The Black Bag: Odds and Ends

Drug news from the world of science and medicine.


--How Marijuana Impairs Memory

Mo Costandi at the UK Guardian expands on his Nature article about the mechanisms that result in memory impairment when people smoke marijuana. Memory formation depends on the neurotransmitter glutamate. What goes wrong when you smoke pot? Enter the astrocyte…

--Coffee Will Disrupt Your Sleep—Unless You’re a Night Owl

From Scientific American comes the news that your “chronotype”—the chronological patterns you naturally favor—may determine whether or not caffeine keeps you tossing and turning and night. Morning people, or “larks,” had more periods of wakefulness during sleep hours than night people, or “owls.” The findings, published in the journal Sleep Medicine, show that “for the early risers, the more caffeine in their bodies, the more time they spent awake during the night after initially falling asleep. This was not seen in the night owls.”

--Brain Scans Get Better

You wouldn’t know it from all the bad press about moving heads and specious interpretations, but fMRI technology continues to improve. Time Healthland reports that new machines will be able to do a better job spotting traumatic brain injury in military personnel, athletes, and accident victims. High-definition fiber tracking, as this article in the Journal of Neurosurgery explains, will allow medical staff to better assess damage to nerve fibers deep in the brain, due to technological improvements in “assessing white matter injuries that are not apparent in standard anatomical imaging.”

--Cig Makers Trump FDA on Free Speech Grounds

The FDA maybe didn’t think this one through quite as thoroughly as they should have. Reuters reports  that a U.S. judge “sided with tobacco companies on Wednesday, ruling that regulations requiring large graphic health warnings on cigarette packaging and advertising violate free-speech rights under the U.S. Constitution.” Evidently, FDA officials didn’t see the 1st Amendment argument coming. By mandating grisly pictures of diseased lungs, rotting teeth, and dying smokers on cigarette packs, “the government has failed to carry both its burden of demonstrating a compelling interest and its burden of demonstrating that the rule is narrowly tailored to achieve a constitutionally permissible form of compelled commercial speech," U.S. District Judge Richard Leon said.

--Meth Head Burns Down Tree Older Than Jesus

And finally, as if we needed any more evidence, here’s a story about bad decision-making among the meth head crowd: WFTV reports that a female meth addict in Seminole County, Florida, burned down a historic cypress believed to have been the world’s 5th oldest tree. Authorities learned that the woman and a friend had been cooking methamphetamine under the 3,500 year-old tree. Officials said the woman took pictures of the disaster with her cell phone, and was quoted saying: "I can't believe I burned down a tree older then Jesus."

Photo Credit: http://www.squidoo.com 

Is Gambling the Opiate of the Masses?

 
Two new books tackle gambling’s addictive mysteries.

Charles Fey, the American who invented the three-reel slot machine in 1898, is a well-known part of gambling history. But few people have heard of Inge Telnaes, the mathematician credited with the invention of the “virtual reel” almost 90 years later, in 1984. The virtual reel worked like this: The Telnaes patent allowed slot machine makers to store the various symbols on the spinning reels as digital data on microprocessor chips. After that, random number generating software produced the actual results in the form of three-symbol sets. So far so good. But inherent in the process was another step—the “virtual stop.” And this idea was a real killer. As gambling guru Donald Catlin wrote at Casino City Times:

Virtual reels contained more stops than were contained on the real reels, which meant that the probability of a particular symbol appearing on the pay line had nothing to do with its frequency on the real reels and everything to do with its frequency on the virtual reels.  If this seems deceptive to you, consider the following quote taken from the Telnaes patent submission: "Thus, it is important to make a machine that is perceived to present greater chances of payoff than it actually has within the legal limitations that games of chance must operate."

Pretty straightforward. You could program a thousand stops per reel, if you wanted to. The advantage was that you could post huge jackpots without the fear of anyone hitting them very often, because when gamblers thought about a line of 7s on those three reels, they were in fact facing many more spin combinations than they realized.

But I digress. We all know the house wins. Gamblers know it, too. Gambling can be defined as an activity in which something of value is put at risk in a situation where the outcome is uncertain. That’s really all there is to it. And for most people, it all adds up to little more than an evening of escapist fun.

