Addiction Doctors Pick Top Ten Journal Articles

A screen for problem gambling, medications for insomniac alcoholics, and more.

A group of addiction doctors presented a Top Ten List of peer-reviewed articles from 2011 at the American Society of Addiction Medicine’s Annual Medical-Scientific Conference in Richmond, VA. Dr. Michael Weaver presented the findings, noting that the list was “reached by consensus, and articles were selected not only for their quality but also to represent different areas of addiction medicine.” Dr. Weaver stressed that “not all published studies were done really well, and some may not apply to the patients treated by a particular clinician.”

According to Dr. Edward Nunes, with the Department of Psychiatry at Columbia University, the journal articles provide a "nice mixture on epidemiology and clinical outcome or clinical trials research,” which represent “the type of evidence most relevant to patient care."

Thanks to Catharine Zivkovic (@ccziv) for drawing attention to this list. The summaries are my own. Disclaimer: In some cases, these brief summaries are based solely on a reading of the journal abstracts.

1. 

Hsueh-Han Yeh, M.S. et al. (2011). Five-Year Trajectories of Long-Term Benzodiazepine Use by Adolescents: Patient, Provider, and Medication Factors. Psychiatric Services 62(8): 900–907.

 A Taiwanese study analyzing benzodiazepine prescription records came up with a simple solution: “Prescribers can reduce the risk of long-term use by assessing whether pediatric patients have received benzodiazepines from multiple doctors for various medical conditions.” Huh. Who’d have thought of that one, eh? But for various reasons, such checks, and the open records required to make them possible, are the exception rather than the rule in current health care systems. The study group found that for long-term users under 21, defined as anyone in receipt of a benzodiazepine prescription for 31 or more days in a calendar year, one in four patients fell into the categories of “accelerating or chronic users.” Specifically, “A history of psychosis or epilepsy, prescription by providers from multiple specialties, and receipt of benzodiazepines with a long half-life or mixed indications significantly increased one's risk of becoming a chronic or accelerating user.”

2. 

McBride, O, and Cheng, Hui G. (2011) Exploring the emergence of alcohol use disorder symptoms in the two years after onset of drinking: findings from the National Surveys on Drug Use and Health. Addiction 106(3): 555-563.

This study looked for clinical features of alcohol dependence and socially maladaptive drinking patterns during the first 24 months of alcohol use, based on stats from the 2004-2007 National Surveys on Drug Use and Health (NSDUH). Result: New alcohol users “frequently experienced problems relating to self-reported tolerance, spending a great deal of time recovering from the effects of alcohol and unsuccessful attempts at cutting down on drinking. The likelihood of experiencing the clinical features increased steadily in the first 9 months after use, but appeared to plateau or only gradually increase thereafter.” The researchers suggest there may be a window of opportunity during the 2nd year of drinking.

3.

Volberg, Rachel A., et al. (2011) A Quick and Simple Screening Method for Pathological and Problem Gamblers in Addiction Programs and Practices. The American Journal on Addictions. 20(3): 220-227.

Doctors, as these researchers point out, don’t often screen their patients for pathological gambling. To combat this, the investigators offer health professionals brief computer screenings they have developed for use in identifying problem gambling. “Given the high rates of comorbidity, routine and accurate identification of gambling-related problems among individuals seeking help for substance abuse and related disorders is important.” 

4.

Alford, Daniel. P., et al. (2011). Collaborative Care of Opioid-Addicted Patients in Primary Care Using Buprenorphine: Five-Year Experience. Archives of Internal Medicine 171(5):425-431.

Buprenorphine remains an underused but often effective treatment for opiate addiction, the authors of this study maintain. The cohort being studied was a group of addicted patients under the dual care of general physicians and nurse care managers. “Of patients remaining in treatment at 12 months, 154 of 169 (91.1%) were no longer using illicit opioids or cocaine based on urine drug test results,” the investigators report. However, dropout rates were high. The researchers did find that the nurse-doctor model was workable: “Collaborative care with nurse care managers in an urban primary care practice is an alternative and successful treatment method for most patients with opioid addiction that makes effective use of time for physicians who prescribe buprenorphine.”

5. 

Kolla, B.P., et. al. (2011) Pharmacological Treatment of Insomnia in Alcohol Recovery: A Systematic Review. Alcohol and Alcoholism 46: 578-585.

In this Mayo Clinic review of drugs used for sleep problems in alcohol recovery, the authors combed through more than 1,200 articles and reported that, of all the old and new drugs being used, an old and rarely used medication—trazadone—improved sleep measures as reliably as anything else that was tested. Gabapentin got good but equivocal marks due to questions about testing and inclusion criteria. Topiramate and carbamazepine helped in some cases. Furthermore, “in single, small, mostly open-label studies, quetiapine, triazolam, ritanserin, bright light and magnesium have shown efficacy, while chlormethiazole, scopolamine and melperone showed no difference or worsening. Conclusion: Trazodone has the most data suggesting efficacy.”

6.

Bohnert, A.S., et. al. (2011). Association between opioid prescribing patterns and opioid overdose-related deaths. Journal of the American Medical Association 305: 1315-1321.

