A Night of Serious Drinking: The Results

"A systematic review of the next‐day effects of heavy alcohol consumption on cognitive performance"

The latest scientific rundown on the ramifications of hangovers, in the journal Addiction, can be found HERE.

 

There Is No "Safe" Amount of Alcohol

 Moderate daily drinking will not improve your health.

As a growing number of addiction and alcohol consumption researchers have been pointing out, the notion of a safe and even beneficial level of daily drinking is outmoded and in error. In an article published in Lancet, researchers offer strong evidence against the theory, based on data from the Global Burden of Diseases, Injuries, and Risk Factors Study of 195 countries and territories.

 In an accompanying commentary, researchers note that the data "clearly demonstrate the substantial, and larger than previously estimated, contribution of alcohol to death, disability, and ill health, globally." Moreover, the Chief Medical Officer of the UK announced that there is “no safe level of alcohol consumption” and suggested that policies designed to decrease daily drinking should receive top priority.


(See my post from 2015 predicting the death of the "moderate drinking" meme.)

Caffeine, Energy Drinks, and Everything Else

It's the everything else that adds up.

A couple of years ago, coffee drinkers were buoyed by the release of a massive study in the New England Journal of Medicine that “did not support a positive association between coffee drinking and mortality.” In fact, the analysis by Neal D. Freedman and associates showed that even at the level of 6 or more cups per day, coffee consumption appeared to be mildly protective against diabetes, stroke, and death due to inflammatory diseases. Men who drank that much coffee had a 10% lower risk of death, and women in this category show a 15% lower death risk. Coffee, it seemed, was good for you.

Hooray for coffee—but lost in the general joy over the findings was the constant association of coffee with unhealthy behaviors like smoking, heavy alcohol, use, and consumption of red meat. And the happy coffee findings did not consider the consumption of caffeine in other forms, such as energy drinks, stay-awake pills, various foodstuffs, and even shampoos.

One of the earliest battles over “energy drinks” was an action taken in 1911 under the new Pure Food and Drug Act—the seizure by government agents of 40 kegs and 20 barrels of Coca-Cola syrup in Chattanooga. Led by chemist Harvey Wiley, the first administrator of the Food and Drug Administration (FDA), agents of the fledgling organization acted on the belief that the soft drink contained enough caffeine to pose a significant public health hazard. The court case went on forever. Eventually Coca-Cola cut back on caffeine content, and the charges were dropped.

Jump cut to 2012, and watch the FDA grapple with the same question a hundred years later, citing concerns about undocumented caffeine levels in so-called energy drinks in the wake of an alleged link between the caffeinated soft drinks and the death of several young people. According to Dr. Kent Sepkowitz, writing in the Journal of the American Medical Association, while only 6% of young American men consume the drinks, “in a recent survey of U.S. overseas troops, 45% reported daily use.” In 2006, more than 500 new energy drinks hit the market. By 2011, sales of energy drinks in the U.S. climbed by more than 15% to almost $9 billion.

Death by caffeine has long been a subject of morbid interest, and an article in the Journal of Caffeine Research  by Jack E. James of Iceland’s Reykjavik University questions these prevailing assumptions, and brings together the latest research on this perennial question, including, yes, a consideration of whether the time has come to regulate caffeine as some sort of controlled substance.

In 2013, the FDA released reports that attributed a total of 18 deaths to energy drinks. Somewhere between 3 and 10 grams of caffeine will kill you, especially if you are young, old, or suffer from various health problems. The generally accepted lethal dose is 10 g. The wide gap in estimates and mortality reports reflects the wide variation in caffeine’s effects.  Half the lethal dose can kill a child, and some adults have survived 10 times that amount. As I wrote in an earlier post (“Energy Drinks: What’s the Big Deal?”): “Energy drinks are safe—if you don’t guzzle several of them in a row or substitute them for dinner, or have diabetes, or an ulcer, or happen to be pregnant, or are suffering from hearth disease or hypertension. And if you do OD on high caffeine intake, it will not be pleasant: Severe cardiac arrhythmias, palpitations, panic, mania, muscle spasms, and seizures.”

Warning signs include racing heart, abdominal pain, vomiting, and agitation. Since the average cup of coffee weighs in at about 100 milligrams, there doesn’t seem to be much to worry about in that regard. Nonetheless, the American National Poison Data System (NPDS) has more than 6,000 “case mentions” related to caffeine. One of these cases generated considerable press coverage: the death of a 14 year-old girl with an inherited connective tissue disorder.

In his article for the Journal of Caffeine Research, James starts by noting other fatalities, including two confirmed caffeine-related deaths in New Mexico, and four in Sweden, among other long-standing historical reports. Still, not much there to wring your hands over—but James insists that data on poisonings “do not show what contributory role caffeine may have had in cases where fatal and near-fatal outcomes were deemed to have been due to other compounds also present.”

Fair enough. But here is where the argument gets interesting. “Considerably smaller amounts of caffeine,” writes James, "may be fatal under a variety of atypical though not necessarily rare circumstances.” Among these, he singles out: 1) Prior medical conditions predisposing patients toward unusual caffeine metabolism. 2) Unknown interactions and synergies with prescription, over-the-counter, and illegal drugs. 3) Physical stress and high-intensity sports. 4) Children, for whom caffeine is easily available.

James claims we don’t know enough to insist caffeine is essentially harmless, let along good for us in large doses. He compiled this eye-opening list of foods and other products that sometimes contain caffeine: ice cream, chewing gum, yogurt, breakfast cereal, cookies, flavored milk, beef jerky, cold and flu medications, weight-loss compounds, breath-freshener sprays and mints, skin lotion, lip balm, soap, shampoo, and, most notably, as a contaminant in illegal drugs. James says that the largest category of incidents with over-caffeinated young people involve “miscellaneous stimulants and street drugs…”

As for energy drinks themselves: “As a nonselective adenosine receptor antagonist, caffeine counteracts the somnogenic effects of acute alcohol intoxication, and alcohol may in turn ameliorate the anxiogenic effects of caffeine.” It’s an age-old practice: caffeine doesn’t sober up drunks, but it does keep them awake. James believes the evidence shows that the combination of caffeine and alcohol increases the risks of unprotected sex, sexual assault, drunk driving, violence, and emergency room visits.

Furthermore, “the ubiquity of caffeine is such that it has become a biologically significant contaminant of freshwater and marine systems….”

Finally, James offers a vision of a caffeine-regulated future, noting that Denmark, France, and Norway have already introduced sales restrictions on energy drinks. Restrictions on the sale of powdered caffeine may follow, as a valid public health measure. “Canada requires labeling in relation to the same product, advising that it should not be mixed with alcohol.” Other countries have labeled energy drinks as “high caffeine content” beverages. And Sweden regulates the number of caffeine tablets that can be purchased at one time from a drugstore.  Meanwhile, in the U.S., makers of energy drinks, unlike makers of soft drinks, do not even have to print the amount of caffeine on the label as dietary information, although this is in the process of changing. Major energy drink makers are moving to put caffeine content labels on their products, in part to shift their relationship with the FDA. Last year, The Food and Drug Administration advised consumers to avoid powdered caffeine due to health risks.

Originally published March 13, 2013

Graphics: http://www.runnersworld.com

Moderate Drinking Doesn’t Help Your Heart

Mendelian meta-analysis and the alcohol “flush” allele.

