Office of Research & Development

VA research on

Substance Use Disorders


Introduction

Substance use and misuse, with its associated health consequences, is a major public health problem. Substance use disorders (SUDs) include dependencies on alcohol, illicit and prescription drugs, and nicotine. SUDs have substantial negative consequences on Veterans' mental and physical health, work performance, housing status, and social function.

SUDs can develop in people who use alcohol or other addicting drugs in harmful quantities. According to the VA/DoD Clinical Practice Guideline for the Management of Substance Use Disorders, about 9 percent of Americans over age 18 have a non-tobacco SUD, and about 1 in 4 Americans will develop a non-tobacco SUD over the course of a lifetime.

Excessive alcohol use alone leads to about 88,000 premature deaths each year.

In service members and Veterans, SUD commonly co-occurs with and complicates other conditions or issues. These conditions or issues may be health-related, such as other mental health conditions. They may also be societal, such as homelessness, criminal justice involvement, or unemployment.

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Selected Major Accomplishments

1956: Linked cigarette smoking with precancerous lesions

1976: Completed a comparison trial of two different types of methadone

1984: Developed the nicotine transdermal patch and other therapies to help smokers quit

1992: Published a study in which the drug naltrexone was shown to be effective in keeping alcoholics from relapsing into heavy drinking and reduced cravings for alcohol

2013:

2016: Developed, and tested on rats, a painkiller as strong as morphine that is unlikely to be addictive and has fewer side effects

2017: VA-DoD-NIH Pain Collaboratory created to fund studies on non-opioid pain treatments

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Historical advances

VA began researching SUDs in the 1940s, through studies on the characteristics of alcoholics that took place at the Northport, New York, VA Medical Center. In the late 1960s and early 1970s, VA collaborated with the White House's Special Action Office for Drug Abuse Prevention in a comparison trial of two different types of methadone, a drug still used in treating heroin addicts.

In 1971, Dr. Marcus Rothschild of the New York VA Medical Center received VA's William S. Middleton Award for outstanding scientific contributions and achievements in the areas of biomedical and bio-behavioral research relevant to Veterans' health care. Rothschild received the award for his research on the pathological biochemistry of the liver in alcoholism and liver disease.

Also in 1971, Dr. Charles P. O'Brien of the Corporal Michael E. Crescenz VA Medical Center in Philadelphia and the University of Pennsylvania founded and became director of the Center for Studies of Addiction. At the center, VA and University of Pennsylvania researchers work to advance knowledge on the nature of addiction and the best ways to relieve this illness.

In the 1980s, O'Brien and his colleagues discovered a new way to treat alcoholism, by providing alcoholic patients with a drug called naltrexone, which had previously been used only for treating addiction to heroin and other opioids. In a study published in 1992, the team found that after three months of treatment, patients receiving naltrexone had fewer relapses to heavy drinking and reported less craving for alcohol and less pleasure when they did drink compared with those receiving a placebo. Based on the team's work, the FDA approved naltrexone for treating alcohol dependence in 1995.

In 1977, Dr. Charles Lieber of the Bronx VA Medical Center received the Middleton Award for his work on the toxicity of alcohol, and the pathogenesis (the manner of development of a disease) of fatty liver and cirrhosis (scarring of the liver) in man and nonhuman primates.

VA researchers have long been involved in documenting the relationship between smoking and cancer. In 1956, Dr. Oscar Auerbach of the East Orange, New Jersey, VA Medical Center found that smoking for three years caused major changes in the lungs of animals that were taught to inhale cigarettes—and that many developed cancer. Auerbach was later a participant in the first Surgeon General's report, published in 1964, which explained the harmful effects of smoking to America and the world.

In 1984, VA Research made a major contribution toward helping Veterans and others quit smoking through the development of the nicotine transdermal patch. The patch transfers nicotine into the bloodstream to reduce cravings for the substance.

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New, Ongoing, and Published Research

VA supports a broad portfolio of research looking at substance misuse prevention, screening, and treatment. Some researchers are looking at treatment-seeking patterns: why and when Veterans ask for help—and why many don't. Treatment strategies, including cognitive behavioral strategies and web-based approaches, are also being studied.

Other researchers are working to identify the most effective therapies for comorbid disorders, such as depression and PTSD, and attempting to determine whether early intervention improves outcomes. Still others are focusing on how readjustment issues relate to substance misuse.

VA is highly engaged in collaborative activities with other federal research agencies—including the departments of Health and Human Services and Defense—especially focused on research that could lead to advances in reducing SUD in Veterans and related to managing opioid use.

The department offers treatments for substance use problems throughout its health care system. A list of VA treatment programs can be found here.

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➤ Alcohol studies

vs. specialty care treatment—In 2014, VA researchers in Philadelphia published the results of a study finding that a 26-week intervention is just as effective as specialty outpatient treatment for treating alcohol dependence.

The study enrolled 163 Veterans and randomly assigned them to treatment or specialty treatment groups. Those receiving treatment were offered medicine and psychosocial support, delivered in person and by phone.

