Alcoholism: The Genetic Puzzle

Fathers and Sons.

The hunt for genetic influences on alcoholism derives largely from the work of Dr. Donald W. Goodwin, chair of the Department of Psychiatry at the University of Kansas Medical Center. Starting in the early 1970s, Dr. Goodwin and co-workers, using computer technology and a detailed database of Scandinavian health records, scrutinized the results of 5,000 adoption cases in Copenhagen. The results of the initial study stunned alcoholism experts around the world. The sons of alcoholics were more likely to become alcoholics themselves, as many had expected. But the relationship held true even when the children of alcoholics were separated from their natural parents shortly after birth, and subsequently raised by foster parents.

In Phase 2 of the Danish studies, Goodwin selected only alcoholic families in which one son had been raised by his biological parents, while the other son had been adopted away early in life. Raised in separate environments, twins of this sort are highly prized for genetic research. Goodwin compared the sons who had been raised by their alcoholic birth parents to their adopted-away brothers. It didn’t seem to make any difference: Rates of alcoholism were roughly the same. Environmental factors alone did not seem to account for it.

“By their late twenties or earlier,” Goodwin wrote, “the offspring of alcoholics had nearly twice the number of alcohol problems and four times the rate of alcoholism as the children whose parents had no record of hospitalization for alcoholism.” It did not look like family environment was the primary determinant.

Perhaps some of the children simply ended up with less effective foster parents, detractors pointed out. Alternatively, some unknown trauma might have been inflicted in the womb. Maybe the pregnant mother drank. Environmental factors can never be ruled out. Nonetheless, the basic implications of Goodwin’s work could not be shaken off. The Danish adoption studies were the first major scientific papers to establish a firm link between heredity and alcoholism.

Beginning in the 1980s, Dr. C. Robert Cloninger, professor of psychiatry and genetics at Washington University in St. Louis, and Michael Bohman, a Swedish pediatrician, began a broader series of adoption studies. The Stockholm Adoption Study scrutinized the records of more than 3,000 adopted individuals, and confirmed the Danish studies: The children of alcoholics, when compared with the children of non-alcoholic parents, were far more likely to become alcoholics themselves—even if they were adopted away. 

Moreover, “Alcohol abuse in the adoptive parents was not associated with an increased risk of abuse in the children they reared,” Cloninger later reported in the journal Science, “so there was no evidence that alcoholism is familial because children imitate their [non-biological] parents.”  

Adapted from The Chemical Carousel: What Science Tells Us About Beating Addiction by Dirk Hanson © 2008.

Graphics Credit: http://www.3dscience.com/

A Seaside Story of Love and Junkies

Documentary airs today on VBS.TV

A reminder that drug addiction is always, at bottom, about real people in the real world: The online video service VBS.TV is offering the first of a 6-part documentary on the underreported heroin epidemic in South Wales.

“Swansea Love Story,” according to its promoters, “follows the lives of a community of young heroin addicts living in an economically ravaged city of South Wales.”

Co-director Andy Kapper said in a press release: “I wanted to make this film because we were tired of seeing homeless young people being portrayed as little more than statistics. Documentaries about drug use often come out pious and fail to really get to know the people behind the drug usage. We wanted to show what it was like to live on the street, under the grip of heroin, as realistically as possible.”

The London Evening Standard called it “stunning, shocking, touching,  and deeply moving.”

I watched Part One. It's only seven minutes long, but it will sit you up straight.

The Nucleus Accumbens

Final destination for addictive drugs.

The release of dopamine and serotonin in the nucleus accumbens lies at the root of active drug addiction. The pattern of neural firing that results from this surge of neurotransmitters is the “high.” It is the chemical essence of what it means to be addicted. Part of the medial forebrain bundle (MFB), which mediates punishment and reward, the nucleus accumbens is the ultimate target for the dopamine released by the ingestion of cocaine, for example.

The release of dopamine and serotonin in the nucleus accumbens appears to be the final destination of the reward pathway—the last act in the pleasure play. If you think about a drug, take a drug, or crave a drug, you are lighting up the nucleus accumbens with a surge of electrochemical activity. These are essentially the same pathways that regulate our food and water-seeking behavior. By directly or indirectly influencing the molecules of pleasure, drugs and alcohol trigger key neurochemical events that are central to our feelings of both reward and disappointment. In this sense, the reward pathway is a route to both pleasure and pain.

