1. New study links opioid epidemic to childhood emotional abuse

    March 24, 2017 by Ashley

    From the University of Vermont press release:

    A study by researchers at the University of Vermont has revealed a link between adult opioid misuse and childhood emotional abuse, a new finding that suggests a rethinking of treatment approaches for opioid abusers.

    To uncover the link to emotional abuse, the study, published in the current issue of Addictive Behaviors, analysed and cross referenced the results of a series of psychological tests administered to a sample of 84 individuals with a history of problem opioid use who had also suffered childhood trauma.

    Earlier research has found that a high percentage of adults who abuse substances were maltreated in a variety of ways as children. But few previous studies have investigated the causes of opioid addiction specifically, and no earlier ones narrowed the link among opioid users to emotional abuse.

    Emotional abuse was much more strongly correlated with survey participants’ problem opioid use than childhood sexual and physical abuse or other kinds of maltreatment such as neglect.

    The study found that children who had been emotionally abused were more likely to engage in rash, risky behavior in adolescence and to suffer posttraumatic stress disorder (PTSD) as adults. Opioid use offered a refuge from PTSD for this group — while causing a host of new problems. The severity of the PTSD was directly linked to the severity of their opioid-related problems.

    “If a person is being physically or sexually abused, it’s easier to put the blame on the person doing the abuse,” said Matthew Price, assistant professor in Department of Psychological Science at the University of Vermont, and the paper’s senior author.

    “With emotional abuse, the abuser is saying ‘You are the problem.’ Being called names, being told you’re not good enough, being told no one cares about you undermines your ability to cope with difficult emotions. To protect themselves from strong emotions and from trauma cues that can bring on PTSD symptoms, people with this kind of childhood experience frequently adopt a strategy of avoidance, which can include opioid use.”

    New treatment approaches

    The findings suggest why some opioid abusers don’t respond to substance abuse counseling or PTSD treatment and point the way toward potentially more productive therapies. Drug addiction and mental health issues are often treated separately by different kinds of specialists, Price said. “Mental health counselors will frequently say, ‘Deal with your drug issues first, then come to see me.'”

    The study suggests “we should really start to explore more integrated treatment,” Price said. “If a patient has had severe emotional abuse and they have a tendency to act out when they’re feeling upset, and then they turn to opioids to deal with the resulting PTSD, it makes sense to address the emotional component and the drug problems at the same time.”

    In the study, participants were interviewed about their childhood experiences and then given a battery of psychological tests that measured the type and extent of any maltreatment they had experienced as children, the extent to which their opioid use was causing life problems, the severity of their addiction, the extent of their impulsive behavior, and the extent and severity of their PTSD.

    The researchers used a sophisticated statistical method known as structural equation modeling, or SEM, to make connections between the data sets each of the individual tests brought to light, which illuminated the pathway from childhood emotional abuse to rash adolescent behavior to PTSD to opioid abuse.


  2. Giving up cigarettes linked with recovery from illicit substance use disorders

    March 22, 2017 by Ashley

    From the Columbia University’s Mailman School of Public Health press release:

    Smokers in recovery from illicit drug use disorders are at greater risk of relapsing three years later compared with those who do not smoke cigarettes. Results of the study by researchers at Columbia University’s Mailman School of Public Health and the City University of New York appear online in The Journal of Clinical Psychiatry.

    Most adults who have illicit drug use disorders also smoke cigarettes. Yet while treatments for substance use disorders traditionally include and require concurrent treatment for addiction to all substances — including treatment for and required abstinence from alcohol and any other illicit substance use — treatment for nicotine dependence has not routinely been part of treatment for illicit substance use problems.

    “The thinking in clinical settings has been that asking patients to quit cigarette smoking while they try to stop using drugs is “too difficult,” or that smoking may be helpful in remaining abstinent from alcohol and drugs, but it is not related whether or not one remains abstinent from illicit drug use over the long term,” said Renee Goodwin, PhD, of the Department of Epidemiology, Mailman School of Public Health, who led the research.

