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FIRE

NO WOMAN NOCRY Congenital insensitivity to pain WITH IT Scientists Discover Possible “Meth Gene”

BORN WITH IT

BORN

Scientists Discover Possible “Meth Gene”

BRAIN DAMAGE GENERATIONAL

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INSERT 2 StartingYoung Insight into adolescent addiction comes as new guidelines urge early prevention

Treatment providers have known for years that adolescents are more susceptible to drug use and consequently, addiction. But now they might know why. Researchers recently discovered a specific pathway in the brain that makes adolescents more prone to problematic substance use, which could lead to stronger prevention efforts. By studying how cocaine affected the behavior of young and adult mice differently, researchers found that a mechanism in the brain which regulates specific protein production also controls addictive behaviors. By manipulating that mechanism, researchers were able to mitigate cocaine’s addictive effects. “Now we have a bidirectional switch that can turn on and off the cocaine-induced changes in the brain,” says lead researcher Dr. Mauro Costa-Mattioli of the Baylor College of Medicine.

“ The excitement of this study is that now perhaps we have a signalling pathway that could be targeted for the treatment of addiction. ”

- Dr. Mauro Costa-Mattioli, Baylor College of Medicine

One size fits all What’s most exciting about the study is that the pathway does not appear to be specific to cocaine. A second study examining nicotine returned similar results, leading researchers to believe any treatments targeting the pathway would be effective for all substances. “In the case of nicotine, it’s exactly the same thing,” Dr. Costa-Mattioli says. “All the drugs of abuse, they reduce the activity, they hijack or change this mechanism.” Researchers say they’re still interested to see if the mechanism plays a role in the transition from social substance use to more problematic use. But they say simply identifying such a crucial link of the substance use chain could lead to significant prevention methods. “Of course, the excitement of this study is that now perhaps we have a signalling pathway that could be targeted for the treatment of addiction,” Dr. Costa-Mattioli says.

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Total improvement Experts say the benefits of implementing early intervention efforts far outweigh the cost. Although limited data exists, studies show investing just one dollar can produce anywhere from a few dollars to $26 in cost savings down the road. “Thus a well-designed, well- implemented early childhood intervention can dramatically benefit the community and society as well as improve children’s and families’ quality of life,” Dr. Volkow says. But the benefits of early intervention go beyond substance abuse. Experts say many of the risk factors for substance abuse are the same indicators for other social, behavioral and academic problems. They say creating a prevention program to address and reduce the risk of substance abuse will pay big dividends across the board. “Interventions designed to reduce early risk factors show benefits in a wide range of areas,” Dr. Volkow says. “Including improved personal and social functioning, better performance in school, and less involvement with the juvenile justice system or mental health services.” 

“ Early childhood intervention can dramatically benefit the community and society as well as improve children ’ s and families ’ quality of life. ” - Dr. Nora Volkow, NIDA director

First eight years To address adolescent drug use, experts say prevention efforts have to start earlier than most would expect.The National Institute on Drug Abuse (NIDA), the government’s top agency on substance use, recently released new guidelines suggesting prevention education should start in the first eight years of a child’s life. Officials acknowledge that early childhood is not a time period normally associated with drug use. But they say factors with family, school and community environments can shape development of certain emotional and behavioral issues that can manifest in substance abuse problems even decades later. “Central to intervening early is the idea of shifting the balance of risk and protective factors in a way that builds a foundation for optimal social development and resilience,” says NIDA Director Dr. Nora Volkow.

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BORN WITH IT Scientists Discover Possible 'Meth Gene’

Researchers have recently identified a gene that may play a role in meth addiction. New findings by Boston University School of Medicine researchers, published in PLOS Genetics, spotlight a gene called heterogeneous nuclear ribonucleoprotein H1 (Hn- rnph1). The research uncovered a link between this gene and how it effects behavior when stimulants are introduced. This new insight can help scientists understand genetic risk factors for addiction, along with some neuropsychiatric disorders. Also, this new understanding about how Hnrnph1 works could lead to the development of a prescription drug to help treat meth ad- diction, researchers say.

