Heroin's use rising, costing society more than $51 billion

Heroin use in the United States was estimated to cost society more than $51 billion in 2015, according to new research at the University of Illinois at Chicago.

Made from morphine, heroin is an opiate commonly used as a recreational drug for its euphoric effects. According to the World Drug Report 2016 from the U.N. Office on Drugs and Crime, heroin use has reached the highest level in 20 years in the U.S. and is the deadliest drug worldwide.

UIC pharmacoeconomists led by Simon Pickard and Ruixuan Jiang created a cost-analytic model to determine how heroin impacts society using several variables: number of imprisoned heroin users and their crimes; treatment costs of heroin abuse; chronic infectious diseases contracted through heroin abuse (HIV, Hepatitis B and C, and tuberculosis), and cost of their treatments; cost of treating newborns with medical conditions associated with heroin; lost productivity at work; and heroin overdose deaths.

The study, published in the journal PLOS ONE, found that heroin users are less productive than others due to premature death; spend more time away from work due to seeking treatment for drug dependence and for drug-related hospitalizations, and have high rates of work absenteeism and unemployment.

On average, the societal cost per heroin user per year is $50,799. An estimated 1 million people are active heroin users in the United States, putting the total societal cost at approximately $51 billion, said Pickard, professor of pharmacy systems, outcomes and policy. The cost per user is significantly higher than for patients suffering from other chronic illnesses, such as chronic obstructive pulmonary disease ($2,567 per patient in 2015 dollars, or $38.5 billion for 15 million patients) and diabetes ($11,148 per patient in 2015 dollars, or $248.59 billion for 22.3 million patients).

“The opioid crisis didn’t happen overnight,” Jiang said. The number of heroin users doubled from 2000 to 2013, rising from one per 1,000 individuals in 2000 to two per 1,000 individuals in 2013, she said.

Pickard has monitored the rise in heroin use for several years, noting that users often start taking the illicit drug after becoming dependent on prescription opioid painkillers. Due to the high cost of opioids and difficulty in obtaining prescriptions, opioid abusers often turn to heroin, which is cheaper and easier to get.

As heroin use has increased, so have overdose deaths, according to the Centers for Disease Control and Prevention. Heroin-related overdose deaths have more than quadrupled since 2010. From 2014 to 2015, heroin overdose death rates increased about 21 percent, with almost 13,000 people dying in 2015. And today, research has shown that heroin use is not confined to urban areas, but has reached rural America as well.

Without meaningful public health efforts, the number of heroin users is likely to continue to grow, Pickard said.

“The downstream effects of heroin use, such as the spread of infectious diseases and increased incarceration due to actions associated with heroin use, compounded by their associated costs, would continue to increase the societal burden of heroin use disorder,” Pickard said.

Why the marijuana and tobacco policy camps are on very different paths

The regulatory approaches to marijuana and tobacco in the United States are on decidedly different paths and, according to researchers from the U.S. and Australia, neither side appears interested in learning from the other.

“The two policy communities have shown very little interest in each other’s policy debates,” Wayne Hall and Lynn Kozlowski write in a new paper published in the journal Addiction.

Hall, the lead author, is a professor at the Centre for Youth Substance Abuse Research at the University of Queensland, Australia, and is an expert on marijuana and other drug use issues. Kozlowski is professor of community health and health behavior in the University at Buffalo’s School of Public Health and Health Professions and an expert on tobacco use and control.

Their paper takes a look at the diverging trajectories of cannabis and tobacco policies in the United States and attempts to explain some of the reasoning behind the different paths, while discussing possible implications.

For tobacco control, the push is toward what Kozlowski calls “a kind of prohibition,” mandating that only very low nicotine cigarettes are sold. The cannabis policy community, however, is advocating for quite the opposite — legal recreational use of marijuana.

Why are the approaches so different?

“One group perceives the downside of banning products and accepts an inevitability of some recreational use,” Kozlowski said, referring to marijuana advocates, “and the other does not accept recreational use and seeks a kind of prohibition.”

The differences can also be explained by examining who’s part of each group. The tobacco control community includes tobacco researchers, public health advocates, non-governmental organizations and government officials. The cannabis community is more diverse, Hall and Kozlowski point out, noting that it comprises civil liberties lawyers, civil rights advocates and supporters of reforming drug laws.

The cannabis community has another thing going for it: the fact that the legalization of recreational marijuana was preceded by legalizing the drug for medical use. In a way, that has softened the response to legalizing marijuana for recreational use, Hall and Kozlowski say.

“If you think the product is able to cure some ills, then that can justify use. The fun of it becomes a kind of bonus,” Kozlowski said.

Despite the differences, the two policy communities could learn a few lessons from each other. “For cannabis, assume that ‘big cannabis’ — large legal cannabis businesses — will behave with the same limited sense of corporate responsibility as has ‘big tobacco,'” Kozlowski said. “For tobacco, give up on moving toward a prohibition of traditional cigarettes — an endgame — and use public health tools to minimize the use of the most dangerous tobacco products, cigarettes.”

The paper also points out that the challenge for public policy makers in regulating marijuana is in applying what has worked in alcohol and tobacco control. That includes such policies as taxes based on potency to mitigate heavy use and dependence, limiting availability through trading hours and the number of outlets that sell the product, and restricting promotional activities.

“Lessons can be drawn from cannabis policy that are relevant to tobacco, and vice versa. Neither a focus on ‘endgames’ nor on burgeoning, legal retail markets should be approached uncritically,” Kozlowski said.

In the end, Kozlowski added, “The proper regulation of recreational drug products that have some adverse effects should be to restrict youth access, promote cessation of use in those who desire to quit, promote less-harmful modes of use by providing accurate and useful information to consumers.”

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Materials provided by University at Buffalo. Original written by David J. Hill. Note: Content may be edited for style and length.

Teen cannabis use and illicit drug use in early adulthood linked

One in five adolescents at risk of tobacco dependency, harmful alcohol consumption and illicit drug use:

Researchers from the University of Bristol have found regular and occasional cannabis use as a teen is associated with a greater risk of other illicit drug taking in early adulthood.