Less than a year after the massive Mendelian randomization meta-analysis published in the British Medical Journal, a group of researchers recently wrote an editorial in the journal Addiction, which would seem to put a lid on the matter:

The foundations of the hypothesis for protective effects of low-dose alcohol have now been so undermined that in our opinion the field is due for a major repositioning of the status of moderate alcohol consumption as protective…. Health professionals should not recommend moderate alcohol consumption as a means of reducing         cardiovascular risk for patients. At the policy level, the hypothesis of health benefits from moderate drinking should no longer play a role in decision making.

To recap: In the Mendelian meta-analysis, drinkers with a genetic variant linked to the so-called alcohol flush reaction, which leads to lower consumption among those who drink, also correlated with a decreased risk of cardiovascular disease. “Carriers of the rs1229984 A-allele had lower levels of alcohol consumption and exhibited lower levels of blood pressure, inflammatory biomarkers, adiposity measures, and non-HDL cholesterol, and reduced odds of developing coronary heart disease, compared with non-carriers of this allele.”

But as it turned out, this relationship only held for drinkers, not for abstainers.

Why, then, have so many epidemiologists agreed for several decades now that “moderate” alcohol intake has a protective effect against heart diseases? According to the editorial authors—drug researchers from Australia, Canada, the U.S., and Sweden—earlier research tended to use “abstainers” as the key reference group to which drinkers were compared. Studies that separated former drinkers and occasional drinkers from abstainers got different results—they didn’t show significant protection correlating with moderate alcohol consumption. The theory, say the researchers, is that non-addicted drinkers spontaneously reduce their alcohol intake with age and medical concerns. Some of these people with a declining health profile are counted as “abstainers.” But when former and current drinkers are combined, then compared with life-long abstainers to address selection bias, “the observed disparity in health status between abstainers and low-dose drinkers was eliminated.”

But it’s not quite over. Michael Rioerecke and Jurgen Rehm at the Center for Addiction and Mental Health in Toronto, argue in another Addiction editorial that there are still a few things unaccounted for: The allele in question is assumed to be randomly spread throughout the population, which may or may not be true, especially since allele carriers are relatively rare in several European countries. The allele is also assumed to be mediated by average alcohol intake. Binge drinking, which allele carriers presuming engage in less, is not assessed in the study.  In short, they write, “we do not know if the average level of alcohol intake of the allele carriers within the strata of average consumption was indeed lower than that of the non-carriers.” Nonetheless, even Rioerecke and Rehm concede that the evidence continues to look promising for this revision of conventional drinking wisdom. More than 100 studies have shown relatively stable associations between alcohol and heart disease, and absent a new breakthrough method of epidemiological study, this one stands a good chance of holding firm.

Graphics credit: http://www.keyingredient.com/

Marijuana Statistics vs. Perception

Who smokes cannabis, and how much?

(First published 12/27/2013)

Most statistical surveys of marijuana focus on a single quantitative measurement: How many people are using? But there’s a problem: More marijuana use does not necessarily translate into more marijuana users. And that’s because a clear majority of the consumption, and black market dollars, come from the heaviest smokers.

Drug policy researchers at the RAND corporation decided that frequency of use and amount of consumption were valuable parameters gone missing in most policy discussions. So they put the focus not just on use, but also on “use-days,” and pulled a number of buried tidbits from a very big data pile. If you zero in on consumption, and not just consumers, they insist, you will find a wholly different set of inferences.

For example: “Although daily/near-daily users represented less than one-quarter of past-month cannabis users in 2002 and roughly one-third of past-month users in 2011, they account for the vast majority of use-days and are thus presumably responsible for the majority of consumption,” write Rachel M. Burns and her RAND colleagues in Frontiers of Psychiatry. As with alcohol, the majority of cannabis consumption can be accounted for by a minority of users. The heaviest users, the upper 20 percent, consume 88 percent of the U.S. marijuana supply, say the RAND researchers. “Furthermore, if over time there were no change in the number of cannabis users, but the ratio of light vs. heavy users switched from 80/20 to 20/80, then consumption would increase by 250% even though there was no change whatsoever in the number of users.”

The RAND group used two data sets on cannabis consumption—the National Survey on Drug Use and Health (NSDUH) in the U.S., and the EU Drugs Markets II (EUMII) in Europe. Data included figures for past-year and past-month use, past-month use days, and past-month purchases.

Other intriguing figures come to light when you study cannabis use, as opposed to cannabis users. The researchers declared that “only 14% of past-year cannabis users [primarily males] meet the criteria for cannabis abuse or dependence, but they account for 26% of past-month days of use and 37% of past-month purchases.”

Happen to smoke blunts? That turns out to be very telling, according to the RAND study. “Perhaps the most striking contrast concerns blunts. Only 27% of past-year cannabis users report using a blunt within the last month, but those individuals account for 73% of cannabis purchases.” Casual users, it seems, don’t do blunts.

Clearly, it takes a lot of casual users to smoke as much marijuana as one heavy user. But exactly how many? The RAND researchers ran the numbers and concluded that, in terms of grams consumed per month, it would take more than 40 casual smokers to equal the intake of a single heavy user. The share of the market represented by daily/near-daily users is clearly the motive force in their analysis.

The study in Frontiers in Psychiatry also found patterns of interest on the buy side. General use took an upswing beginning in 2007. While the probability of arrest per marijuana smoking episode hovers somewhere in the neighborhood of 1 in 3,000, everything changes if you are purchasing cannabis. RAND reported that young people collectively make more purchases per day of reported use than do older users. Therefore, “statistics indicating that the burden of arrest falls disproportionately on youth relative to their share of all users may not be prima facie evidence of discrimination if making more purchases per day of use increases the risk of arrests per year of use.” Once again, those aging Baby Boomer potheads get the best deal. They have more money with which to buy bigger amounts less often, thereby greatly lessening their chances of arrest and prosecution.

This also applies to minority arrests for marijuana offenses. “Non-Hispanic blacks represent 13% of past-year cannabis users vs. 23% of drug arrests reported by those users, but they report making 24% of the buys. Thus, some of their higher arrest rate may be a consequence of purchase patterns… African-Americans may not only make more buys but also make riskier buys (e.g., more likely to buy outdoors).”

The researchers were able to draw some conclusions about the growth in marijuana usage from 2002 through 2011, based on the NSDUH data. Their main conclusion, after exploring the demographics of this 10-year record of use, is that “consumption grew primarily because of an increase in the average frequency of use, not just because of an increase in the overall number of users.”  The driver of consumption turns out to be… greater consumption. And that increased consumption is coming from… older adults. Those older adults, it turns out, are smoking more weed.

The shift is dramatic: “In 2002, there were more than three times as many youth as older adults using cannabis on a daily/near-daily basis; in 2011 there were 2.5 times more older adults than youth using on a daily/near-daily basis.” The record of alcohol and cigarette use over the same period showed no such inversion of use patterns.  And the tweeners? “In 2002, 12-17-year-olds represented 13% of daily/near-daily users; in 2011, that had dwindled to 7%.” These trends are not just the obvious result of an increase in the proportion of older adults in the population at large. Increases in the proportion of older heavy cannabis users were much greater than the general population drift.

Among the questions raised by the RAND analysis:

— Are older marijuana smokers primarily recreational, or medicinal?

—Do increased use days among older, college-educated marijuana smokers indicate greater social acceptance, or something else?

—Are younger people replacing traditional cannabis use with other substances?

—Why did Hispanic use increase more over the study period than other ethnic groups?

Burns R.M., Caulkins J.P., Everingham S.S. & Kilmer B. (2013). Statistics on Cannabis Users Skew Perceptions of Cannabis Use, Frontiers in Psychiatry, 4   DOI: 10.3389/fpsyt.2013.00138

Alcohol and Your Heart

Health benefits of moderate drinking come under fire.

