Monday, October 20, 2014

The End of Combusted Tobacco?

With E-cigarettes, a mixed bag of possible outcomes.

E-cigarettes represent a controversial and uncertain future for nicotine addiction, and for this reason they have attracted acolytes and naysayers in what feels like equal measure.

It has been almost 8 years since e-cigarette imports first reached our shores, and the FDA’s determination that they are subject to regulation as tobacco products brings the industry to a crucial crossroads.

On the one hand: “Marked interdevice and intermanufacturer variability of e-cigarettes… makes it hard to draw conclusions about the safety or efficacy of the whole device class.”

On the other hand: “Published evaluation of some products suggest that e-cigarettes can be manufactured with levels of both efficacy and safety similar to those of NRT [nicotine replacement therapy] products… they could play the same role as NRT but at a truly national, population scale.”

So which will it be? Is there an outside chance that the decision by the FDA’s Center for Tobacco Products will represent the first step in dealing with nicotine products currently “designed, marketed, and sold” outside the regulatory framework established for NRT?  A stalemate presently prevails. Writing in the New England Journal of Medicine, Drs. David Abrams and Nathan K. Cobb, Johns Hopkins professors affiliated with the American Legacy Foundation, a tobacco research and prevention organization funded with lawsuit money from the major tobacco companies, highlight the irony: In order to market e-cigarettes as smoking cessations devices, manufacturers must seek approval from the FDA to market pharmaceutical products, “an expensive and time-consuming process than no manufacturer has yet attempted.”

Thus, questions about nicotine content, additives of various kinds, and assorted carrier chemicals go unanswered. Yet these are precisely the questions that need answers before e-cigarettes can be viewed as tools in the harm reduction armamentarium. Cobb and Abrams note that current e-cigarettes “represent a single instance of a nicotine product on a shifting spectrum of toxicity, addiction liability, and consumer satisfaction.” But the market dictates that “to compete with and displace combusted tobacco products, e-cigarettes will need to remain relatively convenient, satisfying, and inexpensive,” regulation notwithstanding.

Still, the harm reductionists’ dreams for the product remain seductive, because “surely any world where refined nicotine displaces lethal cigarettes will experience less harm, disease, and deaths? That scenario is one endgame model for tobacco control: smokers flee cigarettes en masse for refined nicotine and ultimately quit all use entirely.”

Critics say fat chance: “As Big Tobacco’s scientists shift from blending leaves and additives to manipulating circuit boards, chemicals, and dosing schedules, they’re unlikely to relinquish their tolerance for risk and toxicity that prematurely kills half their users in their efforts to ensure high levels of customer ‘satisfaction,’ addiction, and retention.”

Once again, it is the dictates of the market that may end up shaping the future of tobacco, and making the plans of harm reductionists look naïve indeed. “Tobacco companies and their investors,” write Cobb and Abrams, “need millions of heavily addicted smokers to remain customers for decades, including a replenishing stream of young people. No publicly traded company could tolerate the downsizing implicit in shifting from long-term addiction to harm reduction and cessation.”

The marketing innovations most likely to stem from tobacco companies entering the market for e-cigarettes are those most likely to “sustain high levels of addiction and synergistic ‘polyuse’ of their existing combusted products,” while simultaneously crimping competition from NRT manufacturers and independent e-cigarette manufacturers. Tobacco companies are past masters at manipulating things like nicotine content, vaporization methodologies, flavorings, and unknown additives. They will surely bring this expertise to bear in seeking a major bite out of the e-cigarette market while maintaining acceptable profit margins on traditional cigarettes.

The authors suggest that the FDA could weight the matter in harm reduction’s favor by using its product-standard authority “to cripple the addictive potential of lethal combusted products by mandating a reduction in nicotine levels to below those of e-cigarettes and NRT products and eliminating flavorings such as menthol that make cigarettes more palatable.” Tax breaks for e-cigarettes would further load the dice.

But not today. The FDA’s proposal calls for warning labels or product safety and quality standards for e-cigarettes—but not for at least two years. Two years is a long time in a fast-emerging market already valued in excess of $2 billion. The authors call the delay disturbing, “given the variability in product quality and a documented spike in cases of accidental nicotine poisoning.”

In conclusion, the authors believe that for smokers hoping to quit, “NRT products still represent safer, more predictable choices, even if they are more expensive and less appealing.”

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Tuesday, October 14, 2014

In Search of the Marijuana Breathalyzer

Pissing in a cup may be on the way out.

The good news: Marijuana breathalyzers are coming. The bad news: Marijuana breathalyzers are coming.