The study by Bristol’s Population Health Science Institute, published online in the Journal of Epidemiology & Community Health, also found cannabis use was associated with harmful drinking and smoking.

Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), the researchers looked at levels of cannabis use during adolescence to determine whether these might predict other problematic substance misuse in early adulthood — by the age of 21.

The researchers looked at data about cannabis use among 5,315 teens between the ages of 13 and 18. At five time points approximately one year apart cannabis use was categorised as none; occasional (typically less than once a week); or frequent (typically once a week or more).

When the teens reached the age of 21, they were asked to say whether and how much they smoked and drank, and whether they had taken other illicit drugs during the previous three months. Some 462 reported recent illicit drug use: 176 (38%) had used cocaine; 278 (60%) had used ‘speed’ (amphetamines); 136 (30%) had used inhalants; 72 (16%) had used sedatives; 105 (23%) had used hallucinogens; and 25 (6%) had used opioids.

The study’s lead author, Dr Michelle Taylor from the School of Social and Community Medicine said:

“We tend to see clusters of different forms of substance misuse in adolescents and young people, and it has been argued that cannabis acts as a gateway to other drug use. However, historically the evidence has been inconsistent.

“I think the most important findings from this study are that one in five adolescents follow a pattern of occasional or regular cannabis use and that those individuals are more likely to be tobacco dependant, have harmful levels of alcohol consumption or use other illicit drugs in early adulthood.”

In all, complete data were available for 1571 people. Male sex, mother’s substance misuse and the child’s smoking, drinking, and behavioural problems before the age of 13 were all strongly associated with cannabis use during adolescence. Other potentially influential factors were also considered: housing tenure; mum’s education and number of children she had; her drinking and drug use; behavioural problems when the child was 11 and whether s/he had started smoking and/or drinking before the age of 13.

After taking account of other influential factors, those who used cannabis in their teens were at greater risk of problematic substance misuse by the age of 21 than those who didn’t.

Teens who regularly used cannabis were 37 times more likely to be nicotine dependent and three times more likely to have a harmful drinking pattern than non-users by the time they were 21. And they were 26 times more likely to use other illicit drugs.

Both those who used cannabis occasionally early in adolescence and those who starting using it much later during the teenage years had a heightened risk of nicotine dependence, harmful drinking, and other illicit drug use. And the more cannabis they used the greater was the likelihood of nicotine dependence by the age of 21.

This study used observational methods and therefore presents evidence for correlation but not does not determine clear cause and effect — whether the results observed are because cannabis use actually causes the use of other illicit drugs. Furthermore, it does not identify what the underlying mechanisms for this might be. Nevertheless, clear categories of use emerged.

Dr Taylor concludes:

“We have added further evidence that suggests adolescent cannabis use does predict later problematic substance use in early adulthood. From our study, we cannot say why this might be, and it is important that future research focuses on this question, as this will enable us to identify groups of individuals that might as risk and develop policy to advise people of the harms.

“Our study does not support or refute arguments for altering the legal status of cannabis use — especially since two of the outcomes are legal in the UK. This study and others do, however, lend support to public health strategies and interventions that aim to reduce cannabis exposure in young people.”

Binge drinking associated with higher blood glucose levels in women, but not men

Regular high alcohol consumption and binge drinking from age 16 is associated with higher glucose concentrations in women’s blood — an important risk factor for type 2 diabetes — later in life, according to a study published in the open access journal BMC Public Health.

This study is the first to assess alcohol consumption data, starting in adolescence, over a 27 year period in relation to their blood glucose levels taken when they were 43 years of age. In women, total alcohol consumption and binge drinking behaviour throughout the 27 year period was significantly associated with higher blood glucose levels independent of BMI, hypertension and smoking status at age 43. This association was not true for men, for whom only BMI and hypertension remained associated with increased blood glucose levels.

Dr Karina Nygren, lead author from Umea University, Sweden said: “Our findings show that high alcohol consumption from ages 16 to 43 is associated with higher blood glucose levels in women but not in men. Because higher blood glucose is a risk factor for the development of type 2 diabetes, our data suggest that informing people about the risk of high alcohol consumption at a young age could have positive health impacts further down the line.”

Despite the association between alcohol, binge drinking and blood glucose only being significant in women, men still had higher blood glucose levels than women and consumed nearly 3 times as much alcohol between ages 16 and 43.

Previous studies suggest possible mechanisms for the association between alcohol and elevated blood glucose. For example, human studies have shown that ethanol can increase insulin resistance, which in turn leads to accumulation of glucose in the blood. Studies in rats have also shown that binge drinking behaviour alters the rat’s metabolism in a way that negatively affects insulin.

Dr Nygren commented: “Although there are some biological explanations behind why alcohol can directly lead to increased levels of glucose in the blood, the difference between men and women in our study is more difficult to explain.”

Data included in this study come from the Northern Swedish Cohort study which began in 1981. A total of 897 people from this study answered a questionnaire about alcohol consumption when they were 16, 18, 21, 30 and 43 years old. At age 43 a blood sample was taken from each person to assess blood glucose levels. The questionnaire involved eight questions about alcohol consumption including questions such as “how often do you drink alcohol?” and how much do you drink at each occasion?.” Binge drinking was defined as drinking four or more standard drinks of beer, wine or spirits per occasion for women, and five or more for men, at least once per month. One standard drink was specified to contain 12g of ethanol, which is equivalent to 330ml of a 5-6% beer.

The study shows an association between alcohol consumption and higher blood glucose but cannot show cause and effect. The data is limited by the fact that information on alcohol consumption comes from self-reported questionnaires and could be subject to bias. However, the long term nature of the study, which includes multiple follow ups, offers a unique insight into the drinking behaviours of people throughout their life.

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Feared by drug users but hard to avoid, fentanyl takes a mounting toll

Fentanyl, a highly potent prescription opioid, has Rhode Island drug users on high alert. But despite widespread aversion, fentanyl now causes the majority of the state’s drug overdose deaths.

These bleak findings by teams of Brown University researchers appear in two studies published in the International Journal of Drug Policy. They underscore the urgency of combatting the misuse of fentanyl and undermine a common perception that many users court the drug for its potency.

