Methamphetamine toxicity and messengers of death

Brain Res Rev. 2009 May;60(2):379-407. doi: 10.1016/j.brainresrev.2009.03.002. Epub 2009 Mar 25.


Methamphetamine (METH) is an illicit psychostimulant that is widely abused in the world. Several lines of evidence suggest that chronic METH abuse leads to neurodegenerative changes in the human brain. These include damage to dopamine and serotonin axons, loss of gray matter accompanied by hypertrophy of the white matter and microgliosis in different brain areas. In the present review, we summarize data on the animal models of METH neurotoxicity which include degeneration of monoaminergic terminals and neuronal apoptosis. In addition, we discuss molecular and cellular bases of METH-induced neuropathologies. The accumulated evidence indicates that multiple events, including oxidative stress, excitotoxicity, hyperthermia, neuroinflammatory responses, mitochondrial dysfunction, and endoplasmic reticulum stress converge to mediate METH-induced terminal degeneration and neuronal apoptosis. When taken together, these findings suggest that pharmacological strategies geared towards the prevention and treatment of the deleterious effects of this drug will need to attack the various pathways that form the substrates of METH toxicity.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects
  • Body Temperature Regulation / drug effects
  • Cell Death / drug effects
  • Central Nervous System / drug effects*
  • Central Nervous System Stimulants / toxicity*
  • DNA Damage / drug effects
  • Humans
  • Methamphetamine / toxicity*
  • Neurotoxicity Syndromes* / etiology
  • Neurotoxicity Syndromes* / pathology
  • Neurotoxicity Syndromes* / physiopathology
  • Receptors, Dopamine / metabolism
  • Substance-Related Disorders / etiology
  • Substance-Related Disorders / pathology
  • Substance-Related Disorders / physiopathology


  • Central Nervous System Stimulants
  • Receptors, Dopamine
  • Methamphetamine