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/

“When Did I Become the Junkie Auntie Mame?”

Courtney Love tells her tangled tale in a new e-book.

Maer Roshan, author of Courtney Comes Clean: The High Life and Dark Depths of Music’s Most Controversial Icon, logged a dozen “exhilarating and exhausting” sessions with the widow of Nirvana’s Kurt Cobain over the course of a year, pulling together a definitive look at Love’s drug addictions and other demons. Roshan taped countless hours of interviews, and received additional written material from the “Tolstoy of texting,” as Love refers to herself. The book is highly readable, almost, one is tempted to say, addictively so. Sure, it’s tabloid stuff—let he or she who has never peeked at Gawker or Jezebel cast the first stone.

Roshan, who has performed editorial duties at Radar, New York, Talk, and Interview, does his best to shape the former rock star’s rambling tales into a coherent narrative. (Disclosure: I have contributed articles and blog posts to Roshan’s online addiction and recovery magazine, The Fix.) But coherence is an uphill struggle with Love, who is clearly a highly intelligent, strong-willed woman; an addict who suffers from comorbid mental disorders, including such possibilities as bipolar disorder, borderline personality disorder, and narcissistic personality disorder. Her brief acting career and string of dramatic financial ups and downs, in the grand tradition of Hollywood stars and superstar musicians dragged down by fame, fate, and drugs, has led to her current “florid obsessions” with financial conspiracies against her, Roshan writes. 

At times she has installed a “sobriety minder” in her New York townhouse; at other times she has tried to bash a Vanity Fair reporter over the head with an Oscar snatched from Quentin Tarantino.  None of this would be of anything but passing interest except for the Keith Richards-style Queen of Drugs role that she has either assumed or has had thrust up on her. As she told Roshan: “Kim Stewart called me up screaming, ‘Courtney, what are we going to do? Kelly [Osbourne] is passed out and is blue on the floor!’ She wasn’t doing too okay back then. For some reason, Kim also called me when Paris Hilton got pulled over for her last DUI. And Lindsay Lohan called me after she was arrested…. And then Lindsay’s father called me for advice every day for weeks. It was weird. I mean, I’m not even friendly with these girls. When did I become the junkie Auntie Mame?”

So, is she a sober or an addicted Auntie Mame? Is she the go-to girl for straight talk on drugs and sobriety, or just another enabler? She has been through formal rehab perhaps a dozen times now. At one point in the book, she crows about the fact that all the drugs she’s currently taking are “entirely legal,” then flies to a posh London Hotel, using a personal physician and a 24-hour nursing staff to kick her addiction to Adderall—prescription speed. Love appears to have the “chronic relapsing” part of addiction down pat.

Roshan notes that, “like many addicts, she has found herself increasingly isolated and withdrawn in recent years.”

 I asked Maer Roshan a few questions about the book, to which he kindly responded:

Q. Has this woman every really been clean and sober for an extended period, or is she just conning everybody about her recovery?

Maer Roshan: She's certainly not sober in any way that would pass muster at A.A., but she's come a long way from the demons that plagued her past… She admits to using prescription pills. (She makes a point to note that they're all legally prescribed.) She also enjoys a few drinks now and again. But she's nothing like the addict she was five years ago, when she was shooting smack five times a day or holed up in her house in L.A, watching for police cars and smoking kilos of crack. For someone like Courtney, that's real progress. In light of all the damage that drugs have inflicted on her life and her family, I think she is serious about sobriety. She's seen first-hand the damage that drugs can do. After all, they killed her husband and ruined her relationship with her daughter. But ultimately sobriety means different things to different people. As they say in A.A., it’s about progress rather than perfection, so even though she's far from a teetotaler, her progress is impressive.

Q. Lindsay and Paris and all the young drug people make pilgrimages to her for advice. Is that a good thing or a bad thing?

Roshan: I think it's neither a good thing nor a bad thing. Obviously, Lindsay or Paris would probably get better advice from a person more grounded in sobriety, or from a therapist or doctor. But, as she notes in the interview, being famous does strange things to people's heads, especially famous women, so in a way it's understandable that younger girls in the same position would relate to her. Believe it or not, Courtney's actually pretty shrill on the subject of drugs. She’s been known to reach out to those women, even if they don't reach out to her.

Q. Courtney seems obviously co-morbid. Has she ever sought psychiatric help?

Roshan: Obviously I'm not qualified to diagnose her. I know she's seen a fair share of psychiatrists throughout her life. In my book, her mother notes that Courtney was agitated and anxious from the time she was a toddler. Her parents built her a special hut attached to their main house in New Zealand, in part to keep her from attacking her brothers and sisters. She was prescribed Valium from the time she was seven. Like most crazy people, she has the capacity to be brilliant and funny and extremely entertaining. But she's also filed with bitterness and unbelievable rage, and you never quite know which Courtney you're gonna get. She's a blast to hang out with, but as I can attest from personal experience, it's kind of scary when her rage is directed at you.
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So what to make of her? “Most people think I dry out at these really posh places,” she told Roshan, “but I’ve landed in some pretty gnarly spots.” And that’s when I began to feel some sympathy for Love, seeing her falsehoods and contradictions and obsessions in the light of her addictions, known that there must have been plenty of horrifying nights, and equally agonizing mornings, and self-loathing, and a lot of time surrounded by people, but always alone. What to make of her? I don’t think we know yet. I hope she gets better, stronger, wiser, and ends up making a fool out of me.

