The Perils of Polydrug Abuse

Methadone and benzodiazepines.

For patients in opiate treatment programs, benzodiazepine use represents both a barrier to recovery and a potentially life threatening situation. The combination of benzodiazepines and methadone can lead to fatal overdose.

The five most commonly prescribed benzodiazepines fall into two major categories. High potency medications include Xanax (Alprazolam), with a short half-life of six to 12 hours, and Ativan (Lorazepam), with a slightly longer half-life. The low-potency benzodiazepines are represented by the short-lived Restoril (Temazepam), and the longer-lasting Valium (Diazepam), with a half-life of 20 to 100 hours. The fifth popular benzodiazepine, Klonopin (Clonazepam) is a high-potency drug with a half-life of 18 to 50, the highest in its class. Their primary clinical uses include the treatment of anxiety disorders, insomnia, convulsions, and muscle spasms. They also find use in the treatment of acute mania, catatonia, and detoxification from alcohol.

While some patients are able to use benzodiazepines safely at low dosage for years, patients with a history of opiate addiction are a high-risk category for these medications. Tolerance develops quickly in patients who use benzodiazepines to “boost” the effect of methadone, or as a sedative during opioid withdrawal. Since high doses of benzodiazepines cause respiratory depression, even among opioid users who have developed a high tolerance to such effects, the combination increases the risk of severe intoxication, injuries, or fatal overdose.

In addition, benzodiazepines and methadone interact pharmacologically through the actions of the CYP450 liver enzyme, which detoxifies both substances. If the work load for CYP450 becomes too great, the result can be an accumulation of high levels of methadone in the body.

It has been estimated that “80 percent of benzodiazepine abuse is part of polydrug abuse, most commonly with opioids.” In a two-year study by the National Institute of Drug Abuse (NIDA), 73 per cent of heroin users also used benzodiazepines more often than weekly.

According to a recent Canadian study of 172 subjects, the reported lifetime prevalence of benzodiazepine abuse in methadone maintenance patients ranged from 67 to 94 percent, with two-thirds of the patients reporting benzodiazepine use during the past 6 months. Patients who took benzodiazepines also reported more previous opioid overdoses, according to the study. And women are more likely than men to abuse benzodiazepines. In a study by Australia’s National Drug and Alcohol Research Centre (NDARC), researchers conducting a five-year study of heroin overdoses in New South Wales found that attempted suicide by benzodiazepine overdose was more common than attempted suicide by heroin overdose.

Methadone maintenance patients need to be questioned carefully about benzodiazepine use. By doing so, physicians and other caregivers can work toward actively decreasing the likelihood of treatment failure or fatal methadone overdose.

Photo Credit: www.drug.uz

House Tobacco Bill Moves to Senate

Bill would give FDA control over nicotine products.

It is one of the most popular drugs in America, used and abused by millions. Yet it is not regulated by any government agency. There is no federal testing, no quality control, no standards of any kind. As representative Jared Polis (D-Colorado) memorably told the U.S. House of Representatives: “Tobacco use is the single largest cause of preventable death in our country. Yet it continues to receive less regulation than a head of lettuce.”

That deplorable situation may soon change, as the U.S. Senate takes up a bill recently passed by the House. The legislation would give the Food and Drug Administration (FDA) broad new powers to regulate the tobacco industry for the first time in history.

The house bill is similar to one passed last session, which died in the Senate after it was opposed by the Bush administration. According to reports by Duff Wilson in the New York Times, the legislation would enable the FDA to “approve or reject current and proposed tobacco products and ingredients, based on scientific and health findings.” The FDA would be able to restrict harmful chemicals and reject new tobacco products, but in a major concession to Philip Morris, the nation’s largest cigarette maker, the bill “would not allow a complete ban of tobacco products, or permit the agency to order the complete removal of nicotine.” The Times article also said the bill would lead to larger and more graphic warning labels on cigarette packs.