The researchers found that Veterans in the treatment group were more than five times as likely to complete all 26 weeks. Overall abstinence rates were the same between groups, and the group had a smaller percentage of days with heavy drinking.

HIV, alcohol, and memory—Researchers at the Palo Alto Health Care System conducted a study, published in 2014, that found that human immunodeficiency virus (HIV)-infected patients who had problematic levels of alcohol use also had problems with their memory, both in terms of their ability to recall facts and their activity memory (recalling what they did yesterday). Memory impairment is tied to chronic problem drinking for all populations, but little research has focused on how drinking affects HIV patients in particular, and how their overall health care might suffer.

The HIV-related symptoms of the 172 patients with alcohol problems who were studied were also more severe than those of other patients. The research team concluded that integrated care for HIV and alcohol use disorders is important, and that routine alcohol and cognitive screenings may improve health outcomes among HIV-infected patients.

Counseling for 'hazardous drinkers'—A research team at the VA Pittsburgh Healthcare System is conducting a study to determine the efficacy of providing counseling for Veterans who don't meet the threshold for an alcohol use disorder but who score positive on a screening tool for hazardous drinking. The goal is to help them make positive changes in their lifestyle and phase out their unhealthy alcohol use.

The Veterans' drinking problems were identified during stays at the VA Pittsburgh Healthcare System. Some of the 320 Veterans in the study are receiving individual change plans to reduce or eliminate their drinking while still in the hospital, and are also receiving follow-up afterward. Others are receiving only general attention to their health status and information about healthy lifestyles. Still others are getting a limited amount of counseling on alcohol abuse.

Alcohol and liver disease—Scientists know that alcohol itself can directly damage liver cells. A 2016 study by researchers at the VA San Diego Healthcare System and the University of California reported evidence that alcohol is harmful to the liver for a second reason—it allows gut bacteria to migrate to the liver, promoting alcohol-induced liver disease.

According to the research team, alcohol appears to impair the body's ability to keep microbes in check. When barriers break down, bacteria that don't normally colonize the liver end up there—and this bacterial migration promotes alcohol liver disease.

The team is now working on strategies that can restore the body's defenses against microbes.

Heavy versus light drinking—Heavy drinkers develop behavioral tolerance to alcohol over time on some fine motor tasks, but not on more complex tasks, according to a 2017 study led by a VA San Diego Healthcare System researcher. While heavy drinkers showed less impairment than light drinkers on a rote fine motor test over time, they did not perform better on a test involving more short-term memory, motor speed, and more complex cognitive processing.

The study defined a heavy drinker as a person who drank between 10 and 40 alcoholic drinks per week for at least the past two years at the initial testing. Light drinkers were those who had fewer than six drinks per week. According to the researchers, the results suggest that lower perceived impairment and higher sensitivity to the stimulating and rewarding effects of alcohol for heavy drinkers could make the habit more dangerous for them. They may engage in more potentially risky behaviors while drunk because they see their impairment level as lower.

Residual effects of problem drinking—A 2016 study by Palo Alto VA Health Care System and Hunter Holmes McGuire VA Medical Center researchers found that problem drinking during five years or more in young adulthood appears to increase the risk of health problems later in life, even after decades of remission. The study involved more than 600 Vietnam-era Veterans. Veterans who showed symptoms of problem drinking for at least five years in early adulthood scored lower on measures of physical and mental health as older adults. This relationship held true even for Veterans who had quit drinking after the age of 30.

While stopping drinking almost always results in health improvements for problem drinkers, this study suggests that damage caused early in life could lead to more health problems later in life. Problem drinking as a young adult (younger than 30) was more likely to predict late-life health difficulties than problem drinking in midlife. This could possibly be caused by alcohol-related injury to the still-developing brain in early adulthood.

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➤ Studies of illicit drugs

Stimulant use increases mortality risk for HIV-infected men—Stimulant use increases mortality risk for men with HIV, but cannabis use does not, according to the Veterans Aging Cohort Study. Researchers surveyed more than 3,000 men with HIV. At baseline, 15 percent of participants used cannabis and 24 percent used stimulants, such as cocaine and methamphetamine. Cannabis was not linked to increased mortality risk based on the VACS Index, a measure of the risk of all-cause mortality. Those using stimulants, however, scored five points higher on the risk scale, compared with cannabis and alcohol users. Participants who used stimulants were also more likely to have unhealthy alcohol and opioid use. This was not true for those who used cannabis. The results suggest that efforts to reduce stimulant use in this population may reduce mortality. The researchers do note that demographic factors—such as age, race, and education—seem to impact mortality risk more than alcohol, cannabis, or stimulus use.

Outpatient medical care linked to lower drug use in rural patients—Use of outpatient medical care is linked to reductions in illicit drug use over time in rural areas, found a 2018 study by Central Arkansas VA Healthcare System researchers and their colleagues. The researchers looked at how outpatient medical care for other issues affected substance use in 7,110 stimulant users in rural areas of Arkansas, Kentucky, and Ohio. They found that patients with at least one outpatient medical care visit over a three-year period had lower alcohol, crack cocaine, and meth use over time, compared with patients who did not have any outpatient visits. The findings highlight the importance of medical care contact in addressing unhealthy substance use, say the researchers.

