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Cannabidiol, a nonpsychotropic component of cannabis, inhibits cue-induced heroin seeking and normalizes discrete mesolimbic neuronal disturbances.


There remains debate regarding the impact of cannabis on neuropsychiatric disorders. Here, we examined the effects of cannabidiol (CBD), a nonpsychoactive constituent of cannabis, on heroin self-administration and drug-seeking behavior using an experimental rat model. CBD (5-20 mg/kg) did not alter stable intake of heroin self-administration, extinction behavior, or drug seeking induced by a heroin prime injection. Instead, it specifically attenuated heroin-seeking behavior reinstated by exposure to a conditioned stimulus cue. CBD had a protracted effect with significance evident after 24 h and even 2 weeks after administration. The behavioral effects were paralleled by neurobiological alterations in the glutamatergic and endocannabinoid systems. Discrete disturbances of AMPA GluR1 and cannabinoid type-1 receptor expression observed in the nucleus accumbens associated with stimulus cue-induced heroin seeking were normalized by CBD treatment. The findings highlight the unique contributions of distinct cannabis constituents to addiction vulnerability and suggest that CBD may be a potential treatment for heroin craving and relapse.

Pubmed ID: 19940171


  • Ren Y
  • Whittard J
  • Higuera-Matas A
  • Morris CV
  • Hurd YL


The Journal of neuroscience : the official journal of the Society for Neuroscience

Publication Data

November 25, 2009

Associated Grants

  • Agency: NIDA NIH HHS, Id: DA19350
  • Agency: NIDA NIH HHS, Id: R01 DA019350
  • Agency: NIDA NIH HHS, Id: R01 DA019350-06
  • Agency: NIDA NIH HHS, Id: R21 DA027781
  • Agency: NIMH NIH HHS, Id: T32 MH087004

Mesh Terms

  • Animals
  • Cannabidiol
  • Cannabinoid Receptor Modulators
  • Conditioning (Psychology)
  • Cues
  • Disease Models, Animal
  • Glutamic Acid
  • Heroin
  • Heroin Dependence
  • Limbic System
  • Male
  • Narcotic Antagonists
  • Narcotics
  • Neural Pathways
  • Nucleus Accumbens
  • Rats
  • Rats, Long-Evans
  • Receptor, Cannabinoid, CB1
  • Receptors, AMPA
  • Treatment Outcome
  • Ventral Tegmental Area