Need To Ident i fy Targets

other findings to improve the treatment of both dopamine- related problems like attention- deficit hyperactivity disorder, schizophrenia, and bipolar disor- der, along with dopaminerelated neurodegenerative disorders like Parkinson’s or Huntington’s diseases. Scientists say the genetic epide- miology of meth use disorders is very complex. Efforts to under- stand the biological processes that increase susceptibility to meth use disorders (i.e., abuse, dependence and psychosis) have uncovered several genetic variants. However, more research needs to be done. Though gene research can led to breakthroughs in treatment, Boston University points out in its news release that genetics alone are not responsible for addiction. Environmental and social factors also play an im- portant role.

The BU scientists discovered that Hnrnph1 “codes” for an RNA protein that regulates how other genes are processed in the brain. To better understand the genetic basis of meth addiction, the next step is to figure out the exact genetic targets of Hnrnph1. “A better understanding of the brain region and cell type-specific binding targets of Hnrnph1 will tell us more about the function of this gene and possibly identify new therapeutic strategies for minimizing risk and treating psycho-stimulant addiction — a disorder for which there is currently no FDA-approved drug,” says study co-author Dr. Camron Bryant in a news release from Boston University.

The study could also lead to

Other factors in addict ion According to the National Institute on Drug Abuse (NIDA), these are some of the environmental factors that come into play with ad- diction: • Friends and people addicts spend time with • Age when a person begins using drugs or alcohol • Neighborhood

“A better understanding

of the brain region and

cell typespecific binding

targets of Hnrnph 1 will

tell us more about the

function of this gene.” — Dr. Camron Bryant, study co-author

• Availability of drugs and alcohol • Presence of mental health issues • Gender

These environmental influences interact with genetic factors to influ- ence an individual’s susceptibility to addiction. While scientists hope to better understand the role genetics plays in addiction to meth and other drugs, much more research needs to be done to solve the puzzle.

Genetics alone are not responsible for addiction. Environmental and social factors also play an important role.

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STUDY METHODOLOGY Studying mice genetically modified to be without the Nav1.7 channel, Wood found that such mice had bodies that dis- played a large increase in certain genes responsible for creating opioid peptides. Opioid peptides occur naturally in the body as the body’s painkiller and have a similar effect as opioids. In making more of the opioid pep- tides, the mice were blocking any feelings of pain, which might be the reason people suffering from CIP also don't feel pain. Wood thought that if he gave mice a medicine that reversed the effect of the opioid peptides, it may reverse the disorder. He gave the mice naloxone—a medication used to reverse opioid overdoses—and it worked. Wood figured the same could be done for humans. “After a decade of rather disap- pointing drug trials, we now have confirmation that Nav1.7 is a key element in human pain,” Woods says. “The secret ingredient turned out to be good old-fashioned opioid peptides, and we have now filed a patent for combining low dose opioids with Nav1.7 blockers. This should replicate the pain- lessness experienced by people with rare mutations, and we have already successfully tested this approach in unmodified mice.” CONGENITAL INSEN- SITIVITY TO PAIN (CIP) is a very rare genetic mu- tation that prevents mes- sages of physical pain from reaching the brain.

