Drug-Drug Interactions to Watch Out For

P450 enzymes and “poor metabolizers.”

The finding, published in Science, is a bit arcane to the layperson. The big secret of how the P450 enzyme family metabolizes drugs turns out to be a critical phase change, where an oxygen molecule temporarily joins the mix, forming “Compound I,” a process the scientists documented by cooling the enzymes at just the right rate. 

So what? Well, for starters, “cytochrome P450 enzymes are responsible for the phase I metabolism of approximately 75% of known pharmaceuticals,” write Jonathan Rittle and Michael T. Green at Pennsylvania State University’s Department of Chemistry.  And in fact, only six of the more than 50 enzymes in the P450 family account for 90% of drug metabolization in humans--the compound known as CYP2D6 being the most crucial.

In a Penn State press release, lead author Michael Green, an associate professor of chemistry, noted that human populations vary widely in the version of genes they carry for P450 enzymes. According to Green, “adverse drug-drug interactions are a well-known problem…. Now that we can see those state changes on a molecular level, a deeper investigation is possible.”

The wide variation in enzymatic reactions, says Green, causes very real consequences. People with two copies of variant alleles are poor metabolizers, people with two copies of the standard genetic variety are normal metabolizers, whereas people with one of each are “reduced” metabolizers. (People who inherit multiple copies of the alleles become “ultrarapid” metabolizers.)

 “With a drug such as caffeine, for example, one population of people might be fast metabolizers, while another might metabolize the drug more slowly,” Green said. "Because the risk of caffeine-induced heart attack may be higher in slow metabolizers, the ability to actually take a snapshot of the phase changes of the P450 enzymes could help us to understand better how certain chemicals can affect people in vastly different ways."

There are dozens of specific cases like the caffeine example. Moreover, the genetic situation is complicated by other factors.  Writing in American Family Physician, Tom Lynch and Amy Price explain that cytochrome P450 enzymes “can be inhibited or induced by drugs, resulting in clinically significant drug-drug interactions that can cause unanticipated adverse reactions or therapeutic failures. Interactions with warfarin, antidepressants, antiepileptic drugs, and statins often involve the cytochrome P450 enzymes.” Testing for these interactions is expensive, and “it has not been determined if routine use of these tests will improve outcomes.”

Not a pretty picture. And just to further complicate matters, some drugs can induce or inhibit CYP450 enzymes differentially, depending upon the dosage. “For instance,” write Lynch and Price, “sertraline (Zoloft) is considered a mild inhibitor of CYP2D6 at a dose of 50 mg, but if the dose is increased to 200 mg, it becomes a potent inhibitor. Inhibitory effects usually occur immediately.” Also, drugs can be metabolized by, and at the same time serve to inhibit, the enzyme in question, as in the case of erythromycin.

So it is buyer beware, and listen to your body’s feedback when embarking on a course of new drugs. Recommended dosages are just that: recommendations. If you feel that the drug in question is doing too much or too little, ask your prescribing doctor about drug-drug interactions and about fast and slow drug metabolizers. Of course, they should be telling YOU about that, but.

Some known enzymatic drug interactions to bear in mind:

Drugs that potentially inhibit P450 enzymes—Tagamet, Cipro, Luvox, Prozac, Flagyl, Benadryl, Paxil, Lamisil, and grapefruit juice.

Drugs that potentially increase the activity of P450 enzymes—Tegretol, phenobarbital, tobacco, Dilantin, rifampin, St. John’s wort.

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Adverse drug-drug interactions involving P450 enzymes:

Amiodarone (Cordarone) combined with Warfarin (Coumadin): possible bleeding due to increased warfarin activity.

Tegretol, phenobarbital, and Dilantin combined with contraceptives containing ethinyl estradiol: possible unplanned pregnancies due to reduced contraceptive activity.

Clarithromycin, erythromycin, and telithromycin combined with Zocor: possible muscle disorders due to increased Zocor levels.

Prozac combined with Risperidone (Risperdal): increased risk of adverse effects from the antipsychotic drug risperidone.

Grapefruit juice combined with Buspirone (Buspar): Dizziness and other effects of “serotonin syndrome” due to increased buspirone activity.


