Quantitative determination of total methamphetamine and active metabolites in rat tissue by liquid chromatography with tandem mass spectrometric detection

High-throughput liquid chromatography with tandem mass spectrometric detection (LC-MS/MS) methodology for the determination of methamphetamine (METH), amphetamine (AMP), 4-hydroxymethamphetamine (4-OH-METH), and 4-hydroxyamphetamine (4-OH-AMP) was developed and validated using simple trichloroacetic acid sample treatment. The method was validated in rat serum, brain, and testis. Lower limits-of-quantitation (LOQ) for METH and AMP were 1 ng x mL(-1) using positive ion electrospray tandem mass spectrometry (MS/MS). The accuracy of the method was within 25% of the actual values over a wide range of analyte concentrations. The within-assay precision was better than 12% (coefficient of variation). The method was linear over a wide dynamic range (0.3-1000 ng x mL(-1)). Quantitation was possible in all 3 matrices using only serum standards because of minimal matrix-associated ion effects or the use of an internal standard. Finally, the LC-MS/MS method was used to determine serum, brain, and testis METH and AMP concentrations during a subcutaneous infusion (5.6 mg kg(-1) day(-1)) of METH in rats. Concentrations of 4-OH-AMP and 4-OH-METH were below the LOQ in experimental samples. The bias introduced by using serum calibrators for the determination of METH and AMP concentrations in testis and brain was less than 8% and insignificant relative to the interanimal variability.     

A systematic review of cognitive and behavioural therapies for methamphetamine dependence

Introduction and Aims . The use of methamphetamine is widespread and poses significant challenges for treatment providers. Much of the treatment knowledge about this group has been extrapolated from studies of treatment for cocaine dependence. Medications have been shown to be of limited effectiveness for methamphetamine users, making psychological interventions the treatment of choice. Approach . This paper describes a systematic review of cognitive–behavioural and behavioural interventions for methamphetamine users. A systematic search of published literature was undertaken focusing only on randomised trials. Key Findings . There were a relatively small number of intervention studies that compared cognitive–behavioural or behavioural interventions using randomised trial methodology. Most commonly, studies examined cognitive–behaviour therapy (CBT) and/or contingency management (CM). Treatment with CBT appears to be associated with reductions in methamphetamine use and other positive changes, even over very short periods of treatment (two and four sessions). CM studies found a significant reduction of methamphetamine during application of the procedure, but it is not clear if these gains are sustained at post‐treatment follow‐up. Implications . The review highlights that there are effective treatments for methamphetamine dependence. Alcohol and other drug (AOD) clinicians are familiar with these types of interventions and should use them and convey to clients that they are effective. Services and policy makers should ensure that best practice interventions are implemented within AOD services. Conclusion . Psychological intervention is effective in addressing methamphetamine use and dependence. CBT and contingency management are two accessible interventions that are implemented easily within current AOD services. There is still more work to conduct in improving methamphetamine treatment, however, and further research into cognitive–behavioural and behavioural treatments for methamphetamine users is required, with a focus on improving longevity of the effect of intervention and improving effectiveness among more complex presentations.     

Impaired physical health among methamphetamine users in comparison with the general population: the role of methamphetamine dependence and opioid use

Aim . To examine the extent of physical health impairment among a community sample of methamphetamine users in comparison with the general population, and factors associated with impairment among this group. Method . A cross‐sectional survey of 309 regular methamphetamine users from Sydney. The Physical Component Scale of the Short Form 12 (SF‐12) was used to measure impairment in physical health (score < 40). Age‐matched general population data for the SF‐12 were derived from the Australian National Survey of Mental Health and Well‐Being. Results . Participants had a higher prevalence of impaired physical health compared to the Australian general population (20% vs. 10%, p < 0.05), but this effect occurred among only dependent methamphetamine users over 24 years of age (25 – 34 years, 23% vs. 10%; 35 – 44 years, 41% vs. 12%). Methamphetamine dependence remained significantly predictive of impaired physical health after adjusting for age and other confounding factors. Opioid pharmacotherapy was also related strongly to poor physical health, accounting for 63% of participants with physical impairment. Other factors associated with impaired physical health were being female, having less than 10 years of schooling, and having been diagnosed previously with an anxiety disorder (p 5 0.05). Conclusion . Methamphetamine users are more likely to report impaired physical health than the general population, but this impairment is specific to older methamphetamine users who are dependent on the drug, particularly those who are enrolled in opioid pharmacotherapy.     

Reversible dilated cardiomyopathy induced by methamphetamine

This brief report details the case of a woman who was thought, after extensive evaluation, to have idiopathic congestive cardiomyopathy. It was subsequently found that systolic ventricular dysfunction was due to amphetamine abuse, and that ventricular function normalized after discontinuation of this drug.     

