Gates, Bloomberg Target Cigarettes

Billionaires pledge $500 million, but will it do any good?

If money were all it took, tobacco smoking would be on the run after Bill Gates and Michael Bloomberg jointly pledged last month to fight tobacco use worldwide, especially in low- and middle-income countries, through the Bill and Melinda Gates Foundation and Johns Hopkins University.

Mayor Bloomberg, who has been involved in anti-smoking campaigns for years, admitted at a joint news conference that "all the money in the world will never eradicate tobacco. But this partnership underscores how much the tide is turning against this deadly epidemic."

The program, put together by Bloomberg and Dr. Margaret Chan of the World Health Organization (WHO), is an ambitious, multi-faceted effort to be coordinated by the Bloomberg Initiative to Reduce Tobacco Use, the WHO, the World Lung Foundation, the Johns Hopkins Bloomberg School of Public Health, and the Centers for Disease Control and Prevention (CDC).

As Donald G. McNeil described the $500 million program, dubbed Mpower, in the July 24 New York Times: "It will urge governments to sharply raise tobacco taxes, prohibit smoking in publics places, outlaw advertising to children and cigarette giveaways, start antismoking advertising campaigns and offer people nicotine patches or other help quitting." The program also intends to bring "health officials, consumer advocates, journalists, tax officers and others from third world countries" to the U.S. for workshops and training.

It will not be the first such effort--far from it. Troubled by the rising tide of nicotine dependence among the common folk, Bavaria, Saxony, Zurich, and other European states outlawed tobacco at various times during the 17th Century. The Sultan Murad IV decreed the death penalty for smoking tobacco in Constantinople, and the first of the Romanoff czars decreed that the punishment for smoking was the slitting of the offender’s nostrils.

In America, the Prohibition years from 1920 to 1933 coincided with a short-lived effort to prohibit cigarettes. Leaving no stone unturned in the battle to eliminate drugs and alcohol from American life, Henry Ford and Thomas Edison joined forces to wage a public campaign against the “little white slavers.” Edison and Ford wanted to stamp out cigarette smoking in the office and the factory. Although that effort would have to wait another 75 years or so, New York City did manage to pass an ordinance prohibiting women from smoking in public. (See Siegel, Ronald K. Intoxication: Life in Pursuit of Artificial Paradise). Fourteen states eventually enacted various laws prohibiting or restricting cigarettes. By 1927, all such laws had been repealed.

Finally, Adolf Hitler himself took on the battle against cigarettes--and lost. In 1942, after letting loose a torrent of misbegotten screed about "the wrath of the Red Man against the White Man," Hitler, in one of the most aggressive anti-smoking campaigns in history, banned smoking in public places and slapped heavy taxes on tobacco. But by the mid-1950s, smoking in Germany exceeded prewar levels.

There is no evidence to suggest that any culture that has ever taken up the smoking of tobacco has ever wholly relinquished the practice voluntarily.

Photo Credit: National Health Service

Feeling a Need for Weed?

U.K. book on cannabis dependency.

For James Langton, author of "No Need for Weed: Understanding and Breaking Cannabis Dependency", it was no easy task to find information and support when he sought to rid himself of a 30-year marijuana relationship. Through his own efforts, and the early help of Marijuana Anonymous, Langton became abstinent. And in an effort to help others in the same boat, he published his own account, a combination of personal memoir, anecdotes from pot smokers drawn to his own Clearhead support website, and a thoughtful assessment of the nature of both active marijuana dependency and marijuana withdrawal.

Langton has written a valuable and insightful book, dedicated, he says, to those "who fell blindly in love with the drug, in all its forms, without a second thought. But this book is also for those who, just like me, found that ending this love affair was much more difficult than they could ever have imagined...."

The delights of pot are self-evident: "It didn't feel wrong, dangerous or difficult; I just enjoyed life more when my senses were heightened and when I allowed the reality of everyday life to become a little distorted. After a couple of tokes, I seemed to feel the disparate parts of my consciousness clicking into place."

