10/5/15

The End of Alcoholism? Part 3

© f8grapher | 123rf.com
© f8grapher | 123rf.com

“One of the first duties of the physician is to educate the masses not to take medicine.” Sir William Osler, physician

Olivier Ameisen wrote in The End of My Addiction that thoughts about an addictive substance could insinuate themselves into an addict’s consciousness and quickly preoccupy the whole mind with anxiety about how to get it. “This is a harrowing experience mentally and emotionally as well as physically, because it is charges with shame and self-loathing for even experiencing the craving.” Cravings could propel him into a trance-like state. He would set out to buy liquor, feeling as if someone else was controlling his body. “When craving defeated me, I could only hope, pray, and strive to do a better job of resisting it the next day.”

Ameisen was “a French-American male physician with alcohol dependence and comorbid pre-existing anxiety disorder.”  He said he had been plagued by anxious feelings of inadequacy throughout his life. He’d been seeing therapists for a long time before he started drinking. They were never much help with his anxiety. “Nor was the Xanax they prescribed me.” So he turned to alcohol.

I was terrified of living without alcohol. Without it, I would be an anxious wreck. Admitting my problem drinking to most of my friends and my colleagues terrified me too. I feared being ostracized, and since I felt that drinking should be under my control I felt ostracism would be justified.

He told every physician and therapist he saw that his fundamental problem was anxiety, “which expressed itself in chronic muscle tension, and which intensifying to a panic state, triggered the overwhelming need to drink for relief.” None of the addiction professionals took him seriously. So he looked around to prescribe his own treatment. He thus disregarded another observation of the Canadian physician, William Osler: “A physician who treats himself has a fool for a patient.”

An old girlfriend sent him a copy of a New York Times article that discussed baclofen reduced craving with cocaine, but he was in the midst of a binge and misplaced the copy. He eventually contacted the doctor mentioned in the article and asked her about baclofen. Although he was encouraged by the conversation, his alcohol treatment specialist and psychiatrist weren’t interested in discussing an unproven medication. In early February of 2002 he began doing an internet research into baclofen. Panic was his most crippling symptom, so he searched first under “baclofen panic.” He found several reported studies, including the 2000 study by Addolorato, “Ability of baclofen in reducing alcohol craving and intake.”

Ameisen developed a theory that there is a “threshold dose” of baclofen needed to break the cycle of craving, preoccupation and obsessive thoughts with alcoholism. And he decided to try out the theory on himself. He began his self-medicated treatment with baclofen on January 9, 2004. See “The End of Alcoholism? Part 1” for a fuller description of this process. Ameisen did attempt social, controlled drinking, about fifteen months after establishing alcohol abstinence by taking baclofen. But he said he preferred not drinking. James Medd in The Guardian suggested that “He can now drink socially—an idea entirely counter to the teachings of AA and most other therapies.”

Ameisen saw anxiety as his primary disorder, with his drinking as a way to self-medicate his anxiety. Additionally, he held on to a belief that he should be able to control his drinking: “I should be able to control my urge to drink. . . . Since I felt that drinking should be under my control, I felt ostracism would be justified.” Even though he reportedly went to hundreds of Alcoholics Anonymous (A.A.) meetings, if he held onto a belief that he should be able to control his drinking, he would not be able to effectively use A.A. to remain abstinent, because he didn’t entirely accept their first Step: “We admitted that we were powerless over alcohol, and that out lives had become unmanageable.”

Other medical professionals were concerned with his use of high dose baclofen. Jonathan Crick, the psychiatrist who is the editor-in-chief of Alcohol and Alcoholism, said he’s been encouraged with his own treatment of 50 patients with baclofen, but won’t use the high doses of Ameisen’s method. He stays under 100 mg a day. “I do actually have some concerns about unwanted effects in large doses. . . . This is a drug which is active in the brain, and there are some concerns about some unwanted effects of higher doses.”

I also wonder if he turned a blind eye to some of the concerns raised about baclofen in the literature. He saw it as essential to his own ability to manage anxiety, cravings, and to refrain from compulsive, out of control drinking.