So how do pathological gamblers gets so turned around? Viewing their behavior from the outside, it’s hard to have sympathy with them—the same way it can be hard to have sympathy for alcoholics. Willful self-destruction often looks like the only way to account for it. 

Heavy gamblers, the kind of gamblers who get into major debt, are people who get an unnatural buzz out of winning and losing money. Like most things having to do with addiction, it’s complicated, and involves a spiral of negative, damaging behavior that transcends bad habits or lack of self-control. They’re the ones in the casinos well past midnight, drink in hand, cigarette burning in the ashtray, and perhaps making the occasional sprint to the restroom for a snort of cocaine or meth. Slot attendants tell stories about gamblers who would rather urinate in their clothes than leave a machine. What, exactly, accounts for that kind of behavior?

For one thing, gambling and alcohol go together like…. cigarettes and alcohol. Gambling is being proposed as an addition to the bible of psychiatry, the DSM-5. All three habits often function together as a set of multiple addictions. The reason for this may be biological. Consider the unexpected side effects caused by certain dopamine-active medications for Parkinson’s. Some seniors who take the drugs begin to feel an uncontrollable urge to, that’s right, go to the casino and gamble. They prefer slot machines, and sometimes lose a lot of money. When they go off the medications, they lose interest in their new hobby—which lends a certain weight to the argument that some compulsive gamblers act the way they do because of innate biochemical dysfunctions. They do it, Howard Shaffer believes, because gambling is one manifestation of the disease he calls “addiction syndrome.”

Howard J. Shaffer and Ryan Martin, writing in the Annual Review of Clinical Psychology, note that just as there are divisions between alcoholic drinking, heavy drinking, and social drinking, there are also differences between pathological gambling, excessive gambling, and social gambling. Pathological gambling has proven to be “a more complex and unstable disorder than originally and traditionally thought.” Once the neurophysiology of the gambling state of mind came under scrutiny, the parallels with addiction cropped up everywhere. Shaffer, a professor of psychiatry at Harvard Medical School and director of the Division on Addiction at Cambridge Health Alliance  (see my interview with him here), notes that “the rate of pathological gambling in America has remained relatively constant for the past 35 years, despite a huge expansion in the opportunities on offer.” 

Change Your Gambling, Change Your Life, by Howard Shaffer, written with Ryan Martin, John Kleschinsky, and Liz Neporent, follows a relaxed workbook approach to problem gambling. Perhaps the most useful aspect of the book’s organization is its division into what we could call co-morbid chapters. Gamblers with anxiety, mood disorders, impulse control problems, or drug addictions each warrant their own section of the book, in order to personalize the advice. Organized in this way, the authors explicitly recognize the likelihood that problem gamblers do not normally suffer the condition in isolation from other mental health and substance use issues.

Shaffer gives a variety of useful advice concerning triggers, and methods for controlling urges. He believes that the risk of developing addiction syndrome involves “a complex interaction of genetic, psychological, social, and other factors.” Shaffer estimates that about two million Americans suffer from some level of addictive gambling disorder, with another 3.5 million gamblers with problem behaviors that don’t meet the addictive threshold.

In fact, the overlap between problem gambling, mental health problems, and other forms of addiction is staggering. According to numbers from the National Epidemiologic Survey on Alcohol and Related Conditions cited in the book, more than 11 percent of heavy gamblers suffer from generalized anxiety disorder; up to 50 percent have exhibited mood disorders; 40 percent qualified for an impulse control disorder; and 50 percent can be classified as “alcohol dependent."

Professor Shaffer takes a nonjudgmental stance on the question of moderation versus abstinence, while cautioning the problem gambler about the realities of having “the self-control to bet a little when he has the urge to bet a lot.” To attempt moderation, a gambling addict (or alcoholic for that matter) must be willing to accept the consequences of being unsuccessful. However, some research shows that those who engaged in disordered gambling “move on from excessive gambling to less gambling over time,” according to Shaffer. There may be a simple explanation for this: “Many people with gambling disorders eventually run out of money.” (Back when I used to gamble regularly in casinos, I often joked that there was nothing quite like the uneasy thrill of risking money you really couldn’t afford to lose.)