Photo Credit: http://blogs.sfweekly.com

Army Doctor Sees Victory, and a Dangerous Drug Bites the Dust—Almost.

An interview with the man who blew the whistle on the neurotoxic malaria drug in the U.S. Army’s kit bag.

A dangerous malaria drug invented by the Army and commonly used by soldiers and civilians alike causes everything from episodes of psychotic violence to nightmares more real than reality, and is finally being withdrawn as the first-line treatment for troops in malarial zones.

Lariam, known medically as mefloquine, has also been a licensed treatment for civilians abroad for more than 25 years. Yet it has only been in the recent past that common knowledge of Lariam’s dangers has surfaced publically.

The development of Lariam was a prime example of military-industrial cooperation. Discovered at the Walter Reed Army Institute of Research during the Vietnam war, initially tested on prisoners at the Joliet Correctional Center in Illinois, and marketed worldwide by Hoffmann-La Roche, mefloquine was an urgent response to high malaria rates in U.S. combat troops overseas. Unfortunately, such close cooperation also led to a lack of adequate clinical testing—the practice that underpins the notion of drug safety. Ashley M. Croft of the Royal Army Medical Corps in Britain has written that in the case of Lariam, “the first randomized controlled trial of the drug in a mixed population of general travellers was not reported until 2001.” Croft believes the FDA was influenced by “the powerful military-industrial-governmental lobby into over-hasty decisions.”

In addition, “travel medicine experts in most countries were slow to recognize the danger signals associated with Lariam…. As late as 2005 a reviewer in the New England Journal of Medicine, also an employee of the US military for over 20 years, continued to maintain… that Lariam was a ‘well tolerated’ drug,” according to Croft. The victims of all this pharmacological hoodoo, Croft maintains, “have been those many business travellers, embassy staff, tourists, aid workers, missionaries, soldiers and others who were well at the start of their journeys into malaria-endemic areas…”

Largely due to the efforts of Dr. Remington Nevin, a medical epidemiologist and a physician in the U.S. Army, who went public about Lariam’s potential for causing psychological illness, military officials announced in December that the Army was done with Lariam as a first-line malaria preventative except for “special circumstances.” In the past, such special circumstances have allegedly included its use as an interrogation drug at Guantanemo.

As far back as 2004, an alarming number of suicides among troops in Iraq prompted calls for an investigation of Lariam. “The military is ignoring this drug’s known side effects,” Steve Robinson of the National Gulf War Resource Center told UPI. In October of 2004, Sen. Dianne Feinstein (D-Calif) urged then-Secretary of Defense Donald Rumsfeld to investigate the drug: “Given the mounting concerns about Lariam as expressed by civilians, service members and medical experts about its known serious side effects, I strongly urge you to reassess,” she wrote to Rumsfeld. Meanwhile, Mark Benjamin and Dan Olmsted of UPI were reporting that “mounting evidence suggests Lariam has triggered mental problems so severe that in a small percentage of users it has led to suicide. UPI also reported that soldiers involved in a string of murder-suicides at Fort Bragg, N.C., in the summer of 2002 after returning from Afghanistan had taken the drug.”

Almost ten years later, Sen. Feinstein wrote another letter, this one to Secretary of Defense Leon Panetta, complaining that a 2009 policy limiting the use of mefloquine among U.S. troops was not being followed. Although parent company Roche discontinued Lariam in the U.S., generic versions remain available, and the company continues to sell Lariam in other countries. “My office has been contacted recently by servicemembers who were prescribed mefloquine when one of the other medications would have been appropriate and were not given the FDA information card. These servicemembers are now suffering from preventable neurological side effects,” including  balance problems, vertigo, and psychotic behavior,” she wrote.

In addition, as a military medical instructor told Addiction Inbox: “Some service members might ‘double up’ on their weekly dose, or increase the frequency of dosing, intentionally for recreational purposes. There is no evidence that the military educates service members to avoid this temptation or that it is unsafe. Users might even justify it by believing it could enhance the drug's anti-malarial activity. In the military, it is frequently a tenet of our culture that ‘if one is good, two is better.’"

In November,  military officials overseas stopped almost all use of mefloquine in malaria-prone areas in Africa and the Middle East. Army Col. Carol Labadie, the service’s pharmacy program manager, commented on the long overdue change: “If that means changing from one drug to another because now this original drug has shown to be potentially harmful… it is in our interests to make that change.”

As Croft wrote, it was not a case of inconvenient research being deliberately witheld. Rather, “the necessary pre-licensing research was simply never carried out.”

Questions still remain about the use of mefloquine at Guantanamo as an “enhanced interrogation technique.” Last year, Stars and Stripes ran an investigation of the matter and concluded: “Medical experts say the Defense Department policy of giving detainees large doses of mefloquine is poor medical practice at best and torture at worst.”

