August 29, 2017

Opioid Overdose Deaths Double in 7 Years

A study of the growing United States opioid epidemic reveals that deaths from overdoses have nearly doubled over the past seven years, while increasing acute care costs and hospitalizations are taxing health care systems.

The paper, "The Critical Care Crisis of Opioid Overdoses in the United States" published in the Annals of the American Thoracic Society is believed to be the first to quantify the impact of opioid abuse on critical care resources in the U.S. The findings reveal that opioid-related demand for acute care services has outstripped the available supply.

In the cohort study, researchers from Ben-Gurion University of the Negev (BGU) in Israel, Harvard Medical School and University of Chicago analyzed nearly 23 million adult hospital admissions at 162 hospitals in 44 states over a seven-year period: January 1, 2009 through September 30, 2015. Among the more than 4 million patients requiring acute care, the researchers found 21,705 who were admitted to intensive care units (ICU) due to opioid overdoses. Admissions included overdoses for prescription drugs, methadone or heroin.

Opioid Admissions Up 34 Percent

"We found a 34 percent increase in overdose-related ICU admissions while ICU opioid deaths nearly doubled during that same period," according to Dr. Lena Novack, Ph.D., a lecturer in BGU's School of Public Health. The mortality rates of these patients climbed at roughly the same rate, on average, with a steeper rise in deaths of patients admitted to the ICU for overdose after 2012.

The average cost of care per ICU overdose admission also rose significantly - 58 percent - from $58,517 in 2009 to $92,408 in 2015. In addition, the study indicated that opioid-related ICU admissions increased an average of more than half a percent each year over the seven-year timeframe, jumping from seven percent to 10 percent by the end of the study period.

Patients admitted to the ICU due to an overdose increasingly required intensive care, including high-cost renal replacement therapy or dialysis.

Community Emergency Response

Admissions were identified using the Clinical Data Base/Resource ManagerTM of Vizient, Inc., which is comprised of data mainly from urban academic medical centers and may not reflect overdose-related acute care needs in other settings.

"Our estimates may actually be on the low side," Dr. Novack says. Since our team of researchers analyzed admissions rather than a manual chart review, we may not have captured every admission if opioid-related complications weren't coded as such."

The study also did not determine whether increased ICU admissions for opioid overdoses resulted from improved community emergency response that may have saved lives but then required critical care, or whether the increased ICU admissions indicated that community emergency response needs improvement so patients require a less intensive hospital care.

States With the Highest Opioid Hospitalizations

The researchers found that Massachusetts and Indiana have the highest opioid admission densities in the nation. Pennsylvania experienced the sharpest rise in opioid-related overdoses during the study period, with critical care overdose admissions nearly doubling since 2009. Illinois, California, New York, and Indiana have also experienced ICU admission rate increases during the period.

"Our findings raise the need for a national approach to developing safe strategies to care for ICU overdose patients, to providing coordinated resources in the hospital for patients and families, and to helping survivors maintain sobriety following discharge," the researchers conclude.

Posted by Webmaster at 08:39 AM

August 14, 2017

Aggression Linked to Risk of Substance Abuse

People who have trouble controlling their anger are more likely to abuse alcohol and other substances. Those who display frequent aggressive behavior are at five times greater risk for abusing alcohol, tobacco and marijuana.

According to researchers at the University of Chicago Medical Center, patients with intermittent explosive disorder (IED) are much more likely to become substance abusers compared to those who do not display frequent aggressive behavior.

The study examined data from more than 9,200 subjects in the in the National Comorbidity Survey, a national survey of mental health in the United States.

Aggression Linked to Substance Abuse


The investigators found that as the severity of aggressive behavior increases so do levels of daily and weekly substance abuse. A history of frequent, aggressive behavior is a predictor of later substance abuse, they concluded.

IED is a condition marked by frequent physical or verbal outburts and affects an estimated 16 million people in the United States -- more than bipolar disorder and schizophrenia combined. It is typically diagnosed in adolescents, some as young as 11, long before substance abuse problems develop.

The condition runs in families and is generally treated as a social-behavior issue rather than a true neurobiological disorder with significant genetic components, said Emil Coccaro, MD.

More Than Simply Bad Behavior


"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.

The Chicago study found no relationship between IED and the presences of other psychiatric disorders, as has been implied by previous research.

Although excessive alcohol use can clearly worsen aggressive behavior, Coccaro and colleagues found that IED diagnosis almost always precedes the development of chronic substance abuse. In cases where subjects were diagnosed with both disorders, IED preceded substance abuse in 92.5% of the cases.

Early Treatment Is Effective


The good news is if intermittent explosive disorder and aggression is treated early it can delay or even prevent substance abuse later in life. "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," Coccaro said.