    The researchers studied data from 34,653 adults enrolled in the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) who were assessed at two time points, three years apart, on substance use, substance use disorders, and related physical and mental disorders. Only those with a history of illicit substance use disorders according to DSM-IV criteria were included in the final sample. Daily smokers and nondaily smokers had approximately twice the odds of relapsing to drug use at the end of the three-year period compared with nonsmokers. The relationships held even after controlling for demographics and other factors including mood, anxiety, alcohol use disorders, and nicotine dependence.

    Specifically, among those with remitted substance use disorders who were smokers at the beginning of the study, more than one in ten (11 percent) who continued smoking three years later relapsed to illicit substance use three years later, while only 8 percent of those who had quit smoking and 6.5 percent of never smokers relapsed to substance use three years later. Among those who were non-smokers, smoking three years later was associated with significantly greater odds of substance use disorders relapse compared to those who remained non-smokers.

    “Quitting smoking will improve anyone’s health,” says lead author Andrea Weinberger, PhD, an assistant professor in the Department of Epidemiology and Population Health, Albert Einstein College of Medicine. “But our study shows that giving up cigarettes may be even more important for adults in recovery from illicit substance use disorders since it may help them stay sober.”

    “If research continues to show a relationship between smoking and relapse to substance use among those in recovery, making tobacco treatment a standard part of treatment for illicit substance use disorders may be a critical service to provide to adults toward improving substance treatment outcomes over the long term,” suggested Dr. Goodwin.


  3. Aggression disorder linked to greater risk of substance abuse

    March 16, 2017 by Ashley

    From the University of Chicago Medical Center press release:

    People with intermittent explosive disorder (IED) — a condition marked by frequent physical or verbal outbursts — are at five times greater risk for abusing substances such as alcohol, tobacco and marijuana than those who don’t display frequent aggressive behavior, according to a new study by researchers from the University of Chicago.

    In the study, published Feb. 28, 2017 in the Journal of Clinical Psychiatry, Emil Coccaro, MD, and colleagues analyzed data from more than 9,200 subjects in the National Comorbidity Survey, a national survey of mental health in the United States. They found that as the severity of aggressive behavior increased, so did levels of daily and weekly substance use. The findings suggest that a history of frequent, aggressive behavior is a risk factor for later substance abuse, and effective treatment of aggression could delay or even prevent substance abuse in young people.

    IED affects as many as 16 million Americans, more than bipolar disorder and schizophrenia combined. It is often first diagnosed in adolescents, some of whom are as young as 11, years before substance abuse problems usually develop. IED runs in families and is thought to have a significant genetic component, although Coccaro said people tend to treat it as a social-behavioral issue instead of as a true neurobiological disorder.

    “People don’t see this as a medical problem. They think of it as simply bad behavior they have developed over the course of their lives, but it isn’t. It has significant biology and neuroscience behind it,” said Coccaro, who is the Ellen C. Manning Professor of Psychiatry and Behavioral Neuroscience at UChicago.

    Previous research has implied that aggressive behavior in IED is due to the presence of other psychiatric disorders, such as anxiety or depression. But the new UChicago study found no such relationship. While substance abuse, like excessive drinking, can clearly make aggressive behavior worse, the onset of IED almost always precedes the development of chronic substance abuse. Coccaro and his team found that IED preceded substance abuse in 92.5 percent of the cases where subjects developed both disorders.

    Coccaro emphasized that early psychological intervention, medication and cognitive therapy are the most effective treatments to prevent, or at least delay, substance abuse problems in adolescents diagnosed with IED.

    What you’re really treating is the emotional dysregulation that leads to aggression,” Coccaro said. “The earlier you treat this dysregulation, the more likely you are to offset other disorders that come later down the road.”


