Popular “Bath Salt” Hooks Lab Rats

Mephedrone shows addictive properties in animal models.

Cathinones, like methedrine and other stimulants, are primarily dopamine-active drugs. Though they are now illegal in the U.S., they were formerly of primary interest only to pharmaceutical researchers. The best-known cathinone sold in the form of bath salts and plant food—mephedrone—has both dopamine and serotonin effects. It broke big in the UK a few years ago as a “legal” party drug alternative to MDMA. The idea was to get high without testing dirty, as the saying goes.

Behavioral clues about mephedrone have been teased out of rat studies. The Taffe Laboratory at Scripps Research Institute has been focusing on the cognitive, thermoregulatory, and potentially addictive effects of the cathinones, and mephedrone in particular. Scripps researchers have carried the investigation forward with a recent study in the journal Drug and Alcohol Dependence.

Now comes additional evidence, also from the Taffe Lab at Scripps, that mephedrone, or 4-MMC, looks like an addictive drug. In a paper accepted for publication by Addiction Biology, which Addiction Inbox was allowed to review in advance, Dr. Michael Taffe, along with lead author S.M. Aarde and coworkers, demonstrated in an animal study that lab rats will intravenously self-administer mephedrone under normal lab conditions—roughly analogous to shooting speed.

Without suitable strains of test animals, most genetic and neurobiological research would take centuries, and would involve ethical questions about human testing far stickier than the questions raised by work with animals. Animal models are one of the primary pathways of discovery available to neurobiologists and other researchers.

But it’s tricky. Establishing traditional rodent laboratory conditions is a Goldilocks endeavor: The environment must be not too hot, but not too cold, because this can effect rodent behavior. And the drug must be given at rates that are not too frequent and not too rare.

The curious thing about mephedrone is that it appears to combine the effects of prototypical stimulants like cocaine and methamphetamine, with the trippy, “entactogen” effects of MDMA, aka Ecstasy, in the bargain. The drug rapidly crosses the blood-brain barrier, reaching peak levels two minutes after injection, and full effects last about an hour. In one study, 76% of people who had snorted both cocaine and mephedrone reported that the quality of the mephedrone high was “similar to or better than” cocaine. But the paper also states that “human recreational users report 4-MMC to be subjectively similar to MDMA.”

The investigators ran a series of tests with various groups of rats, and found that 80-100% of the rats would happily reward-press a lever for an infusion of mephedrone. “Under these conditions,” writes Taffe, “methamphetamine and 4-MMC have about equal effect on rat self-administration although the 4-MMC is considerably less potent, requiring about 10 times the per-infusion dose for effect.” Although it wasn’t demonstrated directly in this paper, Ecstasy “is at best unevenly self-administered by rats,” and “despite an MDMA-like serotonin/dopamine neuropharmacological effect, mephedrone has a liability for repetitive intake more similar to the classical amphetamine-type stimulants such as methamphetamine.”

It’s a weaker type of stimulant, mephedrone, but it does the trick. It is highly reinforcing. Mephedrone chemically resembles speed, but also has Ecstasy-like effects. "Furthermore, neurochemical data suggest MDMA-like patterns of relatively greater serotonin versus dopamine accumulation in nucleus accumbens.” Even with its added Ecstasy-like effects, the scientists conclude that “the potential for compulsive use of mephedrone in humans is likely quite high, particularly in comparison with MDMA.”

Photo Credit: Creative Commons

Binge Drinking in America

And the numbers are… fuzzy.

Public health officials in the UK have been wringing their hands for some time now over perceived rates of binge drinking among the populace. In a 2010 survey of 27,000 Europeans by the official polling agency of the EU, binge drinking in the UK—defined as five or more drinks in one, er, binge—clocked in at a rate of 34%, compared to an EU average of 29%. Predictably, the highest rate of UK binge drinking was found in people between the ages of 15 and 24. This still lagged well behind the Irish (44%) and the Romanians (39%). Scant comfort, perhaps, given the historical role drinking has played in those two cultures, but still, clearly, the British and the rest of the UK are above-average drinkers.