There have been a series of studies reporting what has been called a “baclofen withdrawal syndrome.” A 1981 article, Complication of Baclofen Withdrawal, reported that three patients taking baclofen on a long-term basis experienced hallucinogens and/or seizures with abrupt reduction of their dose or discontinuation of baclofen therapy. A 1998 article, “Prolonged Severe Withdrawal Symptoms,” reported that an abrupt decrease or too rapid taper off baclofen could result in a withdrawal syndrome manifesting hallucinations, delirium, seizures and high fever.

A 2005 study, “Delirium Associated with Baclofen Withdrawal,” reviewed 23 published cases of psychiatric symptoms with baclofen withdrawal. Delirium, but not other symptoms was found to arise from abrupt baclofen withdrawal. The delirium appeared to be greater in individuals who received chronic baclofen therapy. A 2001 case study reported on the case of a man with neuroleptic malignant-like syndrome, with disorientation, signs of autonomic dysfunction and rigidity from abruptly stopping his long-term baclofen treatment. “He improved markedly after the reintroduction of baclofen.”

In contrast to published studies saying that baclofen helped with alcohol withdrawal, a Cochrane review published in May of 2015, “Baclofen for alcohol withdrawal syndrome,” concluded that the evidence for recommending baclofen for alcohol withdrawal syndrome was insufficient. “We therefore need more well-designed RCTs to prove its efficacy and safety.”

A 2013 article assessed the potential to confuse baclofen withdrawal for alcohol withdrawal. The authors said the clinical and psychopharmacological overlap between acute intoxication and the withdrawal symptoms of baclofen, alcohol and benzodiazepines could lead to diagnostic uncertainty. “In every case of unexplained confusion, agitation, hallucinations, seizures, and psychosis occurring in patients with current drinking, both AWS and BWS should be systematically considered.”

A small study by Franchitto et al. in 2013 did a retrospective study of the medical records for 12 individuals diagnosed with alcohol dependence who had overdosed on baclofen. The median dose of ingested baclofen was estimated at 340 mg. Ten had a previous suicide attempt. Three had co-ingested benzodiazepines. The “classic” effects of baclofen overdose associated with neurotransmitter inhibitory effects were evident:

Impaired consciousness or coma, generalized muscular hypotonia with absent limb reflexes, respiratory depression, seizures, hemodynamic changes and cardiac abnormalities such as supraventricular tachycardias, premature atrial contractions and first-degree heart block.

Four patients were in coma before admission, and required intubation and respiratory support. Coma after a baclofen overdose may persist for several days because of the drugs’ depression of neuronal activity in the central nervous system. Nevertheless, the authors concluded that consistent with other reports, “most patients with baclofen overdose had a good outcome with adequate supportive care.”

There have been reports of heart problems and even mania. A 2014 case report concluded that cardiac arrest occurred with baclofen withdrawal syndrome. A 2014 article concluded that baclofen-induced manic symptoms could appear in individuals regardless of a history of bipolar or mood disorders. The question to be raised about the use of baclofen for alcohol use disorders is what effects does it have on the brain? To the extent that these effects correspond to the effects of alcohol, or any other potentially “addictive” substance, its use in substance misuse treatment is a double-edged sword.

A 2015 study by Rigal et al. reviewed the records of 146 patients who used baclofen to treat their alcohol use disorder. Ninety (78%) reported at least one adverse effect. The most frequently reported adverse effect was a disruption of the wake-sleep cycle in 73 patients (63%). “Persistent adverse effects occurred in 62 patients (53%).” There were 8 patients who had adverse effects that led them to stop taking baclofen. Women reported more adverse events than men. “High-dose baclofen exposes patients with alcohol disorders to many adverse effects. Generally persistent, some adverse effects appear at low doses and may be dangerous.”

