How fast and how often: The pharmacokinetics of drug use are decisive in addiction

Neurosci Biobehav Rev. 2015 Sep:56:166-79. doi: 10.1016/j.neubiorev.2015.06.012. Epub 2015 Jun 24.


How much, how often and how fast a drug reaches the brain determine the behavioural and neuroplastic changes associated with the addiction process. Despite the critical nature of these variables, the drug addiction field often ignores pharmacokinetic issues, which we argue can lead to false conclusions. First, we review the clinical data demonstrating the importance of the speed of drug onset and of intermittent patterns of drug intake in psychostimulant drug addiction. This is followed by a review of the preclinical literature demonstrating that pharmacokinetic variables play a decisive role in determining behavioural and neurobiological outcomes in animal models of addiction. This literature includes recent data highlighting the importance of intermittent, 'spiking' brain levels of drug in producing an increase in the motivation to take drug over time. Rapid drug onset and intermittent drug exposure both appear to push the addiction process forward most effectively. This has significant implications for refining animal models of addiction and for better understanding the neuroadaptations that are critical for the disorder.

Keywords: Cocaine; Drug addiction; Intermittent drug exposure; Pharmacokinetics; Route of drug intake; Speed of drug delivery.

Publication types

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

MeSH terms

  • Animals
  • Behavior, Addictive / physiopathology*
  • Cocaine / administration & dosage
  • Cocaine / pharmacokinetics*
  • Dopamine Uptake Inhibitors / administration & dosage
  • Dopamine Uptake Inhibitors / pharmacokinetics*
  • Drug Administration Routes
  • Humans
  • Motivation
  • Substance-Related Disorders / psychology*


  • Dopamine Uptake Inhibitors
  • Cocaine