Many brain scan studies that have found relationships between substance abuse problems and brain activity started too late (after the abuse has started) to identify whether differences were causes or results of the substance abuse. Now a study that started with 14-year-olds find that teens with a weak orbitofrontal cortex are more impulsive and more likely to start using drugs and alcohol at an earlier age.
Why do some teenagers start smoking or experimenting with drugs—while others don't?
In the largest imaging study of the human brain ever conducted—involving 1,896 14-year-olds—scientists have discovered a number of previously unknown networks that go a long way toward an answer.
Robert Whelan and Hugh Garavan of the University of Vermont, along with a large group of international colleagues, report that differences in these networks provide strong evidence that some teenagers are at higher risk for drug and alcohol experimentation—simply because their brains work differently, making them more impulsive.
Their findings are presented in the journal Nature Neuroscience, published online April 29, 2012.
This discovery helps answer a long-standing chicken-or-egg question about whether certain brain patterns come before drug use—or are caused by it.
"The differences in these networks seem to precede drug use," says Garavan, Whelan's colleague in UVM's psychiatry department, who also served as the principal investigator of the Irish component of a large European research project, called IMAGEN, that gathered the data about the teens in the new study.
I bet in 5 years we'll know genetic variants that control the strength of the orbitofrontal cortex. My guess is that once it becomes possible for parents to choose genetic variants for their offspring that they'll choose genetic variants for a strong orbitofrontal cortex. Therefore the human race will become much less impulsive. Overall this will be a good thing. Though it might make for less creativity in some situations. Perhaps other genetic variants for creativity will be chosen and we'll get much more creative future humans anyway.
Suppose brain scans can identify the more impulsive. Should something be done to reduce their opportunities for use of illegal drugs, cigarettes, and alcohol? Imagine an implant that filters certain drugs out of the body. Or an implant that alerts others that the kid is on nicotine or cocaine.
In a key finding, diminished activity in a network involving the "orbitofrontal cortex" is associated with experimentation with alcohol, cigarettes and illegal drugs in early adolescence.
"These networks are not working as well for some kids as for others," says Whelan, making them more impulsive.
Faced with a choice about smoking or drinking, the 14-year-old with a less functional impulse-regulating network will be more likely to say, "yeah, gimme, gimme, gimme!" says Garavan, "and this other kid is saying, 'no, I'm not going to do that.'"
Internet addiction disorder may be associated with abnormal white matter structure in the brain, as reported in the Jan. 11 issue of the online journal PLoS ONE. These structural features may be linked to behavioral impairments, and may also provide a method to study and treat the disorder.
Previous studies of internet addiction disorder (IAD), which is characterized by an individual's inability to control his or her Internet use, have mostly focused on psychological questionnaires. The current study, on the other hand, uses an MRI technique to investigate specific features of the brain in 18 adolescents suffering from IAD.
The researchers, led by Hao Lei of the Chinese Academy of Sciences in Wuhan, found that IAD is characterized by impairment of white matter fibers connecting brain regions involved in emotional generation and processing, executive attention, decision making, and cognitive control, and suggest that IAD may share psychological and neural mechanisms with other types of impulse control disorders and substance addiction.
As a heavy internet user I suddenly want to know: is my brain white matter tweaked?
Significantly negative correlations were found between FA values in the left genu of the corpus callosum and the Screen for Child Anxiety Related Emotional Disorders, and between FA values in the left external capsule and the Young's Internet addiction scale.
If you have to feel anxiety to have this abnormality then I'm okay. Anxiety is an emotional that I don't much feel. Okay, do I have, like, anxiety deficit syndrome? Its always something.
Cigarettes and alcohol serve as gateway drugs, which people use before progressing to the use of marijuana and then to cocaine and other illicit substances; this progression is called the "gateway sequence" of drug use. An article in Science Translational Medicine by Amir Levine, MD, Denise Kandel, PhD; Eric Kandel, MD; and colleagues at Columbia University Medical Center provides the first molecular explanation for the gateway sequence. They show that nicotine causes specific changes in the brain that make it more vulnerable to cocaine addiction -- a discovery made by using a novel mouse model.
So teens smoking because they think its cool are putting themselves at greater risk of a long assortment of degenerative diseases (cancer, heart disease, stroke, arthritis, and a huge number of others) plus greater risk of becoming a coke fiend.
Don't let nicotine tweak your brain's striatum and inhibit your histone deacetylase.
Alternate orders of exposure to nicotine and cocaine were examined. The authors found that pretreatment with nicotine greatly alters the response to cocaine in terms of addiction-related behavior and synaptic plasticity (changes in synaptic strength) in the striatum, a brain region critical for addiction-related rewards. On a molecular level, nicotine also primes the response to cocaine by inhibiting the activity of an enzyme -- histone deacetylase -- in the striatum. This inhibition enhances cocaine's ability to activate a gene called FosB gene, which promotes addiction.
The relationship between nicotine and cocaine was found to be unidirectional: nicotine dramatically enhances the response to cocaine, but there is no effect of cocaine on the response to nicotine. Nicotine's ability to inhibit histone deacetylase thus provides a molecular mechanism for the gateway sequence of drug use.
Most coke heads were smokers before cokers.
Nicotine enhances the effects of cocaine only when it is administered for several days prior to cocaine treatment and is given concurrently with cocaine. These findings stimulated a new analysis of human epidemiological data, which shows that the majority of cocaine users start using cocaine only after they have begun to smoke and while they are still active smokers. People who begin using cocaine after they've started smoking have an increased risk of cocaine dependency, compared with people who use cocaine first and then take up smoking.
We need drugs that will reverse the effects of cocaine and nicotine on the brain.
The researchers are interested to find out whether alcohol and marijuana cause similar changes to the brain.
A study in teenagers showed the "reward hub", which is involved in addiction, was larger in regular players.
A report in Translational Psychiatry said it was unknown if games changed the brain or if brain differences made people more likely to play.
What I wonder: have video games shifted people from drug addiction to game addiction? If so, video games might actually be reducing brain damage by giving people something less harmful to get addicted to. On the other hand, since video games are illegal and have less of a stigma about them more people can become addicted to them more easily.
People who are alcohol-dependent and who also carry a particular variant of a gene run an increased risk of premature death. This is a recent finding from the interdisciplinary research at the Department of Psychology and the Sahlgrenska Academy at the University of Gothenburg, Sweden.
Researchers in the longitudinal project Göteborg Alcohol Research Project (GARP) have been investigating the dopamine D2 receptor gene and found that a variant of this gene is overrepresented in people with severe alcohol dependency, and that it is linked to a number of different negative consequences that can be of vital significance to the person affected.
"Our research shows that alcohol-dependent individuals, who are also carriers of this gene variant, run 10 times the risk of dying prematurely, compared with the average population," says Claudia Fahlke, a representative from the research team.
What genetic variants make for a bigger ventral striatum?
Men become alcoholics at higher rates than women. Why? Could be that men get more pleasure from drinking alcohol due to more dopamine neurotransmitter release.
Researchers from Columbia and Yale studied male and female college-age social drinkers in a laboratory test of alcohol consumption. After consuming an alcoholic or non-alcoholic drink, each participant underwent a specialized positron emission tomography (PET) scan, an imaging technique that can measure the amount of alcohol-induced dopamine release.
Dopamine has multiple functions in the brain, but is important in this context because of its pleasurable effects when it is released by rewarding experiences, such as sex or drugs.
When you feel pleasure from drinking alcohol that's your ventral striatum talking.
Despite similar consumptions of alcohol, the men had greater dopamine release than women. This increase was found in the ventral striatum, an area in the brain strongly associated with pleasure, reinforcement and addiction formation.
"In men, increased dopamine release also had a stronger association with subjective positive effects of alcohol intoxication," explained Dr. Nina Urban, corresponding author for this study. "This may contribute to the initial reinforcing properties of alcohol and the risk for habit formation."
If you do repeated heavy drinking episodes you won't experience as much pleasure from the later episodes. So find some other way to get your kicks.
Dr. Anissa Abi-Dargham, senior author on this project, notes that "another important observation from this study is the decline in alcohol-induced dopamine release with repeated heavy drinking episodes. This may be one of the hallmarks of developing tolerance or transitioning into habit."
If you are feeling less pleasure from a potentially addictive substance then stop using it for a while or stop permanently.
A specific and remarkably small fragment of RNA appears to protect rats against cocaine addiction - and may also protect humans, according to a recent study funded by the National Institute on Drug Abuse (NIDA), a component of the National Institutes of Health. The study was published today in the journal Nature.
RNA (ribonucleic acid) molecules are known to play critical roles in the translation of genetic information (DNA) into proteins, which are the building blocks of life. In the past decade, scientists have begun to notice, catalogue and characterize a population of small RNAs, called microRNAs, that represent a new class of regulatory molecules. In this study, researchers at The Scripps Research Institute in Jupiter, Florida found that cocaine consumption increased levels of a specific microRNA sequence in the brains of rats, named microRNA-212. As its levels increased, the rats exhibited a growing dislike for cocaine, ultimately controlling how much they consumed. By contrast, as levels of microRNA-212 decreased, the rats consumed more cocaine and became the rat equivalent of compulsive users.
MicroRNA-212 is a type of small non-protein coding RNA that can regulate the expression levels of hundreds or even thousands of genes. As such, microRNA-212 and other types of microRNAs are considered "master regulators" of gene expression. Because of their ability to coordinate the expression of related genes responsible for brain structure and function, it is thought that microRNAs might play important roles in complex psychiatric disorders, but little has been known about their involvement in addiction—until now.
What the new findings suggest, Kenny said, is that individuals with serious addiction problems may have damaged supplies of this particular non-coding RNA, or the microRNA may not function properly.
"Looking into the future," he said, "It might be possible to develop a small molecule therapeutic that mimics or stimulates the production of this particular microRNA. Once we understand the precise mechanism, we might uncover novel targets that would have a similar effect to acting on the microRNA directly."
Addictions will become curable. Got an addiction you want to cure? If so, is it an interesting addiction?
Blame your genes if you can't stop smoking cigarettes. Researchers at Duke University Medical Center and the National Institute on Drug Abuse (NIDA) find that the best dose nicotine patch for those quitting smoking depends on differences in genetic variants.
In the trial, 479 cigarette smokers who smoked at least 10 cigarettes per day and wanted to quit were categorized as either high- or low-dependence based on their level of nicotine dependence. The smokers in each group were then randomly assigned to wear two nicotine skin patches daily delivering a high dose ( (42mg) or a standard dose (21 mg). Patches were worn for two weeks prior to their quit date, and the nicotine doses were reduced gradually over the 10 weeks following their quit date. Participants were given denicotinized cigarettes during the two weeks before the quit date to minimize any potential adverse effects from the high dose nicotine patches. The treatment phase lasted for 12 weeks in all.
DNA was extracted from participants' blood and was used to assess a quit-smoking success genetic score.
At six months follow up, the researchers were able to confirm which smokers fared better or worse on the high-dose compared to the low-dose patch.
"The genotype score was part of what predicted successful abstinence. In the future such a score could help us make our initial treatment decisions," said Rose. "People who had both high nicotine dependence and a low or unfavorable quit success genetic score seemed to benefit markedly from the high-dose nicotine patch, while people who had less dependence on nicotine did better on the standard patch."
Genetic differences influence not only the difficulty in kicking an addiction but also the susceptibility to becoming addicted in the first place. For example, Mono Amine Oxidase (MAO) inhibition by tobacco compounds probably enhances addiction and genetic variants in MAO appear to influence risk of addiction.
Humans differ genetically in their capacity to be exposed to addictive drugs without becoming addicted. Keep this in mind the next time you see an addicted person acting destructive toward self and others. Some of those addicted people have genetic variants that make kicking their addiction especially difficult.
To get a real-time sense of dopamine activity, Joanna Fowler and her colleague Gene-Jack Wang at Brookhaven, along with Nora Volkow, Director of the National Institute on Drug Abuse, combined positron emission tomography (PET), a medical imaging technology useful for identifying brain diseases, with special radioactive tracers that bind to dopamine receptors. The PET scan highlights the movement of the tracers in the brain, and can be used to reconstruct real-time 3D images of the dopamine system in action.
The scientists tested this procedure on several drug-addicted volunteers as well as age-matched healthy control subjects and found that people with addictions in general have 15-20 percent fewer dopamine receptors than normal and thus cannot bind to a lot of the dopamine released in response to the drugs or natural reinforcers like food.
A treatment that boosts dopamine receptor count would probably make it easier to kick drugs.
Addicts probably do not experience as much pleasure.
"These addicted individuals all had a blunted dopamine response," noted Fowler, a senior scientist in Brookhaven's medical department. "This reinforces the idea that drug addicts experience diminished feelings of pleasure, which drives their continual drug use."
Fowler added that the study looked at multiple recreational drugs and found similar results. "So, while various drugs operate by unique mechanisms, they all share a commonality in that the dopamine receptors in the brains of addicted individuals show an under-stimulated reward system."
How fast do dopamine receptor levels rise after an addict stops using? My guess is that the rate of dopamine receptor recovery is inversely correlated with relapse back into drug use.
This report has important cultural implications as well. So then drug addict "Towelie" has fewer dopamine receptors in his towel brain? Great South Park episode btw. Also, what about Tiger Woods' sex addiction? Does the guy suffer from low dopamine receptor levels? If so, how can he be condemned for medical self treatment?
Researchers at the University of Maryland who asked 200 students to give up all media for one full day found that after 24 hours many showed signs of withdrawal, craving and anxiety along with an inability to function well without their media and social links.
There are two ways to react to this report. Most obviously people could try to kick their internet addiction. But another possible approach is to accept the addiction reshape our society around it. Avoid withdrawal by building a more secure and more widely accessible internet. Internet connectivity devices could be embedded in our brains (kind of like the embedded telephones in The President's Analyst). We need robotic cars that can drive for us so that we do not have to distract ourselves away from the internet in order to drive. We could all have dogs for the handicapped that would guide us when we walk while we do text messaging.
This reminds me of the great South Park internet episode. What happens when the internet goes down in South Park? The result is not pretty. Got to head out to California just like the Okies in the Dust Bowl era.
JUPITER, FL, March 23, 2010 –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.
Think of all those rats eating out of dumpsters behind McDonald's, Wendy's, Burger King, Carl's Jr, Quiznos (yummy bread btw), and other purveyors of addictive substances. Those rats are probably suffering social ostracism in the larger rat community, shunned due to their appearance. Plus, they are suffering from type 2 insulin resistant diabetes. They need help.
Cocaine, heroin, hamburgers, 5 topping pizzas, its all the same in the brain.
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.
Clearly people addicted to junk food need to be isolated for 2 weeks in a treatment center. The Betty Ford Center should diversify into junk food addiction treatment.
"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."
But much goes unsaid. Once those rats finished going thru junk food withdrawal were they able to put their lives back together, reconcile with their families, and stay away from double cheese burgers with large fries? Or were they such hopeless cases that the scientists killed them to dissect their brains?
Some innocent-looking flowers are really dope pushers who hook bees on drugs. Bees prefer nectar that contains caffeine and nicotine.
Bees prefer nectar with small amounts of nicotine and caffeine over nectar that does not comprise these substances at all, a study from the University of Haifa reveals. “This could be an evolutionary development intended, as in humans, to make the bee addicted,” states Prof. Ido Izhaki, one of the researchers who conducted the study.
Do bees get a buzz from the drugged nectar?
The innocent and sweet portions of the plant and animal kingdom never are as sweet and innocent as natural mythologies would have us believe. The never ending competition for survival and reproductive success ensures that the competition is brutal, relentless, and amoral.
Update: Don't start feeling sorry for those drug addicted bees. Oh no. Honey bees are no more innocent than drug pusher flowers. Those supposedly innocent natural honey bees fight bees from rival colonies for food. It is a Malthusian bee-eat-bee world out there.
A biologist at UC San Diego has discovered that honey bees warn their nest mates about dangers they encounter while feeding with a special signal that's akin to a "stop" sign for bees.
The discovery, detailed in a paper in the February 23 issue of the journal Current Biology, which appears online today, resulted from a series of experiments on honey bees foraging for food that were attacked by competitors from nearby colonies fighting for food at an experimental feeder. The bees that were attacked then produced a specific signal to stop nest mates who were recruiting others for this dangerous location. Honey bees use a waggle dance to communicate the location of food and other resources. Attacked bees directed "stop" signals at nest mates waggle dancing for the dangerous location.
The brains of methamphetamine abusers take over a year after they stop using before they develop the ability to ignore distractions and concentrate on a task. This disability makes it a lot easier for them to be tempted to start using again.
In a study published online by the Journal of Substance Abuse Treatment, UC Davis researchers report that it takes at least a year for former methamphetamine users to regain impulse control. The results tell recovering substance abusers, their families and drug-treatment specialists that it can take an extended period of time for the brain functions critical to recovery to improve.
"Recovery from meth abuse does not happen overnight," said Ruth Salo, lead author of the study and a UC Davis assistant professor of psychiatry and behavioral sciences. "It may take a year — or even longer — for cognitive processes such as impulse control and attentional focus to improve. Treatment programs need to consider this when monitoring recovering addicts' progress during their early periods of abstinence."
I see this as further evidence that drug addicts have very impaired free will.
What would help them: A way to totally remove them from access to meth for long enough time for their brains to partially recover (and I say partially because some of the damage is permanent). Put them on an isolated island for over a year where the supplies to the island are highly controlled. For example, have a ship that offloads goods monthly at a port and use a purchasing agent who hides from the sellers where their food and other supplies are really going. Reduce the number of people in the supply chain so that the odds of illicit drugs reaching the island go way down. Freed from drug access for a long enough time they'd have a much better chance for their brains to partially heal to the extent that they'd have a chance of controlling their impulses once released back into society.
Meth uses do poorly in the Stroop attention test for the ability to concentrate on a task and not get distracted.
For the current study, Salo used the widely-validated, computer-based Stroop attention test to measure the abilities of 65 recovering methamphetamine abusers to use cognitive control — or direct their attention to specific tasks while ignoring distractors. Study participants had been abstinent for a minimum of three weeks and a maximum of 10 years, and they had previously used the drug for periods ranging from 24 months to 28 years. The data for the 65 individuals were compared to Stroop attention test data from 33 participants who had never used methamphetamine.
"The test taps into something people do in everyday life: make choices in the face of conflicting impulses that can promote a strong but detrimental tendency," Salo explained. "For meth users, impairments in this decision-making ability might make them more likely to spend a paycheck on the immediate satisfaction of getting high rather than on the longer-term satisfaction gained by paying rent or buying groceries."
MRI studies also show partial return to normality after a year of not using meth.
According to Salo, the new study mirrors previous magnetic resonance imaging (MRI) studies she and her colleagues published in 2005 showing a partial normalization of chemicals in selected brain regions after one year of methamphetamine abstinence.
Stem cell and gene therapies will some day offer prospects for much faster and more thorough recovery. Imagine a stem cell therapy that gives people greater ability to concentrate than they had even before they started using. Imagine a therapy that reduces cravings and makes people feel more calm. The brain is going to be the most difficult to repair organ because it is so incredibly complex. So I'm holding out earlier hope for heart repair or liver repair for example. But I expect brain damage from addiction will become at least partially repairable with stem cells and other new wave treatments that repair tissue.
June 26, 2009 - (BRONX, NY) - A variation in a gene that is active in the central nervous system is associated with increased risk for obesity, according to an international study in which Albert Einstein College of Medicine of Yeshiva University played a major role. The research adds to evidence that genes influence appetite and that the brain plays a key role in obesity.
Robert Kaplan, Ph.D., associate professor of epidemiology & population health, helped direct the international study, which involved 34 research institutions and is published online in PLoS Genetics. Dr. Kaplan and his U.S. and European colleagues found that people who have inherited the gene variant NRXN3 have a 10-15 percent increased risk of being obese compared with people who do not have the variant.
The researchers examined data from eight studies involving genes and body weight. These studies included more than 31,000 people of European origin, ages 45 to 76, representing a broad range of dietary habits and health behaviors.
After analyzing more than two million regions of the human genome, the researchers found that the NRXN3 gene variant ─ previously associated with alcohol dependence, cocaine addiction, and illegal substance abuse ─ also predicts the tendency to become obese. Altogether, researchers found the gene variant in 20 percent of the people studied.
NRXN3 has also been implicated in addiction.
Since NRXN3 is active in the brain and also implicated in addiction, these traits may share some neurologic underpinnings.
Central abdominal fat is a strong risk factor for diabetes and cardiovascular disease. To identify common variants influencing central abdominal fat, we conducted a two-stage genome-wide association analysis for waist circumference (WC). In total, three loci reached genome-wide significance. In stage 1, 31,373 individuals of Caucasian descent from eight cohort studies confirmed the role of FTO and MC4R and identified one novel locus associated with WC in the neurexin 3 gene [NRXN3 (rs10146997, p = 6.4×10−7)]. The association with NRXN3 was confirmed in stage 2 by combining stage 1 results with those from 38,641 participants in the GIANT consortium (p = 0.009 in GIANT only, p = 5.3×10−8 for combined analysis, n = 70,014). Mean WC increase per copy of the G allele was 0.0498 z-score units (0.65 cm). This SNP was also associated with body mass index (BMI) [p = 7.4×10−6, 0.024 z-score units (0.10 kg/m2) per copy of the G allele] and the risk of obesity (odds ratio 1.13, 95% CI 1.07–1.19; p = 3.2×10−5 per copy of the G allele). The NRXN3 gene has been previously implicated in addiction and reward behavior, lending further evidence that common forms of obesity may be a central nervous system-mediated disorder. Our findings establish that common variants in NRXN3 are associated with WC, BMI, and obesity.
Another paper from the same issue of Plos Genetics finds still more genes that influence obesity and fat distribution.
Here, we describe a meta-analysis of genome-wide association data from 38,580 individuals, followed by large-scale replication (in up to 70,689 individuals) designed to uncover variants influencing anthropometric measures of central obesity and fat distribution, namely waist circumference (WC) and waist–hip ratio (WHR). This work complements parallel efforts that have been successful in defining variants impacting overall adiposity and focuses on the visceral fat accumulation which has particularly strong relationships to metabolic and cardiovascular disease. Our analyses have identified two loci (TFAP2B and MSRA) associated with WC, and a further locus, near LYPLAL1, which shows gender-specific relationships with WHR (all to levels of genome-wide significance). These loci vary in the strength of their associations with overall adiposity, and LYPLAL1 in particular appears to have a specific effect on patterns of fat distribution. All in all, these three loci provide novel insights into human physiology and the development of obesity.
Expect to see a continued acceleration of the rate of gene searches looking for genetic variants that cause behavioral and health differences. Genetic sequencing and genetic testing costs have fallen so fast that the full effect of the price drops hasn't filtered through to published papers. The price drops continue because the technology continues to advance rapidly. So the amount of data available for gene searches keeps going up faster. This flood of data is going to lead to a flood of findings. The most dramatic consequence will be a big acceleration in human evolution.
AMES, Iowa -- Parents have been saying for years that their kids are "addicted" to video games, but a new study by an Iowa State University psychology professor is the first to actually report that pathological patterns of video game addiction exist in a national sample of youth, aged 8 to 18.
In a national Harris Poll survey of 1,178 American youths (ages 8-18), ISU Assistant Professor of Psychology Douglas Gentile found nearly one in 10 of the gamers (8.5 percent) to be pathological players according to standards established for pathological gambling -- causing family, social, school or psychological damage because of their video game playing habits.
"Although the general public uses the word 'addiction,' clinicians often report it as pathological use," said Gentile, who is also director of research for the Minneapolis-based National Institute on Media and the Family. "This is the first study to tell us the national prevalence of pathological play among youth gamers, and it is almost 1 in 10."
Don't look at suburban housing tracts as idyllic and happy places. Those manicured lawns hide epidemic levels of substance abuse whether the substance in question is video games or instant messaging phones. Kids are booting up, logging in, and dropping out.
Maybe the games fulfill a need for excitement in brains that crave it?
The study also found that pathological gamers were twice as likely to have been diagnosed with attention problems such as Attention Deficit Disorder or Attention Deficit Hyperactivity Disorder.
But does video game addiction leave kids with little time to smoke pot or take crack cocaine? Do the evil demon video games compete with other forms of vice for attention? Or do they compete with wholesome, fulfilling, and constructive activities? Inquiring minds want to know.
Children whose teachers rated them as more impulsive in kindergarten appear more likely to begin gambling behaviors by the sixth grade, according to a report in the March issue of Archives of Pediatrics & Adolescent Medicine, one of the JAMA/Archives journals.
What I wonder: Since gambling is a lot more accessible online has the internet increased the rate at which people become problem gamblers? I figure the internet enables all sorts of compulsive behaviors like blogging.
Although gambling has become an increasingly common activity among U.S. adults and teens, public health risks remain, the authors write as background information in the article. "Problematic gambling in adults is associated with substance use, depression and suicide, psychopathology, poor general health and a multitude of family, legal and criminal problems," the authors wrote. "Most disconcerting is that young people seem more vulnerable than adults to gambling-related morbidity [illness] and suicidality. Data suggest that in most cases, youthful recreational gambling predates pathological gambling in adulthood."
Card games are the devil's workshop. From there comes video games. Then why not video poker? Before you know it Johnnie is using his lunch money to buy Lotto tickets. A small win hooks him and before you know it he's training to win big like those professional poker players on TV.
Linda S. Pagani, Ph.D., of Sainte-Justine University Hospital Research Center and the Université de Montréal, Canada, and colleagues studied 163 children who were in kindergarten in 1999 (average age 5.5). At the beginning of the school year, teachers were asked to complete a questionnaire rating their students' inattentiveness, distractibility and hyperactivity on a scale from one to nine (with higher values indicating a higher degree of impulsiveness). After six years, when the children were an average of 11.5 years old, they were interviewed by phone and asked whether and how often they played cards or bingo, bought lottery tickets, played video games or video poker for money or placed bets at sports venues or with friends.
After considering other behaviors that may be associated with youth gambling, including parental gambling, a one-unit increase on the kindergarten impulsivity scale corresponded to a 25-percent increase in a child's involvement in gambling in sixth grade.
Controlling for parental gambling probably causes an underestimate of the degree to which innate drives cause gambling. Impulsive parents are going to carry genes for more impulsive behavior. So the impulsive children of impulsive parents are going to have a greater tendency to gamble even if the children are adopted and raised by very unimpulsive controlled people.
NASHVILLE, Tenn.--For risk-takers and impulsive people, New Year's resolutions often include being more careful, spending more frugally and cutting back on dangerous behavior, such as drug use. But new research from Vanderbilt finds that these individuals--labeled as novelty seekers by psychologists--face an uphill battle in keeping their New Year's resolutions due to the way their brains process dopamine. The research reveals that novelty seekers have less of a particular type of dopamine receptor, which may lead them to seek out novel and exciting experiences--such as spending lavishly, taking risks and partying like there's no tomorrow.
The research was published Dec. 31, 2008, in the Journal of Neuroscience.
The neurotransmitter dopamine is produced by a select group of cells in the brain. These dopamine-producing cells have receptors called autoreceptors that help limit dopamine release when these cells are stimulated.
"We've found that the density of these dopamine autoreceptors is inversely related to an individual's interest in and desire for novel experiences," David Zald, associate professor of psychology and lead author of the study, said. "The fewer available dopamine autoreceptors an individual has, the less they are able to regulate how much dopamine is released when these cells are engaged. Because of this, novelty and other potentially rewarding experiences that normally induce dopamine release will produce greater dopamine release in these individuals."
The researchers used positron emission topography (PET) brain scans to help them reach this conclusion.
The researchers used positron emission topography to view the levels of dopamine receptors in 34 healthy humans who had taken a questionnaire that measured the novelty-seeking personality trait. The questionnaire measured things such as an individual's preference for and response to novelty, decision-making speed, a person's readiness to freely spend money, and the extent to which a person is spontaneous and unconstrained by rules and regulations. The higher the score, the more likely the person was to be a novelty seeker.
The researchers found that those that scored higher on the novelty-seeking scale had decreased dopamine autoreceptor availability compared to the subjects that scored lower.
If it becomes possible to use a drug to increase the number of dopamine autoreceptors will some thrill-seekers or perhaps some drug abusers opt to change their brain in such a fundamental way in order to gain greater ability to control and restrict their own actions? I can imagine compulsive spenders opting for such a treatment. But skiers, skydivers, and other thrill seekers might decide they'd rather continue to pursue extreme sports.
Smokers with a certain variant of the a gene involved in neurotransmitter dopamine, catechol-O-methyltransferase (COMT), experience stronger withdrawal symptoms and reductions in working nemory and brain function when they quit smoking. No wonder people with that genetic variant have a higher rate of relapse into smoking.
(PHILADELPHIA) – A new study from the Abramson Cancer Center and Department of Psychiatry in the University of Pennsylvania School of Medicine shows that smokers who carry a particular version of a gene for an enzyme that regulates dopamine in the brain may suffer from concentration problems and other cognitive deficits when abstaining from nicotine – a problem that puts them at risk for relapse during attempts to quit smoking. The findings, newly published in the journal Molecular Psychiatry, pave the way to identify novel medications to treat nicotine addiction.
"These findings also provide an important step toward personalized therapy for nicotine addiction by clarifying the role of inherited genetic variation in smoking abstinence symptoms that promote relapse," says senior author Caryn Lerman, PhD, the Mary W. Calkins Professor in Penn's Department of Psychiatry and Scientific Director of Penn's Abramson Cancer Center.
Smoking can be seen as self medication for the brain. Granted, it is highly toxic self medication. But it provides an immediate benefit along with the many costs.
Spurred by their previous findings that carriers of the catechol-O-methyltransferase (COMT) val gene variant are more susceptible to smoking relapse, the Penn researchers set out to learn if smokers with this genetic background would be more likely to exhibit altered brain function and cognitive deficits during periods of abstinence from smoking.
"Inability to concentrate after quitting is reported by many patients, and this leads them to smoke to reduce these impairments," Loughead says.
In this study, 33 smokers underwent functional magnetic resonance imaging (fMRI) during periods of both abstinence from smoking and while smoking as usual. During the brain scans, subjects were asked to hold in their minds a series of complex geometric figures. Subjects were also asked to complete a withdrawal symptoms checklist and a questionnaire about their smoking urges. Results showed that smokers with the COMT val/val genotype suffered greater deficits in working memory and brain function when they had refrained from smoking for 14 or more hours, compared to their performance on this task when they had been smoking as usual. This group also exhibited significant increases in withdrawal symptoms during the abstinence challenge session, compared to the other two genotype groups in the study.
The development of compounds which share some of nicotine's effects on the brain might enable smokers to both quit and to function at a higher cognitive level.
Inhibitors of this COMT enzyme might work to ease withdrawal from nicotine. Inhibitors of COMT already are known to increase working memory.
One method may be to offer carriers of this gene targeted therapies with drugs like COMT inhibitors, some of which have been shown to increase working memory in healthy volunteers.
PITTSBURGH, Nov. 6 – A new study suggests that genetic factors influence size variations in a certain region of the brain, which could in turn be partly responsible for increased susceptibility to alcohol dependence.
It appears that the size of the right orbitofrontal cortex (OFC), an area of the brain that is involved in regulating emotional processing and impulsive behavior, is smaller in teenagers and young adults who have several relatives that are alcohol dependent, according to a study led by Dr. Shirley Hill, Ph.D., professor of psychiatry, University of Pittsburgh School of Medicine.
In the research, which was published this week in the early online version of Biological Psychiatry, Dr. Hill and her team imaged the brains of 107 teens and young adults using magnetic resonance imaging. They also examined variation in certain genes of the participants and administered a well-validated questionnaire to measure the youngsters' tendency to be impulsive.
The participants included 63 individuals who were selected for the study because they had multiple alcohol-dependent family members, suggesting a genetic predisposition, and 44 who had no close relatives dependent on drugs or alcohol. Those with several alcohol-dependent relatives were more likely to have reduced volume of the OFC.
When the investigators looked at two genes, 5-HTT and BDNF, they found certain variants that led to a reduction in white matter volume in the OFC, and that in turn was associated with greater impulsivity.
The 5-HTT is a transporter gene for the neurotransmitter serotonin. The gene has been linked to depression, hyperactivity, and disruptive behavior in boys. Low levels of BDNF, or Brain-derived neurotrophic factor, have been linked to assorted problematic cognitive phenomena as well. So a role for these genes in influencing the degree of impulsivity is plausible.
If you pride yourself in your self-control don't feel too smug about the wisdom of your free will in choosing to be so controlled. You probably just have a large right orbitofrontal cortex due to getting genes that code for a large right OFC.
CHARLOTTESVILLE, Va., October 13, 2008 - Could an aversion to bitter substances or an overall heightened sense of taste help protect some people from becoming addicted to nicotine? That's what researchers at UVA have found using an innovative new method they've developed to analyze the interactions of multiple genetic and environmental factors. Their findings one day may be key in identifying people at risk for nicotine dependence.
In a study published in the October 10, 2008 issue of The American Journal of Human Genetics, University of Virginia Health System researchers report that two interacting genes related to bitter taste sensitivity, TAS2R16 and TAS2R38, play an important role in a person's development of nicotine dependence and smoking behavior. Researchers found that people with higher taste sensitivity aren't as likely to become dependant on nicotine as people with decreased taste sensitivity.
Greater taste sensitivity might discourage cigarette smoking by making tobacco smoke taste more bitter.
It's long been known that a person's ability to taste bitter substances plays a crucial role in the rejection of potentially toxic foods, but taste sensitivity varies widely among individuals and between ethnic groups.
This is yet another way in which genes control human behavior without our being aware of it.
Using genetic engineering, researchers headed by Professor Dr. Günther Schütz at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have now been able to selectively switch off those protein components in dopamine-producing neurons that are integrated into the receptor complexes under the influence of cocaine. Jointly with the team of Professor Dr. Rainer Spanagel at the Central Institute of Mental Health (Zentralinstitut für Seelische Gesundheit, ZI) in Mannheim and the research group of Professor Dr. Christian Lüscher at Geneva University, the Heidelberg researchers studied the changes in physiology and behavior of the genetically modified animals.
The scientists performed standardized tests to measure addictive behavior in the animals. At first sight, both the genetically modified and the control animals displayed the usual behavior under the influence of cocaine. Forced to increase their agility, the lab animals covered significantly greater running distances and preferentially frequented those places where they had been conditioned to be regularly administered the drug.
If normal mice do not find drugs at the familiar places over a longer period of time, their addictive behavior and preference for the cocaine-associated places subside. However, this is not true for animals whose receptor subunit GluR1 has been switched off: These mice invariably frequent the places where they expect to find the drug, i.e., their addictive behavior persists.
Mice whose NR1 protein has been switched off have surprised scientists with a different conspicuous behavior. If control animals withdrawn from cocaine are readministered the drug after some time, addictive behavior and drug seeking are reactivated. In contrast, NR1 deficient animals proved to be resistant to relapsing into the addiction.
So find a drug that will suppress NR1 in humans and maybe kicking coke addiction would become a lot easier.
Blocking the gene NR1 and activating the gene GluR1 might extinguish cocaine addiction.
"It is fascinating to observe how individual proteins can determine addictive behavioral patterns," says Günther Schütz, and his colleague Rainer Spanagel adds: "In addition, our results open up whole new prospects for treating addiction. Thus, blocking the NR1 receptor might protect from relapsing into addiction. Selective activation of GluR1 would even contribute to 'extinguishing' the addiction."
Imagine a person genetically engineered with an assortment of genes that can be turned on and off to cause changes in behavior. Genetically engineered soldiers could be given a compound in their drinks that turn them alternatively docile in peace time or aggressive for training or war time. Or some really rich guy could pay surrogate parents to raise a genetically engineered daughter who could be made to fall in love with and be totally loyal to whoever she was exposed to after eating a dinner with a special compound in it. The possibilities are endless.
Or how about this: an injectable gene therapy that will cause a person become more easily manipulated to switch loyalties. Spies could kidnap someone and turn them against their nation.
On more than one occasion I've found myself defending drug addicts while arguing with someone who is obese. Basically I argued that their own inability to ignore their hunger is very similar to a drug addict's inabilty to ignore the craving for another dose. Each person who I made this argument to responded like I was insulting them. But the evidence strongly suggests common mechanisms involved in food and drug cravings. Now a new study finds that a drug under development against cocaine and meth causes weight loss in rats.
UPTON, NY -- Vigabatrin, a medication proposed as a potential treatment for drug addiction by scientists at the U.S. Department of Energy's (DOE) Brookhaven National Laboratory, also leads to rapid weight loss and reduced food intake according to a new animal study from the same research group. The study will be published online August 20, 2008, by the journal Synapse. Vigabatrin is currently undergoing U.S. Food and Drug Administration (FDA)-approved Phase II clinical trials against cocaine and methamphetamine addiction across the U.S.
In the current study, animals genetically bred to be obese experienced a loss of up to 19 percent of their total weight while non-obese animals lost 12 to 20 percent following short-term vigabatrin administration.
This might seem like good news for people who weigh too much. But it might also be bad news for coke and meth addicts. Will they eat enough while on this drug? Maybe so. Then again, if the drug works and they stop their drug addiction then that's a huge benefit.
"Our results appear to demonstrate that vigabatrin induced satiety in these animals," said Amy DeMarco, who led the study, working in the laboratory of Brookhaven Lab senior scientist Stephen Dewey. Dewey first identified vigabatrin as a potential addiction treatment and has conducted more than 20 years of preclinical research with this promising medication.
Earlier studies at Brookhaven Lab found a strong connection between obesity and addiction, including similar changes in the brains of the obese and those addicted to drugs like cocaine. Based on these connections, Dewey hypothesized that vigabatrin would quench food cravings in the lab rats.
This drug alters people's basic desires. If our desires can be altered so easily do we really have free will?
If you have the less common rs16969968 form of the CHRNA5 gene and you smoke a cigarette you are more likely to get hooked. Yet another reduction in the possible scope for free will.
In a paper published in the September issue of the journal Addiction, , a multi-university collaborative team of researchers specializing in statistical genetics, gene analysis, and trait analysis reports an association between a variant in the CHRNA5 nicotine receptor gene, initial smoking experiences, and current smoking patterns.
The genetic and smoking data come from 435 volunteers. Those who never smoked had tried at least one cigarette but no more than 100 cigarettes in their lives, and never formed a smoking habit. The regular smokers had smoked at least five cigarettes a day for at least the past five years.
The regular smokers in the study were far more likely than the never-smokers to have the less common rs16969968 form of the CHRNA5 gene, in which just one base-pair in the gene sequence was different from the more common form. This kind of genetic variation is called a single nucleotide polymorphism or SNP.
Smokers were also eight times as likely to report that their first cigarettes gave them a pleasurable buzz.
"It appears that for people who have a certain genetic makeup, the initial physical reaction to smoking can play a significant role in determining what happens next," says senior author and project leader, Ovide Pomerleau, a professor of psychiatry at the University of Michigan Medical School and founder of the U-M Nicotine Research Laboratory.
"If cigarette smoking is sustained, nicotine addiction can occur in a few days to a few months," he adds. "The finding of a genetic association with pleasurable early smoking experiences may help explain how people get addicted — and, of course, once addicted, many will keep smoking for the rest of their lives."
Among those who ever try smoking this gene explains only part of the difference between those who become addicted and those who do not. Expect more discoveries of genes that contribute to the odds of getting addicted.
We are witnessing an acceleration of the rate of discovery of genetic factors that influence behavior. This acceleration in the rate of discovery will accelerate as DNA testing costs continue to drop. So expect to see many more reports of genes that influence behavior.
Drinking at an early age can lead to later alcohol dependence
An early age at onset of drinking (AOD) is a strong predictor of subsequent alcohol dependence (AD). Following through on previous research that found substantial increases in drinking and AD among women born between 1944 - 1983, compared to women born between 1934 - 1943, this study examined the influence of AOD. Results showed that women born after 1944 also began drinking earlier than their predecessors, which might help to explain their higher rates of AD.
- An early age at onset of drinking (AOD) is a strong predictor of subsequent alcohol dependence (AD).
- New findings indicate that an early AOD among women born after 1944 may account for their increased rates of lifetime AD.
- An earlier AOD may be connected to decreased minimum legal drinking age laws.
Results will be published in the August issue of Alcoholism: Clinical & Experimental Research and are currently available at OnlineEarly.
“Previous work had found that about one in three individuals who reported having started drinking at ages 17 or younger also reported having been alcohol dependent, either currently or previously,” explained Richard A. Grucza, an epidemiologist at Washington University School of Medicine and the study’s corresponding author. “For people who reported that they started drinking at age 21 or older, that number is one in ten. In other words, individuals who begin drinking at 17 or younger are more than three times more likely to develop AD than those who begin at age 21 or older.”
“This manuscript has elegantly demonstrated that the reduction in AOD seen in women born after 1944 was associated with an increase in AD,” said Wilson M. Compton, director of the Division of Epidemiology, Services and Prevention Research, at the National Institute on Drug Abuse. “By analyzing information from two large studies [conducted 10 years apart], the researchers have disentangled when in history there was a change in AOD in comparison with rates of AD.”
The two large, national surveys used were the National Longitudinal Alcohol Epidemiologic Survey (NLAES), conducted in 1991 and 1992; and the National Epidemiological Survey on Alcohol and Related Conditions (NESARC), conducted in 2001 and 2002. Grucza and his colleagues looked at changes in AOD as well as the lifetime prevalence of AD, while simultaneously controlling for age-related factors.
I've come across similar research with addictive drugs used with animals. The developing brain is more susceptible to the effects of drugs and alcohol. Adult brains are less malleable and therefore less at risk from drug and alcohol exposure.
Working with a dozen healthy participants who drink socially, research fellow Jodi Gilman, working with senior author Daniel Hommer, MD, at the National Institutes on Alcohol Abuse and Alcoholism, used functional magnetic resonance imaging (fMRI) to study activity in emotion-processing brain regions during alcohol exposure. Over two 45-minute periods, the study participants received either alcohol or a saline solution intravenously and were shown images of fearful facial expressions. (Previous studies have shown that expressions of fear signal a threatening situation and activate specific brain regions.)
The same group of participants received both alcohol and placebo, on two separate days.
Comparing brain activity, Gilman’s team found that when participants received the placebo infusion, fearful facial expressions spurred greater activity than neutral expressions in the amygdala, insula, and parahippocampal gyrus—brain regions involved in fear and avoidance—as well as in the brain’s visual system. However, these regions showed no increased brain activity when the participants were intoxicated.
In addition, alcohol activated striatal areas of the brain that are important components of the reward system. This confirms previous findings and supports the idea that activation of the brain’s reward system is a common feature of all drugs of abuse. Gilman’s team found that the level of striatal activation was associated with how intoxicated the participants reported feeling. These striatal responses help account for the stimulating and addictive properties of alcohol.
Does alcohol have a similar suppressive effect in reaction to a happy face? Or does it amplify our emotional response to happy smiling people?
A hobbled ability to detect threats can get one into trouble.
“The key finding of this study is that after alcohol exposure, threat-detecting brain circuits can’t tell the difference between a threatening and non-threatening social stimulus,” said Marina Wolf, PhD, at Rosalind Franklin University of Medicine and Science, who was unaffiliated with the study. “At one end of the spectrum, less anxiety might enable us to approach a new person at a party. But at the other end of the spectrum, we may fail to avoid an argument or a fight. By showing that alcohol exerts this effect in normal volunteers by acting on specific brain circuits, these study results make it harder for someone to believe that risky decision-making after alcohol ‘doesn’t apply to me’,” Wolf said.
Do some people have minds that naturally fail to identify threatening or fearful or angry faces? Can one lack this ability yet still have the ability to identify happy faces or faces that communicate other emotional states? My guess is that some of these facial expression reading abilities vary separately from each other.
WASHINGTON — New drug research suggests that teens may get addicted and relapse more easily than adults because developing brains are more powerfully motivated by drug-related cues. This conclusion has been reached by researchers who found that adolescent rats given cocaine – a powerfully addicting stimulant – were more likely than adults to prefer the place where they got it. That learned association endured: Even after experimenters extinguished the drug-linked preference, a small reinstating dose of cocaine appeared to rekindle that preference – but only in the adolescent rats.
The research, performed at McLean Hospital, Harvard Medical School’s largest psychiatric facility, was reported in the April issue of Behavioral Neuroscience, published by the American Psychological Association.
Evidence that younger brains get stuck on drug-related stimuli reinforces real-world data. Epidemiological studies confirm that of people in various age groups who experiment with drugs, teens are by far the most likely to become addicted. Thus, the new findings may be useful in developing new treatments for youthful addiction.
Future treatments that rejuvenate the brain might make people more prone to drug addiction.
Picture a recreational drug that temporarily suppresses your ability to learn as a way to protect against the risk of learning to like the drug. Could this approach reduce the risk of drug addiction?
