. Both modafinil and mirtazapine were safe and well tolerated in meth hetamine withdrawal treatment. However, these early findings of efficacy in symptom amelioration should be replicated in an adequately powered, randomized, placebo-controlled double-blind design.
Publisher: Hindawi Limited
Date: 2016
DOI: 10.1155/2016/9485079
Abstract: Little is known about the long-lasting effect of use of illicit stimulant drugs on learning of new motor skills. We hypothesised that abstinent in iduals with a history of primarily meth hetamine and ecstasy use would exhibit normal learning of a visuomotor tracking task compared to controls. The study involved three groups: abstinent stimulant users ( n = 21 27 ± 6 yrs) and two gender-matched control groups comprising nondrug users ( n = 16 22 ± 4 yrs) and cannabis users ( n = 16 23 ± 5 yrs). Motor learning was assessed with a three-minute visuomotor tracking task. Subjects were instructed to follow a moving target on a computer screen with movement of the index finger. Metacarpophalangeal joint angle and first dorsal interosseous electromyographic activity were recorded. Pattern matching was assessed by cross-correlation of the joint angle and target traces. Distance from the target (tracking error) was also calculated. Motor learning was evident in the visuomotor task. Pattern matching improved over time (cross-correlation coefficient) and tracking error decreased. However, task performance did not differ between the groups. The results suggest that learning of a new fine visuomotor skill is unchanged in in iduals with a history of illicit stimulant use.
Publisher: Wiley
Date: 04-2002
DOI: 10.1080/135562102200120442
Abstract: Naltrexone, a mu opioid receptor antagonist, is used in the treatment of opioid and alcohol dependence. Naltrexone's longer duration of action compared to naloxone has been considered to be due partly to its major human metabolite, 6beta-naltrexol. To date, no studies have examined the in vitro or in vivo potency of 6beta-naltrexol compared to naltrexone and naloxone. In the electrically-stimulated guinea pig ileum, 6beta-naltrexol was more potent (K(i) = 94 +/- 25 pM), than naloxone (420 +/- 150 pM), and naltrexone (265 +/- 101 pM). In vivo comparative potencies were assessed using the mouse hotplate test and morphine (agonist), with doses of the antagonists from 0.001 to 30 mg/kg. The order of potency was naltrexone (ID(50) 7 microg/kg), naloxone (ID(50) 16 microg/kg) and 6beta-naltrexol (ID(50) 1300 microg/kg). Antagonist ID(50) doses were then administered at 45, 90, 120, 180 and 1080 minutes prior to morphine administration. The duration of antagonist activity to decrease by 50% was 80, 125 and 340 minutes for naltrexone, naloxone and 6beta-naltrexol, respectively. 6beta-naltrexol is highly potent in the guinea pig ileum, but much less so in vivo after an acute dose. However, the potency of 6beta-naltrexol in vivo is time-dependent, and it has a longer duration of action than naloxone and naltrexone, consistent with a pharmacokinetic longer terminal half-life. Therefore, 6beta-naltrexol is likely to contribute to the efficacy of naltrexone in humans.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.DRUGALCDEP.2017.05.017
Abstract: 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. 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. 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. 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.
Publisher: American Physiological Society
Date: 11-2012
DOI: 10.1152/JAPPLPHYSIOL.00718.2012
Abstract: Illicit use of stimulant drugs such as meth hetamine, ecstasy, and cocaine is a current and growing problem throughout the world. The aim of the current study was to investigate the long-term effect of illicit stimulant use on human motor cortical and corticospinal circuitry. We hypothesized that in iduals with a history of primarily meth hetamine and ecstasy use would exhibit altered corticospinal excitability and intracortical inhibition within motor cortex. The study involved 52 healthy adults (aged 26 ± 7 yr) comprising 26 abstinent stimulant users, 9 cannabis users, and 17 nondrug users. The experiment involved a routine urine drug screen, drug history questionnaire, neuropsychological assessment, and single- and paired-pulse transcranial magnetic stimulation (TMS) over motor cortex. EMG responses to stimulation [motor evoked potentials (MEPs)] were recorded from the contralateral first dorsal interosseus. At a given stimulus intensity, MEP area was significantly larger in abstinent stimulant users than in nondrug users during both relaxation ( P = 0.045) and muscle contraction ( P 0.001). MEP latency was also significantly longer in abstinent stimulant users ( P 0.009), and they exhibited significantly greater muscle activity during performance of a given task ( P = 0.004). However, resting motor threshold and the response to paired-pulse TMS were unaffected. The results suggest that abstinent stimulant users exhibit long-term changes in the excitability of motor cortical and corticospinal circuitry and muscle activity during movement. These changes may partly underlie anecdotal and objective reports of movement dysfunction in chronic stimulant users.
