Repeated Cannabidiol treatment reduces cocaine intake and modulates neural proliferation and CB1R expression in the mouse hippocampus

Neuropharmacology. 2018 Dec:143:163-175. doi: 10.1016/j.neuropharm.2018.09.043. Epub 2018 Sep 28.


Cannabinoid derivatives have shown promising results for treating neuropsychiatric disorders, including drug addiction. Recent studies on the therapeutic effects of Cannabidiol (CBD) on drug abuse showed mixed results, especially with psychostimulant substances such as cocaine. To determine whether CBD can attenuate cocaine reinforcement, we assessed behavioural responses induced by cocaine in mice, using the behavioural sensitization, conditioned place preference and intravenous self-administration paradigms. We show that repeated CBD treatment produces anxiolytic effects in the elevated plus maze test, increases the discrimination index of the novel object recognition task and attenuates cocaine-induced conditioned place preference but does not affect behavioural sensitization. CBD reduced cocaine voluntary consumption and progressive ratio breaking point in the self-administration paradigm, but not drug-induced reinstatement. In parallel, CBD increased expression of type 1 cannabinoid receptor, MAPK-CREB phosphorylation, BDNF expression, and neural cell proliferation in the hippocampus, and reduced the GluA1/2 AMPA subunit receptor ratio in the striatum. In summary, we show that CBD can modulate some behavioural and molecular manifestations of cocaine reinforcement. Moreover, our findings show that CBD has pro-neurogenic effects also in cocaine consuming animals. Overall, this novel evidence provides new perspectives to use CBD as a therapeutic tool.

Keywords: Addiction; Cannabidiol; Cocaine; Neurogenesis; Self-administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / drug therapy
  • Anxiety / metabolism
  • Anxiety / pathology
  • Cannabidiol / pharmacology*
  • Cannabinoid Receptor Agonists / pharmacology
  • Cocaine / administration & dosage
  • Cocaine-Related Disorders / drug therapy*
  • Cocaine-Related Disorders / metabolism
  • Cocaine-Related Disorders / pathology
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology
  • Discrimination, Psychological / drug effects
  • Discrimination, Psychological / physiology
  • Dopamine Uptake Inhibitors / administration & dosage
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Male
  • Mice
  • Neurogenesis / drug effects*
  • Neurogenesis / physiology
  • Psychotropic Drugs / pharmacology*
  • Random Allocation
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Recognition, Psychology / drug effects
  • Recognition, Psychology / physiology
  • Self Administration
  • Spatial Behavior / drug effects
  • Spatial Behavior / physiology


  • CNR1 protein, mouse
  • Cannabinoid Receptor Agonists
  • Dopamine Uptake Inhibitors
  • Psychotropic Drugs
  • Receptor, Cannabinoid, CB1
  • Cannabidiol
  • Cocaine