The chronic effects of cocaine abuse on brain structure and function are blamed for the inability of most addicts to remain abstinent. Part of the difficulty in preventing relapse is the persisting memory of the intense euphoria or cocaine “rush”. Most abused drugs and alcohol induce neuroplastic changes in brain pathways subserving emotion and cognition. Such changes may account for the consolidation and structural reconfiguration of synaptic connections with exposure to cocaine. Adaptive hippocampal plasticity could be related to specific patterns of gene expression with chronic cocaine abuse. Here, we compare gene expression profiles in the human hippocampus from cocaine addicts and age-matched drug-free control subjects. Topping the list of cocaine-regulated transcripts was RECK in the human hippocampus (FC = 2.0; p<0.05). RECK is a membrane-anchored MMP inhibitor that is implicated in the coordinated regulation of extracellular matrix integrity and angiogenesis. In keeping with elevated RECK expression, active MMP9 protein levels were decreased in the hippocampus from cocaine abusers. Pathway analysis identified other genes regulated by cocaine that code for proteins involved in the remodeling of the cytomatrix and synaptic connections and the inhibition of blood vessel proliferation (PCDH8, LAMB1, ITGB6, CTGF and EphB4). The observed microarray phenotype in the human hippocampus identified RECK and other region-specific genes that may promote long-lasting structural changes with repeated cocaine abuse. Extracellular matrix remodeling in the hippocampus may be a persisting effect of chronic abuse that contributes to the compulsive and relapsing nature of cocaine addiction.
If genes cause people to act compulsively then, what, we don't have total free will?
If we don't have total free will then doesn't that at least partially undermine arguments from political ideologies and philosophies that extol free societies? Do we need free wills in order for free societies to be intellectually defendable? I suppose your genes might be getting expressed in way s that will cause you to argue that we really do have free wills or that the real answer doesn't matter and has no implication for debates about freedom.
Also, does this result have any implications for drug legalization debates? (me thinks libertarian legalizers will say NO).
A meta-analysis of 35 longitudinal studies finds more schizophrenia and other psychotic illnesses among past and current users of reefer. (making the term "reefer madness" prophetic)
Cannabis users are 40% more likely than non-users to suffer a psychotic illness such as schizophrenia, say UK experts.
Writing in the Lancet, a team led by Dr Stanley Zammit from Bristol and Cardiff Universities said young people needed to be made aware of the dangers.
Beware the demon weed. Or as Mr. Mackey would say, "Mari-joowanna is bad, mmmkay?".
Zammit and his colleagues combined data from 35 longitudinal trials, in which populations are observed over time. They found that, even after allowing for other factors, such as other substance use and intelligence, people who have taken cannabis are 41% more likely to develop schizophrenia or other psychotic problems than those who have never used it. Those who used cannabis most frequently were more than twice as likely to suffer problems.
It was less clear whether cannabis use was also linked to depression, suicidal thoughts or anxiety.
What I want to know: Are tokers fatter than the average person?
Genetic tests using blood samples already are used to diagnose some diseases and even personalize treatment.
Now it is possible to develop similar tests that reveal a person's potential to become dependent on nicotine or marijuana or have antisocial personality disorder, University of Iowa researchers report online March 6 in the American Journal of Medical Genetics.
Such tests would not dictate who would become substance dependent or have behavioral problems, as genes do not function in isolation but are influenced by other genes and environmental factors, said the study's lead author Robert Philibert, M.D., Ph.D., professor of psychiatry in the UI Roy J. and Lucille A. Carver College of Medicine.
"Our study suggests that analyzing the expression of genes in blood could indicate whether a person is susceptible to having a behavioral disorder. Having a particular gene expression change does not by itself predict that a person will act a certain way. However, it can indicate who might have a greater biological basis for engaging in behaviors such as smoking and alcohol or marijuana use," Philibert said.
"What matters most is not whether you have a particular gene but whether the gene is expressed, and what other environmental factors may be at play. Genetic variation in and of itself is not deterministic," he added.
Panic disorder may be identifiable from a blood test as well.
In a related study also published online March 6, Philibert and colleagues reported a potential blood test for panic disorder. Both the panic disorder study and one on substance abuse used data from the Iowa Adoption Studies, which were established by Remi Cadoret, M.D., an internationally renowned UI professor of psychiatry who passed away in 2005.
In this latest study, the researchers found certain differences in the genes of people with a history of smoking compared to those without such a history. In all, 579 genes were more expressed and 584 genes were less expressed in people who had smoked.
An effective treatment for addiction will have to reset the expression patterns for hundreds of genes. But a small number of genes might get changed by an addictive drug and those genes might cause all the other genes to express differently. So tweaking a small number of genes might be enough to restore people back to gene expression patterns they had before getting addicted.
Smokers with a damaged insula – a region in the brain linked to emotion and feelings – quit smoking easily and immediately, according to a study in the Jan. 26 issue of the journal Science.
The study provides direct evidence of smoking's grip on the brain.
It also raises the possibility that other addictive behaviors may have an equally strong hold on neural circuits for pleasure.
The senior authors of the study are Antoine Bechara and Hanna Damasio, both faculty in the year-old Brain and Creativity Institute at the University of Southern California, in collaboration with graduate students Nasir Naqvi, who was first author on the study, and David Rudrauf, both from the University of Iowa.
"This is the first study of its kind to use brain lesions to study a drug addiction in humans," Naqvi said.
In the 1990s, Antonio Damasio proposed the insula, a small island enclosed by the cerebral cortex, as a "platform for feelings and emotion." The Science study shows that the pleasure of smoking appears to rest on this platform.
"It's really intriguing to think that disrupting this region breaks the pleasure feelings associated with smoking," said Damasio, director of the institute and holder of the David Dornsife Chair in Neuroscience at USC.
"It is immediate. It's not that they smoke less. They don't smoke, period."
Strokes damage many different areas of the brain. A subset of all stroke patients happen to experience damage to their insulas and a reduction in their cravings for cigarettes.
The study, pubished today in the journal Science, was inspired by a patient who smoked 40 cigarettes a day before having a stroke that damaged his insula. He quit immediately, telling doctors that he “forgot the urge to smoke”.
The scientists then turned to a database of stroke patients held by the University of Iowa and identified 69 who had smoked at least five cigarettes a day for at least two years before they suffered brain damage. They found that 19 of these patients had damage to the insula and 13 of them had given up smoking, 12 of them quickly and easily. The other six continued to smoke — possibly reflecting damage to different parts of the insula.
Comparisons of insulas done with brain scanning technologies such as functional magnetic resonance (fMRI) may lead to identification of exactly where the insula must get damaged to stop cigarette craving. I bet some smokers will subject themselves to brain surgery to damage a part of their insula if they could be assured of little or no side effects aside from a decreased desire to smoke.
The patients’ desire to eat, by contrast, was intact. This suggests, the authors wrote, that the insula is critical for behaviors whose bodily effects become pleasurable because they are learned, like cigarette smoking.
The insula, for years a wallflower of brain anatomy, has emerged as a region of interest based in part on recent work by Dr. Antonio Damasio, a neurologist and director of the Brain and Creativity Institute. The insula has widely distributed connections, both in the thinking cortex above, and down below in subcortical areas, like the brain stem, that maintain heart rate, blood pressure and body temperature, the body’s primal survival systems.
Based on his studies and others’, Dr. Damasio argues that the insula, in effect, maps these signals from the body’s physical plant, and integrates them so the conscious brain can interpret them as a coherent emotion.
The search will now start in earnest: Scientists will look for drugs or try biofeedback training methods or try transcranial magnetic stimulation or other therapies in order to tweak the insula to reduce cravings.
ST. PAUL, Minn – Methamphetamine use may be associated with increased risks of major neck artery tears and stroke, according to an article published in the December 26, 2006, issue of Neurology, the scientific journal of the American Academy of Neurology.
“It appears methamphetamine use is toxic to large blood vessels,” said the study’s senior author Wengui Yu, MD, PhD, with the University of California, Irvine Medical Center and a member of the American Academy of Neurology.
The article reviewed the cases of two women, ages 36 and 29, who had sudden onset of speech difficulty and weakness following recent use of methamphetamine.
Brain scans showed both women had severe strokes from carotid artery dissection, which is a tear in the inner lining of one of the major arteries in the neck. On the National Institutes of Health Stroke Scale, the 36-year-old woman received a score of 21 and was treated with tissue plasminogen activator. The 29-year-old woman, who required a stent to treat the blockage in her common carotid artery, received a score of 17. Stroke Scale scores over 16 predict a high probability of death or severe disability.
Toxic drugs that cause cell death accelerate the aging process. Even if abusers stop taking meth or coke they've forced their stem cells to do a lot more dividing to repair the damage they were constantly causing while still using. All that extra cell division causes the stem cells to wear out more quickly. So as they get older they'll probably develop circulatory problems sooner than they otherwise would have.
Meth and coke users probably also get silent strokes due to damage to smaller blood vessels that affect smaller regions in the brain. Brain cell death amounts to loss of part of your identity. Once we gain the ability to grow replacement brain cells from youthful stem cells that won't bring back memories that went away with the cell death caused by stroke.
CHICAGO -- Researchers have discovered that even a small amount of MDMA, better known as ecstasy, can be harmful to the brain, according to the first study to look at the neurotoxic effects of low doses of the recreational drug in new ecstasy users. The findings were presented today at the annual meeting of the Radiological Society of North America (RSNA).
“We found a decrease in blood circulation in some areas of the brain in young adults who just started to use ecstasy,” said Maartje de Win, M.D., radiology resident at the Academic Medical Center at the University of Amsterdam in the Netherlands. “In addition, we found a relative decrease in verbal memory performance in ecstasy users compared to non-users.”
Note that Dr. de Win is in the Netherlands and therefore probably not under the control of what some paranoids see as a US government plot to produce lots of false propagandistic drug research which supposedly has corrupted all drug research in America. But who knows. Maybe the CIA does international work for the US National Institute on Drug Absue
Ecstasy is an illegal drug that acts as a stimulant and psychedelic. A 2004 survey by the National Institute on Drug Abuse (NIDA) found that 450,000 people in the United States age 12 and over had used ecstasy in the past 30 days. In 2005, NIDA estimated that 5.4 percent of all American 12th graders had taken the drug at least once.
Ecstasy targets neurons in the brain that use the chemical serotonin to communicate. Serotonin plays an important role in regulating a number of mental processes including mood and memory.
Research has shown that long-term or heavy ecstasy use can damage these neurons and cause depression, anxiety, confusion, difficulty sleeping and decrease in memory. However, no previous studies have looked at the effects of low doses of the drug on first-time users.
So we know that MDMA in longer term users causes damage. But these researchers wanted to find out how quickly the damage appears to show up. So they recruited malleable young minds who were just about to tune in, turn on, and drop out (anyone else remember that drug documentary with Timothy Leary?).
Dr. de Win and colleagues examined 188 volunteers with no history of ecstasy use but at high-risk for first-time ecstasy use in the near future. The examinations included neuroimaging techniques to measure the integrity of cells and blood flow in different areas of the brain and various psychological tests. After 18 months, 59 first-time ecstasy users who had taken six tablets on average and 56 non-users were re-examined with the same techniques and tests.
The ecstasy users experienced decreased blood flow in some brain regions and decreased verbal memory performance.
The study found that low doses of ecstasy did not severely damage the serotonergic neurons or affect mood. However, there were indications of subtle changes in cell architecture and decreased blood flow in some brain regions, suggesting prolonged effects from the drug, including some cell damage. In addition, the results showed a decrease in verbal memory performance among low-dose ecstasy users compared to non-users.
Unless you happen to have the body and face of a Mischa Barton or a Paris Hilton your brain is probably your most valuable asset. Damaging it for transitory kicks does not seem like a wise strategy. Even Mischa and Paris will reduce their earnings potential if they damage their brains. Please Mischa, be careful. You too Jessica Alba.
Here's yet another way (other ways including lowered offspring intelligence) that women who smoke cigarettes damage their unborn fetal children. Cigarette smoking causes fetuses to grow up into adults who are more likely to smoke.
The authors base their findings on over 3,000 mothers and their children, who were part of a long term pregnancy study in Brisbane, Australia (MUSP) in 1981.
They assessed the smoking patterns of liveborn children when they reached the age of 21 in relation to the behaviour of their mothers during the pregnancy.
Around a third of the women said that they had smoked during their pregnancy.
The proportion of the children who took up regular smoking was greater among those whose mothers had smoked during the pregnancy than among those whose mothers had not.
Children whose mothers had smoked while pregnant were almost three times as likely to start smoking regularly at or before the age of 14 and around twice as likely to start smoking after this age as those whose mothers were non-smokers.
Smoking patterns among children whose mothers stopped smoking while pregnant, but then resumed the habit, were similar to those whose mothers had never smoked.
Note that the kids born to mothers who temporarily stopped smoking while pregnant did not have a higher risk of developing nicotine addiction later in life.
This reminds me of a 2001 study on the effect of meth on developing brains. Fetuses exposed to meth become more prone to brain damage from using meth when adults.
Exposure before birth to methamphetamine, an increasingly popular "club" drug, renders males, even as adults, much more susceptible to the drug's brain-damaging effects, reveals a study performed in mice by researchers at the University of Chicago.
If males who were prenatally exposed to methamphetamine take the drug themselves as teens or adults, the increased toxicity could hasten the onset of brain disorders such as Parkinson's disease, warn the authors in the August issue of the Journal of Pharmacology and Experimental Therapeutics, published electronically on July 13.
"No one who values his or her brain should take this drug," cautions neurotoxicologist Alfred Heller, M.D., Ph.D., professor of neurobiology, pharmacology and physiology at the University of Chicago and director of the study. "If you're male, and if your mother took methamphetamine -- and it's difficult to be certain she didn't -- you should not go near this drug."
My guess is that the biggest cost of addictive drug use comes from the effects on fetuses and babies exposed to the drugs their moms use. Lower IQs, higher irritability, and greater impulsitivty are just some of the ways that fetal drug exposure is causing lifelong costs for exposed offspring and for the rest of us since we have to deal with these damaged people.
Our ancestors did not undergo selective pressures to select for offspring better able to handle addictive drugs. If they had encountered these compounds over tens of thousands of years the compounds would probably not even be addictive. We'd have genetic variations that protect us from opioids, amphetamines, and nicotine.
My guess is that the biggest cost of addictive drugs comes from damage to developing fetuses and babies. Lower IQs, attention deficit disorder, greater impulsivity, and other cognitive changes are among the costs and probably reduce earnings potential as well as increase criminality and other behaviors that harm self and others.
Neuroscientist David Robbe of Rutgers University and his colleagues tested the impact of THC and a synthetic cannabinoid on rats that had their heads restrained. The drugs affected certain brain waves: the theta (four to 12 hertz) and fast ripple (100 to 200 hertz) waves diminished significantly, whereas the drug had a slightly lesser impact on gamma (30 to 80 hertz) waves. Because theta and gamma oscillations are thought to play a critical role in creating and storing short-term memories--and fast ripple oscillations may allow such short-term memories to be moved into long-term storage--this suppression could mean missing memories for the rats.
The stoners ought to try to remember the details of this research to think about it next time they take a toke.
The THC caused hippocampus nerve signal firings to fall out of sync and to fire less powerfully. The rats had been trained to alternate their routes through a maze and the rats on THC did a far worse job of remembering which route to take next based on which route they took previously.
Normal rats accurately alternate their routes about 90% of the time. But rats given THC, which caused asynchronous nerve firing, chose a random direction on each run, and so chose the correct route 50% of the time.
The disruptive effect of THC wore off within a few hours. Robbe says he hopes to find out whether chronic exposure to the drug causes lasting effects on the hippocampus in rats. Scientists studying people have found that long-term marijuana users gradually become worse at learning and remembering things (see Pot-smoking your way to memory loss).
Neurons that spend a lot of time firing in some different way in response to a drug probably reconfigure somehow in response to the different pattern of firing. Brains strengthen and weaken connections in response to stimuli, whether those stimuli come from the environment or from drugs or an interaction of the two.
What I'd like to know: What does the THC do to change the development of a fetal hippocampus?
Periodically I like to harp on the damage that addictive drugs do to brains because some libertarians (and not a few economists) imagine that we all have enough free will to make rational decisions about addictive drug use. I take a more evolutionary approach to humans and free will. Our capacity to think rationally is spotty at best and there are elements of our modern technological societies that we are so maladapted to handle that we are like dogs that want to chase cars. When dogs do it they get injured or killed and we are no different. We aren't wired up to handle some products of our societies and it is naive to pretend otherwise.
Here is yet another study showing impaired ability of addicts to make judgements that would seem like common sense to, say, a free market libertarian. Coke heads have impared abilties to perceive awards and control how they respond to rewards.
ATLANTA, GA -- People addicted to cocaine have an impaired ability to perceive rewards and exercise control due to disruptions in the brain's reward and control circuits, according to a series of brain-mapping studies and neuropsychological tests conducted at the U.S. Department of Energy's Brookhaven National Laboratory.
"Our findings provide the first evidence that the brain's threshold for responding to monetary rewards is modified in drug-addicted people, and is directly linked to changes in the responsiveness of the prefrontal cortex, a part of the brain essential for monitoring and controlling behavior," said Rita Goldstein, a psychologist at Brookhaven Lab. "These results also attest to the benefit of using sophisticated brain-imaging tools combined with sensitive behavioral, cognitive, and emotional probes to optimize the study of drug addiction, a psychopathology that these tools have helped to identify as a disorder of the brain."
Some day drug addicts might be treated by stem cell therapies that go in and restore some missing neurons. Imagine the power of such a therapy. If it can fix damaged brains it will also likely be able to alter the way people with undamaged brains form judgements. Development of repair therapies inevitably leads to development of enhancement therapies and also therapies that are not so much enhancement as simply alteration. For good or bad? I guess we'll find out. Probably some of each, hopefully more good than bad.
The addicts and non-addicts had their brains scanned while they were offered rewards and asked to perform tests.
Goldstein's experiments were designed to test a theoretical model, called the Impaired Response Inhibition and Salience Attribution (I-RISA) model, which postulates that drug-addicted individuals disproportionately attribute salience, or value, to their drug of choice at the expense of other potentially but no-longer-rewarding stimuli -- with a concomitant decrease in the ability to inhibit maladaptive drug use. In the experiments, the scientists subjected cocaine-addicted and non-drug-addicted individuals to a range of tests of behavior, cognition/thought, and emotion, while simultaneously monitoring their brain activity using functional magnetic resonance imaging (fMRI) and/or recordings of event-related potentials (ERP).
Coke addicts couldn't react differently to different levels of reward. They lacked a sense of context for their decision making.
In one study, subjects were given a monetary reward for their performance on an attention task. Subjects were given one of three amounts (no money, one cent, or 45 cents) for each correct response, up to a total reward of $50 for their performance. The researchers also asked the subjects how much they valued different amounts of monetary reward, ranging from $10 to $1000.
More than half of the cocaine abusers rated $10 as equally valuable as $1000, "demonstrating a reduced subjective sensitivity to relative monetary reward," Goldstein said.
"Such a 'flattened' sensitivity to gradients in reward may play a role in the inability of drug-addicted individuals to use internal cues and feedback from the environment to inhibit inappropriate behavior, and may also predispose these individuals to disadvantageous decisions -- for example, trading a car for a couple of cocaine hits. Without a relative context, drug use and its intense effects -- craving, anticipation, and high -- could become all the more overpowering," she said.
So glad my brain hasn't been damaged by extensive coke use.
Coke addicts didn't have their prefrontal cortexes light up in a graded fashion to different sized rewards the way non-addicts did.
The behavioral data collected during fMRI further suggested that, in the cocaine abusers, there was a "disconnect" between subjective measures of motivation (how much they said they were engaged in the task) and the objective measures of motivation (how fast and accurately they performed on the task). "These behavioral data implicate a disruption in the ability to perceive inner motivational drives in cocaine addiction," Goldstein said.
The fMRI results also revealed that non-addicted subjects responded to the different monetary amounts in a graded fashion: the higher the potential reward, the greater the response in the prefrontal cortex. In cocaine-addicted subjects, however, this region did not demonstrate a graded pattern of response to the monetary reward offered. Furthermore, within the cocaine-addicted group, the higher the sensitivity to money in the prefrontal cortex, the higher was the motivation and the self-reported ability to control behavior.
The ERP results showed a similarly graded brain response to monetary reward in healthy control subjects, but not in cocaine-addicted individuals.
Why do addicts relapse? They can't accurately judge the relative rewards of drug use and non-drug use. They simply lack the capacity to arrive at judgements that come easy to most of us.
To rule out social factors, the researchers turned to an animal model. They dosed some rats with the active ingredient of cannabis and others with a neutral compound during their adolescence (when they were about four to six weeks old). After that, they gave the rats intermittent access to heroin for several weeks, obtained by pressing a lever.
Although all rats helped themselves to heroin, the ones given cannabis's key compound, called Delta-9-tetrahydrocannabinol (THC), during their formative years showed a greater escalation in their self-dosing during the experiment. By the end, rats that'd had cannabis in their 'teens' were pressing the lever that delivered heroin about 1.5 times more than the rats that had previously been drug-free.
I find this incredibly unsurprising. The developing brain develops differently if exposed to drugs that activate brain pleasure circuitry.
“At first, all the rats behaved the same and began to self-administer heroin frequently,” says Hurd. “But after a while, they stabilised their daily intake at a certain level. We saw that the ones that had been on THC as teenagers stabilised their intake at a much higher level than the others – they appeared to be less sensitive to the effects of heroin. And this continued throughout their lives.”
Hurd says reduced sensitivity to the heroin means the rats take larger doses, which has been shown to increase the risk of addiction.
Data from a survey of 43,000 U.S. adults heighten concerns that early alcohol use, independent of other risk factors, may contribute to the risk of developing future alcohol problems. Those who began drinking in their early teens were not only at greater risk of developing alcohol dependence at some point in their lives, they were also at greater risk of developing dependence more quickly and at younger ages, and of developing chronic, relapsing dependence. Among all respondents who developed alcoholism at some point, almost half (47 percent) met the diagnostic criteria for alcohol dependence (alcoholism) by age 21.
The associations between early drinking and later problems held even after investigators controlled for other risk factors for dependence, adding to concerns that drinking at a young age might raise the risk of future alcohol problems rather than being an identifying feature of young people predisposed to risky behavior. The study appears in the July issue of Archives of Pediatrics & Adolescent Medicine, Volume 160, pages 739-746.
Timing of first alcohol use leads to a huge difference in risk
In results that echo earlier studies, of those individuals who began drinking before age 14, 47 percent experienced dependence at some point, vs. 9 percent of those who began drinking at age 21 or older. In general, each additional year earlier than 21 that a respondent began to drink, the greater the odds that he or she would develop alcohol dependence at some point in life. While one quarter of all drinkers in the survey started drinking by age 16, nearly half (46 percent) of drinkers who developed alcohol dependence began drinking at age 16 or younger.
New findings showed that among all drinkers, early drinking was associated not only with a higher risk of developing alcoholism at some point, but also within 10 years of first starting to drink, before age 25, and within any year of adult life. Early drinking was also associated with increased risk of having multiple episodes of alcoholism. Further, among respondents who had had alcohol dependence at some point, those who began drinking young had episodes of longer duration and with a wider range of symptoms than those who started later.
