Methamphetamine is a highly addictive psychostimulant drug that is chemically related to amphetamine. Methamphetamine can produce euphoria and stimulant effects like those from other stimulants such as cocaine. In addition, methamphetamine is easily synthesized from inexpensive and readily obtainable chemicals. Those qualities have led to the widespread and rampant abuse of this dangerous drug.
Methamphetamine use has increased rapidly throughout the world, with more than 30 million users worldwide.  Over the past decade, all regions of the United States experienced a significant increase in the number of persons using the drug, and a corresponding increase in the number of patients with medical complications seen in emergency departments (EDs). [1, 2] Fortunately, this trend seems to have reached a plateau in some areas, with the National Institute on Drug Abuse reporting that from 2015 to 2016, methamphetamine use in the past year by those 12 years of age and older decreased from 0.6% to 0.5% of the population. 
Methamphetamine is available in powder and crystalline forms. It may be taken orally or intravenously, or be snorted or smoked. The smokable form of methamphetamine (“ice”) produces an immediate euphoria similar to that of crack cocaine, but the effects may last much longer. [4, 5]
Inadvertent absorption of methamphetamine may occur in “body packers”, who swallow packages of the drug for transportation purposes, or “body stuffers”, who insert bags of methamphetamine rectally or vaginally in an attempt to elude drug enforcement. There are also users who indulge in “parachuting”, in which the drug is loosely wrapped to delay absorption and prolong effect. These persons, and body stuffers, are at high risk for toxicity as the drug wrapping may be compromised and allow complete drug absorption. 
North American methamphetamine abusers are predominantly white males in their 30s and 40s. [7, 8] Epidemic abuse has been described in adolescents; they cite availability, low cost, and a longer duration of action than cocaine as reasons for their drug preference. 
Most cases of methamphetamine toxicity can be managed supportively. In severe overdoses, termination of methamphetamine-induced seizure activity and arrhythmias are of immediate importance. Correction of hypertension, hypotension, hyperthermia, metabolic and electrolyte abnormalities, and control of severe psychiatric agitation are indicated. See Treatment and Medication.
The medical history of amphetamine-like compounds extends back nearly 100 years. [4, 5] A Japanese pharmacologist first synthesized methamphetamine in 1919. A more detailed analysis of the pharmacology of amphetamine derived from the basic phenylethylamine structure was reported in 1930. In the 1930s, amphetamine was introduced in the form of inhalers for rhinitis and asthma treatment. The stimulant, euphoric, and anorectic effects of amphetamine were quickly recognized, leading to its abuse.
In 1937, a report that amphetamine enhanced intellectual performance and wakefulness further contributed to its popularity. Amphetamines were used extensively by Allied and Axis armed forces during World War II and during the recent Iraq and Afghanistan conflicts to increase wakefulness and attention. [4, 10]
In the late 1950s, initial federal controls were enacted; however, in spite of additional regulation and increased enforcement, amphetamines continued to be used by students, athletes, shift workers, long haul drivers, and for weight loss. [4, 5] The Controlled Substance Act of 1970 stringently regulated the manufacture of amphetamine.
In the CNS, amphetamines block presynaptic reuptake of catecholamines (ie, dopamine, norepinephrine), causing hyperstimulation at selected postsynaptic neuron receptors. Indirect sympathomimetic effects result from blockade of presynaptic vesicular storage and by reduction in cytoplasmic destruction of catecholamines by inhibition of mitochondrial monoamine oxidase. [12, 13]
Indirectly, these hyperstimulated neurons can stimulate various other noncatecholaminergic central and peripheral nervous pathways. Changes in mood, excitation, motor movements, sensory perception, and appetite appear to be mediated more directly by CNS dopaminergic alterations. It has been postulated that serotonin alterations also contribute to mood changes, psychotic behavior, and aggressiveness. 
Long-term exposure to methamphetamine results in significant down-regulation of both presynaptic and postsynaptic aspects of the dopamine system in the striatum. Dysregulation of the dopamine system has been proposed as a mechanism of addiction.  Oxidative stress and neuroinflammation appear to play a role in the psychosis and cognitive deficits induced by repeated low doses of methamphetamine. 
In humans, the half-life of methamphetamine ranges from 10-20 hours, depending on the urine pH, history of recent use, and dosage.  Metabolism occurs faster in acidic urine. Methamphetamine has greater CNS effects compared with D-amphetamine of equal milligram quantity. The majority of methamphetamine is metabolized to amphetamine, which provides further CNS stimulation.
Methamphetamine is absorbed readily from the gut, airway, nasopharynx, muscle, placenta, and vagina. [17, 18] Peak plasma levels are observed approximately 30 minutes after intravenous or intramuscular routes and 2-3 hours after ingestion.  Rapid tissue redistribution occurs with steady-state cerebrospinal fluid levels at 80% of plasma levels. Hepatic conjugation pathways with glucuronide and glycine addition result in inactivation and urinary excretion of metabolites.
When methamphetamine is used with ethanol, increased psychological and cardiac effects are observed.  This is presumed to be the result of pharmacodynamic rather than pharmacokinetic interactions. Similarly, the increased toxicity of concomitant opioids and amphetamines (“speedballing”), appear to result from pharmacodynamic interactions.