Marijuana and lung disease—Marijuana, a preparation of the hemp plant that is used both as a recreational drug and as medicine, is commonly smoked to get a "high." However, some sick people, especially cancer patients, can use it to relieve their pain.

In 2014, researchers from the Central Arkansas Veterans Healthcare System in Little Rock and the University of Arkansas reviewed recent studies on the controversial drug and its ties to lung diseases. They determined that smoking marijuana is not as bad as smoking cigarettes when it comes to lung disease.

They found a clear linkage between marijuana use and chronic bronchitis and large airway inflammation, conditions that make breathing difficult. However, they found no links to emphysema, a chronic disease in which the air sacs in the lungs are gradually damaged, and only weak, if any, links to lung cancer.

The researchers concluded, however, that there is unequivocal evidence that habitual or regular marijuana use is not harmless, and that doctors should caution patients about possible lung damage from regular heavy marijuana use.

Cannabis use disorder linked to self-injury—Cannabis use disorder was linked to greater odds of self-injury, in a 2018 study by Durham VA Medical Center and Central Texas VA Health Care System researchers. The researchers interviewed 292 Iraq and Afghanistan Veterans. Of those, 12 percent had engaged in either suicidal or non-suicidal self-injury. Fourteen percent of Veterans interviewed had cannabis use disorder—defined as continued use of marijuana despite impairment and dependence. Participants with cannabis use disorder had three times higher odds of any type of self-injury, compared to those without the disorder. The odds of non-suicidal self-injury were higher than the odds of suicide attempts for participants with cannabis use disorder. While the results may show that cannabis use disorder increases the risk of self-injury, the basis of this link is not yet clear, caution the researchers.

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➤ Smoking cessation studies

Successful counseling method—In 2016, a team led by researchers from the VA New York Harbor Healthcare System and the New York University School of Medicine found that specialized counseling delivered by telephone may be more effective than state quit lines to help smokers in mental health care kick the habit.

The study looked at 522 Veterans with mental health issues, 270 of whom received specialized counseling that incorporated motivational interviewing, problem-solving therapy, and cognitive behavioral therapy. The other 307 Veterans were referred to their local quit lines.

The team found that the specialized counseling yielded a quit rate of 26 percent at six months, versus 18 percent for the state quit lines.

Varenicline and bupropion do not appear to increase neuropsychiatric risk—Varenicline (sold as Chantix) and bupropion (sold as Wellbutrin and Zyban) are prescription medications used to treat nicotine addiction.

A 2016 study by VA researchers in Hines, Illinois; Bedford, Massachusetts; and Pittsburgh, along with researchers from the U.S. Food and Drug Administration and two universities, found that these medications do not appear to increase the incidence of serious neuropsychiatric illnesses such as depression, schizophrenia, or bipolar disorder when compared with placebo.

Participants in the study were more than 8,000 adults aged 18–75 who smoked more than 10 cigarettes a day and were motivated to stop smoking. About half (4,116) had a history of a past or current stable psychiatric condition. For 9 to12 weeks, some received varenicline, some bupropion, some a nicotine patch, and others a placebo.

The participants were assessed to see whether they had any moderate to severe neuropsychiatric events during their treatment and at a follow-up visit 9 to 24 weeks after the treatment ended. The researchers checked for episodes of agitation, aggression, panic, anxiety, or suicidal ideation.

The team found that while there were more adverse events reported in the group that previously had psychiatric disorders, there was no significant increase in the incidence of such events in the groups receiving any of the four kinds of treatment.

Varenicline was more effective in helping people stop smoking than bupropion, nicotine patches, or placebo. Bupropion was about as effective as nicotine patches, and both were more effective than placebo.

QuitNet study—In a four-year study, researchers at the Durham VA Medical Center looked at Web-based methods of quitting smoking as an alternative to clinic-based programs, which are often poorly attended. They examined QuitNet, a website launched in 1995, which offers chat rooms, advice from experts, medication tips, buddy match-ups, and other tools to support smokers in their quest to stop smoking.

The researchers provided half of the 400 Veterans involved in the study with premium memberships in QuitNet and compared their quit rates over a four-year period with those of Veterans enrolled in a clinic at the Durham VA geared toward helping returning Veterans quit smoking. Results showed that participants in the online program had similar quit rates as those who attended smoking cessation care at the clinic at three-month and one-year follow-ups.

VA also offers Veterans hoping to quit smoking a smoker's quitline (1-855-QUIT-VET), and a smoking cessation texting program called SmokefreeVet.

Lung cancer screening issues—A 2015 study by researchers with the VA Puget Sound Health Care System and the University of Seattle found that lung cancer screening can have the unintended consequence of lowering smokers' motivation to quit.

The team studied 37 current smokers who were offered lung cancer screening by their physician during 2014. After the screening, the smokers were interviewed by the research team. The team found nearly half of those interviewed found some reason to believe that just being screened meant that they did not need to stop smoking.