Or are they? And what about the U.S. How do we rank? For comparative purposes, we can use the “Vital Signs” survey in the United States from 2010, performed by the Centers for Disease Control and Prevention, and published in CDC’s Morbidity and Mortality Weekly Report, results of which are pictured above. Using almost the same criteria for binge drinking—five drinks at a sitting for men, four drinks for women—the study concludes that the “overall prevalence of binge drinking was 17.1%. Among binge drinkers, the frequency of binge drinking was 4.4 episodes per month, and the intensity was 7.9 drinks on occasion.”

By the CDC’s definition, the heaviest binge drinking in America takes place in the Midwest, parts of New England, D.C., and Alaska. Survey respondents with an income in excess of $75,000 were the most serious bingers (20.2%), but those making under $25,000 binged more often and had more drinks per binge than other groups, the report says. And binge drinking is about twice as prevalent among men. Binge drinking, the survey concludes, is reported by one of every six U.S. adults.

Even so, it appears that the U.S. does not have the same level of binge drinking as the UK. However, astute readers have no doubt noticed that actual binge drinkers in the U.S. were consuming almost 8 drinks per bout, well above the official mark of four or five drinks at one time. The problem is that there is no internationally agreed upon definition of binge drinking. A 2010 fact sheet from the UK’s Institute of Alcohol Studies (IAS) maintains that “drinking surveys normally define binge drinkers as men consuming at least eight, and women at least six standard units of alcohol in a single day, that is, double the maximum recommended ‘safe limit’ for men and women respectively.”

But referring to binge drinking as “high intake of alcohol in a single drinking occasion” is misleading, says IAS. The problem is biological: “Because of individual variations in, for example, body weight and alcohol tolerance, as well as factors such as speed of consumption, there is not a simple, consistent correlation between the number of units consumed, their resulting blood alcohol level and the subjective effects on the drinker.”

Furthermore, the report charges that “researchers have criticized the term ‘binge drinking’ as unclear, politically charged and therefore, unhelpful in that many (young) people do not identify themselves as binge drinkers because, despite exceeding the number of drinks officially used to define bingeing, they drink at a slow enough pace to avoid getting seriously drunk.”

There you have it. As currently defined and measured, binge drinking is a relatively useless metric for assessing a population’s alcohol habits. “The different definitions employed need to be taken into account in understanding surveys of drinking behavior and calculations of how many binge drinkers there are in the population,” as the UK report wisely puts it. Take the above chart with a few grains of salt.

Photo Credit: CDC

Have We Killed Half of our Soldiers with Cigarettes?

Two long-term studies yield grim stats, and women are no exception.

We know that smoking kills. But until the results of 50 years’ worth of observations on British male smokers was published by Richard Doll and coworkers in the British Journal of Medicine in 2004, we didn’t know how many.  Cigarettes will kill at least half of those who smoke them past the age of 30—possibly more. In older, specific populations, possibly as many as 2/3.

It took a prospective study of more than 34,000 British doctors, starting in 1951 and ending in 2001, to establish the grim parameters with some degree of precision. As the study authors of the 2004 summary paper put it: “A substantial progressive decrease in the mortality rates among non-smokers over the past half century… has been wholly outweighed, among cigarette smokers, by a progressive increase in the smoker v non-smoker death rate ratio due to earlier and more intensive use of cigarettes.” In other words, the great reduction in disease mortality rates achieved in the 20th Century, courtesy of better prevention and treatment, effectively never happened for long-term male smokers. Smoking in Britain and America took off in a major way between the two world wars, and sufficient time has now passed to conclude that “men born in 1900-1930 who smoked only cigarettes and continued smoking died on average about 10 years younger than lifelong non-smokers.”

As for women, it took a few decades longer to nail down the truth, because women did not begin smoking in peak numbers until the 1960s. While men born between 1900 and 1930 took to cigarettes in a big way, women born around 1940 were the first cohort of female smokers to consume a substantial number of cigarettes throughout their adult lives. This 20-year lag is crucial, because it means that solid numbers for female mortality rates require solid figures on mortality rates in the 21st Century. And now we have them, courtesy of the Million Women Study in the UK. The results were recently published in The Lancet by Kirstin Pirie and others. They are just as bad as you might have guessed, putting women on a firm equal footing with their male counterparts when it comes to smoking deaths.

The Million Women Study, a database originally used for the UK’s National Health Service Breast Screening Program, recruited female volunteers between the ages of 50 and 69. The figures were eerily similar to those from the earlier study of male British doctors: “If combined with 2010 UK national death rates, tripled mortality rates among [female] smokers indicate 53% of smokers and 22% of never-smokers dying before age 80 years, and an 11-year lifespan difference…. Although the hazards of smoking until age 40 years and then stopping are substantial, the hazards of continuing are ten times greater.” In this study, the researchers found little difference between female smokers and nonsmokers when it came to confounding variables like weight, blood pressure, or lipid profile. A four-year head start—beginning to smoke at the age of 15 rather than 19, say—can put women at a measurably greater risk for lung cancer deaths.  And a little goes a long way: “Even those smoking fewer than ten cigarettes per day at baseline had double the overall mortality rate of never-smokers.” Low-tar won’t save them, either. “Low-tar cigarettes are not low-risk cigarettes,” the investigators write, “and the Million Women Study shows that more than half of those who smoke them will eventually be killed by them, unless they stop smoking in time to avoid this.”

There it is again: Half of all smokers are going to die from smoking.  As the authors of the Lancet study wrote: “If women smoke like men, they die like men.”

In summary, those who stop smoking at age 50 gain about six years of life expectancy. Quit at 40, and you get an extra nine years. A non-smoker’s chances of living from 70 to 90 are three times higher than a smoker’s. The researchers found that the doctors who stopped smoking by age 30 managed to avoid almost all of the lifespan penalties associated with smoking—primarily lung cancer, COPD, and heart disease. (Only about 3% of smoking deaths are due to fires, accidents, poisonings, etc.). And even lifelong smokers who do not quit until the age of 60 are still rewarded with an extra three years of life span, on average.

Perhaps the saddest thing about the findings is the ways in which they suggest that British and American military commanders may have been sentencing countless numbers of soldiers to death for decades, through the simple act of giving away cigarettes in K-rations, and selling them cheaply in other circumstances. As the report in the British Medical Journal states, “widespread military conscription of 18 year old men, which began again in 1939 and continued for decades, routinely involved provision of low cost cigarettes to the conscripts. This established in many 18 year olds a persistent habit of smoking substantial numbers of manufactured cigarettes, which could well cause the death of more than half of those who continued.” In a perverse reminder of the Agent Orange scandal in Vietnam, American and British military command may have exposed their soldiers to a much greater threat, for a much longer period, with worse odds for survival.

One obvious confounding variable in such studies is alcohol. It requires a sensitive statistical analysis to work through correlations between drinking, smoking, and, say, liver disease.  But “the large majority of the excess overall mortality among smokers is actually caused by smoking,” the Lancet researchers maintain with confidence.  The overall point seems clear: These long-term results show that the risks from continual cigarette smoking are even greater than we thought.

The dismal bottom line of the two smoking studies is that we appear to be right on schedule for meeting the UN’s prediction of one billion tobacco deaths in this brave new century.

Pirie, K., Peto, R., Reeves, G., Green, J., & Beral, V. (2012). The 21st century hazards of smoking and benefits of stopping: a prospective study of one million women in the UK The Lancet DOI: 10.1016/S0140-6736(12)61720-6

Photo Credit: Ianier67 via Creative Commons.

Twelve Months of Addiction Box

(Inspired by Twelve Months of Drug Monkey)

Drug Monkey writes:

The rules for this blog meme are quite simple.
-Post the link and first sentence from the first blog entry for each month of the past year.
I originally did this meme, after seeing similar posted by Janet Stemwedel and John Lynch.

Okay, here we go:

January:

Say what you will about glutamate-gated chloride channels in the parasitic nematode Haemonchus contortus—but the one thing you probably wouldn’t say about the cellular channels in parasitic worms is that a drug capable of activating them may prove useful in the treatment of alcoholism and other addictions.

February:

Here’s a book I’m delighted to promote unabashedly.

March:

Mo Costandi at the UK Guardian expanded on his Nature article about the mechanisms that result in memory impairment when people smoke marijuana.

