Looking For the Science Behind the Twelve Steps

Transcendence, or nonsense?

What is it with the Twelve Steps? How, in the age of neuromedicine, do we account for the enduring concept of spiritual awakening available through “working the steps?” In Hijacking the Brain, Dr. Louis Teresi, former chief of neuroradiology at Long Beach Memorial Medical Center, along with Dr. Harry Haroutunian of the Betty Ford Center, sets themselves a formidable goal: “The sole intention of Hijacking the Brain is to connect the dots between an ‘organic brain disease’ and a ‘spiritual solution’ with sound physical, scientific evidence.” (For those who have grown weary of the overuse of “hijacked” brains in science writing, Teresi notes that an earlier term for the same idea was “commandeered.”)

Twelve Step programs remain popular, work for some addicts, and have their very vocal advocates in the recovery community. Outsiders are sometimes surprised to learn, writes Keith Humphreys, research scientist with the Veterans Health Administration and a professor at Stanford, that many of the people most profoundly and successfully affected by the 12-Step Program had “little or no interest in spirituality.”

The primary manifestation of this is the Twelve-Step Facilitation model (TSF), or Minnesota model, in honor of the Hazelden treatment facility in that state. Put simply, how do we go about explaining, in scientific terms, how a program like AA can have direct effects on a disease of the brain?

According to one strongly held view, we can’t. If there is something spiritual about recovery, it’s not anything that a medical doctor, who should have oversight of drug recovery and treatment programs, ought to be directly concerned with. Since the Twelve Step principles are explicitly spiritual in nature, how they apply to an organic brain disease is not at all clear. If you have cancer, your oncologists first line of thought is not usually, “why don’t you join a self-help group?” Writing for The Fix, health journalist Maia Szalavitz notes that “for no other medical disorder is meeting and praying considered reimbursable treatment: if a doctor recommended these religious or spiritual practices for the primary treatment of cancer or depression, you would be able to sue successfully for malpractice.” 

At an immediate level, the “power of the group,” which AA and other Twelve-Step Programs seems to tap into isn’t so hard to understand. Here are some of the obvious advantages of group work, as Teresi sees it:

--A reduction in the sense of isolation addicts feel.
--Useful information for addicts who are new to the processes of recovery.
--A way for people to see how others have dealt with similar problems.
--Additional structure and discipline for people whose living situations are often chaotic.

Teresi follows a common methodology, splitting the question into three dimensions: physical (an “allergy of the body driven by exaggerated limbic activity), mental (cognitive obsessions and compulsive drug use), and spiritual (an existential dilemma; a malady of the “soul”.) But the “spiritual awakening” that relieves this feeling and allows the addict to enter sobriety remains maddeningly ineffable: “The personality change sufficient to bring about recovery from alcoholism (addiction) has manifested itself among us in many different forms,” the Big Book cryptically affirms.

What makes it click for many addicts is what Teresi terms “empathic socialization,” defined as follows: “Positive socializing experiences received in support and therapeutic groups, such as praise, affection and empathic understanding, activate the brain’s reward centers as much as other natural rewards and similar to addictive substances. More importantly, belonging to an empathetic group reduces stress, a predominant cause and catalyst of addiction.”

Most people have only a hazy idea about what the Twelve Steps entail—something about admitting powerlessness over drugs, making amends for past wrongs, invoking a vague power higher than oneself. And the payoff? The reward for all the strenuous self-searching and personal honesty?

As Teresi sums it up: “inner peace, freedom, happiness, intuition, and alleviation of fear.” A heady package, indeed. All in return for achieving an emotional state called gratitude. Where are we to find the science in these claims?

Even though he doesn't solve the mystery, Dr. Teresi does offer  thoughts on some of the mechanisms in question, one of which is commonly referred to as an “attitude of gratitude” among Twelve-Step practitioners. “Gratitude for blessings received,” as it says the Big Book, is biochemically effective, Teresi argues. “In this regard,” Teresi writes, “grateful people show less negative coping strategies; that is, they are less likely to try to avoid the problem, deny there is a problem, blame themselves, or use mood-altering substances. Those with gratitude express more satisfaction with their lives and social relationships.”

And stress is where Dr. Teresi focuses his argument. More precisely, the working of the steps in Alcoholics Anonymous and kindred organizations involves “letting go” of high-stress states such as fear, guilt, self-loathing, and resentment. In Teresi’s thinking, the “power of the group” resides in its ability to reduce stress responses—and to raise levels of the “tend-and befriend” hormone, oxytocin. Oxytocin interacts with dopamine to increase maternal care, social attachments, and other affiliative behaviors and emotions. Thus, social rewards stir up a fair share of dopamine in reward centers of the brain, too. When alcoholics admit to powerlessness over alcohol, they are moving from a state of high autonomic nervous system tone to a more relaxed, “thank goodness that burden has been dropped” modality. This admission, when made as a conscious cognitive choice, and internalized through repetition and group motivation, lowers blood pressure and stress hormone levels, creating a more relaxed metabolic tone.

That is, in any event, how Teresi sees it. By confronting stress in this fashion, he believes that people with addictions can draw strength from group experience, even in the absence of personal religious belief.

Measures of Twelve-Step success will never be as precise as people would like. Not only does the national organization of AA generally avoid engaging in follow-ups, but the structure, or lack of it, works against precision measurements as well. As Teresi writes, “Anyone can start a Twelve-Step group by contacting the general service counsel of the organization of their interest, finding a meeting place (sometimes a person’s home) and adopting a readily available meeting protocol.” In fully monetized form, the Twelve Steps become Hazelden, or the Betty Ford Center. In supercharged upper income mode, it’s Passages and Promises. There is more going on here than simply a call to the pre-existing church-going addict. “AA,” says Keith Humphreys,  “is thus much more broad in its appeal than is commonly recognized.”

Teresi’s stated goal of connecting the dots isn’t an easy one. AA Twelve Steps and Twelve Traditions states unambiguously that the steps are “a group of principles, spiritual in their nature, which, if practiced as a way of life, can expel the obsession to drink and enable the sufferer to become happily and usefully whole.” In another passage, the Big Book refers to this as a personality change “sufficient to bring about recovery from alcoholism (addiction).” The explanations and definitions are maddeningly circular—unless you happen to be one of the people for whom the obsession to drink has been expelled through this practices.

Teresi believes it is possible to explore this terrain in a “belief neutral” manner, “with findings applicable to those who believe in a single God, multiple gods, or no God at all." Spiritual practices, Teresi believes, promote recovery in three ways. Meditation and some forms of prayer reduce stress levels. Techniques that lower stress have also been shown to stimulate limbic reward centers, “modulating emotion while strengthening attention and memory.” Finally, “spiritual practices, through improving morals and interpersonal behavior, foster closeness and a sense of community with one’s fellows and satisfy our instinctual need for social connection, also reducing stress.”

John Berryman and the Poetry of “Irresistible Descent”

“The penal colony’s prime scribe.”

“Will power is nothing. Morals is nothing. Lord, this is illness.”
—John Berryman, 1971

A year before he committed suicide by jumping off a Minneapolis bridge in 1972, Pulitzer Prize-winning poet John Berryman had been in alcohol rehab three times, and had published a rambling, curious, unfinished book about his treatment experiences. Recovery is a time capsule. If you think we have little to offer addicts by way of treatment these days, consider the picture in the 60s and 70s. In Recovery, treatment consists almost entirely of Freudian group analysis, and while there is regular talk of alcoholism as a disease, AA style, there is no evidence that it was actually dealt with in this way, after detoxification.

Best known for “Dream Songs,” Berryman taught at the University of Minnesota, and was known as a dedicated if irascible professor. Scientist Alan Severence, Berryman’s stand-in persona in the book, comes into rehab hard and recalcitrant, despite his previous failures: “Screw all these humorless bastards sitting around congratulating themselves on being sober, what’s so wonderful about being sober? Great Christ, most of the world is sober, and look at it!” And he is suffering from “the even deeper delusion that my science and art depended on my drinking, or at least were connected with it, could not be attacked directly. Too far down.”

Berryman was a difficult man, and knew it. He quotes F. Scott Fitzgerald: “When drunk, I make them pay and pay and pay and pay.”

Alcoholics, writes Berryman, are “rigid, childish, intolerant, programmatic. They have to live furtive lives. Your only chance is to come out in the open.” Berryman catches the flavor of group interaction after too many hours, too much frustration, and too much craving. One inpatient lashes out: “You’re lying when you say you do not do anything about your anger. You get bombed. It is called medicating the feelings, pal. Every inappropriate drinker does it. Cause and effect. Visible to a child. Not visible to you.”

Berryman was a shrewd observer, a singular writer, and, after all, a poet. He is extraordinary on the subject of alcoholic dissociation: “I found myself wondering whether I would turn off right towards the University and the bus home or whether I would just continue right on to the Circle and up right one block to the main bar I use there, and have a few. Wondering. My whole fate depending on pure chance…. as if one were not even one’s own actor but only a spectator.”

Berryman puts it all together in a horrific capsule description of the “irresistible descent, for the person incomprehensibly determined.”

Relief drinking occasional then constant, increase in alcohol tolerance, first blackouts, surreptitious drinking, growing dependence, urgency of FIRST drinks, guilt spreading, unable to bear discussion of the problem, blackout crescendo, failure of ability to stop along with others (the evening really begins after you leave the party)… grandiose and aggressive behavior, remorse without respite, controls fail, resolutions fail, decline of other interests, avoidance of wife and friends and colleagues, work troubles, irrational resentments, inability to eat, erosion of the ordinary will, tremor and sweating… injuries, moral deterioration, impaired and delusional thinking, low bars and witless cronies….

Berryman had no illusions about his failed attempt to hide behind the mask of a social drinker: “It seems to be loss of control. Unpredictability. That’s all. A social drinker knows when he can stop. Also, in a general way, his life-style does not arrange itself around the chemical, as ours does. For instance, he does not go on the wagon…”

In the end, he was "pleading the universal case of hope for abnormal drinkers, for all despairing and deluded sufferers fighting for their sanity in a world not much less insane itself and similarly half-bent on self-destruction…”

As the head nurse in the facility tells the group: “You are all suffering from the lack of self-confidence… often so powerful that it leads to consideration of suicide, a plan which if adopted will leave you really invulnerable, quite safe at last.”

And as Saul Bellow wrote in the introduction to Recovery: “At last there was no more. Reinforcements failed to arrive. Forces were not joined. The cycle of resolution, reform and relapse had become a bad joke which could not continue.” Berryman agreed. Toward the end, he wrote: “I certainly don’t think I’ll last much longer.”

“There’s hope until you’re dead,” a woman tells him during his final stay in rehab. Sadly, that hope ended a few months later.


Photo posted by Tom Sutpen for the series: Poets are both clean and warm

The Truth About Weight Loss Surgery and Alcohol

Bariatrics and booze don’t always mix.

For many people with obesity, bariatric surgery has proven to be a lifesaver. But for a subset of post-operative patients, the price for losing five pounds every time you step on the scale turns out to be an increased appetite for alcohol.

In a study of almost 2,000 patients who underwent surgery for severe obesity, the patients had either gastric bypass surgery (RYGB) in which a portion of the stomach and small intestine are removed, or gastric banding, a process by which an adjustable “lap band” is tightened around the entrance to the stomach. Those who opted for gastric bypass showed an increase in alcohol consumption two years after surgery, according to a recent study by Wendy C. King and coworkers in the Journal of the American Medical Association.

The notion that weight loss surgery, known as bariatric surgery, was related to increased use of alcohol had been an anecdotal staple among patients with obesity for years. Oprah Winfrey based one of her daytime television shows on the rumor back in 2006. Dr. King and a diverse group of associates concluded last month at the American Society for Metabolic and Bariatric Surgery annual meeting that “a significantly higher prevalence of alcohol use disorder” was associated with the second year following gastric bypass surgery. (During the first postoperative year, patients are strongly advised not to drink at all.)

Moreover, some of the patients who showed high-risk alcohol intake had not been problem drinkers before surgery. Some had not been drinkers at all. But the effects of gastric bypass, coupled with permission to drink a year after surgery, lead to an increase in alcohol abuse and alcoholism. While the overall increase was relatively modest, patients who had gastric bypass surgery were twice as likely to drink heavily than patients who underwent the lap band procedure.

“It’s a great study,” says Dr. Stephanie Sogg, staff psychologist at the Massachusetts General Hospital Weight Center and assistant professor in the Department of Psychiatry at Harvard Medical School, who was not associated with the study group. In an interview for this article, Sogg called the distinction between surgeries “an extremely important finding. They saw changes in alcohol use patterns with gastric bypass, but not with gastric banding. That’s exactly what we would expect.”

The findings make biochemical sense: “Gastric bypass surgery bypasses a part of the stomach that secretes alcohol dehydrogenase,”—a primary enzyme of alcohol metabolization, says Sogg. “And in gastric bypass, the alcohol is not coming into contact with the first part of the intestine, the duodenum. That’s going to cause some changes in the way the body processes alcohol that aren’t true of gastric banding. If this were a case of people who are addicted to food having to change their eating and thus becoming addicted to alcohol, we would expect to see the same changes whether the person had gastric bypass or gastric banding.”

It would be natural to assume that people with prior drinking problems would have the most trouble with alcohol control postoperatively. But things are rarely that simple in medicine. “Previous alcohol history sets up people for risk of relapse, but there’s a significant subset of people having trouble with alcohol who never drank at all,” says Dr. Sogg. “That’s where the real story is.”

Dr. David B. Sarwer, associate professor of psychology and director of clinical services for the Center for Weight and Eating Disorders at the University of Pennsylvania, called the King study “the most definitive evidence to date on the prevalence of alcohol use disorders in persons who undergo bariatric surgery.” In an email exchange, Sarwer said: “Individuals with a history of alcohol or substance abuse are informed that the stress of the dietary and behavioral requirements of bariatric surgery, like all major life stressors, could threaten their sobriety or abstinence. However, we simply do not know enough about the use of alcohol and other substances after surgery to predict this with a great degree of certainty.”

Dr. Sogg agrees. For the bariatric surgery population, the pharmacokinetics of alcohol changes. They become more sensitized to its effects—a little now goes a long way. The main problem, she says, is that “we’re not good yet at predicting exactly whom it’s going to happen to.”

But she has some thoughts about vulnerable subsets. “Some people with obesity have poor coping skills,” she says. “And now alcohol is so much more potent and reinforcing for them that alcohol becomes the coping strategy. When this biological change with alcohol happens, they may be the ones who are at higher risk of responding to that change by developing problems with alcohol.”

Warning patients about alcohol risks of weigh-loss surgery is becoming more common, says Dr. Sogg. “It doesn't change my decision-making about whether somebody should or shouldn't have surgery. But we can evaluate people's coping skills before surgery and point out to them that it is important for them to develop other ways of dealing with negative emotions besides eating." 

She also thinks that “people who have a history of actually becoming abstinent after drug or alcohol dependence may be better equipped for surgery. They will be less likely to put themselves in the path of alcohol use, and they have experience at making major successful long-term behavior changes. Basically, we should not consider past encounters with substance abuse as contraindications for surgery. But we should be carefully evaluating whether people are currently using substances at the time of surgery.”

In the end, she said, “I tell every one of my patients before surgery that they need to be aware of the risks of problem drinking after surgery, monitor their alcohol intake, and come back to us immediately at the first sign of any concerns about their drinking.”

King WC, Chen JY, Mitchell JE, Kalarchian MA, Steffen KJ, Engel SG, Courcoulas AP, Pories WJ, & Yanovski SZ (2012). Prevalence of Alcohol Use Disorders Before and After Bariatric SurgeryAlcohol Use Disorders and Bariatric Surgery. JAMA : the journal of the American Medical Association, 1-10 PMID: 22710289

 Photo credit: http://www.treatment4addiction.com/

What It Means to Say Alcoholism is Genetic

One woman’s journal.

From Insanity to Serenity, by Tommi Lloyd

Excerpts:

"I was born in 1963 in Toronto, Canada, to a family struggling long before I arrived. My dad was an alcoholic, born in Wales in 1921. His father and namesake was also an alcoholic who died at age 28…. My oldest sibling and only brother, Harry, entered a treatment centre at age 36 and has been sober for more than 20 years…. My Uncle Griff died from alcoholism when I was 10 years old…. There were no reprieves by which we spent a day or two in a sober environment. Dad drank from morning until night…. Christmas, Thanksgiving, and Easter—these were some of the worst days of the year…. Santa started leaving a carton of cigarettes next to my stocking at Christmas and I thought it was great.

"I yearned for some quality time before his drinking took center stage for the day… he drank from the minute he got up to the minute he passed out. At the height of his addiction, he was drinking more than 40 ounces of vodka a day…. There were many times when I would walk into the bedroom and see him guzzling the vodka straight from the bottle. It made me feel physical ill and utterly helpless.

"I too, am an alcoholic. In addition to alcohol, my teenage love of marijuana turned into a 30-year affair…. I have two nephews who are addicted to marijuana…. Rather than being sloppy drunks, my nephews opted for the mellow alternative that’s not addictive, (so we like to think) and you can pay for your habit by selling it to your friends.

"By age 11 I tried drinking for the first time…. I recall Susie telling us we could try drinking, but it had to be done quickly so as not to get caught. We poured some very strong rum and cokes and I guzzled mine down by holding my nose with my free hand…. As soon as I lay down on my bed the room started spinning and it wasn’t long before I was throwing up. Mom fussed over me, concluding I had the flu and I recall feeling both happy and guilty at the same time. I loved the attention but felt badly for the cause of my illness. I didn’t drink again for a few years….

"There is nothing more validating for me as a mother than to know I’m an inspiration to my children. I could not have asked for a better gift. This is what sobriety and a renewed spiritual life has brought my children and me…. Intellectually, I recognize how my childhood experiences and the disease of alcoholism molded a lot of my behavior and have been the root of much of my struggle with self-esteem. But self-knowledge does not change our circumstances, action does."

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/

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/

LSD and Alcohol: The History

Back when acid was legal.

After last week’s blitz of coverage concerning studies done in the 60s on the use of LSD for the treatment of alcoholism, I thought it would be useful to provide a bit of background; some pertinent psychedelic history to help put this information in perspective:

It may come as a surprise to many people that throughout the 60s, there were LSD clinics operating in England and Europe. European LSD therapists tended to use very low doses as an adjunct to traditional psychoanalytic techniques. But North American researchers took a different, bolder approach. When “psychedelic” therapy began to catch on in Canada and the United States, therapists typically gave patients only one or two sessions at very high doses. These early efforts were aimed at producing spontaneous breakthroughs or recoveries in alcoholics through some manner of religious epiphany or inner conversion experience. The only other quasi-medical approach of the day, the Schick Treatment Center’s brand of “aversion therapy,” was not seen to produce very compelling long-term recovery rates, and subsequently fell out of favor. In this light, the early successes with LSD therapy, sometimes claimed to be in the 50-75 per cent range, looked noteworthy indeed. However, the design and criteria of the LSD/alcoholism studies varied so widely that it has never been possible to draw definitive conclusions about the work that was done, except to say that LSD therapy seemed to be strikingly effective for certain alcoholics. Some patients were claiming that two or three trips on LSD were worth years of conventional psychotherapy—a claim not heard again until the advent of Prozac thirty years later.

 “I’ve taken lysergic acid several times, and have collected considerable information about it,” Bill Wilson, the co-founder of Alcoholics Anonymous, disclosed in a private letter written in 1958. “At the moment, it can only be used for research purposes. It would certainly be a huge misfortune if it ever got loose in the general public without a careful preparation as to what the drug is and what the meaning of its effects may be.”  Like many others, Wilson was excited by LSD’s potential as a treatment for chronic alcoholism. Even Hollywood was hip to the new therapy. Cary Grant, among others, took LSD under psychiatric supervision and pronounced it immensely helpful as a tool for psychological insight. Andre Previn, Jack Nicholson, and James Coburn agreed. (It could be argued that the human potential movement began here).

No drug this powerful and strange, if American history was any guide, could remain legal for long. Unlike their colleagues in the intelligence agencies, politicians and law enforcement officers didn’t know about Mongolian shamans and their fly agaric mushrooms; about European witches and their use of psychoactive plant drugs like nightshade and henbane; about Persian sheiks with their cannabis water pipes; Latin American brujos with their magic vines.

But for the CIA, the big fish was always LSD.

What interested the Central Intelligence Agency about LSD was its apparent ability to produce the symptoms of acute psychosis. Operation ARTICHOKE was designed to ferret out LSD’s usefulness as an instrument of psychological torture, and as a possible means of destabilizing enemy forces by means of aerosol sprays or contaminated water supplies. (The drug’s overwhelming potency made such parts-per-billion fantasies a possibility.)

The agency knew where to turn for a secure American source of supply. Eli Lilly and Co., the giant drug manufacturer, was already involved in LSD research on behalf of the U.S. government. The trouble was that LSD was expensive, and all roads led to Sandoz Laboratories in Switzerland. Organic LSD had to be painstakingly extracted from ergot, a fungus that grows in kernels of rye. Eventually, Sandoz and Eli Lilly successfully synthesized LSD in their own laboratories. With the advent of a reliable domestic supplier of synthetic LSD, the CIA under Allen Dulles was assured of a steady source for experimental purposes.

When LSD did not pan out as a reliable agent of interrogation, CIA investigators turned their attention to its purported ability to mimic acute psychosis—its “psychomimetic” aspect—which researchers were praising as a new avenue toward a biological understanding of schizophrenia. The CIA funneled grant money for LSD research into the academic and commercial R&D world through a host of conduits. Various experiments with non-consenting subjects—typically military or prison personnel—showed that LSD could sometimes break down established patterns of thought, creating a “twilight zone” during which the mind was more susceptible to various forms of psychological coercion and control. Perhaps, under the influence of LSD, prisoners could be transformed into counter-espionage agents. It also occurred to the CIA that the same drug could be used on their own agents for the same purposes. Numerous CIA agents took LSD trips in order to familiarize them with acid’s Alice-in-Wonderland terrain. Some of these unusual experiments were captured on film for use in military training videos.

One place where ARTICHOKE research took place was the Addiction Research Centre at the Public Health Service Hospital in Lexington, Kentucky—the same hospital that specialized in the treatment of hardcore heroin addicts. Lexington was part hospital and part penitentiary, which made it perfect for human experimentation. The addict/inmates of Lexington were sometimes given LSD without their consent, a practice also conducted at the federal prison in Atlanta, and at the Bordentown Reformatory in New Jersey. 

In 1953, then-CIA director Allen Dulles authorized Operation MK-ULTRA, which superseded earlier clandestine drug investigations. Under the direction of Dr. Sidney Gottlieb, a chemist, the government began slipping LSD and other psychoactive drugs to unwitting military personnel. During a work retreat in Maryland that year, technicians from both the Army and the CIA were dosed without their knowledge, and were later told that they had ingested a mind-altering drug. Dr. Frank Olson, a civilian biochemist involved in research on biological warfare, wandered away from the gathering in a confused state, and committed suicide a few days later by leaping to his death from an upper floor of the Statler Hilton in New York City. The truth about Olson’s death was kept secret from his family, and from the rest of the nation, for more than twenty years. In 1966, LSD was added to the federal schedule of controlled substances, in the same category as heroin and amphetamine. Simple possession became a felony. The Feds had turned off the spigot, and the research came to a halt. Federal drug enforcement agents began showing up at the homes and offices of well-known West Coast therapists, demanding the surrender of all stockpiles of LSD-25. The original acid elite was being hounded, harassed, and threatened in a rancid atmosphere of pharmaceutical McCarthyism. Aldous Huxley, Humphrey Osmond, even father figure Albert Hoffman, all viewed these American developments with dismay. The carefully refined parameters and preparations, the attention to set and setting, the concerns over dosage, had gone out the window, replaced by a massive, uncontrolled experiment in the streets. Small wonder, then, that the circus atmosphere of the Haight-Ashbury “Summer of Love” in 1967 seemed so badly timed. Countercultural figures were extolling the virtues of LSD for the masses—not just for research, not just for therapy, not as part of some ancient religious ritual—but also just for the freewheeling American hell of it. What could be more democratic than the act of liberating the most powerful mind-altering drug known to man?

It is at least conceivable that researchers and clinicians eventually would have backed away from LSD anyway, on the grounds that the drug’s effects were simply too weird and unpredictable to conform to the rigorous dictates of clinical studies. Nonetheless, researchers had been given a glimpse down a long, strange tunnel, before federal authorities put an end to the research.

—Excerpted from The Chemical Carousel: What Science Tells Us About Beating Addiction

Graphics Credit: http://news.sky.com

The Future of Addiction Treatment

Is there some way out of here?

Addictions are chronic diseases. They may require a lifetime of treatment. After a number of severe episodes of alcohol or drug abuse, the brain may be organically primed for more of the same. Long-term treatment is sometimes, if not always, the most effective way out of this dilemma. (The same is true of unipolar depression.)

We will need to learn a lot more about chemicals—the ones we ingest, and the ones that are produced and stored naturally in our bodies—if we plan to make any serious moves toward more effective treatment. What we have learned about the nature of pleasure and reward is a strong start. The guiding insight behind most of the work is that addiction to different drugs involves reward and pleasure mechanisms common to them all. The effects of the drug—whether it makes you sleepy, stimulated, happy, talkative, or delusional—constitute a secondary phenomenon. A good deal of earlier research was directed at teasing out the customized peculiarities of one drug of abuse compared to another. Now most addiction scientists agree that receptor alterations in response to the artificial stimulation produced by the drugs are the biochemical key, and that recovery occurs when the brain’s remarkable “plastic” abilities go to work at the molecular level, re-regulating and adjusting to the new, drug-free or drug-reduced status quo. An addict beats addiction by ceasing the constant and artificial manipulation of neuronal receptors, to be entirely unromantic for a moment about the nature of recovery.

But in order for that to happen most effectively, you have to stop taking the drugs.

Comparing our reservoir of pleasure chemicals to money in the bank, Dr. George Koob, Chairman of the Committee On The Neurobiology Of Addictive Disorders at the Scripps Institute in La Jolla, California, draws the following analogy:

We can expend that money over the course of a single weekend’s binge on cocaine or we can expend it over a two-week period in the normal pleasures of everyday life. If you spend these pleasure neurochemicals in one lump sum such as a crack binge, you use up your supply of pleasure for a certain period, and so you pay for it later.

Addicts vividly demonstrate a compulsive need to use alcohol and other drugs despite the worst kinds of consequences—arrest, illness, injury, overdose. What kind of euphoria could be worth such psychic pain? Even stranger, why continue when the drug no longers works as well as it once did due to tolerance? What makes these people eat their words, shred their best intentions, break their promises, and starting using or drinking again and again?

There really is no cheating in this game. The system has to self-regulate. Craving and drug-seeking behavior, once set in motion, disrupt an individual’s normal “motivational hierarchy.” How does this motivational express train come about? It happens at the point where casual experimentation is replaced by the pharmacological dictates of active addiction. It happens when the impulse to try it with your friends transforms itself into the drug-hungry monkey on your back.

 Formal medical treatment and intervention can work, but the results are inconsistent and often little better than no formal treatment at all. Most alcoholics and smokers and other drug addicts, it is frequently asserted, become abstinent on their own, going through detoxification, withdrawal, and subsequent cravings without benefit of any formal programs. Our health policy should not only encourage addicts to heal themselves, but must also help equip them with the medical tools they need in treatment. After all, behavioral habits as relatively harmless as nail biting can be all but impossible to break.

 As detailed by Dr. Mary Jeanne Kreek, a professor and senior attending physician at the Laboratory of the Biology of Addictive Diseases at Rockefeller University:

Toxicity, destruction of previously formed synapses, formation of new synapses, enhancement or reduction of cognition and the development of specific memories of the drug of abuse, which are coupled with the conditioned cues for enhancing relapse to drug use, all have a role in addiction. And each of these provides numerous potential targets for pharmacotherapies for the future.

In other words, when an addiction has been active for a sustained period, the first-line treatment of the future is likely to come in the form of a pill. New addiction treatments will come—and in many cases already do come—in the form of drugs to treat drug addiction. Every day, addicts are quitting drugs and alcohol by availing themselves of pharmaceutical treatments that did not exist twenty years ago. Sometimes medications work, and we all need to reacquaint ourselves with that notion. As more of the biological substrate is teased out, the search for effective medications narrows along more fruitful avenues. This is the most promising, and, without doubt, the most controversial development in the history of addiction treatment.

Fighting fire with fire is not without risk, of course. None of this is meant to deny the usefulness of talk therapy as an adjunct to treatment.  However, consider the risks involved in not finding more effective medical treatments. Better addiction treatment is, by almost any measure, a cost-effective proposition.

Photo: http://www.manorhouserehab.com/

Interview with Howard Shaffer of the Division on Addiction at Cambridge Health Alliance

Defining addiction, making research more transparent, and dealing with the DSM-V

(The “Five-Question Interview” series.)

Like many incredibly busy people, Dr. Howard J. Shaffer, associate professor of psychology at Harvard Medical School, is generous with his time. This paradox works to the advantage of Addiction Inbox readers, as Dr. Shaffer, the director of the Division on Addiction at the Cambridge Health Alliance, a Harvard Medical School teaching affiliate, has graciously consented to be the next participant in our “Five-Question Interview” series. In addition to maintaining a private practice, Dr. Shaffer has been a principal or co-principal investigator on a wide variety of research projects related to addiction, including the Harvard Project on Gambling and Health, and a federal research project focusing on psychiatric co-morbidity among multiple DUI offenders. He is the past editor of the Journal of Gambling Studies and the Psychology of Addictive Behaviors.


1. Addiction is not like most medical/mental disorders. If you have cancer or schizophrenia, for example, you can’t recover by abstaining from certain things. What’s your response to those who say that the disease model of addiction is misleading?

We should remember that the concept of disease is difficult to define. This makes deciding whether addiction is a disease most difficult. However, I think most people accept the idea that addiction reflects a kind of dis-ease. Whenever people get into this disease model debate, it’s useful to remember that most models of addiction are misleading, and the disease model is no exception. The map is not the territory, the menu is not the meal, and the diagnosis is not the disorder.

Scientific models are simplified representations of complex phenomena. Models of addiction focus our attention to certain features of addiction and blind us to other potentially important aspects of the disorder.1 For example, the moral model of addiction suggested that bad judgment was the cause and piety was the solution. Some neurobiological models of addiction suggest that molecular activity is the cause and medication is the solution. Both of these views are simplifications.

Rather than trying to fit addiction into a particular box, I prefer to think of addiction as a complex multidimensional syndrome – with interactive biological, psychological, and social causes. In this way addiction is similar to other medical, mental and behavioral disorders than we previously have considered. My colleagues and I have been developing a syndrome model of addiction 2-4 that suggests people are vulnerable because of biological, psychological and social influences. When vulnerable people are exposed to a social context that reliably and robustly shifts their subjective state in a desirable direction, they are at the highest risk for developing addiction. What I like about this kind of model is that it holds the potential to help us determine who is at most risk so that we can predict the development of addiction – just like we can predict who is at risk for cardiovascular and other diseases. This kind of etiological model will help us establish primary and secondary prevention programs that can reduce the onset of addiction.

2. You have a book coming out soon about problem gambling and how it can be managed. Is gambling a legitimate addiction?

Gambling, as well as most other behavior patterns, can become excessive, lead to adverse consequences, and squeeze out many previously important and healthy behavior patterns. 5,6 Some behavior patterns like eating broccoli rarely lead to addiction, but other improbable behaviors like listening to music, or playing video games might.

I don’t think about the idea of a “legitimate” addiction anymore, though I used to. Now I think about addiction as a unitary disorder that has a variety of expressions. For example, AIDS is a syndrome with many different expressions. Syndromes like AIDS and addiction are complex because not all of the signs and symptoms associated with the disorder are present all of the time. Gambling addiction is more rare than alcohol dependence. However, the characteristics of different expressions of addiction and the sequelae across sufferers are more similar than different. Further, the treatments – including the medications – that are effective with one expression of addiction often work with another expression. Scientific evidence suggests that behaviors, such as excessive gambling, and substance use, such as cocaine, have similar effects on the neurocircuitry of reward – how the brain processes information to produce the experience of pleasure.

For a pattern of behavior, whether substance involved or not, to be considered as an addiction, it must reliably and robustly shift subjective experience in a desirable direction, lead to adverse consequences, and be associated with identifiable underlying biological and psychological features, for example, genetic influences and trauma.

3. You host the Transparency Project. What is it and why did you create it?

The Transparency Project is the world’s first data repository for addiction-related industry-funded research. Most people don’t realize that private industry funds the majority of scientific research. This particular funding stream is important. However, tobacco industry funded research properly encouraged people to worry that private funding can adversely influence research. In fact, I think observers should worry about the potential bias that might accompany any research, including research supported by public funding sources. There is no warranty that can assure unbiased research, except sound methods and careful data analysis reflecting sound scientific principles. Furthermore, critics shouldn’t presume that research is biased just because it has a particular kind of funding source. We are encouraging scientists who have received industry funding to send their data to the Transparency Project so that others can download and use their data. This should magnify the value of the data by having others analyze it similarly or differently from the original research. This strategy also should help observers both confirm and question findings, thereby leading to important dialogues about the central issues that are so very important to the advance of scientific knowledge.

4. What’s going on right now at the Division on Addiction that you are particularly excited about?

During 2012, we are celebrating our 20th anniversary at the Division on Addiction. The syndrome model is emerging as an important conceptual guide to our work going forward; we are very excited to see that others are similarly interested in this perspective. Very soon, for example, the American Psychological Association will be releasing another of our new books, the APA Addiction Syndrome Handbook. I am also very excited about our DUI research 7-11 as well as our efforts to develop new technology that will help lay interviewers—those often staffing DUI treatment programs—to assess complex psychiatric disorders and triage patients into the care they so desperately need. This is our Computer Assessment and Referral System or CARS project. Lots of people around the world are expressing interest in coming to the Division to study and conduct research focusing on addiction. For me, it is very satisfying to see young people come to the field of addiction with a sense of curiosity, wonder and scientific rigor that have not always been present in this area of interest.