Source: Coccaro EF, et al. "Intermittent Explosive Disorder and Substance Use Disorder: Analysis of the National Comorbidity Survey Replication Sample." Journal of Clinical Psychiatry Feb. 28, 2017

Posted by Webmaster at 03:21 AM

August 13, 2017

Drug-Use Can Hamper Moral Judgment

Regular cocaine and methamphetamine users can have difficulty choosing between right and wrong, perhaps because the specific parts of their brains used for moral processing and evaluating emotions are damaged by their prolonged drug habits. This is according to a study among prison inmates by Samantha Fede and Dr. Kent Kiehl's laboratory at the University of New Mexico and the nonprofit Mind Research Network. The findings of the study, which was funded by the National Institute on Drug Abuse, are published in Springer's journal Psychopharmacology.

Research has shown that stimulant users often find it difficult to identify other people's emotions, particularly fear, and to show empathy. These aspects play an important role in moral decision making. Other studies have pointed to structural and functional abnormalities in especially the frontal regions of their brains among stimulant users. These areas are engaged when moral judgments have to be made.

Drug Use and Criminal Behavior

There is strong link between drug use and criminal behavior, and up to 75 percent of inmates in the US have substance abuse problems. It is not known whether the criminal behavior is in part a result of the drugs' effects on brain function.

Kiehl's team is the first to examine how the neural networks and brain functioning of chronic cocaine and methamphetamine users in US jails relate to their ability to evaluate and decide about moral situations or scenarios. Poor judgment about moral situations can lead to poor decision making and subsequent antisocial behavior.

Chemical Changes in the Brain

The researchers recorded the life history of substance abuse of 131 cocaine and methamphetamine users and 80 non-users incarcerated in New Mexico and Wisconsin prisons. The participants' brains were scanned while they completed a moral decision-making task in which they evaluated whether certain phrases were morally wrong or not.

Compared to the non-users, the regular stimulant users had abnormal neural activity in the frontal lobes and limbic regions of their brains during moral processing. Specifically, lifetime stimulant users showed less activity in the amygdala, a group of neurons in the brain that helps to regulate and understand emotions. The researchers also observed a relationship in the level of engagement of the anterior cingulate cortex: the longer people had been using stimulants, the less activity in this region. This is an area of the brain that coordinates reinforcement, effect and executive action needed in moral decision making.

Impaired Decision-Making

"This is the first study to suggest impairments in the neural systems of moral processing in both cocaine and methamphetamine users," says lead author Fede. "Although further research into the connectivity of systems in stimulant use is needed, this provides promising initial understanding of fronto-limbic deficits in stimulant users."

The research team acknowledges that people who are prone to regular stimulant use might already struggle with moral processing even before they begin to use drugs such as cocaine. The effects found related to use over time in the anterior cingulate cortex and the ventromedial prefrontal cortex, another region implicated in moral decision making, however, indicate that methamphetamine and cocaine may have a serious impact on the brain.

Posted by Webmaster at 08:06 PM

Childhood Defiance Linked to Addiction

Children who exhibit oppositional behavior run the risk of becoming addicted to nicotine, cannabis and cocaine while inattention symptoms represent a specific additional risk of nicotine addiction. Nevertheless, hyperactivity in itself does not seem to be associated with any specific risk of substance abuse or dependence.

This is what researchers at the Sainte-Justine University Hospital Center's (UHC) Research Center and the University of Montreal concluded following a 15-year population-based study published in Molecular Psychiatry.

Evaluated by Their Mothers

In order to delineate the roles played by inattention, hyperactivity, opposition, anxiety and adversity, the behavior of 1,803 children between 6 and 12 years of age were evaluated annually by their mothers and teachers. Over half the participants were females. The study revealed that by the age of 21, 13.4% were either abusing or addicted to alcohol, 9.1% to cannabis, and 2.0% to cocaine. Tobacco addiction was a problem for 30.7 % of the participants.

The link between attention deficit hyperactivity disorder (ADHD) in childhood and substance abuse in adulthood was already known. However, very few studies have been undertaken into the particular and respective roles of behavioural symptoms such as opposition that are often concomitant with ADHD (without being part of the disorder), attention deficit and hyperactivity. Furthermore, at least as many girls as boys were sampled in order to assess the potential impact of gender on the findings.

Cannabis and Cocaine Use

"By taking into account the unique effect of inattention and hyperactivity, which had seldom been considered separately before, we came to realize that the link between ADHD symptoms in childhood and substance abuse in adulthood was overestimated and hyperactivity in itself did not seem, in this study, to predispose for future substance abuse," observed Dr. Jean-Baptiste Pingault, a postdoctoral fellow and first author of the study conducted under the supervision of Drs Sylvana Côté and Richard E. Tremblay, both researchers at the Sainte-Justine UHC's Research Center and professors at the University of Montreal.