“Most people are not asking for it,” said Jennifer Carroll, lead author of one of the studies and an adjunct assistant professor of medicine at the Warren Alpert Medical School of Brown University. “They can’t avoid it, and their desire to avoid it is not reducing their risk.”

The number of overdose deaths in Rhode Island attributable to fentanyl rose to 138 in the first nine months of 2016, compared to 84 in all of 2014, according to the other study led by Brandon Marshall, an assistant professor of epidemiology at the Brown University School of Public Health. In 2014, 35 percent of the state’s fatal overdoses occurred because of fentanyl, but it was involved in 56 percent of drug deaths by 2016.

Moreover, mapping all 778 overdose deaths in the state during the study period showed that fentanyl-related deaths occur virtually everywhere that heroin overdoses are occurring. Fentanyl, is is often used to lace heroin but many users can’t tell if it is present.

“We were surprised that we saw such similar geographic patterns,” Marshall said. “What we’re drawing from that is that there is widespread contamination of the drug supply with fentanyl. It’s not clustered in one city or town.”

The data do show ominous differences with fatal fentanyl overdoses. One is is that they are particularly likely among users who inject drugs. Another is that users are now dying younger. Marshall said his hypothesis is that with fentanyl in the mix, the lifetime risk of a deadly drug overdose accumulates much faster than it used to.

Fear of fentanyl

While Marshall’s study documents the broad extent of the deaths, Carroll’s study gives voice to those who are trying to survive the onslaught. In surveys of 149 users and face-to-face interviews with 47 of them, Carroll’s team found a palpable fear and dislike for fentanyl among drug users. Four in five respondents said they were well aware of fentanyl and its dangers, but many described difficulty in avoiding it.

Traci Green, an associate professor at Brown and Boston University’s schools of medicine and public health and a senior author on both papers, noted that fentanyl’s appearance in the illegal drug trade occurred early on in Rhode Island. The first appearance of acetyl fentanyl was linked to a clandestine Rhode Island lab in spring 2013, she said, possibly foreshadowing the shift to including fentanyl. Unlike heroin, fentanyl can be created synthetically.

Of the 121 users who told Carroll they were aware and wary of fentanyl, 61 said they had been exposed to it. In the prior year before filling out the survey, 51 percent of those with exposure had experienced a non-fatal overdose, while only 17 percent of those who did not report fentanyl exposure said they had overdosed.

Throughout the study, Carroll and her co-authors included direct quotes from user interviews that illustrated the broader trends in the data. Matt, a man in his 20s from western Rhode Island spoke of his fear of fentanyl.

“I’ve seen people OD in front of me from shooting the stuff,” he is quoted as saying. “People are dropping like flies. I’ve had three friends I grew up with since I was 10. They’re all dead from [heroin cut with fentanyl].”

Another user, Jason, said that if he is struggling enough with the onset of withdrawal symptoms, he’ll still use heroin even if he suspects the presence of fentanyl. So he’ll try a little first to see if he feels fentanyl’s very strong effects.

“[It depends on] the availability of other batches and how sick I am,” he said. “If I’m sick, I gotta do it, you know? I won’t do half a gram. You know, I’ll do a little pinch and I’ll figure it out from there, but I won’t start big. It’s scary. I’ve watched overdoses. And I’ve had one in front of my girl.”

Carroll found that heroin users employ a wide variety of strategies to attempt to avoid fentanyl. Matt’s strategy is to snort rather than inject. Jason’s strategy is to try a little bit of the drug first. Sheryl said she tries to inspect the drug visually, while Carl said he can tell by the smell. But users such as Sheryl and Jeff readily acknowledged that their attempts at analysis were not very effective. Marshall’s study notes that a quantity of fentanyl equivalent to just two grains of salt can kill, meaning that very little has to be cut into heroin to pose a threat.

While some users said their long-term experience with their dealers allows them to trust that they won’t be sold heroin with fentanyl, others such as Maggie, a woman in her 40s, has no such trust. She told Carroll that dealers don’t care whether users die because they only care about money.

Given the lack of demand they observed, the researchers suspect that supply side reasons account for the presence of fentanyl in the market.

Possible solutions

In both studies, the researchers identified several measures that can help prevent deadly overdoses.

Marshall’s study notes that because fentanyl acts faster than heroin in suppressing breathing, users need readier access to the overdose-reversing drug naloxone. They also need it in higher doses.

“Programs to increase distribution of naloxone to people who use drugs, their acquaintances and their loved ones are urgently required,” Marshall and co-authors wrote.

Many of the users in Carroll’s study reported frustration in obtaining medication-assisted treatment with methadone or Suboxone to end heroin use because of difficulties with insurance or in finding a doctor. In Marshall’s study, researchers said more doctors should receive training and a subsequent waiver that would allow them to prescribe medication-assisted treatment. The proportion of the state’s physicians authorized to write the prescriptions has been growing but remains low, he said.

“People are trying to help themselves and find their way, but the system isn’t exactly ready to go,” Green said.

Marshall’s study also suggests increasing peer education efforts among users and investigating whether to establish supervised injection facilities, where users could take their heroin with medical providers standing by. Carroll acknowledged that the idea is controversial, but she said purely from a public health standpoint, research shows that such facilities save lives.

Finally, Marshall praised a relatively new development currently being studied in Rhode Island and Massachusetts: the distribution of fentanyl testing strips that can allow users to detect the drug.

Practical cooking tips for your red wine sauce

Postdoc at the Department of Food Science at the University of Copenhagen Pia Snitkjaer has carried out a series of experiments with alcohol in liquid dishes to figure out how to control the alcohol content during cooking for the benefit of large kitchens, the food industry, the gastronomy and restaurant sector as well as in the kitchen at home.

“In the experiments I used 900 ml veal stock plus 150 ml beer or wine. At this mixing ratio, the alcohol concentration starts at approx. 2 %, but drops to 0.2% after a half an hour of cooking,” explains Pia Snitkjaer, who underlines that this example is based on wine.

Precisely how much alcohol is left in, for example, a red wine sauce depends on three factors that you need to check if you want to control the alcohol content in a liquid dish or sauce, namely how much the dish is reduced, whether it is cooked with or without a lid and how much alcohol is added from the start (more about this in the facts section below).