5. How do you feel about the proposed DSM-V changes regarding addiction?

By now, most people interested in addiction are aware that the American Psychiatric Association has expressed some interest in moving Pathological Gambling from the impulse control disorder category to a new Addiction and Related Disorders category. This would represent the first time that the term “addiction” appears in the DSM. If this happens, it is a big deal and, in my opinion, represents a step forward. In many ways it reflects a syndrome model perspective toward addiction. Although pathological gambling has clinical, epidemiological, etiological, physiological, and treatment commonalities with substance use disorders, my colleague Ryan Martin and I have noted that these similarities also exist among the substance use disorders and a variety of other behavioral expressions of addiction (e.g., excessive shopping). A relatively large literature evidences these commonalities. Consequently, we think that the DSM-V work group should avoid creating a long list of addictions and related disorders/diagnoses organized by the objects of addiction. Instead, the syndrome model of addiction encourages an addiction diagnosis that is independent of the objects of addiction, other than as a clinical feature. Diagnostic systems need to identify the core features of addiction and then illustrate these with substance-related and behavioral expressions of this diagnostic class. Conceptualizing addiction this way avoids the incorrect view that the object causes the addiction and shifts the diagnostic focus more sharply toward patient needs.

References

1. Kuhn TS. The structure of scientific revolutions. Second ed. Chicago: University of Chicago Press; 1970.
2. Shaffer HJ, LaPlante DA, LaBrie RA, Kidman RC, Donato AN, Stanton MV. Toward a syndrome model of addiction: multiple expressions, common etiology. Harvard Review of Psychiatry 2004;12:367-74.
3. Shaffer HJ, LaPlante DA, Nelson SE, eds. The APA Addiction Syndrome Handbook. Washington, D.C.: American Psychological Association Press; in press.
4. Shaffer HJ, LaPlante DA, Nelson SE, eds. The APA Addiction Syndrome Handbook. Washington, D.C.: American Psychological Association Press; in press.
5. Shaffer HJ, Martin R. Disordered Gambling: Etiology, Trajectory, and Clinical Considerations. Annual Review of Clinical Psychology 2011;7:483-510.
6. Shaffer HJ, Korn DA. Gambling and related mental disorders: a public health analysis. In: Fielding JE, Brownson RC, Starfield B, eds. Annual Review of Public Health. Palo Alto: Annual Reviews, Inc.; 2002:171-212.
7. Albanese MJ, Nelson SE, Peller AJ, Shaffer HJ. Bipolar disorder as a risk factor for repeat DUI behavior. Journal of Affective Disorders in press.
8. LaPlante DA, Nelson SE, Odegaard SS, LaBrie RA, Shaffer HJ. Substance and psychiatric disorders among men and women repeat driving under the influence: offenders who accept a treatment-sentencing option. Journal of Studies on Alcohol and Drugs 2008;69:209-17.
9. Nelson SE, Laplante DA, Peller A, Labrie RA, Caro G, Shaffer HJ. Implementation of a Computerized Psychiatric Assessment Tool at a DUI Treatment Facility: A Case Example. Administration and Policy in Mental Health and Mental Health Services Research 2007;34:489-93.
10. Peller AJ, Najavits LM, Nelson SE, LaBrie RA, Shaffer HJ. PTSD Among a Treatment Sample of Repeat DUI Offenders. Journal of Traumatic Stress in press.
11. Shaffer HJ, Nelson SE, Laplante DA, Labrie RA, Albanese M, Caro G. The epidemiology of psychiatric disorders among repeat DUI offenders accepting a treatment-sentencing option. Journal of Clinical and Consulting Psychology 2007;75:795-804.

A Drug for Head Lice and Heartworm Shows Promise Against Alcohol Abuse

Unlikely candidate helps alcohol-dependent mice cut back on the sauce.

Say what you will about glutamate-gated chloride channels in the parasitic nematode Haemonchus contortus—but the one thing you probably wouldn’t say about the cellular channels in parasitic worms is that a drug capable of activating them may prove useful in the treatment of alcoholism and other addictions.

When scientists go looking for drugs to use against addiction, they do not typically begin with a class of drugs that includes a medication for use against head lice and ticks. But that is exactly where the trail led Daryl Davies, co-director of the Alcohol and Brain Research Laboratory at the University of Southern California. Davies and his group were interested in a set of molecules in the brain known as P2X receptors. A subtype of these receptors, involved in ion channel gating, cease to function in the presence of ethanol. The researchers found that if you keep flooding the receptor with alcohol, these ion gates shut down permanently—an example of how alcohol abuse can change the brain.

Another compound that works on the same ion gate is ivermectin, an anti-parasitic medicine used around the world in humans and animals. As it turns out, ivermectin blocks the effect that alcohol has on P2X receptor subtypes. In recent research, the USC team demonstrated that alcohol-dependent mice drank half as much when they were also given ivermectin. This “newly identified alcohol pocket” is a mystery at present. But ivermectin does appear to work primarily on glutamate systems. (See previous post). For now, the researchers can’t say for certain why ivermectin makes mice drink less, but suspect it has something to do with how the brain signals that it’s time to stop drinking. Davies has speculated that a drug like ivermectin could be of use in treatment programs other than “abstinence-based models.” As Suzanne Wu reports in USC Trojan magazine, the team is now at work on other drugs based on ivermectin’s molecular structure. “If there was already a drug that was 95 percent effective, I might not be studying ivermectin,” Davies told the magazine. “I might not even be in the alcohol field. The funding for alcoholism research hasn’t caught up with the magnitude of the consequences of not finding a cure.”

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

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/

The Strange and Secret Keeley Cure for Addiction

“Drunkenness is a disease and I can cure it.”

In America in the late 1800s, curing alcoholism was a serious business—and for Dr. Leslie Keeley, a very lucrative one. Dozens of clinics and cures already existed, and some treatment centers had even experimented with franchising. For the late 19th Century alcoholic in search of treatment, what most of them had on offer was either outright patent medicine fraud, or else well intentioned if ultimately misguided “opium” cures. None of them, writes William L. White in Slaying the Dragon, “was more famous, more geographically dispersed, more widely utilized, and more controversial than Leslie Keeley’s Double Chloride of Gold Cure for the treatment of alcoholism, drug addiction, and the tobacco habit.”