But if you are serious about quitting, warns Shaffer, “you also need to be prepared for people who, for their own selfish reasons, deliberately entice you to gamble.” Really? This may sound unlikely, but I recall that in my own case, when I first stopped drinking, an older friend used to pour me drinks and leave them nearby—just in case I came to my senses. If you are a gambling addict, and know it, there are self-exclusion programs at most casinos, designed to allow gamblers to bar themselves for a specified period, in an arrangement rather like Linus and his blanket.

Shaffer also points to continuing work on various drugs for problem gamblers. Naltrexone, used for opiate and alcohol addiction, is one such candidate. (A University of Minnesota study showed that 40 percent of pathological gamblers abstained from gambling for at least a month while taking naltrexone.) So is nalmefene, which also operates on opiate brain receptors. Other medications under study include common SSRI antidepressants like Prozac and Celexa.

Change Your Gambling, Change Your Life is a structured, clearly written, nonjudgmental approach for motivated people wishing to deal seriously with their “disordered gambling.”
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Another book on gambling turned up in the book bag recently. In his e-book called Slots: Praying to the God of Chance, David V. Forrest, M.D., notes that casinos can clear as much as $2,500 per day from a popular slot machine. Not considered sexy or the domain of the high roller, slot machine action accounts for roughly 70 to 80 % of casino income. To attract young players, who tend to favor table games, slot machine manufacturers are experimenting with joysticks and a dollop of skill-based play—but it’s not clear, says Forrest, that older, established slot players want to substitute “a competitive mind-set for the meditative trance induced by the random spinning and stopping of the reels.” (Note: The last time your humble narrator played the slots in Las Vegas, the spinning induced an attack of intense vertigo and dizziness due to a chronic ear disorder. Talk about negative conditioning.)

How do you know if you’re a slot addict, like former Drug Czar William Bennett? “Looking forward to slot playing as the best thing in your future is not a good sign,” Forrest helpfully suggests. One casino on the East Coast uses the ominous advertising tag line: “You’ll Come Back.” Forrest mischievously notes that both “the American Psychiatric Association and the American College of Psychiatrists have traditionally refused to hold their annual conventions in Las Vegas for fear of seeming to endorse a behavior that can become pathological.”

Here are some of Dr. Forrest’s suggestions for the problem gambler:

-- Avoid playing alone.

--Play out your time, not your money.

--Break the hypnotic spell through thought and activity.

--Beware the dangers of comorbidity.

With this final admonition, Dr. Forrest lines up squarely with Howard Shaffer: “In my psychiatric experience,” he writes, “some of the most defenseless to the excesses of gambling have been bipolar patients in the manic phase of their illness.”

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

Harm Reduction Advocate Takes on the Abstinence Question

A guest editorial on “clean and sober” vs “drinking less.”

One of the most divisive issues in the harm reduction movement is the question of abstinence versus controlled drinking. This rift has come to symbolize differences over the AA philosophy, the disease model, the role of will power, and other issues related to addiction. Those who find the disease model unconvincing at best, and some sort of fraud at worst, are more likely to bristle at the notion that total abstinence is the only course available to the addict in treatment. But disease model proponents point out that, for most alcoholics, not drinking at all turns about to be easier than drinking a little. Still, for heavy drinkers who are not addicted to alcohol, cutting down often makes the most sense.

Kenneth Anderson of the harm reduction group HAMS has written an article on the abstinence question which is as straightforward and free of special pleading as any I’ve seen from the harm reduction movement. Bear in mind that I don’t agree with all of the opinions expressed in this guest post, and remain convinced that for most people who abuse alcohol regularly, sustained abstinence is the best policy. But I definitely believe it’s worth a read.


Drinking Again
By Kenneth Anderson

If you have successfully resolved your problems with alcohol via long term (6 months or more) abstinence from alcohol then HAMS urges you to use great caution before you consider drinking again. Studies (NIAAA 2009) show that about half of persons with Alcohol Dependence resolve the problem by quitting completely. HAMS is always supportive of total abstinence as a recovery goal; since the “A” in HAMS stands for Abstinence we like to say that “Quitting drinking is our middle name.” Harm reduction strategies are aimed at those who are unwilling, unable, or not yet ready to abstain from alcohol. This includes people who have attempted abstinence and ultimately not succeeded at it but instead have gone on major benders after short abstinence periods. It also includes those who have never attempted abstinence or who currently have no interest in abstinence. Increased trauma produces increased drinking (Denning & Little 2011). The more resources people have intact, the better their odds of achieving recovery–whether abstinent or non-abstinent recovery. Harm reduction helps keep people’s resources intact enabling them to recover more quickly and easily than if they lost all.

