Advances in the field of cannabinoid--opioid cross-talk

Addict Biol. 2008 Jun;13(2):213-24. doi: 10.1111/j.1369-1600.2008.00107.x.


A remarkable amount of literature has been generated demonstrating the functional similarities between the endogenous opioid and cannabinoid systems. Anatomical, biochemical and molecular data support the existence of reciprocal interactions between these two systems related to several pharmacological responses including reward, cognitive effects, and the development of tolerance and dependence. However, the assessment of the bidirectionality of these effects has been difficult due to their variety and complexity. Reciprocal interactions have been well established for the development of physical dependence. Cross-tolerance and cross-sensitization, although not always bidirectional, are also supported by a number of evidence, while less data have been gathered regarding the relationship of these systems in cognition and emotion. Nevertheless, the most recent advances in cannabinoid-opioid cross-modulation have been made in the area of drug craving and relapse processes. The present review is focused on the latest developments in the cannabinoid-opioid cross-modulation of their behavioural effects and the possible neurobiological substrates involved.

Publication types

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

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / physiopathology*
  • Cannabinoid Receptor Modulators / physiology*
  • Cannabinoids / pharmacology*
  • Cognition / drug effects*
  • Cognition / physiology*
  • Drug Tolerance
  • Emotions / drug effects*
  • Emotions / physiology*
  • Endorphins / physiology*
  • Humans
  • Marijuana Abuse / physiopathology*
  • Motivation*
  • Narcotics / pharmacology*
  • Neurotransmitter Agents / metabolism
  • Opioid-Related Disorders / physiopathology*
  • Receptor Cross-Talk / drug effects*
  • Receptor Cross-Talk / physiology*
  • Receptor, Cannabinoid, CB1 / drug effects*
  • Receptor, Cannabinoid, CB1 / physiology*
  • Receptor, Cannabinoid, CB2 / drug effects
  • Receptor, Cannabinoid, CB2 / physiology
  • Receptors, Opioid / drug effects
  • Receptors, Opioid / physiology
  • Substance Withdrawal Syndrome / physiopathology*


  • Cannabinoid Receptor Modulators
  • Cannabinoids
  • Endorphins
  • Narcotics
  • Neurotransmitter Agents
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • Receptors, Opioid