  4. Anxiety is a stronger harbinger of alcohol problems than stress

    March 15, 2017 by Ashley

    From the Research Society on Alcoholism press release:

    Stress and anxiety are widely believed to contribute to drinking. Alcohol is thought to reduce tension caused by stress (the “flight or fight” response) as well as alleviate the unpleasant symptoms of anxiety (anticipation of the unpredictable, impending threats). Prior research, however, has yielded inconsistent findings as to the unique relations between stress and anxiety, on the one hand, and alcohol consumption and alcohol use disorders, on the other hand. This study was designed to examine how differences in self-reported levels of anxiety, anxiety sensitivity, and perceived stress impact the frequency and intensity of drinking, alcohol craving during early withdrawal, and alcohol craving and stress reactivity.

    Recent drinking was assessed in 87 individuals (70 men, 17 women) with alcohol use disorders (AUDs). Three distinct measures were used to evaluate anxiety, anxiety sensitivity, and perceived stress. A subset of 30 subjects was admitted to a medical center to ensure alcohol abstinence for one week: measures of alcohol craving were collected twice daily. On day 4, subjects participated in a public speaking/math challenge, before and after which measures of cortisol and alcohol craving were collected.

    In these heavy drinkers, measures of anxiety as compared with perceived stress were more strongly associated with a variety of alcohol-related measures. While alcohol studies often use the terms anxiety, anxiety sensitivity, and stress interchangeably, this study showed the importance of differentiating among the three terms given their unique relationships with drinking, craving, and stress reactivity among individuals with AUDs.


  5. Alcoholism may be caused by dynamical dopamine imbalance

    by Ashley

    From the National Research University Higher School of Economics press release:

    Researchers from the Higher School of Economics, Ecole Normale Supérieure, Paris, Indiana University and the Russian Academy of Sciences Nizhny Novgorod Institute of Applied Physics have identified potential alcoholism mechanisms, associated with altered dopaminergic neuron response to complex dynamics of prefrontal cortex neurons affecting dopamine release.

    Interacting neuronal populations in the cerebral cortex generate electrical impulses (called action potentials), that are characterized by specific spatial and temporal patterns of neural firing (or complex neural dynamics). These firing patterns depend on the intrinsic properties of individual neurons, on the neural network connectivity and the inputs to these circuits. Taken as a basis for this computational study is the experimental evidence for a specific population of prefrontal cortex neurons that connects via excitatory synapses to dopaminergic and inhibitory ventral tegmental area (VTA) neurons. Thus, the structure of neural firing in the prefrontal cortex can directly affect dopamine cell response and dopamine release.

    Boris Gutkin leads the Theoretical Neuroscience Group at the HSE Centre for Cognition and Decision Making. One of the group’s research areas focuses on neurobiological processes leading to substance abuse and addiction — specifically, on detecting links between the neurobiological mechanisms of a drug’s action and observable behavioural reactions. In particular, the researchers use mathematical modelling to examine specific characteristics of dopaminergic neuron firing patterns and dynamics which can lead to addiction.

    Dopamine, a neurotransmitter released by dopaminergic neurons in the brain, is a chemical which plays a key role in the internal brain reward system that drives learning of motivated behavior. By acting within the reward systems in the brain (e.g. the ventral tegmental area found deep in the mid-brain; the striatum, responsible for selecting correct actions and the prefrontal cortex that controls voluntary goals and behaviors), it signals either unexpected reward or anticipation of reward resulting from a particular action or event. Thus, dopamine provides positive reinforcement of behaviours that lead to these rewards, causing them to be repeated. Conversely, where a particular action fails to produce the expected positive effect or is followed by an unpleasant event, dopamine release decreases sharply, leading to frustration and an unwillingness to repeat the behaviour in question.

