DARK Classics in Chemical Neuroscience: Methamphetamine

Methamphetamine has the second highest prevalence of drug abuse after cannabis, with estimates of 35 million users worldwide. The (S)-(+)-enantiomer is the illicit drug, active neurostimulant, and eutomer, while the (R)-(-)-enantiomer is contained in over the counter decongestants. While designated a schedule II drug in 1970, (S)-(+)-methamphetamine is available by prescription for the treatment of attention-deficit disorder and obesity. The illicit use of (S)-(+)-methamphetamine results in the sudden "rush" of stimulation to the motivation, movement, pleasure, and reward centers in the brain, caused by rapid release of dopamine. In this review, we will provide an overview of the synthesis, pharmacology, adverse effects, and drug metabolism of this widely abused psychostimulant that distinguish it as a DARK classic in Chemical Neuroscience.