One of those things that “everybody knows” about alcohol is that a drink or two per day is good for your heart. But maybe not as good for your heart as no drinks at all.

Joint first authors Michael V. Holmes of the Department of Epidemiology and Public Health at University College in London, and Caroline E. Dale at the London School of Hygiene & Tropical Medicine in London, recently published a multi-site meta-analysis of epidemiological studies centering on a common gene for alcohol metabolization. The report, published in the UK journal BMJ, brings “the hypothesized cardioprotective effect of alcohol into question,” according to the authors.

People who are born with a particular variant in the gene controlling for the expression of alcohol dehydrogenase, the major enzyme involved in converting alcohol into waste products, will show the familiar flush reaction when they drink. Alcohol, literally, can make many of them sick. This genetic variant, in combination with other enzymes, can be strongly protective against alcohol, and is much more commonly found among Asian populations. Roughly 40% of Japanese, Korean, and Northeastern Chinese populations show the characteristic “Asian glow” to one degree or another if they choose to drink.  (One reason why this effect isn't better known is that the condition is close to nonexistent in Westerners).

 People with this alcohol dehydrogenase deficiency, the researchers found, not only consume less alcohol, for obvious reasons, but “had lower, not higher, odds of developing coronary heart disease regardless of whether they were light, moderate, or heavy drinkers.”  Here are the conclusions in detail: “Carriers of the rs1229984 A-allele had lower levels of alcohol consumption and exhibited lower levels of blood pressure, inflammatory biomarkers, adiposity measures, and non-HDL cholesterol, and reduced odds of developing coronary heart disease, compared with non-carriers of this allele.”

The authors conclude that "reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.”

How does this work? The researchers aren’t completely sure, but note that the “most widely proposed mechanism” is an increase in high-density lipoprotein (HDL) cholesterol. “Although an HDL cholesterol raising effect of alcohol has been reported in experimental studies, the small sample size and short follow-up means existing studies may be prone to bias,” thereby limiting their usefulness. Moreover, the BMJ study itself found “no overall difference between allele carriers and non-carriers in HDL concentration.”

Like most meta-studies, this one has its strengths and weaknesses. The study used a large sample size, used detailed alcohol phenotypic data, and didn't have to deal with the inherent biases of observational-type studies. On the minus side, the lack of a connection between the allele in question and HDL levels is troubling, and stroke data was lacking.

But overall, the authors believe that "social pressure in heavier drinking cultures is unlikely to override the effect of the genetic variant on alcohol consumption."

In retrospect, there have been some trouble spots along the way: A 2008 study in Current Atherosclerosis Reports concluded:

In the absence of large randomized trials of moderate alcohol consumption and heart failure, we cannot exclude residual confounding or unmeasured confounding as possible explanations for the observed relationships. Thus, for patients who do not consume any alcohol, it would be premature to recommend light-to-moderate drinking as a means to lower the risk of heart failure, given the possible risk of abuse and resulting consequences.

At present, the American Heart Association does not recommend drinking any amount of wine or other alcoholic beverages in order to gain potential health benefits.


Holmes M.V.,  L. Zuccolo,  R. J. Silverwood,  Y. Guo,  Z. Ye,  D. Prieto-Merino,  A. Dehghan,  S. Trompet,  A. Wong &  A. Cavadino &  (2014). Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data, BMJ, 349 (jul10 6) g4164-g4164. DOI: http://dx.doi.org/10.1136/bmj.g4164

Photo credit: http://qsystem.gblifesciences.com/

Getting Spiced

Synthetic cannabis is stronger than it used to be.

First published 10/07/2013

I wish I could stop writing blog posts about Spice, as the family of synthetic cannabinoids has become known. I wish young people would stop taking these drugs, and stick to genuine marijuana, which is far safer. I wish that politicians and proponents of the Drug War would lean in a bit and help, by knocking off the testing for marijuana in most circumstances, so the difficulty of detecting Spice products isn’t a significant factor in their favor. I wish synthetic cannabinoids weren’t research chemicals, untested for safety in humans, so that I could avoid having to sound like an alarmist geek on the topic.  I wish I didn’t have to discuss the clinical toxicity of more powerful synthetic cannabinoids like JWH-122 and JWH-210. I wish talented chemists didn’t have to spend precious time and lab resources laboriously characterizing the various metabolic pathways of these drugs, in an effort to understand their clinical consequences. I wish Spice drugs didn’t make regular cannabis look so good by comparison, and serve as an argument in favor of more widespread legalization of organic marijuana.

A German study, published in Addiction, seems to demonstrate that “from 2008 to 2011 a shift to the extremely potent synthetic cannabinoids JWH-122 and JWH-210 occurred…. Symptoms were mostly similar to adverse effects after high-dose cannabis. However, agitation, seizures, hypertension, emesis, and hypokalemia  [low blood potassium] also occurred—symptoms which are usually not seen even after high doses of cannabis.”

The German patients in the study were located through the Poison Information Center, and toxicological analysis was performed in the Institute of Forensic Medicine at the University Medical Center Freiburg. Only two study subjects had appreciable levels of actual THC in their blood. Alcohol and other confounders were factored out. First-time consumers were at elevated risk for unintended overdose consequences, since tolerance to Spice drug side effects does develop, as it does with marijuana.

Clinically, the common symptom was tachycardia, with hearts rates as high as 170 beats per minute. Blurred vision, hallucinations and agitation were also reported, but this cluster of symptoms is also seen in high-dose THC cases that turn up in emergency rooms. The same with nausea, the most common gastrointestinal complaint logged by the researchers.

But in 29 patients in whom the presence of synthetic cannabinoids was verified, some of the symptoms seem unique to the Spice drugs. The synthetic cannabinoids caused, in at least one case, an epileptic seizure. Hypertension and low potassium were also seen more often with the synthetics. After the introduction of the more potent forms, JWH-122 and JWH-210, the symptom set expanded to include “generalized seizures, myocloni [muscle spasms] and muscle pain, elevation of creatine kinase and hypokalemia.” The researchers note that seizures induced by marijuana are almost unheard of. In fact, studies have shown that marijuana has anticonvulsive properties, one of the reason it is popular with cancer patients being treated with radiation therapy.

And there are literally hundreds of other synthetic cannabinoid chemicals waiting in the wings. What is going on? Two things. First, synthetic cannabinoids, unlike THC itself, are full agonists at CB1 receptors. THC is only a partial agonist. What this means is that, because of the greater affinity for cannabinoid receptors, synthetic cannabinoids are, in general, stronger than marijuana—strong enough, in fact, to be toxic, possibly even lethal. Secondly, CB1 receptors are everywhere in the brain and body. The human cannabinoid type-1 receptor is one of the most abundant receptors in the central nervous system and is found in particularly high density in brain areas involving cognition and memory.

The Addiction paper by Maren Hermanns-Clausen and colleagues at the Freiburg University Medical Center in Germany is titled “Acute toxicity due to the confirmed consumption of synthetic cannabinoids,” and is worth quoting at some length:

The central nervous excitation with the symptoms agitation, panic attack, aggressiveness and seizure in our case series is remarkable, and may be typical for these novel synthetic cannabinoids. It is somewhat unlikely that co-consumption of amphetamine-like drugs was responsible for the excitation, because such co-consumption occurred in only two of our cases. The appearance of myocloni and generalized tonic-clonic seizures is worrying. These effects are also unexpected because phytocannabinoids [marijuana] show anticonvulsive actions in humans and in animal models of epilepsy.