"We have rather observed strong oppositional behaviors to be associated with cannabis and cocaine abuse. In ADHD symptoms, only inattention is closely correlated with nicotine addiction," he continued. As for the impact of gender on findings, the study reveals opposition and inattention play a largely identical role in girls and boys. However, within the context of the study, it was established that boys consumed more cannabis and alcohol, while girls smoked more cigarettes.

Opposition and Drug Addiction

The strongest behavioral predictor of substance abuse lies in frequent oppositional behavior in childhood, which can be recognized through traits such as irritability, being quick to "fly off the handle," disobedience, refusal to share materials with others to carry out a task, blaming others and being inconsiderate of others. In fact, in strongly oppositional children, the risk of tobacco abuse, once other factors were taken into account, was 1.4 times higher than in children who exhibited little oppositional behavior.

The risk is 2.1 times higher for cannabis abuse and 2.9 times higher for cocaine abuse. It should be noted that the mothers' evaluations provided further essential information in relation to the teachers' evaluations. In fact, some children who were declared highly oppositional by their mothers, but not at all by their teachers, also ran a higher risk of substance abuse and addiction.

Inattention and Smoking

The other important correlation established by the study was the link between inattention and smoking. Very inattentive children had a 1.7-fold increased risk of becoming addicted to tobacco. The degree of inattention even reveals the intensity of future nicotine addiction. The link supported the hypothesis that inattentive people would use tobacco as a "treatment" to help them concentrate.

"If other studies can establish a chemical relation of cause and effect between ADHD symptoms and smoking, we could suppose that treating inattention symptoms would make it easier to quit smoking. Until this is demonstrated, our study's findings nonetheless suggest that the prevention or treatment of inattention and opposition symptoms in children could reduce the risk of smoking and drug abuse in adulthood," concluded Dr. Pingault.

Posted by Webmaster at 07:23 PM

Substance Use Reduces Educational Achievement

Although various kinds of substance use are associated with reduced educational attainment, these associations have been mixed and may also be partially due to risk factors such as socioeconomic disadvantages. A study of substance use and education among male twins from a veteran population has found a strong relationship among early alcohol use, alcohol dependence, daily nicotine use, and fewer years of educational attainment.

Results were published in Alcoholism: Clinical & Experimental Research.

Mixed Results


"Evidence for an association between substance use/abuse/dependence and reduced lifetime educational attainment is mixed," said Julia D. Grant, research assistant professor of psychiatry at Washington University School of Medicine as well as corresponding author for the study.

"In addition," said Matt McGue, a professor in the department of psychology at the University of Minnesota, "what is missing is an explanation for the basis of the association. We might consider two possibilities. One, adolescent substance use results in diminished educational achievement because substance use is neurotoxic to the developing adolescent brain, or because adolescents who use substances have experiences that reduce the likelihood they will pursue higher education."

Another possibility, he added, is that "individuals who use substances in adolescence differ from those who do not on a range of risk factors prior to substance use exposure, which not only lead to their use of substances but also reduce the likelihood they achieve a college education. This possibility means that adolescent substance use is merely an indicator of the risk factors that diminish the likelihood of college attainment."

Lifetime Educational Attainment


"Because our participants were in their late 30s when their educational attainment was assessed, we were better able to address lifetime educational attainment than most previous studies, which have focused on high school dropouts or educational attainment in 18-25 year-olds," said Grant. "We also examined educational attainment in a veteran cohort that had access to education via benefits of the G.I. bill, thereby alleviating some of the economic barriers to higher education that might otherwise be confounded with alcohol and drug outcomes."

Grant and her colleagues examined data collected from two points in time: a 1987 questionnaire, and a 1992 telephone diagnostic interview of 6,242 male twins (n=3,121 pairs with a mean age of 41.9 years in 1992) who had served in the U.S. military during the Vietnam-era and were therefore eligible for educational benefits after military service. Specific factors addressed were reduced educational attainment – defined as less than 16 years – as well as early alcohol and cannabis use, daily nicotine use, lifetime cannabis use, and alcohol, nicotine, cannabis, and any illicit drug dependence.

"Although all substance use measures were associated with lower educational attainment in preliminary analyses," said Grant, "only early alcohol use, alcohol dependence, and daily nicotine use remained significantly associated with reduced educational attainment in twin pairs discordant for substance use. In contrast, the associations between cannabis/other illicit drugs and educational attainment were not significant, suggesting that this association may be attributable to familial influences shared by the two measures."