Some told the researchers that undergoing the test had the same benefit as stopping smoking, even when precancerous lung nodules were found. Others felt that being able to return for additional screenings would protect them, and still others felt that a cancer-free screening test indicated that they were among the lucky ones who would avoid the harms of smoking.

All of these assumptions are false—as is the assumption many study participants had that lung cancer was the only potentially lethal effect of smoking. The team suggested that counseling for smokers should target these and other rationalizations some people use to avoid quitting.

A 2018 study by the VA Center of Innovation for Veteran-Centered and Value-Driven Care in Seattle found similar confusion on the benefits of lung cancer screening. Researchers asked smokers a series of questions about smoking and lung cancer screening. Their answers showed that most patients were mistaken about the benefits of such screenings and smoking in general. Only 7 percent of patients answered all five questions correctly.

Patients falsely believed that lung cancer screenings could prevent cancer, and were confused about the health risks of smoking. Perhaps most disturbing, nearly half thought that lung cancer screenings were at least as good as, if not better than, quitting smoking as a way of protecting against death. In light of these results, the researchers believe that more efforts within VA are needed to help patients understand what lung cancer screenings can and cannot do.

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➤ Opioid dependence studies

Opioids are medications that relieve pain. They reduce the intensity of pain signals reaching the brain and affect those brain areas controlling emotion, which diminishes the effects of a painful stimulus. Medications that fall within this class include hydrocodones, such as Vicodin; oxycodones, such as OxyContin and Percocet; morphine, such as Kadian and Avinza; codeine; and related drugs.

Taken as prescribed, opioids can be used to manage pain safely and effectively. When abused, however, even a single large dose can cause severe respiratory depression and death. Regular or longer-term use and abuse of opioids can lead to physical dependence, and in some cases addiction.

In 2013, VA launched the Opioid Safety Initiative (see more details below). As a result, by mid-2016 the number of Veterans dispensed an opioid each quarter has decreased by 172,000, or about 25 percent. In 2017, even fewer Veterans are receiving high doses of opioids, and more Veterans are receiving non-opioid pain therapies, naloxone, and treatment for substance use disorders.

Opioids are important in helping people manage their pain, but the long-term effectiveness of opioid therapy for chronic pain is untested.

Opioid use is also associated with a number of serious risks, including death from unintentional overdose, suicide, accidents related to sedation, and interactions with other medications. VA has developed a clinical practice guideline for opioid therapy for chronic pain. The guideline outlines practices designed to reduce the risks and increase the effectiveness of opioid therapy.

Opioid prescription in VA has declined—Opioid prescribing has declined in VA in recent years, found an Iowa City VA Healthcare System study. Researchers looked at data on opioid use in VA between 2010 and 2016. Opioid prescriptions peaked in 2012 at 21.2 percent of all VA patients receiving at least one outpatient prescription. The rate then declined annually to 16.1 percent in 2016. The decline is mostly because of less long-term opioid prescribing, as opposed to short or intermediary opioid use. The results show that recent VA opioid initiatives may be succeeding in preventing patients from beginning long-term opioid use.

Who prescribes opioids?—Most prescriptions for opioid painkillers are made by the broad swath of U.S. general practitioners, not by a limited group of specialists, according to a 2015 study by researchers at the Palo Alto VA Health Care System and Stanford University School of Medicine.

The research team examined Medicare prescription drug claim data for 2013, and found that while the top 10 percent of opioid prescribers account for 57 percent of all opioid prescriptions, this prescribing pattern is comparable to that found in the Medicare data for prescribers of all drugs.

The team's findings contrast with previous studies by others that indicated the high levels of prescribing opioids in the United States is the result of a small population of prolific prescribers operating out of corrupt pill mills. According to the authors of the new study, efforts to curtail national opioid overprescribing must address a broad swath of prescribers to be effective.

Benzos and overdose deaths—In another study published in 2015, researchers with VA, the Alpert Medical School at Brown University, and the University of Michigan Medical School found that nearly half of 2,400 Veterans who died from a drug overdose between 2004 and 2009 while they were receiving opioids for pain were also receiving benzodiazepines, known as benzos for short. These are common medications for the treatment of anxiety, insomnia, and alcohol withdrawal.

The risk of overdose death for Veterans receiving both opioids and benzodiazepines was four times greater than for those receiving opioids alone. In addition, Veterans receiving higher doses of benzodiazepines while concurrently receiving opioids were at greater risk of overdose death than those on lower doses of benzodiazepines. According to the study's lead researcher, prescribing benzodiazepines to patients taking opioids for pain is "quite common," and therefore the team's findings are "deeply troubling."

Lowering opioid and benzo co-prescribing—Electronic medication alerts can lower co-prescribing of opioids and benzodiazepines in high-risk patients suggest the results of a VA Puget Sound Health Care System quality-improvement project. Investigators used VA’s electronic medical record system to automatically alert care providers prescribing either opioids or benzodiazepine when patients with high-risk conditions had prescriptions for the other drug class. Co-prescribing of the two medications dropped by for high-risk patients with SUD, sleep apnea, and suicide risk after the system was implemented.

