Vitamin D Deficiency Exacerbates UV/endorphin and Opioid Addiction

Authors

• Lajos V. Kemeny, Harvard Medical School
• Kathleen C. Robinson, Harvard Medical School
• Andrea L. Hermann, Harvard Medical School
• Deena M. Walker, Icahn School of Medicine at Mount Sinai
• Susan Regan, Harvard Medical School
• Yik Weng Yew, National Skin Centre, Singapore
• Yi Chun Lai, Rutgers New Jersey Medical School
• Nicholas Theodosakis, Harvard Medical School
• Phillip D. Rivera, Harvard Medical School
• Weihua Ding, Harvard Medical School
• Liuyue Yang, Harvard Medical School
• Tobias Beyer, Harvard Medical School
• Yong Hwee E. Loh, Icahn School of Medicine at Mount Sinai
• Jennifer A. Lo, Harvard Medical School
• Anita A.J. Van Der Sande, Harvard Medical School
• William Sarnie, Harvard Medical School
• David Kotler, Harvard Medical School
• Jennifer J. Hsiao, Harvard Medical School
• MacK Y. Su, Harvard Medical School
• Shinichiro Kato, Harvard Medical School

Document Type

Article

Publication Date

6-1-2021

Publication Source

Science Advances

Volume Number

7

Issue Number

24

E-ISSN

23752548

Article Number

eabe4577

Abstract

The current opioid epidemic warrants a better understanding of genetic and environmental factors that contribute to opioid addiction. Here we report an increased prevalence of vitamin D (VitD) deficiency in patients diagnosed with opioid use disorder and an inverse and dose-dependent association of VitD levels with self-reported opioid use. We used multiple pharmacologic approaches and genetic mouse models and found that deficiencies in VitD signaling amplify exogenous opioid responses that are normalized upon restoration of VitD signaling. Similarly, physiologic endogenous opioid analgesia and reward responses triggered by ultraviolet (UV) radiation are repressed by VitD signaling, suggesting that a feedback loop exists whereby VitD deficiency produces increased UV/endorphin-seeking behavior until VitD levels are restored by cutaneous VitD synthesis. This feedback may carry the evolutionary advantage of maximizing VitD synthesis. However, unlike UV exposure, exogenous opioid use is not followed by VitD synthesis (and its opioid suppressive effects), contributing to maladaptive addictive behavior.

Recommended Citation

Published in: Science Advances, Volume 7, Issue 24, June 1, 2021.