The Irish-born Dr. Keeley served as a surgeon in the Civil War, and, as family lore would have it, started a treatment program for alcoholism in a Union hospital during the war. We do know that in 1879, he opened the first Keeley Institute in Dwight, Illinois, south of Chicago. His sales pitches were colorful and varied, but boiled down to this pledge: “Drunkenness is a disease and I can cure it.” He could cure it with a secret, specific formula, injected four times daily, about which all he would hint publically was that it contained, as one of its ingredients, gold. This was not so outlandish as it may seem. Gold, silver, strychnine, and other potentially poisonous ingredients were already employed in dozens of standard medicines—and, in many cases, still are. But everything else about Dr. Keeley’s magic elixir was as secret as the ingredients in Coke.

Nonetheless, something seemed to be working. He claimed an outlandish 95% success rate, bolstered by legions of enthusiastic followers who formed proto-AA groups with the catchy title of Bi-Chloride of Gold Clubs, better known as the Keeley Leagues. And Keeley himself employed the largest collection of formerly addicted doctors in the known world. There were no counselors at Keeley clinics. There were enough doctors on staff to go around, even though an estimated total of half a million alcoholics and other addicts eventually took the Keeley Cure.

Treatment consisted of the infamous injections, a liquid cordial every two hours, and, according to White, the following modalities: “daily rest, nutrition, mutual sharing, and alternative diversions worked to improve the patient’s physical and psychological health.” We can assume, from this regimen, that some alcoholics and addicts probably improved, regardless of what was in the medicine. And there was the frequent suggestion that, really, it was probably best not to ask too many questions about what was in the medicine, anyway.

“The atmosphere was informal and friendly at the clinics,” White writes, “with a marked absence of the bars and restraints that were typical in most inebriate asylums of the period.” There were, of course, some very vocal detractors. Dr. T. D. Crothers, a leader in the inebriate asylum movement, said: “There is no gold cure for inebriety. There are no facts to show that gold has any value in this disease. All the assertions and statements concerning gold as a remedy are delusions, and will not bear the test of critical examination.”  Perhaps not. But success was success, and soon, the marketplace saw the introduction of Dr. Haines Golden Remedy, the Geneva Gold Cure, the Boston Bichloride of Gold Company, and many other knockoffs. (Keeley proclaimed that his Double Chloride of Gold cured all forms of inebriety by “speeding up the restoration of poisoned cells to their pre-poisoned condition.”)

From 1892 through 1900, the Keeley Company pulled in almost $3 million, including mail-order business. There was a Keeley Day at the 1893 World’s Fair in Chicago. Here is an excerpt from the pamphlet, “To the Keeley Graduate,” given to every patient who completed treatment:

You are now numbered among thousands of men and women who have broken the shackles of alcohol and drug addictions by the Keeley method of treatment. Your cure will be as permanent as your life, you will never have any craving for alcohol or other sedative drugs as long as you live, unless you create it by returning to their use, thus re-poisoning your nerve cells.

But by 1900, the bloom was off the Keeley miracle, as insiders fought for financial control, and congressional investigators looked into the affairs of Keeley League president Andrew J. Smith.

Of course, if Keeley had really possessed a specific, replicable formula that took away the craving for alcohol, it would have been monstrously unethical to hold it a secret. And he was constantly accused of using harmful ingredients, such as codeine, strychnine, and cocaine in his magic injections.

Keeley wouldn’t say. And neither did any of his heirs or business partners. The only thing most court records agree on is that the injection didn’t contain any gold—too many possible side effects. According to the testimony of Keeley’s original business partner, “The only patient who ever received Keeley medicine that actually had gold in it almost died.”

The secret ingredient was probably atropine—a powerful compound belonging to a very weird family of plant drugs known collectively as “anticholinergenic deliriants.”  Atropine is the active ingredient in Belladonna, aka Deadly Nightshade. Along with mandrake, henbane, and jimsonweed, the so-called Belladonna alkaloids are among the primary hallucinatory ingredients found in many a witch’s and sorcerer’s brew throughout the ages. Belladonna can cause terrifying hallucinations, feelings of flight or paralysis, blurred vision, impaired motor control, and other side effects usually experienced as highly unpleasant. It was likely Belladonna, not LSD, that served as the basic rocket fuel for the Manson’s family’s horrific activities, according to some accounts. More mundanely, atropine is familiar to armed forces personnel in the form of a self-injection device for serious wounds. Atropine has the ability to speed up a slowing or overworked heart. In ancient times, it was used as an anesthetic for surgery. Atropine is also a poison. (Scopolamine, used medically for motion sickness, is another.)

But one person’s unpleasant side effect is another’s chemical cure. Did the Keeley concoction just terrify the bejesus out of addicts, as some sort of ad hoc version of aversive therapy, or did it sedate his patients into a semi-catatonic, immobile haze, in which they could pass 3 weeks of detox in relative comfort, or at least immobility and minimal disruption? Probably both, depending on drug dosage, drug combination, and patient metabolism. There were widespread reports of Keeley patients who allegedly died or went insane.

“The pulp image of Dr. Leslie Keeley—that of the country physician who had stumbled onto a revolutionary cure for the inebriety problem that had stumped the best medical scientists,” was key to his success, White believes. “Keeley introduced an approach that carried an aura of scientific truth and all the emotional support and intensity of a revival meeting.”

“The likely ingredients of the Double Chloride of Gold remedy and tonics—alcohol, atropine, strychnia, apomorphine —did aid detoxification,” White concludes. And the graduation pamphlet went on to emphasize the importance of “sustaining the new Keeley habits: regular patterns of sleep, regular and balanced meals, regular consumption of water, abstinence from tobacco and caffeinated drinks, healthy recreation, and care in the selection of personal associates.”

If you skip the atropine injections, that series of admonitions remains the bedrock of drug and alcohol treatment programs everywhere.

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