Nicotine and the Humphrey Bogart Gene

You can lead a fish to water, but can you make it smoke?

Zebrafish embryo showing axon tracts in green, viewed from lateral (top) and dorsal (bottom) orientations------>

Common denizens of home aquariums, the humble zebrafish may dart about the tank like any other small tropical specimen, but zebrafish have become one of the hot genetic research tools of the moment. The lab rat may have met its match in the lab zebrafish, a popular non-mammalian organism that is currently playing a leading role in government-sponsored research on the genetic aspects of nicotine addiction.

Scientists are fond of these new fishy animal models because zebrafish are cheap, develop rapidly, and are more biologically similar to humans than anyone might naively assume. Their transparent embryos allow researchers to inject flourescent proteins into living animals, and in some cases to track the regulation of gene expression as it is happening.

Research funded by the National Institute on Drug Abuse (NIDA) and  published in the Proceedings of the National Academy of Sciences used zebrafish in a hunt for genes

affecting nicotine exposure. Like rats, the fish show characteristic behaviorial responses to low doses, high doses, and the nicotine sensitization process. According to NIDA, the scientists “induced mutations in particular DNA segments of the zebrafish and looked at changes in the nicotine response profile of mutant carriers compared to their siblings.” The changes in nicotine response observed between the groups were mediated by two genes, which the scientists dubbed bdav/cct8 (bette davis) and hbog/gabbr1.2 (humphrey bogart), named after “celebrities that suffered from tobacco-related cancers.” These two genes, when expressed, caused zebrafish to respond more positively to nicotine.

“We all know how hard it is to quit smoking,” Dr. Ekker told Mayo’s online research magazine, Discovery’s Edge. “What most people don’t know is that genetic differences significantly contribute to the degree of nicotine dependence. We want to understand the genetics behind different responses to nicotine and come up with more effective and individualized treatments for people addicted to nicotine.”

The Mayo Clinic in Minnesota has taken a leading role in developing the fish for research, having established the Zebrafish Core Facility in 2007 under the direction of Dr. Stephen Ekker. Mayo’s zebrafish are now being used in various research laboratories for research in the fields of developmental biology and functional genomics. The fish are now a crucial part of biological research on cancer and heart disease, as well as addiction.

Graphics Credit: http://www.ucl.ac.uk/

Petzold AM, Balciunas D, Sivasubbu S, Clark KJ, Bedell VM, Westcot SE, Myers SR, Moulder GL, Thomas MJ, & Ekker SC (2009). Nicotine response genetics in the zebrafish. Proceedings of the National Academy of Sciences of the United States of America, 106 (44), 18662-7 PMID: 19858493

National Alcohol and Drug Addiction Recovery Month

Presidential Proclamation

Each day brings new opportunities for personal growth, renewal, and transformation to millions of Americans who have chosen to forge a path toward recovery from addiction to drugs or alcohol.  While addiction can destroy self confidence, family ties, and friendships, recovery can restore the promise of a brighter tomorrow.  During National Alcohol and Drug Addiction Recovery Month, we express support for those living healthy and productive lives in long term recovery, we applaud those working to help struggling Americans break the cycle of abuse, and we encourage those in need to seek help.

This year's theme, "Join the Voices for Recovery:  Now More Than Ever!," calls us to an urgent mission to save lives from the hazards of addiction.  As we make quality and affordable health care more accessible to all Americans, we also resolve to build a healthier Nation by increasing access to treatment and recovery programs in our health care system.  To help achieve this goal, the Affordable Care Act supports services available to address addiction.  Together, we can reduce the harmful consequences of untreated addiction, such as violence, failure in school, job loss, child abuse, crimes, and death.  I encourage all Americans to visit RecoveryMonth.gov for more resources and information.

 The journey to recovery requires great fortitude and a supportive network.  As we celebrate National Alcohol and Drug Addiction Recovery Month, we also express our appreciation for the family members, mutual aid groups, peer support programs, health professionals, and community leaders that provide compassion, care, and hope.  Across America, we must spread the word that substance abuse is preventable, that addiction is treatable, and that recovery is possible.

NOW, THEREFORE, I, BARACK OBAMA, President of the United States of America, by virtue of the authority vested in me by the Constitution and the laws of the United States, do hereby proclaim September 2010 as National Alcohol and Drug Addiction Recovery Month.  I call upon all Americans to observe this month with appropriate programs, ceremonies, and activities, and to celebrate the lives freed from addiction to illicit drugs, alcohol, or prescription medications.

