Fig 2: Protein levels and colocalization in neurons incubated with CBD and/or METH. (A) Levels of pMeCP2 and apoptosis-related proteins. (B) DRD1 and pMeCP2 levels and their colocalization. (C) Cleaved caspase-8 and cleaved caspase-3 levels and their colocalization. ** p < 0.01 or *** p < 0.001 compared with control group, # p < 0.05 or ### p < 0.001 compared with METH group; Tukey HSD post-hoc comparison after significant ANOVA.

Fig 3: Protein levels and colocalization in neurons incubated with CBD and/or SKF81297. (A) Levels of pMeCP2 and apoptosis-related proteins. (B) DRD1 and pMeCP2 levels and their colocalization. (C) Cleaved caspase-8 and cleaved caspase-3 levels and their colocalization. ** p < 0.01 or *** p < 0.001 compared with control group, ## p < 0.01 or ### p < 0.001 compared with METH group; Tukey HSD post-hoc comparison after significant ANOVA.

Fig 4: Protein-drug binding simulations. Seven transmembrane domains of DRD1 are shown as multicolor bands. METH or CBD are marked in cyan, while key DRD1 residues are marked in yellow. (A) Docking pose, binding sites, and interactions between DRD1 model and METH. (B) Docking pose, binding sites, and interactions between DRD1 model and CBD. (C) Docking pose, binding sites, and interactions among CBD, METH, and DRD1 model.

Fig 5: Protein, intracellular Ca2+, and apoptosis levels in prefrontal cortex of rats repeatedly exposed to CBD and/or METH. (A) Levels of DRD1, pMeCP2, and apoptosis-related proteins in prefrontal cortex. (B) Intracellular Ca2+ level in prefrontal cortex. (C) Apoptosis level in prefrontal cortex. ***p < 0.001 compared with control group, ### p < 0.001 compared with METH group; Tukey HSD post-hoc comparison after significant ANOVA.