Sober Twin More Likely to Finish College


"In this study, they conclude that within twin pairs discordant for adolescent substance use, the unexposed twin was more likely to complete college than his/her exposed cotwin," said McGue. "This provides much stronger support for a causal influence than a standard epidemiological study because of the control afforded by comparing the discordant twins. However, it is important to recognize that it does not prove causality."

"It is possible that early alcohol use and alcohol dependence impede later educational attainment," noted Grant. "Possible mechanisms for this include cognitive and motivational changes stemming from early alcohol use/dependence that hinder academic success. Although daily nicotine use is not likely to impair cognitive functioning, it may lead to motivational changes that affect academic performance. It is also possible that the association between these substances and lower educational attainment remains because both are attributable to a factor that we did not control for in our present analyses, such as personality characteristics and cognitive ability prior to substance use."

Complicated Relationship


Grant said these findings underscore the complicated relationship between substance use and educational attainment.

"By controlling for all familial influences that contribute to both substance use and educational attainment, through our discordant twin design, we have a much stronger indicator of the direct association between substance use and educational attainment," she said. "However, because we were studying higher levels of education – 16+ years – in high school graduates, we may have understated the true effect of alcohol on education. It may be that these effects are more pronounced at even lower levels of education. Nonetheless, our findings lend credence to ongoing public health efforts to reduce adolescent smoking and drinking, which in turn may have beneficial effects on school dropout and lifelong educational attainment."

Posted by Webmaster at 07:07 PM

Opioids Linked With Highest Risk of Death

People with an opioid addiction had the highest risk of death when compared with rates for alcohol and other drugs, according to a new study by the Centre for Addiction and Mental Health (CAMH). For those dependent on opioids, the risk of death was 5.71 times higher than healthy individuals in the population of the same age, gender and race.

Those with methamphetamine use disorders were next highest with a 4.67-fold risk, followed by those with addictions to cannabis (3.85), alcohol (3.83) and cocaine (2.96). Alcohol dependence was related to the highest number of deaths overall.

Mortality Rates Among Drug Users

The study, available online in the journal Drug and Alcohol Dependence, is the largest North American study to compare mortality rates among different drug users with the longest follow-up. It tracked records of more than 800,000 individuals hospitalized with drug dependence between 1990 and 2005. Of this group, more than 188,000 died during this period.

The findings mean that if 10 individuals in the general population died, then over the same period there would be 57 deaths among people dependent on opioids, which includes prescription opioids as well as heroin.

"One reason for undertaking this study was to examine whether methamphetamine posed a particular threat to drug users, as it has been called 'America's most dangerous drug,'" says CAMH Scientist Dr. Russell Callaghan, who led the study. Globally, methamphetamine and similar stimulants are the second most commonly used class of illicit drugs.

High Risk of Death

"The risk is high, but opioids are associated with a higher risk. We also wanted to compare mortality risks among several major drugs of abuse, as this comparison hasn't been done on this scale before."

Alcohol dependence affected the highest number of individuals, with 166,482 deaths and 582,771 hospitalizations over the study period. In the methamphetamine group, there were 4,122 deaths out of 74,139 hospitalizations, and for opioids, 12,196 deaths out of 67,104 hospitalizations.

Specific causes of mortality were not examined in this study, so the deaths may not be directly caused by drugs but due to related injuries, infectious disease or unrelated reasons. The researchers are now exploring mortality causes for each drug group, which may also point to reasons why women had a higher risk of death for alcohol, cocaine and opioids than males.

"These are not occasional, recreational drug users, but people who have been hospitalized for drug dependence," notes co-author Dr. Stephen Kish, Senior Scientist at CAMH.

To calculate mortality rates, Dr. Callaghan and colleagues examined hospital records of all California inpatients with a diagnosis of methamphetamine, alcohol, opioid, cannabis or cocaine-related disorders from 1990-2005. They excluded records with evidence of multiple drug use disorders. The inpatient records were then matched to death records from the California Vital Statistics Database. Rates were adjusted by age, sex and race to the California population in 2000.

Risk Greater for Marijuana Users

"One surprising finding was the high rate of death among cannabis users," says Dr. Callaghan. "There could be many potential reasons, including the fact that they may have other chronic illnesses such as psychiatric illnesses or AIDS, which can also increase the risk of death."

The findings point to the importance of brief interventions for people receiving medical care for drug dependence on other related risks such as infectious diseases or injuries, says Dr. Callaghan.

Posted by Webmaster at 06:59 PM

Chronic Cocaine Use Hastens Aging of Brain

Research by scientists at the University of Cambridge suggests that chronic cocaine abuse accelerates the process of brain ageing. The study, published in Molecular Psychiatry, found that age-related loss of grey matter in the brain is greater in people who are dependent on cocaine than in the healthy population.

