Review
Methamphetamine use: A comprehensive review of molecular, preclinical and clinical findings

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Abstract

Methamphetamine (MA) is a highly addictive psychostimulant drug that principally affects the monoamine neurotransmitter systems of the brain and results in feelings of alertness, increased energy and euphoria. The drug is particularly popular with young adults, due to its wide availability, relatively low cost, and long duration of psychoactive effects. Extended use of MA is associated with many health problems that are not limited to the central nervous system, and contribute to increased morbidity and mortality in drug users. Numerous studies, using complementary techniques, have provided evidence that chronic MA use is associated with substantial neurotoxicity and cognitive impairment. These pathological effects of the drug, combined with the addictive properties of MA, contribute to a spectrum of psychosocial issues that include medical and legal problems, at-risk behaviors and high societal costs, such as public health consequences, loss of family support and housing instability. Treatment options include pharmacological, psychological or combination therapies. The present review summarizes the key findings in the literature spanning from molecular through to clinical effects.

Section snippets

The methamphetamine problem

Methamphetamine (MA) is a psychostimulant drug with significant abuse potential and neurotoxic effects that acts principally to cause the release of central and peripheral monoamines (Gold et al., 2009). The compound was first synthesized from ephedrine in 1893 by the Japanese scientist Nagai Nagayoshi, 6 years after the discovery of amphetamine (see Fig. 1). In 1919, Akira Ogata synthesized crystallized MA by reducing ephedrine using red phosphorous and iodine, providing the basis for

Mechanism of action of amphetamines

Methamphetamine is a potent psychostimulant that acts primarily to cause the release of the monoamines dopamine, serotonin and norepinephrine. Norepinephrine is released most efficiently, followed by dopamine and then serotonin (Rothman et al., 2001). The mechanism of action of MA and other amphetamines has been described in extensive detail in several excellent reviews (Weiland-Fiedler et al., 2004, Fleckenstein et al., 2007, Sulzer et al., 2005). However, it is informative to summarize

Physiological and psychological effects of methamphetamine

Methamphetamine is a potent psychomotor stimulant drug with strong physiological effects on peripheral and central systems, resulting in both physical and psychological alterations. The drug can be consumed in multiple different ways and the physiological effects of MA occur rapidly and last for hours (see Table 1 for pharmacokinetics of MA). Through its action on epinephrine and norepinephrine release by the medulla of the adrenal glands, MA simulates the activation of the sympathetic division

Neurotoxicity of methamphetamine

In the animal literature, numerous studies have documented dopamine neuron terminal damage or loss after MA exposure (Krasnova and Cadet, 2009, Ricaurte et al., 1984), while a significantly smaller proportion of studies have reported actual cell loss via apoptosis in the striatum (Commins and Seiden, 1986, Tulloch et al., 2011). The relationship between these two different types of neurotoxicity remains unclear, particularly as the phenotype of apoptotic cells require further study. As of yet,

Neurocognitive effects of methamphetamine

Cognitive deficits have been widely described in “chronic” MA users. Chronicity is variably defined in the literature, with a meta-analysis indicating that 10 years of MA use is the approximate average for subjects enrolled in the various studies of MA use and cognitive sequelae (Scott et al., 2007). Chronic exposure to MA can result in severe neuropsychological deficits (summarized in Nordahl et al., 2003, Scott et al., 2007). Cognitive impairment is a serious concern for MA users, as it has

Treatment of methamphetamine-related disorders

Different pharmacological approaches have been tried in the treatment of MA addiction. The most common classes of drugs include antidepressants, antipsychotics and substitution/replacement therapies (Rose and Grant, 2008). Indirect evidence supports a rationale for the use of antidepressants – particularly those with a serotonergic mechanism of action, based on efficacy in preclinical models, clinical efficacy in treating compulsive behavior, and potential for ameliorating the affective

Conclusion

Methamphetamine is a highly addictive psychostimulant drug that acts on the central nervous system through multiple physiological pathways to cause the release of central and peripheral monoamine neurotransmitters. Recreational use of MA remains high in many parts of the United States and Canada and is increasing in other parts of the world. The highly addictive properties of this drug result in widespread psychosocial issues that include medical and legal problems, at-risk behaviors, and

Role of funding source

Funding for this study was provided by NSERC Grant 356069-09 to Dr. Barr. NSERC had no further role in the writing of the review; or in the decision to submit the paper for publication.

Contributors

All authors participated in the writing and revision of the review.

Conflict of interest

There are no conflicts of interest for any authors with respect to the present review.

Acknowledgments

W.J.P. is a Clinician Investigator Program research fellow. The editorial assistance of Heidi Boyda is appreciated.

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