Clinical Aspects of Methamphetamine

Introduction

Methamphetamine, developed in 1893, is a synthetic stimulant that affects the central nervous system and other major organ systems. Until the 1950s, no prescription was necessary to obtain methamphetamine or other amphetamine-containing products. Prescriptions for variants of these drugs were freely dispensed in the 1960s. Different versions of methamphetamine became popular in the 1960s, and “ice,” a smokable derivative, emerged in the late 1980s in Hawaii. The evolution of methamphetamine use since 1988 has varied. The early to mid-1990s witnessed escalating problems with methamphetamine throughout many parts of the world. In the United States the highest rates of use were in the Western region of the country, particularly in suburban and rural communities. Australia also saw increases in use and, in the same region, Southeast Asia also reported escalating prevalence. Relatively little use is reported in the United Kingdom and the rest of Europe.

One of the key enablers of the growth of methamphetamine use was the wide availability of pseudoephedrine, the primary precursor of methamphetamine, which was contained in many over-the-counter cold medications including Sudafed, Nyquil, and Claritin-D. Methamphetamine was manufactured and distributed by small homemade “kitchen chemists,” as well as larger syndicates and drug cartels. Those exposed to active methamphetamine production sites, including children, can have serious health consequences from explosions, fires, and toxic gases and wastes. Consequently, methamphetamine use and methamphetamine use disorder have had a substantial impact on the treatment, health care, criminal justice, and social welfare systems. From 2003 to 2006, many jurisdictions around the world, including the United States, imposed strict precursor control laws that restrict the retail sales of medications that contain pseudoephedrine. These efforts have substantially reduced the availability of methamphetamine and increased its price in many areas of the United States.

In the United States, from the early 1990s through 2005, numerous indicators have shown steady increases in the use of methamphetamine. However, in the early to mid-2000s, many areas in the world have started to show a reduction in people who use the drug. In 2007 in the United States, 529,000 people 12 years of age or older were current users of methamphetamine, a reduction from 731,000 in 2006. Similarly, the Community Epidemiology Work Group of the National Institute on Drug Abuse reported that methamphetamine indicators from law enforcement (arrests and seizures) and emergency room data from 20 of 22 metropolitan areas, showed either a stable or downward trend of methamphetamine use during 2006 and 2007. Similarly, treatment admissions for methamphetamine, which increased dramatically from the 1990s to 2005, showed a decline in 2006.

In other parts of the world, similar declines have been reported. In Australia, for example, there has been a decreasing trend in reported methamphetamine use since 1998, and the 2016 National Drug Strategy Household Survey shows methamphetamine at its lowest point since recording began. However, harm indicators have continued to increase, including ambulance callouts, treatment presentations, and drug-related deaths, largely due to a change in reported preference for the more potent and pure crystal form (ice) over the powdered form (speed).

Neurobiological Impact of Methamphetamine Use

Some caution is required in interpreting neurocognitive studies, as most are cross-sectional and cannot confirm whether cognitive deficits are predrug or postdrug use. In addition, some longitudinal studies show that childhood deficits in executive function can predict adolescent drug use, suggesting that some of the cognitive problems could be premorbid. Frequency, duration, and quantity of use does not appear to predict level of cognitive impairment, suggesting a vulnerability to the toxic effects of methamphetamine among some people who use it. However, regular long-term methamphetamine use has been associated with significant impairment relative to age- and education-matched controls on a range of cognitive domains and self-reported functional impairments correspond with neurocognitive deficits.

Methamphetamine has a significant impact on the structure and chemistry of the brain, largely through disruption of the dopamine system. Methamphetamine releases stores of dopamine into the synapse, and then blocks its reuptake, resulting in significantly increased levels of dopamine in the synapse of neurons, particularly in the prefrontal cortex and the limbic regions of the brain. Among people who use methamphetamine occasionally, these changes to the dopamine system correct themselves after a few days, and dopamine stores return to preuse levels once the methamphetamine has been eliminated from the body. However, among people who use methamphetamine regularly, depleted dopamine stores do not have sufficient time to replenish. Methamphetamine also increases the cytoplasmic concentration of dopamine, which promotes oxidation products that are toxic to the nerve terminals, and long-term use has been associated with a fourfold increase in risk of Parkinson disease. The neurotoxicity of methamphetamine is further accentuated by its prolonged half-life and long duration of action.

After regular use, there is evidence of damage to the structures of the dopamine system, significantly affecting executive functioning, episodic memory, and motor functioning. The magnitude of the impairments is significant compared to other drugs such as cocaine and cannabis.

For regular and dependent methamphetamine users who enter treatment, attention, memory, and executive function seem to decline further in the first 2 weeks of abstinence potentially due to the deprivation of the acute benefits of methamphetamine on cognition, sleep disturbance, or neuropsychiatric sequelae. After 6 months of abstinence, cognitive test performance is worse than in people who had either relapsed or continued to use, with little significant improvement in the first 12 months. However, one study showed some improvement after an average of 13 months, with the range up to 42 months, on some domains (motor functioning and information processing speed but not learning, memory, and executive functioning).

The level of dopamine depletion is a predictor of relapse risk. People who use methamphetamine over a long period also demonstrate attentional bias for drug-related stimuli, which has been shown to predict poorer treatment outcomes. Cognitive impairment is generally associated with poorer treatment retention.

Effects of Methamphetamine Use and Methamphetamine Use Disorder

Specific Populations