The methamphetamine molecule is structurally similar to amphetamine and to the neurotransmitter dopamine, a brain chemical that plays an important role in the reinforcement of rewarding behaviors, but it is quite different from cocaine.45 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 from 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. Methamphetamine therefore remains in the brain longer, which ultimately leads to prolonged stimulant effects.46
Although both methamphetamine and cocaine increase levels of dopamine, administration of methamphetamine in animal studies leads to much higher levels of dopamine, because nerve cells respond differently to the two drugs. Cocaine prolongs dopamine actions in the brain by blocking the re-absorption (re-uptake) of the neurotransmitter by signaling nerve cells. At low doses, methamphetamine also blocks the re-uptake of dopamine, but it also increases the release of dopamine, leading to much higher concentrations in the synapse (the gap between neurons), which can be toxic to nerve terminals.38,39
| Methamphetamine | Cocaine |
|---|---|
| Stimulant | Stimulant and local anesthetic |
| Man-made | Plant-derived |
| Smoking produces a long-lasting high | Smoking produces a brief high |
| 50% of the drug is removed from the body in 12 hours | 50% of the drug is removed from the body in 1 hour |
| Increases dopamine release and blocks dopamine re-uptake | Blocks dopamine re-uptake |
| Limited medical use for ADHD, narcolepsy, and weight loss | Limited medical use as a local anesthetic in some surgical procedures |