INTERVIEW WITH DR. REMINGTON NEVIN

—Is there any good science behind the notion that mefloquine might be addictive?

Dr. Remington Nevin: I am speaking to you in an individual capacity, and my opinions are my own and in no way reflect those of the U.S. Army or the Defense Department. There is no evidence that mefloquine is addictive per se, but the drug is well-known to produce vivid, technicolor dreams, and as a result it is frequently viewed as an incidental and convenient form of recreation among people, including Peace Corps volunteers and military service members, who find themselves already required to take the drug, and otherwise typically without access to alternative drugs of abuse, such as alcohol. The vivid "rock star" fantasies frequently reported are often perceived as consolation for the isolation and loneliness that typical accompany travel to remote areas where mefloquine is prescribed.

Ann Patchett, a prize-winning author, recently wrote a book called State of Wonder in which mefloquine features prominently, and her writing was likely based to a good degree on her and her acquaintances' experiences with the drug. Patchett herself actually refers to the drug's "recreational" properties and alludes in a recent interview to her having wanted to "take the drug out for a spin" (see http://thedianerehmshow.org/)

REHM: Did you take Lariam when you went to the Amazon?
PATCHETT: I did, I did. And actually, if I hadn't gone to the Amazon, I probably would've just taken it recreationally at home because I really wanted to take it out...
REHM: Experience it.
PATCHETT:...for a spin, right.
REHM: Yeah.
PATCHETT: And the side effects of Lariam listed on the package, psychotic dreams, terrible nightmares, paranoia, suicide is a possible side effect and I've known a lot of people who have had true psychosis on Lariam.

—Can you lay out what you know about mefloquine causing hallucinatory and dissociative effects in travelers who take it for malaria?

Dr. Nevin: [The symptoms] closely mimic those of a condition known as anti-NMDA receptor encephalitis, which an expert in the field, Dr. Dalmau, describes as including "anxiety, fear, bizarre or stereotypical behaviour, insomnia, and memory deficits". It is thought that rising levels of antibody to the NMDA receptor induces… widespread downstream dysregulation of  limbic dopaminergic and noradrenergic tone, which ultimately are responsible for producing the syndrome's psychotic effects… This limbic dysregulation may also be similar to what is seen with the chemical NMDA receptor antagonists, including ketamine and phencyclidine, which share with mefloquine a particular propensity towards impulsivity and dissociation. For these reasons I conclude that mefloquine should be characterized as a dissociative hallucinogen.

—What is a dissociative hallucinogen?

Dr. Nevin: It is this property that also likely explains the drug's association with suicidality and acts of violence. Mefloquine is the only non-psychotropic drug listed among the top ten associated with acts of violence, and there is a growing literature linking it causally to suicide.  It may be that the combination of mefloquine-induced amnesia, dissociation, and hallucinations (many with vivid religious or persecutory themes) creates a perfect storm that can trigger impulsive acts of violence. It is not uncommon for those recovering from (and surviving) mefloquine psychosis to report engaging in suicidal gestures that in retrospect were devoid of any fear of consequences…. Just within the past year, in a paper in the journal Science, Bissiere and colleagues demonstrated mefloquine interfering with context fear response in the hippocampus.


—Could you expand on the notion of "vivid rock star fantasies" experienced by some users?

Dr. Nevin: Extremely vivid dreams are among the most widely reported "adverse effect" of the drug. Users can frequently describe their dreams in great detail even well into the next day and, in some cases, the dreams seem to take on an almost lucid quality. Many experience gratifying and deeply pleasurable dreams that they almost don't wish to awaken from; conversely, for some others, the effect seems to be quite the opposite, with the reported nightmares being particularly haunting the next day.

—You have referred to Lariam as a "zombie" drug. Could you expand on that?

Dr. Nevin: If you must know, the reporter for AP caught me on Halloween, but I believe the term is quite apropos. The drug is the pharmaceutical equivalent of the living dead; it is somehow able to survive controversies that would have quickly killed other drugs. Interestingly, Lariam has been quietly delisted although generics remain widely available. To further stretch the metaphor, the drug is also decidedly neurotoxic and kills brain cells; one can say it "eats brains", and lastly, I would argue that a "zombie-like" state is not an unreasonable description of the most extreme adverse effects of the drug.

—I'm shocked to discover mefloquine on the list of top 10 drugs associated with acts of violence. Could you comment on a non-psychoactive drug making that list?

Dr. Nevin: It is quite shocking. Mefloquine isn't typically considered a psychotropic drug, but it probably should be recharacterized as a psychotropic medication with incidental anti-malarial properties. Of the drug contained in a 250mg tablet, only about 1-2mg, less than 1%, is ultimately found at the site of its intended anti-malarial activity, in the circulation. And although the neuropharmacokinetics are still somewhat unclear, arguably a far greater percentage of the drug is ultimately found in brain tissue than in the circulation. Incredibly, when the drug was undergoing FDA licensing, this brain penetration wasn't even well-characterized. Transcripts from the licensing meetings clearly show committee members skipping over this fact without much consideration. Certainly there seems to have been no requirement to submit the drug to neurotoxicity testing, despite many related quinoline compounds having demonstrated well-characterized, permanent neurotoxicity at least 40 years earlier.


