Monday, January 2, 2012
A Few Words About Glutamate
Meet another major player in the biology of addiction.
The workhorse neurotransmitter glutamate, made from glutamine, the brain’s most abundant amino acid, has always been a tempting target for new drug development. Drugs that play off receptors for glutamate are already available, and more are in the pipeline. Drug companies have been working on new glutamate-modulating antianxiety drugs, and a glutamate-active drug called acamprosate, which works by occupying sites on glutamate (NMDA) receptors, has found limited use as a drug for alcohol withdrawal after dozens of clinical trials.
Glutamine detoxifies ammonia and combats hypoglycemia, among other things. It is also involved in carrying messages to brain regions involved with memory and learning. An excess of glutamine can cause neural damage and cell death, and it is a prime culprit in ALS, known as Lou Gehrig’s disease. In sodium salt form, as pictured---> it is monosodium glutamate, a potent food additive. About half of the brain’s neurons are glutamate-generating neurons. Glutamate receptors are dense in the prefrontal cortex, indicating an involvement with higher thought processes like reasoning and risk assessment. Drugs that boost glutamate levels in the brain can cause seizures. Glutamate does most of the damage when people have strokes.
The receptor for glutamate is called the N-methyl-D-aspartate (NMDA) receptor. Unfortunately, NMDA antagonists, which might have proven to be potent anti-craving drugs, cannot be used because they induce psychosis. (Dissociative drugs like PCP and ketamine are glutamate antagonists.) Dextromethorphan, the compound found in cough medicines like Robitussin and Romilar, is also a weak glutamate inhibitor. In overdose, it can induce psychotic states similar to those produced by PCP and ketamine. Ely Lilly and others have looked into glutamate-modulating antianxiety drugs, which might also serve as effective anti-craving medications for abstinent drug and alcohol addicts.
As Jason Socrates Bardi at the Scripps Research Institute writes: "Consumption of even small amounts of alcohol increases the amount of dopamine in the nucleus accumbens area of the brain—one of the so-called ‘reward centers.’ However, it is most likely that the GABA and glutamate receptors in some of the reward centers of the basal forebrain—particularly the nucleus accumbens and the amygdala—create a system of positive reinforcement.”
Glutamate receptors, then, are the “hidden” receptors that compliment dopamine and serotonin to produce the classic “buzz” of alcohol, and to varying degrees, other addictive drugs as well. Glutamate receptors in the hippocampus may also be involved in the memory of the buzz.
Writing in The Scientist in 2002, Tom Hollon made the argument that “glutamate's role in cocaine dependence is even more central than dopamine's.” Knockout mice lacking the glutamate receptor mGluR5, engineered at GlaxoSmithKline, proved indifferent to cocaine in a study published in Nature.
In an article for Neuropsychology in 2009, Peter Kalivas of the Medical University of South Carolina and coworkers further refined the notion of glutamine-related addictive triggers: "Cortico-striatal glutamate transmission has been implicated in both the initiation and expression of addiction related behaviors, such as locomotor sensitization and drug-seeking," Kalivas writes. "While glutamate transmission onto dopamine cells in the ventral tegmental area undergoes transient plasticity important for establishing addiction-related behaviors, glutamatergic plasticity in the nucleus accumbens is critical for the expression of these behaviors."
The same year, in Nature Reviews: Neuroscience, Kalivas laid out his “glutamate homeostasis hypothesis of addiction.”
A failure of the prefrontal cortex to control drug-seeking behaviors can be linked to an enduring imbalance between synaptic and non-synaptic glutamate, termed glutamate homeostasis. The imbalance in glutamate homeostasis engenders changes in neuroplasticity that impair communication between the prefrontal cortex and the nucleus accumbens. Some of these pathological changes are amenable to new glutamate- and neuroplasticity-based pharmacotherapies for treating addiction.
This kind of research has at least a chance of leading in the direction of additional candidates for anti-craving drugs, without which many addicts are never going to successfully treat their disease.
Graphics credit: http://cnunitedasia.en.made-in-china.com/
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Saturday, December 31, 2011
Wednesday, December 28, 2011
The Economic Cost of Heavy Drinking
Some food, or rather, some drink for thought.
A recently released study conducted for the CDC Foundation estimates that the economic costs of excessive drinking in American totaled $223.5 billion in 2006. Binge drinking accounted for 76.4%, or $170.7 billion of the total costs, according to the report. Binge drinking is defined as 4 or more drinks for women and 5 or more drinks for men within a two-hour period.
The report estimates that the per capita cost of excessive drinking was approximately $746 for every man, woman, and child in the United States in 2006.
