A High Old Time in Rhode Island

Feds release annual drug numbers.

[Map: Illicit drug use other than marijuana in the past month among people aged 12 or older based on 2007-2008 figures.]→

It’s time again for the government’s annual state-by-state survey of drug use in America.  Assembled by the Substance Abuse and Mental Health Services Administration (SAMHSA), the yearly numbers are argued over by states and agencies competing for federal health and medicine dollars. In this year’s sweepstakes, dark horse Rhode Island upset the reigning champion, the District of Columbia, as the state with the highest number of monthly users of illicit drugs other than marijuana. 

Usage figures were based on numbers compiled in 2007 and 2008. Overall, eight per cent of Americans aged 12 or older used an illicit drug other than pot in the prior month, essentially unchanged from last year’s report based on 2006-2007 figures. Using the percentage of monthly users as a yardstick, other states in the highest group included Arizona, Arkansas, Kentucky, Nevada, Oklahoma, Oregon, Colorado, and Tennessee. Among the states in the lowest group were Maine, Minnesota, Nebraska, Mississippi, New Jersey, the Dakotas, Wyoming—and the lowest of them all--Iowa.

According to SAMSHA, five states showed significant changes compared to a year ago. Iowa, Louisiana and Wyoming showed marked decreases, while usage of drugs other than marijuana in Hawaii and Oregon increased.

As for alcohol, SAMSHA pegs the national rate of alcohol use among people age 12 or older at 51.4 per cent. The highest rate of alcohol use was found in the 18-25 age group (big surprise there). This year the state drinking trophy goes to New Hampshire, with Utah coming in dead last, as usual. High-drinking states include Colorado, Massachusetts, New Hampshire, Rhode Island, Vermont, and Wisconsin. (What is it with New England?)

Interestingly, eight out of the ten lowest states for drinking are found in the South: Alabama, Arkansas, North Carolina, and Virginia, among others. However, the South makes up for it in tobacco usage. States with the highest prevalence of tobacco use were Arkansas, Kentucky, Ohio, West Virginia—and, okay, Wyoming. The state with the fewest smokers? Do you have to ask? Utah. The national smoking average still hovers around 24 per cent.

For a longer view, SAMSHA compared the current study figures with numbers compiled in 2002-2003. Iowa, Missouri, and Pennsylvania showed significant drops for drugs other than marijuana. Only Rhode Island and Tennessee showed marked increases.

Tennessee also showed increases in marijuana usage, while less pot was smoked in Florida, Iowa, Missouri, and Pennsylvania. Overall, usage decreased slightly compared to the 2002-2003 period.

The most meaningful change compared to the 2002-2003 period was a 2.5 per cent decrease in the use of cocaine among people 12 or older. Nationwide, the percentage of alcohol use remained almost identical (51.4 per cent).

Photo Credit: SAMSHA

Choline for Fetal Alcohol Spectrum Disorders?

Common supplement may reduce cell death in pregnancies.

A common dietary supplement markedly decreases defects in the skull and brain formation of  lab mice born to mothers exposed to alcohol, say researchers at the Medical College of Georgia.

Among the grisly list of potential effects caused by alcohol consumption during pregnancy, one involves a relatively obscure lipid called ceramide. Ceramide can markedly increase the rate of programmed cell death—a process known as apoptosis—and may be involved in the characteristic cranial defects seen in fetal alcohol syndrome.

In the study, 25 % of the mouse embryos exposed to alcohol showed characteristic defects in skull development, including diminished growth in the multi-layered membrane—the meninges--covering the brain.  Biochemists Erhard Bieberich and Guanghu Wang, in an article published in Cell Death and Disease, found that the supplement CDP-choline decreased cell death and protected the fetal cranium from damage due to maternal drinking episodes. According to Dr. Bierberich in a press release from the Medical College of Georgia, the result of alcohol on pregnancy is “a snowball effect. The neural crest is damaged, the meninges doesn’t develop properly and tissue like bone and brain that are regulated by the meninges don’t develop properly either.”

Choline is a precursor to the neurotransmitter acetylcholine. In addition, it has been known for decades that alcohol increases choline requirements. Choline is already added to some baby formulas and prenatal vitamins. Choline’s effects on stroke and traumatic brain injury are also being investigated.

A similar discovery twenty years ago concerning folic acid led the U.S. Public Health Service (USPHS) to recommend that all women thinking of becoming pregnant should consume supplemental folic acid daily in order to reduce their risk of having a pregnancy affected by spina bifida or other neural tube defects. The rate of occurrence of this kind of birth defect has been dropping ever since.

The researchers believe that “there is just a little window” four weeks after conception—while neural cells are forming numerous organs--when the alcohol-related cranial damage is likely to occur. Unfortunately, this window of disaster opens before many women have discovered that they are pregnant. 