    Many dopamine neurons produce these learning signals by emitting rapid bursts of spikes when the animal receives more reward than expected or pausing when there is less than expected. In order to govern the learning correctly, the number of bursts (and the dopamine released) must be proportional to the discrepancy between the received and the expected reward (for example if one expects to get 50 euros for his work, but gets 100; the dopamine activity should be proportional to 50; when one expects 50 but gets 500; the activity should signal a number proportional to 450). Hence the bigger the mismatch — the stronger the response. Yet another subgroup of dopamine neurons simply signals when stimuli are important for behaviour or not giving binary all or none responses. These binary signals then drive orienting or approach to the important behaviors. So the two dopamine cell populations have different response modes: analogue learning signal or all-or-none important alert.

    Two Modes of neuron Activity

    Recent research by Gutkin’s group conducted jointly with scientists from Indiana University (Alexey Kuznetsov, Mathematics and Christopher Lapish, Neuroscience) and the RAN Institute of Applied Physics (Denis Zakharov) suggests potential mechanisms of alcohol’s effect on dopaminergic neuronal activity. Their paper ‘Dopamine Neurons Change the Type of Excitability in Response to Stimuli’ published in PLOS features a computational model of dopamine (DA) neuron activity, describing its key properties and demonstrating that the DA neuron’s response mode can vary depending on the pattern of the synaptic input (including that from the prefrontal cortex).

    When in the first mode, the amount of dopamine released by the DA neurons reflects the learning signal propotional to the difference between what an animal or human expects and what they actually receive as a result of a certain action. When in the second DA neuron mode, dopamine release serves as a reference binary signal indicating whether or not a certain event is important. Hence the results of the computational study imply that dopamine neurons may not be two distinct populations, but are capable to move flexibly from one response mode to another depending on the nature of the signals they receive.

    In a related study, ‘Contribution of synchronized GABAergic neurons to dopaminergic neuron firing and bursting’, published in the Journal of Neurophysiology the same group suggests that in addition to direct links between DA and prefrontal cortex neurons, indirect neural inputs from the prefrontal cortex via inhibitory (GABAergic) VTA neurons should be considered. In particular, the researchers found that signals from the prefrontal cortex can cause GABAergic neurons to synchronise, producing a strong inhibitory effect on DA neurons. The study found that in some cases, such inhibitory effects can lead to paradoxical results: instead of suppressing DA neuron firing and thus decreasing dopamine release, they can multiply DA firing frequency leading to higher dopamine release and positive reinforcement.

    What It Means for Our Understanding of Alcoholism

    Experimental evidence suggests that alcohol is capable of modifying DA neuron firing patterns, both indirectly via prefrontal cortex and inhibitory VTA neurons, and directly by acting on DA neurons per se. Based on Gutkin and his collaborators findings, one can hypothesise what mechanisms may be involved.

    The VTA has about 20,000 DA neurons, in someone who is not alcoholic, some of these serve to signal that a certain stimulus has importance, while the rest transmit the error signal. A certain balance between the two types of signals is essential for good judgment and proper behaviour. Alcohol disrupts the balance by changing both the pattern of neural activity in the prefrontal cortex and DA neuron properties. This change may bias more neurons to signal importance as opposed to the error. So, under alcohol influence, any stimulus associated with alcohol is treated by DA neurons as having behavioural and motivational importance, regardless of whether or not it matches the anticipated outcome, while in the absence of alcohol, neural firing would normally be consistent with the expected and received reinforcements.

    This effect may be the reason why alcoholics may eventually develop a narrower than normal range of behavioural responses, dooming them to seek to use alcohol. In doing so, they are either unaware of potential consequences of their actions or, even if they can anticipate such consequences, this awareness has little or no effect on their behaviour. According to surveys, most alcoholics understand that they may lose their home and family and even die from binge drinking, but this rarely stops them. To properly assess the consequences of drinking, their prefrontal cortex needs to integrate and learn to properly represent the negative expectations from this behaviour, supported by reinforcement learning signals from DA neurons. This may not happen, however, because alcohol (like other mood-altering substances) can affect both the neural activity in the addict’s prefrontal cortex and their DA neurons directly, blocking the learning.