Rittle, J., & Green, M. (2010). Cytochrome P450 Compound I: Capture, Characterization, and C-H Bond Activation Kinetics Science, 330 (6006), 933-937 DOI: 10.1126/science.1193478

Graphics Credit: http://elcamino.dnadirect.com/

The Day After

How’s that no-smoking pledge going?

This post is not meant for most of you. Those of you who never smoked, or smoked and quit successfully—move along, maybe check out my earlier posts about smoking this month.

But for those of you who have decided to take the 35th annual Great American Smokeout seriously—for those of you who decided today, or yesterday, or recently, to quit smoking—I have a few remarks, if you have a moment. I’m fairly trustworthy on this subject. I’m a science writer, I follow the field of addiction science, and I smoked a pack of Camel filters a day for about 25 years. In addition, I quit smoking using the most recently available smoking cessation aids—nicotine patches and anti-craving medication, in this case Zyban, a.k.a. Wellbutrin.

I had decided, after the usual smoker’s run of unsuccessful independent quitting attempts, that the only real hope I had for success was to throw myself into the hands of my primary care physician. Happily, Dr. Joe is a young example of the last of the breed, a lingering remnant of a tribe that used to be known as family doctors. When I told Dr. Joe of my plans to quit smoking, he was overjoyed. Too overjoyed, it seemed to me. As it turned out, there were grounds for my suspicion. Dr. Joe had recently returned from a smoking cessation seminar at the Mayo Clinic in Rochester, Minnesota, with a grab bag of refinements and alternative approaches for setting up a no-smoking regimen. Furthermore, he made it clear that, if necessary—if I forced him to it through relentless noncompliance—he was fully prepared to order regular blood workups to detect and quantify my nicotine levels.

Of course, I instantly regretted setting a foot into this ring, but once Dr. Joe started flinging prescriptions for patches and pills my way, I realized I was in it up to my wallet (Insurance companies weren’t paying for nicotine cessation products, ever, at that time).

Most smokers know the current drill. A few weeks with nicotine patches or gum or nasal spray, combined with a short course of Zyban or Chantix to further reduce cravings, and then you are expected to fly out of the nest and spread the good news.  Most smokers know that even this controversial armamentarium is not going to completely spare them from a rare and special kind of suffering: addictive craving for nicotine.  It’s a mean, rough ride, as everyone knows.

But if you take a few of the major potholes out of the road, smooth over the really big bumps just a little, fill in the low spots a bit as well, you have a fighting chance—especially if you have tried and failed before (almost nobody pulls it off on the first attempt).

Here are the key features of the program, as my doctor worked it up for me:

--Stronger patches. Mayo Clinic and other institutions had made an important discovery, my doctor said. People weren’t wearing strong enough patches. There was a system of matching up patch strength to amount and duration of smoking, and then a step-down procedure, to less and less powerful patches, and it was all listed on the packages, but because of great nervousness over medical complications by a very few individuals who overdid the patch and then chain-smoked on top of that, the result was that the patches as marketed weren’t strong enough, many doctors felt. The advice was to start strong, with the strongest patch available (and perhaps there was even a patient or two who doubled up, ahem). 

--Longer patches. Start strong—and go long. The whole nicotine replacement plan is supposed to last a month or two. Phooey, said Dr. Joe. No telling in advance how long the process will take. There is no set timetable. How long would I be wearing patches and tapering the dose? As long as it took, Dr. Joe inferred, for me not to need them anymore. He seemed prepared to keep me on patches the rest of my life, if it kept me from picking up a cigarette. In the end, when I took off my final, tiny patch, I had been using them for a little less than six months. The recommended five-star treatment plan in the literature and on the packages calls for only 10 weeks, tops.

--Pharmaceuticals. It is admittedly hard to separate out placebo effects from drug effects, in the case of something as elusive as cigarette urges. But I do believe that Zyban took the edge off the worst of my cigarette cravings. It did not eliminate them, anymore than the patches eliminated them. But the medication effectively dissipated the grip of that moment of panic, when you have risen from your chair and set about finding your coat and car keys for a run to the gas station to buy a pack of cigarettes. Or at least that’s the way it felt to me.

--Exercise. Trite? You bet, and you can be sure that I winced and offered a tired smile when I heard my doctor bore in on the subject. Since I knew him to be a crazed bicyclist, I was prepared to disregard most of what he had to say. But his insistence sent me back to the research literature on exercise and its effect on dopamine, serotonin, acetylcholine, and endorphin levels. So I took him up on that firm suggestion as well, and found that, at the least, it helped with a period of rocky sleep in the beginning.

--Diet. No huge changes, just watching the sweets in an effort to avoid surging blood sugar levels. Fruit helps, since constipation is a common side effect of nicotine cessation—just the opposite of how it works with heroin. I continued to drink coffee, but for a while it didn’t taste as good.

--Relaxation. Quitting smoking makes you tense. You think I’m being funny? Quitting smoking makes you tense all over, mentally and physically. During the first few days you’ll notice that your body is clenched, held rigidly. Your posture is likely to be anything but relaxed; your physical movements can be jerky and awkward. A few minutes a day spent sitting with eyes closed, in a relaxed upright posture, thinking of nothing or concentrating on your breathing or meditating either formally or casually, can bring partial relief from all that tension. And on some days, that can be crucial.

--Determination. Unfortunately, it wasn’t until everyone around me—my wife, children, parents, close friends, work associates—had all, I sensed, basically given up on me, silently condemning me to the category of Lifetime Smoker, that I finally managed to make a successful run at a major life problem. There are better ways to work up your determination. Find and employ them.

With time, an involved partner, nicotine replacement, and the right medication, the deal can be done. There has never been a better time in history to be a smoker who has decided to quit.

Graphics Credit: http://adoholik.com/

New Warning Labels for U.S. Cigarettes; Big Tobacco on the Rampage

Philip Morris Intl. sues Uruguay and Brazil.

Lots of developments on the nicotine front these days. On opposite ends of the news spectrum, so to speak, the Food and Drug Administration (FDA) announced plans to slap new and much more graphic warning stickers on cigarette packs--while elsewhere in the world, the world’s major tobacco companies got busy fighting tougher regulations on cigarette marketing. Meanwhile, the state of California has set limits on the marketing of e-cigarettes, disallowing companies from promoting the nicotine inhalers as “smoking-cessation devices.”

So let’s get busy. In the first significant change for cigarette advertising in 25 years, the FDA, freed by Congress last year to regulate tobacco products, will select nine new designs from among 36 contenders for new, far more graphic warning labels on cigarette packages. The new warning labels will begin appearing in about a year. To view the contenders, go to www.fda.gov/cigarettewarnings.

But will new, grisly images of dying smokers and rotted lungs really make a difference to the roughly one-quarter of adult Americans who still smoke?  “I am pleasantly shocked that [they are] doing this,” Stanton A. Glantz, a tobacco researcher at UC San Francisco, told the Los Angeles Times.  “There is no question but that strong graphic warning labels work,” he said. “Right now we have the weakest warning labels in the world. Now we will be right up there tied for the strongest.”

No so fast, counters John F.  Banzhaf, the executive director of Action on Smoking and Health and a George Washington University law professor. In the same L.A. Times article, Banzhaf said he was “quite disappointed,” stating that the agency “has done nothing more than exactly what Congress told them to do, and not one iota more.” So far, the FDA has banned advertising in magazines for young people, nixed the marketing ploy of handing out free samples on the street, and forbidden tobacco companies from marketing cigarettes by using the words “light” or “low-tar.”

Perhaps a more important result of Congressional approval of FDA oversight is that Medicare has now changed its rules to include smoking cessation products for covered beneficiaries. Previously, only people dying of lung disease were approved for smoking cessation products—a bit late in the disease cycle to do anybody much good.

According to a variety of estimates from government and research agencies, as many as half a million Americans die prematurely from smoking-related diseases. The Department of Health and Human Services has lately been stymied by a smoking rate of about 20%, basically unchanged since 2004. In 1965, about 42% of Americans smoked. The Department of Health and Human Services (HHS) has a stated goal of bringing smoking levels down to 12% by 2020.

That will not be an easy target to hit. And neither Congress nor the FDA nor HHS can count on anything amounting to cooperation from the cigarette giants. The New York Times, in an article by Duff Wilson, notes that worldwide cigarette sales rose 2% last year, as cigarette companies increasingly shift their marketing efforts toward a hunt for new customers in developing countries.  The aggressive nature of the worldwide cigarette marketing push was underscored this year when Philip Morris International sued the governments of Uruguay and Brazil, claiming that those countries had enacted tobacco regulations that were excessive and a threat to the company’s trademark and property rights.