Here is a breakdown of the cost of excessive drinking:
· 72.2% ($161.3 billion) - Lost productivity
· 11% ($24.6 billion) - Healthcare
· 9.4% ($21.0 billion) - Criminal Justice
· 7.5% ($16.7 billion) - Other costs (e.g., property damage)
(The study was conducted for the CDC Foundation, a nonprofit enterprise that creates programs with the Centers for Disease Control for fighting threats to health. The study analyzed 2006 costs obtained from national databases.)
Graphics Credit: http://cdc.gov
Monday, December 26, 2011
Are You Okay?
A variety of drinking tests: the good, the bad, and the silly.
Here’s a short, no-nonsense questionnaire that uses your weekly drinking habits to produce an at-a-glance comparison of how your intake stacks up against others your age and sex. For example, your result might say: “Only 4% of the adult male population drinks more than you say you drink.” Which is food for thought, at least. Join Together (sponsored by The Partnership at DrugFree.org and Boston University School of Public Health) provides this service.
Here is the Mayo Clinic alcohol use self-assessment test, which says with refreshing frankness: “This assessment can’t diagnose you with an alcohol use or abuse problem, but it can help you evaluate your drinking and understand whether you may benefit from seeking help.” Tends to be a bit stern on the drinks-per-day end of things, but otherwise it’s quite straightforward.
Then there is the venerable Michigan MAST Test, first offered in 1971, and revised regularly every since. It’s showing its age a bit as a clinical tool, but here is a link to the 22-question self-administered version: TEST
Iondesign’s Drink-O-Meter is a whimsical test that makes a sober point: “Why not take our test to calculate the state of your kidneys, wallet, and quantity of alcohol you have consumed over the years?” Why not? Well, maybe because you can’t HANDLE the truth: Test results give an estimate of the total number of drinks you have consumed, an estimate of how much money you’ve spent—and an estimate of the number of Ferraris you could have bought instead.
And finally, we have the amazing and ever-popular CAGE Test, so called for the system of naming and memorizing the questions. The CAGE test takes less than a minute, requires only paper and pencil, and can be graded by test takers themselves. It goes like this:
1. Have you ever felt the need to (C)ut down on your drinking?
2. Have you ever felt (A)nnoyed by someone criticizing your drinking?
3. Have you ever felt (G)uilty about your drinking?
4. Have you ever felt the need for a drink at the beginning of the day—an “(E)ye opener?
People who answer “yes” to two or more of these questions should seriously consider whether they are drinking in an alcoholic or abusive manner. Unfortunately, the CAGE test is considered to be an accurate diagnostic tool primarily in the case of adult white males.
Photo Credit: http://tokyotek.com
Tuesday, December 20, 2011
A 12 Days of Christmas Blog Meme
Wrapping it up.
From DrugMonkey’s blog: “The rules for this blog meme are quite simple. Post the link and first sentence from the first blog entry for each month of the past year.” (Credit to Janet Stemwedel and John Lynch for the idea.)
Here are the 12 first lines from 2011 here at Addiction Inbox. Click month for full story:
January: Films popular in Europe feature more drinking episodes per movie than their equally popular American counterparts, according to a report by the European Centre for Monitoring Alcohol Marketing (EUCAM).
February: The Director of the Office of National Drug Control Policy issued a warning about the new synthetic stimulants now being clandestinely marketed as bath salts or insecticide.
March: The U.S. Drug Enforcement Administration (DEA) exercised its emergency scheduling authority yesterday to outlaw the use of “fake pot” products.
April: In the first published examination of thirdhand smoke pollution and exposure, researchers at San Diego State University discovered that non-smokers who move into homes purchased from smokers encounter significantly elevated nicotine levels in the air and dust of their new homes two months or more after moving in.
May: What would it be like to have written a drug memoir and an autobiography before you turned 30? Would it seem like the end or the beginning? Are there any worlds left to conquer?
June: The song is not about cigarette addiction, but it could be.
July: Readers may remember the dark day of January 1, 2008, when the U.S. set an all-time record: One out of every 100 adults was behind bars. That’s more than 2.3 million people
August: The cost of addiction treatment is a legitimate medical expense, as long as you are talking about drug and alcohol addiction, which the IRS recognizes as a genuine medical disease.
September: The DSM-V, when it debuts it 2012, is set to replace the category of “Substance-Related Disorders” with a new category entitled "Addiction and Related Disorders."
October: It’s official: The Obama administration has thrown off the gloves, repudiating Attorney General Eric Holder’s vow of two years ago that the federal government was not interested in prosecuting “state-legal” cannabis activity.
November: They first turned up in Europe and the U.K.; those neon-colored foil packets labeled “Spice,” sold in small stores and novelty shops, next to the 2 oz. power drinks and the caffeine pills.
December: After years of tightening regulation and dramatic declines in the number of adult smokers, Big Tobacco is targeting teenagers like never before.