Publisher: Wiley
Date: 11-2000
DOI: 10.1046/J.1365-2125.2000.00281.X
Abstract: To determine the kinetics of the formation of 6beta-naltrexol from naltrexone in human liver cytosol, and to investigate the role of potential inhibitors. The kinetics of the formation of 6 beta-naltrexol from naltrexone were examined in eight human liver cytosol preparations using h.p.l.c. to quantify 6 beta-naltrexol and, the extent of inhibition of 6 beta-naltrexol formation was determined using chemical inhibitors. The formation of 6 beta-naltrexol and the back reaction of 6 beta-naltrexol to naltrexone were also examined in a microsomal preparation. The Vmax, Km and CLint values for the formation of 6 beta-naltrexol from naltrexone were in the ranges of 16-45 nmol mg-1 protein h-1, 17-53 microM and 0.3-2.2 ml h-1 mg-1 protein, respectively. The steroid hormones testosterone (Ki = 0.3 +/- 0.1 microM) and dihydrotestosterone (Ki = 0.7 +/- 0.4 microM) were the most potent competitive inhibitors of 6 beta-naltrexol formation, with naloxone, menadione and corticosterone also producing > 50% inhibition at a concentration of 100 microM. The opioid agonists morphine, oxycodone, oxymorphone and hydromorphone, and a range of benzodiazepines showed < 20% inhibition at 100 microM. In the microsomal preparation, there was no formation of naltrexone from 6beta-naltrexol nor any formation of 6beta-naltrexol from naltrexone. The intersubject variability in the kinetic parameters of 6beta-naltrexol formation could play a role in the efficacy of and patient compliance with naltrexone treatment. This variability could be due in part to a genetic polymorphism of the dihydrodiol dehydrogenase DD4, one of the enzymes reported to be responsible for the formation of 6beta-naltrexol from naltrexone. DD4 also has hydroxysteroid dehydrogenase activity which could account for the potent inhibition by the steroid hormones testosterone and dihydrotestosterone. The clinical significance of the latter finding remains to be established.
Publisher: Wiley
Date: 26-06-2020
DOI: 10.1002/DTA.2874
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.PHYSBEH.2019.02.004
Abstract: Sleep loss is one of the most common causes of accidents and errors in operational environments. Currently, no single method satisfies all of the requisite criteria of an effective system for assessing the risk of injury prior to safety being compromised. Research has concentrated towards the development of a biomarker for in idualized assessment of sleepiness-related deficits in neurobehavioral alertness, with salivary alpha-amylase (sAA) recently reported as a potential biomarker during acute total sleep deprivation. The present study extends on previous research by investigating the association between sAA and neurobehavioral alertness during simulated night-shift work, during in iduals are required to work at night when biological processes are strongly promoting sleep and sleep during the day when endogenous processes are promoting wakefulness. In a laboratory-controlled environment, 10 healthy non-shift working males aged 24.7 ± 5.3 years (mean ± SD) underwent four consecutive nights of simulated night-shift work. Between 17:30-04:30 h participants provided saliva s les and completed a 3 min psychomotor vigilance test (PVT-B), 40 min simulated driving task, and 3 min digit symbol substitution test (DSST). Higher sAA levels were associated with faster response speed on the PVT-B, reduced lane variability on the simulated driving task, and improved information processing speed on the DSST during the first night-shift. There were no associations between sAA levels and performance outcomes during subsequent night-shifts. Findings indicate that the usability of sAA to assess the risk of neurobehavioral deficits during shift-work operations is limited. However, the robust circadian rhythm exhibited by sAA during the protocol of circadian misalignment suggests that sAA could serve as a potential circadian marker.