—How common is the use of mefloquine in the U.S. as a whole?

Dr. Nevin: There has been a fairly rapid decline in the use the drug, correlating with rising appreciation of mefloquine's dangers and awareness of contraindications to its safe use. Malarone is now the predominant anti-malarial prescribed within a large network of U.S. travel clinics. The U.S. military, which developed the drug just over 40 years ago, recently prohibited the use of mefloquine as first-line agent, and has dramatically curtailed its use after research revealed the drug had been widely prescribed to service members with mental health contraindications. Recently, the U.S. Centers for Disease Control further clarified guidance against routine use of mefloquine in service members, conceding that use of mefloquine may "confound the diagnosis and management of posttraumatic stress disorder and traumatic brain injury".

—What are the consequences of mixing Lariam with alcohol?

Dr. Nevin: There is fairly good evidence from case reports that alcohol may potentiate the deleterious effects of mefloquine, but the mechanism remains controversial. It had been suspected that alcohol simply exerted an inhibitory effect on mefloquine metabolism, but now… it seems likely that alcohol exerts a direct pharmacodynamic effect.


—Lariam is still sometimes prescribed for children traveling in malaria zones. Are there special dangers for kids?

Dr. Nevin: As the popularity of the drug is declining among adults, some experts with ties to industry have been peddling the drug for niche pediatric use, ostensibly because it is well tolerated. Unfortunately, such claims are based on studies which in many cases are deeply flawed and…. even verbally fluent but younger children may not have the experience or perspective to properly describe these symptoms. Apart from these considerations, I would argue that I don't think enough is understood about the neurophysiological effects of the drug to justify its use even in older children and adolescents.  Mefloquine is a psychotropic drug. Given what we are learning of mefloquine's effects on the limbic system, even at relatively low doses, it seems at least plausible that the developing brain might in some way be adversely affected by the drug, particularly during long-term dosing.

—Why was the Army so slow to move on mefloquine?

Dr. Nevin: To put things in perspective, understand that mefloquine is the sole product of an aggressive 20-year, multi-million dollar effort by the U.S. Army. Mefloquine was identified only in the early 1970s after tens of thousands of other quinoline compounds had failed toxicity and efficacy tests. By the time of mefloquine's U.S. licensure in 1989, it was essentially DoD's last and only hope. So, if I could rephrase your question, if mefloquine is as safe as the Army once claimed, then why is it no longer the drug of choice? If we assume that this quiet policy change was made in tacit acknowledge of safety concerns, then the question is, precisely what new information has informed this decision, why has this change taken so long to occur, and most importantly, what harm might this policy change now be seeking to avoid, which may already have accrued among those in whom the drug had been previously used?  

The reasons for the Army's silence on these questions are likely quite banal. Admitting mefloquine is a dangerous drug would be a bitter pill for any Army medical leader to swallow. Many of today's senior medical leaders were intimately involved in the studies that saw the drug rise to prominence, and many are on record over the previous decades publicly defending the drug against the increasingly validated claims of its earlier critics. Absent external pressure to do so, it is likely of little benefit for these senior medical leaders to suffer the humiliation that would come from admitting what they might now otherwise privately concede. Saying nothing is the path of least resistance on their journey to a comfortable retirement.

—Could you comment on allegations of Lariam use as an interrogation drug at Guantanamo?

Dr. Nevin: The use of mefloquine at Guantanamo represents either medical malpractice with culpability at some of the highest levels of military medical leadership, or it suggests something far more intentional and sinister. I typically believe that one should never ascribe to malice what can be attributed to simple incompetence, but in this case, I am not so certain. There are too many inconsistencies and unanswered questions. The issue will ultimately require the release of medical records, open hearings, and testimony to resolve. I am confident this will happen.

Book Review: Writers On The Edge

A compendium of tough prose and poetry about addiction.

Here’s a book I’m delighted to promote unabashedly. I even wrote a jacket blurb for it. I called it an “honest, unflinching book about addiction from a tough group of talented writers. These hard-hitters know whereof they speak, and the language in which they speak can be shocking to the uninitiated—naked prose and poetry about potentially fatal cravings the flesh is heir to—drugs, booze, cutting, overeating, depression, suicide. Not everybody makes it through. Writers On The Edge is about dependency, and the toll it takes, on the guilty and the innocent alike.”

I am happy to stand by that statement, content to note that this collection of prose and poetry on the subject of addiction and dependency by 22 talented writers, with an introduction by Jerry Stahl of “Permanent Midnight” junky fame, includes a number of names familiar to me. That makes it all the easier to recommend this book—I know some of the talent. Take James Brown, a professor in the M.F.A program at Cal State San Bernardino, the book’s co-editor, who offers an excerpt from his excellent memoir, This River.  James is no stranger to the subject, having pulled out of a drug and alcohol-fueled nosedive that would have felled lesser mortals for good. “Even though you’ll always be struggling with your addiction, and may wind up back in rehab,” Brown writes, “at least for now, if only for this day, you are free of the miracle potions, powders and pills. If only for this day, you are not among the walking dead.” Or my friend Anna David, who is an editor at The Fix, an online addiction and recovery magazine to which I frequently contribute, and author of several books, including Party Girl and Falling for Me. Anna poignantly recalls “my shock over the power than booze had… it was the greatest discovery of my life.” And Ruth Fowler, another Fix contributor and author of Girl Undressed, delivers up a brilliantly detached story of her life as an addict on both coasts and just about everywhere else, which begins with the line, “I gravitated to the fucked up writers.”

Then there are the contributors I don’t know but wish I did, like co-editor Diana Raab, a registered nurse and award-winning poet, as well as co-author of Writers and Their Notebooks, who offers a poem to her grandmother: “Your ashen face and blond bob/disheveled upon white sheets/on the stretcher held by paramedics/lightly grasping each end, and tiptoeing.” Or another poet, B. H. Fairchild, author of the marvelous collection, Early Occult Memory Systems of the Lower Midwest: “When I would go into bars in those days/the hard round faces would turn/to speak something like loneliness/but deeper, the rain spilling into gutters/or the sound of a car pulling away/in a moment of sleeplessness just before dawn.”

And more: Frederick Barthelme, author of Double Down: Reflections on Gambling and Loss. Stephen Jay Schwartz, best-selling crime novelist  and former director of development for filmmaker Wolfgang Petersen. Writers Rachel Yoder, Victoria Patterson, David Huddle, and Scott Russell Sanders. Etc. This collection is a rich brew of essay, poetry, and memoir. A tough book, a brutal book, a real heartbreaker with grit. Some people get stronger and rise; some don’t. It is a thoughtful and creative compendium of addiction stories, and some of them will surprise you. All of them are solidly written, laid out with an unrelenting realism.

Here it is, these authors are saying. This is how it plays out. Unforgettable stuff.

Reward and Punish: Say Hello to Dopamine’s Leetle Friend

  Dopamine recruits a helper to track drug rewards.

Ah, dopamine. Whenever it seems like researchers have finally gotten a bead on how that tricky molecule modulates pleasure and reward, and the role it plays in the process of drug and alcohol addiction, along come new findings that rearrange its role, deepening and complicating our understanding of brain function.

We know that the ultimate site of dopamine activity caused by drugs is the ventral tegmental area, or VTA, and an associated structure, the nucleus accumbens. But dopamine neurons in the VTA actually perform two distinct functions. They discriminate acutely between the expectation of reward, and the actual reward itself. Pavlov showed how these dual functions are linked, but the manner in which dopamine neurons computed and then dealt with the differences between expectation and reward—a controversial concept known as reward prediction error—was not well understood.

We all know about reward and punishment, however. Years ago, behaviorism’s emphasis on positive and negative reinforcement demonstrated the strong connection between reward, punishment, and learning. As Michael Bozarth wrote in “Pleasure Systems in the Brain,” addictive drugs “pharmacologically activate brain reward mechanisms involved in the control of normal behavior. Thus, addictive drugs may be used as tools to study brain mechanisms involved in normal motivational and reward processes.”

But how does the evolutionary pursuit of pleasure or avoidance of punishment that guarantees the survival of an organism—fighting, fleeing, feeding, and… fornicating, in the well-known “4-F” configuration—become a pathological reversal of this function? To begin with, as Bozarth writes, “the direct chemical activation of these reward pathways does not in itself represent any severe departure from the normal control reward systems exert over behavior…. Simple activation of brain reward systems does not constitute addiction!”

What does, then? Bozarth believes addiction results from “motivational toxicity,” defined as deterioration in the “ability of normal rewards to govern behavior.” In an impaired reward system, “natural” rewards don’t alter dopamine function as strongly as drug rewards. “Direct pharmacological activation of a reward system dominates the organism’s motivational hierarchy at the expense of other rewards that promote survival,” Bozarth writes. The result? Drug addicts who prefer, say, methamphetamine to food.

How does an addict’s mind become so addled that the next hit takes precedence over the next meal? A group of Harvard-based researchers, writing in Nature, thinks it may have a handle on how the brain calculates reward expectations, and how those calculations go awry in the case of heavy drug and alcohol use.

The dopamine system somehow calculates the results of both failed and fulfilled expectations of reward, and uses that data in future situations. Cellular biologists, with some exceptions, believe that dopamine neurons effectively signal some rather complicated discrepancies between expected and actual rewards. Dopaminergic neurons were, in effect, computing reward prediction error, according to the theory. They were encoding expectation, which spiked when the reward was better than expected, and fell when the reward was less than expected. As Scicurious wrote at her blog, Neurotic Physiology “If you can’t predict where and when you’re going to get food, shelter, or sex in response to specific stimuli, you’re going to be a very hungry, chilly and undersexed organism.” (See her excellent and very readable post on dopamine and reward prediction HERE. )

But nobody knew how this calculation was performed at the cellular level.

Enter research mice.