April:

Our latest participant in the “Five Question Interview” series is Dr. Keith Laws, professor of cognitive neuropsychology and head of research in the School of Psychology at the University of Hertfordshire, UK.

May:

I'm not a huge fan of infographics, mostly because they tend to overpromise and are often marred by factual errors.

June:

Reporting the results of published studies concerned with genetic risk factors has always been a tricky proposition.

July:

Dr. Tom McLellan, chief executive officer of the Treatment Research Institute, who served on President Obama’s healthcare reform task force, called the recent U. S. Supreme Court Decision on the Affordable Care Act “the beginning of a new era in prevention, early intervention, and office based care for patients who are not addicted—but whose drinking, smoking, and use of other substances is harming their health and compromising the effectiveness of the care they are receiving for other illnesses and conditions.

August:

Medical marijuana advocates will finally have their day in federal court, after the United States Court of Appeals for D.C. ended ten years of rebuffs by agreeing to hear oral arguments on the government’s classification of marijuana as a dangerous drug.

September:

Voters in The Netherlands may have lost their final chance to block the nationwide imposition of the wietpas, or so-called "weed pass," as the law of the land in The Netherlands next year.

October:

People who say they are addicted to marijuana tend to exhibit a characteristic withdrawal profile.

November:

Children with heavy alcohol exposure show decreased brain plasticity, according to recent research on fetal alcohol spectrum disorders (FAS) using magnetic resonance imaging (MRI) scans.

December:

When a stroke happens to anyone under the age of 55, a major suspect is drugs, specifically the stimulants—methamphetamine and cocaine.


Photo Credit: lotteryuniverse.com

The Year in Drugs

Top Posts at Addiction Inbox.

By the look of it, readers had marijuana on their minds in 2012. Of the posts at Addiction Inbox with the highest number of page views, an overwhelming majority are concerned with marijuana, and specifically, with marijuana addiction, withdrawal, and brain chemistry. Of the 9 most heavily trafficked posts of the year, only one involved alcohol. Readers were also interested in the safety of e-cigarettes, and the mysteries of neurotransmitters like serotonin and dopamine. Happily, all the top posts were patently science-oriented articles.

See you in the New Year.

•  Marijuana Withdrawal

For Some Users, Cannabis Can Be Fiercely Addictive.

For a minority of marijuana users, commonly estimated at 10 per cent, the use of pot can become uncontrollable, as with any other addictive drug. Addiction to marijuana is frequently submerged in the welter of polyaddictions common to active addicts. The withdrawal rigors of, say, alcohol or heroin tend to drown out the subtler, more psychological manifestations of cannabis withdrawal.

•  Serotonin and Dopamine: A Primer

The Molecules of Reward

Serotonin and dopamine are part of a group of compounds called biogenic amines. In addition to serotonin and dopamine, the amines include noradrenaline, acetylcholine, and histamine. This class of chemical messengers is produced, in turn, from basic amino acids like tyrosine, tryptophan, and choline.

•  Marijuana Fact and Fiction

Why cannabis research is a good idea.

There is little doubt among responsible researchers that marijuana--although it is addictive for some people--is sometimes a clinically useful drug. However, there is little incentive for commercial pharmaceutical houses to pursue research on the cannabis plant itself, since they cannot patent it.

• Anandamide: The Brain’s Own Marijuana

Anxiety and the THC receptor.

Several years ago, molecular biologists identified the elusive brain receptor where THC, the active ingredient in marijuana, did its work. Shortly after that discovery, researchers at Hebrew University in Jerusalem identified the body’s own form of THC, which sticks to the same receptors, in pulverized pig brains.

•  The Mysteries of the Blunt

Why do so many smokers combine tobacco with marijuana?

People who smoke a combination of tobacco and marijuana, a common practice overseas for years, and increasingly popular here in the form of “blunts,” may be reacting to ResearchBlogging.orgsome unidentified mechanism that links the two drugs. Researchers believe such smokers would be well advised to consider giving up both drugs at once, rather than one at a time, according to an upcoming study in the journal Addiction.

•  Are E-Cigarettes a Good Idea or a Bad Idea?

A group of nicotine researchers argue for an alternative.