For the study, the researchers scanned the brains of 120 people with similar age, gender and verbal IQ. Half of the individuals had a dependence on cocaine while the other 60 had no history of substance abuse disorders.

Loss of Brain Volume

The researchers found that the rate of age-related grey matter volume loss in cocaine-dependent individuals was significantly greater than in healthy volunteers. The cocaine users lost about 3.08 ml brain volume per year, which is almost twice the rate of healthy volunteers (who only lost about 1.69 ml per year). The accelerated age-related decline in brain volume was most prominent in the prefrontal and temporal cortex, important regions of the brain which are associated with attention, decision-making, and self-regulation as well as memory.

Previous studies have shown that psychological and physiological changes typically associated with old age such as cognitive decline, brain atrophy and immunodeficiency are also seen in middle-aged cocaine-dependent individuals. However, this is the first time that premature ageing of the brain has been associated with chronic cocaine abuse.

Premature Aging

Dr Karen Ersche, of the Behavioural and Clinical Neuroscience Institute (BCNI) at the University of Cambridge, said: "As we age, we all lose grey matter. However, what we have seen is that chronic cocaine users lose grey matter at a significantly faster rate, which could be a sign of premature ageing. Our findings therefore provide new insight into why the cognitive deficits typically seen in old age have frequently been observed in middle aged chronic users of cocaine."

The scientists also highlight concerns that premature ageing in chronic cocaine users is an emerging public health concern. The United Nations Office on Drugs and Crime estimates that cocaine is used by up to 21 million individuals worldwide, with approximately 1 per cent of these individuals becoming dependent.

Dr Ersche said: "Our findings clearly highlight the need for preventative strategies to address the risk of premature ageing associated with cocaine abuse. Young people taking cocaine today need to be educated about the long-term risk of ageing prematurely."

An Issue for Older Adults Too

The concern of accelerated ageing is not limited to young people but also affects older adults who have been abusing drugs such as cocaine since early adulthood.

Dr Ersche added: "Our findings shed light on the largely neglected problem of the growing number of older drug users, whose needs are not so well catered for in drug treatment services. It is timely for heath care providers to understand and recognise the needs of older drug users in order to design and administer age-appropriate treatments."

Posted by Webmaster at 06:55 PM

Doctors Lax in Monitoring Addicting Drugs

Few primary care physicians pay adequate attention to patients taking prescription opioid drugs — despite the potential for abuse, addiction and overdose, according to a study by researchers at Albert Einstein College of Medicine of Yeshiva University.

The study, published in the Journal of General Internal Medicine, found lax monitoring even of patients at high risk for opioid misuse, such as those with a history of drug abuse or dependence. The findings are especially concerning considering that prescription drug abuse now ranks second (after marijuana) among illicitly used drugs, with approximately 2.2 million Americans using pain relievers nonmedically for the first time in 2009, according to the National Institute on Drug Abuse (NIDA).

Missed Prevention Opportunity

"Our study highlights a missed opportunity for identifying and reducing misuse of prescribed opioids in primary care settings," said lead author Joanna Starrels, M.D., M.S. , assistant professor of medicine at Einstein. "The finding that physicians did not increase precautions for patients at highest risk for opioid misuse should be a call for a standardized approach to monitoring."

The researchers studied administrative and medical records of more than 1,600 primary care patients for an average of two years while they received regular prescription opioids for chronic, non-cancer pain. They looked at whether patients received urine drug testing, were seen regularly in the office, or received multiple early opioid refills.

Few Given Urine Tests

Only a small minority (8 percent) of patients were found to have undergone any urine drug testing. While such testing was more common in patients at higher risk for opioid misuse, the rate of testing among those high-risk patients was still low (24 percent). Only half of patients were seen regularly in the office, and patients at higher risk of opioid misuse were not seen more frequently than patients at lower risk. Although fewer than one-quarter (23 percent) of all patients received two or more early opioid refills, patients at greater risk for opioid misuse were more likely to receive multiple early refills.

"We were disturbed to find that patients with a drug use disorder were seen less frequently in the office and were prescribed more early refills than patients without these disorders," said Dr. Starrels. "We hope that these findings will call attention to this important safety concern."

Prescription Drug Misuse Problem

Prescription drug misuse is a major public health problem. In a 2004 NIDA report , it was estimated that 48 million people over the age of 12 have taken prescription drugs for nonmedical uses in their lifetime – which represents approximately 20 percent of the U.S. population. Opioids, central nervous system depressants and stimulants were the drugs most commonly abused.