Publisher: Wiley
Date: 09-10-2012
Publisher: American Chemical Society (ACS)
Date: 10-08-2021
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.SCITOTENV.2015.07.078
Abstract: Levels of community drug use are usually described by national surveys data relied upon by decision makers in health and law enforcement. In recent years the analysis of wastewater for drugs and their metabolites has become prominent. Both methods convey unique drug use information. This paper demonstrates differences arising from the two approaches, using meth hetamine, 3,4-methylenedioxymeth hetamine (MDMA) and cocaine data from the state of South Australia. The proportion of people using each drug, obtained from three prominent drug surveys, was compared with estimates of total community drug use derived by wastewater analysis. Temporal trends were compared for available years of the surveys and wastewater analysis from 2010 to 2013. Wastewater results showed meth hetamine to be the most prevalent stimulant in Adelaide, South Australia, with an average of 24.4±1.7 doses per day per 1000 inhabitants for 2013, while consumption of MDMA and cocaine were much lower at 0.52±0.12 and 0.42±0.06 doses per day per 1000 inhabitants, respectively. Survey data typically had MDMA as the most used stimulant on a proportion of the population basis. The difference in magnitude of drug use between MDMA and meth hetamine was also less apparent. Temporal trends of the proportion of the population using a drug by surveys did not generally reflect total use within the community which was observed by wastewater analysis. Survey data are excellent for describing users demographically. However, discrepancies between the proportion of the population who are users and the magnitude of drug use can lead to misrepresentation of the overall scale of use. The results from this study indicate meth hetamine was used to a much greater extent than suggested by the surveys. Together, wastewater analysis and survey data give a comprehensive view of the drug problem enabling more informed decisions on drug policy.
Publisher: Elsevier BV
Date: 11-1994
DOI: 10.1016/0091-3057(94)90069-8
Abstract: Recent research suggests that the GABAB receptor may mediate some of the acute effects of alcohol, but little is known of its involvement in alcohol withdrawal. Mice made dependent on alcohol exhibited tremor and tail arch when consumption ceased. Diazepam dose-dependently attenuated both tremor and tail arch, whereas baclofen had no effect on either of these two withdrawal symptoms. However, baclofen dose-dependently induced convulsant behaviour in the withdrawing mice, and this was significantly attenuated by the GABAB antagonists phaclofen (50 mg/kg) and CGP 35348 (300 mg/kg), but not BPBA (50 mg/kg). Phaclofen, BPBA, and CGP 35348, when administered alone and in combination with a single dose of baclofen, did have an effect on tremor, although the magnitude was small in comparison to that seen with diazepam. It appears that the GABAB receptor may play a role in mediating convulsions during alcohol withdrawal, and that in this system baclofen is proconvulsant.
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.PBB.2015.09.005
Abstract: There is a complex relationship between drug dependence and stress, with alcohol and other drugs of abuse both relieving stress and potentially inducing physiological stress responses in the user. Opioid drugs have been shown to modulate hypothalamic-pituitary-adrenal (HPA) activity in animal models and in idual response to this modulation may play a role in continuation of drug use. Healthy young Caucasian adults were administered a single dose of immediate release oxycodone (20mg, n=30) or assigned to a control group (n=19) that was not administered the drug. At 0, 1, 2, 4 and 6h post-administration, blood and saliva s les were collected along with assessment of pupil diameter. The HPA response was determined by measurement of salivary cortisol through a commercially available enzyme-linked immunosorbent assay (ELISA). The results were compared to genotype at the -511 and -31 positions in the interleukin1B (IL1B) gene. No difference in cortisol production was initially observed between the two groups, however, when participants were separated based on their genotype for two single nucleotide polymorphisms in the promoter of the IL1B gene, which have been shown to occur at a higher frequency in opioid-dependent populations, in iduals carrying the -511T and -31 C alleles (-511 C/T, -31 C/T or -511 T/T, -31 C/C) had a significantly (p<0.05) higher cortisol levels compared to in iduals homozygous for the -511 C and -31T alleles. These results suggest that in iduals carrying the -511T and -31 C alleles experience HPA activation in response to opioid administration and therefore may be less likely to undertake subsequent self-administration.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2001