IN WITNESS WHEREOF, I have hereunto set my hand this thirty-first day of August, in the year of our Lord two thousand ten, and of the Independence of the United States of America the two hundred and thirty-fifth.

BARACK OBAMA

Why Drug Stigma Still Matters

More sinned against than sinning?

 “Psychological theories of illness are a powerful means of placing the blame on the ill. Patients who are instructed that they have, unwittingly, caused their disease are also being made to feel that they have deserved it.”

--Susan Sontag, Illness as Metaphor

Addiction is always a hot topic, in its way, if only because of an endless supply of fallible starlets. More seriously, valuable research is taking place in myriad directions—the psychology of addiction, the disease of addiction, the neurobiology of addiction, the neuropsychopharmacology of addiction, etc. What sometimes goes missing is any serious analysis of the stigmatization of drug addiction.

The UK Drug Policy Commission (UKDPC) is an independent research group comprised of 12 “expert commissioners” charged with providing objective analysis on drug policy matters. The group recently issued a paper authored by Charlie Lloyd of the University of York. In “Sinning and Sinned Against: The Stigmatisation of Problem Drug Users,” (PDF) Lloyd set out to pull together the evidence-based research on the effects of stigmatizing  “problem drug users.” The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) defines problem drug use as “injecting drug use or long-duration/regular use of opioids, cocaine and/or amphetamines.”

According to Lloyd’s analysis of the research literature, the groups most frequently referred to as stigmatized are the disabled, the mentally ill, minority ethnic groups—and drug addicts. To make matters worse, multiple problems often attach to addicts: “Problem drug users frequently report suffering from other stigmas: being black, female, Hepatitis C or HIV positive, disabled, or suffering from a mental disorder. However, research shows that problem drug user status is the most stigmatising.” The stigma is continuously cemented in place by rhetoric about the “war on drugs.” There is no comparable public war on disability, or mental illness, or ethnicity—at least not overtly.

I cannot vouch for Lloyd’s analysis, but a good deal of it smacks of common sense at the street level. Others have suggested it is logical to assume that the stigma attached to hard drug addiction serves, by example, to deter others. “However,” Lloyd writes, “attempts to scare young people away from drug use have not proved effective. The evidence reviewed here suggests that stigma keeps users away from treatment.”

So this is not a theoretical concern. Stigmatization “may be a major stumbling block to successful rehabilitation.” Health professionals and hospital staff “can be distrustful and judgmental in dealing with problem drug users but drug users can themselves be aggressive and manipulative. In the United States staff who choose to work in hospitals serving the most deprived, inner-city populations appear to be more compassionate and patient.”

The prevailing public view, Lloyd writes, is that problem drug users tend to be “dangerous, deceitful, unreliable, unpredictable, hard to talk with and to blame for their predicament. Young people may have more negative views in this respect than adults.”

Of course, drug addicts can be all those things at one time or another. Drug abusers often stigmatize themselves. For the user, these conflicted feelings lead some of them to feel that “the very act of seeking treatment serves to cement an ‘addict’ or ‘junkie’ identity, which can lead to further rejection from family and friends.” This is most commonly experienced by users on methadone maintenance treatment, “who feel particularly stigmatised, in comparison to other treatment types.” Lloyd notes that a lifetime stigma sometimes attaches to heroin and cocaine addiction, continuing “to haunt such ex-users, preventing access to good housing and employment.” As he trenchantly observes, there is plenty of room “to stigmatise users less, without rendering heroin or crack-cocaine significantly more attractive.”

Lloyd concludes that the primary culprit, the complicating factor, is “blame.” Compared to “blameless groups” such as the disabled and the mentally ill, problem drug users, he writes, “are blamed for taking drugs in the first place and are also perceived to have a choice whether or not to take drugs in the future.”

If public and professional stigma has the power to prevent addicts from entering treatment (as it formerly held a similar power over the mentally ill, and before that, the disabled), what can be done about it? Lloyd makes several concrete suggestions, most of which center, predictably, on education:

--Drug education in schools should focus on the causes and the consequences of active addiction, rather than relying on scare stories.

--It’s time to teach health care and pharmacy staff about the medical, social, and psychological aspects of drug addiction.

--Treatment agencies need to focus on the whole person, “and not see problem drug users as solely problem drug users. Some drug addicts are also bird-watchers.”

--Users themselves, as well as their families, often benefit from a greater understanding of the mechanisms of addiction. This can have the effect of reducing “the self-blame felt by many drug user’s parents.”