"Most primary care physicians are attuned to these problems," said Dr. Starrels, "but they haven't put sufficient strategies in place to help reduce risks." She and her co-authors recommend that physicians adopt the following risk-reduction strategies: standardize a plan of care for all patients on long-term opioids, which includes urine drug testing; schedule regular face-to-face office visits to evaluate patients' response to opioids and evidence of misuse; and stick to a previously agreed-upon refill schedule.

Posted by Webmaster at 11:49 AM

Child Abuse: Malicious Use of Pharmaceuticals

Child abuse is a serious problem that affects nearly one million children a year in the United States alone. The American Academy of Pediatrics and the US Department of Health and Human Services classify child abuse into four categories including neglect, physical abuse, sexual abuse, and emotional abuse. None of these categories, however, clearly includes the abusive use of drugs on children. A study published in the Journal of Pediatrics investigates the malicious use of pharmaceuticals and attempts to shed light on this under-recognized problem.

Dr. Shan Yin from the University of Colorado and the Rocky Mountain Poison Drug Center at Denver Health reviewed cases of pharmaceutical abuse reported to the National Poison Data System between 2000 and 2008. Dr. Yin included reports of the malicious use of alcohol, painkillers, cough and cold medicines, sedatives and sleeping pills, and antipsychotic medicines.

Using Drugs to Subdue Children

Of the more than 1400 cases studied, nearly 14% resulted in moderate to major consequences, including death. Nearly one-half of the abused children were exposed to at least one sedative. An average of 160 cases, including two deaths, was reported each year. Motives and legal findings were unavailable for these particular cases; however, motives for the abusive use of drugs generally are varied, and can include punishment, amusement, or a wish for a break from childcare responsibilities.

This study illustrates the seriousness of the abusive use of drugs administered to children. According to Dr. Yin, "The malicious administration of pharmaceuticals should be considered an important form of child abuse." He encourages pediatricians and emergency medical personnel to be on the watch for this form of maltreatment, and suggests the use of comprehensive drug screening during the evaluation of a child suspected to be the victim of abuse. Dr. Yin also cautions parents that the "non-therapeutic administration of pharmaceuticals to children can result in serious outcomes, including death."

Posted by Webmaster at 10:26 AM

Addiction: a Loss of Plasticity of the Brain?

Why is it that only some drug users become addicts? This is the question that has been addressed by the teams of Pier Vincenzo Piazza and Olivier Manzoni, at the Neurocentre Magendie in Bordeaux (Inserm unit 862). These researchers have discovered that the transition to addiction could result from a persistent impairment of synaptic plasticity in a key structure of the brain. This is the first demonstration that a correlation exists between synaptic plasticity and the transition to addiction.

The results from the teams at Neurocentre Magendie call into question the hitherto held idea that addiction results from pathological cerebral modifications which develop gradually with drug usage. Their results show that addiction may, instead, come from a form of anaplasticity, i.e. from incapacity of addicted individuals to counteract the pathological modifications caused by the drug to all users.

This research is published in the journal Science.

Developing Drug Addiction

The voluntary consumption of drugs is a behaviour found in many species of animal. However, it had long been considered that addiction, defined as compulsive and pathological drug consumption, is a behaviour specific to the human species and its social structure. In 2004, the team of Pier Vincenzo Piazza showed that the behaviours which define addiction in humans, also appear in some rats which will self administer cocaine. Addiction exhibits astonishing similarities in men and rodents, in particular the fact that only a small number of consumers (humans or rodents) develop a drug addiction. The study of drug dependent behaviour in this mammal model thus opened the way to the study of the biology of addiction.

Today, thanks to a fruitful collaboration, the teams of Pier Vincenzo Piazza and Olivier Manzoni are reporting discovery of the first known biological mechanisms for the transition from regular but controlled drug taking to a genuine addiction to cocaine, characterised by a loss of control over drug consumption.

Chronic exposure to drugs causes many modifications to the physiology of the brain. Which of these modifications is responsible for the development of an addiction? This is the question the researchers wanted to answer in order to target possible therapeutic approaches to a disorder for which treatments are cruelly lacking.

Some Become Addicted, Some Don't

The addiction model developed in Bordeaux provides a unique tool to answer this question. Thus it allows comparing animals who took identical quantities of drugs, but of which only few become addicted. By comparing addict and non-addict animals at various time points during their history of drug taking, the teams of Pier Vincenzo Piazza and Olivier Manzoni have demonstrated that the animals which developed an addiction to cocaine exhibit a permanent loss of the capacity to produce a form of plasticity known as long term depression (or LTD). LTD refers to the ability of the synapses (the region of communication between neurons) to reduce their activity under the effect of certain stimulations. It plays a major role in the ability to develop new memory traces and, consequently, to demonstrate flexible behaviour.