Dr. Douglas Bettcher of the World Health Organization’s Tobacco Free Initiative accused the company of “using litigation to threaten low- and middle-income countries.” Philip Morris subsidiaries are also filing suits in Ireland and Norway over display advertising prohibitions. (Philip Morris USA, a separate division, is not involved in these lawsuits, and did not join with R.J. Reynolds and other tobacco companies in filing suit against the FDA last year.)

In the New York Times article, Wilson writes:

Companies like Philip Morris International and British American Tobacco are contesting limits on ads in Britain, bigger health warnings in South America and higher cigarette taxes in the Philippines and Mexico. They are also spending billions on lobbying and marketing campaigns in Africa and Asia, and in one case provided undisclosed financing for TV commercials in Australia.

As tobacco expert Dr. Cynthia Pomerleau points out on her blog, low smoking rates among women in the developing world make them a particularly tempting marketing target for the tobacco industry. Pomerleau, research professor emerita in the University of Michigan’s Department of Psychiatry, also reminds us that “the real goal here is not to remove health warnings altogether—health warnings have actually worked well for them by legitimizing the claim that if people choose to smoke, it’s not their fault—just to prevent them from dominating the package and actually becoming salient.”

It is important for the industry, says Pomerleau, to publicize “effects that can be achieved or problems that can be addressed by smoking.” In this respect, Pomerleau is concerned about the likelihood that the tobacco industry will seize upon the relationship between smoking and thinness as the wedge for sales campaigns aimed at women. “If it worked in the U.S., why not in Africa or Asia or South America?”

And finally, under a consent judgment worked out with California state Attorney General Jerry Brown, the Florida-based Smoking Everywhere company, a distributor of electronic cigarettes, has agreed not to target minors in its advertising, or to make claims that its products are safe alternatives to tobacco. The move comes shortly after the FDA announced plans to regulated battery-powered e-cigarettes as new drug delivery devices. Smoking Everywhere distributes e-cigarettes manufactured in China. The consent judgment also bars the company from selling its products in vending machines, and requires the products to contain warning labels about the dangers of nicotine.

And don’t forget: Thursday, November 18 marks the 35th annual Great American Smokeout.

More Vanishing Cigarettes

Churchill, Bette Davis, Don Draper, and Pecos Bill.

In my last post, I highlighted some examples of attacks on cultural history represented by cigarette censorship, to wit: a cigarette taken out of the hand of Paul McCartney, and out of the mouths of Jackson Pollock and Burt Reynolds.

But that is only the tip of the iceberg for cigarette revisionism. Other examples:

--Jean-Paul Sartre. A legendary smoking icon, Sartre was no doubt rolling in his grave over the decision by the Bibliotheque Nationale of France to airbrush away his ever-present cigarette in an exhibition poster marking the 100th anniversary of his birth.

--Winston Churchill. Perhaps the most famous cigar smoker in history, the British Prime Minister suffered the indignity of having his cigar air-brushed out of the famous 1948 photograph of him making the “V” sign for victory. As you can see in the photograph above, that moment in history is no longer with us. Instead, Churchill looks like he is beginning to develop lip cancer.

--Tom and Jerry, Fred Flintstone, and Pecos Bill. Famous cartoon characters who occasionally, for purposes of satire or humor, were seen smoking cigarettes, and whose famous smoking scenes have been edited out by nervous broadcasters over the years. 

--Bette Davis. Another iconic cigarette smoker, she also ran afoul of the U.S. Postal Office (see Jackson Pollock in the post below). When the Post Office offered its Bette Davis stamp in 2008, it was inspired by a still photo from the film "All About Eve." As film critic Roger Ebert wrote at the time: “Where's her cigarette? Yes reader, the cigarette in the original photo has been eliminated. We are all familiar, I am sure, with the countless children and teenagers who have been lured into the clutches of tobacco by stamp collecting, which seems so innocent, yet can have such tragic outcomes.”

