Vitamin D deficiency enhances the craving for and effects of opioids, potentially worsening addiction risk, according to a new study.
These findings by researchers at Massachusetts General Hospital (MGH), published in Science Advances, suggest that the opioid crisis could partly be addressed by treating the common problem of vitamin D deficiency with inexpensive supplements.
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 found something unexpected: UVB ray exposure causes the skin to produce endorphin, which is chemically related to morphine, heroin and other opioids, which all activate the same receptors in the brain. Further research found that UV exposure raises endorphin levels in mice, which then display behaviour consistent with opioid addiction.
Endorphin induces a sense of mild euphoria. Research has suggested that some people develop urges to sunbathe and visit tanning salons that mirror the behaviours of opioid addicts. Dr Fisher and colleagues speculated that people may seek out UVB for the endorphin rush. But that suggests a major contradiction. “Why would we evolve to be behaviourally drawn towards the most common carcinogen that exists?” asked Dr Fisher.
Dr Fisher believes that the only explanation for why humans and other animals seek out the sun is that UV radiation exposure is necessary for production of vitamin D. One of vitamin D’s functions is promoting the uptake of calcium, essential for building bone. As humans migrated north during prehistoric times, they must have developed some kind of compulsion to venture outside of caves and on dark days, otherwise the vitamin D level would have debilitated them, especially the children.
This theory led Fisher and colleagues to hypothesise that sun seeking is driven by counteracting vitamin D deficiency 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,” says lead author Lajos V. Kemény, MD, PhD, a postdoctoral research fellow in Dermatology at MGH.
The researchers addressed the question from dual perspectives. One study arm compared normal laboratory mice with mice that were deficient in vitamin D (either through special breeding or by removing vitamin D from their diets). “We found that modulating vitamin D levels changes multiple addictive behaviours to both UV and opioids,” said Kemény. Importantly, when the mice were conditioned with modest doses of morphine, the vitamin D deficient mice continued seeking out the drug, more than the normal mice. Mice with low vitamin D levels were far more likely to develop morphine withdrawal symptoms.
The study also found that morphine relieved pain more effectively in mice with vitamin D deficiency – an exaggerated opioid response in these mice, and possibly concerning if it’s also true in humans, said Dr Fisher. For example, a surgery patient receiving morphine for pain control after the operation, and if they are deficient in vitamin D, the euphoric effects of morphine could be exaggerated, said Dr Fisher, “and that person is more likely to become addicted.”
This data suggesting vitamin D deficiency increases addictive behaviour was bolstered by analyses of human health records. One showed that, compared to those with normal levels, patients with modestly low vitamin D levels were 50 per cent more likely to use opioids, while patients who had severe vitamin D deficiency were 90 percent more likely. Another analysis found that patients with opioid use disorder (OUD) were more likely to be deficient in vitamin D.
Back in the lab, one of the study’s other critical findings could have significant implications, said Dr Fisher. “When we corrected vitamin D levels in the deficient mice, their opioid responses reversed and returned to normal,” he says. In humans, vitamin D deficiency is widespread, but is safely and easily treated with low-cost dietary supplements, notes Fisher. While more research is needed, he believes that treating vitamin D deficiency may be a new way to reduce the risk for OUD and bolster existing treatments for the disorder. “Our results suggest that we may have an opportunity in the public health arena to influence the opioid epidemic,” says Fisher.
Source: EurekAlert!