After short term usage of cocaine, LTD is not modified. However, after a longer use, a significant LTD deficit appears in all users. Without this form of plasticity, which allows new learning to occur, behaviour with regard to the drug becomes more and more rigid, opening the door to development of a compulsive consumption. The brain of the majority of users is able to produce the biological adaptations which allow to counteract the effects of the drug and to recover a normal LTD. By contrast, the anaplasticity (or lack of plasticity) exhibited by the addicts leaves them without defences and hence the LTD deficit provoked by the drug becomes chronic. This permanent absence of synaptic plasticity would explain why drug seeking behaviour becomes resistant to environmental constraints (difficulty in procuring the substance, adverse consequences of taking the drug on health, social life, etc.) and consequently more and more compulsive. Gradually, control of the taking of the drug is lost and addiction appears.

New Treatment for Addiction?

For Pier-Vincenzo Piazza and his collaborators, these discoveries also have important implications for developing new treatment of addiction. "We are probably not going to find new therapies by trying to understand the modifications caused by a drug in the brains of drug addicts," explain the researchers, "since their brain is anaplastic."

For the authors, "The results of this work show that it is in the brain of the non-addicted users that we will probably find the key to a true addiction therapy. Indeed," the authors estimate, "understanding the biological mechanisms which enable adaptation to the drug and which help the user to maintain a controlled consumption could provide us with the tools to combat the anaplastic state that leads to addiction".

Posted by Webmaster at 10:17 AM

Ignoring Stress Leads to Drug Cravings

Recovering addicts who avoid coping with stress succumb easily to substance use cravings, making them more likely to relapse during recovery, according to behavioral researchers. "Cravings are a strong predictor of relapse," said H. Harrington Cleveland, associate professor of human development, Penn State. "The goal of this study is to predict the variation in substance craving in a person on a within-day basis. Because recovery must be maintained 'one day at a time,' researchers have to understand it on the same daily level."

Craving Triggers

Cleveland and his colleague Kitty S. Harris, director, Center for the Study of Addiction and Recovery, Texas Tech University, used data from a daily diary study of college students who are recovering addicts to identify the processes that trigger cravings and prevent some addicts from building a sustained recovery.

The researchers found that how addicts cope with stress -- either by working through a problem or avoiding it -- is a strong predictor of whether they will experience cravings when faced with stress and negative mood.

Coping Skills Important

"Whether you avoid problems or analyze problems not only makes a big difference in your life but also has a powerful impact on someone who has worked hard to stay away from alcohol and other drugs," explained Cleveland. "When faced with stress, addicts who have more adaptive coping skills appear to have a better chance of staying in recovery." The findings appeared in a recent issue of Addictive Behaviors.

Researchers supplied Palm Pilots to 55 college students who were in recovery from substance abuse ranging from alcohol to cocaine and club drugs. The students were asked to record the their daily cravings for alcohol and other drugs, as well as the intensity of negative social experiences -- hostility, insensitivity, interference, and ridicule -- and their general strategies for coping with stress.

"We looked at variations in the number of cravings across days and found that these variations are predicted by stressful experiences," said Cleveland. "More importantly, we found that the strength of the daily link between experiencing stress and the level of cravings experienced is related to the participants' reliance on avoidance coping."

Stress Doubles Cravings

Statistical analyses of the survey data suggests that the magnitude of the link between having a stressful day and experiencing substance use cravings doubles for recovering addicts who cope with stress by avoiding it.

"We found that addicts who deal with stress by avoiding it have twice the number of cravings in a stressful day compared to persons who use problem solving strategies to understand and deal with the stress," explained Cleveland. "Avoidance coping appears to undercut a person's ability to deal with stress and exposes that person to variations in craving that could impact recovery from addiction."

According to Cleveland, the findings suggest the impulse to avoid stress is never going to help recovering addicts because stressful experiences cannot be avoided.

"If your basic life strategy is to avoid stress, then your problems will probably end up multiplying and causing you more problems," he added.

Posted by Webmaster at 10:13 AM

Peer Drug Use Increases Genetic Tendency to Use

The nature-nurture debate is usually about how much of something is due to our genes and how much is caused by our environment. New research just published in the academic journal Addiction shows that the case is more interesting for young women who smoke, drink, or use drugs, for two related reasons.

First, a young woman with a genetic predisposition to substance use is also predisposed to choose friends who smoke, drink, or use drugs, thereby altering her environment in a way that encourages substance use. Second, a young woman's exposure to substance-using friends not only changes her environment but also increases her genetic inclination to use these drugs regularly, thereby raising even higher her already increased likelihood of substance use.

