Vitamin D deficiency greatly exaggerates thirst and the 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, suggest that tackling the common problem of vitamin D deficiency with cheap supplements may play a role in combating the continuing scourge of opioid dependence.
The earlier work of Dr. David E. Fisher, director of the Mass General Cancer Center Melanoma Program and director of the MGH Skin Biology Research Center (CBRC), laid the groundwork for this study. In 2007, Fisher and his team discovered something unexpected: Exposure to ultraviolet (UV) rays (especially a form called UVB) causes the skin to produce the hormone endorphin, which is chemically linked to morphine, heroin and other opioids ̵
Endorphins are sometimes called the “feel good” hormone because they cause a slight feeling of euphoria. Studies show that some people develop urges to sunbathe and visit solariums that reflect the behavior of opioid addicts. Fisher and his colleagues speculated that people may seek UVB because they unconsciously crave the endorphin impulse. But this suggests a great contradiction. “Why would we evolve to be behaviorally attracted to the most common carcinogen that exists?” Fisher asked. After all, sun exposure is the main 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 ultraviolet light is necessary for the production of vitamin D, which our bodies cannot formulate on their own. Vitamin D promotes the absorption of calcium, which is essential for bone building. As human tribes migrated north in prehistoric times, an evolutionary change might be needed to force them out of the caves and into the sun on the bitterly cold days. Otherwise, young children would die from prolonged vitamin D deficiency (the cause of rickets) and weak bones could break when people ran away from predators, leaving them vulnerable.
This theory led Fisher and colleagues to suggest that the demand for the sun is driven by vitamin D deficiency, in order to increase the synthesis of survival hormone, and that vitamin D deficiency can also make the body more sensitive to the effects of opioids. as potentially contributing to addiction. “Our goal in this study was to understand the relationship between vitamin D signaling in the body and behavior seeking ultraviolet rays and opioids,” says lead author Lajos V. Kemény, PhD, a postdoctoral fellow in dermatology at MGH.
IN Scientific progress paper, Fisher, Kemény and a multidisciplinary team from several institutions looked at the issue from a dual perspective. In one part of the study, they compared normal laboratory mice to mice that were deficient in vitamin D (either by special breeding or by removing vitamin D from their diet). “We have found that modulating vitamin D levels repeatedly alters the addictive behavior of both UV and opioids,” says Kemény. Importantly, when mice were conditioned with moderate doses of morphine, those with vitamin D deficiency continued to seek the drug, a behavior that is less common among normal mice. When morphine was withdrawn, mice with low vitamin D levels were much more likely to develop withdrawal symptoms.
The study also found that morphine works more effectively as a painkiller in mice with vitamin D deficiency – meaning opioids have an exaggerated response in these mice, which may be worrying if this is true in humans, Fisher said. After all, consider a patient with surgery who receives morphine to control pain after surgery. If this patient is deficient in vitamin D, the euphoric effects of morphine may be exaggerated, says Fisher, “and this person is more likely to be addicted.”
Laboratory data suggesting that vitamin D deficiency increases addictive behavior are supported by several accompanying analyzes of human health records. One showed that patients with moderately low levels of vitamin D were 50% more likely than others with normal levels to use opioids, while patients who had severe vitamin D deficiency were 90% more likely. Another analysis found that patients diagnosed with opioid use disorder (OUD) were more likely than others to be vitamin D deficient.
Back in the lab, one of the other critical findings of the study could have significant implications, Fisher said. “When we adjusted vitamin D levels in deficient mice, their opioid responses reversed and returned to normal,” he said. Vitamin D deficiency is widespread in humans, but is treated safely and easily with cheap supplements, Fisher said. Although 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 show that we may be able to influence public health in the opioid epidemic,” Fisher said.
Reference: “Vitamin D deficiency exacerbates addiction to UV / endorphins and opioids” June 11, 2021, Scientific progress.
DOI: 10.1126 / sciadv.abe4577
Fisher is Edward Wigglesworth’s professor of dermatology at Harvard Medical School. Kemeni currently works as a resident dermatologist at Semmelweis University in Budapest, Hungary.
This work was supported by a grant from the National Institutes of Health and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation.