Category: Cocaine

NewsPsychology (Apr. 1, 2010) — 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 April issue of 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.

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.

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.

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.

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The above story is reprinted (with editorial adaptations by newsPsychology staff) from materials provided by Lifespan, via EurekAlert!, a service of AAAS.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of NewsPsychology or its staff.

— In a newly published study, scientists from The Scripps Research Institute have shown for the first time that the same molecular mechanisms that drive people into drug addiction are behind the compulsion to overeat, pushing people into obesity.

The new study, conducted by Scripps Research Associate Professor Paul J. Kenny and graduate student Paul M. Johnson, was published March 28, 2010 in an advance online edition of the journal Nature Neuroscience.

The study's startling findings received widespread publicity after a preliminary abstract was presented at a Society for Neuroscience meeting in Chicago last October. Articles heralding the new discovery appeared in news publications around the world, focusing on the point obese patients have been making for years — that, like addiction to other substances, junk food binging is extremely difficult to stop.

The study goes significantly further than the abstract, however, demonstrating clearly that in rat models the development of obesity coincides with a progressively deteriorating chemical balance in reward brain circuitries. As these pleasure centers in the brain become less and less responsive, rats quickly develop compulsive overeating habits, consuming larger quantities of high-calorie, high-fat foods until they become obese. The very same changes occur in the brains of rats that overconsume cocaine or heroin, and are thought to play an important role in the development of compulsive drug use.

Kenny, a scientist at Scripps Research's Florida campus, said that the study, which took nearly three years to complete, confirms the "addictive" properties of junk food.

"The new study, unlike our preliminary abstract, explains what happens in the brain of these animals when they have easy access to high-calorie, high-fat food," said Kenny. "It presents the most thorough and compelling evidence that drug addiction and obesity are based on the same underlying neurobiological mechanisms. In the study, the animals completely lost control over their eating behavior, the primary hallmark of addiction. They continued to overeat even when they anticipated receiving electric shocks, highlighting just how motivated they were to consume the palatable food."

The scientists fed the rats a diet modeled after the type that contributes to human obesity — easy-to-obtain high-calorie, high-fat foods like sausage, bacon, and cheesecake. Soon after the experiments began, the animals began to bulk up dramatically.

"They always went for the worst types of food," Kenny said, "and as a result, they took in twice the calories as the control rats. When we removed the junk food and tried to put them on a nutritious diet — what we called the 'salad bar option' — they simply refused to eat. The change in their diet preference was so great that they basically starved themselves for two weeks after they were cut off from junk food. It was the animals that showed the "crash" in brain reward circuitries that had the most profound shift in food preference to the palatable, unhealthy diet. These same rats were also those that kept on eating even when they anticipated being shocked."

Lethally Simple

What happens in addiction is lethally simple, Kenny explained. The reward pathways in the brain have been so overstimulated that the system basically turns on itself, adapting to the new reality of addiction, whether its cocaine or cupcakes.

"The body adapts remarkably well to change — and that's the problem," said Kenny. "When the animal overstimulates its brain pleasure centers with highly palatable food, the systems adapt by decreasing their activity. However, now the animal requires constant stimulation from palatable food to avoid entering a persistent state of negative reward."

After showing that obese rats had clear addiction-like food seeking behaviors, Johnson and Kenny next investigated the underlying molecular mechanisms that may explain these changes. They focused on a particular receptor in the brain known to play an important role in vulnerability to drug addiction and obesity — the dopamine D2 receptor. The D2 receptor responds to dopamine, a neurotransmitter that is released in the brain by pleasurable experiences like food or sex or drugs like cocaine. In cocaine abuse, for example, the drug alter the flow of dopamine by blocking its retrieval, flooding the brain and overstimulating the receptors, something that eventually leads to physical changes in the way the brain responds to the drug.

The new study shows that the same thing happens in junk food addiction.

"These findings confirm what we and many others have suspected," Kenny said, "that overconsumption of highly pleasurable food triggers addiction-like neuroadaptive responses in brain reward circuitries, driving the development of compulsive eating. Common mechanisms may therefore underlie obesity and drug addiction."

Consistent with common mechanisms explaining addiction and obesity, levels of the D2 dopamine receptors were significantly reduced in the brains of the obese animals, similar to previous reports of what happens in human drug addicts, Kenny noted. Remarkably, when the scientists knocked down the receptor using a specialized virus, the development of addiction-like eating was dramatically accelerated.

"This addiction-like behavior happened almost from the moment we knocked down the dopamine receptors," Kenny noted. "The very next day after we provided access to the palatable food, their brains changed into a state that was consistent with an animal that had been overeating for several weeks. The animals also became compulsive in their eating behaviors almost immediately. These data are, as far as we know, the strongest support for the idea that overeating of palatable food can become habitual in the same manner and through the same mechanisms as consumption of drugs of abuse."

The study was supported by a Bank of America Fellowship, The Margaret Q. Landenberger Research Foundation and the National Institutes of Health.

Journal Reference:

1. Paul M Johnson, Paul J Kenny. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nature Neuroscience, 2010; DOI: 10.1038/nn.2519

More 12 year olds have used potentially lethal inhalants than have used marijuana, cocaine and hallucinogens combined, according to data released March 11 by the Substance Abuse and Mental Health Services Administration (SAMHSA) in conjunction with the 18th annual National Inhalants & Poisons Awareness Week.

The National Inhalant Prevention Coalition (NIPC) and SAMHSA kicked off National Inhalants and Poisons Awareness Week at a press conference featuring information and personal stories about the dangers of inhalant use or "huffing." One of the leading participants in this year's event was the American Osteopathic Association (AOA), which represents more than 67,000 osteopathic physicians (DOs). The organization urged its members to take continuing education programs designed to help enhance physician awareness of this risk to youth.

The need to increase awareness of this public health risk among physicians, parents and others cannot come too soon for Kevin Talley, the father of Amber Ann Suri, who died in February 2009 after huffing. Her parents suspected something was going on when they noticed she had a pungent smell, glassy eyes, and complained about sinus problems. Although she was taken to a doctor, her real problem was not identified and she was treated only for her sinus symptoms. She died shortly thereafter.

Ashley Upchurch, a 17 year-old recovering from addiction to inhalants and other drugs, spoke at the press conference about the consequences of huffing, the importance of identifying and treating inhalant abuse and the hope of recovery. "Inhalants were a cheap, legal, and an intense high that would also enhance the feeling I would get from other drugs," she said. "These highs nearly destroyed my life." In recovery for two years, Ashley now participates in a recovery program and is "giving back by sharing my story of hope with others."

Young people sniff products such as refrigerant from air conditioning units, aerosol computer cleaners, shoe polish, glue, air fresheners, hair sprays, nail polish, paint solvents, degreasers, gasoline or lighter fluids. Youngsters intentionally inhale these substances to get high. Most parents are not aware that use of inhalants can cause "Sudden Sniffing Death" — immediate death due to cardiac arrest — or lead to addiction and other health risks.SAMHSA data from the 2006-2008 National Surveys on Drug Use and Health show a rate of lifetime inhalant use among 12 year olds of 6.9 percent, compared to a rate of 5.1 percent for nonmedical use of prescription type drugs; a rate of 1.4 percent for marijuana; a rate of 0.7 percent for use of hallucinogens; and a 0.1 rate for cocaine use.

"We continue to face the challenge of increasing experimentation and intentional misuse of common household products among the youngest and most vulnerable segments of our population — 12 year olds. The data are ominous and their implications are frightening because of the toxic, chemical effects of these legal products on growing minds and bodies. One of the front-line defenses against inhalant use is the family health care provider. This is why the action of the American Osteopathic Association is so important and why we are so proud that they are joining us and our partners in this public health campaign," Harvey Weiss, NIPC executive director, said.

In a study published online in the journal Addiction, researchers in the United States have discovered that accidental overdose deaths involving cocaine rise when the average weekly ambient temperature passes 24 degrees Celsius (75 degrees Fahrenheit).

Using mortality data from New York City's Office of the Chief Medical Examiner for 1990 through 2006, and temperature data from the National Oceanic and Atmospheric Association, researchers found that accidental overdose deaths that were wholly or partly attributable to cocaine use rose significantly as the weekly ambient temperature passed 24 degrees Celsius. The number of cocaine-related overdose deaths continued to rise as temperatures continued to climb.

Cocaine-related overdose deaths increase as the ambient temperature rises because cocaine increases the core body temperature, impairs the cardiovascular system's ability to cool the body, and decreases the sense of heat-related discomfort that ordinarily motivates people to avoid becoming overheated. Cocaine users who become overheated (hyperthermic) can overdose on lower amounts of cocaine because their bodies are under more stress.

The study's findings correct previous research that associated an increase in cocaine-related mortality with much higher temperatures (31.1 degrees Celsius, or 87.9 degrees Fahrenheit). Because cocaine-related overdose fatalities begin to rise at lower ambient temperatures than was previously thought, it is now apparent that cocaine users are at risk for longer periods of each year. Between 1990 and 2006, the average weekly temperature in New York City rose above 24 degrees Celsius for about seven weeks per year.

The study showed no difference in the number of drug overdoses in New York City among those weeks where the average temperature was between -10 and 24 degrees Celsius. Above 24 degrees Celsius, however, there were 0.25 more drug overdoses per 1,000,000 residents per week for every two degrees increase in weekly average temperature. Given that over 8.2 million people live in New York City, the study's findings predict that at least two more people per week will die of a drug overdose in the city for each two degree rise in temperature above 24 degrees Celsius, compared to weeks with average temperatures of 24 degrees and below.

The authors of this study point out the need for public health interventions in warm weather, such as delivering health-related warnings to high-risk groups. Prevention efforts could also include making air conditioning available in locations where cocaine use is common such as urban areas with a known high prevalence of cocaine use, and within those urban areas, particular neighbourhoods with elevated numbers of cocaine-related deaths or arrests. As lead author Dr. Amy Bohnert explains, "Cocaine users are at a high risk for a number of negative health outcomes and need public health attention, particularly when the weather is warm."

Journal Reference:

1. Bohnert A., Prescott M., Vlahov D., Tardiff K., and Galea S. Ambient temperature and risk of death from accidental drug overdose in New York City, 1990-2006. Addiction, 2010; DOI: 10.1111/j.1360-0443.2009.02887.x

Children exposed to cocaine in the womb face serious consequences from the drug, but fortunately not in certain critical physical and cognitive areas as previously believed, according to a new comprehensive review of research on the subject from scientists at the University of Maryland School of Medicine. When a pregnant woman uses cocaine, it can interrupt the flow of nutrients and oxygen to the baby, putting such children at risk for premature birth, low birth weight and many other problems.

The new review of multiple major studies conducted on cocaine-exposed, school-aged children found this negative impact significantly affected children in subtle areas such as sustained attention and self-regulated behavior. The research, however, showed surprisingly little impairment directly from cocaine in key areas such as growth, IQ, academic achievement and language functioning.

Many of the children did have low IQ and poor academic and language achievement. The research suggested, though, that these apparent impairments were often caused by the troublesome home environment that goes along with cocaine use, rather than directly from the cocaine itself.

The developmental areas that the cocaine exposure seemed to directly impact — sustained attention and self-regulated behavior — could become significantly problematic as children grow into adults. The review is published this month in the journal Pediatrics. It is the first review of cocaine-exposed school-age children six and older; a previous review looked at younger children.

When rates of cocaine use began to grow in America in the 1980s, there was concern that children who had been exposed to the drug or its derivative, crack cocaine, in utero were doomed for a lifetime of poor health, sub-par performance in school, behavior problems and eventually for substance abuse themselves. The new review indicates otherwise, and could change the way medicine and social science approach outreach to and study of cocaine-exposed children, according to senior author Maureen M. Black, Ph.D., professor of pediatrics at the University of Maryland School of Medicine.

"Cocaine can disrupt fetal growth and development, but this review tells us that just because a child has been exposed to cocaine, it is not a foregone conclusion that they're going to be in trouble," says Dr. Black. "No one is saying cocaine use is good. We need prevention programs so women don't use cocaine in the first place. Children experience serious negative effects from drug exposure in the womb. It looks, though, as if cocaine doesn't work alone. Women who use cocaine are often from poor and dysfunctional families, where children do not receive the care and enrichment they need. In addition, women who use cocaine while pregnant often smoke cigarettes and drink alcohol as well, exposing their unborn children to legal substances with extremely negative consequences."

Dr. Black and her colleagues reviewed 32 major studies of school-age children, ages six through their teenage years, conducted between 1980 and 2008. All of the studies compared children who had been exposed to cocaine to those who had not. Dr. Black and postdoctoral fellows John P. Ackerman, Ph.D., and Tracy Riggins, Ph.D., aggregated the data and organized them into charts comparing the healthy children to those who had been exposed to cocaine.

The areas where children showed significant negative impact from cocaine — sustained attention and in self-regulating behavior — could lead to serious problems for children in adolescence or adulthood. "They might have difficulty with impulse control and they might be risk-takers," says Dr. Black. "They might be more likely to be involved with drugs themselves." Innovative techniques, including neuroimaging, have suggested that cocaine exposure impacts specific brain structures and functions. The cocaine-exposed children seem to have differences in both white and gray matter, for example.

The results suggest that the prevention efforts should continue to target reducing drug use among women, especially during pregnancy, but such outreach should continue after the child's birth. Education and support to help caregivers improve the child's environment might be very beneficial to children exposed to cocaine, Dr. Black says. The research will continue to examine the specific areas of the brain that may be vulnerable to cocaine exposure in the hopes of linking neural differences with behavioral outcomes.

A review is an efficient way to examine the larger picture of a public health issue, going beyond just one study, says Dr. Black. A review is particularly useful in a field of research that has not existed for very long, such as the study of cocaine-exposed children. "If you have findings from a single study, you cannot be sure of their significance until the study is replicated," Dr. Black says. "The benefit of a review is that it takes what's in the literature as a whole, puts it together and tries to make sense of it."

"Dr. Black's review has uncovered an entirely new way of thinking about these most vulnerable victims of substance abuse, the children exposed to drugs before birth," says E. Albert Reece, M.D., Ph.D., M.B.A., the John Z. and Akiko K. Bowers Distinguished Professor and dean of the School of Medicine, and vice president for medical affairs of the University of Maryland. "I am hopeful her work will lead to new interventions to prevent prenatal cocaine exposure at the start, and to ensure the success of these children for the benefit of their own health and public health as a whole."

Journal Reference:

1. John P. Ackerman, Tracy Riggins, and Maureen M. Black. A Review of the Effects of Prenatal Cocaine Exposure Among School-Aged Children. Pediatrics, 2010; 125 (3): 554 DOI: 10.1542/peds.2009-0637

Researchers at UT Southwestern Medical Center hope they have begun paving a new pathway in the fight against drug dependence. Their hypothesis — that increasing the normally occurring process of making nerve cells might prevent addiction — is based on a rodent study demonstrating that blocking new growth of specific brain nerve cells increases vulnerability for cocaine addiction and relapse.

The study's findings, available in the Journal of Neuroscience, are the first to directly link addiction with the process, called neurogenesis, in the region of the brain called the hippocampus.

While the research specifically focused on what happens when neurogenesis is blocked, the scientists said the results suggest that increasing adult neurogenesis might be a potential way to combat drug addiction and relapse.

"More research will be needed to test this hypothesis, but treatments that increase adult neurogenesis may prevent addiction before it starts, which would be especially important for patients treated with potentially addictive medications," said Dr. Amelia Eisch, associate professor of psychiatry at UT Southwestern and senior author of the study. "Additionally, treatments that increase adult neurogenesis during abstinence might prevent relapse."

Increasingly, addiction researchers have recognized that some aspects of the condition — such as forming drug-context associations — might involve the hippocampus, which is a region of the brain associated with learning and memory. Only with recent technological advances have scientists been able to test their theories in animals by manipulating the birth of new nerve cells in the hippocampus of the adult brain.

Physical activity and novel and enriched environments have been shown in animal studies to be good for the brain in general, but more research is needed to see if they can increase human adult neurogenesis.

Dr. Eisch and her colleagues used advanced radiation delivery techniques to prevent hippocampal neurogenesis. In one experiment, rats were allowed to self-administer cocaine by pressing a lever. Rats with radiated brains took more cocaine and seemed to find it more rewarding than rats that did not receive radiation.

In a second experiment, rats first self-administered cocaine and then received radiation to decrease neurogenesis during a period of time that they were without drugs. Rats with reduced neurogenesis took more time to realize that a drug lever was no longer connected to the drug dispenser.

"The nonirradiated rats didn't like the cocaine as much and learned faster to not press the formerly drug-associated lever," Dr. Eisch said. "In the context of this experiment, decreased neurogenesis fueled the process of addiction, instead of the cocaine changing the brain."

Dr. Eisch said she plans to do similar studies with other drugs of abuse, using imaging technology to study addiction and hippocampal neurogenesis in humans.

"If we can create and implement therapies that prevent addiction from happening in the first place, we can improve the length and quality of life for millions of drug abusers, and all those affected by an abuser's behavior," she said.

Another study author from UT Southwestern was Sarah Bulin, a graduate student research assistant. Other researchers involved in the work include Dr. Michele Noonan, former graduate research assistant in psychiatry, and Dwain Fuller from the VA North Texas Health Care System.

The study was funded by the National Institute on Drug Abuse.

The brain's innate interest in the new and different may help trump the power of addictive drugs, according to research published by the American Psychological Association. In controlled experiments, novelty drew cocaine-treated rats away from the place they got cocaine.

Novelty could help break the vicious cycle of treatment and relapse, especially for the many addicts with novelty-craving, risk-taking personalities, the authors said. Drug-linked settings hold particular sway over recovering addicts, which may account in part for high rates of relapse.

In the multi-stage study, Carmela Reichel, PhD, and Rick Bevins, PhD, of the University of Nebraska-Lincoln, trained rats to prefer one side of a large Plexiglas apparatus by injecting them with one of three different doses of cocaine before placing them in that side. For the next eight days, the researchers alternated placing rats in one side or the other, injecting cocaine before placing them on one side, or injecting saline solution before placing them on the other.

This simple procedure left the rats, when drug free and given a choice, significantly more likely to visit the side where they had felt the rewarding effects of cocaine, according to the report in the February issue of Behavioral Neuroscience.

In the next stage, for another eight days, the researchers tried to break the tie between drug and place by introducing novelty. Now, when rats were placed into the saline-paired compartment, half found something new there — a white sock, a little piece of PVC pipe, a plastic scouring pad or balled-up newspaper. The remaining rats were given the same bare compartment as before.

Next, the rats were injected with saline solution instead of cocaine and placed — on alternate days — in either the side paired with cocaine or with novelty. That would be like recovering addicts going back to the place they took drugs, a major cause of relapse. Alternating placements helped researchers counteract rats' natural tendency to spend more time in unfamiliar places, and equalize the time they spent in each context.

Finally, to test whether novelty could still compete with drug-linked cues, drug-free rats were placed between compartments to see where they would go. Rats that had been trained on 7.5 and 20, but not 30, cocaine milligrams per kilogram (mg/kg) of weight and then given novel objects spent equal time on both sides. That is, they went back and forth between the places they had experienced both cocaine and novelty. Rats that did not receive the novel objects spent more time where they had experienced the effects of cocaine.

Drugged rats that had been trained on 7.5 mg/kg of cocaine and then given novel objects also gave both sides equal attention. However, rats that had been trained on 20 or 30 mg/kg of cocaine and then given novel objects still preferred the cocaine-paired over the novelty side.

Given the results of the drug-free tests, the findings suggested that employing something new and intriguing could work with drug-free, recovering addicts who are mild but not heavy users, the authors wrote.

In a second experiment, the researchers repeated the procedure with just one dose of cocaine, 10 mg/kg of weight, to test the effect's staying power one, 14 or 28 days after establishing the preference for the cocaine-paired side. Two weeks later, novelty still changed compartment choice for drug-free rats. Four weeks later, however, none of the rats showed a particular preference for either compartment.

"We identified a window of opportunity for conditioned rewards to compete for control over choice behavior," at least among rats, the authors wrote.

By understanding how long and how well novelty can compete with the allure of addicting drugs, researchers may start to consider using it in the real world. The human equivalent of new "toys" — such as scuba diving, mountain climbing, whitewater rafting and snow skiing — could work as a behavioral reward. As the researchers pointed out, novelty does not involve medical treatment or side effects, and could be cheaper as well.

"Treatment programs implementing novel rewards targeted to those individuals that have high novelty/sensation seeking tendencies may offer addicts the opportunity (e.g., with vouchers) to participate in one of the activities mentioned previously in hopes of maintaining abstinence," wrote Reichel and Bevins.

Journal Reference:

1. Carmela M. Reichel, PhD, and Rick A. Bevins, PhD. Competition Between Novelty and Cocaine Conditioned Reward Is Sensitive to Drug Dose and Retention Interval. Behavioral Neuroscience, Vol. 124, No. 1

Forensic pathologists have shown that over three per cent of all sudden deaths in south-west Spain are related to the use of cocaine. They believe their findings can be extrapolated to much of the rest of Europe, indicating that cocaine use is a growing public health problem in Europe and that there is no such thing as "safe" recreational use of small amounts of the drug.

The study published in the European Heart Journal on January 13, carefully investigated all the circumstances surrounding a consecutive series of sudden deaths between 2003 and 2006. During post-mortems the pathologists tested blood and urine for traces of toxic substances, and studied the organs, focusing on the cardiovascular system and toxicological analysis; they also gathered information on substance abuse prior to death, the circumstances of the death and death scene investigations.

Out of 668 sudden deaths during the study period, 21 (3.1%) were related to cocaine use; of these, all occurred in men aged between 21 and 45, and most of the cocaine-related deaths were due to problems with the heart and its related systems.

Dr Joaquín Lucena, MD PhD, Head of the Forensic Pathology Service at the Institute of Legal Medicine (Seville, Spain) who led the study, said: "Our findings show that cocaine use causes adverse changes to the heart and arteries that then lead to sudden death."

Dr Lucena and his colleagues found that median levels of cocaine in blood or urine were 0.1 and 1.15 mg/L respectively, with a range that varied widely but which depended on a number of factors related to the drug itself (how it was taken, how people's bodies processed it and what other substances were taken at the same time), and to the people themselves (body mass index, acute or chronic use of the drug, other underlying health issues, age and sex). They wrote: "Any amount of the drug can be considered to have the potential for toxicity due to the fact that some patients have poor outcomes with relatively low blood concentrations, whereas others tolerate large quantities without consequences."

The researchers also found that 81% of the men who died after cocaine use also smoked, and 76% had drunk alcohol. Ethanol, the intoxicating ingredient in alcoholic drinks, enhances the "high" obtained from cocaine while minimising the subsequent "low." However, both smoking and alcohol are associated with heart disease and Dr Lucena said: "The combination of cocaine with either or both of these habits can be considered as a lethal cocktail that promotes the development of premature heart disease."

The study is the first to investigate the prevalence of cocaine-related sudden deaths in such a detailed and methodical way. The authors highlight the importance of this method of studying sudden deaths.

"For the correct diagnosis of the sudden death, especially in young adults, it is important to use a uniform autopsy protocol, including a toxicology investigation of the blood and urine for illicit drugs," said Dr Lucena. "Cocaine abuse is a growing public health issue in Europe and we can only monitor its prevalence by performing these detailed autopsies whenever someone dies suddenly."

In their study, the authors wrote: "The estimated number of COC [cocaine] consumers is about 12 million Europeans with an overall prevalence of 3.7% of the total adult population (15-64 years). Ever in lifetime experience of COC is reported by more than 5% of the total adult European population in three countries: UK (7.7%), Spain (7.0%) and Italy (6.6%). The prevalence of use of COC is higher among young adults (15-34 years), with around 7.5 million young Europeans (5.4% on average) estimated as having used it at least once in their lifetime. In the year 2007, an estimated 3.5 million (2.4%) European young adults have used COC, with the highest prevalence levels, of over 3%, being found in Spain, Italy and the UK."

Dr Lucena said: "As the estimated number of European young adults cocaine consumers is similar in Spain, UK and Italy, there is no reason to consider that the cocaine-related sudden death in UK and Italy would be different to what we have found in our research in south-west Spain."

To put the rates of sudden deaths in context, he added: "According to our experience in the Forensic Pathology Service at the Institute of Legal Medicine, the rate of cocaine-related deaths per year in Seville, is roughly half the number of people who die suddenly from haemorrhagic stroke."*

Professor David Hillis and Professor Richard Lange, chairman and executive vice chairman respectively of the Department of Medicine at the University of Texas Health Science Center (San Antonio, USA), who were unconnected with the work, wrote an editorial to accompany Dr Lucena's paper. They reported that the prevalence of cocaine use varied in Europe from 0.7% in Romania and Lithuania to 12.7% in the UK, but this was likely to be an under-estimate.

They agreed that uniform protocols were required for post-mortems on victims of sudden death, including toxicological examination of the blood and urine for illicit drugs. "Until these are accomplished, the prevalence of cocaine and other illicit drug use will be underestimated, and cocaine-related complications will not be recognized," they wrote. "Physicians should consider the possibility of cocaine abuse in a young individual with cardiovascular disease or sudden death, especially in those without traditional risk factors for atherosclerosis. Finally, the notion that recreational cocaine use is 'safe' should be dispelled, since even small amounts may have catastrophic consequences, including sudden death."

*Haemorrhagic stroke is a type of stroke that accounts for about 15% of stroke cases. It results from a weakened vessel that ruptures and bleeds into the surrounding brain, accumulating and compressing the surrounding brain tissue.

Journal References:

1. . Cocaine-related sudden death: a prospective investigation in south-west Spain. European Heart Journal, DOI: 10.1093/eurheartj/ehp557
2. . Sudden death in cocaine abusers. European Heart Journal, DOI: 10.1093/eurheartj/ehp503

Researchers have identified a key epigenetic mechanism in the brain that helps explain cocaine's addictiveness, according to research funded by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health.

The study, published in the January issue of the journal Science, shows how cocaine affects an epigenetic process (a process capable of influencing gene expression without changing a gene's sequence) called histone methylation. These epigenetic changes in the brain's pleasure circuits, which are also the first impacted by chronic cocaine exposure, likely contribute to an acquired preference for cocaine.

"This fundamental discovery advances our understanding of how cocaine addiction works," said NIDA Director Dr. Nora D. Volkow. "Although more research will be required, these findings have identified a key new player in the molecular cascade triggered by repeated cocaine exposure, and thus a potential novel target for the development of addiction medications."

Researchers gave one group of young mice repeated doses of cocaine and another group repeated doses of saline with a final dose of cocaine to determine how the effects of chronic cocaine exposure differed from one-time exposure. The study confirms that one of the mechanisms by which cocaine alters the reward pathway is by repressing G9A, a histone demethylating enzyme that plays a critical role in epigenetic control of gene expression.

