Central side-effects of therapies based on CB1 cannabinoid receptor agonists and antagonists: focus on anxiety and depression

Best Pract Res Clin Endocrinol Metab. 2009 Feb;23(1):133-44. doi: 10.1016/j.beem.2008.09.003.


Both agonists (e.g. Delta(9)-tetrahydrocannabinol, nabilone) and antagonists (e.g. rimonabant, taranabant) of the cannabinoid type-1 (CB(1)) receptor have been explored as therapeutic agents in diverse fields of medicine such as pain management and obesity with associated metabolic dysregulation, respectively. CB(1) receptors are widely distributed in the central nervous system and are involved in the modulation of emotion, stress and habituation responses, behaviours that are thought to be dysregulated in human psychiatric disorders. Accordingly, CB(1) receptor activation may, in some cases, precipitate episodes of psychosis and panic, while its inhibition may lead to behaviours reminiscent of depression and anxiety-related disorders. The present review discusses these side-effects, which have to be taken into account in the therapeutic exploitation of the endocannabinoid system.

Publication types

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

MeSH terms

  • Affect / drug effects
  • Animals
  • Anxiety Disorders / chemically induced
  • Anxiety Disorders / drug therapy*
  • Cannabinoid Receptor Modulators / physiology
  • Depressive Disorder / chemically induced
  • Depressive Disorder / drug therapy*
  • Dronabinol / adverse effects*
  • Dronabinol / analogs & derivatives*
  • Humans
  • Piperidines / adverse effects*
  • Pyrazoles / adverse effects*
  • Receptor, Cannabinoid, CB1 / agonists*
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
  • Rimonabant


  • Cannabinoid Receptor Modulators
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • nabilone
  • Dronabinol
  • Rimonabant