Abstract Drugs of abuse induce cell type specific adaptations in D1- and D2-medium spiny neurons (MSNs) in the nucleus accumbens core (NAcore), that can bias signaling towards D1-MSNs and enhance relapse vulnerability. Whether ∆9-tetrahydrocannabinol (THC) use initiates similar neuroadaptations is unknown. D1- and D2-Cre transgenic rats were transfected with Cre-dependent reporters and trained to self-administer THC+cannabidiol (THC+CBD). After extinction training spine morphology, glutamate transmission, CB1R function and cFOS expression were quantified. We found that extinction from THC+CBD induced a loss of large spine heads in D1- but not D2-MSNs and commensurate reductions in glutamate synaptic transmission. Also, presynaptic CB1R function was impaired selectively at...