New research suggests a potential role for vitamin D supplementation in the opioid epidemic—something the Centers for Disease Control and Prevention estimates costs the United States $78.5 billion every year.
Previous studies have found vitamin D deficiency was associated with higher opioid doses among patients with opioid-consuming chronic pain. These studies are confounded by the presence of pain, which is also associated with vitamin D deficiency. With all this in mind, researchers at Massachusetts General Hospital (MGH) examined whether a relationship may exist between opioid use and serum vitamin D levels in humans, independently of pain, using data from the National Health and Nutrition Examination Survey. Their findings suggest an inverse, dose-dependent relationship between vitamin D signaling and opioid use, independent of known opioid use triggers.
In 2007, David E. Fisher, MD, PhD, director of the Mass General Cancer Center's Melanoma Program and director of MGH's Cutaneous Biology Research Center (CBRC) and his team discovered that exposure to ultraviolet rays causes the skin to produce endorphin—which is chemically related to morphine, heroin and other opioids. One thing opioids and opioid peptides have in common is that they all activate the same receptors in the brain.
UV exposure raises endorphin levels in mice, which then display behavior consistent with opioid addiction, Fisher later found in a different study.
Fisher and colleagues hypothesize that sun seeking is driven by vitamin D deficiency, aiming to increase synthesis of the hormone for survival, and that vitamin D deficiency might also make the body more sensitive to the effects of opioids, potentially contributing to addiction.
"Our goal in this study was to understand the relationship between vitamin D signaling in the body and UV-seeking and opioid-seeking behaviors," said lead author Lajos V. Kemény, MD, PhD, a postdoctoral research fellow in Dermatology at MGH.
In the new research, published in Science Advances, Fisher, Kemény and a team from several institutions approached this vitamin D/addictive behavior from several angles.
First, the team compared normal lab mice with mice that were deficient in vitamin D.
"We found that modulating vitamin D levels changes multiple addictive behaviors to both UV and opioids," explained Kemény. The report noted that when the mice were conditioned with modest doses of morphine, those deficient in vitamin D continued seeking out the drug, behavior that was less common among the normal mice. When morphine was withdrawn, the mice with low vitamin D levels were much more likely to have withdrawals.
The study also found that morphine worked more effectively as a pain reliever in mice with vitamin D deficiency, meaning the opioid had an exaggerated response in these mice. Fisher explained that this is concerning if it has the same effect on vitamin D-deficient humans, who could be more likely to grow addicted to morphine after a surgery, for example.
The research goes beyond animal studies. Lab data suggesting that vitamin D deficiency increases addictive behavior was also backed up by several analyses of human health records. One found that patients with modestly low vitamin D levels were 50% more likely than others with normal levels to use opioids, while patients who had severe vitamin D deficiency were 90% more likely to use. Another analysis found that patients diagnosed with opioid use disorder (OUD) were more likely than others to be vitamin D deficient.
Perhaps the most critical discovery was when the researchers corrected vitamin D levels in the deficient mice, which resulted in their opioid responses reversing and returning to normal.
While more research is needed, Fisher believes that addressing vitamin D deficiency may offer a new, highly affordable way to help reduce the risk for opioid use disorder and strengthen existing treatments.
"Our results suggest that we may have an opportunity in the public health arena to influence the opioid epidemic," said Fisher.
Source: Science Advances
“Vitamin D deficiency exacerbates UV/endorphin and opioid addiction”
11 Jun 2021: Vol. 7, no. 24, eabe4577 DOI: 10.1126/sciadv.abe4577
Authors: L. Kemény et al.