The evidence seems clear for a baclofen withdrawal syndrome. There is a state of tolerance or dependence that develops with long term, high dose use. Are patients given baclofen informed of the potential for them to develop a dependency upon this medication? My concern is this dependency is a “sleeper” symptom that initially goes largely unnoticed as with medications used to “treat” opioid use disorders—buprenorphine, and methadone. This same problem with dependency also exists with benzodiazepines prescribed for anxiety or sleep disturbance. They initially work so effectively that the dependency, if it’s noticed at all, is minimized. Only after it becomes seriously entrenched physically and psychologically do people realize what has happened.

So where might all of this lead? Baclofen is a generic drug with no potential for a pharmaceutical company to patent, and thus become a highly profitable product for them. So pharmaceutical companies are largely not interested in developing baclofen as a treatment for addictions. However, there is a prodrug version of baclofen called arbaclofen palcarbil that was initially in development by XenoPort as a treatment for GERD and spasticity due to multiple sclerosis. In May of 2013, XenoPort announced that Phase 3 clinical trials for arbaclofen palcarbil were unsuccessful and they decided to terminate further investment in the program.

In May of 2014, Reckitt Benckiser Pharmaceuticals and XenoPort announced they had entered into a joint license agreement, where Reckitt Benckiser will have the exclusive rights to develop and commercialize arbaclofen palcarbil as a treatment for alcohol use disorder.ClinicalTrials.gov indicated that a Phase 2 study by Reckitt Benckiser was scheduled to begin in September of 2015 and should be completed by April of 2016. The purpose of this clinical trial is to determine the maximum tolerated dose of arbaclofen palcarbil in treating alcohol use disorder.

Reckitt Benckiser appears to be looking for a replacement blockbuster product since its opioid treatment drug, Suboxone, went generic. Before losing its patent rights, Suboxone had become a billion dollar drug for Reckitt Benckiser, rising to the 25th best selling drug of 2010, according to drugs.com. The existing research on baclofen gives us a pretty good idea on what the future holds for any arbaclofen palcarbil product. Also, the potential population for a maintenance drug for alcohol use disorder is significantly larger than there was for an opioid maintenance drug. If Reckitt Benckiser can successfully move arbaclofen palcarbil through the FDA approval gauntlet, we will see a patented knock off product of baclofen on the market to treat alcohol use disorder in a few years.

Suboxone made another top drug list in 2013. It was listed as the #2 most abused prescription drug of 2013 by Genetic Engineering & Biotechnology News. Hopefully, any arbaclofen palcarbil product will not repeat that ‘achievement’ for Reckitt Benckiser.

09/28/15

The End of Alcoholism? Part 2

© Katarzyna Białasiewicz | 123rf.com
© Katarzyna Białasiewicz | 123rf.com

Within an introductory “Note to the Reader,” to his book, The End of My Addiction, Olivier Ameisen said: “By completely suppressing my addiction, baclofen saved my life. I believe it can save and improve the lives of many others by completely suppressing their addictions, and I have written this book to that end.” He ended his note with a caution that his book was not a self-help manual or a guide to self-treatment. Baclofen, a prescription drug, “should be taken only as prescribed … and closely monitored by a licensed physician.” Yet his book is a detailed discussion of how he did exactly the opposite of everything he had just cautioned others not to do.

There had been some ongoing research into the potential of baclofen as a treatment for alcohol use disorders (see the References for Ameisen’s Alcohol and Alcoholism article) before Ameisen wrote his book. But Ameisen’s personal experimentation and its description in his book brought it to the attention of the public and sparked further interest in researching the potential of baclofen to treat addiction. “The End of Alcoholism? Part 1” looks in more detail at that story. Here I want to explore some of the research supportive of using baclofen in treating alcohol use disorders.

Giovanni Addolorato of the Catholic University of Rome was one of the initial baclofen researchers Ameisen read. Eventually they began to correspond and shared their interest its potential to treat alcoholism. A sampling of Addolorato’s published research studies looks at the ability of baclofen to reduce cravings and alcohol intake (2000); the suppression of alcohol withdrawal syndrome with baclofen (2002); a comparison of baclofen to diazepam in treating alcohol withdrawal (2006); the effectiveness of baclofen in maintaining abstinence with patients with cirrhosis of the liver (2007). Addolorato found baclofen to be effective in reducing craving and alcohol intake; it was comparable to diazepam in treating withdrawal; and it promoted abstinence—even in alcohol-dependent patients with cirrhosis of the liver.

Colombo et al. (2002) found that baclofen inhibited the drinking behavior of selectively bred alcohol-preferring rats. Baclofen is a known GABA(B) receptor and the results suggested that the GABA(B) receptor was involved in the disclosure and experience of the psychopharmacological effects of alcohol.

William Bucknam published a case study in 2007 to investigate whether baclofen-induced suppression to consume alcohol in animals could be transposed to humans. The patient, Mr. A., wanted to be able to control his drinking not establish and maintain abstinence. He “experienced a satisfactory response to high-dose baclofen that [was] sustained over ten months without significant side-effect.”

Lorenzo Leggio (2009) suggested that baclofen “represents a promising medication in the treatment of alcohol-dependent subjects.” It demonstrated an ability to reduce alcohol craving and intake. So it could be useful for promoting abstinence “as well as relieving alcohol withdrawal syndromes.”

In 2012 Renaud de Beaurepaire published a 2-year observational study of 100 individuals using baclofen. Initially 132 individuals were included in the study, but 32 were excluded for various reasons. These reasons included: not providing feedback after their first visit, stopping their use of baclofen because of adverse drug effects, and not being motivated to stop drinking. The effects of baclofen in the first three months were not included in the study, “because the effect of the treatment during this period does not represent the full potential of the drug.” (So what was going on in the initial three months that might give an unfavorable view of baclofen, I wonder?) The participants were evaluated before treatment with baclofen and then at 3, 6, 12 and 24 months to fit into three categories: low risk, medium risk and high risk.

In the “at low risk” category, patients experienced a suppression of craving, and their complete control over drinking was effortless. In the “at medium risk” category, patients experienced a clear decrease in craving but, for various reasons (in general, too strong an attachment to their drinking habits associated with an incomplete motivation to cease drinking), they were not able to control completely their drinking compulsions. In the “at high risk” category, patients either experienced an insufficient reduction of craving, or, although they experienced a significant decrease in craving, after a period of decrease in drinking, relapsed in their addiction. The risk category was defined according to the control over drinking during the last 4 weeks [before the evaluation].

Fifty-nine percent of the participants had one or more concomitant psychiatric disorders, including: 53% with anxiety disorder, 34% with depression, 18% with bipolar disorder, 42% with a sleep disorder, 11% with another addiction (mostly cannabis), 8% with psychosis, and 5% with an eating disorder.

At the end of the first visit, participants were told they could drink as usual. Using baclofen was expected to suppress the motivation to drink. No additional therapeutic intervention other than baclofen was given or suggested.

The doses ranged from 20 mg to 330 mg, with an average dose of 147 mg. Eighty-eight percent of the participants reported at least one undesirable side effect. The five most frequently reported were: fatigue or sleepiness (64%); insomnia (31%); dizziness (21%); tingling or abnormal sensations (18%); nausea or vomiting (17%).  There were several others, including: weight loss, memory loss, mental confusion, hypomania, dysphoria (a state of profound unease or dissatisfaction). De Beaurepaire assessed these side effects as “always benign.” However, eleven individuals discontinued treatment because they could not tolerate the side effects. And 20 participants did not reach an optimum dose because of the worsening of side effects.

The study reported that 92% reported a decrease in their motivation to drink at one time or another during the follow up time period. About half reported that at sufficient doses of baclofen, they had “a complete and effortless control” of alcohol craving. All participants were rated “at high risk” initially, but about half were rated “at low risk” at 3, 6, 12, and 24 months of follow up.

De Beaurepaire concluded that baclofen was very effective in treating alcohol dependence, particularly in reducing the motivation to drink. High doses were often necessary to obtain an optimum effect. The principle limitations seemed to be the side effects, the absence of a strong willingness in some to stop drinking, and co-occurring psychiatric illness—with the possibility that the concomitant use of psychotropic medications was a factor. “Baclofen should be considered a major help for drinking cessation, but other factors (psychological and environmental) are likely to play an important role with many patients.”

Ameisen sees baclofen as essentially a miracle cure for alcoholism. “So far it seems to work in all types except for one … and that’s people who turn up once and don’t come again.” He admits that no medication works effectively for everyone, and that includes baclofen. It’s not one size fits all; “you have to refine it.” There is a parallel here to methadone maintenance for opioid addiction. Ameisen’s “threshold dose,” refining the dosage until it’s high enough to eliminate cravings, sounds like raising a person’s methadone dose until they don’t want to get high anymore.

But the miracle cure claims of his treatment have provoked skepticism. Dr. Nicholas Pace, a clinical professor of medicine at New York University said: “I have studied alcoholism for the past 40 years, and there is no single magic bullet. This is a complex disease, and you can’t just flip one switch. The idea that an alcoholic can drink socially is simply a lot of bull.”

Ameisen said this kind of reaction from addiction professionals is because they feel threatened. “If baclofen works, then their specialism is going to fall apart.” But James Medd, writing for The Guardian suggested there could be another reason. This isn’t the first time someone claimed they found a cure for alcoholism. Barbiturates, benzodiazepines like Valium and antidepressants such as Prozac were hyped at one time as an end to addiction. Naltrexone has also been proposed as a “cure” for alcoholism in the Sinclair Method (See A “Cure” for Alcoholism).

At least for Ameisen, baclofen seems to have turned his life around. He reportedly had over nine years without drinking compulsively. There are several studies being done to investigate the treatment potential of baclofen. Here is sample a of some of those listed on clinicaltrials.gov. Assistance Publique – Hôpitaux de Paris (study 8) is completing a study to show the effectiveness of a year of baclofen treatment to that of a placebo. It was planned to increase the dose to a maximum of 300mg daily. In case of intolerance, the dosage would be decreased.  Essentia Health (study 9) is investingating the use of baclofen to prevent the symptoms of Alcohol Withdrawal Syndrome. The University of North Carolina at Chapel Hill (study 14) is investigating whether a 90mg dose of baclofen is effective and safe with individuals with alcohol dependence.

While there are some potential benefits with baclofen in treating alcohol use disorders, there are some clear adverse effects as well. We will look closer at those side effects in Part 3. Amiesen did not describe or dwell on the adverse effects with baclofen. Perhaps this was because he came to it when his own fight against alcoholism was at the point that he thought he was going to die from it. He had a blind spot to its negative effects because baclofen became the miracle drug that saved his life. As a physician writing a book on baclofen he cautioned his readers to not self-treat with baclofen. As an active binge drinker he was desperate to find something—anything—that would put an end to his addiction and did it anyway.

09/21/15

The End of Alcoholism? Part 1

© Katarzyna Białasiewicz | 123rf.com
© Katarzyna Białasiewicz | 123rf.com

There is an existing generic medication called baclofen, a muscle relaxant, which has been primarily used to treat spasticity and multiple sclerosis. Now it is in the early research stages as a treatment for alcoholism. Olivier Ameisen, a French-American cardiologist used himself as guinea pig in testing baclofen to treat his own alcoholism. He said that baclofen saved his life by freeing him of all cravings for alcohol and suppressing his addiction. He’s written several journal articles and a book, The End of My Addiction, describing his active drinking and how baclofen helped him stop. Ameisen died of a heart attack on July 18, 2013, but his “discovery” lives on. Let’s see if it is a miracle treatment; or not.

First we will summarize his experiences by looking at The End of My Addiction and an article he wrote for the journal, Alcohol and Alcoholism about nine months after his “complete liberation from symptoms of alcohol dependence.” Afterwards, we will look at some of what the research literature has to say about baclofen.