Research researcher and his team of researchers studied a 39-year-old woman with CIP. Using a laser beam and a dose of naloxone, Wood helped the woman, who elected to partici- pate anonymously, feel pain for the first time in her life. “Used in combination with Nav1.7 blockers, the dose of opioid needed to prevent pain is very low,” says Wood in an UCL release. “People

Using a test subject with a ge- netic mutation that prevents her from feeling pain, scientists have conducted research that shows promise in creating more effec- tive painkillers—and potentially decreasing the need for addictive opioids. Congenital insensitivity to pain (CIP) is a very rare genetic muta- tion that prevents messages of physical pain from reaching the brain. Sufferers of the disorder, as babies, will chew their lips until they bleed. Toddlers have to deal with more potential for falls, bumps and being hurt by hot or sharp things. Adults are at a high- er risk of dying prematurely. The disorder leaves those afflict- ed without channels known as Nav1.7, which carry sodium to sensory nerves. Understanding this disorder and channels of pain reception and delivery has led re- searchers to study the disorder for ways to block pain in those who don't have the disorder. Research- ers thought they could block pain transporting channels in people without CIP so they can help those with chronic and painful ailments like arthritis. HELPING A WOMAN CRY In a study published by the journal Nature, John Wood, a University College London (UCL) Wolfson Institute for Biomedical

with nonfunctioning Nav1.7 produce low levels of opioids throughout their lives without de- veloping tolerance or experiencing unpleasant side effects.”

As for this work leading to com- plete cessation of pain, Wood tells the New Scientist that some research has found success, but nothing has led to the complete pain loss found in those that are naturally without Nav1.7 channels.

who doesn’t feel the Woman WHAT THE FUTURE HOLDS.... As for people with CIP, Woods says he doesn't know if treatment using nalox- one is an option. Long-term use of naloxone could have side effects. What Woods can say, definitively, is that the mice in the experiment felt as little pain as mice who did not have the Nav1.7 channel naturally. Woods, his team, and the rest of the field are working to fill in the re- search gaps to start answering these questions for humans. “We hope to see our approach tested in human trials by 2017 and

Could help in making better painkillers.

we can then start looking into drug combinations to help the millions of chronic pain patients around the world,” Woods says. Imperial College London professor Kenji Okuse reacted to Wood’s findings to the New Scientist, saying that the research will provide more information to doc- tors about pain.

We hope to see our

“Opioids and Nav1.7 blockers could provide much stronger analgesics, but they will not necessarily be better for patients,” Okuse says. “If we take the combination therapy route, people would have to take opioids throughout the lifetime, which is not a welcome thing.”

approach tested in human trials by 2017 and we can then start looking

into drug combinations to help the millions of chronic pain patients around the world. — John Wood, University College London Wolfson Institute for Biomedical Research researcher

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FIGHTING FIRE WITH FIRE

“I think this opens up a large world view with regards to this system in the brain.” - Dr. Heath Schmidt

“These results are very provocative and suggest these compounds could be repur- posed for drug addiction.” - Dr. Heath Schmidt,

University of Pennsylvania

D espite years of stigma, medication-assisted treatment (MAT) is steadily gaining in popularity among treatment providers. Government groups like the U.S. Department of Health and Human Services are actively campaigning to get more providers to offer MAT as a potentially vital resource for patients. While such groups often promote well-known medications such as methadone and buprenorphine, drug researchers are looking for new medications that could be a lifeline to patients in need. But new medications can cost millions to research and take years to get on the market. That’s why some researchers are taking a closer look, and finding success, with drugs already approved by the FDA. CURBING COCAINE USE Researchers at the University of Pennsylvania say a drug already on the market for diabetes may be able to curb cocaine use. The FDA-approved drug Byetta, used to regulate blood sugar in diabetic patients, is derived from a natural hormone known as GLP-1. The research team looked at how the hormone functioned in rats and found that the same hormone that regulates food intake could be used to suppress cocaine consump- tion. “These results are very provocative and suggest these compounds could be repurposed for drug addiction,” says Dr. Heath Schmidt, one of the lead researchers. “We have seen a reduction in cocaine consumption…but it doesn’t completely abolish it.” Currently, there is no FDA-approved drug for the treatment of cocaine abuse. But because Byetta and a similar drug have already gained federal approval, researchers say that leaves fewer hurdles before they could be used in treatment settings. Although still far from human trials, research- ers say they’re optimistic, especially because their research suggests the hormone is not specific to cocaine and could be used in treatment of other substance abuse disorders. “I think this opens up a large world view with regards to this system in the brain,” Dr. Schmidt says. “There’s really a lot to be explored here and I think it’s really an exciting time to be in the field and exploring the GLP- 1 system.”