The developing brain gets altered by drug and alcohol use. We do not have free will. If legalization would increase the amount of teen drug use then legalization would lead to much more drug abuse and addiction.
Adolescent brains are at much higher risk because they are still developing. Industrialized societies need to do a better job of protected teenagers from subtstances that will mess up their brain development.
Also see my post Adolescence Is Tough On The Brain.
“To make the drug-cues video, we worked with addicts who advised us on how to make it as realistic as possible while simulating scenes involving smoking or snorting cocaine,” said Wang. The scientists also asked the subjects to rate their level of craving while watching both videos, and assessed the severity of their addiction using a standard cocaine craving scale.
Dopamine levels were measured indirectly using positron emission tomography (PET) scanning at Brookhaven’s Center for Translational Neuroimaging. Each subject was injected with a radiotracer designed to bind to dopamine receptors in the brain. During scanning, the PET camera picks up the signal from any bound radiotracer so that levels of tracer bound to receptors can be compared with levels in the blood. As the body’s natural dopamine levels rise, this “endogenous” dopamine competes with the tracer for binding sites, so less radiotracer can bind to the receptors. Therefore, the lower the bound tracer signal, the higher the concentration of endogenous dopamine.
Compared with the neutral video, the cocaine-cues video triggered a significant increase in dopamine in the dorsal striatum, a part of the brain involved in experiencing desire or motivation. The changes in dopamine were associated with the level of craving reported by the subjects and were largest in the most severely addicted subjects.
This finding is consistent with previous animal studies that have suggested a role for the dorsal striatum in cue-induced craving. In those studies, neutral stimuli such as a particular cage environment that had been paired with a drug during “training” sessions later triggered a dopamine increase in both the nucleus accumbens and the dorsal striatum, a response that was correlated with drug-seeking behaviors in the animals.
Frustrated desires for food also cause a rise in brain dorsal striatum dopamine levels.
The finding is also consistent with earlier Brookhaven research documenting dopamine increases in the dorsal striatum induced by exposure to food (see this release). In that study, healthy subjects were allowed to observe and smell their favorite foods, but not eat them; the more the subjects desired the foods, the higher their dopamine levels went.
“Finding this same association between dorsal striatum dopamine levels and cravings for food and drugs suggests that, in the human brain, drug addiction engages the same neurobiological processes that motivate food-seeking behaviors triggered by food-conditioned cues,” Volkow said. This research suggests that compounds that could inhibit cue-induced striatal dopamine increases would be logical targets for medication development to treat cocaine addiction.
These findings suggest to me that compounds which inhibit or reduce desire for cocaine might also reduce cracvings for food. A drug developed to treat coke addicts might also help people to lose weight.
Also, since the vast bulk of us experience food cravings we non-drug addicts probably understand the cravings that drive drug addicts better than many of us realize. Obese people who look down their noses with disapproval at drug addicts ought to go look in the mirror and look at the signs that they have their own very similarly caused cravings which they can not control.
Some day we will gain the ability to tune our desires to better align our daily behavior with our longer term goals. Research into drug addiction, obesity, and other problems with human minds will produce much more than just treatments to suppress desires for food and drugs. We will also gain the ability to mold what causes our minds to feel satisfied, frustrated, impatient, happy, and sad. People will adjust their emotional reactions to make them better able to do tedious work and to pursue longer term goals.
COLUMBUS , Ohio – Researchers found that they could eliminate the rewarding effect of cocaine on mice by genetically manipulating a key target of the drug in the animal's brain.
While the researchers aren't suggesting that these genetic modifications be made in humans, the work brings to light the key protein that controls cocaine's effects in the body, which may help scientists develop medications that achieve the same results and therefore help addicts overcome their dependence.
Humans are not evolutionarily adapted to handle recreational drugs. But some day with genetic engineering our offspring might be adapted to resist drug and alcohol abuse.
Howard Gu and colleagues at Ohio State University showed they could genetically engineer mice to be resistant to the effects of cocaine.
He and his colleagues raised laboratory mice with genetic alterations in the gene that codes for the dopamine transporter.
“By doing so we created a dopamine transporter that resists cocaine but also retains its function of taking up dopamine and carrying it back to the neurons,” Gu said.
I am not surprised that an alteraton of a brain protein could produce a different reaction to a drug will at the same time retaining normal function. But what is amazing is that these scientists - using 2006 biotechnology - were able to find an alteration that produces this outcome.
The behavior of the mice with genetically engineered dopamine transporters suggest that they did not get a high off of cocaine
“The normal mice spent more time in the compartment where they had received the cocaine injections,” Gu said. “These animals were seeking more cocaine. However, the mice with the modified transporters showed no preference for either test compartment within the box.”
The researchers used the video footage to measure each animal's activity level after a cocaine injection. The normal mice on cocaine covered roughly five times the distance than the control mice injected with saline (6 meters vs. 1 meter). In contrast, the cocaine-injected mice with the modified dopamine receptors covered about half the distance that the saline-only injected mice covered (roughly 1.5 meters vs. 3 meters.)
“After the cocaine injections, the normal mice ran all over the place, sniffing and checking everything out in the box over and over again, until we took them out of the box,” Gu said. “But cocaine seemed to calm the modified mice, as they sat in a corner for long periods of time.”
“To the modified mice, cocaine appears to be a suppressant, not a stimulant,” Gu said.
Some people argue it will be hard to discover new ways to enhance cognitive function. But using today's biotechnology these Ohio State scientists found a way to reduce the ability of a drug to alter cognitive function. Imagine what tools will be available 20 years from now to use to search for ways to alter functionality in brain proteins.
Scientists have discovered that our genes have an impact on our reaction to cocaine and our likelihood of developing an addiction to the class A drug. The research is published this week in the online edition of PNAS, the journal of the American Academy of Sciences. It was carried out at the Medical Research Council (MRC) Social, Genetic and Developmental Research Centre at the Institute of Psychiatry, Kingâ€™s College London.
Much of our desire to use/re-use drugs and the process of addiction depend on their impact on brain function. Cocaineâ€™s action within the brain is relatively well understood. It strongly binds and inhibits the action of a protein called the Dopamine Transporter (DAT)1.
In this latest study, researchers examined the DNA of 700 cocaine abusers and 850 ordinary people and found that cocaine abusers had a specific genetic variation in DAT more frequently than the control subjects. People carrying two copies of this variant were 50% more likely to be cocaine dependent.
Expect a continuing stream of reports of genetic variants that heavily influence human behavior. Do humans have any free will at all? Heck if I know. But I'm not betting on it. My guess is my genes insist to me that I have no free will and I believe what they tell me.
Some day we'll all know our complete genetic profiles. We'll know for which drugs we have a greater risk of addiction. Will that knowledge reduce the incidence of drug addiction?
My guess: preventive treatments will play a bigger role in reducing drug addiction than genetic screening. Give Mom and Dad a vaccine or maybe a nanotech implant that'll eat up heroin, cocaine, ecstasy, and other drugs in the bloodstream and Junior won't get high until he can afford medical treatments that'll reverse the drug-neutralizing technologies that his parents had implanted in him when he was 12 years old.
Memory, speed of thinking and other cognitive abilities get worse over time with marijuana use, according to a new study published in the March 14, 2006, issue of Neurology, the scientific journal of the American Academy of Neurology.
The study found that frequent marijuana users performed worse than non-users on tests of cognitive abilities, including divided attention (ability to pay attention to more than one stimulus at a time) and verbal fluency (number of words generated within a time limit). Those who had used marijuana for 10 years or more had more problems with their thinking abilities than those who had used marijuana for five to 10 years. All of the marijuana users were heavy users, which was defined as smoking four or more joints per week.
"We found that the longer people used marijuana, the more deterioration they had in these cognitive abilities, especially in the ability to learn and remember new information," said study author Lambros Messinis, PhD, of the Department of Neurology of the University Hospital of Patras in Patras, Greece. "In several areas, their abilities were significant enough to be considered impaired, with more impairment in the longer-term users than the shorter-term users."
The study involved people ages 17 to 49 taking part in a drug abuse treatment program in Athens, Greece. There were 20 long-term users, 20 shorter-term users and 24 control subjects who had used marijuana at least once in their lives but not more than 20 times and not in the past two years. Those who had used any other class of drugs, such as cocaine or stimulants, during the past year or for more than three months throughout their lives were not included in the study. Before the tests were performed, all participants had to abstain from marijuana for at least 24 hours.
The marijuana users performed worse in several cognitive domains, including delayed recall, recognition and executive functions of the brain. For example, on a test measuring the ability to make decisions, long-term users had 70 percent impaired performance, compared to 55 percent impaired performance for shorter-term users and 8 percent impaired performance for non-users.In a test where participants needed to remember a list of words that had been read to them earlier, the non-users remembered an average of 12 out of 15 words, the shorter-term users remembered an average of nine words and the long-term users remembered an average of seven words.
A longitudinal study would be a lot more convincing. Follow the same tokers for a few years and measure their mental deterioration. Maybe (not that I think this likely) chronic stoners are space cadets even before they become chronic stoners. Or maybe chronic stoners are dumber on average and smarter people decide that getting stoned all the time is just not worth it.
Yeah, maybe. But I doubt it. Heavy duty (multiple times every day) stoner college roommates (not that I ever witnessed criminal activity - this is all hearsay rumours as told to me by other roommates who saw all this while I was at the library of course) whose memories were not first rate came across to me as people who used to be smarter than they were when I knew them. They knew too much about past events and seemed like they once were a lot more together. As kids I figure they didn't used to say "oh wow, I'm supposed to be in class" or "oh wow, I was supposed to meet Lisa for lunch and I like totally spaced". No, I bet they were once a lot more attentive and mentally competent.
If only mainstream left-liberal social scientists hadn't felt the ideological need to collectively decide that the field of psychometrics is the work of Satan some of them would use IQ tests in longitudinal studies of various sorts of drug abusers and we could find out how much damage each recreational drug does to brains.
What practical information I really want to know: Will use of modafinal (Provigil) exact a toll in terms of faster brain aging? Which classes of cognitive-enhancing neuroceuticals won't exact a toll in increased neuronal wear and tear?
When it comes to forming opinions and making judgments on hot political issues, partisans of both parties don't let facts get in the way of their decision-making, according to a new Emory University study. The research sheds light on why staunch Democrats and Republicans can hear the same information, but walk away with opposite conclusions.
The investigators used functional neuroimaging (fMRI) to study a sample of committed Democrats and Republicans during the three months prior to the U.S. Presidential election of 2004. The Democrats and Republicans were given a reasoning task in which they had to evaluate threatening information about their own candidate. During the task, the subjects underwent fMRI to see what parts of their brain were active. What the researchers found was striking.
"We did not see any increased activation of the parts of the brain normally engaged during reasoning," says Drew Westen, director of clinical psychology at Emory who led the study. "What we saw instead was a network of emotion circuits lighting up, including circuits hypothesized to be involved in regulating emotion, and circuits known to be involved in resolving conflicts." Westen and his colleagues will present their findings at the Annual Conference of the Society for Personality and Social Psychology Jan. 28.
Once partisans had come to completely biased conclusions -- essentially finding ways to ignore information that could not be rationally discounted -- not only did circuits that mediate negative emotions like sadness and disgust turn off, but subjects got a blast of activation in circuits involved in reward -- similar to what addicts receive when they get their fix, Westen explains.
"None of the circuits involved in conscious reasoning were particularly engaged," says Westen. "Essentially, it appears as if partisans twirl the cognitive kaleidoscope until they get the conclusions they want, and then they get massively reinforced for it, with the elimination of negative emotional states and activation of positive ones."
The feeling of partisan loyalty is an obstacle to rational thought. Abandon your partisan loyalties and the effect will be to boost your ability to understand political events.
Also, distrust the most partisan commentators who defend the leaders of their factions. Their odds of making sense and being correct are lower than for less partisan commentators.
Addicts of partisanship need treatments that will prevent them from getting high from defending their tribes.
Behavioral data showed a pattern of emotionally biased reasoning: partisans denied obvious contradictions for their own candidate that they had no difficulty detecting in the opposing candidate. Importantly, in both their behavioral and neural responses, Republicans and Democrats did not differ in the way they responded to contradictions for the neutral control targets, such as Hanks, but Democrats responded to Kerry as Republicans responded to Bush.
While reasoning about apparent contradictions for their own candidate, partisans showed activations throughout the orbital frontal cortex, indicating emotional processing and presumably emotion regulation strategies. There also were activations in areas of the brain associated with the experience of unpleasant emotions, the processing of emotion and conflict, and judgments of forgiveness and moral accountability.
Notably absent were any increases in activation of the dorsolateral prefrontal cortex, the part of the brain most associated with reasoning (as well as conscious efforts to suppress emotion). The finding suggests that the emotion-driven processes that lead to biased judgments likely occur outside of awareness, and are distinct from normal reasoning processes when emotion is not so heavily engaged, says Westen.
Political parties harness neural wiring that was probably selected for to encourage tribal solidarity and mutual defense of the tribe. Today it motivates people to defend positions and actions taken by the leaders of their political faction. The human mind was not selected for by evolution to be a perfect reasoning machine.
I feel sorry for the partisans. They are basically drug addicts. But I have greater sympathy for the rest of us who suffer from their actions just as we suffer from the actions of drug addicts.
Update: Think about the pattern of cognitve reaction when people feel loyalties are at stake. Imagine a drug or other treatment could interrupt that reaction. One can imagine why people would want to take such drugs for themselves. One could think more objectively and rationally about business problems or personal problems or political issues. But one can also imagine why governments and other groups would want to avail themselves of neurotechnologies that would allow the disruption of feelings of loyalty.
Millions of people already take drugs to disrupt and prevent feelings of anxiety and depression. The idea of developing pharmaceutical and other medical means to disrupt and prevent other modes of emotional reaction therefore does not seem farfetched. If such disruption can be done with drugs it also probably can be done with genetics to cause offspring to have very different patterns of formation of loyalties. Will people choose to give their offspring different capacities and tendencies to form and defend loyalties? I expect individuals, cults, and governments to do this. I expect humanity to splinter into groups that have greater differences in cognitive function than human groups naturally have due to differences in selective pressures during our evolutionary past.
"Cocaine is highly addictive and can have devastating effects on the health and well being of users," says lead researcher Peter Kalivas, Ph.D., Professor and Chair of the Department of Neurosciences at the Medical University of South Carolina (MUSC). "The discovery that a readily available herbal supplement can reduce the intense cravings associated with cocaine use is an important finding for individuals undergoing treatment for cocaine addiction. Reduced craving might help addicted individuals restrain from abusing cocaine."
In the first phase of the study, Dr. Kalivas and the research team conditioned rats on a regimen of cocaine to establish their addiction. The rats in the treatment group were then treated with NAC. After treatment, the cocaine-addicted rats exposed to NAC were significantly less likely to seek out cocaine than those without NAC. Those treated with NAC ceased to actively seek cocaine, but showed normal food-seeking behaviors.
In the second phase of the study headed by Drs. Robert Malcolm, Hugh Myrick, Steve LaRowe, and Pascale Mardikian in the Department of Psychiatry at MUSC, NAC treatment was investigated in a small inpatient study (n=15) involving non-treatment seeking cocaine-dependent subjects. In this phase of research, subjects were asked to look at pictures that were either neutral (e.g., trees, boats) or cocaine-related (e.g., drug paraphernalia). Those individuals treated with NAC reported less craving for cocaine and spent less time looking at the cocaine-related pictures. In addition, when using a functional magnetic resonance imaging (fMRI) test, subjects treated with NAC had reduced brain activity in the prefrontal cortex, the area of the brain activated during cocaine craving and used to modulate the addictive behavior of chronic cocaine use. An open label trial, which was recently completed, indicated that cocaine-dependent patients could take NAC on an extended outpatient basis, with minimal side effects. More importantly, patients taking higher doses of NAC were more likely to complete the trial, providing further indication of the potential benefits of NAC.
"The potential to use NAC for the treatment of individuals addicted to cocaine is a major finding," emphasized Dr. Kalivas. "For those individuals who have the desire to end their addictive habit, a NAC supplement might help to control their cravings."
A larger clinical trial that will follow 282 cocaine-dependent individuals has just begun in order to further understand and corroborate how NAC works in the brain to reduce cocaine craving. Dr. Kalivas stresses that while the initial findings are very promising, the widespread use of NAC in cocaine treatment is not advised until larger scale studies are complete.
The number of humans involved (15) is too small to know for sure. The bigger study they have begun will provide a more definitive answer.
A new study led by researchers at UCLA's Semel Institute suggests the antidepressant bupropion may help treat methamphetamine addiction. No medications presently are approved for treating methamphetamine addicts.
Appearing Nov. 23 as an advance online publication of the peer-reviewed journal Neuropsychopharmacology, the study finds bupropion blunts the methamphetamine "high" and reduces cravings prompted by visual cues such as ambient drug use.
The research team hypothesizes that bupropion reduces the effects of methamphetamine by preventing the drug from entering brain cells, where methamphetamine can produce release of neurotransmitters that cause feelings of euphoria.
The study is the first to examine the effectiveness of bupropion for treating methamphetamine addiction in humans. A multisite Phase II clinical trial led by UCLA researchers is in progress.
Bupropion is found in the anti-nicotine drug Zyban and the anti-depressant Wellbutrin. So meth addicts could easily start trying to use bupropion right now to help them quit. Since a lot of meth users also smoke cigarettes they might also find it easier to quit smoking at the same time.
Drug addiction is a sign that humans are not adapted to the environments they've created for themselves using advances in technology. We were not selected for by evolution to handle the drugs that scientists have turned up. We need to develop technologies which will allow us to adapt ourselves to the elements in our environment which many of us can not handle. Lest you think the "many of us" doesn't include you I have a few questions to ask you: Are you overweight? Do you get less than an optimal amount of exercise? Ever had any problems with addictions or substance abuse? Have any destructive or at least partially disabling cravings? Spend too much time reading on the internet?
A University of Minnesota study indicates that the nicotine vaccine NicVax, which is now being tested in humans, appears safe, well-tolerated, and a potentially effective method for helping smokers kick the habit.
Dorothy Hatsukami, Ph.D., director of the University of Minnesota Cancer Center's Transdisciplinary Tobacco Use Research Center (TTURC), is the lead author on this study. The 38-week study included 68 active smokers who were randomly assigned to receive one of three different doses of the vaccine or a placebo. The findings are published in the current issue of the journal Clinical Pharmacology and Therapeutics.
"The vaccine works by producing antibodies that specifically bind to nicotine and thereby prevent much of the nicotine from entering the brain," Hatsukami said. "This process potentially reduces the pleasurable effects from smoking and reduces the addiction to nicotine."
The vaccine may become a new option for helping the approximately 45 million people in the United States who smoke. In 2004, the rate for smoking in Minnesota was about the same as the national average of 20.9 percent.
"More research needs to be done, but at this point, our results show the vaccine is safe and well-tolerated," Hatsukami said. "We found the vaccine has few side effects on the central nervous system because the antibody itself is targeted specifically for nicotine and does not alter any functions of the brain."
Additionally, she says that while this study was not designed to test the treatment effect, 38 percent of the participants in the high-dose vaccine group quit smoking for at least 30 days.
"This result was an impressive and completely unexpected finding because the study was not focused on helping smokers quit smoking," she noted. "In fact, to participate in the study, smokers had to attest that they did not have a planned quit date for the next six months."
This is really an ideal addiction treatment because it can just as easily prevent addiction as cure it. However, some drugs might not make good immune system targets. In that case what we need are nanobots that are smart enough to recognize and destroy specific drug targets. Nanobots are a more distant prospect than vaccines though. Another possibility would be to develop gene therapies for the liver that would up a liver's ability to break down a drug compound. Make the drug have a very short half-life in the body. Though people could still get high by use of nasal delivery or other delivery mechanisms that take the drugs to the brain without passing through the liver first.
We also need gene and/or cell therapies that will reverse the effects of addictive drugs on the brain. Also, since some people are genetically more prone to addiction we need gene therapies that will modify the brain to make it less prone to addiction.
Canadian scientists have developed some clever molecular trickery that is helping to reduce the drug cravings of addicted rats. One of the problems in addiction is that neurons in some parts of the brain lose glutamate receptors from the cell surface, and those receptors are important for communication between neurons. The researchers have sidestepped this problem by crafting a peptide that mimics a portion of the tail of the glutamate receptor and, once inside a neuron, serves as a decoy to prevent the loss of glutamate receptors.
Yu Tian Wang, an HHMI international research scholar, and colleagues at the University of British Columbia in Vancouver report their findings in the November 25, 2005, issue of the journal Science.
In addicted rats, cell-to-cell communication is compromised as a result of certain long-term changes at the level of individual neurons. Their research has produced a targeted drug that tricks brain cells into preventing those changes. "We think this is a good candidate for a drug against addiction that has very few side effects," said Wang, a neuroscientist . Although the initial studies are promising, Wang cautioned that the drug is in the early stages of development and is years away from testing in humans.
One obvious problem with this approach is that peptides are hard to deliver. Diabetics have to take insulin shots because the insulin peptide would get digested and broken up if taken orally. So a peptide treatment would probably have to be taken by syringe. Still, diabetics manage to do this and some addicts have plenty of experience with syringes.
Another potential problem is that the peptide might interfere with normal learning or other normal on-going neuronal processes. But such an interference might be worth it given the damage that amphetamine use causes to people's brains and their lives and the lives of other people around them.
The biggest question I see here is whether the peptide will work on existing addicts. Most people aren't going to go to the doctor and say "Hey, I'm about to spend several months abusing amphetamine. Could you prescribe me that peptide drug that'll prevent addiction from developing?". I suspect the peptide will do less to reverse addiction than it will to prevent it. However, the press release isn't clear enough on the protocol used to tell if that is the case.
The peptide has a piece that looks like the glutamate receptor and so competes with the glutamate receptor for getting pulled into the cell.
Wang's team developed a peptide that serves as a decoy to prevent the cell from pulling glutamate receptors in from their surfaces.
The researchers began by building a peptide – a long molecule made from a string of amino acids – with a structure similar to the tail of the glutamate receptor that is anchored inside the cell. In addiction, cellular machinery tugs on this tail, pulling the entire receptor into the cell. Without its business end sticking out into the synapse, or space between neurons, the receptor no longer works.
Wang's peptide tricks the cellular machinery into tugging on it instead of the receptor's tail. "Once it gets inside the neuron, the peptide competes with the receptor for binding to the machinery," Wang explained. With the cellular machinery otherwise occupied, the glutamate receptors stay on the cell surface, where they continue to receive signals.
The peptide prevented sensitization of the rats to amphetamine and therefore probably would block the development of cravings.