As it turns out, dopamine is not the whole story. (A single neurotransmitter rarely is.) Dopaminergic neurons account for only about 55-65% of total neurons on the VTA. The rest? Mostly neurons for GABA, the inhibitory transmitter. “Many addictive drugs inhibit VTA GABAergic neurons,” the researchers note, “which increases dopamine release (called disinhibition), a potential mechanism for reinforcing the effects of these drugs.” By inhibiting the inhibitor, so to speak, addictive drugs increase the dopamine buzz factor.

The researchers used two strains of genetically altered mice, one optimized for measuring dopamine, the other for measuring GABA. The scientists conditioned mice using odor cues, and offered four possible outcomes: big reward, small reward, nothing, or punishment (puff of air to the animal’s face). Throughout the conditioning and testing, the researchers recorded the activity of neurons in the ventral tegmental area. They found plenty of neurons with atypical firing patterns. These neurons, in response to reward-predicting odors, showed “persistent excitation” during the delay before the reward. Others showed “persistent inhibition” to reward-predicting odors.

It took a good deal of sorting out, and conclusions are still tentative, but eventually the investigators believed that VTA dopamine neurons managed to detect the discrepancy between expected and actual outcomes by recruiting GABA neurons to aid in the dendritic computation. This mechanism may play a critical role in optimal learning, the researchers argue.

Furthermore, the authors believe that “inhibition of GABAergic neurons by addictive drugs could lead to sustained reward prediction error even after the learned effects of drug intake are well established.” Because alcohol and other addictive drugs disrupt GABA levels in the brain’s reward circuitry, the mechanism for evaluating expectation and reward is compromised. GABA, dopamine’s partner in the enterprise, isn’t contributing properly. The ability to learn from experience and to accurately gauge the likelihood of reward, so famously compromised in active addiction, may be the result of this GABA disruption.

Naoshige Uchida, associate professor of molecular and cellular biology at Harvard, and one of the authors of the Nature paper, said in a press release that until now, “no one knew how these GABA neurons were involved in the reward and punishment cycle. What we believe is happening is that they are inhibiting the dopamine neurons, so the two are working together to make the reward error computation.” Apparently, the firing of dopamine neurons in the VTA signals an unexpected reward—but the firing of GABA neurons signals an expected reward. Working together, GABA neurons aid dopamine neurons in calculating reward prediction error.

In other words, if you inhibit GABA neurons through heavy drug use, you screw up a very intricate dopamine feedback loop. When faced with a reward prediction error, such as drug tolerance—a good example of reward not meeting expectations—addicts will continue taking the drug. This seems nonsensical. If the drug no longer works to produce pleasure like it used to do, then why continue to take it? It may be because dopamine-active brain circuits are no longer accurately computing reward prediction errors. Not even close. The research suggests that an addict’s brain no longer registers negative responses to drugs as reward errors. Instead, all that remains is the reinforcing signals from the dopamine neurons: Get more drugs.

[Tip of the hat to Eric Barker (@bakadesuyo) for bringing this study to my attention.]

Cohen, J., Haesler, S., Vong, L., Lowell, B., & Uchida, N. (2012). Neuron-type-specific signals for reward and punishment in the ventral tegmental area Nature DOI: 10.1038/nature10754

Photo Credit: http://www.zazzle.com 

Heroin in Vietnam: The Robins Study Reexamined

How everything we knew about heroin was wrong.

Editor's note: The famous Robins study on heroin use among Vietnam veterans has been so often—and so recently—misinterpreted that I felt motivated to reprint an older post on the subject.

[Originally posted 7/24/10]

In 1971, under the direction of Dr. Jerome Jaffe of the Special Action Office on Drug Abuse Prevention, Dr. Lee Robins of Washington University in St. Louis undertook an investigation of heroin use among young American servicemen in Vietnam. Nothing about addiction research would ever be quite the same after the Robins study. The results of the Robins investigation turned the official story of heroin completely upside down.

The dirty secret that Robins laid bare was that a staggering number of Vietnam veterans were returning to the U.S. addicted to heroin and morphine. Sources were already reporting a huge trade in opium throughout the U.S. military in Southeast Asia, but it was all mostly rumor until Dr. Robins surveyed a representative sample of enlisted Army men who had left Vietnam in September of 1971—the date at which the U.S. Army began a policy of urine screening. The Robins team interviewed veterans within a year after their return, and again two years later. 

After she had worked up the interviews, Dr. Robins, who died in 2009, found that almost half—45 per cent—had used either opium or heroin at least once during their tour of duty. 11 per cent had tested positive for opiates on the way out of Vietnam. Overall, about 20 per cent reported that they had been addicted to heroin at some point during their term of service overseas.

To put it in the kindest possible light, military brass had vastly underestimated the problem. One out of every five soldiers in Vietnam had logged some time as a junky. As it turned out, soldiers under the age of 21 found it easier to score heroin than to hassle through the military’s alcohol restrictions. The “gateway drug hypothesis” didn’t seem to function overseas. In the United States, the typical progression was assumed to be from “soft” drugs (alcohol, cigarettes, and marijuana) to the “hard” category of cocaine, amphetamine, and heroin. In Vietnam, soldiers who drank heavily almost never used heroin, and the people who used heroin only rarely drank. The mystery of the gateway drug was revealed to be mostly a matter of choice and availability. One way or another, addicts found their way to the gate, and pushed on through. 