“One should remember that you typically eat only 1/2-1 deciliter of sauce. If we, for example, assume that you eat 100 ml sauce, with a concentration of 2 vol % it corresponds to an intake of 2ml of alcohol. There are 15 ml in a unit of alcohol, so a pregnant woman would also be able to handle it,” explains Pia Snitkjaer.

All other factors the researchers studied — including the dimensions of the saucepan and the cooking temperature — proved to only be significant because they could affect how quickly the sauce was reduced.

Using elementary physical chemistry, which has to do with understanding the volatility of alcohol when mixed with water and heated, Associate Professor Jens Risbo from the Department of Food Science at the University of Copenhagen has developed a model that shows how the alcohol behaves in liquid dishes. That it is the volume of the dish that is the best parameter for determining the alcohol content — and not the cooking time — matters in relation to which techniques you can use if you want to reduce the alcohol content in the finished dish.

“You can reduce the alcohol content quickly by bringing a dish to a rolling boil, because by boiling hard, the volume will also decrease rapidly. But if you do not want the food to boil down too much, you can keep adding water as water evaporates, which will also lower the alcohol content both by dilution and evaporation,” says Pia Snitkjaer.

Put the lid on for a reverse distillation

If you want to reduce the alcohol content, you can put the lid on the saucepan.

“By placing a lid on the saucepan, there is a kind of reverse distillation where the alcohol disappears even more rapidly from the saucepan than the water. This is because alcohol is more volatile than water and thus can more readily evaporate. This is the same effect you use when you distil alcohol — you heat it up, so the alcohol evaporates more than the water, after which you can condense the vapours and obtain more concentrated alcohol,” explains Pia Snitkjaer.

The lid does not sit tightly on the saucepan, allowing the steam escape under the lid so that the alcohol evaporates, while the water condenses more preferential on the colder lid and runs back into the pan. As it cooks, more and more alcohol escapes under the lid, while the contents of the saucepan will contain a higher percentage of water. Experiments show that the use of a lid has a dramatic effect on obtaining a low concentration of alcohol.

Important for the calorie balance

The study has an impact on the calculation of the calorie content in recipes. Alcohol contains a lot of calories, but will probably be listed in a recipe with the calorie content the alcohol has as an ingredient before it is actually added to the dish, which results in a misleadingly high result.

“How many fewer calories there are depends on how much alcohol is evaporated. 1 gram of alcohol gives approx. 7 calories, so every time you evaporate 1 gram of alcohol, you have 7 fewer calories in the saucepan,” explains Pia Snitkjaer, who plans to develop the model to make it even more practical.

“It would be nice to be able to say precisely what this means for a tomato soup, a meat dish, etc. There are many things that can vary the result, but you can get some ideas about what happens when some of the most important parameters are changed — for example, what happens if you have a lot of sugar or a lot of gelatine, like in a veal stock,” says Pia Snitkjaer.

New consensus document for appropriate use of drug testing in clinical addiction medicine

A new Consensus Document from the American Society of Addiction Medicine (ASAM) provides practical, evidence-based recommendations on the use of drug testing for identification, diagnosis, treatment, and monitoring of patients with or at risk for substance use disorders (SUDs). The document appears in the May/June issue of the Journal of Addiction Medicine, the official journal of ASAM. The journal is published by Wolters Kluwer.

“Drug testing is a valuable tool for supporting patients in addiction treatment, and this comprehensive set of recommendations should prove useful to providers in a variety of addiction treatment settings,” comments Margaret Jarvis, MD, DFASAM, Chair of ASAM’s Quality Improvement Council. The Consensus Document and supplemental digital content are available on Journal of Addiction Medicine and ASAM websites.

Evidence-Based Recommendations Aim at ‘Smarter’ Approach to Drug Testing

The Consensus Document provides practical guidance on the use of drug testing across the many clinical settings in which addiction treatment is provided. Based on evidence from more than 100 research studies, the document’s recommendations were developed by a multidisciplinary panel, following an established “Appropriateness Method” process that combines scientific evidence with the collective judgment of experts.

The resulting recommendations focus on “when, where and how often it is appropriate to perform drug testing” in clinical addiction medicine. Based on evidence that drug testing aids in monitoring adherence and abstinence in treatment and can improve patient outcomes, drug testing “should be widely used in addiction treatment settings.” Drug testing should serve as a therapeutic tool, rather than a punitive one: “Providers should utilize drug testing to explore denial, motivation, and actual substance use behaviors with patients.”

Drug testing plays important roles in initial assessment, treatment planning, and monitoring of patients with SUDs, across treatment settings. However, the document emphasizes, “Drug testing should be only one of several methods of detecting substance use or monitoring treatment,” including patient self-reports and other indicators.

The Consensus Document addresses a wide range of daily issues encountered in the process of drug testing, including the choice of tests and appropriate response to test results. Urine tests remain by far the most common category of tests, but are also the most prone to tampering. There is growing interest in using other types of samples for drug testing, although more evidence on these tests is needed.

Drug testing should be done at least weekly at the beginning of treatment, and at least monthly in patients in stable recovery; however, individual consideration may be given for less frequent testing if a patient is in stable recovery. The document recommends that testing be performed on a random schedule, when possible.

The document addresses many other elements of testing programs, including documentation and patient confidentiality, practitioner education and expertise, and test facilities and devices. Issues in inpatient and outpatient treatment as well as opioid treatment services are discussed, along with issues related to special populations, including adolescents, pregnant patients, people in recovery, and health and other professionals. The expert panel also makes recommendations for further research to address gaps in each area.

A previous ASAM White Paper made broad suggestions to improve drug testing in clinical practice, emphasizing a “smarter” approach to drug testing — including avoiding some inappropriate and high-cost practices followed in the past. “The current crisis has many people in desperate need of high-quality addiction care, but many, professionals included, have no way of judging the quality of this kind of treatment,” comments Dr. Jarvis. “This document helps to define that high-quality care.”

