TY - JOUR T1 - Cannabidiol, a Nonpsychotropic Component of Cannabis, Inhibits Cue-Induced Heroin Seeking and Normalizes Discrete Mesolimbic Neuronal Disturbances JF - The Journal of Neuroscience JO - J. Neurosci. SP - 14764 LP - 14769 DO - 10.1523/JNEUROSCI.4291-09.2009 VL - 29 IS - 47 AU - Yanhua Ren AU - John Whittard AU - Alejandro Higuera-Matas AU - Claudia V. Morris AU - Yasmin L. Hurd Y1 - 2009/11/25 UR - http://www.jneurosci.org/content/29/47/14764.abstract N2 - 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. ER -