So why quit at all? "For a start," writes Langton, "I wanted to be clearheaded again; to be able to remember things; to be aware of time passing at normal speed, not stretched or shrunk. I wanted more of a social life. I wanted to be more confident and not so self-obsessed. I wanted to be in control and less lazy." Finally, he felt ready to "turn away from a pleasure that had evolved into a routine, then into a habit, and finally into full-blown dependency."

Metabolically, Langton had reached a point of addiction: "I needed to smoke just to feel normal. My tolerance for dope had reached such a point that if the THC in my system fell below a certain level I would feel a deep lack, a terrible emptiness."

The author found that one aspect made quitting "harder and more demoralizing" than necessary --"the almost universal dismissal from the medical and drug treatment professions about the reality of cannabis withdrawal.... very little specialist help is available to anybody who has lost control over their dope smoking."

Langton's explanation of what had happened to him is simple and understandable: "Our dopamine levels aren't meant to be tuned to such a high pitch on an everyday basis. Maybe a few times a month or the occasional binge, but if you're smoking relentlessly day after day, particularly strong skunk, then is it any wonder you might find it hard to take pleasure in the ordinary things of life?"

Langton also offers vivid descriptions of common withdrawal effects, including "the feeling of being overwhelmed by even the simplest interactions with other people, or becoming frustrated by what you would normally consider straightforward tasks." He also noted that "night sweats are difficult because, combined with light sleeping, they can cause discomfort to your partner as well.... The sweating can last for anything up to 21 days, but usually you are over the worst after about 10." In addition, Langton suggests that if you are experiencing an extreme loss of appetite, "be reassured that this is a very common symptom. The important thing is to make sure you are taking some nutrients onboard, otherwise you will start to feel week, light-headed and slightly sick." He warns of vivid dreams, and episodes of outsized anger. (The author's salient advice on anger: You can take it back.) As for energy levels, the whole withdrawal experience can "feel like jet lag, and the best advice is to treat it as such; in other words, try not to go to bed as soon as you come home from work..."

How long does it take? "At Clearhead we have found that it takes, on average, around four to six weeks for most people to fully adjust to not using cannabis.... others will still hit upon lingering symptoms up to two months after smoking their last joint."

Overall, a good read, full of telling anecdotes, personal honesty, and practical advice.

Ten Ways to Battle Coffee Addiction

Caffeine-free energy boosters

(From the mailbag)

Kelly Sonora at the Nursing Online Education Database (NOEDb) recently sent me an article by Christina Laun, entitled "50 Ways to Boost Your Energy Without Caffeine." The complete article is available on the NOEDb web site. If you are making an effort to decrease reliance on coffee, Laun writes, the suggestions will "give you a boost when you're feeling sleepy or prevent tiredness altogether."

Herewith, a sampling:

--Turn on the lights. Your body responds naturally to changes in light, so if it's unnaturally dark where you're working or sleeping it may make staying alert a lot harder. Try keeping your blinds open a bit so you'll wake up naturally in the morning or adding a few extra lights to your workspace to keep you from feeling sleepy throughout the day.

--Examine your emotions. Stress, depression and other negative emotions can take a heavy toll on your energy levels. Your exhaustion may have a lot to do with how you're feeling mentally, so take the time to deal with your emotions or get help if you need it.

--Don't linger in bed. Hitting the snooze button in the morning may delay the inevitable time when you do have to get up, but it's not doing you any favors in the long run. Challenge yourself to get up and move around for at least 10 minutes to see if you're still super tired. Chances are, once you get up you'll be ready to start your day.

--Eat smaller, more frequent meals. Eating meals that are infrequent can cause your blood glucose to spike and crash, leaving you tired and hungry. And digesting huge meals can steal energy you need for other things. Instead, eat smaller meals throughout the day so you can keep your energy level and keep yourself feeling great.

-- Cut down on alcohol. Alcohol may appear to make you sleepy, but it can actually ensure that you get a much lower quality of sleep than you would otherwise. Keep it in moderation so it won't affect your sleep and make you groggy the next day.

--Get out of the house. Sunlight can help wake you up and help you stay up, so take a trip outside to catch some rays and get some fresh air.