--And finally, there is the contemporary case of Don Draper of TV’s “Mad Men,” the only current television show truly obsessed with the cultural significance of smoking.  Indeed, the series opened its first season with a show called “Smoke Gets in Your Eyes,” in which advertising execs devised a pitch for Lucky Strikes. And the arresting title sequence that opens every show ends with a memorable black and white graphic of Don Draper seen from behind, seated on a couch, a cigarette held firmly in hand. “Bizarrely,” write Chris Harrald and Fletcher Watkins in The Cigarette Book: The History and Culture of Smoking, “this pleasure was denied to the man in the Mad Men promotional video for Season 1, when shown on Apple’s iTunes. The original image of a man seen from behind lounging in silhouette, right hand outstretched with a cigarette in it, has had the cigarette digitally removed.” (It has since been restored).

Photo Credit: CORBIS/Stephanie Schaerer

When Presidents Smoke

And a word about famous cigarettes that vanish.

I gave Obama a pretty hard time during the campaign and the first half of his presidency, for sneaking off to furtively field-strip the odd Marlboro. So it seems only fair to take a moment and point out the illustrious forefathers that have paved the way for today’s presidential indiscretions.

The source here is an illustrative and very funny book of cigarette history called, straightforwardly enough, “The Cigarette Book: The History and Culture of Smoking,” by Chris Harrald and Fletcher Watkins.

In the preface, the authors write: “One day the last cigarette on earth will be smoked. One final puff will be sent heaven-bound, leaving a lingering, evanescent smoke-ring…. The ubiquity of the cigarette is astounding. But soon it will be no more.”

A few factoids about U.S. Presidents and smoking:

-- John Quincy Adams. Pipe. A prodigy, he took up smoking at the age of eight.

-- Zachary Taylor. Chewing tobacco. Claimed he could hit White House spittoons from a distance of 12 feet.

-- Rutherford B. Hayes. First killjoy to ban smoking in the White House.

-- William McKinley. “Frantic cigar smoker.” Was known to break open cigars and chew the tobacco.

-- Calvin Coolidge. 12-inch cigars. Mrs. Coolidge, with her secret cigarette habit, may have been the first smoking First Lady.

--Herbert Hoover. “Chain-smoker.”

-- Franklin D. Roosevelt. “Paraplegic chain-smoker.”

-- Harry Truman. Banned smoking at official White House events.

-- Dwight D. Eisenhower. Rolled his own. Quit before the inauguration.

-- John F. Kennedy. “Cuban cigars.” Bought 1,200 of them the day before signing the Cuban embargo. Jackie was, it is said, good for up to three packs of Salems a day.

-- Lyndon B. Johnson. Ferocious cigarette smoker. A habit of 60 smokes a day is assumed to have caused the first of three heart attacks.

-- Gerald Ford. “Pipe. Eight bowls a day.”

-- Ronald Reagan. Did not smoke as president, but will be forever remembered for shilling Chesterfields in the 1940s: “My cigarette is the mild cigarette… that’s why Chesterfield is my favorite.”

In most of these presidential cases, the smokers in question were less than fully candid with the general public about their habits. But even more interesting, and rather chilling, are examples of revisionist censorship—making famous cigarettes in famous photographs mysteriously disappear, for the sake of cultural correctness.

The authors of “The Cigarette Book” start out with a swift punch to the midsection: “A recent poster featuring the famous album cover of Abbey Road (1969) removes the cigarette from Paul McCartney’s hand” (Italics mine, to reify the significance of the offense).

And readers of a certain age will recall (or recall hearing of) (or deny knowing anything about) a nude Burt Reynolds as a Playgirl magazine centerfold in 1972, with a cigarette dangling suggestively from his mouth. But when the image was reissued 35 years later, as part of an HD TV ad campaign, the cigarette, the authors tell us, “had been Photoshopped out of existence. Now it would probably be more acceptable to see his genitals than to see him smoking.” (Then again, maybe not.)

And in 1999, the U.S. Postal Service issued a Jackson Pollock stamp, using an iconic photograph from Life Magazine, showing the artist with a cigarette between his lips. “The Postal Service used the photo, but digitally removed the cigarette.” And perhaps added a little collagen to the lips, as well?

Finally, there is the case of chain-smoker Joseph Stalin, and the insane anti-smoker Adolf Hitler. Hitler had a cigarette removed from a famous photo of Stalin circulated at the time of the non-aggression pact. “Hitler felt it was bad for Germans to see such a ‘statesman’ (Hitler’s term) with a cigarette between his fingers.”