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.SCITOTENV.2016.04.183
Abstract: Analysis of municipal wastewater for drug metabolites can reveal the scale of drug use within communities. An Australian city with a population of 1.2million inhabitants was assessed for 4 stimulants: cocaine, meth hetamine, 3.4-methylenedioxymeth hetamine (MDMA) and hetamine 6 opioids: codeine, morphine, heroin, fentanyl, oxycodone and methadone 11 new psychoactive substances (NPS) benzylpiperazine (BZP), trifluoromethylphenylpiperazine (TFMPP), methcathinone, methylone, mephedrone, methylenedioxypyrovalerone (MDPV), alpha pyrrolidinopentiophenone (alpha-PVP), paramethoxy hetamine (PMA), 25C-NBOMe, 25B-NBOMe, 25I-NBOMe and cannabis, for up to four years between December 2011 and December 2015. Temporal trends revealed increasing usage rates of meth hetamine, cocaine, oxycodone, and fentanyl, while decreasing rates of use were observed for MDMA, BZP and methylone. Use of other opioids and cannabis was generally stable across years, while use of new psychoactive substances fluctuated without an apparent direction. Opioids and cannabis were used at a consistent level through the course of the week, while use of stimulants and some NPS increased on the weekend. Seasonal differences in use were observed for MDMA and cannabis (p$_ _$lt .05) where, on average, MDMA use was approximately 90% higher in December than in other months and cannabis use was approximately 45% lower in each February. Residual month-to-month variability measures on trend-free data showed NPS use had higher variability than the stimulants and opioids. Frequent wastewater s ling and analysis over prolonged periods has yielded valuable insights into long-term drug use trends, in some instances revealed important within-year trends, and demonstrated the differing patterns of use of drugs on weekends compared to weekdays.
Publisher: Elsevier
Date: 2007
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.PSYNEUEN.2017.01.028
Abstract: During sleep deprivation, neurobehavioral functions requiring sustained levels of attention and alertness are significantly impaired. Discrepancies between subjective measures of sleepiness and objective performance during sustained operations have led to interest in physiological monitoring of operator performance. Alertness, vigilance, and arousal are modulated by the wake-promoting actions of the central noradrenergic system. Salivary alpha-amylase (sAA) has been proposed as a sensitive peripheral measure of noradrenergic activity, but limited research has investigated the relationship between sAA and performance. In a laboratory-controlled environment, we investigated the relationship between sAA levels, subjective sleepiness, and performance during two days (50h) of total sleep deprivation. Beginning at 09:00, twelve healthy participants (5 females) aged 22.5±2.5years (mean±SD) provided saliva s les, recorded ratings of subjective sleepiness, completed a brief 3-min psychomotor vigilance task (PVT-B) and performed a 40-min simulated driving task, at regular 3h intervals during wakefulness. Ratings of subjective sleepiness exhibited a constant linear increase (p<0.001) during sleep deprivation. In contrast, sAA levels showed a marked diurnal profile, with levels increasing during the day (p<0.001) and steadily declining in the evening and early-morning (p<0.001). PVT-B (mean reaction time and mean slowest 10% reaction time) and simulated driving performance (speed deviation and lane deviation) also exhibited diurnal profiles across the two days of sleep deprivation. Performance peaked in the afternoon (p<0.001) and then steadily worsened as wakefulness continued into the evening and early-morning (p<0.001). Further analysis revealed that higher sAA levels in the hour preceding each performance assessment were associated with better PVT-B and driving performance (p<0.001). These findings suggest that sAA measures may be suitable indicators of performance deficits during sustained wakefulness and highlight the potential for sAA to be considered for physiological monitoring of performance. In operational environments sAA levels, as part of a panel of physiological measures, may be useful for assessing fitness-for-duty prior to safety being compromised or when performance deficits are unknown.
Publisher: SAGE Publications
Date: 08-2006
Publisher: Springer Science and Business Media LLC
Date: 12-12-2018
DOI: 10.1007/S00702-017-1822-8
Abstract: 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.