Suppression of hippocampal cell proliferation by short-term stimulant drug administration in adult rats

Sleep loss is known to potently suppress adult hippocampal cell proliferation and neurogenesis. Whether sleep suppression following acute administration of stimulant drugs also decreases hippocampal cell proliferation is not known. The present study examined the effect of three mechanistically distinct stimulants (caffeine, methamphetamine and modafinil) on cell proliferation. To maximize sleep suppression, these drugs were administered to rats (three i.p. injections, once every 4 h) during their sleep period (i.e. 12-h light phase). At the end of the light phase, 5-bromo-2'-deoxyuridine (200 mg/kg, i.p.) was injected and animals were killed 2 h later. Polygraphic recordings and locomotor activity measurements confirmed the wake-promoting and sleep-suppressing actions of each treatment. Results indicate that caffeine (20 mg/kg), methamphetamine (1.5 mg/kg) and modafinil (300 mg/kg) differentially suppressed sleep (45–91%) and selectively reduced cell proliferation in the hilus (12–44%), these results being significant for both caffeine and modafinil. When the same experiment was repeated in the dark (active) phase, the suppressant effect on hippocampal cell proliferation was either absent or greatly attenuated. In a further experiment, the effect of acute modafinil treatment in the light phase was shown to persist for 3 weeks after BrdU administration. We hypothesize that the differential effect of the stimulant drugs in the light vs. dark phase is attributable primarily to sleep suppression in the light. As abuse of stimulant drugs invariably leads to disrupted sleep in humans, our results suggest that they may, at least in part, decrease hippocampal neurogenesis via sleep loss and thereby adversely affect hippocampal-dependent processes.     

The oral health of street‐recruited injecting drug users: prevalence and correlates of problems

Aims To examine the effects of a series of injecting drug users' (IDU) characteristics and drug use behaviours upon the self‐reported oral health of a sample of IDU. Design Cross‐sectional survey. Setting Melbourne, Australia. Participants A total of 285 IDU recruited through needle and syringe programmes, snowballing and outreach across six sites. Measurements Structured survey that collected information on current drug use patterns, self‐reported blood‐borne virus status and general health factors, including open‐ended questions on past‐year dental health problems. Findings Sixty‐eight per cent of the sample reported dental problems that were commonly severe and caused dental pain. Despite these reported problems, almost half the sample had not visited the dentist in the 12 months prior to the survey. Participants who were older, and reported homelessness, not eating every day and more common injection of amphetamines rather than heroin in the previous month, were more likely to report having a past‐year dental problem. Conclusions Dental problems in IDUs are common but few receive treatment. Further, those using amphetamines, with poor housing, hygiene and poor nutrition, are most at risk. Programmes designed to improve the oral health of IDU need to be developed and implemented in a manner amenable to the varying social circumstances of this marginalized group in the community.     

Linked electronic medication systems in community pharmacies for preventing pseudoephedrine diversion: A review of international practice and analysis of results in Australia

Introduction and Aims. Pseudoephedrine is a precursor often diverted into the illegal manufacture of amphetamine type substances (ATS). The aim of this study was to evaluate the effectiveness of a linked electronic medication recording system (LEMS) established in Australian pharmacies in 2005 for preventing the diversion of pseudoephedrine. Design and Methods. The number of illegal ATS laboratories detected in each jurisdiction of Australia from 1996–1997 to 2004–2005 were analysed by linear regression nationally and by each jurisdiction. The statistical significance of seizures in 2005–2006 was based on the comparison of the observed value to the 95% prediction confidence intervals calculated from the historical data for each jurisdiction and nationally. Results. Pharmacies in Queensland commenced an LEMS in late 2005 to minimise retail pseudoephedrine diversion. The number of ATS laboratories seized in 2005–2006 in Queensland was significantly lower (P < 0.05) than predicted by historical data. For all other jurisdictions and nationally the totals of laboratories seized in 2005–2006 were not significantly different from predicted values. Discussion and Conclusions. The significant decline in ATS illegal laboratories seized in Queensland in 2005–2006 suggests the effective use of LEMS in pharmacies to minimise pseudoephedrine diversion. In order to evaluate a national LEMS, more frequent data on numbers of linked pharmacies, ATS laboratories seized and indicators of pseudoephedrine sales and misuse are required. Testing the use of LEMS by pharmacies for preventing the diversion of other medicines seems appropriate.[Berbatis CG, Sunderland VB, Dhaliwal SS. Linked electronic medication systems in community pharmacies for preventing pseudoephedrine diversion: A review of international practice and analysis of results in Australia. Drug Alcohol Rev 2009]