Accidental prescription overdose deaths are on the rise, and this group of university researchers in Ann Arbor and Indianapolis thinks it may have something to do with how the dosing instructions are usually worded.  They set out to investigate “the association of maximum prescribed daily opioid dose and dosing schedule (“as needed,” regularly scheduled, or both) with risk of opioid overdose death among patients with cancer, chronic pain, acute pain, and substance use disorders.” They found from VHA hospital records that “the frequency of fatal overdose over the study period among individuals treated with opioids was estimated to be 0.04%.” The risk for overdose was directly related to the “maximum prescribed daily dose of opioid medication.” And patients who stuck with regular dosages, or took opioids “as needed,” were not at any elevated risk for overdose. Another obvious but frequently overlooked conclusion: “Among patients receiving opioid prescriptions for pain, higher opioid doses were associated with increased risk of opioid overdose death.”

7. 

Allsop, D.J. et al. (2011). The Cannabis Withdrawal Scale development: patterns and predictors of cannabis withdrawal and distress. Drug and Alcohol Dependence 19(1-2):123-9.

Rates of treatment for marijuana abuse and addiction are increasing, say these Australian authors, along with relapse rates. They have devised a Cannabis Withdrawal Scale that measures such withdrawal effects as associated distress, strange dreams, trouble sleeping, and angry outbursts—common manifestations of withdrawal from weed. The scientists maintain that their “Cannabis Withdrawal Scale can be used as a diagnostic instrument in clinical and research settings where regular monitoring of withdrawal symptoms is required.”

8.

West, R., et al. (2011) Placebo-Controlled Trial of Cytisine for Smoking Cessation. New England Journal of Medicine 365: 1193-1200.

This important study assessed the effectiveness of the drug cytisine in smoking cessation programs, and a potential star was born. In a single-center, randomized, double-blind, placebo-controlled trial, the journal paper concluded that “cytisine was more effective than placebo for smoking cessation. The lower price of cytisine as compared with that of other pharmacotherapies for smoking cessation may make it an affordable treatment to advance smoking cessation globally.”

9. 

Elkashef A., et al. (2011) Topiramate for the treatment of methamphetamine addiction: a multi-center placebo-controlled trial. Addiction Published online 12/16.

Conducted at eight medical centers across the U.S., this study found that for most of the 140 methamphetamine-dependent adults under scrutiny, use of topiramate produced “abstinence from methamphetamine during weeks 6-12.” That’s the good news. Unfortunately,  “secondary outcomes included use reduction versus baseline, as well as psychosocial variables… topiramate did not increase abstinence from methamphetamine during weeks 6-12.” That’s the bad news. And here’s the silver lining, as far as the investigators are concerned: “Topiramate does not appear to promote abstinence in methamphetamine users but can reduce the amount taken and reduce relapse rates in those who are already abstinent.”

10.

Levina. A., et al. (2011). Molecular Mechanism for a Gateway Drug: Epigenetic Changes Initiated by Nicotine Prime Gene Expression by Cocaine. Science Translation Medicine 3(107) 107-109.

There really is s a gateway drug. In fact, there are two of them in our culture. Almost every potential addict starts out with alcohol or cigarettes or both. Because they are legal and easily available. So is cocaine and marijuana, once you get the hang of it, but in the beginning, and all around us, it’s booze and cigs. The amazing premise of this final study is this: “Pretreatment of mice with nicotine increased the response to cocaine, as assessed by addiction-related behaviors and synaptic plasticity in the striatum, a brain region critical for addiction-related reward.” Nicotine primes subjects for cocaine addiction, in effect. “These results from mice prompted an analysis of epidemiological data, which indicated that most cocaine users initiate cocaine use after the onset of smoking and while actively still smoking, and that initiating cocaine use after smoking increases the risk of becoming dependent on cocaine, consistent with our data from mice. If our findings in mice apply to humans, a decrease in smoking rates in young people would be expected to lead to a decrease in cocaine addiction.”

Photo Credit: www.flickr.com/

A Drug For Marijuana Withdrawal?

Researchers get good results with gabapentin.

Marijuana, as researchers and pundits never tire of pointing out, is the most widely used illegal drug in the world, by a serious margin. And while the argument still rages, for some years now drug researchers have been migrating to the camp that sees marijuana as an addictive drug for a minority of people who exhibit a propensity for addiction. The scientific literature supporting the contention of marijuana as addictive for some users is robust and growing, as is the body of anecdotal evidence.  It’s also clear that in many countries, cultures, and subcultures, combining cannabis with tobacco is a common practice that increases health risks all around.

Ongoing work at the Scripps Research Institute’s Pearson Center for Alcoholism and Addiction Research in La Jolla, California, has focused in part on the lack of FDA-approved medical therapies for treating marijuana addiction. Barbara J. Mason and coworkers at Scripps have reported preliminary success in a 12-week, double-blind, placebo-controlled pilot study with 50 treatment-seeking volunteers, using the anti-seizure drug gabapentin. Gabapentin, sold as Neurontin, pops up as a possible treatment for various forms of pain and anxiety, and sharp-eyed readers will recall that gabapentin was one of the ingredients in the now-defunct addiction drug Prometa.