--Get away from your desk. Hours upon hours of sitting at your desk can start to sap your energy and make you plead for it to be 5 o'clock already. Give yourself a quick pick-me-up by stepping away from your desk for a bit for a trip to the water fountain, a walk around the office or just a short break.

--Listen to your favorite up-tempo songs. If you can listen to music at work, why not put on some tunes that will get your heart pumping and make you want to dance? It's a surefire way to beat the mid-afternoon slump.

--Stop slouching. Slumping down at your desk isn't doing you any favors in the alertness category. Sitting up at your desk, in an ergonomically friendly way, can make you feel more alert and ready to work.

--Avoid coworkers who sap your energy. Everyone has that one coworker who is so glum, negative or boring that they just suck the energy right out of you. When it's possible, keep this person away from you to save your energy and maybe your sanity too.

Coffee and Cigarettes

Recovering alcoholics and their drugs.

It's no secret that alcohol and cigarettes go together. And it is common knowledge--and an AA truism--that recovering alcoholics take to strong black coffee like ducks to water.

Now comes a study of Alcoholics Anonymous participants in Nashville, to be published in the October issue of Alcoholism: Clinical and Experimental Research, which verifies the obvious, with a twist. Of 289 AA members interviewed by Dr. Peter R. Martin and coworkers at the Vanderbilt Addiction Center, 56.9% of respondents were cigarette smokers (approximately 20% of all adult Americans smoke cigarettes).

When it came to coffee, however, 88.5% of AA attendees were coffee drinkers, and a third of them drank more than 4 cups a day. "The most important finding," said Dr. Martin in a Vanderbilt University press release, "was that not all recovering alcoholics smoke cigarettes while almost all drink coffee."

Does all that coffee guzzling and cigarette smoking help or hinder recovering alcoholics in their quest for sobriety? The answer is: nobody quite knows. Dr. Martin, professor of psychiatry and pharmacology at Vanderbilt and lead investigator of the study, entitled "Coffee and Cigarette Consumption and Perceived Effects in Recovering Alcoholics Participating in Alcoholics Anonymous in Nashville, TN," put it this way in Science Daily: "Is this behavior simply a way to bond or connect in AA meetings, analogous to the peace pipe among North American Indians, or do constituents of these natural compounds result in pharmacological actions that affect the brain?"

"It's possible that coffee is even a gateway drug, with coffee drinking beginning at about the time persons begin using alcohol," said Robert Swift of the Brown University Medical School. "In addition, a potential negative interaction is coffee's known negative effects on sleep."

Selena Bartlett of the Ernest Gallo Clinic and Research Center of the University of California, San Francisco, offers the same concerns about cigarettes. A reliance on smoking by recovering alcoholics has a biological basis, she believes, and may increase the odds of relapse. In a HealthDay article by Steven Reinberg, Bartlett said: "My prediction would be that the relapse rates among smokers is higher." Since nicotine and alcohol addiction are so often found together, Bartlett thinks they should also be treated together, and is studying the anti-smoking drug Chantix for this purpose. "The drug inhibits the effect of nicotine, and by doing that, you may also reduce the euphoric effects of alcohol at the same time," she said. "We already have some evidence that it may work."

Varenicline, currently marketed by Pfizer for smoking cessation under the trade name Chantix, caught the attention of alcohol researchers when it dramatically curbed drinking in alcohol-preferring rats. The synthetic drug was modeled after a cytosine compound from the European Labumum tree, combined with an alkaloid from the poppy plant. An estimated 85 per cent of alcoholics are also cigarette smokers. (Chantix has lately been implicated, along with a dozen other anti-seizure medications, in suicidal ideation in some patients).

"I think it is important for alcohol researchers and clinicians to know that alcoholics, even those who do not use other illicit drugs, are not just addicted to alcohol, but use other psychotropic drugs like caffeine and nicotine," said Professor Swift of Brown University. "A second important aspect is the finding that rates of smoking are much higher in alcoholics in recovery than in the general population.... Yet, AA tolerates or otherwise does not address smoking in its members."