Photo Credit: http://simplemom.net
Sunday, December 18, 2011
Heavy Drinking Impairs Serotonin Function More Rapidly in Women
My article on women and alcohol.
There are very real gender differences in the way men and women are affected by alcohol. Here's my summary of the subject in a December 16 article for Scientific American Online:
"Women's Response to Alcohol Suggests Need for Gender-Specific Treatment Programs"
A new study underscores that the physical consequences of alcoholism appear faster and are more severe for women than for men...
Article continues HERE.
Monday, December 12, 2011
A Six-Pack of Prior Posts
Don’t fear the chemistry.
This isn’t a top 10 list, just a compilation of five previous posts here at Addiction Inbox that have continued to draw reader interest since they were first published. If there is a theme running through this set, it is neurochemistry at its most basic level. Take a look, if any of the subjects interests you. (My most popular post of all, on Marijuana Withdrawal, has turned into a self-help message board. I note it here, but leave it off the list, as it has become a blog of its own for all practical purposes.)
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1) Don’t let anyone tell you that the basic notions involved in neurotransmitter action in the brain are over everyone’s head. This post about serotonin and dopamine basics has always been popular, partly because serotonin and dopamine have gone from obscure abstractions to pop buzzwords. But I think it also shows a growing awareness of brain science and its real-world applications among interested readers.
“…. Addictive drugs have molecules that are the right shape for the amine receptors. Drugs like LSD and Ecstasy target serotonin systems. Serotonin systems control feeding and sleeping behaviors in living creatures from slugs to chimps. Serotonin, also known as 5-HT, occurs in nuts, fruit, and snake venom. It is found in the intestinal walls, large blood vessels, and the central nervous system of most vertebrates. The body normally synthesizes 5-hydroxytryptamine, as serotonin is formally known, from tryptophan in the diet….”
Serotonin and Dopamine: A primer on the molecules of reward
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2) Continuing on the chemistry theme, this post on anandamide, the brain’s own form of internal marijuana, has garnered steady attention since 2008. It may be coincidental, but the post also makes mention of serotonin and dopamine.
“…Several years ago, molecular biologists identified the elusive brain receptor where THC, the active ingredient in marijuana, did its work. Shortly after that discovery, researchers at Hebrew University in Jerusalem identified the body’s own form of THC, which sticks to the same receptors, in pulverized pig brains. They christened the internally manufactured substance “anandamide,” after the Sanskrit ananda, or bliss…”
Anandamide, the Brain’s Own Marijuana: Anxiety and the THC receptor.
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3) Interest in the anti-craving drug Topamax, an anti-seizure medication used to treat alcoholism, remains strong with blog readers, although the drug has not become the universal blockbuster many advocates had hoped.
“…Dr. Bankole Johnson, chairman of Psychiatry and Neurobehavioral Sciences at the University of Virginia, told Bloomberg News that Topamax does everything researchers want to see in a pharmaceutical treatment for alcoholism: “First, it reduces your craving for alcohol; second, it reduces the amount of withdrawal symptoms you get when you start reducing alcohol; and third, it reduces the potential for you to relapse after you go down to a low level of drinking or zero drinking…"
Topamax for Alcoholism: A Closer Look. Epilepsy drug gains ground, draws fire as newest anti-craving pill
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4) One of the most popular posts to date was this examination of neurological questions surrounding marijuana and memory loss. Inquiring minds, uh, forget the question. Oh yeah: Does the strain of dope you smoke determine how forgetful you’ll become?
“…As far as memory goes, THC content didn't seem to matter. It was the percentage of cannabidiol (CBD) that controlled the degree of memory impairment, the authors concluded. "The antagonistic effects of cannabidiol at the CB1 receptor are probably responsible for its profile in smoked cannabis, attenuating the memory-impairing effects of THC. In terms of harm reduction, users should be made aware of the higher risk of memory impairment associated with smoking low-cannabidiol strains of cannabis like 'skunk' and encouraged to use strains containing higher levels of cannabidiol..."
Marijuana and Memory: Do certain strains make you more forgetful?
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5) Finally, a popular post focusing on the biochemistry of nicotine in e-cigarettes, the new, smokeless nicotine delivery system. Are they safe? The latest in harm reduction strategies, or starter kits for youngsters?
“…You may never have heard of it—but it’s the newest drug in town. It’s called an electronic cigarette, or “e-cigarette.” Electronic cigarettes use batteries to convert liquid nicotine into a fine, heated mist that is absorbed by the lungs. No smoke, but plenty of what makes cigarettes go, if you don’t account for taste—or ashtrays and smoke rings….”
E-Cigarettes and Health: Smokeless nicotine comes under scrutiny.
Photo Credit: http://www.livingim.com/
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