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.
Ren
Yanhua
Y
Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.
Whittard
John
J
Higuera-Matas
Alejandro
A
Morris
Claudia V
CV
Hurd
Yasmin L
YL
D000818:Animals; D002185:Cannabidiol / Q000494:pharmacology* / Q000627:therapeutic use; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D003463:Cues; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism; D003932:Heroin / Q000009:adverse effects*; D006556:Heroin Dependence / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008032:Limbic System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000009:adverse effects; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D020318:Rats, Long-Evans; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects / Q000378:metabolism; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology
D002185:Cannabidiol; D063385:Cannabinoid Receptor Modulators; D018698:Glutamic Acid; D003932:Heroin; D009292:Narcotic Antagonists; D009294:Narcotics; D043884:Receptor, Cannabinoid, CB1; D018091:Receptors, AMPA