Dr. Martin said that more detailed analyses of the results will help determine "whether these changes in coffee and cigarette use are predictive of recovery from alcoholism per se."

Photo credit: AA-Carolina.org


alcoholics anonymous smoking nicotine

Drugs for Alcoholism

Different meds for different drinkers


Although there are still only three drugs officially approved by the FDA for the treatment of alcoholism, the research picture is beginning to change. In an article by Greg Miller published in the 11 April 2008 edition of Science, alcoholism researcher Stephanie O'Malley of Yale University said: "We have effective treatments, but they don't help everyone. There's lots of room for improvement."

The medications legally available by prescription for alcoholism are: disulfiram (Antabuse), naltrexone (Revia and Vivitrol), and acamprosate (Campral), the latest FDA-approved entry. A fourth entry, topiramate (Topamax), is currently only approved by the Food and Drug Administration (FDA) for use against seizures and migraine. The controversial practice of “off-label” prescribing—using a drug for indications that are not formally approved by the FDA—has become so common that Johnson & Johnson said it had no plans to seek formal approval for the use of Topamax as a medicine for addiction. (See my post,"Topamax for Alcoholism: A Closer Look").

Addiction experts are beginning to focus on which treatment drugs work best for different types of alcoholics. Two recent discoveries might help clarify the picture. Psychopharmacologist Charles O'Brien at the University of Pennsylvania reported that alcoholics with a specific variation, or allele, of a prominent opioid receptor gene were more likely to respond positively to treatment with naltrexone. Other work reported in the February 2008 Archives of General Psychiatry came to the same conclusion.

The second research insight builds on a lifetime of work by Robert Cloninger at Washington University in St. Louis. Cloninger discovered that alcoholics come in two basic flavors--Type 1 and Type 2. Type 1, the more common form, develops gradually, later in life, and does not necessarily require structured intervention. Type 1 alcoholics do not always experience the dramatic declines in health and personal circumstances so characteristic of acute alcoholism. These are the people often found straddling the line between alcoholic and problem drinker. In contrast, so-called Type 2 alcoholics are in serious trouble starting with their first taste of liquor during adolescence. Their condition worsens with horrifying speed. They frequently have a family history of violent and antisocial behavior, and they often end up in prison. They are rarely able to hold down normal jobs or sustain workable marriages for long. Type 2s, also known as “familial” or “violent” alcoholics, are likely to have had an alcoholic parent.

Type 1 drinkers, who only get in trouble gradually, are also known as "anxious" drinkers, and research suggests that they may respond better to medicines that alleviate alcohol-related anxiety, such as Lilly's new suppressor of stress hormones, known as LY686017. (See my post, "Drug That Blocks Stress Receptor May Curb Alcohol Craving "). Researchers at the National Institute of Alcohol Abuse and Alcoholism (NIAAA), working with colleagues at Lilly Research Laboratories and University College in London, announced the discovery of a drug that diminished anxiety-related drug cravings by blocking the so-called NK1 receptor (NK1R). The drug “suppressed spontaneous alcohol cravings, improved overall well-being, blunted cravings induced by a challenge procedure, and attenuated concomitant cortisol responses.”

The NIAAA researchers are making effective use of recent findings about the role played by corticotrophin-releasing hormone (CRH) in the addictive process. CRH is crucial to the neural signaling pathway in areas of the brain involved in both drug reward and stress. As it happens, NK1R sites are densely concentrated in limbic structures of the mid-brain, such as the amygdala, or so-called “fear center.”

Researchers are understandably excited about these developing insights. Psychopharmacologist Rainer Spanagel of Germany's Central Institute of Mental Health in Mannheim called such research "a milestone in pharmacogenetics." In Greg Miller's Science article, Willenbring of NIAAA predicted that the field is poised for a "Prozac moment," marked by the discovery of "a medication that's perceived as effective, that's well-marketed by a pharmaceutical company, and that people receive in a primary-care setting or general-psychiatry setting."

