Cannabidiol, a Nonpsychotropic Component of Cannabis, Inhibits Cue-Induced Heroin Seeking and Normalizes Discrete Mesolimbic Neuronal Disturbances
Yanhua Ren,1 John Whittard,1 Alejandro Higuera-Matas,2 Claudia V. Morris,1 and Yasmin L. Hurd1
1Departments of Psychiatry and Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, New York 10029-6574, and 2Psychobiology Department, School of Psychology, Universidad Nacional de Educación a Distancia, 28040 Madrid, Spain
Correspondence should be addressed to Yasmin Hurd, Departments of Psychiatry, Pharmacology and Systems Therapeutics, and Neuroscience, Mount Sinai School of Medicine, One Gustave Levy Place, Box 1603, New York, NY 10029-6574. Email: Yasmin.Hurd@mssm.edu
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.