Cellular and molecular mechanisms involved in the neurotoxicity of opioid and psychostimulant drugs

Brain Res Rev. 2008 Jun;58(1):192-208. doi: 10.1016/j.brainresrev.2008.03.002. Epub 2008 Mar 27.


Substance abuse and addiction are the most costly of all the neuropsychiatric disorders. In the last decades, much progress has been achieved in understanding the effects of the drugs of abuse in the brain. However, efficient treatments that prevent relapse have not been developed. Drug addiction is now considered a brain disease, because the abuse of drugs affects several brain functions. Neurological impairments observed in drug addicts may reflect drug-induced neuronal dysfunction and neurotoxicity. The drugs of abuse directly or indirectly affect neurotransmitter systems, particularly dopaminergic and glutamatergic neurons. This review explores the literature reporting cellular and molecular alterations reflecting the cytotoxicity induced by amphetamines, cocaine and opiates in neuronal systems. The neurotoxic effects of drugs of abuse are often associated with oxidative stress, mitochondrial dysfunction, apoptosis and inhibition of neurogenesis, among other mechanisms. Understanding the mechanisms that underlie brain dysfunction observed in drug-addicted individuals may contribute to improve the treatment of drug addiction, which may have social and economic consequences.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amphetamine / pharmacology
  • Amphetamine / toxicity
  • Analgesics, Opioid / pharmacology*
  • Analgesics, Opioid / toxicity
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Central Nervous System Stimulants / pharmacology*
  • Central Nervous System Stimulants / toxicity
  • Cocaine / pharmacology
  • Cocaine / toxicity
  • Humans
  • Models, Biological
  • Neurotoxicity Syndromes / metabolism
  • Neurotoxicity Syndromes / pathology*
  • Neurotoxicity Syndromes / physiopathology
  • Substance-Related Disorders / metabolism
  • Substance-Related Disorders / pathology
  • Substance-Related Disorders / physiopathology


  • Analgesics, Opioid
  • Central Nervous System Stimulants
  • Amphetamine
  • Cocaine