The reason for all this may be related to the fact that low potassium was observed “in about one-third of the patients of our case series.” Low potassium levels in the blood can cause muscle spasms, abnormal heart rhythms, and other unpleasant side effects.

One happier possibility that arises from the research is that the fierce affinity of synthetic cannabinoids for CB1 receptors could be used against them. “A selective CB1 receptor antagonist,” Hermanns-Clausen and colleagues write, “for example rimonabant, would immediately reverse the acute toxic effects of the synthetic cannabinoids.”

The total number of cases in the study was low, and we can’t assume that everyone who smokes a Spice joint will suffer from epileptic seizures. But we can say that synthetic cannabinoids in the recreational drug market are becoming stronger, are appearing in ever more baffling combinations, and have made the matter of not taking too much a central issue, unlike marijuana, where taking too much leads to nausea, overeating, and sleep.

(See my post “Spiceophrenia” for a discussion of the less-compelling evidence for synthetic cannabinoids and psychosis).

Hermanns-Clausen M., Kneisel S., Hutter M., Szabo B. & Auwärter V. (2013). Acute intoxication by synthetic cannabinoids - Four case reports, Drug Testing and Analysis,   n/a-n/a. DOI: 10.1002/dta.1483

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

Tripling the Tax on Alcohol

Would it do any good?

A recent article in Slate by Reihan Salam, a sort of modest proposal on behalf of a big boost in alcohol excise taxes, caught considerable flack from free market advocates and conservative bloggers last week.

Salam says Americans agree on the fact that marijuana is not as dangerous a drug as alcohol, and that this agreement offers us an opportunity to “regulate alcohol more stringently than we regulate marijuana.” In fact, Salam argues, why not push the envelope: “Raise the alcohol tax to a point just shy of where large numbers of people will start making moonshine in their bathtubs.”

Salam tries to head off some of the usual criticisms by noting that Prohibition was an unmitigated disaster, but that “what most of us forget is that the movement for Prohibition arose because alcohol abuse actually was destroying American society in the first decades of the 20th Century," and that companies like Anheuser Busch and MillerCoors are plotting with national retail chains as you read this, scheming to make alcohol as cheap and easy to buy as humanly possible.

Salam further justifies a tripling of alcohol taxes by viewing it as a tactical offset to the efforts of liquor companies to focus on their best customers: “the small minority of people who drink the most.” Salam says that right now, it costs about two bucks per inebriated hour to get your drink on. Can we really argue that this price level is just too unsustainably high? Drug expert Mark Kleiman, Professor of Public Policy at UCLA, agrees.  In his book Marijuana Legalization: What Everyone Needs to Know, Kleiman and co-authors argue that “tripling the tax would raise the price of a drink by 20 percent and reduce the volume of drinking in about the same proportion. Most of the reduced drinking would come from heavy drinkers, both because they dominate the market in volume terms and because their consumption is more price-sensitive…."

Minnesota legislators recently passed a bill that opponents say would increase state excise taxes on alcoholic beverages to six times the current levels. Supporters of the alcohol tax say it means an extra $200 million per year to the state, at a cost to drinkers of about seven cents per drink. Or, in Salam's example: “Charging two-drink-per-day drinkers an extra $12 per month seems like a laughably small price to pay to deter binge drinking…. If you’re going to tax tanning beds and sugary soft drinks, why on earth wouldn’t you raise alcohol taxes too?”

Why wouldn’t you? Because it doesn’t accomplish what you want to accomplish, writes Michelle Minton at openmarket.org, the blog of the Competitive Enterprise Institute.  After a bit of throat clearing about the Nanny State, Minton writes that “fortunately, a society’s relationship with alcohol isn’t based solely on the price of alcohol…. Research shows that alcohol price is not an effective means of achieving lower total consumption or reducing binge drinking.” As evidence, Minton points to studies showing that Luxembourg and the Czech Republic “have both the highest priced alcohol and the highest rates of consumption in Europe.”

As for a comparison favored by Salam—New York’s anti-smoking campaign—Minton admits that the new higher cost of cigarettes cut the adult smoking rate dramatically, but points out that “New York is now the number-one market for smuggled cigarettes—which account for more than half of all cigarettes smoked in the state.” This is a powerful argument. If we triple the taxes on alcohol, do we risk a black market of dangerous home-brew bootlegger booze?

In my view, such threats are real, but they are theoretical. The current costs of alcohol in socioeconomic terms are enormous and undeniable. Tripling the alcohol tax might be asking for trouble, but we could get there in stages if Americans saw it as a desirable goal. Arguments against tax increases tend to ignore the fact that alcohol is a different kind of product, capable of addicting a significant minority of users, in addition to killing a certain percentage of drinkers outright through alcohol poisoning and traffic accidents. If we ignore the issue of drug dependence, and the health and legal costs of assorted alcohol-related mayhem, and simply lean on the fact that most people who drink use alcohol responsibly, then it gets easier to argue against increases in alcohol and cigarette taxes. Alcohol is not like other household products, and needn't be regulated like them.

Who Smokes Dope, And How Much?

Marijuana stats skew perceptions of use.

Most statistical surveys of marijuana focus on a single quantitative measurement: How many people are using? But there’s a problem: More marijuana use does not necessarily translate into more marijuana users. And that’s because a clear majority of the consumption, and black market dollars, come from the heaviest smokers.

Drug policy researchers at the RAND corporation decided that frequency of use and amount of consumption were valuable parameters gone missing in most policy discussions. So they put the focus not just on use, but also on “use-days,” and pulled a number of buried tidbits from a very big data pile. If you zero in on consumption, and not just consumers, they insist, you will find a wholly different set of inferences.

For example: “Although daily/near-daily users represented less than one-quarter of past-month cannabis users in 2002 and roughly one-third of past-month users in 2011, they account for the vast majority of use-days and are thus presumably responsible for the majority of consumption,” write Rachel M. Burns and her RAND colleagues in Frontiers of Psychiatry. As with alcohol, the majority of cannabis consumption can be accounted for by a minority of users. The heaviest users, the upper 20 percent, consume 88 percent of the U.S. marijuana supply, say the RAND researchers. “Furthermore, if over time there were no change in the number of cannabis users, but the ratio of light vs. heavy users switched from 80/20 to 20/80, then consumption would increase by 250% even though there was no change whatsoever in the number of users.”

The RAND group used two data sets on cannabis consumption—the National Survey on Drug Use and Health (NSDUH) in the U.S., and the EU Drugs Markets II (EUMII) in Europe. Data included figures for past-year and past-month use, past-month use days, and past-month purchases.

Other intriguing figures come to light when you study cannabis use, as opposed to cannabis users. The researchers declared that “only 14% of past-year cannabis users [primarily males] meet the criteria for cannabis abuse or dependence, but they account for 26% of past-month days of use and 37% of past-month purchases.”

Happen to smoke blunts? That turns out to be very telling, according to the RAND study. “Perhaps the most striking contrast concerns blunts. Only 27% of past-year cannabis users report using a blunt within the last month, but those individuals account for 73% of cannabis purchases.” Casual users, it seems, don’t do blunts.

Clearly, it takes a lot of casual users to smoke as much marijuana as one heavy user. But exactly how many? The RAND researchers ran the numbers and concluded that, in terms of grams consumed per month, it would take more than 40 casual smokers to equal the intake of a single heavy user. The share of the market represented by daily/near-daily users is clearly the motive force in their analysis.