Alcohol, heroin, cigarettes, and other drugs caused a surge of dopamine production, which is then released onto the nucleus accumbens. The result:  Pleasure. When scientists pipe a dopamine-mimicking substance into the nucleus accumbens, targeting dopamine D2 receptors, withdrawal symptoms are blocked in morphine-addicted rats. Similarly, when scientists block dopamine receptors in the accumbens, the morphine-dependent rats exhibit withdrawal symptoms.

When you knock out large slices of the nucleus accumbens, animals no longer want the drugs. So, one cure for addiction has been discovered already—but surgically removing chunks of the midbrain just won’t do, of course.

Dopamine is more than a primary pleasure chemical—a “happy hormone,” as it has been called. Dopamine is also the key molecule involved in the memory of pleasurable acts. Dopamine is part of the reason why we remember how much we liked getting high yesterday. The nucleus accumbens (also known as the ventral striatum) seems to be involved in modulating the emotional strength of the signals originating in the hippocampus. This implicates the hippocampus in relapse, even though this area of the brain does not light up as strongly during actual episodes of craving.

The fact that we know all this is nothing short of amazing, but it is part of a larger perspective afforded by the insights of contemporary neurobiology. We know, for example, that the emotion of fear arises, in large part, through chemical changes in a peanut-sized limbic organ called the amygdala. Does this information make fear any less, shall we say, fearful? It merely locates the substrate upon which the sensation of fear is built.

Studies of the nucleus accumbens have demonstrated abnormal firing rates in scanned addicts who were deep into an episode of craving. The craving for a reward denied causes dopamine levels in the nucleus accumbens to crash dramatically, as they do when users go off drugs. Dopamine, serotonin, and norepinephrine activity soars just as dramatically when a drug user relieves withdrawal symptoms by relapsing. Drug hunger in abstinent addicts is not all in the head, or strictly psychological. Craving has a biological basis.  

Finding a way to override serotonin- and dopamine-mediated mid-brain commands is the essential key to recovery from addiction. One of the aims of a biological understanding of addiction is to tease out the mechanisms by which the reinforcing effects of addictive drugs become transformed into long-term adaptive changes in the brain.

Graphics credit: http://thebrain.mcgill.ca/

Adapted from The Chemical Carousel: What Science Tells Us About Beating Addiction by Dirk Hanson © 2008.

Rethinking the Patch

Quitters do better on 6-month regimen.

It may sound like dream propaganda for the makers of nicotine patches. And it is. Moreover, at least one of the study authors has worked in the past as a consultant for GlaxoSmithKline, maker of Nicoderm CQ, one of the best-selling brands of transdermal nicotine patches.

So there is every reason to dismiss a recent study by researchers at the University of Pennsylvania School of Medicine, published in the Annals of Internal Medicine, which strongly suggests that the currently recommended regimen of two months isn’t long enough. It should be tripled. Which also triples sales.

There’s only one catch: There is reason to believe that the results are legitimate, and that smokers who are trying to quit would be more successful if they stuck with the patch for longer periods than currently recommended on the manufacturer’s box.  For some time now, tobacco addiction researchers, and centers such as Mayo Clinic’s Stop Smoking facilities, have recognized the need for extending the manufacturer’s suggested period of use.

Referring to the patch on its Stop Smoking web site, Mayo Clinic says: “You typically use the nicotine patch for eight to 12 weeks. You may need to use it longer if cravings or withdrawal symptoms continue.”

And from the field come reports of abstaining smokers independently choosing to use the patch longer, often by cutting the patches into eighths or sixteenths in order to accomplish a long, slow taper at the end of the process. By following this route, a nicotine addict need not be aware of the precise day or moment when his nicotine fix from the patch has dropped to placebo levels—further evidence that nicotine addiction is a chronic condition that may not respond to treatments of only two to three months in duration. 

One early development during the marketing of the patch that helped set the short-term use pattern were reports in the 1990s of heart attacks by patch users. Subsequent research showed that rare cardiac problems had arisen in patients who had continued heavy smoking while on the patch, and that there was little evidence of a direct link between nicotine patches and heart attacks. (Recent heart attack victims are advised to wait six weeks and use patches with caution.)

The study concludes: “Transdermal nicotine for 24 weeks increased biochemically confirmed point-prevalence abstinence and continuous abstinence at week 24, reduced the risk for smoking lapses, and increased the likelihood of recovery to abstinence after a lapse compared with 8 weeks of transdermal nicotine therapy.”

