The End of My Addiction

body. The nature of the role of endogenous GHB in the body remains unknown, but it seems to me likely to depend on the sedative-hypnotic effects of GHB and thus to be involved in the body’s ability to relax and to recover from stress. In a recent peer-reviewed article in Alcohol and Alcoholism (see the appendix ), I postulated that a GHB deficiency may underlie substance dependence through a GABA B -mediated dysphoric syndrome. A biological deficit of GHB would thus be experienced as a loss of sedative effect, leading to anxiety, muscular tension, insomnia, and/or depression. Alcohol and other drugs would serve to “correct” these uncomfortable states. The fact that the sedativehypnotic effects of GHB are mediated by the GABA B receptor could explain why baclofen, the only other substance known to act on that receptor, can be so useful against addiction and its underlying dysphoria. After the article was published, Giancarlo Colombo, the GHB researcher Fabio Caputo, George Koob, Michel Le Moal, Jerry Posner, and Dave Roberts told me they were very interested in the idea and thought it worth investigating.
    I also discussed the role that GHB deficiency may play in alcoholism in a peer-reviewed article in The American Journal of Drug and Alcohol Abuse , commenting on an article in the journal by Felice Nava et al. about GHB’s use in alcoholism treatment. ( See Appendix .)
    In a reply to my article, Dr. Nava, writing on behalf of himself and his coauthors, including Gian Luigi Gessa, who is world-renowned in addiction medicine as a major figure in research on GHB, baclofen, and related topics, called my comment “appealing.” He wrote, “In light of the…evidence [of GHB and baclofen both acting on the GABA B receptor] and our recent work, Dr. Ameisen is correct in pointing out that alcoholism may be a disease characterized by a GHB-deficiency in the brain…Furthermore, since baclofen has been shown to suppress both in animals and humans the intake of several drugs including alcohol, we may suppose a key role of the endogenous GHB not only in alcoholism but in several other forms of drug dependence.” Dr. Nava concluded, “If [Ameisen’s] hypothesis will be demonstrated, the role of endogenous GHB will be elucidated,” something that has eluded medical science since Henri Laborit began studying GHB in connection with GABA in the 1960s. 11

    As I’ve described, I was initially intrigued by baclofen because of my conviction that my lifelong muscular tension was an important symptom of the anxiety that motivated my alcoholism. Recent research has suggested why baclofen’s GABA B -mediated muscle-relaxant effects could have so much potential in addiction treatment.
    Addiction-related brain research has concentrated on the amygdala—part of the brain’s limbic system, which processes physical sensations, feelings, and emotions—as the site where the most relevant neurotransmission occurs. The amygdala has also been shown to be prominently involved in the experience of anxiety. The neuroscientist Antonio Damasio and his colleagues at the University of Iowa and the University of Southern California have cast light on the insula, a neighboring brain region that is also part of the limbic system. The insula plays a crucial role in integrating feelings and desires, including addictive cravings, and making us conscious of them. Early in 2007, four of Professor Damasio’s colleagues, the neuroscientists Antoine Bechara, Hanna Damasio, Nasir Naqvi, and David Rudrauf, reported in the journal Science that injuries to the insula suffered during strokes eliminated craving for nicotine in people who were previously addicted to smoking tobacco. 12
    When Science announced the insula finding, I was in New York City for discussions connected with this book, and I learned that Antonio Damasio and I share the same literary agent. Professor Damasio was also passing through New York, and we had a lengthy talk. Having read my self-case report, Professor Damasio said with a smile, “Your method is better than ours. You suppress craving with medicine. A stroke is not exactly the treatment one would recommend to a patient.”
    He continued, “I have an idea why baclofen could work.”
    I said, “I think I do, too.”
    Professor Damasio said, “What is it?”
    I said, “Baclofen is a muscle relaxant, and I’m sure that the muscles play a direct role in the clinical expression of addiction.”
    Professor Damasio said, “I