Methamphetamine: Important Clinical Guidance for Healthcare Providers

Grant N. Colfax, MD


October 17, 2005

Methamphetamine -- The Scope of the Problem

Methamphetamine is a synthetic psychomotor stimulant closely related to the decongestants ephedrine and phenylpropanolamine.[1] Methamphetamine can be injected, smoked, snorted, or taken orally or rectally with effects lasting for up to 12 hours.[2] Administration results in feelings of euphoria and increased energy.[3]

Amphetamines were first synthesized in 1887, with various amphetamine compounds being licensed and marketed for medical conditions ranging from weight loss to asthma.[4] Methamphetamine is synthesized by converting ephedrine or pseudoephedrine into methamphetamine via a series of steps usually involving additions of phosphorous and iodine.[1] This distillation process is commonly employed in large "meth labs," which have been the focus of most law-enforcement efforts to control methamphetamine use in the United States. While much attention has been paid to local, backyard methamphetamine manufacture in these labs, the US Drug Enforcement Agency (DEA) estimates that 80% of methamphetamine available in the United States is manufactured in other countries, primarily Mexico.[5] However, definitive data on methamphetamine distribution and supply are not available.

Researchers have identified multiple epidemics of amphetamine abuse dating back to the 1930s.[4,6] The current epidemic originated in Hawaii and the western United States, but the epidemic is now well established throughout the country.[7] This spread is paralleled by a 5-fold increase in admissions for stimulant treatment between 1992 and 2002.[8] Methamphetamine now accounts for the majority of amphetamine used in the United States, with over 12 million adults using methamphetamine in 2003.[9]

Methamphetamine use is particularly common among men who have sex with men (MSM), with use as much as 10 times higher than in the general population.[10] Rates of stimulant use, thought to be mainly methamphetamine, are high among both HIV-uninfected and HIV-infected MSM, with 10% to 20% of samples reporting recent methamphetamine use.[11,12,13] In a probability-based sample of young MSM in the United States, 20% reported methamphetamine use in the prior 6 months, with 6% reporting at least weekly use.[14,15] Studies of targeted populations of MSM in San Francisco show even higher rates of methamphetamine use. For example, in a study of circuit parties (weekend-long dance party events) attended by MSM participants, 43% reported methamphetamine use in a 72-hour period.[16]

The "rush" that follows methamphetamine use is associated with the release of neurotransmitters, including dopamine, serotonin, and epinephrine. Most research has focused on the high levels of dopamine released in the central nervous system (CNS).[17,18,19] Amphetamines increase synaptic levels of dopamine by inhibiting the activity of dopamine reuptake transporters and by increasing release of vesicular dopamine stores.[6] Brain imaging studies show that amphetamines increase dopamine levels especially within the nucleus accumbens, the major reward center in the brain that is thought to be central to mediating addictive behavior.[20,21,22] Supporting this hypothesis is that stimulant-induced euphoria is related to dopamine levels and occupancy of the dopamine receptor.[19,23,24,25]

While acute use of methamphetamine results in increased dopamine levels, prolonged use results in chronically depressed dopaminergic activity.[6,26,27] This is thought to be due to the neurotoxic effects of chronic methamphetamine use, which leads to the reduction of axonal dopamine transporters, vesicular monoamine transporters, and synthesis pathways in dopaminergic neurons.[28,29,30] In animal studies, repeated exposure to methamphetamines results in degeneration and destruction of dopamine axon terminals within the CNS.[31,32,33] Other animal studies show depleted brain stores of dopamine and long-term decreases in biochemical markers of dopamine.[34,35,36]

Methamphetamine use can lead to substantial morbidity and mortality. While methamphetamine dependence may be characterized by daily use, many methamphetamine users go on intermittent methamphetamine "binges" that last 24-72 hours during which they are hypervigilant, do not sleep, and often engage in high levels of sexual activity. Persons using methamphetamine can exhibit severe intoxication symptoms that include agitation, anxiety, and acute paranoia, and these conditions can progress to mimic acute schizophrenia.[2] Methamphetamine use is associated with rapid weight loss, likely due to its sympathomimetic properties.[4] Skin lesions are common among methamphetamine users and are due to the obsessive, excessive picking and scratching that accompanies methamphetamine use. These lesions often become infected and develop into bacterial cellulitis that requires antibiotic treatment. Methamphetamine use has been associated with methicillin-resistant Staphylococcus aureus (MRSA) infection.[37]

Many methamphetamine users also experience severe dental decay, which has been attributed to a number of factors, including: (1) decreased attention to dental hygiene due to drug use; (2) excessive bruxism (teeth grinding) and clenching due to the effects of the drug; (3) increased intake of soft drinks high in sugar that methamphetamine users often crave; (4) persistent dry mouth due to methamphetamine; and (5) detrimental effects of residual products used in producing methamphetamine.[38]

Whatever the underlying causes, the combination of weight loss, skin lesions, and dental decay can lead to a decline in general appearance and is likely to account for the rapid aging effect often seen among heavy methamphetamine users. Additional consequences of acute methamphetamine use, while rare, can be severe and include convulsions, stroke, cardiomyopathy, myocardial infarction, and pulmonary compromise.[39,40,41,42]

Methamphetamine withdrawal is well characterized and is associated with increased anxiety, agitation, and depression.[43,44] Symptoms may persist, to varying degrees, over several months.[4,45] In animal studies, depressive behavior following methamphetamine withdrawal has been linked to decreased dopamine levels in the nucleus accumbens.[46] It is postulated that methamphetamine relapses are due primarily to the need to alleviate symptoms by restoring dopamine levels in the CNS to levels that can be observed in the presence of drug.[47,48,49]


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