If you are succeeding at abstinence and your alcohol related problems have disappeared or are disappearing then we strongly urge you to continue with what you find to be working–i.e. abstinence. However, if you have already decided that you are going to dink again then HAMS is a safe place to experiment with controlled drinking and you will be far safer here than if you attempt this on your own with no support at all.

If you are wavering and have not yet decided whether or not you wish to drink again then we strongly suggest that you do a Cost Benefit Analysis (aka a Decisional Balance Sheet) which compares the pros and cons of continuing to abstain with the pros and cons of drinking again. We also suggest that you write out a list of alcohol related losses and problems and a list of what you have gained as a result of abstinence from alcohol.

Some people are more likely to succeed in drinking again than others:

People whose drug of choice was not alcohol. If you went to rehab for heroin or some other drug which was not alcohol you were probably told that you were cross addicted to all mood altering drugs and that you must never drink again or you would relapse. The simple fact is that this is not true. You may well have noticed your rehab counselors using mood altering drugs like caffeine and nicotine all the time and not calling this a relapse. The fact is that if you try to use alcohol as a direct substitute for heroin and get as drunk as possible all the time instead of shooting heroin then you will certainly have alcohol problems. However, if you get your life together and become a whole new person with a whole new life there is no chemical reason in your brain why you should not have an adult beverage at times. Opioids are directly cross-tolerant with each other; they are only slightly cross-tolerant with alcohol. Other drugs like speed are not cross tolerant with alcohol at all.

We do, however, very strongly recommend that if you are an ex drug user who is choosing to drink in moderation that you track your drinks by charting. Keeping a drinking chart will help you keep your drink numbers under control and let you know if you are starting to slip out of bounds. If you find your drinking is showing a tendency to “creep” up more and more you might wish to opt to return to abstinence from alcohol. We also strongly suggest that you do your experimenting within the safety net of a HAMS group and that you write out a Cost Benefit Analysis.

Another group who may tend to succeed with drinking again are those who were sowing a lot of wild oats in high school or college and wound up in rehab or an abstinence program in their teens or early twenties. If you are now in your forties you might have matured a great deal and no longer be interested in being the wild man. If you now find that moderate drinking is appealing to you but the thought of being a drunk teenager throwing up on your date’s shoes at a party is repulsive to you then you may well find success at becoming a moderate drinking. Again we suggest that you do your experimenting within the safety of a HAMS group and that you chart and do a Cost Benefit Analysis.

If you had a long drinking career and a long history of alcohol related problems then the odds of returning to controlled drinking are greatly reduced. The longer the drinking career and the more problems the lower the chances of successful controlled drinking.

If you think that you have a shot at becoming a successful controlled drinker, then write down what it is that has changed in your situation that you believe will make you a successful controlled drinker this time around. If nothing has changed then it may well be excruciatingly difficult to try to use the HAMS harm reduction and moderate drinking tools to become a controlled drinker. Not only may you find that your odds of success are low, but you may also find that staying within the moderate drinking limits you have set for yourself is a form of torture and that abstinence is far simpler and more pleasant.

HAMS harm reduction strategies are not a magic bullet which can turn everyone into a successful controlled drinker. For many, many people abstinence remains the best choice. Abstinence is simple and clear cut and avoids the problem of shades of gray

And whether you opt to continue to abstain or you choose to drink again, always remember that you and no one but you are responsible for your choices.


REFERENCES:

Denning P, Little J. (2011). Practicing Harm Reduction Psychotherapy, Second Edition: An Alternative Approach to Addictions. The Guilford Press.

NIAAA (2009). Alcoholism Isn’t What It Used To Be. NIAAA Spectrum. Vol 1, Number 1, p 1-3. (PDF)


Photo Credit: http://www.rehabinfo.net

Interview with Michael Farrell of Australia’s National Drug and Alcohol Research Centre.

On prisons, pot, and the DSM-V.

(The “Five-Question Interview” series.)