Since warnings about the dangers of drinking during pregnancy are either not known or are ignored in many cases, researchers are always on the lookout for medications that could be given after exposure to alcohol--or even after birth of a baby to an alcoholic mother.  As early as 2005, researchers at Tripler Army Medical Center in Honolulu demonstrated that adding choline to the pre-natal diet of pregnant alcoholic rats suppressed physiological symptoms of fetal alcohol syndrome in the offspring. In a press release from the American Physiological Society, lead researcher John Claybaugh asserted that the results “are consistent with the hypothesis that supplemental dietary choline fed to the pregnant dam can prevent the alcohol-induced partial diabetes insipidus seen in the young adult offspring.”

The American Psychological Association, in the wake of a 2007 study published in Behavioral Neuroscience, announced that “giving choline to infants who were exposed in the womb to alcohol may mitigate some of the resulting problems” related to learning, attention, and motor skills. The researchers gave choline to rat pups exposed to alcohol during the third trimester. Alcohol-related hyperactivity and learning deficits decreased, the researchers say. “The data suggest that early dietary interventions may reduce the severity of some fetal alcohol effects, even when administered after birth."

 Despite such optimism, the issue is whether a choline supplement would be capable of rescuing cells after alcohol exposure, or whether choline would need to be taken ahead of time as a supplement.

What is not at issue is that pregnant women should not drink, and should be aware that fetal damage can occur very early in a pregnancy.

Graphics Credit: http://www.cholineinfo.org/

Wang, G., & Bieberich, E. (2010). Prenatal alcohol exposure triggers ceramide-induced apoptosis in neural crest-derived tissues concurrent with defective cranial development Cell Death and Disease, 1 (5) DOI: 10.1038/cddis.2010.22

Noteworthy Recent Posts on Drugs and the Brain

A few good articles.

Teasing Out the Effects of Environment on the Brain.

By Moheb Costandi

The Dana Foundation

Antidepressants: Are They Effective or Just a Placebo?

By Maia Szalavitz

Time Magazine

SSRIs and Suicide.

By Neuroskeptic

Neuroskeptic blog

Cannabis and mental health – two new studies give the “wrong” results!

UKCIA Newsblog

Under the Microscope: How does caffeine work?

By Professor Andrew Smith.

UK Independent

Photo Credit: http://degweb.org/

Gambling and Parkinson’s Disease

An addendum to the previous post.

Today, a group of Australians taking medications for Parkinson's Disease have filed a class action suit against makers of the drugs, according to a report in the Sydney Morning Herald.

 The Australian newspaper said that "The group includes people who sustained losses of hundreds of thousands of dollars and were involved in family breakdowns as a result of compulsive gambling allegedly linked to drugs they took between 1997 and last year. Most of the claimants developed gambling addictions but a few exhibited compulsive sexual behavior such as looking at pornography on the Internet.”

The drugs involved are dopamine agonists Cabaser and Permax. An agonist binds to particular receptor sites and mimics the action of the substance that normally occupies the site.

A study published in the May issue of Archives of Neurology concluded that, “Dopamine agonist treatment in PD (Parkinson's Disease) is associated with 2- to 3.5-fold increased odds of having an ICD (impulse control disorder)."

According to the study, 13% of the patients were adversely affected by the drugs, exhibiting impulse control problems with gambling (5 percent), sexual behavior (3.5 percent), shopping (5.7 percent) and binge eating (4.3 percent).

The case is not without precedent, according to the Herald. In 2008, “a jury in Minnesota awarded $8.2 million to a man who became a compulsive gambler after using Mirapex (made by Boehringer Ingelheim) to treat his Parkinson's disease. Other lawsuits are being considered in Canada, Britain and France.”


Photo Credit: http://gamingzion.com/

Triple Play for Addicts

Why cigarettes, alcohol and gambling are such a perfect fit.

The newer views of addiction as an organic brain disorder cast strong doubt on the longstanding assumption that different kinds of people become addicted to different kinds of drugs. By 1998, the Archives of General Psychiatry had already flatly stated the reverse: “There is no definitive evidence indicating that individuals who habitually and preferentially use one substance are fundamentally different from those who use another.” This quiet but highly influential breakthrough in the addiction paradigm has paid enormous dividends ever since.

From a genetic standpoint, the implication was that an addiction to alcohol, heroin, or speed did not necessarily “breed true.” The sons and daughters of alcoholics could just as easily grow up to be heroin addicts, and vice versa, due to the same brain anomalies.

There are numerous examples at hand. Recovering alcoholics and heroin addicts tend to be notorious chain-smokers, for one. Many prominent nicotine researchers lean toward the theory that those Americans who continue to be hard-core smokers, unwilling or unable to stop, may represent a biological pool of people who are genetically prone to addiction. Alcohol researcher George Vaillant,  who directed the seminal Harvard Medical School longitudinal studies, sees it the same way: “Alcoholism is a major reason that people don’t stop smoking. Those who keep on smoking after age 50 tend to be alcoholics.” 