After confirming these results in cell cultures, Wang and colleagues tested the peptide in rats that had been given amphetamine once every other day for 20 days. During this period, the animals displayed stereotypical behavior such as repeated sniffing, licking, and grooming, indicating a craving for the drug. Such behavior parallels the compulsive thought patterns that people addicted to drugs experience, said Anthony Phillips, Wang's colleague at the University of British Columbia and a co-author of the article.
After keeping the rats drug-free for 21 days, the researchers gave the animals a small amount of drug again. The rats immediately displayed intense stereotypical behavior – a sign of behavioral sensitization. The behavior meant that the glutamate receptors in the animals' neurons were rapidly internalized, said Wang. "It's the trigger that leads to sustained motivation to seek a drug."
In contrast, addicted animals who received an intravenous injection of the artificial peptide displayed no sensitized behavior. "The effect was immediate and very noticeable," said Wang.
An ideal anti-addiction drug would allow someone in the early stages of addiction to pull out when they realize they've become hooked. But if such a drug existed how many early stage addicts could be convinced to use it before they racked up a lot of brain damage?
Scripps researchers Athina Markou and Paul Kenny found that in rodents nicotine causes an elevation in mood that lasts for weeks after the nicotine is gone.
Nicotine induces a long-lasting activation of the brain's reward systems that is not seen after excessive consumption of other drugs of abuse, such as cocaine or heroin. This slight elevation in mood is there regardless of how much nicotine is consumed, and it persists long after the nicotine is gone from the body.
"It's almost a memory of nicotine in the brain," says Kenny, who is now a staff scientist at Scripps Florida. "The reward system becomes hyperactive, even when the nicotine isn't there."
This persistence of reward activity, Kenny adds, appears unique to nicotine among drugs of abuse and is probably crucial in maintaining the nicotine habit. Knowing this may have relevance to prevention of nicotine addiction and smoking cessation programs.
Weeks after the nicotine was gone the effects on rodent brain reward systems remained. Normal pleasures were still enhanced by the long gone nicotine.
In their study, Markou and Kenny looked at the effect of nicotine self-administration on brain reward systems in laboratory rodents. They allowed the rodents to have extended access to nicotine self-administration, and they directly measured the changes in neuronal activity in the brain.
As predicted, the scientists found that nicotine acutely stimulates the brain's reward system and seems to enhance the normal pleasures in the environment for hours. Unexpectedly, however, rather than the depression-like state induced when cocaine and heroin leave the system, nicotine's elevation of mood persists. The measurements of neuronal activity in the brain's reward system one hour after the nicotine consumption looked similar to those twelve hours after consumption.
In fact, this increased sensitivity to reward persists for days or weeks after the nicotine disappears. The excitation of these systems cannot be due to the presence in the brain of nicotine, which is readily metabolized by enzymes in the body so that all traces of it are gone after a matter of about three to four hours.
So if the nicotine is metabolized and cannot be responsible for the elevation in mood, what is the explanation? One possibility is that nicotine leads to an upregulation of the brain receptors to which it binds--the nicotinic receptors. Since the neurotransmitter acetylcholine also binds to these receptors, the elevation in nicotinic receptors due to nicotine may be behind the persistent elevation in mood.
Do addicts of the demon weed tobacco experience increased pleasure from life as a result of smoking tobacco? Had they never started smoking would their average level of experience of pleasure be lower?
What I'd like to see: A study of twins in their 20s (i.e. young enough not to have too much accumulated damage from cigarette smoking) where one member of each twin smokes and the other doesn't. Test them for average level of mood. See if the smoker experiences more daily pleasure than the non-smoker. Perhaps though the toxic effects of the cigarettes cause damage that reduces pleasure other ways. I'd expect that to be the case after enough years of smoking.
In the long run I expect to see the development of wide spectrum long lasting feel good drugs that do as nicotine does but without undesired side effects such as addiction and without a delivery mechanism such as smoke that brings along lots of toxins. One reason that some people are happier than others is that they are wired up that way due to their genes. Those who go through life generally less joyful (and not just those who are depressed) will some day have the option of getting their average pleasure level turned up by adjustment of receptor concentrations in their neurons.
Over 80% of UK bingo players surveyed were generally superstitious - some attributing lucky seats, lucky friends and lucky nights of the week to gambling success.
Just one-third of the larger UK population are thought to be superstitious - the most commonly reported behaviours being: avoiding walking under ladders, touching wood for good luck and throwing salt over shoulders.
Could training in statistics and physics reduce the belief in luck? My guess is those with lower aptitudes for math and physics are more likely to believe in luck. So better training probably would not help much. Future geneticallly engineered neural stem cell therapies for boosting IQ will probably reduce the desire to gamble though.
Another recent study found that alcoholics and gamblers are motivated by different kinds of emotions.
Tavares said that positive emotions and negative emotions are two separate, distinct and independent dimensions, possibly regulated by different brain systems. "We found that alcohol craving was based on the temperament factor responsible for negative emotions," he said. "This suggests that those individuals who are especially vulnerable to negative emotions are the ones who will miss alcohol the most when trying to abstain. Conversely, gambling craving correlated to the temperament factor responsible for positive emotions.
"This suggests that those individuals who naturally lack positive emotions and require intense stimuli to experience elation are the ones who will miss gambling the most when trying to abstain."
As I reported in another recent post fetal alcohol exposure in early pregnancy or during the full length of pregnancy in rhesus macaque monkeys resulted in macaques that had blunted responses to stimuli. Humans exposed to alcohol during fetal development and born with less ability to respond to stimuli might take up gambling as a source of more intense experiences. So alcohol abuse in one generation might lead to compulsive gambling in a successive generation.
If the need to experience an intense stimulus could be met by some other source of a stimulus would gambling compulsion be easier to break? How about putting gambling treatment centers next to amusement parks and taking the gamblers on roller coaster rides? The problem is that it is a lot easier and faster to log on to a gambling web site or do off-site betting on track races than to go to an amusement park. Most people do not live near roller coasters. Could video games provide the craved level of intense stimulation?
Gene therapies and neural stem cell therapies will eventually provide ways to supply neurons that reduce the need for the stimulus high that comes from gambling.
Technological advances are making gambling problems easier to develop (while producing lots of email and blog spam in the process).
Today more young people gamble once a week than smoke, drink or take drugs combined.
"Poker playing seems to have grown to the point where now you've got about 20% of young males, who are either in high school or in college playing poker with their friends on a weekly basis," says Dan Romer, who runs the Annenberg Adolescent Risk Communication Centre at the University of Pennsylvania.
"Of those at least a quarter of them would be exhibiting some form of problem gambling symptoms."
Human beings did not evolve to handle the types of artificial environments that technologies are producing. The range of technologies which humans are not adapted to handle keeps growing. Home methamphetamine labs and internet gambling web sites are just two manifestations of a larger problem: Humans find themselves in technological environments very unlike the environments for which they evolved.
Some humans are lucky enough to have combinations of alleles, embryonic environments, and childhood environments that make them still able to function well in the face of so many potentially harmful activities. Some can gamble occasionally without developing a compulsion to do so. Some can have a drink of alcohol without developing a need for it. Some feel great enough to see no temptation from cocaine or methamphetamine.
But others less lucky are caught up in a growing number of temptations which they are genetically and cognitively ill-suited to handle. The weakening of belief in religious codes that used to justify many restrictions on vices combined with liberal and libertarian views of human ability to exercise free will leave those with neurological vulnerabilities insufficiently defended against a proliferation of ways to develop compulsive, addictive, and destructive vices. Only the acceptance of a more biological view of human nature can restore some of the wisdom about vices lost in the decline of religious beliefs.
Researchers working with rats have zeroed in on the brain circuitry mechanism whose disruption contributes to the impulsive behavior seen in users of cocaine as well as other psychostimulant drugs. The same circuitry has been implicated in such disorders as schizophrenia, depression, and post-traumatic stress disorder, wrote the researchers.
Yukiori Goto and Anthony A. Grace of the University of Pittsburgh described their findings in the July 21, 2005, issue of Neuron. In their studies, they sought to understand the effects of cocaine sensitization on the connections between two higher brain regions--the prefrontal cortex and the hippocampus--and the nucleus accumbens, which is the region in the limbic system involved in processing reward behavior. The prefrontal cortex is involved in processing information, and the hippocampus is involved in learning and memory.
The connections to the nucleus accumbens seem to be bidirectional, said the researchers, and the interactions with the prefrontal cortex and hippocampus could affect the "plasticity" of connections in the neurons of the nucleus accumbens. This means that disruptions to the normal connections could affect behavior.
The researchers' electrophysiological studies of the effects of cocaine on this circuitry demonstrated that the drug did disrupt this normal plasticity. They found that the cocaine induced abnormal enhancement of neuronal connections--a phenomenon called long-term potentiation (LTP).
The researchers also performed behavioral studies on the cocaine-sensitized rats, to explore the behavioral effects of this disruption. In these studies, they placed the rats in a plus-shaped maze. The rats were taught that in response to a visual cue they should turn left or right toward one arm or the other of the maze to obtain a piece of cereal.
Goto and Grace found that, while the cocaine-sensitized rats learned the correct response strategy faster than normal rats, they were significantly less able to change strategies when they were required to ignore the cue and always make a left or right turn to receive the reward.
"Thus, although abnormally induced LTP by psychostimulants at limbic inputs might not interfere with learning a response strategy, it may reduce the capacity of these animals to consider alternate response strategies," concluded Goto and Grace. "In this way, the disruption of synaptic plasticity by cocaine sensitization may contribute to the affective- and context-inappropriate impulsive behaviors that are characteristic of drug addiction."
A drug that increases impulsive behavior in its users creates problems (e.g. crime, poorer relations with friends, neighbors, familiies) for the rest of us. Cocaine addicts have a harder time modifying some behavior or lesson already learned. One can imagine how that would cause them to get stuck in ruts of repetitive behavior that is destructive to themselves and to other people..
“It may explain why cocaine addicts are oriented towards pleasure rather than other goals, and have an impaired ability to make decisions. It could be why addicts go back to taking more of the drug and ex-addicts often become addicted again faster than those who have never taken it,” says Grace
Drugs that reduce cognitive competence increase the costs that users impose on the rest of us while at the same time the drugs make the users less productive. Users simultaneously increase the costs they impose while giving less in return. We need treatments that cure addictions. We also need better drugs that make us more adaptive, not less.
Young drug abusers are up to three times more likely to suffer brain damage than those who don't use drugs, according to research published online by Neuropathology and Applied Neurobiology.
The brains of 34 intravenous drug abusers, who had mainly used heroin and methadone, were examined after death and compared with 16 young people who had not used drugs.
This revealed that the drug abusers sustained a level of brain damage normally only seen in much older people and similar to the early stages of Alzheimer's disease.
"Our study shows evidence of an increased risk of brain damage associated with heroin and methadone use, which may be highest in the young, when individuals are most likely to acquire the habit" says co-author Jeanne Bell Professor of Neuropathology at the University of Edinburgh.
Damaged nerve cells were identified in the key areas of the brain involved in learning, memory and emotional well-being.
"We found that the brains of these young drug abusers showed significantly higher levels of two key proteins associated with brain damage" adds Professor Bell.
"In a previous study we found out that drug abuse causes low grade inflammation in the brain. Taken together, the two studies suggest that intravenous opiate abuse may be linked to premature ageing of the brain."
The 34 documented drug users had a history of opiate abuse – mainly heroin and methadone – but were HIV negative and had no history of head injury. The 16 control cases had no history of drug abuse or neurological impairment.
The average age in these two groups was only 26 years and included drug abusers as young as 17.
Toxic proteins were found in the brain cells of drug abusers.
Tau protein, which in its soluble form is essential for communication and transport within brain cells, had become insoluble in some cells, causing nerve cell damage and death in selected areas of the brain.
Other nerve cells showed an accumulation of the amyloid precursor protein, which suggests that protein transport had been disrupted and the nerve cell functions affected.
"This study shows that drug abuse can lead to a build up of proteins which cause severe nerve cell damage and death in essential parts of the brain. This is very worrying as there are strong indications that drug use in the UK, in particular opiates like heroin and methadone, has continued to rise in recent years" says Professor Bell.
If you damage your brain with drugs now you will have to wait for decades before stem cell therapies can fix all the damage. Whatever you become after the future damage repair will be someone else different than who you were before you damaged your brain in the first place.
Also see my post "Partial Recovery From Methamphetamine-Induced Brain Damage" and be sure to read the comments by some of the ex-meth users who describe the symptoms of their own brain damage.
In experiments with mice, researchers have found that nicotine triggers the same neural pathways that give opiates such as heroin their addictively rewarding properties--including associating an environment with the drug's reward. However, unlike opiates, nicotine does not directly activate the brain's opiate receptors, but activates the natural opioid reward pathway in the brain.
The researchers, led by Julie Blendy of the Transdisciplinary Tobacco Use Research Center (TTURC) at the University of Pennsylvania, said their findings suggest more effective ways that opiate blockers could be used to help smokers quit.
In their experiments reported in the June 16, 2005, issue of Neuron, the researchers administered nicotine to mice and analyzed the levels of a protein called CREB--known to control genes involved in the reward pathway of opiates and other abused drugs. They found that not only was CREB activated in the reward regions of the nicotine-treated animal's brains, but also that the drug naloxone, which blocks the opiate receptors, blocked CREB activation. Also, mutant mouse strains lacking the opioid receptor did not show an increase in CREB activity when they received nicotine.
The researchers also studied the relationship among nicotine, the environment, and this reward pathway. They conditioned mice to associate a specific test chamber with receiving nicotine, finding that the mice would prefer to stay in that chamber when given a choice. The researchers found that just placing the conditioned mice in the chamber activated CREB. They also found that naloxone blocked this conditioned increase in CREB, and that mutant mice lacking CREB or pretreated with naloxone did not show any reward response to nicotine.
However, naloxone did not block the chamber choice of mice conditioned with cocaine, found the researchers, indicating that cocaine activates the brain reward pathway in a different way from nicotine and opiates.
"The present results demonstrate that nicotine-associated environmental stimuli can activate the same molecular signal transduction molecules as the drug itself," wrote Blendy and her colleagues. They wrote that the activation of CREB "is evident not only after acute and repeated nicotine administration, but also following exposure to an environment in which the animal has previously received nicotine."The researchers noted that clinical studies of opioid receptor blockers to relieve cigarette cravings "so far have produced mixed results, ranging from ineffectiveness at smoking cessation to mild reduction in the desire to smoke." The researchers wrote that their findings "suggest that the timing and context of opioid receptor antagonist administration are critical for determining the effectiveness of blocking nicotine reward . . . . Given the results reported here, clinical studies designed to evaluate administration of opioid antagonists just prior to cues associated with smoking could lead to a more promising treatment regimen."
The brain reward system is effectively hijacked by recreational drugs. Normally the brain reward circuitry activates to encourage adaptive behavior such as getting food and doing other life-promoting work. Addictive drugs that activate reward circuitry drugs are dangerous because they subvert the purposes of the reward system and reduce or eliminate the motivations for adaptive behaviors.
Note that animals can be conditioned to associate being in a particular room with getting a reward. When medical treatments that control reward responses are developed they'll be used to cure drug addictions. But the understanding of brain reward circuity resulting from addictive drug studies will also point the way toward the development of treatments which can be used to manipulate human behavior in sophisticated ways. Will the greater use of such treatments be by governments and other entities to manipulate the behavior of individuals? Or will individuals use such treatments to manipulate their own behavior?
Self manipulation might sound counter-intuitive at first. But we all end up doing things we think we shouldn't do while at the same time we don't do other things that we think we really ought do so. So will the frontal lobes of our brains choose to administer treatments to ourselvse that realign the motivations of other parts of the brain? Picture the forebrain exclaiming "Bow to me now limbic system. You are no longer in control. I am finally your complete master."
Once the neurotechnologies exist to control rewards I expect a lot of people to modify their reward systems to favor the pursuit of longer term goals. As I've previously argued I also expect people to selectively turn off love as a motivation when they find that feeling stands in the way of reaching their goals.
François Frenois, PhD, of Université Victor Segalen Bordeaux 2 in France, and colleagues analyzed the brains of rats that had been addicted to morphine, denied access to the drug, and then re-exposed to the environment where withdrawal was experienced.
“This paper defines regions of the brain that are important for memories of withdrawal in rats, providing new insight into the development of new treatments for withdrawal syndromes in humans,” said Eric Nestler of the University of Texas Southwestern Medical Center at Dallas.
Frenois and his team compared the neural pathways activated during both the initial formation and subsequent retrieval of withdrawal memories. They analyzed the activity of a gene called c-fos, an indicator of stress and adaptation. Drugs and other stimuli can trigger c-fos expression and alter long-term brain function—even if used only once. In this study, the stimuli used were a precipitated withdrawal from morphine (implanted as pellets under the rats' skin) or an environment previously associated with withdrawal.
Being reminded of the withdrawal episode caused rats to reactivate circuitry in ways analogous to how the brain functioned while going through withdrawal.
The team found that re-exposure to an environment associated with withdrawal reactivated part of the withdrawal neural circuitry, which can drive behavioral changes causing drug relapse. Addiction, the authors say, is a chronic, recurrent disorder involving motivation, emotion, and memory. Frenois and his team say their work is an important step in helping to determine how specific environments associated with drug withdrawal might encourage drug seeking.
There are two obvious ways this knowledge could be utilized. First off, a drug that prevents memory formation could be used during addictive drug withdrawal in order to prevent a person from being able to later recall the experience of withdrawal. Then there would be no chance of cravings for the addictive drug from being intensified by remembering the withdrawal experience. This is a pretty drastic measure. But if it would help a person stay off something really damaging like methamphetamine it might be worth it to some people.
Less radically, a person about to go through withdrawal could be put in an environment very unlike any environment that person usually spends time in. That way the odds of encountering environmental cues that would recall the withdrawal episode could be decreased. The challenge then would be to figure how to construct an environment that would be least likely to be recalled by a later set of environmental stimuli. One difficulty in developing such an environment is that movies and TV shows present a much larger set of environments than most people would encounter in their own lives. Perhaps sensory deprivation environments would be best. But then just turning out the lights to go to bed might serve as a trigger to recall withdrawal. Total inability to recall withdrawal would be a far more certain method to prevent reactivation of the withdrawal response in the brain.
In the future withdrawal will be greatly helped by a number of therapies that are in the pipeline. Vaccines that cause the immune system to attack and destroy addictive drugs will reduce the satisfaction from using addictive drugs. Also, gene therapies and cell therapies will modify the brain to make it less prone to craving a drug in the first place.
Professor Malcolm Horne of the University of Melbourne's Howard Florey Institute has found that a drug which blocks the D2 receptor on dopamine neurons eliminates cocaine cravings in rats previously addicted to cocaine.
The Howard Florey Institute’s Prof Malcolm Horne and his team successfully cured cocaine addiction without withdrawal symptoms in rats - a discovery that could help develop drug addiction treatments for humans.
Cocaine increases dopamine, the body’s own ‘feel good’ drug produced by the brain. Repeated use causes tolerance for the drug so that withdrawal results in low levels of dopamine and continuous use is required to keep dopamine at normal levels, and even higher doses to get the ‘high’ levels of initial use. Cocaine withdrawal is often accompanied by mental and physical symptoms.
The Florey scientists cured cocaine addiction in rats by fooling their brain cells into thinking that there was a shortage of dopamine. As a result, their brain cells made more dopamine, which meant cocaine was not needed to increase dopamine levels and the addiction was cured.
Dopamine production and nerve cell endings capable of releasing dopamine were increased when the D2 receptor was blocked by the drug.
Dopamine is released by specialised nerve endings in the brain called terminals. The amount of dopamine is sensed by the D2 receptor, which regulates whether more or less dopamine needs to be released. Horne’s team discovered that the number of terminals increase or decrease according to the levels of dopamine and found that when dopamine levels are high, the D2 receptor not only shuts down dopamine synthesis, it also reduces the number of terminals. When dopamine is low, it gives the signal to produce dopamine and make more terminals.
Prof Horne’s team gave a drug that blocks the D2 receptor to cocaine addicted rats and found that they could increase the number of terminals even while the animals had free access to cocaine. With time, the rats stopped seeking cocaine, and even when re-exposed to the drug some weeks later, did not relapse in the way that would be expected. The rats’ normal dopamine levels had increased, curing the addiction and removing withdrawal symptoms such as anxiety.
The news release excerpted above and various Australian media reports on this study do not provide a name for the antipsychotic medication used by Professor Horne's team. However, many antipsychotics bind to D2 receptors including risperidone and olanzipine. Some of those drugs bind at serotonin receptors and other sites as well. So without more details from Horne's lab we can not be certain that the effect he saw was really due to the D2 receptor blocking effect. Still, if it works on humans the mechanism of operation is of secondary concern.
The paper that will provide the details is not out yet but you can watch for it in the journal Neurobiology of Disease.
Symptoms of hyperprolactinaemia include amenorrhoea, galactorrhoea, infertility, loss of libido and erectile dysfunction. Resulting hypogonadism may cause osteoporosis.
My guess is that many of those effects come from prolonged use of a D2 receptor blocker drug. This may not be a problem for cocaine addicts since Horne's work showed that the antipsychotic drug he used did not have to be taken indefinitely. The D2 receptor was blocked by the antipsychotic drug he used, more dopamine was produced by the brain, compulsion to use cocaine dropped, and then administration of the antipsychotic was halted.
The ability to cure drug addictions would reduce crime, child abuse, birth defects from pregnant moms on drugs, brain damage, and a whole host of other problems. Therefore we all stand to gain enormously from the development of effective treatments for curing drug addiction.
Compared with the controls, the pathological gamblers showed a lower level of activity in the ventral striatum, the dopamine-producing brain region that provides the pleasure in winning, suggesting gamblers remain unsatisfied even when winning. The scans also showed decreased activation of the ventrolateral prefrontal cortex -- the brain's "superego," which keeps people from acting impulsively.
Mick Jagger would understand. Gamblers "just can't get no satisfaction".
In the study, the brains of 12 compulsive gamblers and 12 non-gamblers were monitored using functional magnetic resonance imaging (fMRI) while they played a simple card guessing game.
If dopamine levels could be boosted in the brains of compulsive gamblers they might not feel as great a need to gamble. However, another group found in results they published in May 2004 that dopamine release increases in one area of the brain while decreasing in other areas when an unpredictable monetary award arrives.
Zald and his colleagues used positron emission topography (PET scanners) to view brain activity in nine human research subjects who had been injected with a chemical that binds to dopamine receptors in the brain, but is less able to bind when the brain is releasing dopamine. A decrease in binding to the receptors is associated with an increase in dopamine release, while an increase in binding indicates reduced release of dopamine. This technique allows researchers to study the strength and location of dopamine release more precisely than has previously been possible.