Opioids and depression—While opioids may cause short-term improvements in mood, their long-term use brings the risk of new-onset depression, according to a study published in 2016 by a team of researchers from VA and several academic institutions. The study looked at more than 107,000 patients from VA, Baylor Scott & White Health (BSWH), and the Henry Ford Health System (HFHS). The patients were new opioid users, ages 18 to 80, who did not have a diagnosis of depression when they began taking their medication.

Twelve percent of the VA patients, 9 percent of the patients from BSWH, and 11 percent of the HFHS sample experienced new-onset depression after using opioid analgesics. The research team speculated that the findings may be explained by the possibility that using opioids for more than 30 days can lead to changes in neuroanatomy, and low testosterone.

Opioid doses and risk of suicideResearchers with the Serious Mental Illness Treatment Resource and Evaluation and the Center for Clinical Management Research at the VA Ann Arbor Healthcare System, along with colleagues from the University of Michigan, reported in 2016 that Veterans receiving the highest doses of opioid painkillers were more than twice as likely to die by suicide, compared with those receiving the lowest doses.

The research team looked at nearly 124,000 Veterans who received VA care in 2004 and 2005. All had non-cancer chronic pain and received prescriptions for opioids. Using the National Death Index, the researchers identified 2,601 patients who died by suicide before the end of 2009.

They found that the suicide risk rose as dose increased. The researchers could not tell, however, whether there was a direct causal link between the pain medications and suicide risk. Instead, the high doses may be a marker for other factors that drive suicide, including unresolved severe chronic pain.

Discontinuing long-term opioid therapy—Close monitoring of Veterans on long-term opioid therapy will likely lead to a decrease in opioid prescription, according to a 2017 HSR&D retrospective study. The researchers compared the reasons opioid therapy was discontinued for a group of Veterans with and without an SUD. They found that 85 percent of these Veterans stopped opioid use because their clinician stopped prescribing, rather than the patients deciding to stop. Of this group, 75 percent were discontinued due to suspected opioid-related substance misuse or a positive urine drug test.

Forty-three percent of Veterans who tested positive for illicit drugs or non-prescribed controlled substances were referred to SUD treatment. However, only 20 percent actually engaged in the treatment. Integrating non-opioid pain therapies and SUD treatment into multiple settings—such as and specialty SUD care—is one possible approach to enhancing this care, say the researchers.

Opioid Safety Initiative dashboard—One key component of VA's OSI is a dashboard tool that uses VA electronic health record data to generate displays of real-time opioid-related prescribing. It also identifies a clinical leader at each facility to implement the tool and promote safer prescribing. A QUERI study published in 2017 showed that the use of the dashboard decreased the number of Veterans receiving risky opioid regimens over a two-year period. Between 2012 and 2014, the number of Veterans receiving more than 100 morphine-equivalent milligrams (mEq) decreased by 16 percent, and the number receiving more than 200 mEq decreased by 24 percent. The number of Veterans who received benzodiazepines together with opioid medications decreased by 21 percent.

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➤ Alternatives to opioids

Development of a new non-addictive pain drug—A team including a researcher from the W.G. Hefner VA Medical Center in Salisbury, North Carolina, are working on a pain medication that could potentially work as well as opioids without being addictive. They developed a new compound, AT-121, that works on the mu opioid receptor, a type of neuron that opioids interact with to block pain. AT-121 also activates the nociceptin receptor, which blocks the addictive side effects of opioids. Using non-human primates, the researchers showed that AT-121 gave the same level of pain relief as opioids without the risk of addition. The results suggest that this new drug could have potential to both safely and effectively relieve pain, and also treat prescription opioid abuse. More studies will be needed before AT-121 can be tested in humans.

Peptide-based painkiller—In 2016, researchers at the Southeast Louisiana Veterans Health Care System and Tulane University announced that they have developed a painkiller that is as strong as traditional painkillers like morphine, but that has fewer side effects and less potential for addiction.

The team compared several engineered variants of the neurochemical endorphin, which is found naturally in the body, to morphine to measure their effectiveness and side effects. These peptide-based drugs target the same pain-relieving opioid receptor as morphine.

In a study, the new drug produced longer pain relief without substantially slowing breathing in rats. A similarly potent dosage of morphine produced significant respiratory depression. The new drug also did not produce significant impairment of motor coordination, as morphine does, and it appears not to be addictive in rats. The rats also were not more tolerant of the drug over time, which lessens the likelihood that it will be abused in humans, and reduces the chance of an overdose.

Behavioral therapy as a pain-relief alternativeVA's Care Management for the Effective Use of Opioids (CAMEO) trial is a randomized clinical trial now underway at the Richard L. Roudebush VA Medical Center in Indianapolis to compare pharmacological pain relievers with behavioral approaches such as cognitive behavioral therapy for the relief of chronic lower back pain.

The study is comparing the two interventions' effects on pain intensity, function, and other pain-relevant outcomes at 6 and 12 months. The study will also compare their cost-effectiveness.

Opioid Safety Initiative results—In 2013, the Minneapolis VA Health Care System launched the Opioid Safety Initiative (OSI). OSI was designed to decrease high-risk opioid prescribing practices, and to improve the safety of opioid prescribing while providing high-quality pain care for Veterans.