The study in Frontiers in Psychiatry also found patterns of interest on the buy side. General use took an upswing beginning in 2007. While the probability of arrest per marijuana smoking episode hovers somewhere in the neighborhood of 1 in 3,000, everything changes if you are purchasing cannabis. RAND reported that young people collectively make more purchases per day of reported use than do older users. Therefore, “statistics indicating that the burden of arrest falls disproportionately on youth relative to their share of all users may not be prima facie evidence of discrimination if making more purchases per day of use increases the risk of arrests per year of use.” Once again, those aging Baby Boomer potheads get the best deal. They have more money with which to buy bigger amounts less often, thereby greatly lessening their chances of arrest and prosecution.

This also applies to minority arrests for marijuana offenses. “Non-Hispanic blacks represent 13% of past-year cannabis users vs. 23% of drug arrests reported by those users, but they report making 24% of the buys. Thus, some of their higher arrest rate may be a consequence of purchase patterns… African-Americans may not only make more buys but also make riskier buys (e.g., more likely to buy outdoors).”

The researchers were able to draw some conclusions about the growth in marijuana usage from 2002 through 2011, based on the NSDUH data. Their main conclusion, after exploring the demographics of this 10-year record of use, is that “consumption grew primarily because of an increase in the average frequency of use, not just because of an increase in the overall number of users.”  The driver of consumption turns out to be… greater consumption. And that increased consumption is coming from… older adults. Those older adults, it turns out, are smoking more weed.

The shift is dramatic: “In 2002, there were more than three times as many youth as older adults using cannabis on a daily/near-daily basis; in 2011 there were 2.5 times more older adults than youth using on a daily/near-daily basis.” The record of alcohol and cigarette use over the same period showed no such inversion of use patterns.  And the tweeners? “In 2002, 12-17-year-olds represented 13% of daily/near-daily users; in 2011, that had dwindled to 7%.” These trends are not just the obvious result of an increase in the proportion of older adults in the population at large. Increases in the proportion of older heavy cannabis users were much greater than the general population drift.

Among the questions raised by the RAND analysis:

— Are older marijuana smokers primarily recreational, or medicinal?

—Do increased use days among older, college-educated marijuana smokers indicate greater social acceptance, or something else?

—Are younger people replacing traditional cannabis use with other substances?

—Why did Hispanic use increase more over the study period than other ethnic groups?

Burns R.M., Caulkins J.P., Everingham S.S. & Kilmer B. (2013). Statistics on Cannabis Users Skew Perceptions of Cannabis Use, Frontiers in Psychiatry, 4   DOI: 10.3389/fpsyt.2013.00138

Photo Credit: http://www.sho.com/sho/weeds/home

What Mark Kleiman Wants You To Know About Drugs

The public policy guru guiding state legalization efforts.

Mark A. R. Kleiman is the Professor of Public Policy at UCLA, editor of the Journal of Drug Policy Analysis, author of many books, and generally regarded as one of the nation’s premier voices on drug policy and criminal justice issues. Mr. Kleiman provides advice to local, state, and national governments on crime control and drug policy. When the state of Washington needed an adviser on the many policy questions they left unanswered with the passage of I-502, which legalized marijuana in that state, they turned to Kleiman.

In the past two years, Kleiman has co-authored to Q and A-style books: Drugs and Drug Policy: What Everyone Needs to Know (2011) with Jonathan P. Caulkins and Angela Hawken; and Marijuana Legalization: What Everyone Needs to Know (2012) with Hawken, Caulkins, and Beau Kilmer.

Here, excerpted from the two books, is a brief sampling of Kleiman and his colleagues on a variety of drug and alcohol issues.

Is marijuana really the nation’s leading cash crop?

“Alas, the facts say otherwise. Analyses purporting to support the claim must contort the numbers, citing the retail price of marijuana but the farmgate price of other products, or pretending that all marijuana consumed in the United States is sinsemilla, or ignoring the fact that most marijuana used in the United States is imported, or simply starting with implausible estimates of U.S. production…. marijuana [is] in the top fifteen, but not the top five, cash crops, ranking somewhere between almonds and hay, and perhaps closest to potatoes and grapes.”

How much drug-related crime, violence, and corruption would marijuana legalization eliminate?

“Not much…. Eighty-nine percent of survey respondents report obtaining marijuana most recently from a friend or relative, and more than half (58 percent) say the obtained it for free. That stands in marked contrast to low-level distribution of heroin and crack which often occurs in violent, place-based markets controlled by armed gangs.”

How much would legal marijuana cost to produce?

“The punch line is that full legalization at the national level—as opposed to only legalizing possession and retail sale—could cut production costs to just 1 percent of current wholesale prices…. This would make legal marijuana far and away the cheapest intoxicant on a per-hour basis.”

How would legalization affect me if I’m a marijuana grower?

“It would almost certainly put you out of business. At first glance, legalization might seem like a great opportunity for you…. But legalization will completely upend your industry, and the skills that made you successful at cultivating illegal crops will not have much value. A few dozen professional farmers could produce enough marijuana to meet U.S. consumption at prices small-scale producers couldn’t possibly match. Hand cultivators would be relegated to niche markets for organic or specialty strains.”

Would marijuana regulations and taxes in practice approach the public health ideal?

“If there is a licit, for-profit marijuana industry, one should expect its product design, pricing, and marketing actions to be designed to promote as much frequent use and addiction as possible. Efforts to tax and regulate in ways that promote public health would have to contend with an industry mobilizing its employees, shareholders, and consumers against any effective restriction. Since the industry profits from problem users, we should expect that lobbying effort to be devoted to blocking policies that would effectively control addiction. The alcohol and tobacco industries provide good examples.”

Can we persuade children not to use drugs?

"Even the best prevention programs have only modest effects on actual behavior, and may programs have no effect at all on drug use…. Anesthesiologists know far more about drugs and drug abuse than could possibly be taught in middle-school prevention programs; nonetheless, they have high rates of substance abuse, in part because they have such easy access.”

Why is there a shortage of drug treatment?

“Some specific categories—especially those in need of residential care, and more especially mothers with children in need of residential care—face chronic shortages. But if we had enough capacity for all those who need treatment, many of those slots would be empty because not all the people who ought to fill them want treatment.”

How much money is involved?

“Most of the numbers about drug abuse and drug trafficking that officials peddle to credulous journalists are little better than fiction. Estimates of hundreds of billions of dollars per year in international drug trade—which would make it comparable to food, oil, and arms—do not have a basis in the real world. The most recent serious estimate of the total retail illicit drug market in the United States—by all accounts the country whose residents spend the most on illicit drugs—puts the figure at about $65 billion.”

When it comes to drugs, why can’t we think calmly and play nice?

“American political analysts talk about ‘wine-track (college-educated) and ‘beer track’ (working-class) voters…. So the politics of drug policy is never very far from identity politics…. The notion that illicit drug taking is largely responsible for the plight of minorities (and of poor people generally) and that income-support programs have the perverse consequence of maintaining drug habits has been a staple of a certain form of American political rhetoric at least since Ronald Reagan.”

Are we stuck with our current alcohol problem?

"By no means…. tripling the tax would raise the price of a drink by 20 percent and reduce the volume of drinking in about the same proportion. Most of the reduced drinking would come from heavy drinkers, both because they dominate the market in volume terms and because their consumption is more price-sensitive…."

Grab Bag of Addiction Links

Recent reading from around the net.

Can Medical Marijuana and Recreational Marijuana Coexist?

“The Washington State Liquor Control Board released recommendations for what to do with the state's medical marijuana system now that recreational marijuana is legal.” [Atlantic Cities]

Premature claims of a cannabis addiction "cure"

“Have scientists found a ‘cure’ for marijuana addiction? New treatment blocks the kick that users get from the drug,” reports the Mail Online. Based on the evidence presented in the study, which involved animals, the answer to the Mail’s question is 'not yet'. [NHS Choices]

Can Gambling Machines Prevent Addiction?