The team studied the subjects under three different scenarios. Under the first scenario, the subject selected one of four cards and knew a monetary reward of $1 was possible but did not know when it would occur. During the second scenario, subjects knew they would receive a reward with every fourth card they selected. Under the third scenario, subjects chose cards but did not receive or expect any rewards.
Zald and his team found that over the course of the experiment, dopamine transmission increased more in one part of the brain in the unpredictable first scenario, while showing decreases in neighboring regions. In contrast, the receipt of a reward under the predictable second scenario did not result in either significant increases or decreases in dopamine transmission.
The most effective treatments for gambling and drug addictions are going to have to involve manipulation of pleasure regions of the brain. Well, that is quite the Rubicon to cross. Once pleasure centers are effectively rewired to treat addictions rewiring for other purposes will not be too far behind. Imagine the possibilities for individual and group manipulation if the brain regions for pleasure and pain can be reorganized to any significant extent.
Another interesting consequence of the ability to conduct experiments that show neurological differences between addicts and normal people is that this will eventually lead to very objective methods for diagnosing addictions. Junior just got busted for using. Oh my, is Junior a crackhead? Or is he just recreationally using cocaine on occasion? Mom and dad will demand a brain scan test to find out. Or juvenile courts will require the brain scan. Similar work is bound to lead to effective means by which to reliably diagnose assorted compulsions and preferences. I predict that some day successful lack of response to child pictures while being brain scanned will be a required condition for parole of convicted pedophiles. Also, one can imagine recovering addicts to be required to pass a neurological test for lack of craving for an addictive drug as a condition for parole or to regain custody of children taken away by the state.
A brain chemical that stokes hunger for food and fat also triggers thirst for alcohol and may play a role in chronic drinking, according to a study led by Princeton University scientists.
The study showed that rats injected with galanin, a natural signaling agent in the brain, chose to drink increasing quantities of alcohol even while consuming normal amounts of food and water. The finding helps explain one of the mechanisms involved in alcohol dependence and strengthens scientists' understanding of the neurological link between the desires for alcohol and food.
"There seems to be a cycle of positive feedback," said Bartley Hoebel, co-author of a paper appearing in the December issue of Alcoholism: Clinical and Experimental Research. "Consumption of alcohol produces galanin, and galanin promotes the consumption of alcohol. That would perpetuate the behavior."
This suggests the obvious possibility that a compound that blocked the synthesis or binding of galanin to some target would help alcoholics stop drinking.
The research was conducted by Michael Lewis, a visiting research fellow in Hoebel's lab, in collaboration with Hoebel, a professor of psychology; Deanne Johnson, a research staff member; Daniel Waldman, a senior undergraduate; and Sarah Leibowitz, a neurobiologist at Rockefeller University.
Galanin, a kind of small protein fragment called a neuropeptide, had previously been shown to play a role in appetite, particularly for fatty foods. Consumption of fat causes a part of the brain called the hypothalamus to produce more galanin, which, in turn, increases the appetite for fat. In a healthy person, however, there are counteracting signals that break this loop, said Hoebel.
In animals given galanin and access to alcohol, the role of the chemical appeared to be subverted: it boosted alcohol intake instead of eating. The effect was especially noticeable during daylight hours, when the nocturnal animals normally do not eat and drink much. Those given galanin drank alcohol during the day, but did not consume any more food or water than normal.
"Alcohol is the only drug of abuse that is also a calorie-rich food, and it undoubtedly has important interactions with systems that control food intake and nutrition," said Lewis, who is also a senior fellow of the National Institute on Alcohol Abuse and Alcoholism (NIAAA).
A drug that blocks the efect of galanin reduced alcohol consumption. However, it would be difficult ot make a drug that would do the same in humans.
When the animals were given a drug that blocked the effects of galanin, they maintained normal eating and drinking habits. This observation helps confirm the conclusion that galanin affects alcohol consumption and also suggests the possibility of someday creating a drug that blocks galanin in order to fight alcoholism. However, Hoebel noted that such an achievement would be a long way off, because it is hard to make drugs that cross from the blood into the brain and interact with neuropeptide receptors. In addition, galanin plays many roles in other parts of the brain, which could be adversely affected by trying to block its effects related to food or alcohol.
The researchers plan to explore further the role of galanin and other neuropeptides in alcohol use, as well as the role of fat intake and metabolism on alcohol intake.
An effective drug to stop alcohol cravings would prevent enormous economic losses from brain damage in alcoholics, brain damage to fetuses of alcohol abusing pregnant women, work time lost, crimes committed while drunk, accidental deaths and injuries, and still other losses. Addictions cost the US economy hundreds of billions per year. In 1992 a US government study tallied up total alcohol abuse costs as about $150 billion yearly. The health care costs alone were $18 billion in 1992. A separate category for motor vehicle crash costs was $24.7 billion. My guess is these costs are higher today.
My guess is that there are some major categories of cost which are not captured by that analysis. For example, there are children who have a genetic variation in Mono Amine Oxidase A (MAOA) which causes them to react to child abuse by becoming permanently more impulsive and violent and to lack remorse for their assaults upon others. Well, how many of those children were sent down the path of a life of crime by fathers abusing them while on alcoholic benders? WHat is the cost to the rest of us from the assaults, murders, rapes, and other acts that come as a result of that abuse?
Previous research has implicated the brain's opioid system in the development of alcohol-use disorders. The mu-opioid receptor, which is encoded by the OPRM1 gene, is the primary site of action for opiates with high abuse potential, such as opium and heroin, and may also contribute to the effects of non-opioid drugs, such as cocaine and alcohol. Findings published in the December issue of Alcoholism: Clinical & Experimental Research indicate that individuals with the G variant of the A118 polymorphism of the OPRM1 gene have greater subjective feelings to alcohol's effects as well as a greater likelihood of a family history of alcohol-use disorders.
"Alcohol releases endogenous opiates which, in turn, seem to influence the mesolimbic dopamine system," said Kent E. Hutchison, associate professor of psychology at the University of Colorado at Boulder and lead author of the study. "This system is involved in craving and the motivation to use alcohol and drugs. Thus, it is alcohol's effects on endogenous opioids that act as the gateway through which alcohol may influence this system."
"It is well known that alcohol dependence tends to run in families," said Robert Swift, professor of psychiatry and human behavior at Brown University and Associate Chief of Staff for Research at the Providence VA Medical Center. "The inheritance of alcoholism is complex, but there are suggestions that the opiate systems in the brain are involved. Our brains contain proteins, called enkephalins and endorphins, that act like morphine and other opiates derived from the poppy plant. Several researchers have shown that persons with a family history of alcoholism tend to have differences in blood levels of beta-endorphin, a natural opiate hormone, compared to persons without a family history of alcoholism. Children of alcoholics, who are not themselves alcoholics, have lower levels of beta-endorphin than do children of non-alcoholics. Also, when young adults with a family history of alcoholism drink alcohol, they increase their blood levels of beta-endorphin more than those without a family history of alcoholism."
A special protein called the mu-opioid receptor, which is located in the membranes of nerve cells, detects internal opiate neurotransmitters, such as beta-endorphin, that the brain uses to allow nerve cells to communicate with each other. Previous research has shown that the G variant of this gene has a slightly different receptor protein, which causes a big difference in how well the receptor connects with beta-endorphin. For example, the G variant receptor binds three times more tightly than the A variant to beta-endorphin, which means that a nerve cell with the G variant is more greatly affected by beta-endorphin. The net result is that dopamine cells, which play a role in motivation and reinforcement, become more stimulated.
For this study, participants comprised 38 students (20 male, 18 female) at the University of Colorado, 21 to 29 years of age, who indicated drinking patterns classified as moderate to heavy. Participants were either homozygous for the A allele (n=23) or heterozygous (n=15). Each received intravenous doses of alcohol that were designed to cause breath alcohol concentration (BAC) levels of .02, .04, and .06. Researchers measured subjective intoxication, stimulation, sedation, and mood states at baseline and at each of the three BAC levels.
Results indicate that individuals with the G allele had higher subjective feelings of intoxication, stimulation, sedation, and happiness across trials as compared to participants with the A allele.
The OPRM1 gene is likely one of dozens of genes that influence the odds that a person who drinks alcohol will eventually become an alcoholic. Once DNA sequencing costs fall a couple more orders of magnitude all the genes that influence the risk of alcoholism (and the risks of all other diseases - addictive or otherwise) will be identified in short order.
The identification of genes that are involved in addiction will eventually lead to the development of drugs that suppress and increase their expression and other drugs that work at receptors that the genes code for. As a result addiction will become much more easy to treat and even to cure.
Paul Thompson, Ph.D. of the UCLA Lab of Neuro-Imaging and Brain Mapping Division and a number of colleagues have published new research on the extensive brain damage caused by methamphetamine addiction.
A new UCLA Neuroscience imaging study shows for the first time the selective pattern of destruction to the brain's memory, emotion and reward systems experienced by chronic methamphetamine users. Color, three-dimensional visualizations created from magnetic resonance images vividly show the damage. The study reveals the mechanism by which drug abuse damages the brain and suggests potential targets for therapy in recovering drug users. The research appears in the June 30 online edition of the peer-reviewed Journal of Neuroscience. Authors Dr. Paul Thompson, associate professor of neurology, and Dr. Edythe London, professor at the UCLA Neuropsychiatric Institute, are available for interviews.
If you click through on that previous link you'll see a graphic showing the scale of the loss in different parts of the brain. Note that the legend puts the red color level of loss at 5% and most of the brain shows a 5% loss of volume. White matter swelling makes the brain larger overall due to inflammation. But obviously there is extensive cell death.
Brain regions involved in drug craving, emotion and reward, and hippocampal brain regions involved in learning and memory, lose up to 10% of their tissue. Red colors denote brain regions with greatest tissue loss, blue colors regions that remain relatively intact. Hippocampal volume reductions are linked with poorer memory performance in the methamphetamine users. At the same time, a 7% volume increase occurs in the brain's white matter, suggesting an inflammatory response to chronic drug use.
The first high-resolution M.R.I. study of methamphetamine addicts shows "a forest fire of brain damage," said Dr. Paul Thompson, an expert on brain mapping at the University of California, Los Angeles. "We expected some brain changes but didn't expect so much tissue to be destroyed."
The actual research paper is available on the web and reports that the average length of time using methamphetamine (MA) was 10.5 years and brain volume losses ran as high as 10%.
The MA abusers had used the drug (primarily by smoking) for 10.5 years on average, beginning in their mid-twenties. They consumed ~3 gm MA per week, having used MA on most of the 30 d before entering the study. The groups reported similar alcohol use (Table 2). Most of the MA abusers but only two of the controls, however, smoked tobacco cigarettes. All analyses were run with and without six MA subjects who reported remarkable levels of mari-juana use (more than one joint per week or a history of marijuana dependence, as determined by the SCID-I interview). Although p values changed slightly, this did not affect whether each result was statistically significant, so we present results for the full sample.
As South Park character Mr. Mackey says "Drugs are just bad, mmm'kay?"
"Now as I was saying, drugs are bad. You shouldn't do drugs. If you do them, you're bad, because drugs are bad, mkay? It's a bad thing to do drugs, so don't be bad by doing drugs, mkay? That'd be bad, because drugs are bad, mkay?"
ATLANTA -- Researchers at the Yerkes National Primate Research Center of Emory University are the first to demonstrate a combination of drug therapies targeting the region of the brain that controls drug abuse and addiction significantly reduces cocaine use in nonhuman primates. These findings, which appear in the June issue of the Journal of Pharmacology and Experimental Therapeutics, have implications for developing treatments for cocaine addiction in humans.
Led by Leonard Howell, PhD, an associate professor in Yerkes' Neuroscience Division, the Yerkes researchers observed the innovative combination of dopamine transporter (DAT) inhibition and serotonin transporter (SERT) inhibition was effective in limiting cocaine use in rhesus macaques who are trained to self-administer cocaine. "It appears DAT inhibition serves to substitute for cocaine, while SERT inhibition may limit the abuse potential of the medication," said Howell. "Our results, therefore, showing a combination of DAT and SERT inhibition were more effective than either alone are very promising."
This first-time finding was the promising end result of a several-step process. Howell and his colleagues began by administering a pretreatment of DAT inhibitors to confirm their effectiveness in reducing drug use. DAT inhibitors have long been used in addiction studies because they elicit reinforcing properties in the brain similar to those experienced as a result of taking cocaine.
The research team then substituted the DAT inhibitors for cocaine in order to determine their effectiveness in maintaining the use of the medications. Finally, Howell and the team administered a pretreatment with combined DAT inhibition and SERT inhibition, which is known to block the chemical effects of cocaine in the brain and reduce addictive properties, to determine if cocaine use was further reduced. "Pretreatments with the combination therapy were very effective in eliminating cocaine use. Moreover, drug substitution tests with the medication indicated it should have limited abuse potential in humans," added Howell.
Compliance is going to be a problem with any use of drugs which must be used continually to treat abuse of other drugs. Gene therapies against substance cravings or other therapies that cause lasting changes in the brain would be far more reliable. However, the discovery of effective drug therapies would point the way toward what gene or cell therapies would need to alter in order to be effective.
As I've argued in my previous post the potential savings from successful drug treatments run into the hundreds of billions per year.
Alcoholism tends to run in families, suggesting that addiction, at least in part, has an underlying genetic cause. Now, researchers at the University of Illinois at Chicago have discovered a gene linked to alcohol dependency.
Laboratory mice deficient in the gene were found to consume excessive amounts of alcohol, preferring ethanol to water and evincing highly anxious behavior in a maze test.
Results of the study are published in the May 26 issue of the Journal of Neuroscience.
The gene the researchers investigated manufactures a protein called CREB, or cyclic AMP responsive element binding protein, which is known to regulate brain function during development and learning.
"This is the first direct evidence that a deficiency in the CREB gene is associated with anxiety and alcohol-drinking behaviors," said Subhash Pandey, associate professor of psychiatry and director of neuroscience alcoholism research at the UIC College of Medicine.
When CREB is activated, it regulates the production of a brain protein called neuropeptide Y. Low levels of active CREB or of neuropeptide Y correlate with symptoms of anxiety and excessive alcohol consumption, the scientists showed in a previous study.
In the present study, mice that had only one copy of the CREB gene -- healthy mice have two copies -- produced lower-than-normal levels of the CREB protein, neuropeptide Y and another compound in the brain linked with alcohol drinking (called brain derived neurotrophic factor).
The mice consumed about 50 percent more alcohol than normal littermates and showed higher baseline anxiety-like behaviors, as measured by a maze test.
Alcohol exposure reduced their anxiety, though less so than in normal mice, and increased levels of active CREB protein and neuropeptide Y in parts of the amygdala, the area of the brain associated with emotion, fear and anxiety.
Pandey speculated that the animals' preference for alcohol suggested they used ethanol to lessen their anxiety, a situation than is not uncommon in humans."Some 30 to 70 percent of alcoholics are reported to suffer from anxiety and depression. Drinking is a way for these individuals to self-medicate," Pandey said.
According to the National Institute on Alcohol Abuse and Alcoholism, an estimated 14 million Americans suffer from alcohol problems. Alcohol abuse costs the economy roughly $185 billion per year.
Other researchers involved in the study were Adip Roy, Huaibo Zhang and Tiejun Xu, postdoctoral research associates in the UIC department of psychiatry. The National Institute on Alcohol Abuse and Alcoholism and the U.S. Department of Veterans Affairs provided support.
The point the article makes about the cost of alcoholism is important. Suppose in the next 10 to 20 years truly effective treatments are developed for alcoholism and drug addiction. Literally hundreds of billions of dollars will be saved per year in everything from increased production at work, fewer car accidents, less crime, families that do not fall apart and yet other changes. The future economic value from research on addiction will pay for the cost of the research many times over.
A lot of alcohol and other drug abuse amounts to self medication for anxiety, depression, and other emotional problems. Therefore ideal treatments for alcohol and drug abuse would need to reduce the feelings that encourage abuse. Though not all drug and alcohol abuse is a result of pre-existing emotional problems. Brain exposure to drugs at key stages of brain development increases cravings for drugs. Therefore the drugs themselves create the structural changes in the brain that cause addiction and it is too simplistic to see all drug abuse as only the product of self-medication against previously existing emotional problems.
As a follow up to previous work showing that gene therapy can reduce drinking in rats trained to prefer alcohol, scientists at the U.S. Department of Energy's Brookhaven National Laboratory have used the same technique to cut drinking in rats with a genetic predisposition for heavy alcohol consumption. The findings, along with additional results on the effects of long-term ethanol consumption on certain aspects of brain chemistry, are published in the May 2004 issue of Alcoholism Clinical and Experimental Research.
"Though we are still early in the process, these results improve our understanding of the mechanism or mechanisms of alcohol addiction and strengthen our hope that this treatment approach might one day help people addicted to alcohol," said Panayotis (Peter) Thanos, who lead the study in Brookhaven Lab's medical department.
The method of gene therapy used apparently did not allow delivery of genes to locations in cells that protected the genes from being broken down. The gene therapy was not long-lasting. But surely more lasting methods of delivering gene therapy will be developed.
Genetically predisposed alcohol-preferring rats are a much better model for human alcoholism than the rats used previously, which the scientists had to train to prefer alcohol. Without any training, the genetic alcohol-preferring rats drink, on average, more than five grams of ethanol per kilogram of body weight per day when given a free choice between alcohol and plain water. Genetically non-preferring rats, in contrast, typically consume less than one gram of ethanol per kilogram of body weight per day.
In this study, both groups were treated with gene transfer to increase the level of a brain receptor for dopamine, a chemical important for transmitting feelings of pleasure and reward and known to play a role in addiction. After the gene treatment, the alcohol-preferring rats exhibited a 37 percent reduction in their preference for alcohol and cut their total alcohol consumption in half -- from 2.7 grams per kilogram of body weight before treatment to 1.3g/kg after. Non-preferring rats also reduced their drinking preference and intake after gene treatment, but not in nearly as dramatic a fashion. The greatest reductions in alcohol preference and consumption were observed within the first few days after gene treatment, and both preference and consumption returned to pre-treatment levels by day 20.
The gene administered was for the dopamine D2 receptor, a protein shown in various studies to be relevant to alcohol and drug abuse. For example, low levels of dopamine D2 receptors in the brain have been postulated to lead to a reward deficiency syndrome that predisposes certain people to addictive behaviors, including drug and alcohol abuse. The alcohol-preferring rats used in this study have about 20-25 percent lower levels of dopamine D2 receptors when compared to the non-preferring rats, which may, in part, explain their tendency toward heavy drinking.
The scientists delivered the gene by first inserting it into a virus that had been rendered harmless. They then injected the virus directly into the rats' nucleus accumbens, the brain's pleasure center. The idea behind this type of gene therapy is to use the virus as a vector to carry the gene to the brain cells, which can then use the genetic instructions to make the D2 receptor protein themselves.
As an additional measure in this study, the scientists used micro-positron emission tomography (microPET) imaging to non-invasively assess the effects of chronic alcohol consumption on D2 receptor levels in alcohol-preferring and non-preferring rats. They measured D2 levels seven weeks after the gene therapy treatment (well after the effects of gene therapy had worn off). D2 receptor levels in alcohol-preferring rats were significantly lower (about 16 percent) compared to that in non-preferring rats. These levels were similar to previous data in naïve preferring and non-preferring rats.
Other research is suggestive of the idea that gene therapy that boosts D2 dopamine receptor levels will reduce human cravings for drugs other than alcohol. For instance, one study found a negative correlation between D2 dopamine receptor concentrations and "drug-liking" to intravenous methylphenidate.
The development of gene therapy to alter dopamine receptor levels in humans would open up the possibility of personality engineering. A version of the dopamine receptor D4 is correlated with both extraversion and a tendency to abuse drugs. Will some people opt to modify their personalities to be more outgoing but at the risk of becoming more prone to become drug addicts? Dopamine receptor activity is also tied to novelty-seeking behavior and also thrill-seeking behavior. If gene therapy could be selectively targetted to up dopamine receptor concentration only in specific parts of the brain and if gene therapy could deliver different genetic variants of genes for each receptor then lasting personality modification and behavior modification become real possibilities.
Many personality-altering treatments will be developed first to treat mental illnesses, drug addictions, and other severe mental problems. But then once the treatments are available it is inevitable that people who do not have obvious mental problems will choose to use them as well.
Teens are known to be more likely to smoke if their mothers smoked during pregnancy. Among the possible explanations for this phenomena could be a genetic predisposition that increased the odds of mothers being smokers in the first place. However, epidemiological studies which have controlled for many factors support the idea of a biological cause that is a result of the prenatal exposure. Dr. Theodore Slotkin of Duke University has produced evidence in a rat model that suggests prenatal nicotine exposure causes brain damage that creates a predisposition to nicotine addiction.
The rats exposed to nicotine before birth suffered loss of brain cells and a decline in brain activity that persisted throughout adolescence and into adulthood, the team found.
When given doses of nicotine for a two-week period as adolescents, the earlier exposed rats showed a weaker brain response in circuits using acetylcholine -- a natural chemical messenger that plays a critical role in learning and memory -- as compared to rats that did not experience the prenatal exposure. Nicotine's activity in the brain stems from its ability to mimic acetylcholine. The earlier exposure also worsened the decline in brain activity during nicotine withdrawal and led to an increase in the amount of brain cell injury induced by the drug, they reported.
"The current study suggests that the lasting neurotoxic effects of prenatal exposure to nicotine from maternal smoking during pregnancy may worsen the long-term consequences of adolescent smoking -- effects that may increase the likelihood that an individual will take up and keep smoking," Slotkin said.
Specifically, the team explained, the reduced response of acetylcholine systems in the adolescent brain following prenatal exposure might lead teens to self-administer nicotine in an attempt to replace the brain's functional loss. Furthermore, that deficient brain response might drive higher cigarette consumption.
Here is the abstract of the paper and that includes a link to the full paper.
Another group of Duke researchers has previously shown in a rat model that initial exposure to nicotine more strongly predisposed the rats toward later nicotine cravings if the initial exposure first happened in adolescence rather than in adulthood. Brains that are still developing are generally more vulnerable to toxins and so this result is not too surprising.
It is also worth noting that hostile personalities are more prone to nicotine addiction. This latest result suggests the possibility that prenatal nicotine exposure might make people more hostile later in life.
UPTON, NY— Scientists at the U.S. Department of Energy’s Brookhaven National Laboratory have produced new evidence that brain circuits involved in drug addiction are also activated by the desire for food. The mere display of food — smelling and tasting favorite foods without actually eating them — causes increases in metabolism throughout the brain. Increases of metabolism in the right orbitofrontal cortex, a brain region that controls drive and pleasure, also correlate strongly with self-reports of desire for food and hunger.
