Brain Scans and Addiction Research: The Early Years

X-ray specs for drug effects.

The science of addiction and the technology of brain scans have both developed exponentially in the past two decades. The search for specific neurobiological markers for addiction was made possible by positron emission tomography, better known as the PET scan. Known more casually as the PET/CT scanner, the device was named the Invention of the Year in 2000 by Time Magazine. (The CT scan, for computerized tomography, uses an X-ray machine and a contrast die to measure absorption rates in different brain areas.)

The idea of a PET scan is simple: Doctors inject test subjects with radioactively tagged glucose, which passes the blood-brain barrier with ease. The more electrochemically active portions of the brain burn extra glucose for energy. So, by noting precisely where the tagged glucose has gone, and converting that information into a digital two-dimensional array, a PET scan serves as a neurobiological map of brain activity in response to specific stimuli. Functionally, PET scans are admittedly imperfect pictures of the brain, showing general areas that “light up” during the performance of a task, or in response to a drug. Technically, a PET scanner is detecting gamma rays given off when particles from the radioactive tracer collide with electrons in the brain. A variation on this approach is the SPECT scan (single photon emission tomography).

The neuroimaging techniques that followed, like nuclear magnetic resonance imaging, or MRI, provided an additional level of analysis. MRI machines look similar to PET scanners, but are essentially large magnetic field generators. They were originally known as NMRIs, for nuclear magnetic resonance imagers, but the “nuclear” part seems to have disappeared over the years. MRI scans don’t involve radioactive tracers—they track blood flow, often by means of a contrast agent. Hydrogen, a major component of water and blood, gives off identifiable energy signatures when surrounded by giant magnets. If an area of the brain is showing increased activity, it means that somewhere in that area, some brain cells are demanding more oxygen.  A rush of blood to that area supplies it, an MRI scan detects it, and a computer plots it.

 With PET and MRI scans, scientists could study the brain as a set of molecules in motion. They could create a three-dimensional picture of the brain, with the sagittal, transaxial and coronal planes all visible at once—almost a brain hologram. Addiction scientists could watch tiny areas of the brain light up with activity under the influence of specific mood-altering chemicals. Two areas of the brain were of particular interest. One was the nucleus accumbens, which was involved in the regulation of dopamine and serotonin synthesis. The other was the locus ceruleus—a tiny area of the brain saturated with cells involved in the production and release of the neurotransmitter norepinephrine.

Alcohol, cocaine, the opiates, and other drugs made the nucleus accumbens and associated regions bloom with activity on the MRI and PET scans. These early snapshots of your brain on drugs specifically showed that psychoactive drugs of abuse, the ones that altered mood and emotion, did so at the very sites in the brain known to be involved in regulating emotional states and primary drives. Without scans, scientists would not have been able to confirm the workings of the brain’s reward system in specific anatomical detail.

 As a rule, the same areas of the brain tended to light up no matter what addictive drug was under study. Whether it was a molecule of stimulation, or a molecule of sedation, sooner or later it went surging through the diffuse aggregation of mid-brain structures involved with emotion, memory, mood, sleep, and a host of specific behaviors ranging from appetite to risk-taking.

That the subjects also showed similar brain activity when they quit doing drugs was of equal interest in the beginning. Early work by Dr. Kenneth Blum at the University of Texas Health Science Center and others demonstrated that certain characteristic forms of brain activity took place in the locus ceruleus whenever abstinent addicts experienced strong cravings. The locus ceruleus helps control levels of the original “fight or flight” chemical, norepinephrine, and when an addict in withdrawal panics, the locus ceruleus lights up. Other studies of the nucleus accumbens showed abnormal firing rates in scanned addicts who were deep into an episode of craving. Drug hunger in abstinent addicts, it appeared, was not all in the head, or strictly psychological. Cravings have a biological basis, and brain scans helped to clinch the case.

Graphics credit: http://learn.genetics.utah.edu

A 12 Days of Christmas Blog Meme

Wrapping it up.

From DrugMonkey’s blog: “The rules for this blog meme are quite simple. Post the link and first sentence from the first blog entry for each month of the past year.” (Credit to Janet Stemwedel and John Lynch for the idea.)

Here are the 12 first lines from 2011 here at Addiction Inbox. Click month for full story:

January: Films popular in Europe feature more drinking episodes per movie than their equally popular American counterparts, according to a report by the European Centre for Monitoring Alcohol Marketing (EUCAM).

