Envisioning Cannabinoid CB1 Receptor Biased Signaling as a Therapeutic Target for Schizophrenia

-tetrahydrocannabinol, targets the cannabinoid CB1 receptor (CB1R), a G protein-coupled receptor (GPCR). This brief review focuses on recent advances that may enable effective therapeutic targeting of CB1R for the treatment of schizophrenia, especially in individuals with comorbid schizophrenia and cannabis use. The authors summarize the current understanding of CB1R relevant to schizophrenia in sections covering the basic cortical biology and sex differences of CB1R; current knowledge of CB1R alterations in schizophrenia and the potential impact of comorbid cannabis use; recent cell type-specific findings that reconcile past discrepant research in the field; and advances in understanding of GPCR pharmacology and biased ligands that provide new opportunities for CB1R-targeted therapeutics. Derived from this more nuanced understanding of CB1R, the authors propose future directions with the potential to develop a CB1R-targeted treatment of schizophrenia.