Altered energy production, lowered antioxidant potential, and inflammatory processes mediate CNS damage associated with abuse of the psychostimulants MDMA and methamphetamine

Eur J Pharmacol. 2014 Mar 15:727:125-9. doi: 10.1016/j.ejphar.2014.01.032. Epub 2014 Jan 28.

Abstract

Central nervous system (CNS) damage associated with psychostimulant dependence may be an ongoing, degenerative process with adverse effects on neuropsychiatric function. However, the molecular mechanisms regarding how altered energy regulation affects immune response in the context of substance use disorders are not fully understood. This review summarizes the current evidence regarding the effects of psychostimulant [particularly 3,4-methylenedioxy-N-methylamphetamine (MDMA) and methamphetamine] exposure on brain energy regulation, immune response, and neuropsychiatric function. Importantly, the neuropsychiatric impairments (e.g., cognitive deficits, depression, and anxiety) that persist following abstinence are associated with poorer treatment outcomes - increased relapse rates, lower treatment retention rates, and reduced daily functioning. Qualifying the molecular changes within the CNS according to the exposure and use patterns of specifically abused substances should inform the development of new therapeutic approaches for addiction treatment.

Keywords: 2-Fluoro-2-deoxy-d-glucose (PubChem CID: 315411); 3,4-Methylenedioxy-N-methylamphetamine (MDMA); 3,4-Methylenedioxy-N-methylamphetamine (MDMA) (PubChem CID: 1615); 3,4-Methylenedioxyethamphetamine (MDE) (PubChem CID: 105039); Bioenergetics; Cocaine (PubChem CID: 5760); Inflammation; Methamphetamine; Methamphetamine (PubChem CID: 10836); Neurodegenerative diseases; Oxidative stress.

Publication types

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

MeSH terms

  • Amphetamine-Related Disorders / complications*
  • Amphetamine-Related Disorders / immunology
  • Amphetamine-Related Disorders / metabolism
  • Amphetamine-Related Disorders / pathology
  • Amphetamine-Related Disorders / rehabilitation
  • Animals
  • Brain / drug effects*
  • Brain / immunology
  • Brain / metabolism
  • Brain / pathology
  • Central Nervous System Stimulants / adverse effects
  • Energy Metabolism / drug effects*
  • Humans
  • Inflammation Mediators / metabolism*
  • Methamphetamine / adverse effects*
  • N-Methyl-3,4-methylenedioxyamphetamine / adverse effects*
  • Oxidative Stress / drug effects*
  • Recurrence
  • Substance Withdrawal Syndrome / etiology
  • Substance Withdrawal Syndrome / metabolism

Substances

  • Central Nervous System Stimulants
  • Inflammation Mediators
  • Methamphetamine
  • N-Methyl-3,4-methylenedioxyamphetamine