In "Days of Wine and Roses, " the 1960s film about alcoholism, Jack Lemmon played a character who embodied Type 2 characteristics--early trouble with alcohol, extreme behavioral dysregulation, poor long-term planning, and a hollow leg. His wife, played by Lee Remick, demonstrates the slower, more measured descent from problem drinking into clinical alcoholism that characterizes Type 1 alcoholics. Research now suggests that Lee Remick might do better on LY686017, while Jack Lemmon's character would be a promising candidate for treatment with naltrexone.

Photo credit: About Alcohol Information

alcoholics anonymous

Drugs for Cocaine Addiction

Researchers target GABA, noradrenaline.

According to Catalyst Pharmaceutical Partners, a company conducting research on drugs for the treatment of addiction, "The U.S. Food and Drug Administration has recognized that cocaine addiction is a 'serious, life-threatening condition for which there is no current drug treatment,' and the National Institute on Drug Abuse (NIDA) has stated that finding a pharmacological treatment for cocaine addiction is their number one research priority."

Other researchers view it differently, however. Allan Parry, a drug counsellor in Liverpool, U.K., told New Scientist that such work was "only likely to be relevant to a tiny minority of people. People often give up cocaine because their lifestyle changes or they just grow up."

Fighting fire with fire--using drugs to treat drug addiction--will likely remain a controversial approach for years to come.

What is the rationale for the use of drugs in the treatment of drug addiction? There are two basic approaches. Scientists look for medications that help patients initiate abstinence, and they look for drugs that help prevent relapse once the patient has achieved abstinence. The categories are not hard and fast. For example, a drug that effective reduces the reinforcing effects of cocaine by reducing the intensity of withdrawal can theoretically perform both functions at once. On the other hand, a drug that blunts the euphoric effects of cocaine--a drug that takes away the best of the buzz, no matter how much cocaine is ingested--can also succeed at the twin tasks of abstinence initiation and relapse prevention.

The search for medications with which to treat cocaine addiction has been in progress much longer than equivalent efforts aimed at methamphetamine addiction. One research target of long standing is modafinil, an odd-duck drug sold as Provigil for the treatment of narcolepsy. A mild stimulant, modafinil does a little bit of everything, pharmacologically tweaking dopamine, noradrenaline, anandamide and GABA receptor systems. Perhaps for this reason, the drug seemingly has been tried for almost everything, from Alzheimer's to atypical depression to jet lag. The U.S. military has reportedly shown some interest in it.

According to published research by Kyle M. Kampman in the June 2008 Addiction Science and Clinical Practice (PDF), modafinil-treated human subjects used less cocaine than placebo-using counterparts did in several recent small-scale studies. "In a double blind pilot trial with 62 cocaine-dependent patients, those who received modafinil submitted more cocaine-metabolite-free urine samples than placebo-treated patients (42 vs. 22 percent; Dackis et al., 2005)."

Propranolol, better known as the beta-blocker Inderal, works primarily by suppressing adrenaline and noradrenaline levels. In human studies to date, propranolol has shown itself most effective with the most severely cocaine-addicted patients. Studies by Kampman have shown that propanolol-treated patients stay in treatment longer than patients in control groups do.

Specific research on relapse prevention strategies has focused on GABA-enhancing drugs that inhibit cocaine reinforcement by secondarily blocking the dopamine surge characteristic of cocaine intoxication. In addition to vigabatrin, discussed in the previous post, topiramate is another particularly well-suited candidate for relapse prevention. Known as Topamax, and prescribed for seizures and migraines, the drug has shown early promise: "In a 13-week, double-blind, placebo-controlled pilot trial of topiramate involving 40 cocaine-dependent patients.... more of those on topiramate achieved at least 3 weeks of continuous abstinence (59 vs. 26 percent)."

Surprisingly, the granddaddy of all anti-addiction drugs--Antabuse--has made a comeback as a subject of study for cocaine addiction, even though it has never been spectacularly effective in its original application as a relapse prevention drug for alcoholics. Disulfiram, as it is known chemically, causes unpleasant physical sensations, including vomiting, when combined with even small amounts of alcohol. It does so by inhibiting the enzymes responsible for degrading alcohol. Even a little becomes too much. In similar fashion, disulfiram retards the breakdown of cocaine, leading to extremely high levels that induce paranoia and anxiety rather than a pleasurable, if extreme, high. At least four published trials have demonstrated reduced cocaine use in disulfiram-treated patients, according to Kampman's paper . One important downside to using Antabuse for cocaine addiction is that serious complications might occur if alcohol is added to the mix.