Marijuana addiction numbers are hard to come by, and often inflated, since many small-time pot offenders end up in mandatory treatment programs, where they tend to be classified as marijuana addicts, whether or not that is objectively the case. Nonetheless, there are plenty of people seeking treatment on their own for cannabis dependence. For people strongly addicted to pot, the problems are very real, and withdrawal and abstinence pose serious challenges. People for whom marijuana poses no addictive threat should bear this in mind, the way casual drinkers bear in mind the existence of alcoholism in others.

The study, published recently in Neuropsychopharmacology, says that “activation of brain stress circuitry caused by chronic heavy marijuana use” can lead to withdrawal symptoms that persist “for weeks or even months, as in the case of marijuana craving and sleep disturbances.” A variety of existing medications have been tested in recent years, including buspirone, an anti-anxiety medication; Serzone, an antidepressant; and Wellbutrin, an antidepressant commonly used for smoking cessation. None of these treatments has shown any effect on cannabis use or withdrawal, according to Mason.

Gabapentin, as the name suggests, was modeled after the neurotransmitter GABA, and works via a transporter protein to raise GABA levels. Effective only for partial-onset seizures, common side effects include drowsiness, dizziness, and possible weight gain. It is a popular anti-epileptic drug, because it is relatively safe, with a low side-effect profile, compared to many of the medications in its class. For the same reasons, it is a common treatment for neuropathic pain. In addition to neuralgia, it has found some use as a migraine preventative.

Gabapentin normalizes GABA activation caused by corticotrophin-releasing factor, or CRF. CRF is a major player in the brain’s stress responses. As it turns out, withdrawal from both cannabis and alcohol ramp up anxiety levels by increasing CRF release in the amygdala, animal studies have shown. “Gabapentin had a significant effect in decreasing marijuana use over the course of treatment, relative to placebo,” the authors report. In addition, gabapentin produced “significant reductions in both the acute symptoms of withdrawal as well as in the more commonly persistent symptoms involving mood, craving, and sleep.”

As a bonus, the researchers discovered that “overall improvement in performance across cognitive measures was significantly greater for gabapentin-treated subjects compared with those receiving placebo.” Gabapentin was associated with improvement in “tasks related to neurocognitive executive functioning”—things like attention, concentration, visual-motor functioning, and inhibition. Counseling alone, represented by the placebo group, “resulted in less effective treatment of cannabis use and withdrawal, and no improvement in executive function.”

As in the case of Chantix for cigarette cessation, a treatment, which now requires additional caveats about possible suicidal ideation, researchers looking for a treatment for drug withdrawal, must weigh the benefits of pharmacological treatment against the possible side effects of the treatment itself. Does gabapentin for marijuana withdrawal pass the “Do No Harm” test? According to Mason, it does. “Gabapentin was well tolerated and without significant side effects” in the admittedly small trial study. The two groups did not differ in the number of adverse medical events reported in the first two weeks, when dropout rates due to side effects are highest in these kinds of studies. The investigators were not relying solely on self-reporting, either. They used urine drug screens, and verified that only 3% of the study sample tested positive for other drugs.

In short, the authors report that gabapentin reduced cannabis use and eased withdrawal with an acceptable safety profile and no signs of dependence. Gabapentin, the authors conclude, “may offer the most promising treatment for cannabis withdrawal and dependence studied to date.” Further clinical research is needed, of course, but the positive results of this proof-of-concept study should make funding a bit easier.

Mason, B., Crean, R., Goodell, V., Light, J., Quello, S., Shadan, F., Buffkins, K., Kyle, M., Adusumalli, M., Begovic, A., & Rao, S. (2012). A Proof-of-Concept Randomized Controlled Study of Gabapentin: Effects on Cannabis Use, Withdrawal and Executive Function Deficits in Cannabis-Dependent Adults Neuropsychopharmacology DOI: 10.1038/npp.2012.14

Photo Credit: http://pep3799.hubpages.com/

Dude, where’s my metaconsciousness?

“Lost in the sauce.”

I have to admit I was taken with the opening sentence of this 2009 study published in Psychological Sciences: “Alcohol consumption alters consciousness in ways that make drinking both alluring and hazardous.”

Indeed it does. There’s no improving on that direct statement about the basic paradox presented by booze: Like so many pleasures, it is both seductive and dangerous. I was further intrigued by the prospects held out by the abstract, which promised “a rigorous examination of the effects of alcohol on experiential consciousness and metaconsciousness.” After all, we have come a long ways from the 50s, when alcohol was seen in Freudian terms, as a way of releasing tension, steam-engine style.

The study, by Michael A. Sayette and Erik D. Reichle of the University of Pittsburgh in Santa Barbara, along with Jonathan Schooler of the University of California at Santa Barbara, walks us through the salient recent theories, including the alcohol-myopia theory that gained a foothold in the 90s. In this theory, alcohol “reduces processing capacity so that a great proportion of this capacity has to be devoted to the demands of immediate, ongoing activity.” Like remaining upright, or inserting a key in the lock of a door. It also means that alcohol consciousness is precarious. The pissed-off office worker who comes home to drink may relieve his worries “if he is distracted by television, but he may ‘cry in his beer’ if no such distraction is available.”