“Today's digital slot machines and poker screens in casinos and at online gambling sites are capable of amassing a wealth of behavioral data on individual players, and they are on the verge of altering game play on the fly.” [Scientific American Mind]

Food for thought: UF researcher’s book lays out evidence for food addiction

“For some, the famous potato chip slogan “Betcha can't eat just one” isn’t a wager — it’s a promise.” [University of Florida Health]

New Zealand’s bold experiment with regulating recreational drugs

“It’s been nearly a century since the United States began its experiment in prohibiting recreational drugs besides alcohol, caffeine and tobacco — and virtually no one sees the trillion dollar policy as a success.” [Reuters]

More Than 1,000 Meet in Denver to Develop Drug War Exit Strategy

“Which state will be next to legalize marijuana? What do the Obama administration's recent announcements about marijuana legalization and mandatory minimums really mean?” [Huffington Post]

This Is Why Social Media and Drinking Alcohol Don't Mix (Infographic)

“Engaging with peers and customers on social platforms can be dangerous. Doing so while you’re under the influence of alcohol is downright irresponsible. “ [Entrepreneur]

Economists Predict Marijuana Legalization Will Produce "Public-Health Benefits"

“In their 2012 book Marijuana Legalization: What Everyone Needs to Know, Jonathan Caulkins and three other drug policy scholars identify the impact of repealing pot prohibition on alcohol consumption as the most important thing no one knows.” [Forbes]

Photo Credit: http://lifeonthebalcony.com/

Spiced: Synthetic Cannabis Keeps Getting Stronger

Case reports of seizures in Germany from 2008 to 2011.

I wish I could stop writing blog posts about Spice, as the family of synthetic cannabinoids has become known. I wish young people would stop taking these drugs, and stick to genuine marijuana, which is far safer. I wish that politicians and proponents of the Drug War would lean in a bit and help, by knocking off the testing for marijuana in most circumstances, so the difficulty of detecting Spice products isn’t a significant factor in their favor. I wish synthetic cannabinoids weren’t research chemicals, untested for safety in humans, so that I could avoid having to sound like an alarmist geek on the topic.  I wish I didn’t have to discuss the clinical toxicity of more powerful synthetic cannabinoids like JWH-122 and JWH-210. I wish talented chemists didn’t have to spend precious time and lab resources laboriously characterizing the various metabolic pathways of these drugs, in an effort to understand their clinical consequences. I wish Spice drugs didn’t make regular cannabis look so good by comparison, and serve as an argument in favor of more widespread legalization of organic marijuana.

A German study, published in Addiction, seems to demonstrate that “from 2008 to 2011 a shift to the extremely potent synthetic cannabinoids JWH-122 and JWH-210 occurred…. Symptoms were mostly similar to adverse effects after high-dose cannabis. However, agitation, seizures, hypertension, emesis, and hypokalemia  [low blood potassium] also occurred—symptoms which are usually not seen even after high doses of cannabis.”

The German patients in the study were located through the Poison Information Center, and toxicological analysis was performed in the Institute of Forensic Medicine at the University Medical Center Freiburg. Only two study subjects had appreciable levels of actual THC in their blood. Alcohol and other confounders were factored out. First-time consumers were at elevated risk for unintended overdose consequences, since tolerance to Spice drug side effects does develop, as it does with marijuana.

Clinically, the common symptom was tachycardia, with hearts rates as high as 170 beats per minute. Blurred vision, hallucinations and agitation were also reported, but this cluster of symptoms is also seen in high-dose THC cases that turn up in emergency rooms. The same with nausea, the most common gastrointestinal complaint logged by the researchers.

But in 29 patients in whom the presence of synthetic cannabinoids was verified, some of the symptoms seem unique to the Spice drugs. The synthetic cannabinoids caused, in at least one case, an epileptic seizure. Hypertension and low potassium were also seen more often with the synthetics. After the introduction of the more potent forms, JWH-122 and JWH-210, the symptom set expanded to include “generalized seizures, myocloni [muscle spasms] and muscle pain, elevation of creatine kinase and hypokalemia.” The researchers note that seizures induced by marijuana are almost unheard of. In fact, studies have shown that marijuana has anticonvulsive properties, one of the reason it is popular with cancer patients being treated with radiation therapy.

And there are literally hundreds of other synthetic cannabinoid chemicals waiting in the wings. What is going on? Two things. First, synthetic cannabinoids, unlike THC itself, are full agonists at CB1 receptors. THC is only a partial agonist. What this means is that, because of the greater affinity for cannabinoid receptors, synthetic cannabinoids are, in general, stronger than marijuana—strong enough, in fact, to be toxic, possibly even lethal. Secondly, CB1 receptors are everywhere in the brain and body. The human cannabinoid type-1 receptor is one of the most abundant receptors in the central nervous system and is found in particularly high density in brain areas involving cognition and memory.

The Addiction paper by Maren Hermanns-Clausen and colleagues at the Freiburg University Medical Center in Germany is titled “Acute toxicity due to the confirmed consumption of synthetic cannabinoids,” and is worth quoting at some length:

The central nervous excitation with the symptoms agitation, panic attack, aggressiveness and seizure in our case series is remarkable, and may be typical for these novel synthetic cannabinoids. It is somewhat unlikely that co-consumption of amphetamine-like drugs was responsible for the excitation, because such co-consumption occurred in only two of our cases. The appearance of myocloni and generalized tonic-clonic seizures is worrying. These effects are also unexpected because phytocannabinoids [marijuana] show anticonvulsive actions in humans and in animal models of epilepsy.

The reason for all this may be related to the fact that low potassium was observed “in about one-third of the patients of our case series.” Low potassium levels in the blood can cause muscle spasms, abnormal heart rhythms, and other unpleasant side effects.

One happier possibility that arises from the research is that the fierce affinity of synthetic cannabinoids for CB1 receptors could be used against them. “A selective CB1 receptor antagonist,” Hermanns-Clausen and colleagues write, “for example rimonabant, would immediately reverse the acute toxic effects of the synthetic cannabinoids.”

The total number of cases in the study was low, and we can’t assume that everyone who smokes a Spice joint will suffer from epileptic seizures. But we can say that synthetic cannabinoids in the recreational drug market are becoming stronger, are appearing in ever more baffling combinations, and have made the matter of not taking too much a central issue, unlike marijuana, where taking too much leads to nausea, overeating, and sleep.

(See my post “Spiceophrenia” for a discussion of the less-compelling evidence for synthetic cannabinoids and psychosis).

Hermanns-Clausen M., Kneisel S., Hutter M., Szabo B. & Auwärter V. (2013). Acute intoxication by synthetic cannabinoids - Four case reports, Drug Testing and Analysis,   n/a-n/a. DOI: 10.1002/dta.1483

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

Dr. David Nutt on Alcohol

Rebutting industry myths.

A couple of years ago, the European Alcohol Policy Alliance, known as EuroCare, put together a brochure addressing the common messages the liquor industry attempts to drive home through its heavy spending on advertising. The messages are not just designed to sell product, but also to influence alcohol policy at the political level. According to EuroCare, the “industry”—the alcohol and tobacco companies—“has traditionally worked closely together, sharing information and concerns about regulation. They have used similar arguments to defend their products in order to prevent or delay restrictions being placed on them.”