There you have it. Throw a lasso around America’s cigarette smokers, and you are likely to snare the lion’s share of “drug abusers” and “problem drinkers” as well. This may also explain why there is such a huge overlap between gamblers and alcoholics, and between gambling and cigarette addiction. It is no secret to anyone who has been inside a casino that a striking percentage of the patrons are also smokers and drinkers. If gambling were truly capable of producing the hallmark symptoms of addiction, we would also expect to see such manifestations as continued use despite adverse circumstances, escalating use, and various forms of self-destructive behavior. It depends on whether the dopamine/serotonin patterns produced by addiction, involving midbrain dopamine neurons with divergent connections to the frontal cortex and other forebrain regions, are the same in compulsive gamblers as in alcoholics and other addicts. Many researchers simply do not believe that the alterations in neurotransmission brought about by behaviors are as powerful as the chemical surges produced by drugs, and therefore cannot result in a state technically called addiction. Others disagree.

Nonetheless, human neurostudies continue to show intriguing dopamine patterns during gambling and certain other forms of game playing. Part of what drives the destructive gambling cycle appears to be the intense, dopamine-driven arousal produced by the anticipation of reward—the jackpot.  Recent research has focused on the part played by midbrain dopamine in the anticipation of reward, otherwise known by addicts as “waiting for the man.” In the world of gaming, it is known as the classic “gambler’s fallacy—the expectation that after a series of losses, a win is “due.” Statistics say otherwise, and gamblers certainly know all about house percentages. Yet, the expectation effects of beating those odds may produce the same anticipatory effect on a disordered metabolism as drug-related activities. A very small, speculative, and intriguing study at Duke University suggested that dopamine agonists given for Parkinson’s disease might sometimes be a catalyst for excessive gambling behaviors in elderly patients, even those who had never shown an interest in gambling before.

As for shopping and sex, even an informed guess seems premature at this point.

Photo Credit: http://www.health.com/

Life After Cigarettes: Book Review

Why Women Smoke.

Women are different from men. Well, maybe you already knew that.  But did you know that women smoke differently than men, and quit smoking differently than men?

Dr. Joseph Califano, the U.S. Secretary of Health, Education, and Welfare under President Jimmy Carter, once said that even though he gained thirty pounds when he quit cigarettes, he did not then appreciate the importance to women of the link between smoking cessation and weight gain. As Dr. Cynthia Pomerleau, formerly the director of the Nicotine Research Laboratory at the University of Michigan and now Research Professor Emerita in the Department of Psychiatry, remarks in her new book, Life After Cigarettes: “If we’d had a woman HEW Secretary at that time, and she had stopped smoking, I’m sure a thirty-pound weight gain would have grabbed her attention!”

In her book, Dr. Pomerleau makes clear that the challenges of quitting smoking are even greater for women than they are for men. She is refreshingly frank: “Face it; There are definitely some plusses to smoking. If there weren’t, you wouldn’t have done it, and neither would anyone else.”

For women, one of the primary pluses is, and has always been, weight control.  Pomerleau offers up the image of smoking ballerinas, women performing in a business where gaining two pounds can mean the loss of a job. Models, gymnasts, and ice skaters have also looked to cigarettes for help with weight control.

When women quit smoking, here are the facts of the matter: They will begin gaining weight almost the minute they quit—as much as three pounds in the first week—and will stabilize within three to six months. The average weight gain for women, writes Pomerleau, is ten pounds, with a quarter of female quitters gaining five pounds or less, and about a quarter gaining more than 15 pounds.  And the longer women smoke, the harder it is to battle the weight gain when they eventually quit.

The problem, Pomerleau discovered when screening patients for her Nicotine Research Lab, was that 75 per cent of the women who wanted to quit smoking said that they were unwilling to gain more than five pounds while doing so. 40 per cent of the women responded that they were unwilling to gain ANY pounds in pursuit of tobacco abstinence.

In an email exchange with Addiction Inbox, Professor Pomerleau was kind enough to expand on her message.  

When I asked her about reports that the dopamine D2 receptor gene has been implicated in both weight gain and smoking, she responded:

“In a laboratory study of food reward in smokers attempting to quit, Caryn Lerman and colleagues found that carriers of the DRD2 A1 minor allele exhibited significant increases in the rewarding value of food following abstinence from smoking, and that higher levels of food reward after quitting predicted a significant increase in weight by 6-month follow-up in participants receiving placebo.  Both effects were attenuated in participants receiving bupropion, leading them to conclude that bupropion’s efficacy in attenuating abstinence-induced weight gain may be attributable, in part, to decreasing food reward.  How well these findings will hold up to further scrutiny in larger samples remains to be seen.”