“These results could explain the deleterious effects of constant exposure to food stimuli, such as advertising, candy machines, food channels, and food displays in stores,” says Brookhaven physician Gene-Jack Wang, the study’s lead author. “The high sensitivity of this brain region to food stimuli, coupled with the huge number and variety of these stimuli in the environment, likely contributes to the epidemic of obesity in this country.” The study appears in the April 2004 issue of NeuroImage.
This reaction is an example of an evolutionary adaptation that is no longer adaptive in modern environments. While calorie malnutrition was a major cause of death for almost all of human history in many parts of the world today calorie malnutrition is rarely a cause of death. Human brain reactions to food are therefore more often maladaptive than adaptive. Humans need biotechnologies that will help them adapt themselves to the new environments they have created for themselves and our response to plentiful food is a major cause of the need for adaptive biotechnologies.
Previous Brookhaven work has shown similarities between the brains of food addicts and drug addicts.
Brookhaven scientists have conducted previous research showing that the right orbito-frontal cortex is involved in compulsive behaviors characteristic of addictive states, and that this brain region is activated when addicted individuals crave drugs such as cocaine (see related story). They have also shown that food stimulation, as done in this study, increases levels of dopamine, a neurotransmitter involved in pleasure and reward, in the brain’s dorsal striatum (see related story). Additionally, to better understand the relationship of the dopamine system to obesity, they looked at the brain circuits of obese individuals and found that, like drug addicts, these individuals had fewer dopamine receptors than normal control subjects (see related story).
In their most recent research the Brookhaven scientists used positron emission tomography (PET) scans to study the response of normal people to food and found that food exposure increases metabolism in almost all major areas of the brain.
The researchers found that food stimulation significantly increased whole brain metabolism. Metabolism was higher in all regions of the brain examined, except for the occipital cortex, which controls vision and would not be affected. The areas most affected were the superior temporal, anterior insula, and orbitofrontal cortices. Food stimulation also resulted in increases in self-reports of hunger and desire for food. Increases in metabolism in the right orbitofrontal cortex were the ones that were most significantly correlated with increased reports of hunger.
People suffering from food addiction problems would benefit from removing reminders about food from their environment. That is hard to do because of the sheer number of sources of food reminders ranging from street signs of restaurants, billboards, advertisements in magazines, on radio and on TV, TV portrayals of people eating, and the presence of a kitchen in most dwellings. Still, there are ways to reduce one's exposure to food smells and images. For instance, remove all visible food in a house by having no fruit basket on a table and no food cans visible on shelves. One could listen to commercial-free satellite as a way to avoid food ads. Also, avoid looking at the types of magazines that have a lot of food ads.
Technology may eventually provide greater control over one's environmental stimuli. For instance, some web sites already provide ways to configure personalized ad profiles of areas of interest. Digital TV advances ought to allow one to separate what show one is going to watch from what ads one sees. Perhaps some day TV channels will let one specify the types of ads one wants to watch and thereby provide a way to avoid, say, food or alcohol ads.
In the longer run food addiction problems will be controllable by drugs that will suppress appetite. Also, it will eventually become possible to turn up the amount of brown fat cells that burn off excess calories.
Gene-Jack Wang has done other interesting work about addiction. Wang and his colleagues previously showed that methamphetamine-induced brain damage is long-lasting. For details see my previous post Partial Recovery From Methamphetamine-Induced Brain Damage.
It will be interesting to see whether the lower dopaminergic neuron levels in the right orbito-frontal cortex of people with addiction problems in all cases precede the addiction or are caused by the addiction or a mixture of both. Also, are obese people more prone to drug addictions? Given that some obese people feel motivated to take methamphetamine to suppress appetite separating out the causes and effects is difficult.
Gene-Jack Wang of Brookhaven National Laboratories (also assistant professor of radiology at SUNY Stony Brook) and coworkers used positron emission tomography (PET scans) to show only part of the damage caused by methamphetamine abuse is repaired 12 to 17 months after the end of the drug abuse.
Researchers found that former meth abusers showed improved glucose metabolism in a brain region called the thalamus after staying off the drug for 12 to 17 months.
The striatum does not appear to recover.
There was, however, no evidence of improved metabolism in a brain region called the striatum -- suggesting, researchers say, that some meth-induced brain changes are long lasting.
RESULTS: Significantly greater thalamic, but not striatal, metabolism was seen following protracted abstinence relative to metabolism assessed after a short abstinence interval, and this increase was associated with improved performance in motor and verbal memory tests. Relative to the comparison subjects, the methamphetamine abusers tested after protracted abstinence had lower metabolism in the striatum (most accentuated in the caudate and nucleus accumbens) but not in the thalamus.
Take home lesson: addictive drugs really do fry the brain and should be avoided. Not a particularly novel observation? Yes, that is true. But evidence from brain scans makes obvious truths harder to deny.
Previous studies have also shown that alcohol enhances GABA neurotransmission in the amygdala, the so-called pleasure center of the brain. Interestingly, the brain corticotropin releasing factor (CRF) stress system also increases GABA transmission in the amygdala.
CRF is a common peptide in the brain that is responsible for activating the hypothalamic-pituitary-adrenal stress response and in the amygdala for activating sympathetic and behavioral responses to stressors. CRF is found in lots of different parts of the brain and is known to be involved in the brain in response to stress, anxiety, and depression.
Significantly, the CRF system also seems to be central to alcoholism, and scientists at Scripps Research and elsewhere have shown that CRF is involved in the transition from alcohol use to alcohol dependence. Scripps Research Professor George Koob and his colleagues found recently that levels of CRF increase in brains treated with alcohol. Other studies have shown that CRF levels increase when animals are withdrawing from alcohol as well—a situation analogous to an alcoholic's protracted abstinence.
In their latest paper, Siggins and his colleagues show, at the cellular level, how alcohol and CRF interact. When neurons are exposed to alcohol, says Siggins, they release CRF, and this causes the release of GABA in the amygdala. And when the CRF receptor is removed altogether (by genetic knock out), the effect of alcohol and CRF on GABA neurotransmission is lost.
Siggins and his colleagues say that this suggests a cellular mechanism underlying involvement of CRF in alcohol's behavioral and motivational effects. During withdrawal, CRF levels increase and these changes may persist for a long time.
It also suggests a possible way of treating alcoholism—using CRF antagonists, or compounds that block the effects of CRF. In the current study, when the scientists applied an antagonist of CRF, they found that alcohol no longer had an effect.
"Not only did the antagonists block the effect of CRF in enhancing GABA transmission, it also blocked the effect of alcohol," says Siggins. "The response was totally gone—alcohol no longer did anything."
An understanding of mechanisms by which ethanol acts on the brain will lead to better treatments of alcoholism. But an understanding of the various mechanisms by which ethanol intervenes in brain function will also lead to the identification of targets for drug development to develop treatments that will emulate some of the effects of alcohol while avoiding many of the harmful side effects.
It seems likely that in the next few decades a deeper understanding of how drugs cause addiction will lead to the development of effective treatments for many and perhaps even all forms of addiction. Addiction may become much less common as a result.
Howard Hughes Medical Institute investigators at Duke University Medical Center have linked a gene previously shown to play a role in learning and memory to the early manifestations of drug addiction in the brain. Although scientists had previously speculated that similar brain processes underlie aspects of learning and addiction, the current study in mice is the first to identify a direct molecular link between the two.
"There has been the idea that brain changes in response to psychostimulants may be similar to those critical for learning and memory," said Marc G. Caron, Ph.D., an HHMI investigator at Duke. "Now, for the first time, we have found a molecule that links drug-induced plasticity in one part of the brain to a mechanism that underlies learning and memory in another brain region." Caron is also interim director of the Center for Models of Human Disease, part of Duke's Institute for Genome Sciences and Policy, and James B. Duke professor of cell biology.
Previous work by other researchers revealed that exposure to cocaine triggers changes in a brain region called the striatum -- a reward center that also plays a fundamental role in movement and emotional responses. Cocaine leads to a sharp increase in communication among nerve cells in the striatum that use dopamine as their chemical messenger. This brain chemical surge is responsible for the feeling of pleasure, or high, that leads drug users to crave more.
"Drugs essentially hijack the brain's natural reward system," thereby leading to addiction, explained Wei-Dong Yao, Ph.D., an HHMI fellow at Duke and first author of the new study.
Humans have a problem with addictive drugs because humans did not get much exposure to these drugs as humans evolved. The limited previous exposure means there was little selective pressure to select for genetic variations that would make humans less susceptible to drug addiction. Addictive drugs in the quantity and quality now available are, evolutionarily speaking, new to human experience and humans are not adapted to deal with them.
Note the sheer number of genes which were compared for activity under different conditions and in different strains of mice. Most likely the researchers used gene array chips that allow the expression levels of thousands of genes to be compared at the time. As gene array chip technology improves the ability to do this kind of work becomes cheaper and easier.
The study sought to identify genes involved in the brain's heightened response after drug use. The researchers compared the activity of more than 36,000 genes in the striatum of mice that had "super-sensitivity" to cocaine due to a genetic defect or prior cocaine exposure, with the gene activity in the same brain region of normal mice. The genetic screen revealed six genes with consistently increased or decreased activity in super-sensitive versus normal mice, the team reported.
There is a difference between easily addicted mice and regular mice in the change of their PSD-95 gene expression when exposed to cocaine.
The protein encoded by one of the genes -- known as postsynaptic density-95 or PSD-95 -- dropped by half in the brains of super-sensitive mice, the researchers found. The protein had never before been linked to addiction, Caron said, but had been shown by Seth Grant, a member of the research team at the Wellcome Trust Sanger Institute, to play a role in learning. Mice lacking PSD-95 take longer than normal mice to learn their way around a maze. In other words, mice with normal amounts of PSD-95 appear less likely to become addicted and more likely to learn.
Two of the other five genes had earlier been suggested to play a role in addiction. The function of the remaining three genes is not known, Caron said, and will be the focus of further investigation.
If the human equivalent of the PSD-95 gene reacts to cocaine in the same manner then a fairly small amount of cocaine use may hobble learning for weeks and perhaps even for months.
Among the mice more responsive to the effects of cocaine, the decline in PSD-95 occurred only in the striatum, while levels of the protein in other brain regions remained unaffected. In normal mice, the protein shift occurred after three injections of cocaine and lasted for more than two months.
The researchers also measured the activity of nerve cells in brain slices from the different groups of mice. Neurons in the brains of super-sensitive mice exhibited a greater response to electrical stimulation than did the nerve cells of control mice. Neurons from mice lacking a functional copy of PSD-95 showed a similar increase in activity, the team reported.
Mice deficient in PSD-95 also became more hyperactive than normal mice following cocaine injection, further linking the protein to the drug's brain effects. However, the deficient mice failed to gain further sensitivity upon repeated cocaine exposure, as mice typically do.
"Drug abuse is a complex disorder and will therefore be influenced by multiple genes," Caron noted. "PSD-95 represents one cog in the wheel."
The brain protein likely plays a role in addiction to other drugs -- including nicotine, alcohol, morphine and heroine -- because they all exert effects through dopamine, Caron added. Natural variation in brain levels of PSD-95 might lead to differences in individual susceptibility to drugs of abuse, he suggested. The gene might therefore represent a useful marker for measuring such differences.
It would be interesting to know how PSD-95 expression responds to various drugs which are used to treat a variety of mental illnesses. For instance, how do SSRI (Selective Serotonin Reuptake Inhibitor) antidepressants such as Prozac and Zoloft change PSD-95 expression? Or how does Ritalin, which is used to treat youthful ADHD (Attention Deficit Hyperactivity Disorder), change PSD-95 expression?
“We call this brain response a ‘born to smoke’ pattern,” said study leader Dr. Steven Potkin, professor of psychiatry and human behavior. “Based on these dramatic brain responses to nicotine, if you have hostile, aggressive personality traits, in all likelihood, you have a predisposition to cigarette addiction without ever having even touched a cigarette.” Study results appeared in the January issue of Cognitive Brain Research.
Potkin and Dr. James H. Fallon, professor of anatomy and neurobiology, gave study subjects standard psychiatric personality exams and separated them into two groups — those with high-hostility personality traits, which are marked by anger, aggression and anxiety, and those with low-hostility traits. Both groups included smokers and non-smokers. The groups were given nicotine patches of strengths of 3.5 or 21 milligrams, or placebo, and later subjected to PET scans to see if the nicotine triggered any responses in brain metabolism of glucose energy.
While the PET scans showed no metabolic changes in the low-hostility subjects, nicotine induced dramatic metabolic responses in the high-hostility group individuals in the limbic system and the cortical and subcortical sectors of the brain. Among members of the high-hostility group, smokers showed a metabolic reaction only to the more powerful 21 milligram nicotine patch, while non-smokers reacted to both patches.
The fact that non-smokers in the high-hostility group showed a significant metabolic response to nicotine provides the first biological evidence that people with high-hostility personalities are likely to become dependent on cigarettes because of their brains’ strong response to nicotine, said Potkin. “In turn, this might also help explain why other people have no compelling drive to smoke or can quit smoking with relative ease,” he added.
It is conceivable that a drug that can make a person less hostile and less aggressive could make it easier for that person to quit smoking.
Another speculation: the association between drug use and crime may in part be due to the fact that the kinds of personalities most prone to become drug addicts are more aggressive in the first place. What would be interesting to know is whether people with high levels of hostility who never try drugs or cigarettes are more or less likely to become criminals than those who do. The answer may depend in part on which drug a hostile person becomes addicted to. Some addictive drugs might even have net calming effects that make a hostile and aggressive person less hostile.
Another interesting question: Suppose people with criminal records who smoke who were trying to stop smoking were studied. Would criminals who have a hard time quitting cigarettes who finally manage to quit become more or less likely to commit violent crimes than they were when they were still smoking?
One complication of studying links between nicotine and crime is that nicotine causes brain damage.
Nicotine causes degeneration in one part of the brain, according to professor of psychology Gaylord Ellison, who announced the finding in the journal Neuropharmacology, and at this year's meeting of the Society for Neuroscience.
Ellison found that nicotine causes selective degeneration of the fasciculus retroflexus, the part of the higher brain that primarily controls the dopamine and serotonin levels in the body.
Dopamine controls movement, emotional response, and the ability to experience pleasure and pain, while serotonin regulates a person's mood.
Suppose a person has a brain that is aggressive and hostile and that person becomes a nicotine addict and basically racks up a bunch of brain damage. Then suppose that person manages to quit smoking. Is that person then even more hostile as a result of the brain damage? Or does the type of damage done have the effect of reducing violent behavior? A similar question can be asked about other addictive drugs because lots of addictive drugs cause brain damage.
There is increasing evidence that the fasciculus retroflexus (FR) represents a 'weak link' following the continuous administration of drugs of abuse. A variety of drugs which predominantly potentiate dopamine, including D-amphetamine, methamphetamine, MDMA, cocaine, and cathinone, all induce degeneration in axons from lateral habenula, through the sheath of FR, to midbrain cells such as SN, VTA, and raphe. For some drugs, such as cocaine, this is virtually the only degeneration induced in brain. Continuous nicotine also selectively induces degeneration in FR, but in the other half of the tract, i.e. in axons from medial habenula through the core of the tract to interpeduncular nucleus. This phylogenetically primitive tract carries much of the negative feedback from forebrain back onto midbrain reward cells, and the finding that these descending control pathways are compromised following simulated drug binges has implications for theories of drug addiction but also psychosis in general.
I am a skeptic on the issue of addictive drug legalization because if the barrier to access to addictive brain-damaging substances is lowered then more people will become addicts and damage their brains. What will be the net result? The legalization advocates can't answer that question. It may depend on the drug. Some drugs might damage circuits that cause hostility. Other drugs might damage circuits that suppress hostility. Also, hostility is not the only factor in play here. Impulsiveness, happiness, anxiety, and other aspects of personality may be enhanced or decreased by the sorts of selective brain damage various addictive drugs cause.
Three new studies conducted in animals, published in the December issue of the journal Biological Psychiatry, provide evidence that misuse of the stimulant methylphenidate (Ritalin) may have long-term effects on the brain and behavior. While methylphenidate and other stimulant medications are the recommended treatments for Attention Deficit Hyperactivity Disorder (ADHD), based on the more than 150 controlled studies demonstrating their safety and efficacy when used as prescribed, these three studies showed changes in the brains of young (adolescent or pre-adolescent) animals that persisted into adulthood. In both animals and humans, the brain continues to develop throughout adolescence. If the current studies are applicable to humans, they could have important implications for young people who use stimulants for recreational purposes.
In the first study, Dr. Cindy Brandon and her colleagues at the Finch University of Health Sciences/The Chicago Medical School examined how low doses of methylphenidate affect dopamine cells in the brains of adolescent rats. Dopamine is a brain chemical that has been implicated in natural rewards, such as food and sex, as well as in drug abuse and addiction. The study showed that the rats experienced brain cell changes that subsequently made them more sensitive to the rewarding effects of cocaine.
In the second study, Dr. William Carlezon, Jr., and his colleagues at Harvard Medical School and McLean Hospital in Belmont, Massachusetts, looked at how pre-adolescent exposure to methylphenidate affected certain behaviors in rats when they reached adulthood. They found that early exposure to twice-daily injections of methylphenidate actually reduced the sensitivity to cocaine reward, but increased other behaviors that could indicate depression. The timing of exposure to methylphenidate may be important — in this study the rats were exposed at an age corresponding to childhood, whereas in the study by Dr. Brandon et al., the rats were slightly older, more akin to adolescence.
In the third study, Dr. Carlos Bolaños and his colleagues at the University of Texas Southwestern Medical Center in Dallas assessed certain behaviors of adult rats given methylphenidate prior to adolescence. They found that compared to drug-naive rats, those chronically exposed to methylphenidate were less responsive to natural rewards, such as sugar and sex, and more sensitive to stressful situations. The methylphenidate-exposed animals also had increased anxiety-like behaviors, and enhanced blood levels of stress hormones.
Adolescent exposure to Ritalin may increase sensitivity to cocaine but pre-adolescent exposure may decrease cocaine sensitivity. That a drug can have different effects depending on the age of the patient is not surprising when we consider the amount of brain growth and changing in configuration that happens during adolescence. A drug is going to have a different effect on a rapidly growing nervous system as compared to its effects on a nervous system that is growing less rapidly or which is going through different kinds of changes.
One big caveat about these studies is that children with ADD (attention deficit disorder) or ADHD (attention deficit hyperactivity disorder) may be so different cogntively than other children that the long term effects of methylphenidate on ADD/ADHD children may be substantially different than that reported for what are considered to be "normal" mice. But it is unclear whether that means methylphenidate will have worse or better effects on ADD/ADHD children. Also, the rats were given the drug intravenously whereas children usually take it as a pill which means the drug is not going to reach the brain as quickly or not necessarily even in the same chemical state.
What is amazing about this is the scale on which doctors and parents have embarked upon a massive experiment that may cause a variety of lasting changes on cognitive function. As of 1995 2.8 percent of American children were on methylphenidate (Ritalin) and that represented a sharp increase from 1.2% in 1990. Methylphenidate use is also up in Canada and some other Western countries in about the same time period.
If anyone doubts whether, when it becomes possible to do so, humans will be willing to reengineer their minds or the minds of their offspring consider the use of nervous system-altering drugs on children today. Look at how willing parents and authority figures are to embrace treatments that are not sufficiently well understood and which probably have a number of lasting effects on cognitive function thoroughout the rest of the lives of the children who are given methylphenidate and other nervous system drugs.
Harvard School of Public Health Associate Professor of Society, Human Development, and Health Stephen Buka and colleagues have published a study that finds a link between maternal cigarette smoking and later nicotine dependence of offspring.
Participants in the study were the grown children of mothers enrolled in the Providence, Rhode Island site of the National Collaborative Perinatal Project (NCPP), a multi-site study that involved the observation and examination of more than 50,000 pregnancies through the first seven years of life. Participants for the NCPP were enrolled between 1959 and 1966 and were visited regularly by NCPP investigators. Beginning with the first prenatal meeting and in each subsequent meeting until delivery, the mothers in the study were asked if they smoked, and if so, the number of cigarettes per day. From these data the researchers were able to establish the maximum number of cigarettes smoked at any point during the pregnancy. More than 60 percent of the women smoked during their pregnancies; approximately 35 percent smoked more than a pack per day (20 cigarettes) and nearly 25 percent smoked less than a pack per day.
Offspring whose mothers reported smoking a pack or more of cigarettes per day during their pregnancy were significantly more likely to meet DSM criteria for lifetime nicotine dependence than offspring of mothers who never smoked during their pregnancy. Among offspring who tried cigarettes, the odds of progressing to nicotine dependence was almost twice as great for those whose mothers smoked heavily during pregnancy. In contrast, the use of marijuana was not increased among children whose mothers smoked cigarettes during pregnancy. Marijuana use among the adult offspring was of particular interest to the researchers because of its similar route of administration (inhalation) and because research has shown an association between cigarette smoking and marijuana use.
Stephen Buka, lead author of the study and an associate professor in the Department of Society, Human Development and Health at the Harvard School of Public Health said, “More than half a million infants each year are exposed to cigarette smoke before birth. In the short term, this increases the risk of low birthweight and birth defects, and in the longterm, this adds to the likelihood that children will become heavy smokers, dependent on nicotine. Eliminating smoking during pregnancy and afterwards remains a critical challenge for clinicians and for public health practionners.”
The exposure that altered the brain may not necessarily have come during pregnancy. Since women who smoked during pregnancy were likely to smoke after birth the babies might have had their brains modified by the exposure during the period of postnatal brain development.
The lack of an increase in marijuana smoking among children exposed to nicotine during fetal development is not too surprising. The mechanisms for causing craving for different kinds of drugs are not all identical. A predisposition to become addicted to nicotine may not necessarily translate into a predisposition to become addicted to opiates either.
It is very valuable to identify factors that cause brains to develop in ways that predispose people to become addicts of various sorts. For some types of addiction (e.g. heroin) the success rate of getting off and staying off is less than 50%. The kinds of changes that happen to brains of addicts to make them desire drugs are often very long lasting and possibly permanent in many cases. Techniques are sorely needed to be able to change brains in ways that reduce the cravings for addictive drugs.
In an interview, Buka explained that pregnant women were interviewed many years ago, when people were not yet aware of the health effects of smoking. Consequently, more than 60 percent of the women smoked, and around 35 percent smoked at least one pack on at least one day of their pregnancies.
These poisonous chemicals pose unique and real threats to the unborn child. Smoking during pregnancy is associated with low birth weight, premature delivery, placenta previa (a complication that could cause bleeding and become a medical emergency), miscarriage and post-delivery death. It has also been associated with a 50 to 70 percent higher chance of delivering babies with a cleft lip or palate, and this risk is believed to increase with the number of cigarettes smoked per day
University of Wisconsin-Madison researchers have discovered that the same brain pathways involved in rewarding addictive drug use appear to reward compulsive running behavior.