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Where to look for new treatments for alcoholism? The matrix

A new study in Biological Psychiatry may pave the way for treating alcohol addiction by reducing motivation to drink, rather than by altering the effects of alcohol itself. Led by Drs. Kasia Radwanska and Leszek Kaczmarek of the Nencki Institute, Warsaw, Poland, the study reports a new mechanism behind alcohol seeking behavior.

When people think about drugs to treat alcoholism, their first thought is usually a drug that stimulates or blocks a receptor for a chemical messenger. However, the new study highlights a process that changes brain activity by altering the network of proteins that surrounds nerve cells. This network of proteins, called the extracellular matrix, provides active support for the development and activity of nerve cells. The functions of the matrix are regulated, in part, by enzymes that break down matrix proteins; one of these enzymes is matrix metalloproteinase-9 (MMP-9).

In the study, while mice had free access to alcohol to establish addiction-like behavior, those missing the enzyme MMP-9 (MMP-9 KO) drank just as much as normal mice. However, first author Dr. Marzena Stefaniuk and colleagues found that MMP-9 KO mice were less motivated to obtain alcohol when its access was restricted, and less persistent to seek alcohol during withdrawal — behaviors normally characteristic of addiction. The researchers were able to restore the impaired motivation by replacing MMP-9 in the central amygdala, a part of the brain’s emotional center that has also been implicated in alcohol dependence.

“Interestingly, in human alcoholics, the MMP-9 gene polymorphism that leads to a higher MMP-9 production correlates with greater motivation to drink alcohol,” said Dr. Kaczmarek, referring to their analysis of 167 alcohol-addicted males compared with 199 control males, also included in the new study. Using a clinical assessment of alcoholism behavior, the researchers found that addicted people with a T allele in the MMP-9 gene continued to drink alcohol despite the negative consequences more frequently than patients with a C allele. The findings further support the role of MMP-9 in motivation for alcohol.

“Matrix metalloproteinases play critical roles in brain function and disease that have only recently received intensive study,” said Dr. John Krystal, Editor of Biological Psychiatry. “The exciting study by Stefaniuk and colleagues implicates them in alcohol use disorders, but they are likely to play roles quite broadly in psychiatric disorders. It will be important to determine whether these proteins may be targeted therapeutically.”

In previous studies, MMP-9 has been demonstrated to be mandatory in the central amygdala for formation of appetitive memory traces via synaptic plasticity — the structural and physiological alteration of synapses, the connections that facilitate communication between neurons. Indeed, the loss of MMP-9 in mice impaired structural and physiological alcohol-related alterations in the central amygdala, leading the authors to suggest MMP-9-dependent synaptic plasticity in this brain region as a new mechanism behind alcohol craving.

“In aggregate, these findings point to MMP-9 as a novel therapeutic target in fighting alcohol addiction,” said Kaczmarek.

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Game changing strategy for pain relief developed

Researchers from Monash University have developed a new drug delivery strategy able to block pain within the nerve cells, in what could be a major development of an immediate and long lasting treatment for pain.

More than 100 million Americans suffer from chronic pain and this figure is expected to grow, driven by the increased life expectancy, increasing incidence of diabetes and cancer, combined with better survival rates, often leaving patients with severe and poorly treated pain. The global market for nerve pain treatments is over US$600 billion and yet current pain therapies are not completely effective and often suffer from unwanted side effects.

Research published in the journal, Science Translational Medicine, reveals how a target protein, long known to be associated with both chronic and acute pain, works within the nerve cell. This protein is the NK1 receptor, the receptor of the neuropeptide substance P, which mediates pain transmission. Because of its association with pain and other diseases of the nervous system, many drug development attempts have focused on inhibiting this receptor, but the efficacy of these treatments has been very limited. This new work shows that such ineffectiveness could be in part because the treatments targeted the protein on the surface of the nerve cell.

Dr Michelle Halls and Dr Meritxell Canals from the Monash Institute of Pharmaceutical Sciences (MIPS) and the ARC Centre for Excellence in Bio-Nano Science (CBNS) at Monash University, have worked with Professor Nigel Bunnett, previously at Monash and now at Columbia University in the US, and Professor Chris Porter from MIPS and CBNS.

Together they have found that the NK-1 receptor controls pain once it is inside the cell — so drugs that merely block it when it is on the surface of the cell have little efficacy. Instead, this new research shows that, in animal models, if the NK-1 receptor is blocked once it enters the nerve cell, it is possible to suppress pain more effectively.

Dr Halls said that the new strategy of “targeting receptors inside the cell represents a new frontier in drug delivery and a novel therapeutic strategy for dealing with pain.”

Working with a multidisciplinary team of cell biologists, pharmacologists, physiologists and drug delivery experts, the researchers developed drugs that specifically target NK-1 receptors within the nerve cell. Animal studies showed that using the drugs — which have an engineered lipid attachment that targets the drug to the NK-1 receptor inside the cell, could block pain for extended periods in several animal models.

Dr Canals said: “This is a proof-of-concept study that shows that we can re-engineer current pain drugs and make them more effective. The challenge is now to translate the technology into human clinical trials. This is a complex and challenging path — but the ultimate benefits to patients with nerve pain are potentially highly significant.”

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Oxytocin reduces cravings for methamphetamine

Many people have suggested that addiction hijacks the body’s natural drives in the service of compulsive drug use. A new study now suggests that hijacking another natural system in the brain may help overcome drug addiction. Published in Biological Psychiatry, the study shows that administration of oxytocin — a naturally occurring molecule well known for its role in social bonding and childbirth — reduces drug-seeking behavior in methamphetamine-addicted rats.

“There are virtually no pharmacotherapeutics for methamphetamine addiction, a chronically relapsing disease that destroys many lives,” said first author Dr. Brittney Cox, now at the University of California Irvine. “Our results are important because they support development of novel, oxytocin-based therapeutics for methamphetamine abuse in humans.”

To show this, Cox and colleagues developed a new method to assess addiction-like behaviors with meth, which could not be studied with previous techniques because of the drug’s long-acting effects. The researchers allowed rats to self-administer meth using a paradigm designed to examine individual differences in the rats’ drug-taking behavior, then tested the effects of oxytocin on their motivation to acquire the drug.