ADJUSTING ALCOHOL CONSUMPTION Another team of researchers at the University of Queensland in Australia believe the FDA-approved drug pindolol could be used to stop alcohol abuse. Pindolol is an anti-hypertensive medication used to treat high blood pres- sure. But because of the way it interacts with neurotransmit- ters in the brain, they believe it could also be effective in treating alcohol use disorders (AUDs). To study the drug’s effect, the team used mice and exposed them to an alcohol consump- tion regimen similar to a binge drinking cycle common in humans. For mice also given pindolol, the team found they were able to reduce drinking in the long term (after at least 12 weeks). The team did not see as positive of results in the short term (only four weeks), but they say they’re still excited about its potential uses. “Although further mechanistic investigations are required, this study demonstrates the poten- tial of pindolol as a new treat- ment option for AUDs that can be fast-tracked into human clin- ical studies,” the authors wrote.

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Drinking during pregnancy presents parents with challenges beyond their own sobriety

Since its first diagnosis in 1973, Fetal Alcohol Spectrum Disorders (FASD) have shown how devastating drinking during pregnancy can be for an unborn child. Despite this fact, at least one in 10 pregnant women drink in the U.S. every year, according to a recent study by the Centers for Disease Control and Prevention. The CDC says children with FASD have physical issues like low birth weight and growth, problems with organ systems and damage to parts of the brain.These issues lead to behavioral and intellectual disabilities, hyperactivity, difficulty with attention, and poor communication, reasoning and judgment skills. The incurable situation can produce lifelong issues with school and social problems, mental health and substance abuse issues, difficulty keeping a job, living independently and having trouble with the law. In 2010, drinking while pregnant cost the U.S. $5.5 billion, says the CDC.

“ In 2010, drinking while pregnant cost the U.S. $5.5 billion. ” — Centers for Disease Control

“ I don’t know how I’m going to tell her. It was something I could have prevented. ” —mother of an FASD infant

Dysfunction in the family tree FASD can be multi-generational. Besides the common familial curse of addiction, the disability itself can contribute to bad impulse decisions, making it more likely for one to drink in the present moment and ignore the possible consequences. For that reason, a mother who has FASD herself may not recognize the symptoms of FASD in her child, because she views her own symptoms as normal. A mother in Tucson, Ariz., who was in recovery before realizing her drinking had caused FASD in her child, says the guilt was tremendous. Having to explain to her daughter why she had FASD was going to be the hardest thing she had ever done. “I don’t know how I’m going to tell her. It was something I could have prevented,” she says. Early diagnosis is key Diagnosing fetal alcohol syndrome can be difficult. A simple blood test will not suffice. Doctors typically look for abnormal facial features, such as a smooth fulcrum (the ridge most of us have between our nose and lips), lower than average height and weight, a small head and the birthmother’s admission of alcohol use during pregnancy. There are many treatment options, including medication for certain symptoms, behavioral therapies, education and training for parents. It is most helpful for children to be diagnosed before the age of six, be in a nurturing family environment and have access to special education and social services. Having FASD is not a hopeless situation. Implementing treatment strategies at a young age can help a child thrive despite the disorder.

 Regardless, it is never too late to quit drinking. Since brain growth takes place throughout a woman’s pregnancy, the sooner a woman quits drinking, the better off her baby will be. Prevention is best To prevent FASD, the best scenario is for a woman to refrain from drinking any amount of alcohol during pregnancy. Ideally, women should quit drinking the moment they go off birth control. “About half of all pregnancies in the United States are unplanned, and even if planned, most women won’t know they are pregnant for the first month or so, when they might still be drinking,” says Anne Schuchat, principal deputy director at the CDC.

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