    Finding a way to balance out the dopamine function in the addicted brain and to elicit adequate neural responses to environmental stimuli even under the influence could offer hope to people with substance abuse problems.


  6. Pinpointing the mechanisms that underlie emotional responses to pain

    March 14, 2017 by Ashley

    From the JCI media release:

    Pain serves as a warning signal to indicate the intensity and location of damage to the body. In addition to unpleasant sensations, painful events trigger negative emotional responses that may serve to reinforce pain-avoiding behaviors. However, in chronic inflammatory conditions, negative emotional states associated with long-term pain can put affected individuals at a higher risk for psychiatric complications such as depression or substance abuse.

    Signaling by molecules called prostaglandins plays a key role in the body’s response to inflammation. Prostaglandins been linked to the sensory perception of pain, but their role in the emotional response to pain is unclear. This week in the JCI, a study conducted by David Engblom’s lab at Linköping University in Sweden has demonstrated that the aversive effects of inflammatory pain are driven by prostaglandin signaling specifically on serotonin-producing neurons in the brainstem.

    When the researchers selectively blocked prostaglandin synthesis in neurons, mice displayed reduced aversive responses to inflammation-induced pain. Furthermore, mice lacking prostaglandin receptors on serotonin-producing neurons and mice lacking the serotonin transporter also exhibited less pain-avoidance behavior. Prostaglandin signaling in serotonin neurons was not required for aversive responses to high temperatures, suggesting that this pain-aversive signaling pathway is specific to inflammatory pain. These findings suggest that the effects of prostaglandin on serotonin signaling are key drivers of the emotional response to pain, implicating a pathway that may be targeted in future therapeutics for managing pain in chronic inflammatory conditions.


  7. How dopamine governs ongoing decisions

    March 13, 2017 by Ashley

    From the Salk Institute media release:

    Say you’re reaching for the fruit cup at a buffet, but at the last second you switch gears and grab a cupcake instead. Emotionally, your decision is a complex stew of guilt and mouth-watering anticipation. But physically it’s a simple shift: instead of moving left, your hand went right. Such split-second changes interest neuroscientists because they play a major role in diseases that involve problems with selecting an action, like Parkinson’s and drug addiction.

    In the March 9, 2017 online publication of the journal Neuron, scientists at the Salk Institute report that the concentration of a brain chemical called dopamine governs decisions about actions so precisely that measuring the level right before a decision allows researchers to accurately predict the outcome. Additionally, the scientists found that changing the dopamine level is sufficient to alter upcoming choice. The work may open new avenues for treating disorders both in cases where a person cannot select a movement to initiate, like Parkinson’s disease, as well as those in which someone cannot stop repetitive actions, such as obsessive-compulsive disorder (OCD) or drug addiction.

    “Because we cannot do more than one thing at a time, the brain is constantly making decisions about what to do next,” says Xin Jin, an assistant professor in Salk’s Molecular Neurobiology Laboratory and the paper’s senior author. “In most cases our brain controls these decisions at a higher level than talking directly to particular muscles, and that is what my lab mostly wants to understand better.”

    When we decide to perform a voluntary action, like tying our shoelaces, the outer part of our brain (the cortex) sends a signal to a deeper structure called the striatum, which receives dopamine to orchestrate the sequence of events: bending down, grabbing the laces, tying the knots. Neurodegenerative diseases like Parkinson’s damage the dopamine-releasing neurons, impairing a person’s ability to execute a series of commands. For example, if you ask Parkinson’s patients to draw a V shape, they might draw the line going down just fine or the line going up just fine. But they have major difficulty making the switch from one direction to the other, and spend much longer at the transition. Before researchers can develop targeted therapies for such diseases, they need to understand exactly what the function of dopamine is at a fundamental neurological level in normal brains.