Electronic cigarettes are here to stay. If you're not familiar with them, e-cigarettes are designed to look exactly like conventional cigarettes, but they use batteries to convert liquid nicotine into a fine, heated mist that is absorbed by the lungs. Last summer, even though the FDA insisted on referring to e-cigarettes as “untested drug delivery systems,” Dr. Neal Benowitz of the University of California in San Francisco--a prominent nicotine researcher for many years--called e-cigarettes “an advancement that the field has been waiting for.”

•  Cannabis Receptors and the “Runner’s High”

Maybe it isn't endorphins after all.

A perennial favorite, the runner’s high post shows what long-distance running and marijuana smoking have in common. Quite possibly, more than you’d think. A growing body of research suggests that the runner’s high and the cannabis high are more similar than previously imagined….Endocannabinoids—the body’s internal cannabis—“seem to contribute to the motivational aspects of voluntary running in rodents.” Knockout mice lacking the cannabinioid CB1 receptor, it turns out, spend less time wheel running than normal mice. 

• Topamax for Alcoholism: A Closer Look

Epilepsy drug gains ground, draws fire as newest anti-craving pill.

A drug for seizure disorders and migraines continues to show promise as an anti-craving drug for alcoholism, the third leading cause of death in America, the Journal of the American Medical Association (JAMA) reported in its current issue.

•  Is Marijuana Addictive?

The argument continues.

Marijuana may not be a life-threatening drug, but is it an addictive one?
There is little evidence in animal models for tolerance and withdrawal, the classic determinants of addiction. For at least four decades, million of Americans have used marijuana without clear evidence of a withdrawal syndrome. Most recreational marijuana users find that too much pot in one day makes them lethargic and uncomfortable. Self-proclaimed marijuana addicts, on the other hand, report that pot energizes them, calms them down when they are nervous, or otherwise allows them to function normally.


Graphics Credit:  http://1.bp.blogspot.com (Creative Commons)

Have a Smart Christmas and a Harm-Reduced New Year

Thoughts on addiction and the holidays.

Addiction During the Holidays: Recovered or Not, It’s Important to be Prepared 
[Adi Jaffe, Psychology Today]

“The holidays are a stressful time for everyone. Between gift-giving, travel, and keeping up with all parts of the ever-complicated modern family unit, nearly anyone can find themselves driven towards the nearest coping mechanism, whatever that may be….”

The Season to be Jolly Careful 
[Paula Goodyer, Sydney Morning Herald]

“More parties, more time with family and less time at work help make Christmas special, but these ingredients can also make it harder for anyone trying to rein in their eating, drinking or drug use….”

Families and Addiction: Surviving the Season of Stress
[Christina Reardon, Social Work Today]

“The holidays usually evoke images of family bliss: —Uncle Joe carving up a big turkey for a traditional family dinner, Aunt Mary bestowing her wonderful gifts, Grandmom sharing cherished stories with the children. The reality is that this dreamy scene usually is nothing more than that—a dream. For many families, the holidays can be a time of great anguish, strife, and overindulgent behavior that is later regretted….”

Addiction and the Holidays
[Danielle B. Grossman, PsychCentral]

“Ah, the holidays: Candy canes, cozy slippers, festive lights, family peace, marital joy, and grateful children. Or not. The holidays are stressful. There are the challenges of too much family, not enough family, not enough money, continual exposure to food and alcohol, and perhaps worst of all, the gap between our actual life and our fantasy life….”

Rehab for the Holidays
[Nic Sheff, The Fix]

“It’s no big revelation to say that the holidays can fucking suck—and that being around family can be stressful as hell….”

Tips for Preventing the Holiday Blues, Staying Sober
[Hazelden]

“Most people know the holidays can be a period of emotional highs and lows. Loneliness, anxiety, happiness and sadness are common feelings, sometimes experienced in startling succession. The bad news is the holiday blues can trigger relapse for people recovering from alcoholism and other drug addiction. The good news is the blues can be remedied by planning ahead….”

Addiction and Christmas Chaos 
[Candace Plattor, Vancouver Observer]

“Even before Halloween came and went, I noticed that several of my clients were already becoming quite antsy about the upcoming holiday season—for a variety of reasons. People who struggle with addictive behaviors—anything from drugs and alcohol to eating disorders, gambling, sex addiction, or relationship addiction—wondered if they would be able to maintain their sobriety when they began to actually feel the loneliness, fear, and isolation that they had used these behaviors and substances to avoid experiencing….”
 