--Finally, “police need to reflect on their practice in policing problem drug users at street level.” ‘Nuff said on that.

DrugScope, a leading U.K. charity with a membership drawn in part from the ranks of drug treatment and education workers, praised the report as “timely and insightful.” Martin Barnes, chief executive of DrugScope, said that the report effectively “evidences stigma as a barrier to recovery and reintegration.”

Photo Credit: http://www.zazzle.com/

Is Post-Traumatic Stress Medication a Danger to Veterans?

I have not run any guest posts lately, but some months ago the AllTreatment site was kind enough to feature a guest post of my own, so I've arranged to return the favor with an article by Brandon Yu. He is a Managing Editor of Alltreatment.com. AllTreatment is an online rehab center directory and substance abuse information resource.‬

Opinions expressed in guest posts are not necessarily those of Addiction Inbox.
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By Brandon Yu

After spending weeks, months, or years on the battlefield, veterans often experience Post-Traumatic Stress Disorder (PTSD) when returning to civilian life. The Department of Veteran Affairs reports that 60% of men and 50% of women, not just veterans, experience some sort of trauma in their lifetimes. PTSD has been known to cause insomnia, depression, and a sense of detachment, making it difficult for veterans to readjust to society, and throwing their personal and professional lives into disarray.

While there may not be a cure for Post-Traumatic Stress Disorder, there are treatments, and certainly medication, to sooth its side-effects. The most popular medication for PTSD is the pharmaceutical Quetiapine, marketed as Seroquel by the biologics company AstraZeneca. A potent antipsychotic, Seroquel is often prescribed to treat symptoms of psychoses including schizophrenia, bipolar disorder, and acute manic episodes; numerous physicians claim that it is one of the few treatments that curbs the nightmares, insomnia and anxiety that come with PTSD. It is not considered a controlled substance, and not deemed addictive like other sleeping pills.

However, several families of veterans are calling for a Congressional investigation of Seroquel after reports of mistreatment over the drug have arisen. After some complaints that the treatment was not working, some doctors prescribed progressively larger doses for given patients, with certain ones receiving more than double the maximum recommended. Though only six similar deaths have been noted, there is a belief that there have been others. The New England Journal of Medicine recently published a report linking Seroquel use to heart failure, noting that 3 of 1,000 patients who suffered from cardiac arrest were noted to be on Seroquel at the time of death.

Seroquel is one of the more common medications in America, as it is one of the Department of Veterans Affairs’ most prescribed drugs and the fifth best-selling drug in the nation. It has been reported to help schizophrenia and PTSD, but some of its side effects, such as diabetes, weight gain, and uncontrollable muscle spasms, have caused AstraZeneca to receive multiple trips to court, with an estimated 10,000 product liability lawsuits. It is noted that although it is commonly prescribed for those suffering PTSD, Seroquel has not received FDA approval as proper treatment for insomnia. Families of veterans who are attempting a Congressional investigation on Seroquel are hoping for a clearer guideline of the side effects as well as the risk to one’s health.

Today is Overdose Awareness Day

Annual global day of action coordinated by Red Cross.

According to the most recent figures from the Centers for Disease Control and Prevention (CDC),  more than 26,000 Americans die needlessly, pointlessly, from accidental drug overdoses.  For example, in San Francisco, there were more drug-related accidental deaths in 2007 than there were deaths by automobile crash. These days, oxycodone is  our leading killer, followed by cocaine and heroin.

The Harm Reduction Coalition notes the success of the DOPE project (Drug Overdose Prevention and Education) in San Francisco. DOPE is a community group composed of members trained to recognize and respond to drug overdoses. In San Francisco, one person dies every other day from a preventable drug overdose death.

"Overdose Awareness Day is a time for us to remember the thousands of lives lost to accidental drug overdose every year and to restate our commitment to effective strategies to reduce overdose deaths in our community," said DOPE Project Director Eliza Wheeler.  "This year, we would like to publically thank the courageous people who have successfully revived their friends, family members and partners using naloxone."

Over at Injecting Advice, they have gathered together twitter hashtag posts about Overdose Awareness Day:

“Today (31st August) is International Overdose Awareness day and all around the world there are services (and individuals) working hard to raise awareness of the main course of death for people who use drugs. As you'd expect a lot of these people are now using social media like twitter, so I've decided to collect together the mentions of the official 'hashtag' for overdose awareness day.”