    Jin’s team designed a study in which mice chose between pressing one of two levers to get a sugary treat. The levers were on the right and left side of a custom-built chamber, with the treat dispenser in the middle. The levers retracted from the chamber at the start of each trial and reappeared after either two seconds or eight seconds. The mice quickly learned that when the levers reappeared after the shorter time, pressing the left lever yielded a treat. When they reappeared after the longer time, pressing the right lever resulted in a treat. Thus, the two sides represented a simplified two-choice situation for the mice — they moved to the left side of the chamber initially, but if the levers didn’t reappear within a certain amount of time, the mice shifted to the right side based on an internal decision.

    “This particular design allows us to ask a unique question about what happens in the brain during this mental and physical switch from one choice to another,” says Hao Li, a Salk research associate and the paper’s co-first author.

    As the mice performed the trials, the researchers used a technique called fast-scan cyclic voltammetry to measure dopamine concentration in the animals’ brains via embedded electrodes much finer than a human hair. The technique allows for very fine-time-scale measurement (in this study, sampling occurred 10 times per second) and therefore can indicate rapid changes in brain chemistry. The voltammetry results showed that fluctuations in brain dopamine level were tightly associated with the animal’s decision. The scientists were actually able to accurately predict the animal’s upcoming choice of lever based on dopamine concentration alone.

    Interestingly, other mice that got a treat by pressing either lever (so removing the element of choice) experienced a dopamine increase as trials got under way, but in contrast their levels remained above baseline (didn’t fluctuate below baseline) the entire time, indicating dopamine’s evolving role when a choice is involved.

    “We are very excited by these findings because they indicate that dopamine could also be involved in ongoing decision, beyond its well-known role in learning,” adds the paper’s co-first author, Christopher Howard, a Salk research collaborator.

    To verify that dopamine level caused the choice change, rather than just being associated with it, the team used genetic engineering and molecular tools — including activating or inhibiting neurons with light in a technique called optogenetics — to manipulate the animals’ brain dopamine levels in real time. They found they were able to bidirectionally switch mice from one choice of lever to the other by increasing or decreasing dopamine levels.

    Jin says these results suggest that dynamically changing dopamine levels are associated with the ongoing selection of actions. “We think that if we could restore the appropriate dopamine dynamics — in Parkinson’s disease, OCD and drug addiction — people might have better control of their behavior. This is an important step in understanding how to accomplish that.”


  8. Baby boomers on a bender: Emerging trends in alcohol binge and use disorders among older adults

    December 12, 2016 by Ashley

    From the New York University media release:

    Alcohol is the most commonly used psychoactive substance among older adults, and this group can have unique risks associated with alcohol consumption — in even lower amounts — compared to younger persons.

    Older adults have particular vulnerabilities to alcohol due to physiological changes during aging, including increasing chronic disease burden and medication use,” said Benjamin Han, MD, MPH, a geriatrician and health services researcher at the Center for Drug Use and HIV Research (CDUHR) and in the Division of Geriatric Medicine and Palliative Care at NYU Langone Medical Center (NYU Langone). “However, no recent studies have estimated trends in alcohol use, including binge alcohol use and alcohol use disorders among older adults.”

    To address the lack of research, Dr. Han and his team examined data from the National Survey on Drug Use and Health (years 2005 to 2014) in a paper published in the journal Drug and Alcohol Dependence. Trends of self-reported past-month binge alcohol use and alcohol use disorder were examined among adults age 50 and older. The researchers found significant increases in past-year alcohol use, past-month alcohol use, past-month binge drinking, and alcohol use disorders. The paper, “Demographic trends of binge alcohol use and alcohol use disorders among older adults in the United States, 2005-2014.” Published on-line 12 December 2016.

    Results also suggest that while men had a higher prevalence of binge alcohol use and alcohol use disorders than women, binge alcohol use and alcohol use disorder increased among women in this nationally representative sample.

    “As females age, they tend to experience a larger impact of physiological changes in lean body mass compared to men,” commented Dr. Han. “Thus, they may experience the adverse effects associated with consuming alcohol even in lower amounts.”

