Thursday, September 23, 2010

How Naltrexone cuts down on cravings

A patient I saw 2 weeks ago had an implant put in and he kept raving to me about how well it was working. He said that as soon as he had it put in his cravings went away. What he said next was fascinating to me. He said that what had changed was that he couldn’t bring up the memories of getting high any more.

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He was a patient at Williamsville Wellness, an inpatient program where I am the Medical Director. He was in early recovery. Often patients in early recovery like to bring up memories of getting high. They get a bit of a rush from the memories and this temporarily can feel pretty good – until they realize they aren’t actually going to get high! It is hard to stop our brains thinking about and romanticizing those euphoric feelings. I think it is a bit like thinking about a girl we just started dating or if we are remembering those fabulous brownies we love so much. So, my patient said that if he would try to conjure up those euphoric memories he just couldn’t do it. He said it was like the connection just wasn’t there anymore. He felt so good to be free of the obsession.

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When I asked my next patient, an alcoholic, about his experience with the implant he said the same kind of thing. From the moment he got his implant he said he had completely lost his cravings. He particularly noticed it when he went to the grocery store. Normally he would look at bottles of wine and remember how good it used to be. With the implant in he went to look at the wine bottles and realized he just had no interest in them. He had lost the memories of how the wine might make him feel. Like my earlier patient, he felt so great to be free of the obsession.

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I got to wondering if there was anything in the literature that would help me understand this. The prevailing wisdom is that Naltrexone works because it partially blocks the endorphin receptors. The endorphin system (our natural morphine) helps us feel energetic and euphoric. Alcohol and other drugs work by stimulating this system and releasing endorphins so blocking parts of the endorphin system reduces cravings because our brains know that they can’t get high anymore. Naltrexone shouldn’t be doing anything to patient’s memory systems. But does it?

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We have known for a while now that alcoholics and patients with drug addiction get cravings when they are exposed to triggers – small amounts of their drug, or pictures or other memories associated with their drug and alcohol use. When patients get these cravings their pleasure center (Ventral Striatum or Nucleus Accumbens) is activated – just like when they use the actual drug. So could Naltrexone be actually blocking the way these memories activate the pleasure center?

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To my surprise I did find that there is some information about how Naltrexone can interrupt and block memories of getting high. I found some fascinating research and a very informative article written by Dr Hugh Myrick and his colleagues who are affiliated with the Medical University of South Carolina (Archives of General Psychiatry, volume 65, April 2008).

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It turns out there was already some animal research that does indicate that Naltrexone may exert a lot of its effect by reducing what is called “cue-induced reinforcement” – a fancy term meaning that if alcoholics have triggers – pictures or other memories - they will have cravings. The area that is affected by these “cue-induced reinforcements” is our old friend the Dopamine rich Pleasure Center (also called the Ventral Striatum, Nucleus Accumbens or Ventral Tegmental area).

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Myrick and his group wanted to see if Naltrexone would work the same way in humans. Whether Naltrexone would reduce the amount these memories of getting high would activate the pleasure center. They studied about 90 alcoholics and 17 social drinkers. They put some of them on a placebo sugar pill and others on oral Naltrexone. After 7 days they gave them all a taste of alcohol and showed them some alcohol related pictures. The results were exactly as they predicted. The social drinkers had no activation of their pleasure center with the small taste of alcohol or with the pictures. When the alcoholics had either a small drink or saw a picture of a drink they had an increase in cravings and they had an increase in activity of their Ventral Striatum. The social drinkers didn’t get either the cravings or the increased activity in the Ventral Striatum.

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But after the test subjects were on put on Naltrexone they had significantly less craving and significantly less activation of their Ventral Striatum following a drink of alcohol or after they were shown a triggering picture. The results were dramatic.

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In conclusion, it seems pretty clear that one of the major ways Naltrexone works is to interrupt the memory pathways that cause triggers or memories to induce cravings and relapse. This completely fits in with what my patients were telling me. Of course patients don’t really care exactly how Naltrexone Implants work – they just love the fact that the implants work so well. With cravings greatly reduced it makes it so much easier for them to stay clean and sober and start building up a new lifestyle.

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Dr Peter Coleman

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