“Perhaps our most remarkable finding,” Robins later noted, “was that only 5% of the men who became addicted in Vietnam relapsed within 10 months after return, and only 12% relapsed even briefly within three years.” What accounted for this surprisingly high recovery rate from heroin, thought to be the most addictive drug of all? As is turned out, treatment and/or institutional rehabilitation didn’t make the difference: Heroin addiction treatment was close to nonexistent in the 1970s, anyway. “Most Vietnam addicts were not even detoxified while in service, and only a tiny percentage were treated after return,” Robins reported. It wasn’t solely a matter of easier access, either, since roughly half of those addicted in Vietnam had tried smack at least once after returning home. But very few of them stayed permanently readdicted.

Any way you looked at it, too many soldiers had become addicted, many more than the military brass had predicted. But somehow, the bulk of addicted soldiers toughed their way through it, without formal intervention, after they got home. Most of them kicked the habit. Even the good news, then, took some getting used to. The Robins Study painted a picture of a majority of soldiers kicking it on their own, without formal intervention. For some of them, kicking wasn’t even an issue. They could “chip” the drug at will—they could take it or leave it. And when they came home, they decided to leave it.

However, there was that other cohort, that 5 to 12 per cent of the servicemen in the study, for whom it did not go that way at all. This group of former users could not seem to shake it, except with great difficulty. And when they did, they had a very strong tendency to relapse. Frequently, they could not shake it at all, and rarely could they shake it for good and forever. Readers old enough to remember Vietnam may have seen them at one time or another over the years, on the streets of American cities large and small. Until quite recently, only very seriously addicted people who happened to conflict with the law ended up in non-voluntary treatment programs.

The Robins Study sparked an aggressive public relations debate in the military. Almost half of America’s fighting men in Vietnam had evidently tried opium or heroin at least once, but if the Robins numbers were representative of the population at large, then relatively few people who tried opium or heroin faced any serious risk of long-term addiction. A relative small number of users were not so fortunate, as Robins noted. What was the difference?

Quotes from: Robins, Lee N. (1994). “Lessons from the Vietnam Heroin Experience.” Harvard Mental Health Letter. December.

See also:

Robins, Lee. N. (1993) “Vietnam veterans' rapid recovery from heroin addiction: a fluke or normal expectation?” Addiction. 88(8), 1037 – 1167.

Origins of the Disease Model of Addiction (Part 1) can be found HERE.

Photo Credit:  soldiersupportproject.org

Mike Doughty Talks About “The Book of Drugs”

Former Soul Coughing front man on sobriety and life as a solo artist.

Over the phone, Mike Doughty doesn’t have much to say about his former band, Soul Coughing. When I mention it, he gives out a low growl as a warning. He said it all in The Book of Drugs, and it doesn’t sound like he had much fun. Although the avant-garde rock band created music that was spiky and sneaky and immensely popular, topped off by Doughty’s monotonic but strangely penetrating vocal delivery on such classics as “Super Bon Bon,” “True Dreams of Wichita,” and “Circles,” Doughty was drug-dependent and miserable. Musician pitted against musician, egos battered and bruised, credit taken and not taken—and Doughty busily running the gamut of addictions from Jack Daniels to heroin, with a ton of marijuana in the bargain. 

But that was the 90s. Since then, Doughty has done two things of note—three, if you count teaching himself German. He has crafted an innovative solo career, and he has escaped from a cornucopia of addictions that had almost buried him alive.

It seems almost unfair that a talented singer/songwriter like Doughty should also turn out to be a good writer, but there you have it. The Book of Drugs is informative but not confessional, rock-snarky but tempered with a round of amends. It is also whip-smart and bitterly funny:

--“Lars would go out and get drunk every night, then stumble in, sounding for all the world like he was going around moving absolutely everything in the room a foot to the left.”

--“Currently, in the studio next door, guitar overdubs were being recorded for a Meatloaf record. Meatloaf was not in attendance.”

--“I smoked three packs a day. Ridiculous. It was like a job. I woke up, and began the work of the first pack. It was a repetitive, manly task, like getting up early every day to chop down pine trees.”

--“Weed addicts are along among drug users in that they think their shit is cute.”

--“The unsingable girl yelled at me, ‘You don’t get HIGH, you just get FUCKED UP!”

Told in an episodic, chapter-free style, the book lays the foundations for Doughty’s future by page 3. “My dad’s dad,” he writes, “was the town drunk in Tullos, Louisiana.” Doughty's father was an alcoholic as well. From the outside, the process is unfathomable: Doughty relates what is known as the parable of the jaywalker: “Guy’s really into jaywalking, his friends are all like, ha ha funny, then he gets hit, they figure he’s done, he does it again, this time gets both legs broke, the friends are like, whoa that’s weird, and then he does it again and they’re bewildered, and he does it again, and they abandon him, and he does it again, and he does it again.”

Here's what Doughty had to say last week in our interview:

--You got sober after embarking on your solo career. Did you hit bottom, in the classic AA sense?