Our latest participant is Professor Michael Farrell, director of the National Drug and Alcohol Research Centre (NDARC) at the University of New South Wales in Sydney, Australia. Before that, he was Professor of Addiction Psychiatry at the Institute of Psychiatry at Kings College, London. He has been a member of the WHO Expert Committee on Drug and Alcohol Dependence since 1995, and chaired the Scientific Advisory Committee of the European Monitoring Centre on Drugs and Drug Abuse (EMCDDA) in 2008 for three years. The NDARC does a wide variety of research and data collection on drug abuse, including longitudinal studies of heroin dependence, studies on the prevalence of ADHD among addicts, and evaluation studies of inner city youth at risk. Professor Farrell is a recognized expert on drug abuse in Europe, and was kind enough to share some of his thoughts with Addiction Inbox.

1. Does the National Drug and Alcohol Research Centre (NDARC) of Australia have a specific research slant, or area or interest, or do you try to cover the waterfront?

Michael Farrell: The research base of NDARC is very broad. The Australian Federal Government provides a fifth of our funding under the National Drug Strategy and this includes a brief for national monitoring of drug trends among illicit drug users and improving the evidence base around effective treatment and prevention. Our projects cover the majority of illicit drugs as well as alcohol, prescription drugs and more recently tobacco, and we have a strong international presence through our collaborations with the United Nations, the World Health Organisation and the Global Burden of Disease project.

Our current research programs include prevention, treatment evaluation, policy, law enforcement, health economics and epidemiology. NDARC has two “Centres within the Centre”—NCPIC (see below) and the Drug Policy Modelling Program (DPMP). We have teams working with school-aged children, mothers and babies, and injecting drug users. So it would be fair to say that we are covering the waterfront!

2. You have been critical of proposed revisions in the Diagnostic and Statistical Manual of Mental Disorders (DSM), particularly as they relate to alcoholism. What do you think is going wrong, and what’s going right, when it comes to DSM-V changes?

Farrell: The change in overall terminology is probably the most controversial with the reintroduction of “addiction” into the terminology. Personally I prefer “dependence” and think the measurement of dependence has continued to improve over the years. It is important that we use terms that we can measure carefully and be confident that we are all talking the same language. Alcohol abuse and alcohol dependence have been combined into a single disorder of graded severity, the criterion reflecting substance-related legal problems has been removed, and a new diagnostic criterion representing craving has been included. Finally, new diagnostic thresholds for alcohol use disorder (AUD) have been proposed. It seems that there is strong support for the first three changes. However, there is little published literature regarding the impact of the revised diagnostic threshold. Using data from a survey of over 10,000 people in the Australian general population, Mewton and colleagues at NDARC (2010) demonstrated that the prevalence of alcohol use disorder defined according to the DSM-5 was 60 per cent higher than the prevalence of the same disorder according to DSM-IV. A disorder which increases so dramatically in prevalence after applying a new definition is surely problematic.

3. Increasingly, the study of addiction has moved away from traditional medicine and psychiatry, becoming a recognized area of study in molecular biology and neuroscience. How do you personally view this shift in emphasis toward hard science?

Farrell: In reality, no professional groups have been jumping at the chance to handle addiction problems. In the early phases of treatment development it was often religious groups and humanitarian social activist groups who pioneered helping responses for marginalised groups. As the size of the problem and response has grown, thankfully it has been possible to get mainstream health and social care professionals more involved. There is still a need for more involvement. Modern young doctors need addiction treatment skills if they are to be properly equipped to practice in the 21st century.

Greater involvement of the biological sciences in the study of addiction holds out the possibility that we might get some exciting breakthroughs in understanding of behaviour, prevention, and treatment.  Goodness knows we could do with some new breakthroughs or advances in treatment! A focus on biological sciences does not need to be at the expense of the other social and epidemiological approaches, and ideally, with further investment in research around drugs, we might better understand the interactions between genes and environment.

4. NDARC also houses the National Cannabis Prevention and Information Centre (NCPIC). What is the mission there, and do you see marijuana as an addictive drug?

Farrell: NDARC is privileged to have NCPIC funded by the Federal Government as a “Centre within a Centre” and to the best of my knowledge there is nowhere like it anywhere else in the world. The mission of NCPIC is to reduce the use of cannabis in Australia. Cannabis is the most commonly consumed illicit drug in the country, with one in three (33.5%, 5.8 million) Australians aged 14 years and older reporting having used it in their lifetime. Just over one in ten (10.3%, 1.9 million) had used it in the previous twelve months. The burden of disease associated with cannabis is substantial. I have no doubt that cannabis can result in dependence, and that the stronger, more potent forms of cannabis give rise to more physical and mental health problems. Cannabis dependence seems to occur at rates similar to alcohol, but the effects of cannabis dependence can be mild, and may be associated with otherwise high levels of social function. Equally, dependence at the severe end is associated with significant harms, including poor social functioning and reduced participation in the education and the workforce.

5. You have a long-standing interest in the question of substance abuse in the prison system. Why can’t prison officials eliminate the drug trade behind bars?

Farrell: The prison authorities cannot eliminate drugs from behind bars because nearly half of all prisoners have a history of serious drug involvement. It is no more likely that we will have a drug free prison than it is that we will have a drug free society. The serious gaps in response in prisons are often quite shocking. The near complete absence of methadone or buprenorphine treatment in American prisons is hard to understand, when you see what a great contribution US research and treatment with methadone and buprenorphine has had globally. Now there are over 300,000 people on methadone in China as part of HIV and AIDS prevention.  Most countries in Europe have methadone in their prisons, and many emerging countries have developed prison methadone programmes. But in the US there are only a handful of programmes. There is a need for real change in this area as it is an incredible gap that could be readily addressed.

Overall we still have a long way to go in building an evidenced-based approach to drug prevention and treatment. We have come a fair distance in the past twenty years, but the road remains long and winding.

Photo Credit:  http://ndarc.med.unsw.edu.au/ 

Book Review: Addiction Noir

 
The Next Right Thing by Dan Barden

To date, I’ve only reviewed one novel here at Addiction Inbox—Steve Earle’s I’ll Never Get Out of This World Alive, featuring the ghost of Hank Williams standing in for the addictive pleasures that musicians are heir to. Now comes The Next Right Thing by Dan Barden, an exemplar of a new literary genre I am going to call addiction noir. Dial Press, the Random House imprint that published the book, is putting Barden forward as a recovering alcoholic who has grokked this scene from the inside. “Dan Barden knows firsthand the difficulties of sobriety…. The Next Right Thing is a powerful new take on the recovery narrative.”

“I’m a recovering alcoholic,” Barden said in the press release, “and I had always wanted to write something about that experience but I couldn’t find a way to tell that story that didn’t seem stupid.”

That changed one morning while Barden was reading the New York Times. “It occurred to me that I could put everything I knew about recovery into a crime story…. There are a lot of great novels about the disease of addiction itself but not so many about recovery, mostly because there’s something very oblique and mysterious about recovery.”

The elements of Barden’s novel certainly aren’t new—a knowing, seen-it-all reformed alcoholic who happens to be an ex-cop, for starters—and plenty of unsavory bad guys. Add in the requisite women, attractive and troubled, or, as our hero Randy Chalmers prefers them, “insane and beautiful.” Chalmers is looking into the suspicious heroin overdose of his AA sponsor, Terry, in a rundown Santa Ana motel, fifteen years sober at the time of his death. The investigation leads Chalmers, sober himself for 8 years, into a tangle of recovery houses fronting as marijuana grow sites and secret shooting sets for amateur porn videos. The crisp quips and one-liners are often focused on the world of addiction. There are nice set pieces, and Chandleresque observations:

--“Those were the days of crack pipes and precious little eating. Even after she got her bearings back, she moved with the anxious, staticky jerks of a cartoon cat. She radiated disease.”

--“I hit him without thinking… but I was surprised to be once again acting without my own consent. That’s the way people talk about taking a drink, as though it’s happening to someone else at some gauzy distance. Like your arm is lifting the glass, and your consciousness has nothing to do with it.”

--“Even with all the step work and therapy and success, people still imagine they will be okay when the are rich. Or married. Or have a baby. Life for an alcoholic is often a process of discovering all the things that don’t make any difference.”

However, the book is marred by the kind of bewildering rumination that can result when a soap opera full of characters is at full boil: “Something about the recovery house scheme didn’t sit right with me. And why was this Simon Busansky character missing in action? Why had Mutt Kelly parked outside my house? Who had made that call to Cathy? Who was the business partner who so preoccupied Terry during the birth of the child he’d always wanted?”