February: The Director of the Office of National Drug Control Policy issued a warning about the new synthetic stimulants now being clandestinely marketed as bath salts or insecticide.

March: The U.S. Drug Enforcement Administration (DEA) exercised its emergency scheduling authority yesterday to outlaw the use of “fake pot” products.

April: In the first published examination of thirdhand smoke pollution and exposure, researchers at San Diego State University discovered that non-smokers who move into homes purchased from smokers encounter significantly elevated nicotine levels in the air and dust of their new homes two months or more after moving in.

May: What would it be like to have written a drug memoir and an autobiography before you turned 30? Would it seem like the end or the beginning? Are there any worlds left to conquer?

June: The song is not about cigarette addiction, but it could be.

July: Readers may remember the dark day of January 1, 2008, when the U.S. set an all-time record: One out of every 100 adults was behind bars. That’s more than 2.3 million people

August: The cost of addiction treatment is a legitimate medical expense, as long as you are talking about drug and alcohol addiction, which the IRS recognizes as a genuine medical disease.

September: The DSM-V, when it debuts it 2012, is set to replace the category of “Substance-Related Disorders” with a new category entitled "Addiction and Related Disorders." 

October: It’s official: The Obama administration has thrown off the gloves, repudiating Attorney General Eric Holder’s vow of two years ago that the federal government was not interested in prosecuting “state-legal” cannabis activity.

November: They first turned up in Europe and the U.K.; those neon-colored foil packets labeled “Spice,” sold in small stores and novelty shops, next to the 2 oz. power drinks and the caffeine pills.

December: After years of tightening regulation and dramatic declines in the number of adult smokers, Big Tobacco is targeting teenagers like never before.

Photo Credit: http://simplemom.net

Drug Addiction in 10 Slides or Less

Dr. David Friedman explains it all.

Dr. David Friedman, a professor of physiology and pharmacology at Wake Forest University School of Medicine, is also the co-founder and director of the Addiction Studies Program, a workshop for science journalists in Washington, D. C., funded by the National Institute on Drug Abuse (NIDA).

Sometimes it helps to step back and attempt to make the scientific case for addictive disorders as simply as we are able. Herewith, some highlights from Dr. Friedman’s useful presentation at the recent Addiction Studies Program workshop. Slides reproduced with Dr. Friedman’s kind permission. The comments adjacent to the slides are my own, as are any errors of fact or interpretation.

 There are important distinctions to be made between drug abuse and drug addiction, as Dr. Friedman makes clear in the slide to the right and the slide below. Unfortunately, government agencies have tended to take the position that any drug use is ipso facto drug abuse; a political position not well supported by the relevant science

  As a chronic medical condition, or “brain disorder,” addiction has a fair amount in common with other diseases, like hypertension, asthmas and diabetes, Friedman said. Relapses and setbacks are frequent, but not found in every case. 

  The key questions, indeed: What is different about the brains or the genes or the nerve cells of those who become dangerously addicted, compared to those who can take it or leave it? Scientists have discovered various so-called “markers” over the years in the brains of the children of adult alcoholics, but none of these have been broad enough in scope to point toward anything like an effective near-term treatment. However, the recent shift from chasing genes to studying neurobiological brain processes is a hopeful turn of events.

Again, a crucial distinction must be made between a state of physical dependence (at right) and a state of withdrawal (below). Non-addicts can become physical dependent on a variety of prescription medications. Such physical dependence precedes a full-blown state of addiction, but is not to be confused with addiction itself.

 The symptoms and intensity of drug withdrawal can vary from horrifying to essentially non-existent. It depends upon the drug, the drug taker’s metabolism, the social setting, environment and expectations of the users, etc. Craving and withdrawal represent the basic mechanism responsible for relapse.

 Most people are familiar with the “rebound effect” sometimes produced by over-the-counter nose sprays. Whey you inhale these medications regularly enough, the result of going turkey is… a profoundly stuffed-up nose.

In an effort to expand on the “chronic disease of the brain” label affixed by former NIDA director Alan Leshner, Dr.Friedman directs our attention toward specific brain mechanisms: reward, motivation, and memory.

Addiction is a pediatric disorder, Friedman emphasizes. This is particularly true with marijuana abuse and addiction.  Lke sugar in your blood, you can choose to control the amount of drugs you take, but you cannot choose your reaction to them.

We know for certain these days that adolescent brains are not yet fully formed, and that adolescent brains react to drugs differently than adult brains. For example, recent studies show that the actual composition of adult nicotine receptors in the brain is affected by exposure to nicotine in adolescence.