Senator Edward Kennedy (D-Massachusetts) said he plans to introduce the bill later this month. The legislation is supported by President Obama. An official statement released by the administration said that tobacco use “is a major factor driving the increasing costs of health care in the U.S. and accounts for over a hundred billion dollars annually in financial costs to the economy.” Attempts to mandate FDA regulation of tobacco have been made repeatedly over the past decade.

Tobacco industry supporters have vowed to fight the bill on the Senate floor. Senator Richard Burr (R-North Carolina) said he was considering a filibuster. House Republican Virginia Foxx, also of North Carolina, derided the legislation as “an unnecessary and expensive regulatory scheme at the expense of our rural farming communities.” North Carolina is the country’s leading tobacco growing state.

A spokesperson for the American Heart Association said the Senate was expected to act quickly on the bill: “This has certainly been a passion of Senator Kennedy’s and a legacy he can leave to the public health of America.”

Photo Credit: Winston-Salem Journal

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Gimme a Drink--But Hold the Acetaldehyde

Another look at alcohol and cancer.

If beverage alcohol were a new drug, it would face an uphill battle to make it through the Food and Drug Administration (FDA) pipeline. Why? Because the amount of acetaldehyde in alcoholic drinks—combined with acetaldehyde from other sources—might be too carcinogenic to pass muster under existing regulations.

When drinkers drink, the first thing that happens is that enzymes convert the alcohol into acetaldehyde. Previous research has shown that this common organic chemical is implicated in certain cancers, particularly cancers of the digestive tract. Studies at the National Institutes of Health (NIH) showed that the concentration of acetaldehyde measured in human saliva during drinking episodes was sufficient to produce the kind of damage to DNA that can result in cancer.

In a study published recently in the journal Addiction, researchers from Canada and Germany showed that heavy drinkers ingest enough acetaldehyde to raise their lifetime cancer risk to as high as 1 in 1,000. The study concludes: “The life-time cancer risks from acetaldehyde from alcoholic beverages greatly exceed the usual limits for cancer risks from the environment.”

The real problem comes when alcohol is used in combination with acetaldehyde from other sources, such as tobacco, food flavorings, pesticides, and perfume. Heavy drinkers “face a magnitude of risk requiring intervention.” According to Dr. Jurgen Rehm at Canada’s Centre for Addiction and Mental Health (CAMH), quoted in Science Daily: “Most risk assessments to date were based on one source of exposure only. This has led to a negligence of the overall risk.”

According to the Science Daily article, “Alone, the risks associated with surpassing limits of acetaldehyde from the air may not yet be alarming, but for heavy drinkers and smokers, it adds to the acetaldehyde levels already received from these sources. This overall risk then surpasses established safety limits.” To make matters worse, acetaldehyde is a common substance in tobacco smoke—and alcoholics are often heavy cigarette smokers.

A Finnish drug company is currently conducting clinical trials of a time-release capsule of the amino acid cysteine, which can bind with acetaldehyde and render it inactive.

In a related development, a study in PLoS Medicine appeared to demonstrate that people who suffer from the so-called alcohol flush reaction—primarily Japanese, Chinese, and Koreans—are at increased risk for throat cancer. The culprit? An excess of acetaldehyde.

Photo Credit: National Institute of Standards and Technology

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Drug Addicts Punished in New York Prisons

Drug offenders get “the box” instead of treatment.

The common practice of placing drug addicts in “disciplinary segregation” for drug use violations in New York state prisons has drawn fire from Human Rights Watch. The international human rights group issued a report condemning the practice of placing addicts in “the box” and denying them treatment for their drug dependence, calling it “cruel, inhuman, and degrading treatment.”

In the report, entitled “Barred from Treatment: Punishment of Drug Users in New York State Prisons,” Human Rights Watch notes that even addicts who are allowed to seek treatment face major delays “because treatment programs are filled to capacity.” New York State Assemblyman Jeff Aubry, chair of the State Committee on Corrections, told the investigators: “Denying treatment to inmates who suffer from a drug dependency is illogical and counterproductive to the goal of rehabilitation.”

