Mechanism of Action

Methamphetamine dog

Methamphetamine acts on the pleasure circuit in the brain by altering the levels of certain neurotransmitters present in the synapse. Chemically, Methamphetamine is closely related to amphetamine, but its effects on the central nervous system are greater than those of amphetamine.

Methamphetamine is also chemically similar to dopamine and another neurotransmitter, norepinephrine. It produces its effects by causing dopamine and norepinephrine to be released into the synapse in several areas of the brain, including the nucleus accumbens, prefrontal cortex, and the striatum, a brain area involved in movement. Specifically, Methamphetamine enters nerve terminals by passing directly through nerve cell membranes. It is also carried into the nerve terminals by transporter molecules that normally carry dopamine or norepinephrine from the synapse back into the nerve terminal. Once in the nerve terminal, Methamphetamine enters dopamine and norepinephrine containing vesicles and causes the release of these neurotransmitters. Enzymes in the cell normally chew up excess dopamine and norepinephrine; however, Methamphetamine blocks this breakdown. The excess neurotransmitters are then carried by transporter molecules out of the neuron and into the synapse. Once in the synapse, the high conce ntration of dopamine causes feelings of pleasure and euphoria. The excess norepinephrine may be responsible for the alertness and anti-fatigue effects of Methamphetamine.

Methamphetamine can also affect the brain in other ways. For example, it can cause cerebral edema, brain hemorrhage, paranoia, and hallucinations. Some of the effects of Methamphetamine on the brain may be long-lasting and even permanent. Recent research in humans has shown that even three years after chronic Methamphetamine users have discontinued use of the drug there is still a reduction in their ability to transport dopamine back into neurons. This clearly demonstrates that there is a long-lasting impairment in dopamine function as a result of drug use. This is highly significant because dopamine has a major role in many brain functions, including experiences of pleasure, mood, and movement. In these same studies, researchers compared the damage to the dopamine system of Methamphetamine users to that seen in patients with Parkinson's disease. Parkinson's disease is characterized by a progressive loss of dopamine neurons in brain regions that are involved in movement. Although the damage to the do pamine system was greater in the Parkinson's patients, the brains of former Methamphetamine users showed similar patterns to that seen in Parkinson's disease. Scientists now believe that the damage to the dopamine system from longterm Methamphetamine use may lead to symptoms of Parkinson's disease. (It should be noted that Parkinson's disease itself is not caused by drug use.) In support of this, research with laboratory animals has demonstrated that exposure to a single, high dose of Methamphetamine or prolonged exposure at low doses destroys up to fifty 39 percent of the dopamine-producing neurons in certain parts of the brain.

Methamphetamine also has widespread effects on other parts of the body. It can cause high blood pressure, arrhythmias, chest pain, shortness of breath, nausea, vomiting, and diarrhea. It can also increase body temperature, which can be lethal in overdose situations.

The following activities, when used along with the magazine on Methamphetamine, will help explain to students how this substance changes the brain and the body.

This publication is available for your use and may be reproduced in its entirety without permission from NIDA. Citation of the source is appreciated, using the following language: Source: National Institute on Drug Abuse; National Institutes of Health; U.S. Department of Health and Human Services.