Ameisen said he began to struggle with symptoms of alcohol dependence in the 1990s. In his struggles to stop drinking, he had numerous emergency hospitalizations, emergency room visits, detoxifications, and years of both inpatient and outpatient rehabilitation services. Because of his persistent and strong cravings for alcohol he tried disulfiram (Antabuse), but drank on it. He tried Naltrexone and acamprosate, which didn’t stop his cravings or his relapses. He achieved periods of prolonged abstinence, but always struggled with cravings and a preoccupation with alcohol.

He attended Alcoholics Anonymous—sometimes as often as two, three or four meetings a day. He had a sponsor and a home group. Twice he did a “90 in 90,” attending ninety meetings in ninety days. He achieved prolonged periods of abstinence, but continued to relapse. By his estimate, he attended roughly 700 meetings a year, over a period of 7 years between 1997 and 2004. But until he began using baclofen to treat himself, he was unable to maintain abstinence.

Ameisen noted that physicians are notoriously bad patients “who often inhibit their recovery by trying to run their own cases.” And he seems to have been one of the worst. Long before he experimented with baclofen, he preferred to administer his own detox at home after his binges. He objected to CPH (the Committee for Physician Health of the New York Medical Society) refusal for him to continue using benzodiazepines for his anxiety. “Being denied a standard medication for severe anxiety, the condition that triggered and fueled my craving for alcohol, was at best counterproductive and at worst callous and cruel.”

He moved back to France in 1999, where he continued to drink off and on; and continued to seek help to stop his drinking. His binge cycles became shorter and shorter. A treating psychiatrist told him he was afraid he would not live much longer. In the midst of a binge, a friend from New York sent him an article on baclofen treatment for cocaine craving she saw in the New York Times. He was in the midst of a binge and misplaced it. A year later in November 2001 he remembered the article and had the friend track it down and send him another copy. Thus began his investigation and growing belief that baclofen could be a treatment for his alcoholism.

He contacted the doctor mentioned in the New York Times article. In February of 2002 he bought a PC and began to search the internet for information on “baclofen and panic.” He added “baclofen anxiety;” and finally baclofen alcohol.” This led him to a 2000 research article written by an Italian researcher, Giovanni Addolorato on the ability of baclofen to reduce alcohol craving and intake. Ameisen checked with a neurologist friend who told him it was a safe drug; not addictive (Baclofen is not a controlled substance, but can impair thinking or reactions. Withdrawal can result in seizures and hallucinations in some long term users). He decided to order some baclofen and try it on himself. In The End of My Addiction, Ameisen wrote:

Until this point, I had steadfastly tried to be a good patient and had avoided benig my own physician, but it seemed to me that in order to save my life from alcoholism, I had no choice but to risk walking out onto a tightrope without the normal safety net of another physician’s supervision.

This seems to be an inconsistent memory by Ameisen. He had been acting as his own doctor from the time of preferring his own detox at home. Nevertheless, he started using baclofen on March 22, 2002 and gradually increased his dose to 180 mg daily. He found some immediate relief of his muscular tension. He slept better and felt calmer. But he continued to binge drink and he continued to do research into baclofen. Eventually he saw an animal study that suggested even higher doses of baclofen could suppress cocaine intake in rats addicted to cocaine. “The more I learned, the more I came to believe that at a high enough dose of baclofen, I too could reach a point where I would lose the motivation to consume alcohol.”

Then on January 8, 2004, he decided it was now or never. “If I continued to follow my doctor’s advice and the conventional treatments for alcoholism, I was going to keep lapsing into binges and eventually die from drinking. I had to take my treatment into my own hands.”

From the first day, he reported his anxiety was substantially reduced and his sleep became restful. By the 37th day on 270 mg of baclofen, “I experienced no craving or desire for alcohol for the first time in my alcoholic life.” He reported that even in a restaurant with friends, he was indifferent to people drinking. Drowsiness became an inconvenient side effect, so he tapered his dose down to 120 mg per day from days 49-63 of his abstinence from alcohol. He stabilized at that dose, with occasional additions of 40 mg as needed in stressful situations.