Some of the findings in the report are shocking: “Despite overwhelming evidence that medication-assisted therapy is the most effective treatment for opiate addiction, the majority of New York State prisoners dependent on heroin or other opiates have no access to methadone or buprenorphine.” Furthermore, the state’s Department of Correctional Services “has conducted few evaluations of its own treatment programs.” Prison officials have estimated that as many as eight out of ten inmates have substance abuse problems. A National Institute of Drug Abuse (NIDA) study earlier this year, covered in a previous post, estimated that only one-fifth of the nation’s inmates needing formal treatment are able to get it.

The report comes just as New York legislators have agreed to revamp the so-called Rockefeller drug laws, which are among the strictest in the nation. “Reforming the Rockefeller drug laws to prevent drug users from being sentenced to long prison sentences is critically important, said Megan McLemore, a researcher with Human Rights Watch. “But timely and effective programs must be available to serve the inmates still in prison.” McLemore said in a press release that “discipline should be proportionate to the offense, and should never prevent prisoners from getting the treatment they need.”

As a prisoner at Attica told Human Rights Watch, “Here is a notice telling me ‘it could be a long time’ until I get into treatment again. There’s plenty of room for me in the box, but not in a program.”

Photo Credit: ACS blog

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Economy Down, Addictions Up?

Do people drink more or less during a recession?

According to a report from Mintel, a consumer research firm, "sin stocks" historically have performed well during times of economic recession. "Chocolate, cigarettes and alcohol again seem relatively recession-proof," comments Marcia Mogelonsky, senior analyst at Mintel.

Lest anyone think that somehow the tobacco dragon has been tamed after 45 years of public health announcements (surely no one can afford cigarettes anymore?), Mintel documents that "cigarette and tobacco product sales increased 44% from 2003 to 2007 to $103 billion.” Moreover, “as price and tax increases continue to take hold, Mintel projects that the cigarette and tobacco market will grow 28% through 2011 (to $132 billion).”

There is also a bull market for chocolate: “Innovative, dark and premium chocolates are extremely popular, so Mintel expects Americans to continue indulging in this favorite treat. The market research firm predicts 4% annual sales increases each year for the next six years.”

As for alcohol, a mixed picture: “Motivated by high gas prices and expensive bar tabs, more Americans are opting to drink at home. But that doesn't mean they're drinking less. New research from Mintel reveals the market for at-home alcohol is expected to reach $77.8 billion in 2008, a 32% increase from 2003.” Mintel expects in-home alcohol sales to rise as much as 5% per year.

However, earlier studies of the matter have been inconclusive. Melissa Healy reported in the Los Angeles Times that the connection between “hard times and hard drinking isn't clear. In the U.S., a state's alcohol consumption declined by 3% for every one percentage point increase in that state's unemployment rate, according to one study. But another study found that rates of binge drinking went up 8% when unemployment rose 5%. The increase in binge drinking was concentrated most heavily among adults who were still employed.”

In the Los Angeles Times article, Andrew Barnes of the UCLA School of Health Services, estimates that “during this economic decline, those who drink alcohol will consume 12% less (10% less nationally), there will be a 13% reduction in alcohol-impaired driving, and a 1.2% decrease (1% nationally) in the number of people who drink at all. The probability of being a heavy drinker (consuming 60 or more drinks per month) is predicted to decline in California by 31%.”

Graphics Credit: www.bloggingstocks.com

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Modafinil May Be Addictive

NIDA study casts doubt on safety of “brain booster” drug.

Despite the headlines, most new drugs are not addictive. Very few medications show the distinctive side effects associated with clinical drug addiction: tolerance, withdrawal, and continued use despite adverse consequences. Such drugs are relatively rare—so it was with interest and alarm that addiction specialists confronted a small pilot study, led by Dr. Nora Volkow of the National Institute on Drug Abuse (NIDA), which appeared to demonstrate that the sleep drug modafinil has addictive potential.