The net result of all this? Things happen at the biochemical level that change how things play out at the behavioral level.







Photo Credit: http://www.wakehealth.edu/

Book Review of "Drunken Angel"

A hipster gets his shit straight—sort of.

Addiction memoirs remain one of the most popular forms of autobiography on the shelves. But now, when considering a new addition to the genre, it’s impossible not to wonder whether the claims being made by the author are genuine. Since serious drunks often end up visiting the lower circles of hell during the course of their disease, hair-raising and improbable scenes are lamentably common—that is part of the genre’s charm, if that is the right word for it. But how are we to react now? The answer is, you can’t know, and you never really could, that bastard James Frey notwithstanding.

But read them we do. Alan Kaufman, the author of the lively but exasperating autobiography of alcoholism, Drunken Angel, sweetens the pot considerably. He drops so many names, and finds himself involved in so many improbably episodes of transnational mayhem and kinky sex, that the escapades could almost fill a Bond novel. But to be fair, there’s nothing debonair going on here; not from a man who describes himself at one stage as “filthy, nauseous, hungover, astonished at my gargantuan appetite for the abyss.” And a willing suspension of disbelief, an attitude of innocent until proven guilty, must hold sway in the end, else why read them at all?

Alan Kaufman is more Jack Kerouac than James Bond: One of the founding members of California’s Spoken Word scene, editor of The Outlaw Bible of American Poetry, Kaufman bounced through the beat/hippie/downtown scenes in New York, and San Francisco and Israel, writing for Jewish publications, treating his wives shabbily, and blacking out all over whatever town he happened to be in. It’s not pretty, and it’s not meant to be. The deep layer of poverty and grunge that settles over the author’s existence between bouts of the literary high life caused Kirkus Reviews to complain that “Drunken Angels” was marred by the author’s tendency to whip schizophrenically “between manic moments of literary self-aggrandizing and deeply depressive moments of shocking wreckage.” That’s true—but Kaufman is also a classic case of dual diagnosis, an alcoholic who also suffers from delusions, hallucinations, and Post Traumatic Stress Disorder after his time spent in the Israeli Army. (It’s complicated.) Also known as co-morbidity, this combination often makes for complicated, even potentially fatal difficulties, as on a bus ride with his wife one night, when he “realized that certain passengers were Satanists who had singled out Anna and me for human sacrifice.” Not good.

Down and almost out, he is scooped from the gutter by an acceptance letter from the Columbia University Master of Fine Arts program, where he hobnobs with Tama Janowitz and Steve Jobs’ sister, the writer Mona Simpson. But always, there are “the nightmares, the operatives, the unfolding skein of sinister designs” that Kaufman must negotiate as his mental health deteriorated. And the drinking never really stopped.

Finally, in order to both prove he’s sick and to signal his distress, Kaufman slit his wrists, then “staggered to the bathroom, wrapped white towels around the bloody wounds, and with a sense of exhilaration, called 911.” Perhaps the reader may be forgiven for not sharing in the exhilaration at this stage of the narrative, after reading about the author being ejected from crash pads by acid dealers for bad debts, dodging alimony and child support, neglecting a daughter on another continent, veering into sadomasochistic sex (in considerable detail), sleeping in filthy gutters, on warm street grates, on park benches. Kaufman made a habit of sitting down at restaurant tables to finish off the leftovers. “Ate donuts from garbage cans, pizza crusts from sidewalks, half-rotten fruit found in doorways. I kept my cash for booze…” In one excruciating scene, he tracks down an ex-girlfriend in her class at Columbia, calls her a whore in front of the class, and hits her in the face. A roomful of witnesses to that one, presumably. “In all this,” he tells us,” I never once lost my grip on the scotch bottle. Not a drop lost.”

So, that was it for Columbia. “All my life,” Kaufman writes, “ I had been going, fleeing. Leaving. Home, friends, jobs. Cities, countries, armies. Marriages, families—everything…. Anything but this, anyone but you, anywhere but here.” That was also about it for common sense from our anti-hero. We are pretty safe, it seems to me, in assuming that only a blackout alcoholic with severe mental problems is likely to wake up with a cruel hangover, married to the total stranger he finds lying in bed next to him. And then proceed to try and make the marriage work.

But in time, the story arc swings toward redemption, and Kaufmann falls in with AA and the Twelve Steppers.  “You’re allergic to alcohol and obsessed with it at the same time," an AA companion tells him. “The combination is fatal and unstoppable. Once booze hits your system, the jig’s up: you must drink.” And, to his immense credit, at long last, Kaufman gets straight, and eventually stays that way, even if the sordid circumstances of his life do not instantly change for the better. One of the most valuable lessons Kaufman takes away from AA (one of the most valuable lessons many people learn there) is a hoary old maxim called HALT: Don’t get too Hungry, Angry, Lonely, or Tired. All serious trigger conditions for relapse in freshly abstinent alcoholics and other drug addicts.

His book is a reminder that all of an addict’s life problems do not blessedly vanish the instant he or she stops drinking or using, any more than a regular schedule of insulin injections ends all problems for diabetics—the more so in cases where addiction is mixed with diagnosable mental illness. Getting clean and sober does not eliminate Kaufman’s sexual aggression, his tendency to lie to his wives, or bring back his ability to write steadily for a living.

In the end, Kaufman met a lot of famous people, managed to get published in some very hip venues, helped spark a poetry movement in San Francisco—and has now been clean and sober for more than 20 years. So what does he have to say about the prime mover of this amped-up narrative, alcoholism itself? It happened in the usual way—a formative alcohol experience at a young age. In early high school, a football player, Kaufman went out with some school buddies and without much thought began passing around those big gallon jugs of cheap Gallo wine. “I felt the universe swim into view. I stumble, drunk, to the grass and lay with arms and legs akimbo, like an altar sacrifice smiling at the blazing stars. For the first time in my life, I felt connected, happy, sure that life belonged to me and I to it. And I drank myself unconscious.”

Travelling alone in Germany, late in the book, after a nightmarish tableaux of temptation arranged for him by a cadre of Russian soldiers ready to pour vodka down his gullet in the spirit of macho brotherhood, Kaufman breaks away and finds a quiet spot in a deserted train car, and holds his own AA meeting in his head. “My name is Alan, I’m an alcoholic,” he says silently to himself. And then he says the Serenity Prayer, “then the 12 steps, and, appointing myself as guest speaker, shared about the experience I’d just had with Russian soldiers and endless vodka.” The phantom faces of his AA friends “kept me company right until I reached Berlin. And they are always with me, to this day, the meeting that I carry in my soul.”

Photo credit: http://www.booksmith.com/

Addiction Specialist Kicks Off A3 Academy in L.A.

Filling the void between “doing nothing and formal treatment.”

Good news for recovering addicts and addiction experts in Los Angeles: Dr. Adi Jaffe, a well-known addiction psychologist from UCLA and a longtime friend of Addiction Inbox, is kicking off a new venture: the A3 Academy.

 Dr. Jaffe, who runs the All About Addiction website, and writes a column for Psychology Today, knows whereof he speaks, having spent 8 years as a meth addict and drug dealer in a former lifetime. “The A3 Academy is specifically formulated to fill the void between doing nothing about addiction and formal addiction treatment,” Dr. Jaffe said. The inaugural academy will be held on Tuesday, September 6th, in West Los Angeles (2001 Barrington Ave.) at 6:00 PM, and is intended to become a weekly event. Information, tickets, and details of online participation are available HERE. Or you can email for information at academy@allaboutaddiction.com.

“If it has to do with addiction,” we’ll probably cover it,” Dr. Jaffe said. He plans to integrate “informational sessions, process groups, life planning, mindfulness, nutrition, and expert consultation with leading addiction experts from the Los Angeles area and beyond.”

Dr. Adi told Addiction Inbox that “local LA people can attend the event, and others can stream and watch, and the cost is purposefully low. It's going to be an educational/empowerment sort of thing that will adapt to the needs of the specific group attending.”

Judging by his blog postings at All About Addiction, Dr. Jaffe brings a wealth of information and experience to the task—as well as being an accomplished public speaker. “I’ve learned a lot about the genetic, behavioral, and environmental influences on addiction and drug-abuse,” he says. “Whatever you’re comfortable calling addiction, there’s no doubt that it’s having a great, negative, impact on those it affects. More than 500,000 deaths and a burden of more than $500 million dollars are attributed to substance abuse every year in the United States alone. I think it's time we get real about the problem and stop using stigma and misinformation to hide behind.”

Photo Credit: http://www.findallvideo.com/tag/live-in-fitness

On Harm Reduction and Metabolic Chauvinism

My WebTalk Radio interview for the podcast, “Addicted to Addicts.”
  

 Listen to the podcast at WebTalkRadio HERE.
(Addiction Inbox is now on vacation. Hot fun in the summer sun...)