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Marijuana Use Takes Toll On Adolescent Brain Function, Research Finds

Posted on 21 Oct 2008


Brain imaging shows that the brains of teens that use marijuana are working harder than the brains of their peers who abstain from the drug.

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At the 2008 annual meeting of the American Academy of Pediatrics in Boston, Mass., Krista Lisdahl Medina, a University of Cincinnati assistant professor of psychology, presented collaborative research with Susan Tapert, associate professor of psychiatry at the University of California, San Diego.

Medina’s Oct. 12 presentation, titled, “Neuroimaging Marijuana Use and its Effects on Cognitive Function,” suggests that chronic, heavy marijuana use during adolescence – a critical period of ongoing brain development – is associated with poorer performance on thinking tasks, including slower psychomotor speed and poorer complex attention, verbal memory and planning ability. Medina says that’s evident even after a month of stopping marijuana use. She says that while recent findings suggest partial recovery of verbal memory functioning within the first three weeks of adolescent abstinence from marijuana, complex attention skills continue to be affected.

“Not only are their thinking abilities worse, their brain activation to cognitive tasks is abnormal. The tasks are fairly easy, such as remembering the location of objects, and they may be able to complete the tasks, but what we see is that adolescent marijuana users are using more of their parietal and frontal cortices to complete the tasks. Their brain is working harder than it should,” Medina says.

She adds that recent findings suggest females may be at increased risk for the neurocognitive consequences of marijuana use during adolescence, as studies found that teenage girls had marginally larger prefrontal cortex (PFC) volumes compared to girls who did not smoke marijuana. The larger PFC volumes were associated with poorer executive functions of the brain in these teens, such as planning, decision-making or staying focused on a task.

Medina says adolescence is a critical time of brain development and that the findings are yet another warning for adolescents who experiment with drug use. She says more study is needed to see if the thinking abilities of adolescent marijuana users improve following longer periods of abstinence from the drug. “Longitudinal studies following youth over time are needed to rule out the influence of pre-existing differences before teens begin using marijuana, and to examine whether abstinence from marijuana results in recovery of cognitive and brain functioning,” says Medina.

The research was supported by the National Institute on Drug Abuse (NIDA).

Adapted from materials provided by University of Cincinnati.

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Methamphetamine Enters Brain Quickly And Lingers

Posted on 21 Oct 2008


Using positron emission tomography (PET) to track tracer doses of methamphetamine in humans’ brains, scientists at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory find that the addictive and long-lasting effects of this increasingly prevalent drug can be explained in part by its pharmacokinetics — the rate at which it enters and clears the brain, and its distribution.

This study in 19 healthy, non-drug-abusing volunteers includes a comparison with cocaine and also looked for differences by race. It will appear in the November 1, 2008, issue of Neuroimage.

“Methamphetamine is one of the most addictive and neurotoxic drugs of abuse,” said Brookhaven chemist Joanna Fowler, lead author on the study. “It produces large increases in dopamine, a brain chemical associated with feelings of pleasure and reward — both by increasing dopamine’s release from nerve cells and by blocking its reuptake.”

Studies by Fowler and others have shown that drugs that produce greater elevations in brain dopamine tend to be more addictive. But other factors, including the speed with which a drug enters and clears the brain and its distribution within the brain, can also be

important in determining its addictive and toxic potential.

In undertaking this first study of methamphetamine pharmacokinetics, the researchers also wanted to know if there were differences between Caucasians and African Americans. “Reports that the rate of methamphetamine abuse among African Americans is lower than for Caucasians led us to question whether biological or pharmacokinetic differences might explain this difference,” Fowler said.

The scientists measured brain uptake, distribution, and clearance of methamphetamine by injecting 19 normal healthy men (9 Caucasian, 10 African American) with a radioactively tagged form of the drug in “trace” doses too small to have any psychoactive effects. They used PET scanning cameras to monitor the concentration and distribution of the tagged methamphetamine in the subjects’ brains. On the same day, the same subjects were injected with trace doses of cocaine and scanned for comparison. The scientists also used PET to measure the number of dopamine reuptake proteins, known as dopamine transporters, available in each research subject’s brain.