Modafinil, sold as Provigil, has found increasing off-prescription use for the treatment of ADHD and other psychiatric disorders. The drug is also being used as a so-called “cognitive enhancement” drug or “brain booster,” particularly among college students and military field personnel. Modafinil had even shown early promise as a drug for the treatment of cocaine addiction.

In the March 18 issue of the Journal of the American Medical Association (JAMA) , the researchers reported on levels of extracellular dopamine in the brains of 10 healthy men on either placebo or modafinil.

According to the researchers, “Modafinil acutely increased dopamine levels and blocked dopamine transporters in the human brain. Because drugs that increase dopamine have the potential for abuse, and considering the increasing use of modafinil for multiple purposes, these results suggest that risk for addiction in vulnerable persons merits heightened awareness.”

Scientists were initially excited about a drug which showed stimulant properties but did not appear to have a direct effect on the dopamine pleasure systems of the brain—a finding that set it apart from drugs like amphetamine and cocaine. However, as reported online by Heidi Ledford of Nature, “Animal studies showed that rodents that lack dopamine receptors are unresponsive to the drug, and in 2006, researchers found that modafinil affects dopamine levels in the brains of rhesus macaques.”

Dr. Volkow stressed that patients taking modafinil for recognized medical conditions such as narcolepsy should continue to do so, while doctors should monitor modafinil patients for signs of dependency.

Still, dopamine is not all there is to addiction. As reported in Nature, Bertha Madras of Harvard Medical School notes that some drugs that boost dopamine have other properties that make them aversive, and therefore not addictive. “The full spectrum of the pharmacology of the drug is what drives the abuse potential,” she said.

[The following added 8.00 pm 3-18-09]: In addition, Corpus Callosum has an excellent in-depth look at why the results of the study should be interpreted conservatively.]

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Utah Legislator Calls for Tax on Coffee

States look to addictions as a revenue stream.

Are caffeine revenue streams the next big thing, or a bright idea whose time will never come? Will we see the staging of a Boston (make that Salt Lake City) Coffee Party by disgruntled, under-caffeinated voters, if the state of Utah has its way?

We do it with tobacco products. We do it with alcoholic beverages. We slap a hefty extra “sin tax” on addictive but legal products as an easy source of revenue. Times are tough. State revenue streams have dried up. But coffee? Caffeinated soft drinks?

Taxing caffeine would be “like taxing candy,” according to one Utah resident, reacting to a state legislator’s call for a tax on caffeine products. The legislator in question, Republican state representative Craig Frank, suggested the measure after efforts to raise cigarette taxes in the state failed. The initial proposal centered on “cold caffeine” such as canned sodas, but was quickly broadened to include coffee and other caffeine products

Frank told the Salt Lake City Tribune in an article by Robert Gehrke that if the state was intent on “going after people who have problems with addiction for a revenue stream,” a tax on caffeine would be more broad-based than existing “sin taxes” on alcohol and cigarettes—two other highly addictive but legal substances. The government itself, said Frank, is “addicted to the fee revenues. So in light of that... why not cold caffeine?” Ultimately, why not caffeine, period? Frank pointed out that caffeine, like alcohol and nicotine products, has been linked to health problem, such as spontaneous abortion.

A recent study by the Rockefeller Institute of Government showed that Utah lost 16.5 per cent in tax revenues in the fourth quarter of 2008. The National average was 3.6 per cent.

In 2003, Seattle voters rejected a similar initiative that would have imposed a 10-cent tax on every cup of espresso-based coffee. Vancouver, B.C., tried and failed to enact a similar measure. Recently a councilperson in Nashville, TN, has also suggested a coffee tax. Last month, California Assemblyman Tom Ammiano proposed to extract substantial state revenue from a sales tax on marijuana.

All of these efforts have met with a significant lack of enthusiasm on the part of the citizenry.

Picture Credit: Worth1000

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