Although oxytocin administered to rats had no effect on the amount of methamphetamine they wanted when it required minimal effort, it strongly decreased the amount of effort rats were willing to exert to obtain the drug they desired, and it decreased relapse to methamphetamine seeking in both males and females.

“Intriguingly, these effects were strongest in animals with the greatest motivation to seek methamphetamine, indicating that oxytocin has potential as a treatment for addiction,” said Cox.

The study also pinpoints the brain region where the oxytocin has its effect. When Cox and colleagues infused oxytocin specifically into the nucleus accumbens, a small brain region implicated in drug addiction, they found that it had the same effects as when they administered it systemically. Infusion of an oxytocin blocker to the brain region blocked the systemic effects of oxytocin, driving home the necessary role of the nucleus accumbens for oxytocin’s effects.

“It will be interesting to learn whether oxytocin has a direct effect on the rewarding effects of methamphetamine or whether these effects are modulated by this hormone’s effects on natural rewards, particularly social activity,” said Dr. John Krystal, Editor of Biological Psychiatry, referring to the mechanism behind the effects that remains to be determined.

The researchers also found that using their new method, measures of motivation accurately predicted relapse behavior, which was not predicted by drug-taking itself when low effort was required. The technique used to assess addiction-like behavior in rats can also be used in humans, so if similar results are found in addicted people, the researchers hope the technique may help identify people most susceptible to addiction and be useful for predicting the efficacy of oxytocin treatment.

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Opioid abuse following urologic surgery documented

About 1 in 1,111 patients who undergo urologic surgery for conditions such as prostate cancer and kidney stones experience opioid dependence or overdose (ODO), a Loyola Medicine study has found.

Patients at highest risk for ODO were younger, underwent inpatient surgery, had longer hospital stays, were on Medicaid or Medicare or had a history of depression or chronic obstructive pulmonary disease.

The study by co-first authors Arpeet Shah, MD, and Robert Blackwell, MD, and senior author Gopal Gupta, MD, is published in the Journal of Urology.

The opioid epidemic is a growing problem in the United States. Every day, more than 90 Americans die after overdosing on opioids, and the economic burden of prescription opioid misuse in the United States totals $78.5 billion per year, according to the National Institute on Drug Abuse. In 2012, 259 million prescriptions were written for opioids — enough to supply every American adult with a prescription.

“With the rates of opioid dependence and overdose skyrocketing and physician prescriptions representing the center of the supply chain, it is imperative for surgeons to balance the pain-control needs of patients with the devastating consequences of America’s epidemic,” researchers wrote.

Opioids are a class of drugs that include illegal drugs such as heroin and legal pain relievers including Oxycontin, Vicodin, codeine and morphine.

“It is a surgeon’s ethical duty and legal responsibility to help minimize patient discomfort after surgery,” Loyola researchers wrote. “However, the ubiquitous use of opioids has led to a growing epidemic of addiction, dependence and overdose.”

Researchers reviewed the records of 675,527 patients who underwent inpatient and outpatient urologic surgery between 2007 and 2011. Researchers used powerful computers to mine data from the Healthcare Cost and Utilization Project Inpatient, Ambulatory Surgery and Emergency Department data sets. Patients who had been diagnosed with ODO prior to surgery were excluded from the study.

Urologic surgeries include kidney stone removals, hernia repairs and surgeries involving the prostate, kidney and bladder. Overall, 0.09 percent of patients were diagnosed with ODO within a year of surgery. This is consistent with findings from previous studies.

“While rare, this potentially devastating complication is likely under-reported, as many of those with an opioid dependence are not diagnosed until they seek treatment or have a complication from the dependence such as overdose,” researchers wrote.

The highest rates of ODO occurred among patients who underwent kidney stone procedures (0.15 percent) or major kidney surgery (0.12 percent).

Physicians can reduce ODO by implementing such measures as screening for ODO risk factors when scheduling surgery and using the shortest duration and lowest effective doses possible. No patient should be prescribed opioids for more than two weeks, and patients should be re-evaluated to determine whether refills are necessary.

The study is titled “Rates and risk factors for opioid dependence and overdose after urologic surgery.”

Safe space for illegal drug consumption in Baltimore would save $6 million a year

A new cost-benefit analysis conducted by the Johns Hopkins Bloomberg School of Public Health and others suggests that $6 million in costs related to the opioid epidemic could be saved each year if a single “safe consumption” space for illicit drug users were opened in Baltimore.

It would also reduce overdose deaths, HIV and hepatitis C infections, overdose-related ambulance calls and hospitalizations — and bring scores of people into treatment, they found.

Carefully monitored “safe consumption” spaces, which are not legal in the United States but have been used in dozens of cities around the world, provide a clean indoor environment in which people can use their own drugs with medical personnel on hand to reverse overdoses should they occur. These facilities serve as access points to substance use disorder treatment and other vital social services for drug users, such as medical care and housing.

The authors of the study, published this month in the Harm Reduction Journal, say that the findings add economic evidence to the body of research that already links such spaces to a reduction in fatal drug overdoses and an increase in people seeking treatment. “Safe consumption” spaces are especially critical right now: Last year, the United States hit a record for the number of people who have died from drug overdose, and fentanyl, a more dangerous and powerful drug than heroin, is increasingly being added to heroin in places like Baltimore.

“No one has ever died from an overdose in a safe consumption space,” says the study’s senior author, Susan G. Sherman, PhD, MPH, a professor in the Department of Health, Behavior and Society at the Bloomberg School. “Thousands of lives have been saved. There are lots of doors people can walk through when they are addicted to drugs. We want them to walk through a door that may eventually lead to successful treatment — and keep them alive until they are ready for that.”

Says Amos Irwin, MA, the study’s lead author and program director at the Law Enforcement Action Partnership in Washington, D.C.: “Today, thousands of Baltimoreans are risking their lives to inject drugs instead of seeking treatment. We estimate that more than 100 new people would enter treatment every year if the city had a supervised injection facility. Bringing these people into a safe space actually helps reduce drug use, not increase it.”

For their study, the researchers looked at the costs of operating a safe consumption space in Vancouver, the only one in North America. Then they estimated the impact on several health outcomes, based on Baltimore data.

