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Envisioning Cannabinoid CB1 Receptor Biased Signaling as a Therapeutic Target for Schizophrenia
Shih-Hsuan Ku1, Sierra J Stringfield2, Mary M Torregrossa1
1Department of Psychiatry, University of Pittsburgh, Pittsburgh.
The American Journal of Psychiatry
|April 17, 2026
Summary
Cannabis use exacerbates schizophrenia symptoms and prognosis by affecting the cannabinoid CB1 receptor (CB1R). Targeting CB1R offers potential new treatments for schizophrenia, especially with co-occurring cannabis use.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- The endocannabinoid system and its role in schizophrenia are of significant psychiatric interest.
- Cannabis use is prevalent in schizophrenia patients and may worsen the condition.
- Δ9-tetrahydrocannabinol in cannabis targets the cannabinoid CB1 receptor (CB1R).
Purpose of the Study:
- To review recent advances in targeting CB1R for schizophrenia treatment.
- To explore CB1R's role in schizophrenia, especially with comorbid cannabis use.
- To identify new therapeutic opportunities for CB1R-targeted treatments.
Main Methods:
- Review of current literature on CB1R in schizophrenia.
- Analysis of basic cortical biology and sex differences of CB1R.
- Examination of CB1R alterations in schizophrenia and cannabis use impact.
- Assessment of cell type-specific findings and GPCR pharmacology.
Main Results:
- Cannabis use dose-dependently increases schizophrenia diagnosis likelihood and symptom severity.
- CB1R alterations in schizophrenia are influenced by comorbid cannabis use.
- Biased ligands and GPCR pharmacology offer novel therapeutic avenues.
Conclusions:
- A nuanced understanding of CB1R is emerging for schizophrenia treatment.
- Targeting CB1R presents a promising strategy for managing schizophrenia.
- Future research directions focus on developing effective CB1R-targeted therapies.
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