    “The increase in binge drinking among older women is particularly alarming” said Dr. Palamar, PhD, MPH, a CDUHR affiliated researcher and an assistant professor of Population Health at NYU Langone. “Both men and women are at risk for getting themselves into risky sexual situations while drinking, but women are at particularly high risk.” Dr. Palamar also stated that “heavy drinking can not only have unintended health consequences, but it can also lead to socially embarrassing or regretful behavior.”

    For the researchers, the results also raise public health concerns, given the significant increases in binge alcohol use among older adults who reported “fair/poor” health and/or multiple chronic conditions. This population is particularly vulnerable to the negative effects of alcohol as it can impact chronic disease management or increase the risk of injury.

    Health care providers need to be made aware of this increasing trend of unhealthy alcohol use, particularly among older females, and ensure that screening for unhealthy alcohol use is part of regular medical care for this population” said Dr. Han.


  9. Telephone-based intervention shows promise in combating alcohol abuse among soldiers

    November 8, 2016 by Ashley

    From the University of Washington media release:

    alcohol bottlesAlcohol abuse is pervasive in the military, where a culture of heavy drinking and the stress of deployment lead many soldiers down a troubled path.

    Almost half of active-duty military members in the United States — 47 percent — were binge-drinkers in 2008, up from 35 percent a decade earlier. Rates of heavy drinking also rose during that period, according to a 2012 report by the Institute of Medicine. But many in the military avoid seeking help for alcohol abuse, fearing disciplinary action or other repercussions, and few soldiers are referred for evaluation or treatment.

    “If you’re in the military and you seek substance abuse treatment, your commanding officer is notified and it goes on your medical record and your military record. That’s a huge barrier,” said Denise Walker, director of the Innovative Programs Research Group at the University of Washington School of Social Work.

    Not surprisingly, there is little research on what type of treatment is most effective for active-duty military members. To shed new insight on that question and remove obstacles to seeking treatment, Walker and a team of researchers tested a telephone-based intervention geared specifically to military members struggling with alcohol abuse — with promising results.

    The study, published online Oct. 13 in October in the Journal of Consulting and Clinical Psychology, found that participants in the telephone intervention significantly reduced their drinking over time, had lower rates of alcohol dependence and were more likely to seek treatment.

    The trial involved 242 military members at Joint Base Lewis-McChord in western Washington, who were recruited through advertisements and informational booths at military events. All met the criteria for alcohol use disorder, though none were enrolled in substance abuse treatment programs.

    Participants had an initial interview by phone to assess their daily and monthly alcohol consumption. They were also asked a series of questions about the consequences of their drinking — for example, whether it had impacted their physical training or interfered with their ability to fulfill their duties.

    Then participants were randomized to a treatment or control group. The control group received educational information about alcohol and other drug use, while the treatment group got a one-hour personalized intervention session over the phone that used “motivational interviewing,” a goal-oriented approach intended to help people make positive behavioral changes.

    “The intervention really connects their behavior with their values and goals and wants for themselves,” Walker said. “It’s a safe place to talk confidentially and freely with someone on the other end who is compassionate and non-judgmental.”

    The counselors also asked participants about their alcohol consumption versus that of their peers, to gauge whether excessive drinking was in part spurred by normative perceptions about alcohol use in the military.

    “The army has a culture of drinking, so there’s a heightened sense among soldiers that their peers are drinking more than they actually are,” said Thomas Walton, project director for the study and a UW doctoral student in social work.

    When those perceptions are corrected, it can have a strong effect, as heavy-drinking soldiers often reduce their intake to more typical levels.”

    Follow-up interviews were conducted three and six months after the sessions and showed significant decreases in both drinking rates and alcohol dependence. Intervention group participants went from drinking 32 drinks weekly on average to 14 drinks weekly after six months, and their rates of alcohol dependence dropped from 83 to 22 percent. Alcohol dependence also decreased in the control group, from 83 to 35 percent.