In addition, www.injectingadvice.com offers a downloadable OD Awareness Workshop. 

Bio Firm Working on New Technology for E-Cigarettes

Key tobacco scientist endorses “going vape.”

Cypress Bioscience of San Diego hopes to enter the controversial and potentially lucrative market for so-called e-cigarettes, which deliver nicotine by heating it to produce an inhalable, smoke-free vapor. The company announced last week that it had acquired a $5 million license for Staccato nicotine technology—“A novel electronic multidose delivery technology designed to help people stop smoking.”

The company claims that the “the electronics embedded within the Staccato delivery system could allow for the programmed, over-time reduction in the overall daily dose of nicotine, and ultimately may lead to the better management of nicotine cravings and eventual sustained smoking cessation”

Critics of e-cigarettes have maintained that the devices were not meant to curb smoking but to enable it, by allowing smokers to circumvent no-smoking regulations. Fears have also been voiced that children might be tempted to make use of them. Makers of electronic cigarettes, primarily in Asia, have maintained that the devices are perfect for the management of nicotine cravings when smokers quit, and may have significant advantages over nicotine gums and patches.

The press release from Cypress Bioscience makes the claim explicitly: “The Staccato technology may be capable of mimicking the pharmacokinetics of smoking cigarettes through the delivery of optimally-sized nicotine particles to the deep lung. Staccato nicotine may also provide some of the psychological aspects of smoking (e.g., hand-to-mouth movement, oral inhalation) and could allow smokers to self-administer and possibly titrate to the dose to treat cravings.”

Up until now, electronic cigarettes have been opposed by the Food and Drug Administration (FDA) on the grounds that e-cigarettes were novel and untested drug delivery systems. Signaling a possible change in official attitudes, Dr. Neal Benowitz, professor of Medicine at the University of California, San Francisco--and a prominent nicotine researcher for many years--said in the Cypress Bioscience press release that a delivery device like Staccato nicotine “may be useful in addressing a pressing pharmacological problem in overcoming nicotine addiction; namely, that acute cravings during quit attempts are inadequately treated by current nicotine replacement therapies.” Dr. Benowitz called the nicotine delivery device “an advancement that the field has been waiting for.”

Cypress Bioscience said it plans to take the technology into Phase 1 clinical trials next year. The company reported a net loss of 5 cents per share in the second quarter, compared to a loss of 23 cents per share during the same period a year ago.

The Centers of Disease Control and Prevention (CDC) estimate that almost 450,000 people die annually in the U.S. from smoking. One in five deaths in the U.S. are due to smoking-related illness, according to the CDC.

Earlier posts:

Leave Cigarettes Along, Judge Tells FDA

E-Cigarettes: Another Look

Graphics Credit: http://www.ecigarettebuyer.co.uk/

Smoking and Baby Poop

Telltale metabolites in meconium.

Attention pregnant smokers: You can run, but you can’t hide. A chemical analysis of your baby’s first official poop can establish whether your infant has suffered from prenatal exposure to tobacco smoke. The higher the levels of tobacco metabolites, the more likely the mother was an active smoker.

The authors of a study published in Environmental Health found that nicotine and assorted tobacco metabolites were easily detectable in an infant’s meconium, the black, tar-like substance that comprises the first stools from newborns. In a study of 337 babies, tobacco metabolite concentrations were higher in active smokers than in non-smoking women exposed to second-hand smoke only.

The researchers say the meconium method is not superior to other methods of measurements, but suggest it may be a useful adjunct in estimating “gestational exposure to other environmental toxicants that exhibit more variability during pregnancy, especially non-persistent compounds like bisphenol A and phthalates.”

One striking aspect of the study is that the researchers found nicotine and cotinine—a common nicotine metabolite--in most of the meconium samples analyzed. 80% of the samples contained nicotine. So it is not a question of exposure, it’s a question of the degree of exposure. Should we be concerned about the lower levels of exposure registered from second-hand smoke? Apparently so, since “meconium tobacco smoke metabolites were inversely associated with birth weight,” according to Joe M. Braun and coworkers. Braun suggested that additional biomarkers for tobacco exposure were important, based on his belief that tobacco smoke exposure during pregnancy is under-reported.

This looks like a potentially useful tool for epidemiological studies that enroll women and infants at birth. More studies of this kind are needed, because prenatal tobacco smoke exposure is increasingly implicated in “adverse infant and childhood health outcomes.”

Graphics Credit: http://www.youquittwoquit.com/