One of the alluring and hazardous affects of alcohol is its tendency to cause what the study authors meticulously refer to scientifically as: zoning out. That is to say, episodes of mind wandering.

Enjoy drinking while you read? Listen to this: “Participants who drank alcohol were mind-wandering without awareness of doing so about 25% of the time that they were engaged in the reading task. This frequency was more than double that for participants in the placebo condition.”

The study—“Lost in the Sauce: The Effects of Alcohol on Mind Wandering?”—investigated “the effect of alcohol on both the occurrence of mind wandering and the capacity to notice that one’s mind has wandered.” The psychologists gathered 50 men between 21 and 35, put them in a lab, and then split them into a control group and test group. The participants entered the “drink-mixing room where a research was waiting with a tray containing a chilled vodka bottle, a bottle of chilled cranberry-juice cocktail (Ocean Spray), a glass, a graduate cylinder, and a beaker.”

Participants are never in short supply for this kind of clinical study. For half the group, the bottle contained 100-proof Smirnoff. The placebo group got flattened tonic water in a glass pre-slimed with vodka, and were later given fake blood-alcohol test results to further the illusion that they’d had a little alcohol. The drinking participants achieved a mean blood alcohol level of 0.067. Participants in the placebo group received a bogus reading of 0.045, which is the “highest credible reading for deceived participants.”

How did the researchers know if the drinkers were zoning out? They asked. But first, they set them to work reading the first five chapters of War and Peace on a computer. The experimenters asked each participant if they had read War and Peace, in whole or in part, before the experiment, and “all indicated that they had not.” (Men aged 21 to 35, recall.) Their task was to read the first 34 pages of the book, or read for 30 minutes, whichever came first. Before starting, the researchers drilled them on the technical description of zoning out: “At some point during reading, you realize that you have no idea what you just read.”

That’s it in a nutshell, and as we all know, you don’t have to be drunk to experience that effect—but it helps. We have all been witness to the drunk who “loses the thread” of his or her monologue and heads off in another linguistic direction altogether, without apparently noticing the shift. The researchers asked participants to hit a special key, helpfully marked “ZO,” when they noticed during reading that they had zoned out. And they used an additional probe measure, interrupting the readers with a tone and asking them if their mind was wandering or concentrated on the text at that moment. At the end of the session, both groups took a 20-question true/false test on what they had read.

So, what were the differences? Both the placebo group and the drinking group spend about the same amount of time reading, and scored roughly the same on the reading comprehension test. No significant differences in reading rates or immediate retention. And when the researchers compared the first, self-reported measure of mind wandering, the two groups were also “similar in the frequency with which they caught themselves zoning out.”

The big difference showed up when researchers compared the frequency of mind wandering as measured by the arbitrary prompts. In that case, the drinkers zoned out twice as often, but were less likely to catch themselves at it. What the drinkers appeared to be sacrificing was a significant degree of meta-awareness, the act of “thinking about thinking.”

So, when they got probed, what were the drinkers thinking about instead of War and Peace? According to the authors, “alcohol seemed to particularly increase distraction related to sensory states, such as hunger, thirst, and other consummatory motives.” One might be tempted to call them “mammalian motives,” in the sense that alcohol intoxication sometimes reduces drinkers to back-brain, lower-order, fight-or-flight responses not highly compatible with meta-cognition.

This is not exactly a groundbreaking study, it’s fair to say. But it does point up the fact that only a few ounces of alcohol can induce episodes of mind wandering which are not detected by the drinker—mini-blackouts, in a manner of speaking.

Although a reduction in working memory capacity is part of the answer, it is not the whole story. What else fuels this “alcohol myopia” is unclear, but the authors suggest that their findings represent the first practical demonstration that “alcohol disrupts individuals’ meta-awareness of the current contents of thought.” Or, as a heavy drinker might be prone to put it, “Now where was I?”

Graphics Credit: http://www.pnas.org/

“Addiction Fiction”

Coming-of-Age Drug Novels

Call it “addiction fiction.” In the past few years we have seen a blossoming of this genre, where the private eye goes to 12-Step meetings, and one day your sponsor may just save your life by gunning down a rival in the street. Or, where the wise-beyond-their-years prep school drug addicts engage in Brett Easton Ellis-style sex and ennui.

Fiction readers of a certain age will recall that this is not a new thing under the sun. From Junky to The Man With the Golden Arm, from Naked Lunch to Less Than Zero, drug novels have always been with us. Addiction fiction has two distinct subgenres: addicts with money, and addicts without money. For obvious reasons, the latter genre is the prevailing one—Trainspotting and Requiem for a Dream come to mind. But the wealthy end of the spectrum is not without representation. Consider The Basketball Diaries, or Bright Lights, Big City.

As an example of the first type of book, the one where the addict has no money, we have Spoonful, by first-time author Chris Mendius. As for the upscale second type, there is the recently released novel, No Alternative,  by William Dickerson, a budding film director with an MFA. I would judge both authors to be well south of the age of 40, making both of them pure examples of Generation X. 

Ah, the 90s. As time passes, it seems clear that the death of Kurt Cobain has been added to the touchstones of American youth culture, in a tradition going back to the 60s. Where were you when Kennedy died? When Lennon died? When Cobain died? This last question matters, since Nirvana and Cobain are threaded thematically through both of these new novels. As Chris Willman wrote at Stop the Presses: “April 5 is to many contemporary rock fans what November 22 is to older baby boomers: the day you can almost certainly remember where you were or what you were doing when you heard that ___ died. That's not to say that Kurt Cobain's suicide represented a loss of national innocence in the same way that JFK's assassination did. For one thing, Cobain's whole life and career already symbolized lost innocence, long before he died.”

In Generation X drug novels, lost innocence isn’t lost—there was never any innocence in the first place.

Michael, the narrator of Spoonful, is the kind of drug addict with no money. Michael is forthright, if not one to probe the philosophical ironies of his condition: “Nobody ever says, ‘When I grow up, I want to be a junkie.’” End of story. Well, the beginning, really. In this well-written junky novel, author Chris Mendius brings his tragic characters to life in a manner that calls to mind Hubert Selby, Jr.’s stark New York classics of addiction without redemption.

Set in Chicago’s Wicker Park area, young Michael and his pal Sal find their way to heroin in a hurry. They also quickly learn the flip side of the illness—the sickness of withdrawal, “like having a debilitating combination of food poisoning and the flu, with periodic muscle cramps.” No matter. “Once we made it through all that, we decided to stay off dope. A month passed with no discernible improvement in our lives and we promptly resumed getting high.”

It’s heroin he craves. Michael is no fan of cocaine: “You’re up all night, running your mouth, jaw twitching, nose burning. You might want to fuck but you can’t. All you can do is keep going. Before you know it, the birds are chirping and the garbage trucks are rolling. You’re out hundreds of dollars and for what?” And they scoff at pharmaceutical efforts at non-addictive synthetic opiates, “engineered to not let anyone feel a moment of undeserved pleasure.” One character likens kicking methadone to “getting your skin pulled off with pliers.”

The debate over freely distributing the drug naloxone as an anti-OD safety measure is referred to obliquely: “That’s the thing with smack. It’s a fine line between the time of your life and the end of your life…. More often than not, the difference between life and death was having someone there to revive you or call somebody who could.”

Mendius is good at drawing a picture of the addict’s endless grind: “Finding the ways and means to score is a twenty-four-seven gig. You might get lucky and hit it big now and then but you’re always looking ahead. Plotting. Planning. No matter how much you get or how close the scrape, you always gotta keep at it. Day in and day out.”

Michael never quits for long, and when he is off heroin, he buries himself in marijuana and booze. There is no redemptive ending. He walks off into the sunset.

From seedy Chicago to the upper reaches of Westchester, New York. Like Spoonful, No Alternative by William Dickerson features characters whose collective memory goes back no farther than the 80s. Which sucked, as we all know, and as Thomas, the narrator, never tires of telling us. Thomas and his friends are drug and alcohol abusers with money. The drugs of choice are prescription medications, not heroin or cocaine, for these products of Fordham Prep. 

It is 1994, and the grunge youth of Yonkers, the children of Vietnam vets and hippies, are rootless and confused. “There was no clear-cut path beckoning them. No modus operandi.” It was a generation, Dickerson writes, that “earned a label that was just about as vague as their sense of what to do with their lives: Generation X.” In this version, not much has changed since the crack-crazy L.A. 80s of Brett Easton Ellis. The names and the drugs have been altered, but otherwise the trappings are indistinguishable: high disposable income and excessive ennui.

Thomas supports his crazy little sister Bridget, who becomes a white rapper named Bri Da B. His sister’s drug of choice is cutting herself: “She was determined to be in control. If she was going to bleed, it was going to be a decision, it was going to be controlled, and she was going to bleed everywhere, not just from the abyss between her legs. If pain was to be a constant, might as well get used to it and build up a tolerance.”

No Alternative is readable enough, but it does not carry the campy forward motion of other rich-kid addiction books. It is more measured, dry, and there is an odd hitch in the narration, which is resolved, rather shakily, at the end, with a big Reveal that distracts the reader from the central relationships in the story.

So, two early novels, by promising young writers, about drugs and what they do to you. It will be interesting to find out what becomes of these authors, and what manner of new work they get up to in the future. The story never ends where you think it does.

Ivan Oransky on the Disease Model at TEDMED 2012

What we think about when we think about “disease.”

It’s a safe bet that the number of M.D.s who have made a mid-career switch to journalism is rather small. And when Dr. Ivan Oransky did it, he didn’t go in for half measures. The former online editor of Scientific American, and the former deputy editor of The Scientist, Oransky now serves as Executive Editor of Reuters Health. He teaches medical journalism at New York University, where he also holds an appointment as clinical assistant professor of medicine—while maintaining three, yes three, separate blogs. He is well known for two innovative blogs known as Retraction Watch and Embargo Watch. And he recently kicked off a personal blog, the Oransky Journal.