Publisher: Springer Science and Business Media LLC
Date: 03-2002
DOI: 10.1007/S00213-001-0984-Z
Abstract: Para-methoxy hetamine (PMA) is a substituted hetamine that has been responsible for a number of fatalities in Australia and North America. Previous investigators have shown that p-hydroxy hetamine (PHA), the primary metabolite of PMA, has effects on central neurotransmitter kinetics in vitro that are similar to those of the parent compound. In order to understand the role of PHA, it is necessary to determine both the in vivo actions and the concentrations achieved relative to those of PMA. The effects of PHA and PMA on 5-hydroxytryptamine (5HT) and dopamine kinetics in brain were determined and the concentrations of each compound measured in blood and brain. Animals were housed at 20-22C on a standard 12/12-h light/dark cycle. High speed chrono erometry was used to compare the ability of PMA and PHA to alter 5HT and dopamine kinetics in the rat striatum in vivo. Concentrations of PHA and PMA in blood, whole brain and striatum were determined following a dose of PMA (10 mg/kg, IP.) using HPLC with fluorescence detection. PHA was more effective than PMA at evoking neurotransmitter release and inhibiting the uptake of dopamine. However, both compounds were approximately equipotent 5HT uptake inhibitors. PMA and PHA concentrations in whole brain and striatum peaked within 30 min of the administered dose, whereas blood concentrations of both compounds peaked 1 h after the dose. PHA concentrations in both blood and brain were consistently much lower than PMA concentrations. These data indicate that although PHA is more effective than PMA at altering 5HT and dopamine kinetics in vivo, it is unlikely to achieve sufficient brain concentrations to contribute to the central effects of PMA.
Publisher: Wiley
Date: 05-04-2012
Publisher: Springer Science and Business Media LLC
Date: 04-1994
DOI: 10.1007/BF01828833
Publisher: Wiley
Date: 14-12-2010
DOI: 10.1111/J.1360-0443.2009.02717.X
Abstract: To investigate the safety and efficacy of once-daily supervised oral administration of sustained-release dex hetamine in people dependent on meth hetamine. Randomized, double-blind, placebo-controlled trial. Forty-nine meth hetamine-dependent drug users from Drug and Alcohol Services South Australia (DASSA) clinics. Participants were assigned randomly to receive up to 110 mg/day sustained-release dex hetamine (n = 23) or placebo (n = 26) for a maximum of 12 weeks, with gradual reduction of the study medication over an additional 4 weeks. Medication was taken daily under pharmacist supervision. Primary outcome measures included treatment retention, measures of meth hetamine consumption (self-report and hair analysis), degree of meth hetamine dependence and severity of meth hetamine withdrawal. Hair s les were analysed for meth hetamine using liquid chromatography-mass spectrometry. Treatment retention was significantly different between groups, with those who received dex hetamine remaining in treatment for an average of 86.3 days compared with 48.6 days for those receiving placebo (P = 0.014). There were significant reductions in self-reported meth hetamine use between baseline and follow-up within each group (P < 0.0001), with a trend to a greater reduction among the dex hetamine group (P = 0.086). Based on hair analysis, there was a significant decrease in meth hetamine concentration for both groups (P < 0.0001). At follow-up, degree of meth hetamine dependence was significantly lower in the dex hetamine group (P = 0.042). Dex hetamine maintenance was not associated with serious adverse events. The results of this preliminary study have demonstrated that a maintenance pharmacotherapy programme of daily sustained-release hetamine dispensing under pharmacist supervision is both feasible and safe. The increased retention in the dex hetamine group, together with the general decreases in meth hetamine use, degree of dependence and withdrawal symptom severity, provide preliminary evidence that this may be an efficacious treatment option for meth hetamine dependence.
Publisher: Elsevier BV
Date: 11-2015
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.DRUGALCDEP.2019.107595
Abstract: 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. 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 meth hetamine use (ecstasy group, n = 190, 20 ± 3 yrs.), meth hetamine users (meth hetamine group, n = 331, 23 ± 5 yrs.), and non-stimulant users (control group, n = 228, 25 ± 8 yrs.). Movement data was analyzed with logistic regression. 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 meth hetamine 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. 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 c aigns that target prevention or harm minimization.
No related grants have been discovered for Jason White.