How is methamphetamine different
from other stimulants, such as cocaine?

Methamphetamine is structurally similar to amphetamine and the neurotransmitter dopamine, but it is quite different from cocaine. Although these stimulants have similar behavioral and physiological effects, there are some major differences in the basic mechanisms of how they work. In contrast to cocaine, which is quickly removed and almost completely metabolized in the body, methamphetamine has a much longer duration of action and a larger percentage of the drug remains unchanged in the body. This results in methamphetamine being present in the brain longer, which ultimately leads to prolonged stimulant effects. And although both methamphetamine and cocaine increase levels of the brain chemical dopamine, animal studies reveal much higher levels of dopamine following administration of methamphetamine due to the different mechanisms of action within nerve cells in response to these drugs. Cocaine prolongs dopamine actions in the brain by blocking dopamine re-uptake. While at low doses, methamphetamine blocks dopamine re-uptake, methamphetamine also increases the release of dopamine, leading to much higher concentrations in the synapse, which can be toxic to nerve terminals.

What are the long-term effects
of methamphetamine abuse?

Long-term methamphetamine abuse has many negative consequences, including addiction. Addiction is a chronic, relapsing disease, characterized by compulsive drug seeking and use, accompanied by functional and molecular changes in the brain. In addition to being addicted to methamphetamine, chronic abusers exhibit symptoms that can include anxiety, confusion, insomnia, mood disturbances, and violent behavior. They also can display a number of psychotic features, including paranoia, visual and auditory hallucinations, and delusions (for example, the sensation of insects creeping under the skin). Psychotic symptoms can sometimes last for months or years after methamphetamine abuse has ceased, and stress has been shown to precipitate spontaneous recurrence of methamphetamine psychosis in formerly psychotic methamphetamine abusers.

With chronic abuse, tolerance to methamphetamine's pleasurable effects can develop. In an effort to intensify the desired effects, abusers may take higher doses of the drug, take it more frequently, or change their method of drug intake. Withdrawal from methamphetamine occurs when a chronic abuser stops taking the drug; symptoms of withdrawal include depression, anxiety, fatigue, and an intense craving for the drug.

Chronic methamphetamine abuse also significantly changes the brain. Specifically, brain imaging studies have demonstrated alterations in the activity of the dopamine system that are associated with reduced motor speed and impaired verbal learning. Recent studies in chronic methamphetamine abusers have also revealed severe structural and functional changes in areas of the brain associated with emotion and memory, which may account for many of the emotional and cognitive problems observed in chronic methamphetamine abusers.

Fortunately, some of the effects of chronic methamphetamine abuse appear to be, at least partially, reversible. A recent neuroimaging study showed recovery in some brain regions following prolonged abstinence (2 years, but not 6 months). This was associated with improved performance on motor and verbal memory tests. However, function in other brain regions did not display recovery even after 2 years of abstinence, indicating that some methamphetamine-induced changes are very long-lasting. Moreover, the increased risk of stroke from the abuse of methamphetamine can lead to irreversible damage to the brain.