A 2015 study found that OSI, which emphasizes patient education, close patient monitoring with frequent feedback, and the use of complementary and integrative medicine practices such as acupuncture and behavior therapy, can produce dramatic results.

The Minneapolis researchers found that, from 2011 through 2014, the number of Veterans prescribed more than 200 morphine-equivalent milligrams worth of opioids decreased from 342 to 65. Overall, the number of unique pharmacy patients who received at least one opioid prescription decreased by almost 1,000 and the number of Veterans receiving oxycodone dropped from 292 to 3.

Engaging patients in non-opioid pain treatment—Researchers at the VA Connecticut Healthcare System are using the VA compensation and pension exam to engage Veterans who are applying for a service-connected disability about pain and substance use. A pilot study looked at the effects of delivering counseling by phone during compensation exams for musculoskeletal pain. The idea is to inform Veterans of alternative pain treatments they are entitled to while discussing their service-connected disability claims. A pilot study showed that Veterans assigned to brief counseling for pain were more likely to obtain pain treatment at a VA facility than those receiving the usual compensation and pension exam without additional counseling. When Veterans with risky substance use were assigned to counseling, they were significantly less likely to engage in risky use than those not assigned to this counseling.

The study is part of a series of grants to study non-drug approaches to pain management co-funded by VA, the Department of Defense, and the National Institutes of Health.

Opioid vs. non-opioid treatment—A 2018 study called the Prescribing Analgesics Comparative Effectiveness (SPACE) trial found that treatment for 12 months or more with opioid medications was not superior to non-opioids when it came to improving pain-related function. And, in fact, non-opioid medications were more effective than opioids for reducing pain intensity. The study found no advantages to opioids that would outweigh their greater risk of serious harm.

The study lends support to recent guideline recommendations. The 2016 Centers for Disease Control and Prevention opioid guideline advised that non-drug therapies and non-opioid medications are preferred for chronic pain, and the 2017 VA opioid guideline advised against starting long-term opioids for chronic pain.

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➤ CREATE on substance use disorders

"Promoting Value and Access in VA's Substance Use Disorder Services" is one of 10 CREATE programs recently funded by VA Research. The CREATE acronym stands for Collaborative Research to Enhance and Advance Transformation and Excellent. The program involves groups of coordinated research projects conducted in a focused area by independent, collaborating investigators and VA clinical or operations partners. The studies within each CREATE group address distinct but complementary areas of investigation. They work together to advance knowledge and care on behalf of VA patients.

The CREATE on substance use disorders includes four projects:

  • Web-based Intervention to Reduce Alcohol Use in Veterans with Hepatitis C is a multi-site, randomized clinical trial of a self-administered web-based brief alcohol intervention to reduce alcohol consumption in Veterans with hepatitis C. It is important because the VA Office of Public Health considers improving these patients' access to quality alcohol treatment among its highest priorities.

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➤ Interrelationship with mental health issues

Substance use disorders and suicide risk—Researchers at the VA Ann Arbor Healthcare System found that SUD sharply increased the risk of suicide for Veterans, in a 2017 study. The study looked at data on more than 4.8 million Veterans. About eight percent of men and three percent of women studied had problems with drugs or alcohol. These Veterans had more than twice the risk of suicide than those without an SUD. Women had a higher risk than men—women Veterans with an SUD had more than five times the rate of suicide than women who did not misuse substances.

Complex relationship between alcohol consumption and psychiatric distress—Hazardous drinking was linked to higher likelihood of psychiatric symptoms, while results of moderate drinking were mixed, in a 2018 study by Durham VA Health Care System researchers and colleagues. Previous studies have linked heavy drinking with increased depression and anxiety, but it is not clear what cause-and-effect relationships, if any, may exist.

The researchers collected data on alcohol use and psychiatric conditions for 3,003 Veterans. They found that hazardous drinkers were more likely to have PTSD, depression, and suicidality, compared with moderate drinkers. For men, moderate drinkers were less likely than nondrinkers to have depression and suicidality. However, this relationship disappeared when nondrinkers with past alcohol use disorder were removed from the calculations. Women moderate drinkers had lower rates of PTSD than nondrinkers and light drinkers, even when those with past AUD were removed. More research is needed on the possible protective effects of moderate drinking, say the researchers. Also, patients with a history of AUD may benefit from mental health screening and treatment, they say.

Postconcussive symptoms predict opioid prescriptions—Traumatic brain injury symptoms predicted opioid prescriptions for chronic pain for Veterans, in a 2018 San Francisco VA Health Care System study. Opioids are not recommended for patients with neuropsychological impairment from traumatic brain injury. However, clinical guidelines are not always adhered to in actual practice. Researchers studied the records of 53,124 Iraq and Afghanistan Veterans with chronic pain diagnoses from VA providers during a nine-year period. Self-reported severe and very severe postconcussive symptoms predicted starting long-term or short-term opioid use for chronic pain. The results indicate a need to educate prescribers and make non-opioid pain management options more available for Veterans.