They determined that running a 1,000-square-foot, 13-booth space in Baltimore for 18 hours a day would cost $1.8 million a year. Insite, the Vancouver facility, serves about 2,100 unique individuals a month, who perform roughly 180,000 injections per year in a space the same size.

Based on research done at Insite, they estimate that a Baltimore facility would generate $7.8 million in annual savings, preventing four HIV infections, 21 hepatitis C infections, 374 days in the hospital for skin and soft-tissue infections, six overdose deaths, 108 overdose-related ambulance calls, 78 emergency room visits and 27 overdose-related hospitalizations.

At the same time, an estimated 121 additional people would enter treatment.

“Six million dollars is a lot of money for one facility to save,” Irwin says. “It is almost a third of Baltimore City’s entire budget for HIV, sexually-transmitted infections and substance abuse treatment and prevention.”

A bill allowing safe consumption spaces failed in the Maryland General Assembly this year. Last month, the Massachusetts Medical Society recommended opening safe consumption spaces in that state. These supervised injection facilities are a widely used public health intervention in 11 countries, mostly in Europe.

Sherman says many drug users in Baltimore are injecting on the streets or in abandoned houses, exposing them to possible violence, arrest and overdose death. Safe consumption spaces would provide clinical supervision and a clean environment, and they allow health professionals to connect drug users to critical health services. Such spaces maintain a strict prohibition on drug sharing or selling. These programs are not condoning illicit behavior, she says. They are meeting people where they are and connecting them with lifesaving resources.

The researchers did not estimate how many safe consumption spaces would be needed to service Baltimore’s drug using population.

“We know what doesn’t work when it comes to the so-called ‘War on Drugs’ in the United States because we have an opioid epidemic that is only getting worse,” Sherman says. “The stakes are even higher now with so much heroin and other drugs adulterated with fentanyl. You can keep doing what you are doing or you can try something that has been proven by evidence and is considered usual care in a dozen nations.”

Resetting balance in reward centers may help treat alcohol addiction

The human brain functions on a delicate balance of reinforcing positive behaviors and suppressing negative ones, which takes place in the dorsal striatum, a brain region critical for goal-directed behavior and implicated in drug and alcohol addiction.

According to a new study in Biological Psychiatry, two pathways in the dorsal striatum that regulate this process — the “Go” pathway, which hits the gas for rewarding behaviors, and the “No-Go” pathway, which hits the brakes — have opposite effects to control alcohol drinking behavior. Led by Dr. Jun Wang of Texas A&M Health Science Center, the study reports that alcohol-induced alterations in the signaling of these two pathways reinforce alcohol consumption, possibly leading to alcohol abuse or addiction.

Co-first authors Dr. Yifeng Cheng, Dr. Cathy Huang, and Dr. Tengfei Ma and colleagues trained mice to become heavy drinkers by repeated cycles of consumption and withdrawal of 20% alcohol — slightly higher than the average alcohol content in a glass of wine — and measured the effects on the balance of this delicate control of reward behavior.

“To the best of our knowledge, this article demonstrated, for the first time, that excessive alcohol consumption suppresses activity of the No-Go pathway,” said Wang. By recording the activity of cells, the researchers found substantially increased GABA signaling, the primary inhibitory neurotransmitter of the brain, which quieted the No-Go pathway. Excessive alcohol consumption had the opposite effect in the Go pathway. These cells had increased glutamate signaling, the primary excitatory neurotransmitter in the brain, ramping up the Go signal.

The findings reveal detailed information on the mechanisms underlying control of alcohol consumption. “Both of these effects serve to reinforce alcohol consumption, leading to pathological excessive use of alcohol,” wrote the authors.

Through manipulation of cells specific to each pathway to mimic either increased glutamatergic or GABAergic activity, Cheng and colleagues confirmed that inhibition of cells in the No-Go pathway and excitation of cells in the Go pathway promotes alcohol consumption. The findings indicate that either of these alterations is sufficient to drive alcohol drinking behavior.

The researchers dug deeper into the mechanism and found that activation of dopamine D2 receptors, the type that mediate the No-Go pathway, also reduced GABAergic activity and alcohol consumption. The regulation in GABAergic activity was mediated by a downstream target of D2 receptors called GSK3β, which altered the expression of GABA receptors in the cells.

“These findings identified potential therapeutic targets,” said Wang, referring to GSK3β and GABA signaling in the No-Go pathway, which the researchers hope will aid development of new ways to treat alcohol abuse.

The study may have even broader implications, according to Dr. John Krystal, Editor of Biological Psychiatry. “The balance between signaling in the [Go] and [No-Go] pathways is likely to be a critical factor influencing motivated behavior, generally. This balance might be targeted to treat alcoholism, but also other addictions, mood disorders, and perhaps OCD,” he said.

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Cost-effective ways to combat HIV risk among intravenous drug users identified

With the abuse of opioids on the rise in the United States, Stanford University researchers are concerned that increased HIV transmission from shared needles won’t be far behind.

“There’s an opioid epidemic in our country, and there’s a real public health crisis associated with injecting,” said Cora Bernard, a graduate student in management science and engineering. “We think it’s important to understand what investments give highest value because HIV prevention programs, and especially programs that reduce the prevalence of injection drug use, can have outsized, positive impact on individuals, families and public safety.”

Bernard is the lead author of a study on prevention programs that could head off a resurgence of HIV and perhaps decrease the effects of the opioid crisis. The study will be published online May 24 in PLOS Medicine. The senior author is Margaret Brandeau, PhD, professor of management science and engineering.

In July 2016, Bernard and her co-authors published a different study examining pre-exposure prophylaxis, or PrEP, a pill that reduces a person’s risk of infection when they come into contact with the HIV virus. The researchers found that PrEP was effective, but expensive.

The new study examines alternatives that also reduce the risk of HIV infection but are more cost-effective. They created a model to determine how many quality-adjusted life years — a metric that incorporates both life expectancy and quality of life — a person could gain from four HIV prevention methods, and what those years would cost.

“The dynamics of HIV prevention and treatment are complex,” Brandeau said. “Our model allows us to evaluate the costs and effects of the interventions, singly and in combination, to determine what programs would be effective and cost-effective in preventing the spread of HIV among persons who inject drugs.”

