The End of My Addiction

amount of a substance can be crucial to its having one effect on neurotransmission rather than another. For example, low doses of alcohol activate mainly (GABAA), receptors, stimulating areas of the brain devoted to thinking, pleasure seeking, and relaxing the body. High doses also activate receptors for glutamate, disturbing learning and memory, as occurs in blackouts.
    Taken together, the functions and characteristics of neurotransmitters and receptors determine how we respond physically, emotionally, and mentally to different substances and behaviors. Our responses—sensations, moods, images, and thoughts—become part of the process and contribute to their own propagation through self-organizing and self-reinforcing feedback loops. Thus an imbalance that generates overly anxious or depressed feelings may be imbalanced further by the strength of that feeling, helping anxiety or depression to recur with greater strength and frequency.
    At the same time, this imbalanced neurotransmission is no more subject to conscious influence or control than any other organic disease process. Research has shown that closely similar patterns of neurotransmission apply not only to all drug addictions, but also to so-called nondrug addictions such as binge eating, compulsive gambling, compulsive shopping, and sex addiction. There is also a very close overlap with the neurotransmission seen in anxiety, depression, and impulse disorders. 2
    The identification of characteristic patterns of neurotransmission associated with both addiction and underlying dysphoria suggests that addicted patients can be helped with medication that affects brain activity. The first medication for alcoholism, disulfiram (Antabuse), might be said to do so indirectly. The primary effect of disulfiram is to prevent the body from metabolizing alcohol. This leads to the buildup of formaldehyde in the body, which makes people physically sick if they drink alcohol, the hope being that this will in turn create a mental aversion to drinking.
    Beginning in 1984, with the FDA’s approval of naltrexone for use in treating heroin addiction, a new class of addiction medications appeared that directly affect neurotransmission. Naltrexone (brand names Revia and Depade), which the FDA specifically approved for treating alcoholism in 1994, inhibits the release of dopamine by acting on the brain’s opioid receptors. It was followed by medications such as acamprosate (brand name Campral), which reduces glutamate by acting on the NMDA receptors in the brain; topiramate (brand name Topamax), an anti-epileptic drug that activates GABA A receptors and reduces glutamate; and ondansetron (brand name Zofran), which increases serotonin. These medications are known as anticraving agents, and they are used to reduce craving as an adjunct to twelve-step programs, psychotherapy, and rehab.
    The craving-reduction approach was an important development in addiction medicine. It responded to the centrality of craving as the primary debilitating symptom of addiction and the primary predictor and cause of relapse, even after lengthy abstinence. Yet even the most enthusiastic proponents of the craving-reduction approach admit that it at best achieves only modest results.
    Although European studies have shown somewhat greater effects in reduced craving, American studies have found acamprosate to be no better than placebo. All studies agree that acamprosate has no serious limiting side effects.
    Besides acamprosate, the anticraving agents most commonly used in alcoholism treatment, naltrexone and topiramate, have been found in randomized trials to reduce craving, producing a modest decrease in the number of heavy drinking days and a modest increase in the period before the first heavy drinking day. The modest effects of oral naltrexone tend to fade after about three months; with injectable naltrexone (brand name Vivitrol), these effects have been shown to continue over a six month follow-up, but craving persisted throughout the trial and there was no progressive decrease in heavy drinking days. 3 In addition, naltrexone and topiramate have potential side effects that limit their use.
    Naltrexone can damage the liver, which rules it out for patients with liver cirrhosis.
    Topiramate, developed as an antiseizure drug and marketed under the brand name Topamax, commonly affects memory, thinking, speech, and movement. Some disgruntled patients have dubbed it “Dopamax.” Topiramate can also