On smoking and bulimia: “As I’m sure you’re aware, the question of ‘self-medication’ is a complicated one, but it seems likely that some women ‘use’ nicotine to hold the symptoms of bulimia in check; when they quit, the underlying predisposition reemerges – which helps to explain why these women may be more prone to larger weight gain than other quitting smokers.” 

On smoking as a weight management tool: “Using a variety of different measures, it’s probably safe to say that around 40% of women qualify as serious weight-control smokers.  (The proportion is much lower in men.)  By the way, though findings are mixed, these women don’t necessarily fare worse than other women when they quit, even if they do gain weight; the real challenge is bringing them to the point of even considering quitting.”

And finally, when I asked Professor Pomerleau about the role of primary care physicians in promoting smoking cessation, she noted that she was “concerned about possible attempts to downplay the amount of weight quitters can expect to gain or to overstate the ease with which it can be avoided – which can backfire and lead to relapse when the needle on the scale begins to creep up.  I personally think it’s better to be realistic about the likelihood of weight gain after quitting and to concentrate on keeping it in the 5-10 pound range (approximately one unit of BMI and less than a dress size) – something that is in fact an achievable goal for most women.”

Photo Credit: http://www.mapleplaceventures.com/

X-ed Out.

Another look at MDMA and serotonin.

A study by Canada’s Centre for Addiction and Mental Health (CAMH) has confirmed earlier findings that chronic users of ecstasy (MDMA) have abnormally low levels of serotonin transporter molecules in the cerebral cortex.

While a decade of research on the effects of ecstasy on brain serotonin has been controversial and largely inconclusive, the latest study used drug hair analysis to confirm levels of MDMA in 49 users and 50 controls. An additional division was made between chronic X users who also tested positive for methamphetamine, and those who did not. Regular usage of MDMA was defined as two tablets twice a month.

The Canadian study, funded by the U.S. National Institute on Drug Abuse (NIDA) and published in the journal Brain, suggests that the serotonin surge responsible for ecstasy’s effects results in a net depletion in regular X users. That is not a new finding--but the Canadian study goes further, suggesting that the serotonin depletion is localized in one area of the brain.

“We were surprised to discover that SERT was decreased only in the cerebral cortex and not throughout the brain,” said study leader Stephen Kish in a press release, “perhaps because serotonin nerves to the cortex are longer and more susceptible to changes.”

Low serotonin transporter (SERT) levels in the cerebral cortex were found in all X users, with or without amphetamine. Dr. Kish noted that the CAMH findings replicate what Kish referred to as “newer data” from Johns Hopkins University. In 1999, a controversial serotonin study of ecstasy users at Johns Hopkins laboratory was criticized for overestimating the level of danger posed by ecstasy-induced serotonin impairments.

Okay, the finding is becoming more robust. But what does it mean? According to co-author Isabelle Boileau, a low SERT level does “not necessarily” indicate structural brain damage. “There is no way to prove whether low SERT is explained by physical loss of the entire serotonin nerve cell, or by a loss of SERT protein within an intact nerve cell.”

For his part, Dr. Kish indicated that his concerns centered on the connection between lower serotonin measurements and MDMA tolerance levels. “Most of the ecstasy users of our study complained that the first dose is always the best, but then the effects begin to decline and higher doses are needed,” he said. “The need for higher doses, possibly caused by low SERT, could well increase the risk of harm caused by this stimulant drug.” The published study concluded that “behavioural problems in some ecstasy users during abstinence might be related to serotonin transporter changes limited to cortical regions.”

However, in addition to the confounding variable of methamphetamine (see my post, “How Pure is Ecstasy?”), it remains unclear whether the SERT alterations detected in the study are transient or permanent. Moreover, the nature of the link that “might” exist between lower SERT levels and cognitive impairment in the brains of regular ecstasy users remains a subject of dispute in the drug research community, as in this earlier post.  (And just to emphasize that drugs are complicated things, a spate of promising recent research has suggested that ecstasy might be an effective option for treating people with post-traumatic stress disorder).

The CAMH, affiliated with the University of Toronto, is Canada’s largest mental health and addiction teaching hospital.

Kish, S., Lerch, J., Furukawa, Y., Tong, J., McCluskey, T., Wilkins, D., Houle, S., Meyer, J., Mundo, E., Wilson, A., Rusjan, P., Saint-Cyr, J., Guttman, M., Collins, D., Shapiro, C., Warsh, J., & Boileau, I. (2010). Decreased cerebral cortical serotonin transporter binding in ecstasy users: a positron emission tomography/[11C]DASB and structural brain imaging study Brain DOI: 10.1093/brain/awq103

Graphics Credit: pubs/teaching/teaching4/Teaching3.html