One limitation of this particular study, acknowledged as such by the authors, is that “participants were smokers without medical comorbid conditions who were seeking treatment.” In other words, the study cohort consisted of highly motivated smokers.

And another problem is cost: Few health insurance companies cover the full cost of patches, including Medicaid. The additional cost per quitter, the study found, was about $2,400 for the extended regimen.

Nonetheless, any uptick in success rates for smoking cessation programs should be noted and taken under consideration.

Photo Credit: www.drugabuse.gov

The Low Cost of Drinking

Does cheap liquor encourage excess?

Last year, Sir Liam Donaldson, the Chief Medical Officer in England, touched off a storm of controversy with his call for a government-mandated minimum pricing schedule for the sale of alcohol.

Donaldson’s pricing plan would set a minimum of 50p per unit of alcohol, or roughly 80 cents. This floor on alcohol pricing would mean that a bottle of wine could not be sold for less than $7.20, a bottle of whisky for less than $22, or a six-pack for less than about $9.50. Such a measure would effectively double the price of the cheapest alcohol sold in some discount supermarkets.  Sir Liam Donaldson and other health officials have pointed out that, while alcohol consumption in many European countries has fallen since 1970, consumption in England has increased by 40%.

 Sir Liam estimated that the pricing minimums would save more than 3,000 lives and result in 100,000 fewer hospital admissions per year.

Further roiling the waters was a London Times article in December titled “Alcohol now costs less than water.” The Times found that cut-price deals at British supermarkets were endemic. Don Shenker, chief executive of Alcohol Concern, said that supermarket discounting was undermining the government’s efforts to curb binge drinking in the UK: “The evidence shows young people and harmful drinkers are drawn to very cheap alcohol.” The British Medical Association also threw its support behind a crackdown on deeply discounted alcohol sales.

However, Prime Minister Brown announced his government’s opposition to minimum pricing, arguing that the proposal would penalize the majority of sensible drinkers due to the actions of a few. It was also suggested that the measure might be illegal under EU competition laws.

As it turned out, alcohol was only cheaper than water if you bought the most expensive water and the least expensive booze. But no matter—the point had been made. “We have a huge problem with alcohol abuse in the UK,” said a spokesperson for the British Medical Association, “so we want a clampdown on these cut-throat price deals.”

Scotland also announced it was considering a minimum pricing plan. However, a study by Deloitte Research, reported in the Herald Scotland, found that only one out of five adults would be likely to buy less alcohol under a minimum price system.  52% said they would spend more money for the same amount of alcohol or else seek out cheaper brands.  In addition, the Deloitte research suggested that people use cheap supermarket alcohol for “pre-fueling” or “pre-loading” before going out for the night.  Scotland’s alcohol intake per person is higher than Britain’s. Recently, the Scottish government released a report from the University of York, which estimated that alcohol abuse cost Scottish taxpayers almost $7.5 billion a year.

British Health Secretary Andy Burnham told the UK Telegraph that while he did not wish to “punish the majority of people who drink responsibly,” he maintained there was no argument about “the link with price and people drinking harmful levels of alcohol—there is no debate about that.” Government officials note that the imposition of some form of levy might be required to keep the drinks industry from reaping windfall profits from a price increase. To date, the British Cabinet has taken no formal action on the matter.

Starting in April, British pubs and clubs will be banned from running “all you can drink” nights and other “irresponsible drink promotions,” according to The Independent. The plans have met with stiff opposition from pub owners, the alcohol industry, and the public.

All of this may be in vain: The demand for alcohol, in economic terms, may be highly inelastic, like the demand for cigarettes and coffee. Price hikes for those two items over the years have not been accompanied by similar declines in usage.

Photo Credit: www.design4retail.co.uk

The Three-Headed Dragon

A symbol of need.

 Getting off drugs, or learning to stop drinking, is very often easier than staying off them. As Mark Twain remarked about tobacco, quitting was easy—he’d done it dozens of times. Relapse, the biological imperative, will have its way with most of those abstaining for the first time. Addiction is a psychological disorder with strongly cued behavioral components, whatever its dimensions as a biochemically-based disease.

The three-headed dragon is a metaphor first popularized by alternative therapists at the Haight Ashbury Free Medical Clinic in San Francisco. The first head of the dragon is physical. Addiction is a chronic illness requiring a lifetime of attention. The second head is psychological. Addiction is a disorder with mental, emotional, and behavioral components. And the third head of the dragon is spiritual. Addiction is an existential state, experienced in isolation from others.