Nevertheless, the book reads quickly, like a noirish mystery should. For influences, Barden lists the usual suspects—Raymond Chandler, Elmore Leonard, Robert B. Parker, George Pelecanos. With decent sales, I could see this becoming a book series, with our sober ex-cop getting himself involved in helping the wrong addict, or helping acquit the right one. With the public recognition of addiction seemingly at an all-time high, and with the ranks of the recently recovered always in the process of being replenished, there just might be a market for this sort of thing.

In a press release, Barden said the book was about “people who are trying to live sober lives against all odds. And what that’s like for me and my friends is complicated and beautiful and dramatic and terrifying. What’s it like to try to do the right thing by your family and friends when many of your instincts run against that?”

Or, as Randy Chalmers puts it: “Here’s another thing you learn in A.A.: when the drunk loses the woman he loves, you know you’re not at the end of the story. You know it’s going to get much worse.”

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

Interview with Dr. Bankole Johnson of the University of Virginia

Tailoring addiction medicine to fit the disease.

(The “Five-Question Interview” series.)

25 years ago, when Dr. Bankole Johnson first began giving lectures about addiction and neurotransmitters in the brain, he had a hard time getting a hearing. That’s because 25 years ago, everybody knew what addiction was: a lack of “moral willpower.” Or, at best, some sort of psychological “impulse control” disorder.  

As a neuropharmacologist by training, and currently professor and chairman of the University of Virginia’s Department of Psychiatry and Neurobehavioral Sciences, Dr. Johnson thought otherwise, and went on make a name for himself by discovering that topiramate, a seizure drug that boosts levels of the neurotransmitter GABA, could be used in the treatment of alcoholism. “I just wasn’t a hospital-type doctor,” he once said. “I was for more intersted in research than clinical practice.” Johnson’s work was featured in the 2007 HBO series, "Addiction."

Born in Nigeria, Dr. Johnson attended the University of Oxford and received his medical degree in Glasgow, Scotland in 1982. At the time, medical understanding of addiction was poor to nonexistent. “Everything we knew—really knew—probably could be written on the back of a postage stamp,” he recalled.

Since then, Dr. Johnson has published numerous articles on psychopharmacology and addiction, and has served on several National Institutes of Health committees and panels. (See my earlier POST on Johnson’s study of drugs for addiction in the American Journal of Psychiatry.)


1. You’re a native of Nigeria. How did you first become interested in medicine?

Bankole Johnson: My father was a doctor and encouraged me. Back then, I had little interest in medicine and was more interested in the arts and perhaps going to law School, for which I had been promised a scholarship.

2. Addiction is called a “disease of the brain,” in Alan Leshner’s famous phrase, but it is still a hugely controversial subject. Are innate biological differences the cause of addiction?

Johnson: Addiction is a brain disease. The roots of the disease lie in brain abnormalities, and these are exacerbated when a vulnerable person uses alcohol excessively or takes illicit drugs.

3. How did you discover that topiramate helped some alcoholics drink less?

Johnson: It was an idea that developed from a hypothesis I came up with based on brain neurochemistry. The central idea was to alter the signals of dopamine, a critical path for the expression of rewarding behavior, through two different and opposite systems—glutamate and GABA.

4. That work led to Topamax for alcoholism, and your more recent work with ondansetron, another GABA antagonist. But what role do environmental and sociocultural factors play in the development of addiction?

Johnson: The environment interacts with genes and brain chemistry to govern behavior. But in the end, it is the changes in the brain that ultimately direct alcohol and drug taking behavior.  The environment therefore provides the context and tuning of the neurochemical signals in the brain.

5. Some people find the notion of addiction as a progressive and incurable condition a hard pill to swallow, so to speak. Why has effective medical treatment for addiction been so slow to develop, and why hasn’t talk therapy been more effective?

Johnson: Talk therapy has some effectiveness, but alone it is not a comprehensive or robust treatment. Progress in the last two decades has been quite rapid. With growing and clear acceptance of the neurobiological underpinnings of addiction, the next decade should herald even more exciting discoveries.  For example, our work on pharmacogenetics promises to provide effective medications—such as ondansetron—that we can deliver to an individual likely to be a high responder, based on his or her genetic make up.

Photo Credit: Luca DiCecco

PROMETA Postmortem

How the latest miracle cure for addiction failed to deliver.

PROMETA™: Last seen going down fast, smoke pouring from all engines.

