Vitamin D deficiency greatly exaggerates the craving for and effects of opioids, potentially increasing the risk of addiction and dependence, according to a new study led by researchers at Massachusetts General Hospital (MGH). These findings, published in Scientific progress, suggests that addressing the common problem of vitamin D deficiency with inexpensive supplements may play a role in combating the ongoing plague of opioid dependence.
Previous work by David E. Fisher, MD, PhD, director of the Mass General Cancer Center̵
Endorphins are sometimes called a “feel good” hormone because they evoke a feeling of mild euphoria. Studies have suggested that some people develop urges to sunbathe and visit tanning salons that reflect the behavior of opioid addicts. Fisher and his colleagues wondered that people might be looking for UVB because they unconsciously crave the endorphin rate. But that suggests a major contradiction. “Why would we evolve to be behaviorally drawn to the most common carcinogen that exists?” asked Fisher. After all, sun exposure is the primary cause of skin cancer, not to mention wrinkles and other skin damage.
Fisher believes that the only explanation for why humans and other animals seek the sun is that exposure to UV radiation is necessary for the production of vitamin D, which our bodies cannot formulate alone. Vitamin D promotes the uptake of calcium, which is important for building bones. As tribes migrated north in prehistoric times, an evolutionary change might have been necessary to force them to step out of the caves and into the sunshine on bitterly cold days. Otherwise, young children would have died of prolonged vitamin D deficiency (the cause of rickets), and weak bones could be crushed when people ran away from predators, leaving them vulnerable.
This theory led Fisher and colleagues to assume that sunscreen is driven by vitamin D deficiency with the goal of increasing the synthesis of the hormone for survival, and that vitamin D deficiency can also make the body more sensitive to the effects of opioids, which potentially can contribute 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 behavior,” says lead author Lajos V. Kemény, MD, PhD, a postdoc fellow in dermatology at MGH.
IN Scientific progress paper, Fisher, Kemény and an interdisciplinary team from several institutions addressed the issue from two perspectives. In one part of the study, the normal laboratory mice compared with mice that were deficient in vitamin D (either through special breeding or by removing vitamin D from their diet). “We found that modulating vitamin D levels alters more addictive behaviors to both UV and opioids,” Kemény says. More importantly, when the mice were conditioned with modest doses of morphine, those who lacked vitamin D continued to seek out the drug, behaviors that were less common among the normal mice. When morphine was withdrawn, mice with low vitamin D levels were far more likely to develop withdrawal symptoms.
The study also showed that morphine worked more effectively as a painkiller in mice with vitamin D deficiency – that is, the opioid had an exaggerated response in these mice, which can be worrying if it is also true in humans, Fisher says. After all, consider a surgery patient who is receiving morphine for pain control after surgery. If the patient is deficient in vitamin D, the euphoric effects of morphine may be excessive, Fisher says, “and that person is more likely to become addicted.”
Laboratory data suggesting that vitamin D deficiency increases addictive behaviors were supported by several concomitant analyzes of human health records. One showed that patients with modestly low vitamin D levels were 50 percent more likely than others with normal levels to use opioids, while patients with severe vitamin D deficiency were 90 percent more likely. Another analysis showed that patients diagnosed with opioid disorder (OUD) were more likely than others to be deficient in vitamin D.
Back in the lab, one of the study’s other critical findings could have significant consequences, Fisher says. “When we corrected the vitamin D content in the deficient mice, their opioid reactions returned and returned to normal,” he says. In humans, vitamin D deficiency is widespread, but is treated safely and easily with cheap supplements, Fisher notes. While more research is needed, he believes that treating vitamin D deficiency may offer a new way to help reduce the risk of OUD and strengthen existing treatments for the disorder. “Our results suggest that we may have an opportunity in the area of public health to influence the opioid epidemic,” Fisher said.
Reference: “Vitamin D deficiency exacerbates UV / endorphin and opioid dependence” 11 June 2021, Scientific progress.
DOI: 10.1126 / sciadv.abe4577
Fisher is Edward Wigglesworth Professor of Dermatology at Harvard Medical School. Kemény currently works as a GP in dermatology at the University of Semmelweis in Budapest, Hungary.
This work was supported by a grant from the National Institutes of Health and Dr. Miriam and Sheldon G. Adelson Medical Research Foundation.