Prevention models studied

Of the prevention programs simulated in the model, the authors found that opioid agonist therapy, or OAT, was the most cost-effective. OAT replaces drugs like heroin with a prescription that provides similar effects under safer conditions. Methadone and buprenorphine maintenance therapies are the most common.

Needle-syringe exchange programs, in which people swap their dirty needles for clean ones, were the next most cost-effective option. This was followed by test-and-treat programs, which identify people with a high risk of contracting HIV, test them for the virus and treat them before the disease has much chance to spread — both within their own bodies and to others who are exposed.

The study estimated that PrEP can also successfully reduce HIV, but not in a cost-effective way. The authors write that the other three techniques could all cost less than $50,000 for each quality-adjusted life year gained by individuals. PrEP would likely cost more than $600,000 per quality-adjusted life year.

The prevention programs were most effective when used in combination. The authors project that combining OAT and needle-syringe exchanges could avert up to 40,000 HIV infections over 20 years among people who inject drugs, not to mention preventing downstream sexual transmission of HIV to others in the population.

According to Bernard, one of the benefits of OAT in particular is that in addition to reducing the risk of HIV, it can also help people stop injecting drugs. The authors project that expanding OAT access could decrease the size of the injection population by up to 23 percent over 20 years for low-coverage expansions and up to 37 percent over 20 years for more extensive program expansions.

OAT found to be ‘highest-value investment’

“We started out thinking about this as an HIV problem, but we realized that the majority of health benefit actually comes from reducing injection drug use and improving quality of life for drug users,” said Bernard. “This is why we found OAT to be the highest-value investment.”

Bernard and her co-authors believe that employing techniques like OAT could help reduce the effects of the opioid crisis.

“Our study aims to help policymakers and clinicians understand how a variety of interventions can help improve health outcomes and prevent HIV,” said study co-author Douglas Owens, MD, professor of medicine and internist at the Veterans Affairs Palo Alto Health Care System. “We hope our analyses help show how to use limited resources efficiently to prevent the devastating consequences of substance use.”

Street gangs, crime serve as deviant leisure activities for youths

Although at-risk youths may have a variety of reasons for joining street gangs, a new study suggests that gang membership and criminal acts often serve as deviant leisure activities, fulfilling young people’s needs for excitement, a sense of belonging and social support.

Based on interviews with 30 former street gang members in Illinois, the study is one of the first to explore gang involvement as leisure activity. The paper was co-written by Liza Berdychevsky, Monika Stodolska and Kim Shinew, all professors of recreation, sport and tourism at the University of Illinois.

“Studies like this are particularly important right now, given the incidence of gun violence in cities such as Chicago and the renewed attention to gang crime nationwide,” Berdychevsky said. “Developing an in-depth understanding of what drives delinquent and criminal activities — and ways that sports and other leisure activities can be used for prosocial purposes — can help create more effective prevention, intervention and rehabilitation programs for at-risk youths and young offenders.”

The researchers interviewed former members of the Latin Kings/Latin Queens, Satan’s Disciples, the Vice Lords and other street gangs operating in Chicago and downstate Illinois. Some participants had left gang life as recently as the prior year, while others had desisted for decades, sometimes after serving lengthy prison sentences.

While active with a gang, each of the participants had been a perpetrator, victim and/or witness to violent crimes — including murders, rapes, beatings, shootings and stabbings. Some had trafficked drugs, stolen cars or committed arson or vandalism.

For some of the participants, the gang lifestyle was an intergenerational legacy -grandparents, parents and other family members taught criminal behaviors and values to the generations that followed. Delinquent and deviant activities were accepted or even expected in their families and neighborhoods, they told the researchers.

“One of the most heartbreaking things was these young people’s fatalism and defeatist outlook on life — they thought there was no future for them other than dying young or going to prison,” Berdychevsky said.

Many of the participants had dropped out of school or attended only sporadically. With no responsibilities and few recreational opportunities in their neighborhoods, the youths felt a pervasive need for stimulation, and they satiated their boredom with parties that were rife with sex, drugs and alcohol; violent clashes with rival groups; and crimes such as stealing and crashing cars into vehicles driven by rivals.

Gang members’ reasons for engaging in crime and other gang activities were similar to those that motivate other young people to engage in sports or other positive recreational activities, the researchers found.

“They even spoke about their violent acts using leisure and sports terminology, such as describing how they ‘hunted’ their victims,” said Stodolska, the lead author of the paper. “One man said he felt as if he were on a football team and the bystanders, fellow gang members or people in his community who encouraged these behaviors were cheering him on from the stands.

“What was really striking about the people we interviewed was how much many of them enjoyed the violence. Some participants likened it to a drug addiction, which increased their attachment to that lifestyle.”

Many of the interviewees described experiencing a “rush” — a surge of adrenaline, or a sensation similar to sexual arousal, according to one woman — during gunfights and other violent incidents. While many of them attributed much of their criminal activity to drugs or alcohol, others told the researchers they preferred to be sober while committing violent crimes for the sheer pleasure of seeing people suffer.

The use of leisure activities in gang prevention, intervention and rehabilitation of offenders is underrecognized currently by cities and organizations seeking to develop solutions for gang-related crime and delinquency, Berdychevsky said.

“People in the parks and recreation field need to be involved in developing these strategies, as they’re one among a number of stakeholder groups that can help combat gang involvement,” Stodolska said.

Since leaving gang life and/or prison, many of the interviewees currently are involved in gang prevention organizations such as Cure Violence/Ceasefire and the Chicago Dream Center.

“One of the things that struck me was how smart, charming, articulate and talented many of the interviewees are,” Shinew said. “And they have leadership skills. On several occasions, I thought, ‘Wow. If you had just made a few different decisions in your life, your future might have been so different.'”

The study, which was funded by a Campus Research Board grant, has been accepted by the journal Leisure Sciences. Stodolska, Berdychevsky and Shinew have presented their findings at five symposia thus far, including the Academy of Leisure Sciences Research Institute in Indianapolis in February; and at the Illinois Parks and Recreation Association Conference, held in Chicago in January.