A review of the clinical pharmacology of methamphetamine

Abstract

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.

Trace Amine-Associated Receptor 1 Regulation of Methamphetamine Intake and Related Traits

“…Risk for drug use is affected by the balance of positive and negative experiences with a drug (Cruickshank and Dyer, 2009;Davis and Riley, 2010). Considerable attention has been given to positive rewarding effects associated with MA addiction (Beckmann et al, 2010;Horton et al, 2011;Kamens et al, 2005;Mahler et al, 2013;Meyer et al, 2011;Mizoguchi et al, 2004;Shabani et al, 2011Shabani et al, , 2012aWheeler et al, 2009), whereas aversive effects that could limit intake have been given less consideration (Harrod et al, 2010;Pringle et al, 2008;Shabani et al, 2011Shabani et al, , 2012bWheeler et al, 2009).…”

Exposures associated with clandestine methamphetamine drug laboratories in Australia

“…The detection times differ depending on whether exposure occurred from a single dose, repeated doses or chronic exposures. Most data are available following a single dose where the detection time is reported to range from 24 to 48 h in plasma to 87 h in urine (177). Limited data are available in relation to repeated doses of methamphetamine, however, the detection time is in the range of 3 days in saliva/oral fluid to 8 days in urine and sweat (177,(179)(180)(181).…”

“…These mechanisms do not appear to be changed by chronic exposure (177). The major pathways of methamphetamine metabolism involve (170,176,177): -n-demethylation to form amphetamine, that can then be metabolised via several pathways -aromatic hydroxylation to form 4-hydroxymethamphetamine and then 4-hydroxyamphetamine and 4-hydrocynorephedrine -β-hydroxylation to form norephedrine.…”

“…Most data are available following a single dose where the detection time is reported to range from 24 to 48 h in plasma to 87 h in urine (177). Limited data are available in relation to repeated doses of methamphetamine, however, the detection time is in the range of 3 days in saliva/oral fluid to 8 days in urine and sweat (177,(179)(180)(181). Accumulation of amphetamines in a keratin matrix is more complex (174) but has been shown to provide a stable measure of temporal exposures with the distribution of drugs along the shaft of the hair expected to reflect historical month-by-month exposures (174).…”

Cortisol Reactivity in Two-Year-Old Children Prenatally Exposed to Methamphetamine

“…Rates of methamphetamine use among pregnant women have been reported to be as high as 5.2% . Although the deleterious effects of methamphetamine on the female adult user are well documented (Cruickshank and Dyer, 2009), less is known about the effects on a developing fetus and child.…”