Like cocaine, methamphetamine entered the brain quickly, a finding consistent with both drugs’ highly reinforcing effects. Methamphetamine, however, lingered in the brain significantly longer than cocaine, which cleared quickly. In fact, some brain regions, particularly white matter, still showed signs of tracer methamphetamine at the end of the 90-minute scanning session, by which time all cocaine had been cleared. The distribution of methamphetamine in the brain was remarkably different from that of cocaine. Whereas cocaine was concentrated only in the ‘reward’ center and cleared rapidly, methamphetamine was concentrated all over the brain, where it remained throughout the study.

“This slow clearance of methamphetamine from such widespread brain regions may help explain why the drug has such long-lasting behavioral and neurotoxic effects,” Fowler said. Methamphetamine is known to produce lasting damage not only to dopamine cells but also to other brain regions, including white matter, that are not part of the dopamine network.

Surprisingly, the researchers found significant differences in cocaine pharmacokinetics between African Americans and Caucasians, with the African Americans exhibiting higher uptake of cocaine, a later rise to peak levels, and slower clearance. In contrast, the scientists found no differences in methamphetamine pharmacokinetics between these groups.

“This suggests that variables other than pharmacokinetics and bioavailability account for the lower prevalence of methamphetamine abuse in African Americans,” Fowler said. “The differences observed for cocaine pharmacokinetics are surprising considering there are no differences in cocaine abuse prevalence between these two ethnic groups.” These differences may merit further study, and also suggest the need to match subjects by ethnic group in future studies to avoid interference from this potentially confounding variable.

Another interesting finding was that across all research subjects, the level of dopamine transporters was directly related to the level of methamphetamine taken up by the brain. This finding suggests that transporter proteins somehow play a role in regulating the brain’s uptake of this drug.

This research was funded by the National Institute on Drug Abuse, the National Institute on Alcohol Abuse and Alcoholism Intramural Program, and by the Office of Biological

and Environmental Research within DOE’s Office of Science. Brain-imaging studies such as PET are a direct outgrowth of DOE’s long-standing investment in basic research in chemistry, physics, and nuclear medicine. The ongoing neuroimaging research at Brookhaven is a prime example of how DOE’s national laboratories bring together the expertise of chemists, physicists, and medical scientists to address questions of profound significance for society.

Adapted from materials provided by DOE/Brookhaven National Laboratory.

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Illicit drugs used by 20 Million within past 30 days

Posted on 21 Oct 2008


A National Survey on Drug Use and Health will be released today, stating that about 20 Milion people used illicit drugs during the past month.

Drug use increased among those 50-59 years old as more baby boomers joined that age group. Previously, their drug use rose from 4.3 percent in 2006 to 5 percent in 2007.

According to John Walters, director of the White House Office of National Drug Control Policy, “Baby boomers have much higher rates of self-destructive behaviors than any other age group from which we have statistics.”

About 20% of young adults acknowledged illicit drug use within the previous month last year, a rate that has held steady. However cocaine use declined by 25% and meth by 33%. Cocaine and methamphetamine use declined last year mainly due to dwindling supplies which lead to higher costs and less potency.

Across the board, the overall use of illicit drugs showed little change.

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Cross-Behavioral And Dual-Behavioral Addiction

Posted on 21 Oct 2008


Reality is that if you have an addiction to one thing the chances are very good that you have other addictions as well. Smoke cigarettes and Gamble? Do Coke and Drink? Very few people have one addiction and one addiction only, they have cross-behavioral addiction or dual-behavioral addiction.

People have mumerous methods of making themselves feel good - otherwise known as cross-addiction or dual-addiction.

Quite often, if you ask someone to give up one addiction - (give up the way they know how to make themselves feel good) they will pick up another addiction almost immediately. They substitute one way of feeling good for another way of feeling good.

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Cocaine-induced Brain Plasticity May Protect The Addicted Brain: Findings May Lead To New Drug-abuse Treatments

Posted on 17 Oct 2008


Increased connections among brain cells caused by excessive drug use may represent the body’s defense mechanism to combat addiction and related behaviors, scientists at UT Southwestern Medical Center have concluded.