So clearly, he’s a very lazy man. Nonetheless, he found time to give a very popular talk on the shortcomings of the disease model of medicine at last week’s TEDMED conference in Washington, D.C. And he found additional time to grant me an interview afterwards, with some interesting thoughts on how the mania for medicalization could affect addiction treatment.

Speaking at the Kennedy Center for the Performing Arts, Oransky compared patients in the nation’s current medical system to baseball coach Billy Beane, a once-promising player who washed out in the minors and was recently portrayed by Brad Pitt in the movie Moneyball. “Our medical system is just as bad at predicting what’s happening to patients as baseball scouts were at predicting what would happen to Billy Beane,” Oransky told the audience of 1,500.

“Every day, thousands of people across the country are diagnosed with pre-conditions,” he said. “We hear about pre-hypertension, we hear about pre-dementia and pre-anxiety. We also refer to sub-clinical conditions, like sub-clinical hardening of the arteries. One of my favorites is called sub-clinical acne. If you look up their website as I did, you’ll see that they say this is the easiest acne to treat. You don’t have any pustules or inflammation—you don’t actually have acne.  I have a name for preconditions—I call them preposterous.”

Every year, according to Oransky, “we are spending more than two trillion dollars on health care," and yet more than 100,000 people a year are dying from complications of the treatments they're getting, rather than from the conditions that are being treated. [Revised 4-15]. And most patient advocacy groups eventually learn to “expand the number of people who are eligible for a given treatment” for fundraising purposes, he said.

As evidence of this trend toward medicalization, Oransky pointed to the novel notion of a “previvor.” According to FORCE, the cancer research advocacy group that coined the term: "A previvor is a survivor of a predisposition to cancer.” The term is used to describe someone who, for example, has a genetic risk for breast cancer, but has not been diagnosed with the disease. “Previvor was coined in 2000 after a challenge from a community member who said she ‘needed a label,’” according to the group’s web site.

We are all previvors of some disorder, Oransky argues. In the spirit of giving everyone a precondition, Oransky coined the term “pre-death.” What is pre-death? “Every single one of you has it,” Oransky told the audience, “because you have the risk factor for it, which is being alive."

Using his favorite metaphor—baseball—Oransky explained the secret of Billy Beane’s revolutionary success as a coach: “The secret wasn’t to swing at every pitch, like the sluggers do. You had to find the guys who liked to walk, because getting on base by a walk is just as good. And in our health care system, we need to figure out, ‘is that really a good pitch, or do we need to let it go by, and not swing at everything?’ We all need to keep in mind that in medicine, sometimes less is more.”

After his talk, I asked Oransky how the theme of medicalization might apply to the disease of addiction. Medicalization, he said, is a matter of “taking advantage of people, manipulating them so they can’t make informed decisions.” In the case of addiction treatment, Oransky pointed to the “proliferation of ads for treatment in beautiful places. It’s all selling and self-diagnosis. They’re selling you on the fact that you need to be treated.” He also pointedly referred to the practice of “medical astro-turfing,” where a supposedly grass roots effort by patients or advocates is “usurped by interest group pressure.” Sometimes that usurpation is patently obvious, is in the case of many advocacy groups set in motion and funded by pharmaceutical companies or the liquor industry.

Sometimes, of course, you do need to be treated. And Oransky notes that in health areas such as addiction and mental illness—disorders where social stigma remains high, compared to, say, a blood infection—there are “fewer pressures to medicalize.” And possibly, too few pressures to medicalize. “There’s no quick and easy test, no MRI where you can point to the place in the brain that lights up and say, “you are an alcoholic.” The science of addiction, which has been moving by fits and starts into the medical mainstream, has a long way to go, compared with many other disease categories. And it has left a gap through which medical workers and treatment staff can march, chanting, “I have a system,” Oransky says.

Perhaps, then, the study of addiction to alcohol and other drugs requires both more medicalization of the research kind, and less of the “precondition” or “sub-clinical” kind. As for the second kind, Oransky believes we are already medicalizing binge drinking in a counterproductive way. In addition, “there are always attempts to widen the market. Look at how obesity has been made to overlap with addiction.” As for medications being used to combat craving among addicts in treatment, Oransky noted the tendency to “repurpose” drugs on the basis of soft data. “They took wellbutrin, an antidepressant that didn’t work very well, and offered it for smoking cessation. So I would want to see data that is really robust” before treating addicts with such medications.

On the other hand, Oransky noted, “We don’t have to worry about malaria, we don’t need to medicalize tuberculosis. But do diseases that have a strong stigma, like addiction, actually benefit from medicalization?  If we find out that they do, than we should do it.”

There’s something else Oransky believes is overdue for true medicalization: “The social determinants of health care—poverty, the way we build our suburban environments. Concentrate on stuff that we know kills people. Medicalize that.”

In the end, he said, “we need to use marketing strategies to effectively get treatment to the people who need it, not to the people who don’t.”

From Their Mouth to Your Ear: Researchers Talk Drugs

A collection of five-question interviews.