Photo credit: LBJ Library

Meet Sara Bellum

It’s National Drug Facts Week.

Let’s face it: Most groups, movements, associations, programs, textbooks, and videos that attempt to instill an anti-drug message in our nation’s youth are lame beyond belief. From “Reefer Madness” to “This is Your Brain on Drugs,” adults have managed to inculcate one overriding message in the nation’s young people: When it comes to drugs and alcohol, you can’t count on older people to tell you the truth.

So, in honor of National Drug Facts Week, it is with pleasure that I point to the Sara Bellum Blog, maintained by the National Institute on Drug Abuse (NIDA) and dedicated to the notion that tweens and teens might be as interested in straightforward drug facts as anybody else. Here is what the blog has to say about itself:

The Sara Bellum Blog is written by a team of NIDA scientists, science writers, and public health analysts of all ages. We connect you with the latest scientific research and news, so you can use that info to make healthy, smart decisions.

Sometimes it can be hard to know where to go for the truth about drugs. Here at NIDA, we learn from science—not from rumors or gossip. We have thousands of researchers around the world who study drug addiction and come up with ways to help people recover and live healthy lives. Every day, scientists and physicians discover more about how drugs affect your brain and body.

You owe it to yourself to ask the right questions, look for the facts, and think hard about what you find out and what it means for you. We’re here to help you do that.

The year-old blog has been recognized as one of the top government blogs, and is targeted primarily at 12 to 17 year-olds. There is an “Ask Dr. NIDA” feature, and a National Drug I.Q. Challenge, which you can take here.

I scored 18 out of 20. But I nailed the bonus round, 5 for 5.

Articles at the site include:

· How Does Cocaine Work? It's Partly In Your Genes

· NIDA News: NIDA's Chat Day, More Questions on Marijuana

· Real Teens Ask: Do Many Kids in High School Do Drugs?

· Real Teens Ask: Can inhaling Sharpie markers make you high?

· Binge Drinking Matters--To Your Brain

· NIDA News: Back to the Future?

· Meth Mouth and Crank Bugs: Meth-a-morphosis

· Real Life: Eminem and Elton John

· NIDA News: Who Gets Fooled by Flavors?

In addition, here are some comments made by the blog's editor, Jennifer Elcano, and posted at Sara Bellum:

We thought it would be a good strategy for conveying drug abuse facts and prevention messages to teens, because we could tweak a blog format to offer brief and regularly updated content and keep it current and interesting. And a lot of our other publications geared to teens were longer or in book or brochure format. The blog allowed us a way to post short and topical items of interest to teens and also to elicit their instant feedback on what they were reading about, what we were offering them, so we could continue to adjust it as time went on since it was such a new thing.

Sara Bellum has a long history at NIDA and has appeared in a lot of our print publications in prior years. If you Google her, you can see some of our past publications where she appears as a fictional NIDA adventurer, scientist, and explorer with a big looking glass. She would be investigating the science behind drugs and their effects on the brain and the body. So what we did with the blog is basically update this character to be more of a “chic geek” type.”

I am really proud of the fact that we took a risk as a federal government agency in allowing a blog where moderated comments were permitted. We have fairly liberal guidelines, so we will only not post comments if they contain profanity, denigrate people or groups of people, or contain spam or link to outside websites. They are very basic rules mainly to protect the site’s integrity and the commenters themselves, who sometimes disclose identifying information that should stay private. I am glad we have been able to do this in a climate that tends to be averse to taking these kinds of risks.

Photo Credit: http://teens.drugabuse.gov

Mephedrone, the New Drug in Town

Bull market for quasi-legal designer highs.

Most people in the United States have never heard of it. Very few have ever tried it. But if Europe is any kind of leading indicator for synthetic drugs (and it is), then America will shortly have a chance to get acquainted with mephedrone, a.k.a. Drone, MCAT, 4-methylmethcathinone (4-MMC), and Meow Meow--the latter nickname presumably in honor of its membership in the cathinone family, making it chemically similar in some ways to amphetamine and ephedrine. But its users often refer to effects more commonly associated with Ecstasy (MDMA), both the good (euphoria, empathy, talkativeness) and the bad (blood pressure spikes, delusions, drastic changes in body temperature).