The thing that really made me think was when I was actually addicted to alcohol, and I started waking up in the morning with the shakes, and I just had this very logical reaction, which was like, oh, I’m addicted, this is horrible, so I’ll just start drinking first thing in the morning. And that’s when it was like, holy shit, I’m an alcoholic, there’s alcoholism in my family, and it’s not just a "drug thing." It was kind of acceptable to be a heroin addict for me, but it was not acceptable for me to be a morning drunk.

--Was alcohol your drug of choice, or heroin?

Well, I went through about thirty-five different drugs. I was always good at finding drugs. My struggle was to manage it. If I had to call something my drug of choice, it would be heroin, in terms of the thing that killed the most pain effectively. Eventually, when it stopped working, I’d say, okay, well, I’ll just do it on the weekends, or detox for a couple of days, and I’ll smoke a lot of weed and I’ll drink and I’ll do some coke or ecstasy, and then I can be back on the heroin on weekends.”

--What’s your opinion of addiction as a biological disorder—the disease model approach to it?

I don’t really know any addicts that don’t have trauma in their backgrounds. I think, to activate this thing, there is generally pain that needs to be numbed, or trauma that needs to be gotten away from. One of the things about the disease model is that so many people of the non-alky variety are just so indignant about it. I think we should just give it up. It’s maybe not worth the fight over the semantics of it. It’s like, addicts are killing themselves, they’re unable to stop using drugs, I would think that would be more important than what to call it.

--Did you use any anti-craving drugs, or do any medication-assisted recovery?

I was on naltrexone for a while, but I was getting high on everything but opiates at the time, so it was just a way of not using opiates. I was shit-faced drunk, and stoned, so I don’t know what eliminating one specific drug—I don’t what the ultimate effect of that was, because for me, I would just go out and find something else.

--Did you do any formal detox or treatment before you went into the rooms, as AA is often called?

No. I had a couple of prescribing shrinks and they suggested treatment, because I had insurance, but I was like, fuck that, no way. It’s funny, they cover detoxes and rehabs but they don’t cover talk therapy. Most of my struggle to get into the path of non-self destruction was because of a shrink who just nailed me as an addict the moment I met her. Within probably twenty minutes she was like, "you know, there are AA meetings above St. Mark’s Place." And I was so angry, like, "what are you talking about?" So a lot of the struggle, of, you know, am I an addict, or do I just have a problem with a single drug, or are the rooms just a cult, it’s a religion—somehow she got me to keep showing up. I don’t know what kind of hook she put in me, but I was showing up, strung out, falling asleep in the chair, and she kept me coming back week after week. I don’t know what kind of Jedi mind trick she used.

--You’re one of the few performers who have been willing to admit that for a minority of people, marijuana is addictive and has its own characteristic set of withdrawal effects.

Yeah, my basic line is, if you know a thirty-six year-old wake-and-bake guy, that guy is probably a marijuana addict. I don’t know the science, I don’t know shit about withdrawal, the mentality of addiction, but I know plenty of people that were stoned all day. And they kept doing it. But I definitely believe weed should be legal. First of all, it doesn’t make any sense if alcohol is legal. Second, it’s such a dirty weapon in the drug war. And the drug war is a war on the poor.

-- You’re "co-morbid." You're an addict, and you’re diagnosed as bipolar.

I do know that there was a part of it that was relieved tremendously by meds—a very careful construction of a cocktail of meds by a super-smart prescribing shrink. Really being very cautious and gradual about it. But if I’m really messed up about something emotionally, talk therapy has the most immediate effect. Just being in touch with dudes from the rooms, a sponsor, friends, I’m on a gratitude list with a bunch of guys, we email each other every day—that stuff is a lot more effective in the short term.

--As a polydrug addict and an artist who has seen his way through to sobriety, what message what you like to send to people working in the treatment and recovery fields?

You know, advice is not my scene. I lucked into the right kind of treatment. Something I hear over and over again from people is that they end up with the wrong therapist. It’s like a relationship, essentially. I think it would be great if therapists were very upfront about saying, "If I’m not the right person, then let’s find you the right person.”

--“Don’t push against your own weight,” you sing in “Diane.” It got me thinking about how hard it is for addicts to lift themselves by their own bootstraps through sheer willpower.

If you let go, if you just get out of your own damn way, it will be so much easier. David Mamet wrote a book about the theater, and he has this thing about how directors overmanage plays when they direct them. And his metaphor was that when the airplane was being developed, they had this terrible problem with spinouts. All the time, the pilot would lose control of the plane; it would start spinning and spinning, and crash and hit the ground. So they invented the ejector seat, so if you’re having a spinout, you just hit the button and zoom out into the air with a parachute. And they discovered that pretty much immediately when the pilot was out of the plane, the airplane straightened out and righted itself. That’s how it is, you try to control too much shit, you’re more likely to fuck it up.

--So, things are good?

-- I’m stoked to be sober. I’ve got eleven years now. Things are really good, even when they’re bad, like a bad year financially or whatever, it’s like, oh my god, I’m doing really good. As long as I’m loving the work I’m making, and I have an audience, and I can make a living, those are pretty much the only things I really have any control over.