Cannabidiol and Beta-Caryophyllene: Chronic inflammatory pain

Authors

Mohammed Alnoud, The University of Texas Rio Grande ValleyFollow
Mohammad Hussain, The University of Texas Rio Grande ValleyFollow
Jose Rios, The University of Texas Rio Grande ValleyFollow
Emmanuel Franco, The University of Texas Rio Grande ValleyFollow
Justin D. Mills, The University of Texas Rio Grande ValleyFollow
Joshua Nwose, The University of Texas Rio Grande ValleyFollow
Maria Sophia Malbas, The University of Texas Rio Grande ValleyFollow
Hiram L. Garcia, The University of Texas Rio Grande ValleyFollow
Sophia Leslie, The University of Texas Rio Grande ValleyFollow
Manish Tripathi, The University of Texas Rio Grande ValleyFollow
Khalid Benamar, The University of Texas Rio Grande ValleyFollow

Document Type

Article

Publication Date

12-2025

Abstract

While chronic pain is challenging to manage, it always co-exists with depression. Currently, chronic pain and depression are usually treated separately with distinct approaches, yet effectiveness remains elusive. Consequently, the development of integrated therapeutic strategies for pain while addressing depression is a high public health priority and unmet need that affects millions of people. This study aims to determine if the combination of the two phytocannabinoids Beta-Caryophyllene (BCP) and cannabidiol (CBD) is effective for chronic pain while simultaneously showing antidepressant effects. We used a chronic inflammatory pain model (Complete Freund's Adjuvant, CFA) and a battery of pain and depression-like behavior tests in mice. Proteomics and immunohistochemistry (IHC) were used to explore the potential mechanisms of the effect of the combination on pain and depression. We found that mice treated with the CBD and BPC combination produced a synergistic pain-relieving effect in the chronic inflammatory pain model and exhibited antidepressant properties. Our IHC data also show that the CBD and BCP combination significantly reduced the neuroinflammation produced by CFA, and the proteomics showed downregulation of selected proteins involved in inflammation by the combination, compared to the individual effects of CBD and BCP. In conclusion, our current findings show that, in the CFA pain model, the combination of CBD and BCP produces a synergistic pain-relief effect while also having antidepressant properties. Additionally, our data show that the anti-inflammatory action of this combination may explain its beneficial effects on pain and depression. Therefore, our data suggest this combination as a potentially effective treatment for chronic pain and related depression.

Comments

http://creativecommons.org/licenses/by-nc-nd/4.0/

Recommended Citation

Alnoud, M., Hussain, M., Rios, J., Franco, E., Mills, J., Nwose, J., ... & Benamar, K. (2025). Cannabidiol and Beta-Caryophyllene: chronic inflammatory pain. Pharmacological research, 107987. https://doi.org/10.1016/j.phrs.2025.107987

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Publication Title

Pharmacological Research

DOI

10.1016/j.phrs.2025.107987

Academic Level

faculty

Mentor/PI Department

Immunology and Microbiology