I wrote a blog post on EuroCare’s list of alcohol untruths called “7 Myths the Alcohol Industry Wants You to Believe." Here they are:

Message 1: Consuming alcohol is normal, common, healthy, and very responsible.

Message 2: The damage done by alcohol is caused by a small group of deviants who cannot handle alcohol.

Message 3: Normal adult non-drinkers do not, in fact, exist

Message 4: Ignore the fact that alcohol is a harmful and addictive chemical substance (ethanol) for the body.

Message 5: Alcohol problems can only be solved when all parties work together.

Message 6: Alcohol marketing is not harmful. It is simply intended to assist the consumer in selecting a certain product or brand.

Message 7: Education about responsible use is the best method to protect society from alcohol problems.

Recently, I ran across a great response to these same 7 myths by Dr. David Nutt, the British psychiatrist perhaps best known in the states as the scientist who got fired a few years ago from his post on the government’s Advisory Council on the Misuse of Drugs. Nutt’s primary sin was to suggest that, on a straightforward calculation of risks and harms, horseback riding was probably a more dangerous activity than taking the drug Ecstasy. The Home Secretary at the time insisted that you couldn’t compare a legal activity to an illegal one, or something like that, and Nutt compounded his sins by suggesting that marijuana was a safer drug than alcohol. British politicians took a serious dislike to him, the more so since most of the published medical science was on his side. After the dust settled, Nutt was one of the primary founders of the Independent Scientific Committee on Drugs (ISCD), formed to offer alternative views on drugs and addiction grounded in science.

Anyway, in his book, Drugs Without the Hot Air, Nutt has his own responses to the 7 Myths, which I excerpt here:

1. Consuming Alcohol is Normal: It’s normal, so long as you have the “normal” high-activity variant of the ALDH2 enzyme. If you don’t have that form of the enzyme, Nutt reminds his readers, as many Asians and Aleuts do not, then alcohol will affect you quite non-normally through the so-called alcohol flush reaction. Moreover, many cultures and societies unfamiliar with its effects “suffer hugely when new types of alcohol appear, particularly if they are aggressively marketed.”

2. Alcohol damage is caused by a small group of deviants: According to Dr. Nutt, statistics show that “millions of people, NOT a tiny minority, suffer harm from their own alcohol consumption, or cause harm to others…. It is the everyday drinking of people who have come to see alcohol as an essential part of life rather than the luxury it used to be, that has created a spike in cancers and stomach problems, and will see liver disease match heart disease as the leading cause of death in the UK by 2020.”

3. Normal adult non-drinkers do not exist: The alcohol industry is forever reminding politicians of how unpopular alcohol restrictions are to the voting populace. “The existence of non-drinkers obviously threatens this portrayal of society, so the industry tends to dismiss them as having something wrong with them. While some teetotalers are recovering alcoholics, many others have made a positive choice not to drink.” And there are others, I would add, often referred to as “sick” teetotalers, who have quit drinking for medical reasons unrelated to alcoholism.

4. Ignore alcohol’s harm to the body: Nutt reminds us that “there is no other drug which is so damaging to so many different organ systems in the body…. Most other drugs cause damage primarily in one or two areas—heart problems from cocaine, or urinary tract problems from ketamine. Alcohol is harmful almost everywhere.”

5. Alcohol problems can be solved when everybody works together: “In practice, what the industry means by ‘working together’ is bring in voluntary codes rather than statutory regulation—solving problems through rules that the industry CHOOSES to comply with, rather than laws which they MUST comply with.”

6. Alcohol marketing is intended to assist consumers in selecting products: Specifically, 800 million British pounds every year for advertising and promotion, according to Nutt. That’s just the kind of civic-minded bunch those alcohol sellers are. The reality, of course is that “marketing communications do have a marked effect on consumption…. All this further entrenches the false division between alcohol and illegal drugs, persuades people that consuming alcohol is safe, and makes realistic discussions of the harm alcohol causes very difficult.”

7. Education about responsible use is the best approach: “It is useful for the drinks industry,” Nutt explains, “to emphasize the value of education, because it takes the focus off regulation…. There is also extensive evidence gathered by the WHO from around the world, showing that merely providing information and education without bringing in other policy measures doesn’t change people’s drinking behavior.”

As I wrote in my original post: Who could be against the promotion of responsible alcohol use? Irresponsible zealots and deviants, that’s who. Why should all of us happy drinkers be made to suffer for the sins of a few rotten apples?

Indeed, all of the messages, overtly or covertly, send the same signal: You should drink more. It’s good for you.

Graphics Credit: http://www.holyrood.com/2011/04/at-what-price/

Building Better Baby Brains: Just Say No To FAS

Fetal Alcohol Syndrome is our most preventable form of disability.

Despite a growing focus on the hazards of prescription painkillers for newborns, drinking during pregnancy remains the nation’s leading preventable cause of birth defects and developmental disorders in children. Fetal Alcohol Spectrum Disorders (FASD) encompass a wide variety of neurobehavioral and central nervous system disabilities related to alcohol use during pregnancy, including, but not limited to, developmental delays, growth retardation speech disabilities, and poor social skills. The classic physical characteristics of FASD, such as small head size, wide-set eyes and a thin upper lip, are not always present.

September 9th is International Fetal Alcohol Spectrum Disorders Awareness Day. Kenneth Warren, acting director of the National Institute on Alcohol Abuse and Alcoholism, said in a prepared statement that “Almost 40 years have passed since we recognized that drinking during pregnancy can result in a wide range of disabilities for children, of which fetal alcohol syndrome (FAS) is the most severe. Yet up to 30 percent of women report drinking alcohol during pregnancy.”

NIAAA, in a brief history of the disorder, calls fetal alcohol syndrome the “most common known cause of mental retardation.” Tragically, the knowledge of alcohol as a teratogen responsible for birth defects was not widely recognized by the medical community in American until the 1970s, when a group of crusading physicians began reporting observations of clustered birth defects among alcoholic mothers. (French doctors were on to FAS in the 1960s). In short order, the Surgeon General issued an FAS advisory, the U.S. Congress passed laws requiring pregnancy warning labels on alcoholic beverages, and doctors began warning their pregnant patients about the hazards of heavy drinking while pregnant. Nonetheless, CDC studies have shown that 0.2 to 1.5 cases of fetal alcohol syndrome (FAS) occur for every 1,000 live births.

Not surprisingly, the NIAAA finds that the risk for teratogenic injury and the severity of injury “appear to increase with greater levels of alcohol consumption.” Facial features associated with FAS are linked to early fetal exposure, so it is possible that “an embryo may escape the injury necessary to develop the characteristic FAS face but receive sufficient injury later in development to exhibit all the FAS-associated CNS and neurobehavioral deficits.”

Organ abnormalities are also characteristic of early exposure, while growth deficits are more likely the result of alcohol exposure later in pregnancy. Binge drinking—high peak dose drinking—is especially troublesome, as it has a great negative impact than low-dose steady drinking. But no period is risk-free. Genetic and environmental factors are plausibly invoked as contributors, but nobody knows what they are at present.

The disabilities caused by FASD often linger throughout adulthood, burdening families with anguish and heavy medical costs. “The message is simple, not just on Sept. 9, but every day,” says Warren. “There is no known safe level of drinking while pregnant. Women who are, who may be, or who are trying to become pregnant, should not drink alcohol.”

Graphics Credit: http://edmontonfetalalcoholnetwork.org/

Fruit Fly Larvae Go Cold Turkey and Forget the Car Keys

Not a pretty sight.

