Abstract
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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cannabidiol / pharmacology*
-
Cannabidiol / therapeutic use
-
Cannabinoid Receptor Modulators / metabolism
-
Conditioning, Psychological / drug effects
-
Conditioning, Psychological / physiology
-
Cues
-
Disease Models, Animal
-
Glutamic Acid / metabolism
-
Heroin / adverse effects*
-
Heroin Dependence / drug therapy*
-
Heroin Dependence / metabolism
-
Heroin Dependence / physiopathology
-
Limbic System / drug effects*
-
Limbic System / metabolism
-
Limbic System / physiopathology
-
Male
-
Narcotic Antagonists / pharmacology
-
Narcotics / adverse effects
-
Neural Pathways / drug effects
-
Neural Pathways / metabolism
-
Neural Pathways / physiopathology
-
Nucleus Accumbens / drug effects
-
Nucleus Accumbens / metabolism
-
Nucleus Accumbens / physiopathology
-
Rats
-
Rats, Long-Evans
-
Receptor, Cannabinoid, CB1 / drug effects
-
Receptor, Cannabinoid, CB1 / metabolism
-
Receptors, AMPA / drug effects
-
Receptors, AMPA / metabolism
-
Treatment Outcome
-
Ventral Tegmental Area / drug effects
-
Ventral Tegmental Area / metabolism
-
Ventral Tegmental Area / physiopathology
Substances
-
Cannabinoid Receptor Modulators
-
Narcotic Antagonists
-
Narcotics
-
Receptor, Cannabinoid, CB1
-
Receptors, AMPA
-
Cannabidiol
-
Glutamic Acid
-
Heroin
-
glutamate receptor ionotropic, AMPA 1