I’ll be away from the Addiction Inbox office this week, attending the big TEDMED health and medicine powwow in Washington, D.C.

In the meantime, here’s a summation (with links) of the interviews I’ve been doing recently in the “five-question interview” series. I’ve been very lucky to nab some state-of-the-art thinkers, working at the top of their fields, from psychiatry to pharmacology to neuroscience.

See below for the story thus far:



David Kroll, former Professor and Chair of Pharmaceutical Science at North Carolina Central University in Durham, is now Science Communications Director for the Nature Research Center at the North Carolina Museum of Natural Sciences.

“The attraction to users was, until recently, that Huffman cannabis compounds (prefixed with "JWH-" for his initials) could not be detected in urine by routine drug testing. Hence, incense products containing these compounds have been called ‘probationer's weed.’" MORE

Vaughan Bell is a Senior Research Fellow at the Institute of Psychiatry, King’s College, London. He is also honorary professor at the Universidad de Antioquia in Medellín, Colombia.

"I was very struck by the appearance of classic Kluver form constants [after taking ayahuasca], geometric patterns that are probably caused by the drug affecting the visual neurons that deal with basic perceptual process (e.g. line detection)." MORE

Jon Simons, a cognitive neuroscientist, is a lecturer in the Department of Experimental Psychology at the University of Cambridge, UK, and principal investigator at the University’s Memory Laboratory.

“If you’re at a party and happen to drunkenly strike up conversation with Angelina Jolie (or Brad Pitt, if you prefer) and, bowled over by your charm and witty repartee, she tells you her phone number, you may well not remember it when you wake up sober the next morning. However, the evidence suggests that you would have a better chance of recalling the number if you got drunk again." MORE

Bankole Johnson is professor and chairman of the University of Virginia’s Department of Psychiatry and Neurobehavioral Sciences.

“With growing and clear acceptance of the neurobiological underpinnings of addiction, 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." MORE

Michael Farrell is the 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.

“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." MORE

Deni Carise is a clinical psychologist who serves as senior vice president and chief clinical officer at Phoenix House, a leading U.S. non-profit drug treatment organization with more than 100 programs in 10 states.

“Those in recovery see the disease of alcoholism or addiction as a moral obligation to get well. If you know you have this disease and the only way to keep it under control is not to use alcohol or drugs, then that’s what you have to do." MORE


Keith Laws is professor of cognitive neuropsychology and head of research in the School of Psychology at the University of Hertfordshire, UK.

"Some may tolerate 100s or even 1000s of E tablets, but for others far fewer may lead to memory problems. We can predict that 3 in 4 users will develop memory problems, but not which 3 or after how many tablets." MORE

photo credit: http://www.startawritingbusiness.co.uk

Interview with Cognitive Neuropsychologist Keith Laws

LSD, E, CBT, and “Mind-Pops.”

Our latest participant in the “Five Question Interview” series is Dr. Keith Laws, professor of cognitive neuropsychology and head of research in the School of Psychology at the University of Hertfordshire, UK. Dr. Laws holds a Ph.D. from the Department of Experimental Psychology at the University of Cambridge, and is the author of Category-Specificity: Evidence for Modularity of Mind. He has written extensively on cognitive deficits resulting from certain types of neurological injury, and has won several awards for his research on cognitive functioning in schizophrenia. He also maintains an active interest in the challenges of functional brain imaging. Professor Laws is frequently quoted in the British media, and is the author of more than 100 peer-reviewed articles. He is a Chartered Psychologist and an Associate Fellow of the British Psychological Society. And recently, Professor Laws became a blogger, launching the LawsNeuroBlog. He maintains a web homepage, and is virtually unbeatable in the category of obscure British rock trivia.

1. LSD is back in the news, with a rehash of several old studies on acid and alcoholism. A lot of people would like to revive research interest in LSD, MDMA, magic mushrooms, and other psychedelics. What’s your view?

Keith Laws: Yes, “re-hash” is an appropriate phrase—we are witnessing a rebranding of “counter-culture” as “over-the-counter-culture.” The history of LSD research is frequently retold as if grand therapeutic advances were halted because hostile governments criminalised LSD. The bottom-line, however, is that most studies of the 50s and 60s produced little worthy of further scientific pursuit. The recent meta-analysis of 60s studies examining whether LSD reduces “alcohol misuse” is a case in point.

That meta-analysis consisted of 6 trials—none of which produced a significant effect, but their total pooled effect suggested some impact on alcohol misuse. In my recent post on this study, I highlighted a series of points, including: how it is likely that further negative studies have been gathering dust in the file drawers of researchers over the years; how some samples consisted of people with serious comorbid mental health and neurological problems (schizophrenia, epilepsy, organic brain disorder, low IQ); and crucially, how the authors made the totally unfounded assumption that anyone dropping-out of the studies had relapsed into drinking. This had a large and disproportionate impact on the control samples in those studies—as many more dropped out from control groups. Combined with the lack of significant effects in any one study, doubts exist about relying on these data as a justification for starting large-scale trials of LSD for alcoholism. We should certainly skeptically regard statements by some, such as Professor David Nutt, that LSD is “as good as anything we’ve got for treating alcoholism.”