Let’s start with the fruit fly, your basic Drosophila. A fruit fly, like a human, can become addicted to alcohol even at a very young age. The larval age. In other words, even as a maggot. And, just like humans, alcohol degrades a fruit fly maggot’s ability to learn. But adaption is an amazing thing, and drunken larvae eventually learn as well as their teetotaling cousins. That is, until the alcohol is taken away, in which case, the maggots become impaired learners once again. The larval nervous system goes haywire, and hyperexcitablity sets in. They can’t concentrate on their work. But one hour of “ethanol reinstatement” restores larval learning to normal levels.

It looks and sounds like withdrawal. Such effects in human alcoholics are often chalked up to state-dependent memory, but neurobiologists at the Waggoner Center for Alcohol and Addiction Research at the University of Texas, whose maggots these are, believe that state-dependent memory is not at work in the case of invertebrate ethanol dependence.

Brooks G. Robinson and associates fed the larvae a 5% ethanol supplement to their daily food. The maggots, incredibly enough, can reach blood-alcohol concentrations as high as 0.08, or roughly the legal limit for humans. If you blew a 0.08, the official chart says you would be suffering from impaired reasoning, disinhibition, and visual disturbances. For the maggots, no different. Larvae that fed on “ethanol food” for one hour learned poorly compared to straight maggots. The learning test, done before introducing alcohol into the picture, used a heat pulse to condition larvae away from an otherwise attractive odor. The reduced attraction to the odor is a form of associative learning.  Figuratively speaking, the drunken maggots kept burning themselves on the stove as they reached for the soup. They failed the field sobriety test.

But was it truly a case of impaired learning? Perhaps the drunken larvae had an impaired sense of smell. But the researchers could not document a reduced sense of odor based on responses with untrained animals. And both groups of maggots sensed heat equally, so the reduction in learning was not due to simple alcoholic anesthesia. Could the withdrawal response be due to the fact that alcohol is a calorie-rich food? To test that possibility, the researchers ran the experiment with sucrose instead of alcohol, and didn’t record any learning impairment in that case. As for state-dependent memory, the researchers assert in Current Biology that withdrawal effects “cannot be attributed to state-dependent learning, because the less than 20 minute training and testing assay for all treatment groups occurs on nonethanol plates.”

And finally, the investigators write, “the fact that both the withdrawal-induced learning deficit and the neuronal hyperexcitability responses are reversed by ethanol reinstatement suggests that they have related origins, and that withdrawal learning may suffer because the nervous system is overly excitable.”

So what have we learned? Well, alcohol dependence in humans is clearly associated with learning and memory deficits that can last for a year or more after quitting. Now that the researchers have demonstrated cognitive alcohol dependence in invertebrates—for the first time ever, they say—it may open the door to more sophisticated genetic analyses of alcoholism in Drosophila, for all the reasons that have drawn other biologists to the study of fruit flies over the years.

And there is more research to be done relative to the finding that neuronal hyper-excitability is linked in some way to the learning deficits caused by alcohol. A brief article by Stefan Pulver in the Journal of Experimental Biology  notes that the work of Robinson and colleagues “reinforces how eerily conserved ethanol’s physiological effects are across animal taxa. Alcohol addiction is truly the great leveller. It doesn’t matter whether you are man, mouse or maggot—over-consumption of alcohol will trigger very similar cellular and behavioral responses, with devastating consequences.” 

Robinson B., Khurana S., Kuperman A. & Atkinson N. (2012). Neural Adaptation Leads to Cognitive Ethanol Dependence, Current Biology, 22 (24) 2338-2341. DOI: 10.1016/j.cub.2012.10.038

Marijuana and Strokes: Medical Reality or Scare Story?

Heavy tokers may be at higher risk, but alcohol is the hidden confounder.

Young people don’t suffer from strokes, as a rule. And when they do, at least half the time there is no obvious cardiovascular explanation. So it’s not surprising that drugs are often invoked as the culprit.

A New Zealand study earlier this year once again raised the specter of a possible link between stroke and marijuana smoking. As reported by Maia Szalavitz at Time Healthland, the confounding issue, as is typical of such studies, is the coexisting use of other drugs, like alcohol and cigarettes. As Szalavitz writes:

The stroke study, which incorporated preliminary data, is the first trial of its kind to study a possible connection between marijuana use and stroke. It included 160 patients aged 18 to 55 who had suffered a stroke connected to a blood clot in the brain, and who agreed to have their urine tested for marijuana within 72 hours of the stroke.  These results were compared to those from 160 controls who had not had a stroke but came to the hospital for other reasons. They were matched on age, gender and ethnic background, all of which can also affect the risk for this type of stroke. About 16% of the stroke patients showed traces of marijuana in their urine, compared to 8% of those in the control group, suggesting a doubling of the risk of stroke.

However, because of nicotine and other confounding variables, that study was considered inconclusive. In an earlier study published in Stroke, the journal of the American Heart Association, Valerie Wolff and colleagues from the University of Strasbourg in France searched the medical literature and found 59 cases of stroke in which cannabis could be considered a cardiovascular risk factor. The investigators used only cases that had been confirmed by neuroimaging. The researchers focused on cases where a stroke had occurred while smoking marijuana, or within a half hour after the last joint or bong hit.

But proving a cause and effect relationship is tricky. Assuming, for now, that all of the strokes in question were not caused or compounded by alcohol or drugs other than marijuana, the French scientists postulated several mechanisms that could conceivably account for a cannabis-related ischemic stroke (a stroke caused by obstruction of a blood vessel). These include orthostatic hypotension, altered cerebral vasomotor function, major swings in blood pressure, and cardiac arrhythmias. However, the only solid commonality in cannabis-related strokes was that the users were more likely to be heavy smokers.

In the 50 strokes the researchers were able to confirm by cerebral imaging, the patterns in some patients were similar to those observed in a syndrome called reversible cerebral vasoconstriction syndrome (RCVS). RCVS  is marked by severe headaches, strokes, and brain edema, but symptoms typically resolve in a few months.  “Reversibility of the vasoconstriction within 12 weeks is a key point of this syndrome,” the authors write. “The long duration of stenosis [blockage] argues in favor of a drug-induced immunoallergic vasculitis rather than vasospasm. Our point of view is that this disorder may be considered as a variant of RCVS,” rather than as a garden-variety ischemic stroke triggered by excessive use of cannabis.

According to the French study, “The most frequently presented characteristics of cannabis users who experienced a stroke are young male chronic tobacco and cannabis abusers who have had an unusual high consumption of cannabis and alcohol before stroke.” The most convincing mechanism to explain ischemic strokes in young people, the researchers say, is “reversible cerebral angiopathy involving several arteries, associated with cannabis consumption in association with tobacco and alcohol use.”

And there you have it. Smoke weed, and you appear to have a slight risk of suffering stroke, which, under age 50, is an extremely uncommon medical event.  Add tobacco, and the stroke risk goes up. Add alcohol, and the stroke risk ratchets even higher. By itself, marijuana appears to be a minor factor in strokes—but it appears likely that pot is indeed the culprit at least some of the time.

“Cannabis-related stroke is not a myth,” the scientists conclude, “and a likely mechanism of stroke in most cannabis users is the presence of reversible multifocal intracranial stenosis (MIS) induced by this drug. The reality of the relationship between cannabis and stroke is, however, complex, because other confounding factors have to be considered (ie, lifestyle and genetic factors).”

Wolff V., Armspach J.P., Lauer V., Rouyer O., Bataillard M., Marescaux C. & Geny B. (2013). Cannabis-related Stroke: Myth or Reality?, Stroke, 44 (2) 558-563. DOI: 10.1161/STROKEAHA.112.671347

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