For years now, urinalysis using a mass spectrometer has been, if you’ll excuse the expression, the gold standard for drug testing. But in the case of alcohol, exhaled breath has always been the detection matrix of choice. And now, after the publication of several papers analyzing the detection of various drugs of abuse in exhaled breath, companies are hoping to leap into the market for cannabis breathalyzers.

A 2013 paper in the delightfully named Journal of Breath Research, written by neuroscience researchers at the Karolinska Institute in Stockholm, sought to confirm recent research suggesting that amphetamine, THC, and other drugs can be reliably detected in users who exhale into specially treated breath pads. The researchers collected breath, plasma, and urine samples from 47 patients. They tested for metabolites of methadone, amphetamine, morphine, benzodiazepines, cocaine, buprenorphine, and THC.

The results of the testing “provide further support to the possibility of using exhaled breath as a readily available specimen for drugs of abuse testing…. The detection rate for most investigated substances appears to be high, and higher than previously reported, with the exception of benzodiazepines.” The false positive rate was about 8%, which is very good, and is due, presumably, to improved sampling sensitivity.

In collaboration with Karolinska, NIDA researchers published a paper in Clinical Chemistry showing that cannabinoids blown onto breath pads were stable for up to 8 hours at room temperature—and up to 6 months in cold storage evidence lockers. The researchers tested 13 chronic smokers and 11 occasional smokers. Analysis of breath pad samples nailed all 13 of the serious smokers, and all but one of the casual smokers an hour after smoking. With current technology, the cannabis detection window remains very small, somewhere between 30 minutes and two hours. However, testing positive tells us nothing about when, and how much, marijuana was smoked.

Furthermore: “If a correlation to blood concentration can be shown for exhaled breath levels, it may become a substitute matrix for monitoring impairment.” And that, readers, is the Big If. What, exactly, are we testing FOR? Impairment, or just any and all use? Is there a reliable standard for marijuana, like the 0.08 blood level standard for alcohol? Or is a plethora of spurious positives on the horizon?

Roadside drug breathalyzers are presently under development or are in the prototype stage at several North American companies. One such device is a marijuana breathalyzer with a two-hour test window soon to be on offer from Cannabix Technologies. It was developed by a former member of the Royal Canadian Mounted Police because, says the company, there is no standardized way “to detect whether someone has been using marijuana on the spot like a breathalyzer does for alcohol.” So Cannabix is collaborating with Field Forensics Inc. to develop a testing device for roadside use.

An analysis last month at  saw a silver lining in the Cannabix breathalyzer, calling it “possibly the next major step towards normalization of more widespread marijuana use being allowed as such a device would offer a ready means of addressing key sticking points that have kept industry, legislators and law enforcement from agreeing on how best to regulate cannabis.”

North America is viewed as a “target-rich market” that is “ripe for the advent of a pot breathalyzer.” In the end, “roadside blood draws by law enforcement and other invasive methods of screening for THC intoxication, like zero-tolerance urine testing at the workplace, are increasing impractical as medical and even recreational cannabis gain ground throughout North America.”

The coming cannabis breathalyzers will be able to tell us the “when.” And soon they may even be able to tell us how much. But it remains unclear whether marijuana breathalyzers will ever be able to tell us how high—to reliably measure cannabis impairment behind the wheel. Somewhat mysteriously, the level of 5 nanograms of THC per blood milliliter has emerged as the de facto standard. But it’s clear to people who are actually familiar with marijuana’s effects that experienced users don’t react the same way as naïve users, and it’s perfectly logical to presume that some users can drive with complete safety at the 5ng level—users such as daily consumers of medical cannabis, whose tolerance is high even though daily quantities smoked is usually low.

One inspiration behind the cannabis breathalyzer is law enforcement’s love of the alcohol breathalyzer. In 1938, Dr. Rolla Harger of Indiana University introduced his Drunkometer, the first device for testing alcohol on a person’s breath. But it wasn’t portable. And it wasn’t until 1954 that Indiana University’s Robert Borkenstein came up with the portable Breathalyzer. The rest is drunk driving history.

In the bad old days before anybody “blew” a 0.08, prosecuting a DUI required court evidence—dash cam footage, field sobriety tests, officer assessments and testimony, and on and on. At present, that’s the situation for law enforcement when it comes to prosecuting a DUI for marijuana. For years, the prevailing court test has been the Duquenois-Levine test—the dominant method for field-testing marijuana since 1930—and it is considered by many to be wildly inaccurate. It involves inserting a bit of the substance in question into a prepared pipette, then waiting to see if it turns purple. If it does, the suspect can be charged with possession. (One U.S. Superior Court judge referred to the test as “pseudo-scientific”).

