Aims To examine the literature regarding clinical pharmacokinetics, direct effects and adverse clinical outcomes associated with methamphetamine use. Methods Relevant literature was identified through a PubMed search. Additional literature was obtained from relevant books and monographs. Findings and conclusions The mean elimination half-life for methamphetamine is approximately 10 hours, with considerable inter-individual variability in pharmacokinetics. Direct effects at low-to-moderate methamphetamine doses (5-30 mg) include arousal, positive mood, cardiac stimulation and acute improvement in cognitive domains such as attention and psychomotor coordination. At higher doses used typically by illicit users (Ն50 mg), methamphetamine can produce psychosis. Its hypertensive effect can produce a number of acute and chronic cardiovascular complications. Repeated use may induce neurotoxicity, associated with prolonged psychiatric symptoms, cognitive impairment and an increased risk of developing Parkinson's disease. Abrupt cessation of repeated methamphetamine use leads to a withdrawal syndrome consisting of depressed mood, anxiety and sleep disturbance. Acute withdrawal lasts typically for 7-10 days, and residual symptoms associated with neurotoxicity may persist for several months.

The open channel diameter of Escherichia coli recombinant large-conductance mechanosensitive ion channels (MscL) was estimated using the model of Hille (Hille, B. 1968. Pharmacological modifications of the sodium channels of frog nerve. J. Gen. Physiol. 51:199-219) that relates the pore size to conductance. Based on the MscL conductance of 3.8 nS, and assumed pore lengths, a channel diameter of 34 to 46 A was calculated. To estimate the pore size experimentally, the effect of large organic ions on the conductance of MscL was examined. Poly-L-lysines (PLLs) with a diameter of 37 A or larger significantly reduced channel conductance, whereas spermine (approximately 15 A), PLL19 (approximately 25 A) and 1,1'-bis-(3-(1'-methyl-(4,4'-bipyridinium)-1-yl)-propyl)-4,4'-b ipyridinium (approximately 30 A) had no effect. The smaller organic ions putrescine, cadaverine, spermine, and succinate all permeated the channel. We conclude that the open pore diameter of the MscL is approximately 40 A, indicating that the MscL has one of the largest channel pores yet described. This channel diameter is consistent with the proposed homohexameric model of the MscL.

Introduction and Aims. As an antidepressant with sedative and anxiolytic properties, mirtazapine may be an appropriate pharmacotherapy for methamphetamine withdrawal. This study sought to examine whether mirtazapine improves retention and alleviates methamphetamine withdrawal symptoms in an out-patient setting. Design and Methods. An out-patient double-blind, randomised placebo-controlled trial of mirtazapine for the treatment of methamphetamine withdrawal was conducted (15 mg nocte for 2 days, 30 mg nocte for 12 days). Both groups were offered narrative therapy counselling. Measures recorded on days 0, 3, 7, 14 and 35 included: treatment retention, Amphetamine Cessation Symptoms Assessment, the Athens Insomnia Scale, the Brief Symptom Inventory, the Depression -Anxiety -Stress Scale (DASS), Severity of Dependence scale and the Opiate Treatment Index Drug Use subscale. Results. Thirty-one participants were recruited (18 placebo, 13 mirtazapine) and 52% completed the 2-week medication phase. No significant differences between the mirtazapine and placebo groups in retention, or any symptom measure were observed, except greater DASS -anxiety and longer sleep duration were measured at baseline among the mirtazapine group. Discussion and Conclusions. Results suggest that mirtazapine does not facilitate retention or recruitment in out-patient methamphetamine withdrawal treatment, although recruitment may have been insufficient to identify a significant treatment effect. The potential role of narrative therapy for methamphetamine dependent patients deserves further exploration. [Cruikshank CC, Montebello ME, Dyer KR, Quigley A, Blaszczyk J, Tomkins S, Shand D. A placebo-controlled trial of mirtazapine for the management of methamphetamine withdrawal. Drug Alcohol Rev 2008;27:326-333]

Amphetamines are second to cannabis as the most prevalent illicit drug used in Australia, and amphetamine abuse and dependence are associated with significant health and psychosocial harms. The current paper presents a series of studies investigating the prevalence of depression and other psychological problems among Western Australian patients receiving treatment for methamphetamine dependence. In the first study, a medical case-note audit explored the psychological profile among 218 consecutive admissions to an inpatient methamphetamine detoxification program. In the second study, the Beck Depression Inventory (BDI-II, Beck, Steer, & Brown, 1996) was administered to 367 patients receiving outpatient treatment for methamphetamine or heroin dependence (Phase 1), and the relationship between scores on the BDI-II and methamphetamine intoxication was explored (Phase 2). High rates of depression and other psychological problems were identified. Approximately 46% of methamphetamine-dependent individuals entering an inpatient treatment unit had been previously diagnosed for a psychological health problem, with approximately 30% requiring admission into a psychiatric hospital. In the second study, the mean total BDI-II score was approximately 22, which is in the moderate range of depression. Methamphetamine-dependent patients' total BDI-II score was similar to that of psychiatric outpatients with clinical depression, but significantly greater than college students and psychiatric outpatients with anxiety disorders (Beck et al., 1996). Methamphetamine use was associated with responses on the BDI-II corresponding with cognitive symptoms, whereas combined methamphetamine and heroin use was associated with responses indicating problems in the somatic domain. Finally, it was found that methamphetamine intoxication at the time of testing, as indicated by a positive saliva methamphetamine screen, affected responses to the BDI-II. These data demonstrate that methamphetamine-dependent individuals will present with significant psychological symptoms that may affect the response to treatment for drug dependence.