Finally, and still well into the future, is the prospect of relapse prevention therapy by means of a vaccine--an entirely different mechanism of approach. Research has shown that it is possible to produce "cocaine-specific antibodies that bind to cocaine molecules and prevent them from crossing the blood-brain barrier, thereby blunting the drug's euphoric and reinforcing effects," Kampman's paper asserts. A vaccine called TA-CD has tested well in preliminary studies.

No Pill for Stimulant Addiction

Meth and cocaine continue to elude researchers.

Despite promising trials of several compounds, methamphetamine addiction remains largely impervious to anti-craving pills and other forms of drug treatment. According to a paper in the June issue of Addiction Science and Clinical Practice, "currently, no medications are approved by the FDA for the treatment of stimulant dependence. However, recent advances in understanding... have allowed researchers to identify several promising candidates."

The paper's author, Dr. Kyle Kampman of the University of Pennsylvania School of Medicine and Treatment Research Center, notes that "the demand for treatment for cocaine dependence remained roughly level from 1992 to 2005, while the demand for treatment for amphetamine dependence increased about eight-fold." (See chart above).

As I wrote earlier ("FDA Puts Coke/Meth Treatment on Fast Track"), the U.S. Food and Drug Administration (FDA) in January gave Fast Track designation to vigabatrin, sold as Sabril by Ovation Pharmaceuticals. Ovation is collaborating with the NIDA on Phase II studies to evaluate the safety of Sabril, with Phase III trials scheduled for the end of this year.

Vigabatrin, an anti-epilepsy drug called Gamma-vinyl-GABA, or GVG for short, showed early promise for use with cocaine addicts in a 60-day study and appears to increase GABA transmission. GABA has an inhibitory effect on dopamine and serotonin release.

Another entry in the vigabatrin sweepstakes, Catalyst Pharmaceuticals, is also testing its version of the drug, dubbed CPP-109, for the treatment of methamphetamine addiction in Phase II double-blind, placebo-controlled studies. Patrick J. McEnany, chief executive officer of Catalyst, commented, "We are excited to follow up on our cocaine trial with the initiation of our second, large-scale U.S. Phase II trial with CPP-109, this time as a potential treatment for methamphetamine addiction. As with cocaine, we believe that CPP-109 may offer the potential to provide patients suffering from methamphetamine addiction, as well as the physicians and clinicians that treat them, with a safe and effective pharmacotherapy option."

What, in essence, are such pills designed to accomplish? The primary avenue of research has centered upon medications that decrease the addict's experience of withdrawal and craving. According to Kampan, "several studies have demonstrated that patients who experience severe cocaine withdrawal symptoms... are twice as likely to drop out of treatment and less likely to attain abstinence in outpatient programs."

However, questions remain about the safety of vigabatrin. Although available abroad, it is not approved for use in the U.S., due to an association with serious visual effects after long-term use. The use of vigabatrin for stimulant addiction, if approved, might require associated eye examinations.

Buproprion, a drug that has shown some promise in the treatment of cocaine addiction, is also a candidate for meth addiction. The drug inhibits the reuptake of dopamine, thus allowing more dopamine to circulate in the brain. In addition, there are plans to test other drugs being investigated for cocaine craving, such as topiramate and modafinil.

According to the 2005 SAMHSA Survey on Drug Use and Health, an estimated 10.4 million people age 12 or older (4.3 percent of the population) have tried methamphetamine at some time in their lives. Approximately 1.3 million reported past-year methamphetamine use, and 512,000 reported current (past-month) use. Approximately 535,000 patients sought treatment for methamphetamine and other stimulant abuse in 2006.

Next post: Drugs for cocaine craving

Photo Credit: National Drug Intelligence Center

dopamine