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More on Our Website

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Selected Scientific Articles by Our Researchers

Smokers’ inaccurate beliefs about the benefits of lung cancer screening. Heffner JL, Krebs P, Johnson H, Greene PA, Klein DE, Feemter LC, Slatore CG, Au DH, Zeliadt SB. Smoker receiving low-dose computed tomography screening for lung cancer were confused about the benefits and limitations of the screening, and smoking in general. Ann Am Thorac Soc. 2018 Sep;15(9):1110-1113.

A bifunctional nociception and mu opioid receptor agonist is analgesic without opioid side effects in nonhman primates. Ding H, Kiguchi N, Yasuda D, Daga PR, Polgar WE, Lu JJ, Czoty PW, Kishioka S, Zaveri NT, Ko MC. Researchers are working on a pain medication, AT-121, that could potentially work as well as opioids without being addictive. Sci Transl Med. 2018 Aug 29;10(456).

The association between alcohol consumption, lifetime alcohol use disorder, and psychiatric distress among male and female Veterans. Wilson SM, Burroughs TK, Newins AR, Dedert EA, Medenblik AM, McDonald SD, Beckham JC, VA Med-Atlantic MIRECC Workgroup, Calhoun PS. Hazardous drinking was linked to higher likelihood of psychiatric symptoms, while results of moderate drinking were mixed. J Stud Alcohol Drugs. 2018 Jul;79(4):591-500.

Decline in prescription opioids attributable to decreases in long-term use: a retrospective study in the Veterans Health Administration 2010-2016. Hadlandsmyth K, Mosher H, Vander Weg MW, Lund BC. Opioid prescribing trends followed similar trajectories in VHA and non-VHA settings, peaking around 2012 and subsequently declining, with changes in long-term opioid prescribing accounting for most of the decline in the VHA. J Gen Intern Med. 2018 Jun;33(6):818-824.

The impact of cannabis used disorder on suicidal and nonsuicidal self-injury in Iraq/Afghanistan-era Veterans with and without mental health disorders. Kimbrel NA, Meyer EC, Bryann B, DeBeer BB, Gulliver SB, Morissette SB. The findings suggest that cannabis use disorder may increase Veterans’ risk for self-injurious behavior. Suicide Life Threat Behav. 2018 Apr;48(2):140-148.

Association of cannabis, stimulant, and alcohol use with mortality prognosis among HIV-infected men. Adams JW, Bryant KJ, Edelman JE, Fiellin DA, Gaither JR, Gordon AJ, Gordon KS, Kraemer KL, Mimiaga MJ, Operario D, Tate JP, van den Berg JJ, Justice AC, Marshal BDL. Findings show no evidence of a negative effect of cannabis use on mortality risk, while stimulant use was associated with increased mortality risk among HIV-infected men. AIDS Behav. 2018 Apr;22(4):1341-1351.

Effect of opioid vs nonopioid medications on pain-related function in patients with chronic back pain or hip or knee osteoarthritis pain: the SPACE randomized clinical trial. Krebs EE, Gravely A, Nugent S, Jensen AC, DeRonne B, Goldsmith ES, Kroenke K, Bair MJ, Moorbaloochi S. Treatment with opioids was not superior to treatment with nonopioid medications for improving pain-related function over 12 months. JAMA. 2018 Mar 6;319(9):872-882.

Electronic medical record alert associated with reduced opioid and benzodiazepine coprescribing in high-risk Veteran patients. Malte CA, Berger D, Saxon AJ, Hagedorn HJ Achtmeyer CE, Mariano AJ, Hawkins EJ. Medication alerts hold promise as a means of reducing opioid and benzodazepine coprescribing among certain high-risk groups. Med Care. 2018 Feb;56(2):171-178.

Do postconcussive symptoms from traumatic brain injury in combat veterans predict risk for receiving opioid therapy for chronic pain? Bertenthal D, Yaffe K, Barnes DE, Byers AL, Gibson CJ, Seal KH. Increased opioid prescribing in Veterans with self-reported severe persistent postconcussive symptoms indicates a need to educate prescribers and make non-opioid pain management ptions available for Veterans with TBI and neuropsychological sequelae. Brain Inj. 2018;32(10):1188-1196.

Longitudinal associations between outpatient medical care use and substance use among rural stimulant users. Cucciare MA, Han X, Imko C, Zaller N, Kennedy KM, Booth BM. Contact with an outpatient medical care clinic is associated with reductions in substance use over time among rural substance users with especially poorer functioning. Am J Drug Alcohol Abuse. 2018;44(2):235-243.

Marijuana use and estimated glomerular filtration rate in young adults. Ishida JH, Auer R, Vittinghoff E, Pletcher MJ, Reis JP, Sidney S, Johansen KL, Bibbins-Domingo K, Peralta CA, Shlipak MG. Long-term marijuana use does not appear to harm kidney function in young adults. Clin J Am Soc Nephrol. 2017 Oct 6;12(10):1578.