Some of the best stateside coverage has come from the anonymous NIH researcher who blogs on science topics as DrugMonkey. The whole business of what mephedrone does is complicated, he writes. The cathinone structure is “very similar to amphetamine and supports parallel modifications,” but there is clearly an “MDMA-like component to this mephedrone stuff.” (See additional DrugMonkey coverage here  and here.)

Until earlier this year, mephedrone was in that weird state of limbo LSD found itself occupying in the mid-1960s: legal, but not for long. States are attempting to sweep synthetic drugs of abuse like Spice and other cannabinioid derivatives into a proscribed package that includes mephedrone.  Federal authorities are able to prosecute under The Analogue Drug Act of 1986, which was designed to combat this dilemma in the United States by outlawing drugs “substantially similar” to any drug that is already illegal. However, “chemical experts disagree on whether a chemical is 'substantially similar' in structure to another chemical—so much so that Federal Analogue Act litigation often degenerates into a 'battle of experts,' which is founded more on opinion than on actual scientific evidence,” writes Gregory Kau in an article for the University of Pennsylvania Law Review.

It is clear by now that this cat-and-mouse game is rigged in favor of the designers and suppliers of new drugs under the sun. Exploiting the gray zone of quasi-legality is extremely profitable. One outlaw chemist told Jeanne Whalen of the Wall Street Journal that by the time law enforcement closes in, “we are going to bring out something else.” At which point, prosecutorial mechanisms put in place for mephedrone must be laboriously recreated for the new drug.

This drug entrepreneur, and others like him, makes extensive use of the Internet, especially in Europe, since mephedrone is not universally banned. To keep the business technically legal, sellers label mephedrone “not for human consumption” and market it as anything from plant food to bath salts.  Sometimes they draw unwanted attention to themselves through the purchase of lab equipment, like the rotary evaporator pictured above. 

Mephedrone has lately been covered relentlessly by the British press, after the deaths of three young people in the U.K. and Sweden were attributed to mephedrone. Part of the difficulty in assessing the danger and addictiveness, if any, of these newer substances is that most of them have not been subjected to controlled clinical testing on humans. (One hardy purveyor of mephedrone snorted half a gram of the drug on a Belgian news program to demonstrate his side of the argument.)

Media hysteria in the U.K. led to reports of dozens of deaths due to mephedrone, none of which have thus far proven to be indisputably the result of ingesting mephedrone. As British politicians rushed to enact a ban, Danny Kushlick of the drug charity Transform told the U.K. Guardian in April: “The misreporting of mephedrone deaths is a crass example of the potentially lethal alliance between press and politicians that by default ends in a ban that often creates far greater harms than those caused by use.”  In July, BBC News reported that the mephedrone crackdown was “floundering”, even though the ban had been widened to included a near-beer version of mephedrone called Naphyrone (sold as NRG1). But a spokesperson for Lifeline, another British drug charity, argued that “you can’t just ban your way out of a problem because it could result in far more dangerous chemicals coming onto the market.” According to the European Monitoring Centre for Drugs and Drug Addiction, which operates the EU early-warning system on new drugs in cooperation with Europol,  “24 new psychoactive substances were officially notified for the first time to the two agencies in 2009.”

The National Drug Intelligence Center at the U.S. Department of Justice reported that early in the year, “several individuals in the Bismarck [North Dakota] area ingested or injected illicit products containing mephedrone and required hospitalization. In addition, the Oregon State Police Forensic Laboratory (Bend, Oregon) received two submission of white power that users referred to as ‘sunshine.’ Both submissions tested as mephedrone.”

And now comes a report from North Carolina of two fatalities allegedly linked to the use of mephedrone, as reported by David Kroll at Terra Sigillata.

Narcotics officials and toxicologists say that the raw materials for many of the new drugs appear to be manufactured in China and trans-shipped to other countries in Southeast Asia and the Middle East. DrugMonkey also notes that it will be interesting to see “if actions such as Cambodia, Vietnam, and Thailand finally getting serious about controlling the production of the safrole oil used as a precursor in MDMA manufacture is having a lasting effect on world markets.”

Photo Credit: http://www.ipfw.edu/