Addicts speak of “chasing the dragon” in an effort to catch the high that they used to achieve so easily. It is also drug slang for the use of small metal pipes to catch and inhale the wisps of smoke from a pile of burning opium, crack, or speed. We can picture the dragon chasing his own tail, snapping at it with all three hungry mouths, in an endless escalation of tolerance and need.

“Because of the unique reaction that the genetically addiction-prone individual experiences to his drug of choice, he or she programs his or her belief system with the deep conviction that the substance is ‘good,’” writes Richard Seymour. “This is where self-help becomes intrinsic to recovery. Unless one deals with the third head, unless one changes the belief system and effects a turning-about in the deepest seat of consciousness, there is no recovery.” The “X” factor in recovery, for many people, turns out to be a form of inner self-awareness; something that includes the attributes of will power and determination yet transcends them through a form of surrender.

And speaking of changing one’s belief system, experience has shown that it is a spectacularly bad idea to sit around and do nothing but stare at the wall during the early phase of recovery. Psychologist Mihaly Csikszentmihalyi argues, in The Evolving Self, that when attention wanders, and goal-directed action wanes, the majority of thoughts that come to mind tend to be depressive or sad. (This does not necessarily apply to formal methods of meditation, which cannot be described as states marked by wandering attention.) The reason that the mind turns to negative thoughts under such conditions, he writes, is that such pessimism may be evolutionarily adaptive. “The mind turns to negative possibilities as a compass needle turns to the magnetic pole, because this is the best way, on the average, to anticipate dangerous situations.” In the case of recovering addicts, this anticipation of dangerous situations is known as craving. The next step is often drug-seeking behavior, followed by relapse.

For a highly motivated addict with a stable social life, a safe and effective medication to combat craving might be all that is needed. For many others, however, attention to the other two heads of the dragon is going to be necessary. An addict’s ability to experience pleasure in the normal way has been biochemically impaired. It takes time for the addict’s disordered pleasure system to begin returning to normal, just as it takes time for the physical damage of cigarette smoking to partially repair itself.

Alternative therapists are fond of referring to recovery as a process, with an emphasis on the importance of time. Medication of any disease, even if successful, does not treat the continuing need for healing. It is now well understood that mood and outlook can have an effect on healing. Positive emotional states can be beneficial to the maintenance of good health. Thoughtful physicians make the distinction between a disease and an illness. A disease is a chemically identifiable pathological process. An illness, by contrast, is the disease and all that surrounds it—the sociological environment, and the individual psychology of the patient who experiences the disease.

From The Chemical Carousel By Dirk Hanson, pp. 311-313.  © Dirk Hanson, 2008.

Graphics Credit: wwwwilliammorristile.com

Pot Advocates Overreach Themselves

L.A. set to close most marijuana dispensaries.

Medical marijuana advocates in Los Angeles appear to have overreached themselves, angering the City Council by establishing more than a thousand medical marijuana dispensaries in commercial and residential neighborhoods around the city.

According to a report by Jennifer Steinhauer in the New York Times, a board member for the neighborhood council in Studio City called the 13 dispensaries in her 3.5 square miles-neighborhood “unbelievable.”

The City Council struck back hard on Tuesday, passing a city ordinance that would “shutter the majority of the nearly 1,000 medical marijuana dispensaries in Los Angeles and make the use of marijuana in the remaining outlets illegal,” according to the New York Times article. Claiming that Los Angeles now had more marijuana dispensaries than Starbucks outlets, Councilman Ed Reyes, chairman of the planning and land-use management committee, called the situation “out of control.”

Two years ago, Los Angeles imposed a moratorium on the establishment of new dispensaries, pending further study. But medical marijuana advocates flouted the temporary ban with impunity. According to the article, “The measure, which passed on a 9-to-3 vote, imposes strict rules on the location of the dispensaries — essentially moving them to more densely industrial zones — and restricts their hours. The ordinance, which city officials acknowledge would be difficult to enforce, will limit the number of dispensaries to 70….”

According to the Los Angeles Times :  “In a 9-3 vote, the Los Angeles City Council today gave its final approval to an ordinance that will shut down hundreds of medical marijuana dispensaries and impose strict rules on the location and operation of the dispensaries that are allowed. The ordinance, which the council first began discussing more than 4 1/2 years ago, will cap the number of dispensaries at 70 but make an exception to allow all those that registered with the city in 2007 and have remained open. City officials believe that number is around 150.”

Photo Credit: http://seattletimes.nwsource.com/html/nationworld/2010085782_lapot18.html