Cigarette smoking and musculoskeletal pain severity among male and female Afghanistan/Iraq era Veterans. Green KT, Wilson SM, Dennis PA, Runnals JJ, Williams RA, Bastian LA, Beckham JC, Dedert EA, Kudler HS, Straits-Tröster K, Gierisch JM, Calhoun PS. Female Veterans who smoked had more moderate to severe musculoskeletal pain than female nonsmokers, in a survey of more than 1,000 Veterans. Pain Med. 2017 Sep 1;18(9):1795-1804.

Cigarette smoke destabilizes NLRP3 protein by promoting its ubiquitination. Han SH, Jerome JA, Gregory AD, Mallampalli RK. In mouse models, cigarette smoke decreases NLRP3 protein abundance, which could suppress the immune system. Respir Res. 2017;18:2.

Comparative effectiveness of an internet-based smoking cessation intervention versus clinic-based specialty care for veterans. Calhoun PS, Datta S, Olsen M, Smith VA, Moore SD, Hair LP, Dedert EA, Kirby A, Dennis M, Beckham JC, Bastian LA. J Veterans offered telehealth programs to help them quit smoking had about the same quit rates as those participating in smoking cessation programs in the clinic. Reach of the internet interventions was significantly higher than the in-person program. Subst Abuse Treat. 2016 Oct;69:19-27.

Endomorphin analog analgesics with reduced abuse liability, respiratory depression, motor impairment, tolerance, and glial activation relative to morphine. Zadina JE, Nilges MR, Morgenweck J, Zhang X, Hackler L, Fasold MB. Endomorphin analogs could provide gold standard pain relief but with remarkably safer side effect profiles compared to opioids like morphine. Neuropharmacology. 2016 Jun:105:215-27.

Telephone smoking-cessation counseling for smokers in mental health clinics: a patient-randomized controlled trial. Rogers ES, Smelson DA, Gillespie CC, Elbel B, Poole S, Hagedorn HJ, Kalman D, Krebs P, Fang Y, Wang B, Sherman SE. A specialized counseling intervention was more effective at helping patients quit than transfer to a state quit-line. Am J Prev Med. 2016 April;50(4):518-27.

Intestinal REG3 lectins protect against alcoholic steatohepatitis by reducing mucosa-associated microbiota and preventing bacterial translocation. Wang L, Fouts DE, Starkel P, Hartmann P, Chen P, Llorente C, DePew J, Moncera K, Ho SB, Brenner DA, Hoper LV, Schnabel B. Alcohol appears to impair control of mucosa-associated microbiota, and subsequent breach of the mucosal barrier facilitates progression of alcoholic liver disease. Cell Host Microbe, 2016 Feb 10; 19(2):227-39.

Distribution of opioids by different types of Medicare prescribers. Chen JH, Humphreys K, Shah NH, Lembke A. Most prescriptions for opioid painkillers are made by the broad swath of U.S. general practitioners, not by a limited group of specialists. JAMA Intern Med. 2016 Feb 1;176(2):259-61.

A comparison of neuropsychiatric adverse events during early treatment with varenicline or a nicotine patch. Cunningham FE, Hur K, Dong D, Miller DR, Zhang R, Wei X, McCarren M, Mosholder AD, Graham DJ, Aspinall SL, Good CB. Use of varenicline for smoking cessation was not associated with a detectable increase compared with nicotine patches in hospitalization for any mental health outcomes. Addiction. 2016 Jul;111(7):1283-92.

Electronic cigarette inhalation alters innate immunity and airway cytokines while increasing the virulence of colonizing bacteria. Hwang JH, Lyes M, Sladewski K, Enany S, McEachern E, Mathew DP, Dae S, Moshensky A, Bapat S, Pride DT, Ongkeko WM, Crotty Alexander LE. E-cigarettes may be toxic to airway cells, suppress host defenses, and promote inflammation over time, while also promoting virulence of colonizing bacteria. J Mol Med (Berl). 2016 Jun;94(6):667-79.

Opioid dose and risk of suicide. Ilgen MA, Bohnert AS, Ganoczy D, Bair MJ, McCarthy JF, Blow FC. The risk of suicide mortality was greater among individuals receiving higher doses of opioids, and treatment providers may want to view high opioid doses as a marker of an elevated risk for suicide. Pain, 2016 May;157(5):1079-84.

Electronic cigarettes induce DNA strand breaks and cell death independently of nicotine in cell lines. Yu V, Rahimy M, Korrapati A, Xuan Y, Zou AE, Krishnan AR, Tsui T, Aguilera JA, Advani S, Crotty Alexander LE, Brumund KT, Wang-Rodriguez J, Ongkeko WM. E-cigarette vapor, both with or without nicotine, is cytotoxic to epithelial cell lines and is a DNA strand break-inducing agent. Further assessment of the potential carcinogenic effects of e-cigarette vapor is urgently needed. Oral Oncol. 2016 Jan;52:58-65.

Prescription opioid duration, dose, and increased risk of depression in 3 large patient populations. Scherrer JF, Salas J, Copeland LA, Stock EM, Ahmedani BK, Sullivan MD, Burroughs T, Schneider FD, Bucchols KK, Lustman PJ. Patients and practitioners should be aware that opioid analgesic use of longer than 30 days imposes risk of new-onset depression. Ann Fam Med, 2016 Jan;14(1):54-62.

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