The researchers studied changes in brain activity in two groups of rodents: typical laboratory mice and a special breed of mice selected over 29 generations for their affinity for voluntary wheel running.
"All mice run on wheels, and, therefore, have a motivation to run," says Justin Rhodes, a postdoctoral fellow at Oregon Health & Science University who completed the study while a graduate student at UW-Madison. But he adds that the specially bred mice have a genetic predisposition to run longer distances.
"They represent those few extreme individuals in the population with an intense desire or compulsion to run," he says.
To understand what drives these mice to run faster and farther than the average mouse, Rhodes and his colleagues at UW-Madison designed a study to measure changes in brain activity when both groups of mice were granted or denied access to the running wheel. For six days, they let all mice run as long as they wanted, and they recorded their distances. By and large, the high wheel running mice, compared to the other group, covered more ground in the same amount of time on their spinning treadmills. On the sixth day, for example, these mice averaged about six miles, compared to about two miles among the controls.
On the seventh day, the researchers blocked half the mice in each group from the wheel while giving free access to the other half. Five hours later, when the mice usually reach their running peak, the researchers compared brain activity in each mouse by measuring levels of Fos, a gene that's expressed in response to neuronal excitement.
"We thought we'd see more activity in the mice doing the running, but that's not what we saw at all," says Stephen Gammie, assistant professor of zoology at UW-Madison and senior author of the recent paper.
Instead, Gammie, Rhodes and their Wisconsin colleague Theodore Garland, Jr., (now at the University of California, Riverside) found that all the mice denied access showed higher levels of neuronal stimulation in 16 out of 25 brain regions.
Stimulation was even greater in mice that typically ran longer distances, showing a correlation between brain activity levels and average amount of wheel running.
"In the high-running mice, certain brain regions displayed extremely high levels of activity, more than normal," says Rhodes. "These were the same brain regions that become activated when you prevent rats from getting their daily fix of cocaine, morphine, alcohol or nicotine."
The researchers explain that blocking the running behavior in the mice bred to do more voluntary wheel spinning triggers a neuronal response - activation of brain regions involved in reward circuitry - that drives them to run. Explains Gammie, "These mice have run for six days. They want to run, and they're ready to run, but they can't. Change in brain activity is an indication of their motivation to run."
These findings then would suggest that all mice have the motivation to run, since each blocked mouse showed neuronal stimulation, but that some mice may actually crave it. After all, abstaining from their running regimen signals the same pathways involved in the craving for drugs of abuse, says Rhodes.
Whether these findings on exercise motivation hold true for humans remains to be studied. If it does, anecdotal evidence from Rhodes and Gammie would suggest that they've got more in common with the study's control mice: While they bike or play ultimate Frisbee, neither one says he feels the compulsion to do it on a regular basis.
One big reason cited for pursuing research into addiction is that such research may eventually point the way toward way to treat and stop addictions. Also, since addiction shows up as a form of compulsion the study of addiction may lead to better treatments of Obsessive Compulsive Disorders (OCDs). But isn't it easy to imagine all sorts of Obsessive Compulsive Adaptations (let's call them OCAs) where the compulsion is to do things that you really think you ought to do? The most obvious example for this is running. But suppose you want to study math or clean the house but never seem to get a strong enough urge to do it. Wouldn't it be handy to be able to flip a neural switch to engage a compulsive desire for, say, 30 minutes and then have the desire automatically shut down?
Our real problem is not that we have addictions or compulsions. Our problem is that we have compulsions that are counterproductive and harmful. What we need is the ability to shape our compulsions to make our compulsions more adaptive. It would be very handy to be able to do some behavior and while doing it send a signal to one's brain to reward that behavior and to record that as reward should be delivered when that behavior is done. One could set that up when faced with the need to do a large amount of fairly repetitive and boring but necessary work. This would probably dramatically enhance productivity for many tasks. Though it would also be necessary to be able to turn off a compulsion so that in situations where it is not appropriate one could turn one's attention to other activities.
Of course, with any new capability comes new ways for it to be abused. The ability to program in compulsions would open up the potential for both self-abuse (imagine a really depressed person with low self-esteem programming in a compulsion to commit physical self-torture) or a military programming in a compulsion to obey a particular person or a pimp programming young girls to have the desire to be a prostitute. When technologies are developed that make the mind more reprogrammable the issue of who does the programming and for what purposes may become one that wars are fought over. Still, I'd like to be able to shape and control the intensity of my compulsions in order to make myself more productive.
A number of recent reports underscore how much various drugs and stress can cause lasting changes to brains, and particularly to younger brains that are still developing. Adolescent brains even appear to be more vulnerable in some cases than younger brains. First off, here is a report on stress-induced permanent changes to the hippocampus.
Studies by Susan Andersen, PhD, of McLean Hospital in Belmont, Mass., and colleagues show that stressful events experienced during adolescence can lead to enduring changes in brain structure in adulthood. This work is the first to demonstrate that exposure to a significant stress during adolescence can impact neuronal connections in the adult brain.
The researchers found that adult rats exposed to a social stress during adolescence (ages approximating 13 to 15 years in humans) showed a significant decrease in a specific protein found in the hippocampus, a brain region important for learning and memory. In fact, the loss of this protein, synaptophysin, is at least as great as that occurring in animals exposed to more severe stressors at a younger age, suggesting that adolescents may be more vulnerable to the effects of stress than younger animals.
Under typical conditions, synaptophysin, which is often used as an index of the number of neuronal connections, or synapses, reaches a peak during young adulthood (approximately ages 18 to 20), with the rise occurring primarily during adolescence. The team tested whether a social stress during this key developmental period might alter this pattern. A control group of rats was housed with their peers, and an experimental group of rats was housed individually during adolescence; individual housing in normally social animals such as rats is a stressful experience. The brains of both groups were then examined during young adulthood. The team found that rats exposed to the social stressor did not show the normal increase in synaptophysin during this period. These data suggest that social stress during adolescence causes either a loss of synapses or a decrease in the synaptophysin protein.
The researchers then compared the loss of synaptophysin in rats that were stressed during adolescence with rats that experienced significant stress during ages comparable to childhood. The stressor used for this age group was repeated maternal separation (RMS). The scientists found no significant difference in synaptic density between rats that had social stress during adolescence or rats that had early RMS. However, the density of synapses in the hippocampus of both groups was reduced significantly when compared with control rats.
These findings are the first to demonstrate that exposure to a significant stress during adolescence can have enduring consequences on the connections formed in the hippocampus in adulthood. These data may suggest why early traumatic stress, such as physical or sexual abuse or neglect, is associated with a decrease in the size of the hippocampus in adulthood.
“These preclinical data suggest that stress experienced early in life alters the normal developmental trajectory of the hippocampus, but that these changes are not apparent until later in life,” says Andersen.
Adolescent brains undergo a great amount of change and therefore anything that interferes with development during that stage has the potential of creating lasting impacts on cognitive function. See the previous post Adolescence Is Tough On The Brain for reports on some of the changes that happen in adolescence.
So what to do about stress causing harmful effects on the brain? Picture at some point in the future nanotech sensors injected into a child's body to provide Mom and Dad with a daily report of whether the kid is feeling enough stress for it to have a harmful effect on cognitive development. If that happens the kid will be put in stress-dampening drugs in order to protect the brain. Sound far-fetched? Sensors will eventually become sensitive enough, small enough, and sufficiently long lasting for that part of this scenario to work. A sensor reader could be mounted on the front door or perhaps in internal house rooms with the sensor data getting routed to the house computer. As Amy Arnsten explains in the following article, drugs with the desired effects already exist.
Amy F.T. Arnsten wrote an interesting article a few years ago in J Am Acad Child Adolesc Psychiatry that explains a different mechanism by which stress causes the result of catecholamines which produce temporary or even permanent changes to the prefrontal cortex.
Animals or humans with lesions to the PFC exhibit poor attention regulation, disorganized and impulsive behavior, and hyperactivity. Recent research in animals indicates that exposure to stress can produce a functional “lesion” of the PFC. During stress exposure, catecholamines are released in both the peripheral and central nervous systems. In the periphery, the catecholamines norepinephrine and epinephrine are released from the sympathetic nervous system and adrenal gland, respectively. These catecholamine actions serve to “turn on” our heart and muscles and “turn off” the stomach to prepare for fight-or-flight responses during stress.
In the brain, high levels of the catecholamines dopamine and norepinephrine are released in the PFC during stress exposure, even during relatively mild psychological stress. As basal levels of dopamine and norepinephrine have essential beneficial influences on PFC function, it was originally presumed that high levels of catecholamine release during stress might facilitate PFC function. However, research in monkeys and rats demonstrated the contrary: exposure to stress impairs the working memory functions of the PFC.
If you read Arnsten's full article you will see where she talks about drugs that can prevent the damage caused by catecholamines released during stress. Keep that in mind when reading below how nicotine can provide the brain with protection against stress. Nicotine, being an addictive drug that also causes other and perhaps undesireable changes to the brain, is far from the ideal compound to use for stress protection. But it does point the way toward the development of compounds that would provide stress protection without the various harmful side-effects caused by nicotine.
The children of women who smoke during pregnancy have been found to be at greater risk for a wide variety of emotional and behavioral disorders, such as attention deficit hyperactivity disorder (ADHD) and conduct disorder. Now, new animal studies from the Yale University School of Medicine demonstrate that the effects of developmental nicotine on emotional learning last into adulthood.
“If we can identify the mechanism for this long-term behavioral change, we may be able to develop new therapies for human emotional disorders that are linked to prenatal nicotine exposure,” says Sarah King, PhD.
For their most recent study, King and her colleague, Marina Picciotto, PhD, used an animal model of emotional learning known as passive avoidance. This model measures how long an animal avoids a dark chamber in which it had previously received a mild electric shock. King and Picciotto found that nicotine-treated mice showed a hypersensitive response and avoided the dark compartment longer than non-exposed mice.
This response was identical to one the researchers had reported on previously (Journal of Neuroscience, May 2003) in genetically altered mice that lack high affinity nicotine receptors as a result of a knockout mutation. “We believe that nicotine exposure during development— the same kind of exposure that occurs in mothers who smoke during pregnancy — disrupts normal nicotine receptor activity, much like the knockout mutation, and that this leads to altered emotional learning in adulthood,” says King.
King and Picciotto have also identified a novel brain circuit — glutamate neurons, which originate in the cortex and project to the thalamus (corticothalmic neurons) — as the likely site where changes occur in the brain during early nicotine exposure. They are currently working to identify the molecular changes that developmental exposure to nicotine triggers in the corticothalamic neurons.
Each year, about 2 million teenagers become regular smokers, according to the American Lung Association. Because the brain continues to develop during adolescence — and beyond — scientists at George Mason University decided to investigate the effect that exposure to nicotine during adolescence has on later behavioral functioning. The researchers implanted 46 rats with small minipumps that dispensed either 3 or 6 mg of nicotine per kilogram of body weight per day — or no nicotine at all (controls). When the animals reached adulthood, they were tested for spatial learning and memory.
Nicotine made a significant difference in the animals’ performance in the tests. Low and high doses of nicotine altered behavior in opposite directions: The low-dose group tended to learn faster and the high-dose group tended to learn slower than the control animals. “Whether performance improved or declined is probably less important than the demonstration that nicotine does produce long-lasting changes in the animals’ performance, presumably reflecting long-lasting effects on brain development,” says Robert Smith, PhD.
Although this research was done in rats, the processes of brain development are similar in humans, which leads Smith to believe that teenagers who smoke aren’t risking only addiction, but also lasting changes in the development of their brains. Smith and his colleagues are now examining the genetic mechanisms that are involved in producing this lasting change in behavior.
During times of stress, smokers tend to increase the number of cigarettes they light up — perhaps as a form of self-medication to counteract the harmful effects of stress on the brain. Stress, which may range from mild anxiety to posttraumatic stress disorder, has been shown to impair normal brain function, including learning and memory.
Researchers in the laboratories of Karim Alkadhi, PhD, at the University of Houston College of Pharmacy recently studied the effect of nicotine on stress-induced memory impairment in rats. They found that when stressed animals were given nicotine, they performed significantly better at short-term memory tests than stressed animals not given the chemical. In fact, the nicotine-treated stressed animals performed the same as unstressed (control) animals.
“Our findings are important to the understanding of the mechanism by which nicotine repairs stress-damaged brain function,” says Abdulaziz Aleisa, a doctoral student at UH. “This research may eventually help in the designing of new, safe approaches to the treatment of Alzheimer’s and Parkinson’s diseases — approaches that mimic the beneficial effect of nicotine on stress.”
Before you start thinking that nicotine would be great to give to adolescents to learn more quickly check out an previous post: Early Nicotine Exposure Increases Nicotine Craving. Nicotine is one of many addictive drugs which cause problems. See also: Adolescent Mice More Sensitive To Addictive Drugs.
Also, note the opposite effects of the lower and higher nicotine doses on speed of learning. The brain is a finely balanced device. Likely some day it will become possible to use drugs to guide brain development to improve long-term memory and other cognitive abilities. But there are more ways to go wrong than to go right with this kind of intervention and at this point there are no clear safe ways to try to guide brain development to yield some desired outcome.
Not all drug use during adolescence primes the brain to want more drugs later in life. The same Susan Andersen mentioned above has previously found evidence that Ritalin given to juveniles may decrease their desire for cocaine later in life.
December 2, 2001 -- Belmont, MA -- Exposure to Ritalin early in life may make one less vulnerable to the allure of cocaine later, according to a new report by McLean researchers. Susan Andersen, PhD, William Carlezon, PhD, and their colleagues found adult rats that were given Ritalin as juveniles spent less time seeking out cocaine than did their Ritalin-free peers. Moreover, in some cases, the rats appeared to actively avoid places where they had been exposed to cocaine in the past.
The findings, which appear in the Dec. 3 online version of Nature Neuroscience, could help resolve several controversies surrounding the use of Ritalin, or methylphenidate, a stimulant prescribed for children who have an abnormally high level of activity or attention deficit hyperactivity disorder (ADHD).
Also see a more recent report on Ritalin's effect on long term drug and alcohol use: Ritalin For Children Reduces Later Alcohol and Drug Abuse.
"The results indicate that early nicotine exposure can leave a lasting imprint on the brain," said Edward Levin, Ph.D., professor in the psychiatry and behavioral sciences department at Duke University Medical Center and a researcher at Duke's Nicotine Research Center. The study was supported by grants from the National Institute on Drug Abuse and the National Institute of Mental Health.
Most tobacco use begins during adolescence, Levin pointed out. Among smokers in the United States, 88 percent smoked their first cigarette before the age of 18 and 60 percent before age 14. Adolescence is also a crucial period for the brain, he said, in which the final phase of neuron development occurs.
If humans minds react similarly to those of rats the effect of the early exposure is quite deleterious:
To clarify the basis of early nicotine addiction, Levin and colleagues tested for a link between the age of initial nicotine use and addiction in female rats in the laboratory. The researchers provided some rats with nicotine at 40 to 46 days of age, while others were provided nicotine only after 70 to 76 days, once they had reached adulthood. Rats could self-administer a dose of nicotine by pressing a lever.
The adolescent rats self-administered significantly more nicotine than did adults, the researchers found. In a test for chronic nicotine use in the rats during a period of four weeks, animals that began using nicotine during adolescence continued to use more of the drug even after they became adults.
The results suggest that people who begin using nicotine during adolescence may be at greater risk for long-lasting addiction, the team reports.
"The brain continues to develop throughout the teenage years," Levin said. "Early nicotine use may cause the wiring of the brain to proceed inappropriately. In essence, the brains of adolescents who use tobacco may be sculpted around an addiction to nicotine."
This is not an entirely surprising result and, in my view, will eventually be confirmed in humans. The minds of adolescents are undergoing a lot of changes. This suggests a higher degree of plasticity that probably means younger growing minds will change more in response to exposure to drugs. Allowing adolescents easy access to drugs will result in changes to their minds that will last for many years and perhaps for their lifetimes.
Update: The rats used for this experiment were the age equivalent of 14 year old girls.
Update II: Drugs vary in their addictiveness.
According to the Institute of Medicine of the National Academy of Science, 32 percent of people who try tobacco become dependent, as do 23 percent of those who try heroin, 17 percent who try cocaine, 15 percent who try alcohol and 9 percent who try marijuana.
Dr. Cami and Dr. Farré observed that personality traits like risk-taking and novelty-seeking tendencies, as well as mental disorders, are "major conditioning factors in drug addiction."
It would be interesting to see how those figures break out by age, race, and sex. If the results of exposing rats to nicotine at different ages are a measure of a general phenomenon them we'd expect to see higher rates for those who try a gven drug in adolescence as compared to trying it at a later age.
Update III: Technological advances are reducing the need to smuggle drugs as synthetic drug manufacture can be done close to the point of consumption and synthetic drug abuse has now surpassed cocaine and heroin drug abuse.
Ecstasy abuse spiralled 70 percent and amphetamines, such as speed, by 40 percent between 1995 and 2001. By contrast, cocaine and heroin abuse worldwide grew less than one percent each.
Addictive drugs that alter and damage the mind are going to become easier to make and their use is likely to grow.
Some people argue about whether Attention Deficit Hyperactivity Disorder (ADHD) is overdiagnosed. The use of Ritalin on children is linked to a larger debate on whether the mind's function can be explained as a bunch of biochemistry and electrical patterns. The argument against evolutionary psychology on the grounds that evolutionary psychology relies upon "an evolutionary past which is permanently inaccessible to empirical research" is not persuasive because the evolutionary past really is scientifically accessible in a number of ways. For instance, comparative DNA sequence analysis within and across species combined with measures of various attributes can yield a great deal of useful information about selective pressures that must have acted on humans and other species (e.g. mutations that provide resistance to particular illnesses are found in people from parts of the world where those diseases are endemic).
While the debate continues about whether various aspects of human nature are genetically specified the reductionist neurobiologists continue to find ways to manipulate the mind biochemically. While the rate of occurrence of AHDH is debated the use of Ritalin has recently been found to have long term effects on behavior.
A study by researchers at Harvard University has provided more evidence that using stimulant medications such as methylphenidate to treat children with attention-deficit/hyperactivity disorder (ADHD) may reduce their risk of developing drug and alcohol use disorders later in life.
Dr. Timothy Wilens, lead investigator, and colleagues used a statistical method called meta-analysis (an examination of whether data compiled from multiple scientific studies provides evidence for statistical significance) to evaluate the relationship between stimulant therapy and subsequent substance use disorders (SUD) in youths with ADHD. After searching the literature for studies of children, adolescents, and adults with ADHD that had information on childhood exposure to stimulant therapy and later SUD outcomes, the researchers applied meta-analyses to six long-term studies. Two studies followed patients into adolescence and four followed patients into young adulthood. These studies comprised data from 674 youths receiving medication therapy for ADHD and 360 unmedicated youths with ADHD. Of those receiving medications, 97 percent were taking the stimulants methylphenidate or amphetamine.
From the compiled data, researchers found that youths with ADHD who were treated with stimulants had an almost two-fold reduction in the risk for developing SUD when compared with youths with ADHD who did not receive stimulants. Examination of each study individually suggested that stimulant medications might have a protective effect against the development of SUD.
Analysis of studies that reported follow-up into adolescence revealed that youths treated with stimulants were 5.8 times less likely to develop SUD than those not treated. However, analysis of studies that followed subjects into adulthood found that those treated with stimulants were about 1.5 times less likely to develop SUD. The researchers say that the less robust effect during adulthood may have occurred because the patients discontinued stimulant treatment when they reached a certain age or that parents may closely monitor the medications of youths with ADHD.
Overall, treating ADHD pharmacologically appears to reduce the risk of substance abuse by half. Untreated, ADHD is associated with a two-fold increased risk for developing a substance abuse disorder. Hence, while not truly immunizing against substance abuse, treating ADHD pharmacologically reduces the risk for drug and alcohol abuse and addiction to the level of risk faced by the general population. The report's findings are among the most robust in child psychiatry demonstrating a protective effect of pharmacological treatment on reducing the risk for later substance abuse.
The study, funded by the National Institute on Drug Abuse (NIDA), is published in the January 6, 2002, issue of Pediatrics.
Think about some of the implications if this report turns out to be correct. A drug has been identified that will affect the development of the mind in such a way that it produces behavior which is more adaptive. Surely this will not be the last such drug found.
It may turn out that gene therapy will not be necessary in order to cause children to develop different personalities or higher intelligence. Surely gene therapy will turn out to be a more powerful technique than drug use. But if drug use alone can affect cognitive development in a way that is not damaging then engineering of personality types may become more widespread more quickly.
It is possible that Ritalin's effect works for only as long as the drug is taken. It may block pleasure caused by other drugs or may provide some of the same pleasure and therefore reduce the size of the increase in pleasure caused by recreational drugs.
The reason it is plausible that Ritalin may have enduring effects is that during adolescence the human mind undergoes a lot of growth and reorganization. Drugs taken during that time that affect mental state likely affect the pattern of connections that form and hence should have lasting effects. Also, an injectable protein has already demonstrated the ability to enhance learning in rats. It should be possible to develop drugs that will affect gene expression of assorted proteins involved in nerve growth and therefore to change the course of brain development during adolescence.
Researchers at Jefferson Medical College have evidence in animals that the young, adolescent brain may be more sensitive to addictive drugs such as cocaine and amphetamines than either the adult or newborn. The work may help someday lead to a better understanding of how the adolescent human brain adapts to such drugs, and provide clues into changes in the brain that occur during drug addiction.
Scientists led by Michelle Ehrlich, M.D., professor of neurology at Jefferson Medical College of Thomas Jefferson University in Philadelphia and a member of the Farber Institute for Neurosciences at Jefferson, and Ellen Unterwald, Ph.D., associate professor of pharmacology at the Temple University School of Medicine in Philadelphia, found a greater increase in a certain protein in the part of the adolescent mouse brain called the striatum following chronic exposure to drugs such as amphetamine or cocaine than they did in either very young mice or adults.
Such psychostimulant drugs affect the brain’s striatum in different ways, potentially affecting both movement and locomotion, or the “reward” system. This “molecular adaptation,” says Dr. Ehrlich, could be significant. “An increase in this protein may be important because it could also affect other molecules that could lead to long-lasting changes in the brain in response to psychostimulant drugs.” The protein, called Delta FosB, is a transcription factor and plays a role in regulating gene expression. Earlier research by other scientists had shown increased amounts of Delta FosB in adult brains following chronic exposure to psychostimulants.
The team, which includes scientists at the Nathan Kline Institute in Orangeburg, New York, reports its findings November 1 in the Journal of Neuroscience.