Neurobiology, Clinical Presentation, and Treatment of Methamphetamine Use Disorder: A Review

JAMA Psychiatry. 2020 Sep 1;77(9):959-966. doi: 10.1001/jamapsychiatry.2020.0246.


Importance: The prevalence of and mortality associated with methamphetamine use has doubled during the past 10 years. There is evidence suggesting that methamphetamine use disorder could be the next substance use crisis in the United States and possibly worldwide.

Observation: The neurobiology of methamphetamine use disorder extends beyond the acute effect of the drug as a monoaminergic modulator and includes intracellular pathways focused on oxidative stress, neurotoxic and excitotoxic effects, and neuroinflammation. Similarly, the clinical picture extends beyond the acute psychostimulatory symptoms to include complex cardiovascular and cerebrovascular signs and symptoms that need to be identified by the clinician. Although there are no pharmacologic treatments for methamphetamine use disorder, cognitive behavioral therapy, behavioral activation, and contingency management show modest effectiveness.

Conclusions and relevance: There is a need to better understand the complex neurobiology of methamphetamine use disorder and to develop interventions aimed at novel biological targets. Parsing the disorder into different processes (eg, craving or mood-associated alterations) and targeting the neural systems and biological pathways underlying these processes may lead to greater success in identifying disease-modifying interventions. Finally, mental health professionals need to be trained in recognizing early cardiovascular and cerebrovascular warning signs to mitigate the mortality associated with methamphetamine use disorder.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amphetamine-Related Disorders / metabolism*
  • Amphetamine-Related Disorders / physiopathology*
  • Amphetamine-Related Disorders / therapy*
  • Central Nervous System Stimulants*
  • Humans
  • Methamphetamine*


  • Central Nervous System Stimulants
  • Methamphetamine