Friends Influence Substance Abuse

Using a sample of over 2,000 female twins, researchers from Washington University in St. Louis looked for links between two types of data: 1) women in the sample who regularly used tobacco, alcohol, or drugs and 2) women whose friends were involved in regular substance use. The links they found showed that genetic vulnerability to regular use of alcohol, cigarettes and cannabis is exacerbated by exposure to friends who use alcohol, cigarettes and drugs.

It is well known that adolescents often select peers who engage in behaviors similar to their own. But this study showed that peer selection has a genetic basis whereby one's genetic predisposition to regular substance use is correlated with the likelihood of choosing friends who also use psychoactive substances. The genetic factors that influence our own likelihood of using drugs thus also modify our likelihood of associating with friends who do the same.

Interited Factors

However, exposure to these drug-using peers has a second, important influence on our own liability to use drugs. The study found that heritable influences on an individual's own regular substance use increased as they affiliated with more drug-using peers – in other words, affiliations with substance-using peers enhances the role that heritable factors play in our own regular substance use. Put simply, increasing affiliations with drug-using peers is correlated with a more 'genetic' form of regular substance use.

According to lead author Dr. Arpana Agrawal, "Nature and nurture don't just combine to produce a woman who smokes, drinks, or uses drugs – nurture can also increase the effect of nature."

Posted by Webmaster at 10:10 AM

Cocaine Use a Significant Teen HIV Risk Factor

Teens with a history of crack or cocaine use are significantly more likely to engage in unprotected sex than youth who have never used these drugs, putting themselves at increased risk for HIV, according to a study in the Journal of Child and Adolescent Substance Abuse.

Researchers from the Bradley Hasbro Children's Research Center report that teens in psychiatric care who used crack and/or cocaine at least once were six times more likely to use condoms inconsistently, which was defined as "sometimes," "never" or "rarely." The findings suggest that crack cocaine appears to have more of an influence on risky teen behaviors than other factors, like alcohol and marijuana use, which are more routinely incorporated into adolescent HIV prevention interventions.

Cocaine and Unprotected Sex


The study is one of the first to look at the link between crack and cocaine use and HIV risk behaviors in adolescents. Previous research has demonstrated this association in adults.

"Unprotected sex is the most common way that HIV is transmitted among teens, so if we can develop a clearer picture of why some kids engage in high-risk sexual behaviors, we will be better prepared to educate them about safe sex," says lead author Marina Tolou-Shams, PhD, of the Bradley Hasbro Children's Research Center. "Our findings suggest that future HIV prevention interventions should include content specific to crack and cocaine use, just as they do with drugs that are more commonly used by teens, like alcohol and marijuana."

Overall, nearly 280 teens between the ages of 13 and 18 from therapeutic psychiatric day programs took part in the study. Participants exhibited a range of psychiatric diagnoses, including mood disorders, post-traumatic stress disorder and disruptive behavior disorders. More than half of all adolescents were male, and more than three-quarters were Caucasian. Approximately 13 percent of teens in the study reported trying crack or cocaine at least once.

Not Using Condoms


After controlling for known adolescent HIV risk factors, such as gender, race, age and psychiatric status, researchers found that only 47 percent of teens with a history of crack and/or cocaine use said they used condoms "always or almost always." In addition, 15 percent of these adolescents have a history of sexually transmitted diseases (STD), nearly three-quarters reported using alcohol at least once and more than half indicated prior marijuana use.

In comparison, 71 percent of teens who never used crack or cocaine reported using condoms consistently.

Tolou-Shams says it was important to look at the association between crack and cocaine use and HIV risk behavior in adolescents with psychiatric disorders, since previous research has shown that teens in mental health treatment have high rates of risky sexual behavior and are more likely to engage in substance use.

"Our study clearly shows that youth in psychiatric treatment are using other drugs – and not just alcohol or marijuana – at high rates and that a history of drug use should alert clinicians to a wide variety of possible behavioral risks in their young patients," she adds.

Provide Interventions


The authors recommend that all clinicians who treat adolescents – including pediatricians, social workers and psychologists – routinely discuss their patients' mental health history, lifetime use of all substances and sexual activity, as well as provide appropriate interventions when necessary in order to reduce their HIV risk.

The research is supported by grants from the National Institute of Mental Health and the Lifespan/Tufts/Brown Center for AIDS Research (CFAR).

Tolou-Shams is also an assistant professor of psychiatry at The Warren Alpert Medical School of Brown University. Study co-authors include Larry K. Brown, MD, and Nicholas Tarantino, BS, both from the Bradley Hasbro Children's Research Center and Alpert Medical School, and Sarah W. Feldstein Ewing, PhD, at the University of New Mexico.

Posted by Webmaster at 09:01 AM