Showing posts with label drug research. Show all posts
Showing posts with label drug research. Show all posts

Wednesday, January 22, 2014

Drug Craving, or How to Be Your Own Worst Enemy


Plus the disease model, warts and all.

Bielefeld, Germany—
The second in an irregular series of posts about a recent conference, Neuroplasticity in Substance Addiction and Recovery: From Genes to Culture and Back Again. The conference, held at the Center for Interdisciplinary Research (ZiF) at Bielefeld University, drew neuroscientists, historians, psychologists, philosophers, and even a freelance science journalist or two, coming in from Germany, the U.S., The Netherlands, the UK, Finland, France, Italy, Australia, and elsewhere. The organizing idea was to focus on how changes in the brain impact addiction and recovery, and what that says about the interaction of genes and culture. The conference co-organizers were Jason Clark and Saskia Nagel of the Institute of Cognitive Science at the University of Osnabrück, Germany.  Part One is here.


Marc Lewis, a developmental neuroscientist who is currently professor of human development and applied psychology at Radboud University in The Netherlands, and who spent five days discussing addiction with the Dalai Lama and a small group of scientists, scholars, and addiction specialists in Dharamsala, India, last year, was a late but welcome addition to the speaker list at the conference.

Author of Memoirs of an Addicted Brain, and a self-confessed “drug addict turned neuroscientist,” Dr. Lewis always brings a thought-provoking dual perspective to his work on addiction. (See my review of his book here.) He also blogs here.

In Bielefeld, Dr. Lewis offered up a wide-ranging view of what addiction is and is not, linking neuroscience, psychology, and Buddhism in the process. 

Craving is “the one condition all addicts agree is their worst enemy,” Lewis said. “This is one place where science and subjectivity have to come together. Scientists need to focus on this, because addicts are completely unanimous about it. This is the enemy. It’s not physical withdrawal symptoms, it’s not relief. It is craving.”

Buddhism teaches that “craving is the fundamental engine of personality development,” Lewis said. “It’s what keeps us going around and around.” But if you don’t much like the notion of the wheel of reincarnation, Lewis suggested, then you can contemplate “the cyclical nature of how we repeat patterns in life that lead to suffering.”

“Craving is such an unpleasant state, that after a while, you end up doing it, you get the drugs. I did opiates, and I would spend hours and hours trying to sit on my hands, trying to watch something on TV, trying to go for a walk, and finally, there’s this thing that keeps rising in the background, and it doesn’t go away. It was a constantly growing tension, an anxiety and discomfort, that came from very deep down. You spend most of your energy trying to hold this thing at bay, and according to the ego depletion literature, you can’t do that for very long. These cognitive control centers just give up. They are limited resources.”

Craving is not a steady state. It grows. “Neuroscience helps us understanding why craving is so nasty.” Enter “delay discounting,” a term from behavioral economics used by several speakers during the conference. Delay discounting is the proposition that the perceived value of something rises steeply as the reward gets closer in time. A variation of this idea is seen in the classic marshmallow test for children: One marshmallow now, or two if you wait until later?

“Craving traps you in delay discounting,” said Lewis. “Immediate reward is worth more than imagined future happiness. The job of dopamine in the striatum is to increase the attractiveness or value of one goal, and to reduce the attractiveness and value of all the other goals. This is a brain that is well designed for addiction. You get tons of dopamine rising up in anticipation of reward. So you’re really stuck in the immediate. At which point you’ve effectively lost contact with the rest of your life. In the narrative of who you are, you can’t even include next week, or the next morning.”

Nonetheless, Lewis finds serious problems with the standard disease model of addiction, as championed by NIDA’s Nora Volkow and other in the NIH, however brain-based he may be. As a developmental neuroscientist, Lewis is predisposed to viewing the brain as a locus of change by definition. “The disease model uses brain change as a foundational premise. But brains change with development, anyway. And in fact, brains are designed to change.”

Any proper model of addiction, he insisted, has to correspond with what we know about brain change. “But it also has to correspond with addicts’ experiences. I was a drug addict from about age 25 to 30. I was in really bad shape. And now I talk with a lot of drug addicts, and one of the things that I keep hearing is that scientists and clinicians don’t really know what they’re doing—they don’t know where to go with it. They know that addiction is really nasty, but they don’t know what it’s like, unless they’ve been there.”

Lewis offered a view of addiction that shifts the semantic focus from disease to development. The drug is not the culprit. By reconceptualizing addiction as a developmental disorder, he suggested, we can move the debate forward into the world, where the action is:

Addiction results from accelerated learning, the acquisition of thought patterns that rapidly self-perpetuate because of the brain’s tendency to become sensitized to highly attractive rewards. This is a developmental process, accelerated by a neurochemical feedback loop that is particular to strong attractions. Like other developmental outcomes, addiction isn’t easy to reverse, because it’s based on synaptic restructuring. Like other developmental outcomes, it arises from neural plasticity, and uses it up at the same time.

And the mechanisms responsible are the same ones responsible for many things that involve desire, learning, reward seeking, and compulsive behavior—including the so-called behavioral addictions like overeating and compulsive sex. However, “the severe consequences of addiction don’t make it a disease, any more than the consequences of violence make violence a disease.”

In an email exchange after the conference, I followed up with Dr. Lewis on some of these matters, and he sent me the following additional thoughts on the “diseasing” of addiction:

Proponents of the disease model argue that addiction changes the brain. And they're right: it does. But the brain changes anyway, at every level, from gene expression, to cell density, to the size and shape of the cortex itself. Of course, neuroscientists who subscribe to the disease model must know that brains change over development. Their take on pathological brain change would have to be very specific in order to be convincing. For example, they would have to show that the kind (or extent or location) of brain change characteristic of addiction is nothing like that observed in normal learning and development. But this they cannot do. The kind of brain changes seen in addiction also show up when people take up rock collecting, fall in love, learn how to cook, or become obsessed with their appearance. The brain contains only a few major traffic routes for learning and goal seeking. And, like the main streets of a busy city, they are often under construction.  Brain disease may be a useful metaphor for how addiction seems, but it's not a valid explanation for how it actually works.



Sunday, April 8, 2012

From Their Mouth to Your Ear: Researchers Talk Drugs


A collection of five-question interviews.

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

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

See below for the story thus far:



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

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

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

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

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

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

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

“With growing and clear acceptance of the neurobiological underpinnings of addiction, our work on pharmacogenetics promises to provide effective medications—such as ondansetron—that we can deliver to an individual likely to be a high responder, based on his or her genetic make up." MORE

Michael Farrell is the director of the National Drug and Alcohol Research Centre (NDARC) at the University of New South Wales in Sydney, Australia. Before that, he was Professor of Addiction Psychiatry at the Institute of Psychiatry at Kings College, London.

“The near complete absence of methadone or buprenorphine treatment in American prisons is hard to understand, when you see what a great contribution US research and treatment with methadone and buprenorphine has had globally. Now there are over 300,000 people on methadone in China as part of HIV and AIDS prevention." MORE

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

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


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

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

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