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

"Rogue Pharmacies" on the Internet

You've got drugs!

No prescription? No problem. Of 365 web sites advertising or selling controlled drugs, fully 85 percent do not require a written prescription, according to the 5th annual White Paper from the National Center on Addiction and Substance Abuse at Columbia University (CASA).

Although the overall number of drug-peddling web sites declined from 2007, the report found that benzodiazepines like Xanax and Valium were the most frequently offered online drugs, followed by painkillers like Oxycontin and Vicodin. 27 percent of the sites also offered Ritalin, Adderall, and other stimulants.

The paper, entitled "'You've Got Drugs!' V: Prescription Drug Pushers on the Internet," reported that only two of the 365 sites were certified by the National Association of Boards of Pharmacy, an official body which represents state pharmacy examination boards. The total number of drug sites was down from 581 such web sites in 2007.

"This problem is not going away," said Joseph A. Califano, Jr., chairman and president of CASA, and a former secretary of Health, Education and Welfare under President Jimmy Carter. "It is morphing into different outlets for controlled prescription drug trafficking like Internet script mills and membership sites that sell lists of online pharmacies, and different payment methods like eChecks, COD and money orders."

In addition, some of the sites sell "medical consultations" which can be used to procure controlled drugs without a formal prescription. In 2007, 80 percent of prescriptions filled by Internet pharmacies were for controlled substances. According to figures from the Drug Enforcement Administration (DEA), only 11 percent of business at traditional pharmacies involves scheduled drugs.

In April, the U.S. Senate passed a bill endorsed last year by the Senate Judiciary Committee, which seeks to control the Internet traffic in prescription drugs. The bill, introduced by Senators Diane Feinstein (D-CA) and Jeff Sessions (R-AL), now goes to the U.S. House. According to Senator Feinstein, "This [CASA] report emphasizes the need to take immediate action to stop rogue pharmacies on the Internet.... Our Internet pharmacy legislation has passed the Senate. It's time for the House to take action and pass this important bill."

Photo Credit: Next Thing

If the Genes Fit....

U.K psychiatrists agree addiction is "genetically determined."

Although the verdict is very little in doubt these days, the heritability of addictions was reaffirmed by the U.K.'s Royal College of Psychiatrists in London on July 4th.

In a presentation at the group's annual meeting, held at Imperial College, Professor Wim van den Brink of the University of Amsterdam's Academic Medical Center pinned the blame for addiction squarely on the absence of a sufficient number of dopamine receptors in the brain. "Addicts find it difficult to receive pleasure," he said. "They are not likely to enjoy most of the ordinary things most of us enjoy... they are looking for more stimulus."

Professor van den Brink also made clear the importance of environmental interactions for gene expression: "You might start off smoking or taking cocaine, and that first introduction is very much determined by your environment. But to stick with it and become dependent on it is genetically determined."

The self-defeating nature of addiction is graphically illustrated by the overall decrease in the number of pleasure receptors for dopamine and serotonin over time, as drug use escalates. Moreover, addicts show a striking deficiency in the ability to engage in long-term thinking. This behavioral link, the Royal College maintained, is the reason addicts fail to realistically differentiate between short-term pleasure and long-term negative effects.

This inability of drug addicts to engage in effective long-term thinking is well summarized in the old Reverend Gary Davis song: "Cocaine's for horses and it's not for men/Doctor said it kill you, but he didn’t say when."

Photo Credit: National Institute on Drug Abuse

dopamine addiction drugs

Pain Patients Sue State of Washington

Do doctors suffer from "opiophobia?"

The opium family of painkillers has always been a bane and a boon to the human race, as evidenced by nurses injecting morphine into agonizingly wounded soldiers, and street junkies selling the clothes off their back for another fix.

However, as I wrote in an earlier post, "The Morphine Scandal," the ironies fly thick and fast: In many cases, pain relief is the one thing doctors can offer their patients, and the one thing they withhold. Studies show that 70 per cent of patients present with painful conditions. Typically, non-addicted patients take morphine therapeutically for pain at doses in the 5 to 10 mg. range. But experienced morphine addicts regularly take several hundred milligrams a day—a huge difference.

Now, a lawyer for a pain relief advocacy group has filed suit against the state of Washington, claiming that overly stringent guidelines on prescription pain medications have had a negative effect on pain management across the country. Attorney Laura D. Cooper, who filed the suit on behalf of a group of Washington residents being treated for pain, said in an Associated Press article by Donna Gordon Blankinship that the state's regulations were comparable to setting a limit on the amount of insulin a doctor could prescribe for diabetic patients. Cooper alleged that the Washington standards have been used as guidelines by insurance companies and workman's compensation boards.

The AP article also quoted Siobhan Reynolds of the Internet-based Pain Relief Network: "The ramifications are enormous. You never see on a death certificate that people died of pain, but people die of pain all the time."

The lawsuit features an excerpt from a University of Wisconsin textbook on pain medicine, Bonica's Management of Pain, 3rd edition:

"Opiophobia is the syndrome of failure to administer adequate opioid analgesics because of the fear of producing addiction or toxicity. The etiology of opiophobia is multifactorial: Peer pressure (provider and patient), regulatory agency pressure (real or perceived), and lack of education on opioids and the fundamentals of pain management all contribute to its persistence.... All of these factors contribute to the underuse of these relatively simple and very effective medications, due to no fault of the patients. "

According to Drug Law Blog, the complaint "asks the court to declare that the state guidelines 'do not constitute enforceable law of any kind and should be stricken and removed from all state publications of every variety,' and seeks other additional relief, including an injunction against enforcement."

As for concerns about addiction, recent evidence for the heritability of opiate addiction looks strong. “Harvard did some really superb studies using a huge cohort of military recruits in the U.S. Army,” according to Mary Jeanne Kreek, a specialist in opiate addiction at Rockefeller University in New York. “Heroin addiction has even a larger heritable component than any of the other addictions, so that up to 54% of heroin addictions seem to be on a genetic basis or a heritable basis.”

Photo Credit: Opioid.org