Neurobiology, Clinical Presentation, and Treatment of Methamphetamine Use Disorder

Abstract

In the wake of the opioid crisis, methamphetamine has reemerged as a challenge to mental health clinicians and researchers alike. Methamphetamine is now available in different forms such as ice, powder, and pills, with different pharmacokinetic characteristics that make them popular among certain types of individuals. 1 Recent seizure data suggest that methamphetamine production and trafficking are spreading into new areas of the globe. 2 According to the Automation of Reports and Consolidated Orders System, methamphetamine consumption increased 4-fold between 2015 and 2016 and total stimulant use doubled in the last decade. 3 From 2011 through 2016, the age-adjusted rate of drug overdose deaths involving methamphetamine more than tripled. 4 Moreover, drug overdose deaths involving cocaine, amphetamines, or both substances combined increased 42.4% from 12 122 in 2015 to 17 258 in 2016. 5 Based on the most recent data from the National Survey on Drug Use and Health, 6 the 12-month prevalence of individuals aged 12 years or older reporting methamphetamine use has increased by 195% from its low in 2010 to 2018 (Figure 1), and it is estimated that 1.86 million Americans used methamphetamine in 2018. These numbers underline the importance of paying attention to the possibility of the next substance use crisis. However, whereas opioid use disorder can be treated pharmacologically 7 and behaviorally, 8 there are significant challenges for the treatment of methamphetamine use disorder (MUD). This review focuses on 3 specific aspects of MUD. First, the neurobiology of methamphetamine is more complex than the traditional view of it as a monoaminergic modulator. Second, the clinical presentation is not limited to the symptoms associated with use disorder but extend to medical presentations, most notably the cardiovascular and cerebrovascular systems. Third, pharmacologic interventions focused on modulating the monoaminergic pathways have largely failed, and new pharmacologic approaches are necessary to focus on novel treatment targets. In the final section, several suggestions will be proposed for both clinicians and researchers to advance the understanding of MUD. Biological Pathways, Neural Basis, and CognitionMethamphetamine has been conceptualized primarily as a releaser of dopamine, serotonin, noradrenaline, and adrenaline from nerve terminals in the central and peripheral nervous system, 9 which occurs via several different mechanisms, including (1) redistributing catecholamines from synaptic vesicles to the cytosol, (2) reversing the plasma membrane transport of neurotransmitters, (3) blocking the activity of monoamine transporters, (4) decreasing the expression of dopamine transporters at the cell surface, (5) inhibiting monoamine oxidase activity, and (6) increasing the activity and IMPORTANCE The prevalence of and mortality associated with methamphetamine use has doubled during the past 10 years. There is evidence suggesting that methamphetamine use disorder could be the next substance use crisis in the United ...

Cue-Induced Craving and Negative Emotion Disrupt Response Inhibition in Methamphetamine Use Disorder: Behavioral and fMRI Results from a Mixed Go/No-Go Task

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