As a powerful stimulant, methamphetamine, even in small doses, can increase wakefulness and physical activity and decrease appetite. A brief, intense sensation, or rush, is reported by those who smoke or inject methamphetamine. Oral ingestion or snorting produces a long-lasting high instead of a rush, which reportedly can continue for as long as half a day. Both the rush and the high are believed to result from the release of very high levels of the neurotransmitter dopamine into areas of the brain that regulate feelings of pleasure.

Methamphetamine has toxic effects. In animals, a single high dose of the drug has been shown to damage nerve terminals in the dopamine-containing regions of the brain. The large release of dopamine produced by methamphetamine is thought to contribute to the drug's toxic effects on nerve terminals in the brain. High doses can elevate body temperature to dangerous, sometimes lethal, levels, as well as cause convulsions.

Long-term methamphetamine abuse results in many damaging effects, including addiction. Addiction is a chronic, relapsing disease, characterized by compulsive drug-seeking and drug use which is accompanied by functional and molecular changes in the brain. In addition to being addicted to methamphetamine, chronic methamphetamine abusers exhibit symptoms that can include violent behavior, anxiety, confusion, and insomnia. They also can display a number of psychotic features, including paranoia, auditory hallucinations, mood disturbances, and delusions (for example, the sensation of insects creeping on the skin, which is called "formication"). The paranoia can result in homicidal as well as suicidal thoughts.

With chronic use, tolerance for methamphetamine can develop. In an effort to intensify the desired effects, users may take higher doses of the drug, take it more frequently, or change their method of drug intake. In some cases, abusers forego food and sleep while indulging in a form of binging known as a "run," injecting as much as a gram of the drug every 2 to 3 hours over several days until the user runs out of the drug or is too disorganized to continue. Chronic abuse can lead to psychotic behavior, characterized by intense paranoia, visual and auditory hallucinations, and out-of-control rages that can be coupled with extremely violent behavior.

Although there are no physical manifestations of a withdrawal syndrome when methamphetamine use is stopped, there are several symptoms that occur when a chronic user stops taking the drug. These include depression, anxiety, fatigue, paranoia, aggression, and an intense craving for the drug.

In scientific studies examining the consequences of long-term methamphetamine exposure in animals, concern has arisen over its toxic effects on the brain. Researchers have reported that as much as 50 percent of the dopamine-producing cells in the brain can be damaged after prolonged exposure to relatively low levels of methamphetamine. Researchers also have found that serotonin-containing nerve cells may be damaged even more extensively. Whether this toxicity is related to the psychosis seen in some long-term methamphetamine abusers is still an open question.