As previously observed, animals exposed to chronic cocaine displayed dramatic alterations in gene expression as well as a strong preference for cocaine. For the first time, the authors were also able to show that by experimentally reversing the cocaine induced repression of G9a, they could block the changes in gene expression and inhibit the enhanced preference for cocaine.

"The more complete picture that we have today of the genetic and epigenetic processes triggered by chronic cocaine give us a better understanding of the broader principles governing biochemical regulation in the brain which will help us identify not only additional pathways involved but potentially new therapeutic approaches," said Dr. Eric J. Nestler, study investigator and director of the Brain Institute at Mount Sinai School of Medicine.

 When asked to inhibit their response to a "cocaine-cues" video, active cocaine abusers were, on average, able to suppress activity in brain regions linked to drug craving, according to a new study at the U.S. Department of Energy's Brookhaven National Laboratory. The results, to be published in an upcoming issue of NeuroImage, suggest that clinical interventions designed to strengthen these inhibitory responses could help cocaine abusers stop using drugs and avoid relapse.

"Exposure to drugs or stimuli associated with using drugs is one of the most common factors leading to relapse in drug-addicted individuals," said Nora Volkow, Director of the National Institute on Drug Abuse and lead author on the paper.

"We know from previous studies that drug cues can trigger dramatic changes in the brain that are linked to a strong craving response," added co-author Gene-Jack Wang, Chair of Brookhaven's medical department. "This study provides the first evidence that cocaine abusers retain some ability to cognitively inhibit their craving responses to drug-related cues."

Added Volkow, "Our findings provide enormous hope because they imply that cognitive interventions might be developed to maximize cocaine abusers' success in blocking the drug-craving response to help them avoid relapse."

The scientists used a brain-scanning technique called positron emission tomography (PET) and a radioactively "tagged" form of glucose — the brain's main fuel — to measure brain activity in 24 active cocaine abusers during three different conditions:

1. while subjects simply lay in the scanner with eyes open;
2. while subjects watched a "cocaine-cues" video with scenes simulating the purchase, preparation, and smoking of crack cocaine; and
3. while subjects watched the video but were told to try to inhibit their craving response.

Scans were performed in random order and on separate days.In each scan, the PET camera tracked the radioactive signal from the tagged glucose as it was taken up by various regions of the brain. A stronger signal indicates higher metabolic activity in a particular brain region where more glucose is being used. This technique allows scientists to accurately monitor which brain regions are most active and how that activity changes with time or in response to different situations.

The scientists also monitored the research subjects’ heart rate and blood pressure and asked them to describe their level of craving during the scans. Compared with the baseline condition, the cocaine-cues video triggered increases in brain activity in several brain regions associated with drug craving, as well as increases in research subjects’ self-reports of craving.

When the research subjects were asked to inhibit their response to the video, and those scans were compared with the no-inhibition condition, metabolic activity decreased dramatically in brain regions involved in experiencing and anticipating rewards, and in a part of the brain that plays a role in assigning value, or salience, to different stimuli. During inhibition, research subjects also reported lower levels of craving compared with the no-inhibition video condition.

The researchers say the findings have significant clinical implications: “Many current drug treatment programs help addicted individuals predict when and where they might be exposed to drug cues so that they can avoid such situations,” Volkow said. “While this is a very useful strategy, in real-word situations, cues may come up in unexpected ways. Our findings suggest that a clinical strategy that trains cocaine abusers to exert greater cognitive control could help them selectively inhibit the craving response whenever and wherever drug cues are encountered — whether expectedly or unexpectedly.”

Because inhibitory control is crucial for regulating emotions and desires, the findings from this study could have implications for other disorders involving loss of behavioral control, such as gambling and obesity.

This study was supported by the intramural program from the National Institutes of Health Intramural Research Program at the National Institute on Alcohol Abuse and Alcoholism. Brookhaven Lab’s infrastructure for PET imaging and radiotracer development also receive support from the DOE Office of Science.