The Holidays and “Food Addiction”
[Vicky Hallett, Washington Post]

“If Santa really does stuff his face with every cookie he encounters after shimmying down those chimneys, that explains the big belly. But health and fitness expert Pam Peeke might say Saint Nick's behavior also could be a sign of something commonly found south of the North Pole: food addiction….”

Holiday Season Can Trigger Substance Abuse
[WIBW, Topeka]

“The holiday season is a busy and stressful time. All the festivities - and preparing for them - also can bring a spike in substance abuse. Stormont-Vail West chemical dependency counselor Fiana Martin says alcohol is commonly served at celebrations this time of year. But she says people recovering from addiction don't have to miss out on the fun if they arrive with what she calls a safety plan….”


Graphics Credit: pareeerica, Creative Commons.

States Quietly Defunding Anti-Smoking Programs For Kids

Only 2 cents of each tobacco settlement dollar goes to smoking prevention plans.

If there’s one thing we know about smoking, it’s that for every smoker who quits, we gain a net financial benefit. These health cost savings can be huge for states, which is why all of them have put in place smoking cessation plans and programs for their citizens. And they are able to run this programs because of the monies that come to them under the 1998 master tobacco settlement.

Perhaps it doesn’t come as a huge surprise, but it’s depressing, all the same: The Campaign for Tobacco-Free Kids estimates that states will spend less than 2 per cent of these court-mandated funds on actual programs to prevent kids from smoking. The report accuses the states of failing to reverse budget cuts to “programs that have set back the nation’s efforts to reduce tobacco use.”

The report was undertaken to access whether states have been using the estimated $246 billion over 25 years—plus cigarette taxes—to reduce tobacco use. What they found was that “states have failed to reverse deep budget cuts that reduced funding for tobacco prevention by 36 percent” from 2008 to 2012. Only North Dakota and Alaska are currently funding smoking cessation programs at the level recommended by the Centers for Disease Control and Prevention (CDC). Four states—New Hampshire, New Jersey, North Carolina, and Ohio—have allocated ZERO funds for tobacco prevention programs in FY 2013.

“Given such a strong return on investment,” the report concludes, “states are truly penny-wise and pound-foolish in shortchanging tobacco prevention and cessation programs.” The report declined to speculate on where the money actually goes, but noted that this was the “second lowest amount states have spent on tobacco prevention programs since 1999, when they first received tobacco settlement funds.”

The cries of outrage came thick and fast:

“The states have an obligation to use more of their billions in tobacco revenues to fight the tobacco problem. Their failure to do so makes no sense given the evidence that tobacco prevention programs save lives and save money by helping reduce health care costs."—Matthew L. Myers, President of the Campaign for Tobacco-Free Kids

"States with comprehensive tobacco control programs experience faster declines in cigarette sales, smoking prevalence and lung cancer incidence and mortality than states that do not invest in these programs."—John R. Seffrin, CEO of the American Cancer Society Cancer Action Network

"The paltry amount of money that states spend on tobacco prevention and cessation programs is extremely disappointing…. These programs work and it’s time for states to put more skin in the game."—Nancy Brown, CEO of the American Heart Association

"Too many states are failing their citizens by abandoning their responsibility to invest in proven programs that prevent people from smoking and help smokers quit…. Supporting these programs at recommended levels is not only the right thing to do, it's the smart thing to do — quitting smoking or never starting saves lives and saves money."—Paul G. Billings, senior vice president of Advocacy & Education at the American Lung Association

In 2007, the CDC concluded: “We know how to end the epidemic. Evidence-based, statewide tobacco control programs that are comprehensive, sustained, and accountable have been shown to reduce smoking rates, tobacco-related deaths, and diseases caused by smoking.”

Two cents on every dollar. About 20 percent of Americans smoke. “Tobacco companies spend more than $18 to market tobacco products for every one dollar the states spend to reduce tobacco use.” What’s wrong with this picture?

Photo Credit: http://www.tobaccofreekids.org