Previous studies have shown that repeated use of drugs such as cocaine, amphetamines and nicotine increase the number of anatomical structures called dendritic spines in brain regions associated with pleasure and reward. These dendritic spines represent sites where brain cells communicate with one another. Many scientists believe that this long-lasting brain rewiring underlies the similarly persistent behaviors of drug-taking and drug-seeking associated with addiction and relapse. The mechanism that controls this brain rewiring, however, and its relationship to addiction-related behaviors were previously unknown.

In a study appearing in the Aug. 28 issue of Neuron, researchers found that cocaine suppresses the activity of the protein MEF2 in mice. Because MEF2 normally reduces the number of brain connections, suppressing MEF2 leads to an increase in dendritic spine density. The researchers also found that when they enhanced MEF2 activity in the brain this blocked the drug-induced increase in dendritic spine density and increased addiction-related behavioral responses to cocaine.

“Our findings suggest that increased brain connections during chronic drug use may actually limit behavioral changes associated with drug addiction, rather than support them,” said Dr. Christopher Cowan, assistant professor of psychiatry at UT Southwestern and senior author of the study.

Researchers said they hope this finding could lead to a pharmaceutical treatment for addiction.

“Relapse, or the resumption of active drug-taking and drug-seeking, is very common in drug addicts,” Dr. Cowan said. “Addiction-related brain changes and behaviors seem to be hardwired and semipermanent, and there are limited treatment options. Our data suggest that rather than trying to block the process of increasing dendritic spine density, we may actually want to look at treatments that try to enhance this process.”

MEF2 is activated in response to brain activity. It provides negative feedback to eliminate the potential growth of too many communication sites between nerve cells. Repeated exposure to cocaine disrupts this function of MEF2, resulting in new brain connections.

To investigate the relationship between MEF2 and spine-density changes, the researchers varied the level of the protein in an area of the brain called the nucleus accumbens. This region is associated with the feelings of reward that drug addicts seek. Brain imaging done after mice were given cocaine showed that cocaine stopped MEF2 from limiting dendritic spine increases.

To test MEF2’s relationship to behavior, researchers monitored the movement of mice after repeated daily exposure to the same amount of cocaine. This same dose of cocaine produced a larger behavioral response after repeated days of drug injections, resulting in a “sensitized” response. This sensitized behavioral response to the drug is very stable, lasting for many months after the drug is discontinued.

When the researchers manipulated animals so that their MEF2 levels remained high in the presence of cocaine, the animals were more sensitive to the drug. This suggested that increased communication sites might help combat the addiction process.

“This suggests the exciting possibility that MEF2 proteins may control expression of key genes that modulate drug-related brain changes and behavior,” Dr. Cowan said. “If we understand which genes are influenced by MEF2, we can intervene and try to help the system resist or reverse these sensitization processes.”

In 2006, 23.6 million people ages 12 and older needed treatment for drug or alcohol abuse, according to a Substance Abuse and Mental Health Services Administration survey. Substance abuse costs the U.S. more than half a trillion dollars annually, according to the National Institute on Drug Abuse.

Future research will focus on determining MEF2 target genes and exploring drug-related density changes in other regions of the brain associated with addiction, Dr. Cowan said.

Other UT Southwestern researchers involved in the study were Dr. Suprabha Pulipparacharuvil, instructor of psychiatry; William Renthal, graduate student in psychiatry and neuroscience; Carly Hale, research technician in psychiatry; Dr. Makoto Taniguchi, postdoctoral researcher in psychiatry; Colleen Dewey, graduate student in neuroscience; Dr. Scott Russo, assistant instructor of psychiatry; Dr. Devanjan Sikder, instructor of internal medicine; and Dr. Guanghua Xiao, assistant professor of clinical sciences. Dr. Eric Nestler, former chairman of psychiatry, and former instructor Dr. Arvind Kumar were also involved. Researchers from Yale and Rockefeller University also participated.

The work was funded by the Whitehall Foundation, the National Institute on Drug Abuse and the National Institute of Mental Health.

 

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