According to the official drug policy of the United Nations, a positive marijuana ID requires gas chromatography/mass spectrometry analysis. But even sophisticated tests have angered courts, due to the DEA’s muddled standards for lab protocols. A former FBI agent told the Texas Tech Law Review: “We are arresting vast numbers of citizens for possession of a substance that we cannot identify by utilizing the forensic protocol that is presently in use in most crime labs in the United States.”

Russ Belville, writing at the Huffington Post, concludes in a similar vein: “Until science shows a reliable test that only snares pot-impaired drivers and not unimpaired drivers who happen to be pot smokers, [prosecutors] are just asking for an easier way to discriminate against legal cannabis consumers.”

Thursday, October 2, 2014

Strokes in Young People

Drug use as a risk factor.

(First published 12-09-12)

When a stroke happens to anyone under the age of 55, a major suspect is drugs, specifically the stimulants—methamphetamine and cocaine. In the journal Stroke, researcher Brett Kissela and his associates provided additional evidence to support that unpleasant truth.

“We know that even with vascular risk factors that are prevalent—smoking, high blood pressure—most people still don’t have a stroke until they’re older,” Kissela said in a Reuters article. “When a young person has a stroke, it is probably much more likely that the cause of their stroke is something other than traditional risk factors.”

The modest study involved residents of Cincinnati and Northern Kentucky who had suffered a stroke before turning 55. The researchers found that the rate of substance abuse among the stroke group was higher than in control populations. This doesn’t prove that drug or alcohol addiction lead directly to strokes, since drug users often have additional risk factors for stroke and heart disease, particularly if they are also cigarette smokers.

But the suspected link between strokes and young drug abusers is by no means a new one. In 2007, scientists at the University of Texas Southwestern Medical Center in Dallas published a massive survey of more than 3 million records of Texas hospital patients from 2000 through 2003 in the Archives of General Psychiatry. This gigantic database gave the researchers access to the records of virtually every stroke patient in the state of Texas. The researchers found that strokes associated with amphetamine use among young people 18 to 44 years of age represented a rapidly growing category. In fact, the Texas group found that “the rate of strokes among amphetamine abusers was increasing faster than the rate of strokes among abusers of any other drug.”

Curiously, amphetamine and cocaine are responsible for different kinds of strokes. An ischemic stroke, the classic blood clot, is caused by a blockage of blood vessels to the brain. Hemorrhagic strokes result from bleeding caused by the rupture of a weakened blood vessel. In general, hemorrhagic strokes are more severe and more likely to cause death. And what the researchers found was more bad news for speed freaks: “Amphetamine abuse was strongly associated with hemorrhagic stroke, but not with ischemic stroke.” Cocaine abuse was more robustly linked to ischemic strokes. So, it’s not surprising that when it comes to drug and fatal strokes, the clear winner was amphetamine. It’s not entirely clear what causes the difference, but the investigators pointed out that meth injections in lab animals can cause microhemorrhaging, heart attacks, fragmentation of capillary beds, and something called “poor vascular filling.” For cocaine, the culprits are vasoconstriction and disrupted regulation of blood pressure.

More than 14 percent of strokes in hospitals “were accounted for by abuse of drugs,” the researchers wrote. The data showed that for patients with hemorrhagic strokes, “only amphetamine abuse, coagulation defects, and hypertension were strong independent predictors of in-hospital death.”

So what can we conclude? Either the number of speed users in these communities is increasing, or the existing speed communities are using the drug more intensely. Since the rate of increase of speed use was relatively modest during the study years, the researchers concluded that “increased rate in our hospital population is because of the increased intensity of methamphetamine use.” Meaning higher dosages, stronger meth, and more needles.

Sadly, much of this has been known since it least 1990. In that year, research published in the Annals of Internal Medicine, based on a study of stroke victims at San Francisco General Hospital, concluded that “the possibility of serious and sometimes fatal cerebrovascular accidents in people taking potent stimulants and using the intravenous route of administration is not as widely known as it needs to be.”

About 800,000 people in the U.S. suffer a stroke each year, according to figures from the U.S. Centers for Disease Control and Prevention. Strokes are considered America’s leading cause of serious long-term disability.

de los Rios F., Kleindorfer D.O., Khoury J., Broderick J.P., Moomaw C.J., Adeoye O., Flaherty M.L., Khatri P., Woo D. & Alwell K.;  (2012). Trends in Substance Abuse Preceding Stroke Among Young Adults: A Population-Based Study, Stroke, 43 (12) 3179-3183. DOI: 10.1161/STROKEAHA.112.667808