The euphoric effects produced by methamphetamine, cocaine, and various designer amphetamines are similar and may be difficult to clinically differentiate.  A distinguishing clinical feature is the longer pharmacokinetic and pharmacodynamic half-life of methamphetamine, which may be as much as 10 times longer than that of cocaine. Because of the variability in quality and concentration of illicitly purchased methamphetamines, the clinical observation of toxic effects is more relevant than estimated total ingested dose. 
Methamphetamine use is widespread in the United States but varies regionally, with higher use in Hawaii, the West, and parts of the Midwest.  The Drug Abuse Warning Network estimates that methamphetamine was involved in 102,961 emergency department visits in 2011. 
According to the 2016 National Survey on Drug Use and Health (NSDUH), approximately 667,000 people were current methamphetamine users. Approximate numbers of users by age group and percentages of that age group were as follows  :
The United Nations Office on Drugs and Crime estimates that worldwide in 2015 there were 37 million users of amphetamine-type stimulants, which includes methamphetamine. Methamphetamine is a feature of amphetamine-type stimulant markets worldwide, but is particularly dominant in East and Southeast Asia and North America In East and Southeast Asia, the market for both tablet and crystalline methamphetamine is large and growing. 
An Australian study that used liquid chromatography–mass spectrometry to analyze wastewater (an increasingly popular method for monitoring trends of illicit drug use) reported that from 2009-2015, methamphetamine consumption increased fivefold. In the study, which involved wastewater from wastewater treatment plants in South East Queensland, methamphetamine residues were consistently detected in both urban and rural catchments. 
Acute methamphetamine overdose may result in sympathetic overdrive, intracranial hemorrhage,  cardiovascular collapse, rhabdomyolysis, ventricular tachyarrhythmia, and death. Injuries from blunt and penetrating trauma are common. [4, 11, 25, 26]
Long-term methamphetamine use may result in the following  :
In a study of 590 patients between 18 and 50 years old with cardiomyopathy or heart failure who were seen at a single medical center from 2008-2012, the 223 patients with a history of methamphetamine use were more likely to have a moderately or severely reduced ejection fraction ≤40%). In addition, male patients were more likely to have worse left ventricular systolic dysfunction. 
Methamphetamine abuse has severe adverse effects on oral health, colloquially termed “meth mouth”. As a result of its sympathomimetic effects, methamphetamine results in significantly reduced saliva production and pH, and increased bruxism. Consequently, long-term abusers are at increased risk for caries, dental erosion, periodontal lesions, and temporomandibular joint pain. 
Use of methamphetamine during pregnancy has been associated with intrauterine growth restriction and preterm birth. Neonates have an increased incidence of poor cardiorespiratory adaptation, cardiac defects, and floppy muscle tone.  Prenatal exposure may have a long-term impact on cognitive skills that becomes more pronounced with age. 
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John R Richards, MD, FAAEM Professor, Department of Emergency Medicine, University of California, Davis, Medical Center
Disclosure: Nothing to disclose.
Robert W Derlet, MD Professor of Emergency Medicine, University of California at Davis School of Medicine; Chief Emeritus, Emergency Department, University of California at Davis Health System
Robert W Derlet, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Association for the Advancement of Science, Infectious Diseases Society of America, Society for Academic Emergency Medicine, Wilderness Medical Society
Disclosure: Nothing to disclose.
Timothy E Albertson, MD, PhD, MPH Professor of Pharmacology and Toxicology, Professor of Medicine, Division of Pulmonary and Critical Care Medicine, Chair, Department of Internal Medicine, University of California, Davis, School of Medicine; Professor of Anesthesiology, Professor of Emergency Medicine and Clinical Toxicology, Davis Medical Center; Chief of Pulmonary and Critical Care, Veterans Affairs, Northern California Health Care System; Medical Director of Poison Control System, University of California, San Francisco, School of Pharmacy
Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: La Jolla Pharm<br/>Received research grant from: UC Davis received from La Jolla Pharm; TEA honorarium for speaking from La Jolla Pharm.
John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph’s Hospitals
John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists
Disclosure: Nothing to disclose.
Fred Harchelroad, MD, FACMT, FAAEM, FACEP Attending Physician in Emergency Medicine and Medical Toxicology, Excela Health System
Fred Harchelroad, MD, FACMT, FAAEM, FACEP is a member of the following medical societies: American College of Medical Toxicology
Disclosure: Nothing to disclose.
Jeter (Jay) Pritchard Taylor, III, MD Assistant Professor, Department of Surgery, University of South Carolina School of Medicine; Attending Physician, Clinical Instructor, Compliance Officer, Department of Emergency Medicine, Palmetto Richland Hospital
Jeter (Jay) Pritchard Taylor, III, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, Columbia Medical Society, Society for Academic Emergency Medicine, South Carolina College of Emergency Physicians, South Carolina Medical Association
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Employed contractor – Chief Editor for Medscape.
Edward A Michelson, MD Associate Professor, Program Director, Department of Emergency Medicine, University Hospital Health Systems of Cleveland
Disclosure: Nothing to disclose.
Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital
Disclosure: Nothing to disclose.
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