2. Tell us about your research interest in the effect of Ecstasy (MDMA) on memory.

Keith Laws: First, I think its crucial not to confuse E and MDMA. Studies of MDMA in humans are few, and mostly examine acute effects via self-report. The vast majority of studies though, including our work, examine the residual effects of street-E in abstinent users i.e. taking largely unknown compounds mixed with varying degrees of MDMA. For me, the real public health issue relates to street-E since most people outside of the lab rarely get to consume pure MDMA.

In 2007 we meta-analysed 26 studies that had examined memory on standardized tests in over 600 ecstasy users and 600 non-users and found significant long and short-term verbal memory impairments in 75% of users. Intriguingly, E was unrelated to visual memory problems; however those who also smoked cannabis did display significant visual memory impairment. A key finding of ours was that the lifetime number of E tablets consumed was unrelated to the degree of memory impairment. This led to a host of misrepresentations in the media and amongst E users who saw it as license to take as many Es as they want. I view this finding, however in a much starker light—taking E is akin to playing Russian Roulette with your memory. Some may tolerate 100s or even 1000s of E tablets, but for others far fewer may lead to memory problems—we can predict that 3 in 4 users will develop memory problems, but not which 3 or after how many tablets. Of course, ecstasy (like Cannabis) is often advocated as a safe-ish drug because it rarely kills. Indeed, metrics of drug harm developed in the UK emphasise physical and social harm, but fail to explicitly acknowledge the cognitive problems associated with E and other recreational drugs. Given that as many as 500,000 young people in the UK use E each week and 75% are affected, then that’s 375,000 young people developing significant verbal memory problems!

3. You’re not convinced by the findings of a recent study of magic mushrooms, where the researchers documented an overall decrease in brain activity. What else could account for this effect?

Keith Laws: Well, the surprising thing about the Carhart-Harris et. al. psilocybin study was the general pattern of brain deactivation, which contrasts with the findings of activation in others such as Vollenweider and colleagues in Switzerland who find increased activation. The decreased activation especially in the medial prefrontal cortex (mPFC) and the posterior cingulate cortex (PCC) were curious and reminded me of the similar deactivation in these areas linked both to anxiety and to the anticipation of unpleasant events. It occurred to me that the prospect of tripping in a scanner may be quite anxiety provoking, and several features of the study led to me to think this may have been the case. First the order of testing was always the same - participants received the placebo scan always before the psilocybin scan and so, could always anticipate the trip— potentially heightening anxious anticipation in that condition. Second, Carhart-Harris et. al. measured “anxiety” and “fear of losing one’s mind” and both multiplied many fold in the psilocybin condition. Interestingly and subsequently, Vollenweider and colleagues pooled date from 23 studies and found that experimental settings involving scanning most strongly predicted unpleasant and/or anxious reactions to psilocybin - converging directly on my suspicion. Although nobody would deny that hallucinogens such as psilocybin impact brain function - the question is which parts reflect the “trip” and which parts reflect “anxiety about the trip”?

4. You have also looked at the matter of using cognitive behavioral therapy for various kinds of mental disorders. How does CBT measure up, in your opinion? Is it useful for addiction?

Keith Laws: Yes, unlike any other country, the UK endorses using CBT to treat psychotic symptoms and to prevent relapse in schizophrenia. Indeed, “NICE” (the National Institute of Clinical Excellence), which decide which treatments are made available to UK patients, suggest that we offer CBT to “all people with schizophrenia”. Anyway, we meta-analysed the data for whether CBT reduces symptomatology or prevents relapse and came to the conclusion that the evidence supports neither. Crucially, CBT only appeared to “work” when the therapists were not blind at outcome assessment i.e. they knew to which group the patient was assigned (CBT or control)! The irony is that CBT therapists sing the mantra of evidence-based practice!

In terms of the use of CBT in people with substance abuse problems, it produces a small impact on abstinence with opiates, stimulants and cocaine, but has little or impact on alcohol use; and as one might expect, these effects disappear across time. Some evidence also suggests that women respond better to CBT than men. Perhaps the most intriguing finding in this area is that CBT has had much greater success in reducing cannabis use, with up to 80% showing significant reduction in use.

5. What else have you been investigating recently? What are you excited about?

Keith Laws: Over the past 3 years or so I have been doing more work with individuals suffering from the obsessive compulsive syndrome of disorders i.e. OCD, Body Dysmorphic Disorder, Trichotillomania, Schizo-Obsessive disorder, Tourette’s, and Perfectionism. Our work is looking at phenotypes that might be expressed through this range of disorders and in their first-degree unaffected relatives. 

Other things we are working on include what we call “Mind-Pops”—those little thoughts, words, images, or tunes that suddenly pop into your mind at unexpected times and are totally unrelated to your current activity—described long ago by novelists such as Marcel Proust and Vladimir Nabokov.  We have just published a paper showing that verbal hallucinations, the core symptom of schizophrenia, may be related to the mind-pop phenomenon that almost everybody experiences, but just manifests itself in a different way.