As reported here at Addiction Inbox, a double-blind placebo-controlled evaluation of PROMETA™ by W. Ling and associates, published online last month in the journal Addiction, found that the much-publicized treatment protocol for meth addiction “appears to be no more effective than placebo in reducing methamphetamine use, retaining patients in treatment or reducing methamphetamine craving.” The authors of the journal paper didn’t accuse Hythiam, the company that makes and sells the product, of not telling the truth. They just said that the treatment didn’t work. The study authors did, however, find evidence of “potential financial conflicts of interests among its advocates…”

An earlier CBS News "60 Minutes" news report in 2009 had raised similar questions, but generated a great deal of publicity for PROMETA™. And the only testing available, a small open study from Texas, had shown positive results. Testimonials began mounting, and a few prominent doctors in the addiction field lent their names to the marketing effort. More conservative voices, like Richard Rawson and the University of Pennsylvania’s Tom McClellan, warned that there was insufficient scientific evidence to push forward with the new treatment—but their concerns were swept aside amid the general enthusiasm for a long-sought antidote to the ravages of methamphetamine addiction.

So how did it happen? And what, if anything, does it teach us about the enterprise of addiction research and treatment?

An editorial by Dr. Keith Humphreys of the Stanford University Medical Centers, which  accompanied the report of the clinical trial in Addiction, attempted to analyze the saga of how “a former junk bond trader with no medical background raised $150 million in capital to market a combination of three medications (gabapentin, flumazenil and hydroxyzine) as a treatment for methamphetamine addiction.” Bear in mind that only one of the drugs—gabapentin—had ever been involved in clinical trials against addiction, with decidedly mixed results. As for the other ingredients, a prominent neuroscientist who blogs pseudonymously as Neuroskeptic, commented at the time: “What the hell kind of a cocktail is that? Gabapentin—OK, it might reduce anxiety and stabilize mood, although the evidence is poor and if you wanted to do that, there are better drugs. Ditto for hydroxazine. And why you want both of those is unclear. But flumazenil? That doesn't do much if you haven't taken a benzodiazepine. But if it did do anything it would be to antagonize the gabapentin.”

All in all, not a promising analysis.

The three drugs are approved for various uses by the FDA, and there is the rub: Off-label practices allow physicians to prescribe medications for uses other than those listed on the official package insert. As useful as this practice can be, it creates a situation in which a “combination of previously approved medications can be marketed without review as a new treatment protocol, despite the fact that none of the individual medications had any evidence nor were originally approved as a treatment for the condition the new protocol targets.”

Under this directive, Hythiam was free to promote the combination of approved medications as a new addiction treatment advance without any significant testing, Humphreys contends.

If the treatment, in the end, proved to be no better than placebo for meth addiction, what made it seem like such a successful new thing under the sun at the outset? Wishful thinking, Humphreys believes: “Many serious, good-hearted people will be shocked at Ling’s negative results because they believed sincerely… we must not yield to our powerful collective desire to believe before we have hard evidence of effectiveness from disinterested, respected sources. The simpler, faster and more miraculous-seeming the cure, the greater should be our skepticism.”

Furthermore: "As was the case with another would-be ‘miracle cure’—ultra-rapid opiate-detoxification—a manufacturer was able to market an untested treatment protocol to addicted patients…”

Why? Because “off-label use of medications is well-established in medical practice and has significant value in many cases, but a balance must be struck with the risk this creates for evasion of the normal safety and efficacy checks by creators of new treatment protocols."

"We have a huge advantage at this historical moment which was not available to people in prior eras who could not determine whether ‘Dr. Keeley’s Double Chloride of Gold Injections’, ‘Dr. Revaly’s Guaranteed Remedy for the Tobacco Habit’ and ‘Dr. Meeker’s Addiction Antidote’ were effective,” writes Humphreys. Namely, “a well-developed addiction treatment research enterprise." And because of that, we should “point with pride to Ling et.al.’s work as an example of how high-quality science can inform suffering people about what will help them and what will not; and those who set public research budgets need look no further for an example of return on investment.”

HUMPHREYS, K. (2012). What can we learn from the failure of yet another ‘miracle cure’ for addiction? Addiction, 107 (2), 237-239 DOI: 10.1111/j.1360-0443.2011.03652.x

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