At first he avoided situations and places where alcohol was present. But then believed he did not have to be concerned about this. Even when socializing with friends who were drinking, he had no cravings for alcohol. He realized he was “completely and effortlessly indifferent” to alcohol. He was encouraged by a friend and physician to write a paper of his self experiment, which was eventually published in the journal Alcohol and Alcoholism. In the article he said:

At the end of my ninth month of complete liberation from symptoms of alcohol dependence, I remain indifferent to alcohol. Abstinence has become natural to me. I no longer plan my life around alcohol. Alcohol thoughts no longer occur. . . . I no longer suffer anticipatory anxiety of relapse, of embarrassing or dangerous alcohol-related situations. I am no longer depressed about having an incurable stigmatizing disease.

Eventually he wondered if he was vulnerable to relapse. “Would one drink plunge me back into the hell of alcoholism?” So in May of 2005, sixteen months after his abstinence with baclofen, he decided to put his recovery to the test with three successive challenges.

First, while continuing his maintenance dose of 120 mg of baclofen, he had three standard drinks over a few hours at a social gathering. He didn’t guzzle his first drink. He also didn’t finish his third drink. The second test was increasing his alcohol intake to five standard drinks over a six-hour span. Again, he had no urge to drink rapidly and experienced only a mild euphoria. But the following afternoon, he had a serious craving that he said an additional dose of 40 mg of baclofen suppressed within an hour.

His final test was to consume a massive amount of alcohol; similar to that he ingested during active relapse. Over an evening, he drank about 600 milliliters of Scotch. The next day he had a mild hangover, but no cravings. “It was good to discover that with baclofen I could drink in a nondependent way.” On occasions he said he would have a glass or two of champagne or a mixed drink. But he preferred to not drink. In a 2010 article for The Guardian, James Medd, reported Ameisen can now even drink socially. “I became disease free-free,” he said.

After his “self-case report” was published in Alcohol and Alcoholism, it didn’t cause much professional excitement. “But he found that potential patients were much more interested.” After two unsuccessful years of trying to work up interest within the medical system, Ameisen decided to write The End of My Addiction, published in France as Le Dernier Verre (The Last Glass). Small groups using high-dose baclofen sprung up around doctors who adopted Ameisen’s ideas and who were willing to prescribe baclofen off-label. Interest in researching the potential treatment benefits of baclofen also began to occur.

Ameisen did begin to gather some research and media interest in his treatment method with baclofen. Here is a 2009 video of Diane Sawyer interviewing him after the publication of his book.  Ameisen began to correspond with George Koob in 2005, who would become the Director of the NIAAA, the National Institute on Alcohol and Alcoholism in January of 2014. He reported agreeing to act as a consultant to a prospective study Koob planned to do on baclofen. There was a mention in a report by the Committee on the Neurobiology of Addictive Disorders (where Koob was the Committee Chair before moving to the NIAAA) that baclofen could block alcohol self-administration in rats. Here is a link to Koob’s 2007 published study.

Ameisen was not the first person to theorize baclofen could be useful in the treatment of alcoholism. But his self-experimentation and the publication of his results spurred an interest in baclofen. His theories may or may not be ultimately demonstrated as valid. But what is clear is that while he claimed baclofen ended his cravings for and addiction to alcohol, it didn’t end his drinking. Ameisen believes that “In addiction the symptoms ARE the disease.” So he sees suppressing his symptoms as “curing” his alcoholism. Since he doesn’t have cravings and doesn’t obsess over alcohol and drinking, he’s “cured.”

But what are the long-term consequences of high-dose baclofen treatment for alcoholism? It isn’t listed as a controlled substance, but there is a baclofen withdrawal syndrome and high dose users are discouraged from rapid tapering or withdrawal. So is there a slow developing physical dependency or dysregulation of the GABA system in the brain from long term use of baclofen? Is taking a dose of a drug daily to not drink alcohol really a cure for alcoholism? Ameisen asserted that he has yet to find a patient where it hasn’t been a success. But is that the whole story? Ameisen’s death came before there was an answer to these questions.