    “Those are pretty dramatic reductions in drinking, particularly for one session with a counselor,” Walker said. “That was really encouraging.”

    Participants increasingly sought treatment over time; by the six-month follow-up, nearly one-third of soldiers in both groups had made some move toward seeking treatment, such as discussing substance abuse concerns with an army chaplain or making an appointment for treatment intake. While the intervention led to more dramatic decreases in drinking, providing educational information may be enough to prompt some to take a first step toward making a change, the researchers said.

    Walker and Walton attribute the intervention’s success to its convenience and confidentiality. Participants could enroll without fear of their superiors finding out — recruitment materials made it clear that military command was not involved — and could schedule the phone calls at their convenience.

    “Some did the session on their lunch breaks or in the garage while their family was in the house,” Walker said. “They didn’t have to walk into a building that says ‘army substance abuse program.’ It was private and a low-burden intervention.”

    And though the military offers substance abuse programs, Walker said, many soldiers avoid seeking help and are not referred to treatment until their problems reach a crisis point.

    People who get into army substance abuse programs are often mandated to go or have gotten into trouble,” she said. “That leaves out a huge proportion of the population who are struggling and not doing well.”

    That reality and the protracted conflicts in Iraq and Afghanistan, Walker said, have intensified the need for additional options to help soldiers grappling with substance abuse and other problems. Telephone-based counseling, she said, is a cost-effective way to encourage military members to seek help confidentially, without the barriers of more traditional approaches.

    This intervention has the potential to be used for soldiers and military personnel worldwide. It would really help fill the gap in service provision that is currently available to soldiers.”


  10. First atomic-level image of the human ‘marijuana receptor’ unveiled

    October 21, 2016 by Ashley

    From the Scripps Research Institute media release:

    marijuanaIn a discovery that advances the understanding of how marijuana works in the human body, an international group of scientists, including those from the Florida campus of The Scripps Research Institute (TSRI), have for the first time created a three-dimensional atomic-level image of the molecular structure activated by tetrahydrocannabinol (THC), the active chemical in marijuana.

    The new insights into the human cannabinoid receptor 1 (CB1) will provide an essential tool for understanding why some molecules related to THC have unexpectedly complex and sometimes harmful effects. The findings also have the potential to guide drug design for pain, inflammation, obesity, fibrosis and other indications.

    The new study, published by the journal Cell, was led by a quartet of scientists: TSRI’s Laura Bohn, Northeastern University’s Alexandros Makriyannis, Shanghai Tech University’s Zhi-Jie Liu and Raymond C. Stevens (also of the University of Southern California).

    At the beginning of the study, the team struggled to produce a crystal form — needed to obtain data to recreate the high-resolution structure — of the receptor bound with AM6538, a stabilizing a molecule that blocks the receptor’s action.

    The CB1 receptor proved as challenging for crystallization as it did for understanding its functional regulation and signaling,” said Bohn, who is a professor in TSRI’s Department of Molecular Therapeutics.

    When the scientists succeeded in crystalizing the receptor and collecting the data, the structure of the cannabinoid receptor complex revealed an expansive and complicated binding pocket network consisting of multiple sub-pockets and channels to various regions of the receptor.

    Cannabinoid receptors are part of a large class of receptors known as G protein-coupled receptors (GPCR), which account for about 40 percent of all prescription pharmaceuticals on the market, and play key roles in many physiological functions. When an outside substance binds to a GPCR, it activates a G protein inside the cell to release components and create a specific cellular response.

    AM6538, is an antagonist/inverse agonist that binds tightly to the receptor; it has a long half-life, making it potentially useful as a treatment of addiction disorders.

    As marijuana continues to become more common in society, it is critical that we understand how it works in the human body,” said Liu, who is professor and deputy director of the iHuman Institute of Shanghai Tech and is also affiliated with the Chinese Academy of Sciences.