Sober Now

Herein are some ideas that helped me stop abusing alcohol.

Monday, March 13, 2017

Charles Bukowski Urban Philosopher

Things I Learned from Charles Bukowski


couple 
 

Bukowski was disgusting, his actual real fiction is awful, he’s been called a misogynist, overly simplistic, the worst narcissist, (and probably all of the above are true to an extent) and whenever there’s a collection of “Greatest American Writers” he’s never included.
And yet… he’s probably the greatest American writer ever. Whether you’ve read him or not, and most have not, there’s 6 things worthy of learning from an artist like Bukoswski.

 
I consider “Ham on Rye” by Bukowski probably the greatest American novel ever written.  It’s an autobiographical novel (as are all his novels except “Pulp” which is so awful it’s unreadable) about his childhood, being beaten by his parents, avoiding war, and beginning his life of destitution, hardship, alcoholism, and the beginnings of his education as a writer.
I’m almost embarrassed to admit he’s an influence. Many people hate him and I’m much more afraid of being judged than he ever was.
1)      Honesty. His first four novels are extremely autobiographical. He details the suffering he had as a child (putting his parents in a very bad light but he didn’t care), he details his experiences with prostitutes, his lack of interest in holding down a job, his horrible experiences and lack of real respect for the women he was in relationships with, and on and on.  His fiction and poetry document thoroughly the people he hates, the authors he despises, the establishment he could care less about (and he hated the anti-establishment just as much. One quote about a potential plan the hippie movement was going to do: “Run a pig for president? What the fuck is that? It excited them. It bored me.”)
 
Most fiction writers do what fiction writers do: they make stuff up. They tell stories that come from their imagination. Bukowski wasn’t really able to do that. Whenever he attempted fiction (his last novel being a great example) it fell flat. Even his poetry is non-fiction.
There’s one story he wrote (I forget the name) where he’s sitting in a bar and he wants to be alone and some random guy starts talking to him: “its horrible about all those girls who were burned” and Bukowski says (I’m getting the words a little off. Doing this from memory), “I don’t know.” And the guy and everyone else in the bar starts yelling, “This guy doesn’t care that all those little girls burned to death”. But Bukowski was honest, “It was a newspaper headline. If it happened in front of me I’d probably feel different about it.” And he refused to back down and stayed in the bar until closing time.


(Matt Dillon playing a young Bukowski in "Factotum")
He had very few boundaries as to how far his honesty could go. He never wrote about his daughter after she reached a certain age. That’s about the only boundary I can find. Every other writer has so many things they can’t write about: family, spouses, exes, children, jobs, bosses, colleagues, friends. That’s why they make stuff up. Bukowski didn’t let himself get hampered by that so we see real raw honest, a real anthropological survey of being down and out for 60+ years without anything being held back. No other writer before or since has done that. For a particular example, see his novel, “Women” which detailed every sexual nuance of every woman who dared to sleep with him after he achieved some success. Most of these women were horrified after the book came out.
I try as hard as possible to remove all boundaries. But it’s a challenge with each post I do.
2)      Persistence. Bukowski got two stories published when he was young (24 and 26 years old) but almost all of his stories were rejected by publishers. So he quit writing for ten years. Then, in the mid 1950s he started up again. He submitted tons of poems and stories everywhere he could. It took him years to get published. It took him even more years to get really noticed. And it finally took him about 15 years of writing every day and writing thousands of poems and stories before he finally started making a living as a writer. He wrote his first novel at the age of 49 and it was financially successful. After 25 years of plugging away at it he was finally a successful writer.
25 years!
Most people give up much earlier, much younger. Both my grandfather and father wanted to be musicians, for instance. Both gave up in their 20s and 30s and took what they thought was the safer route. (The safer route being, in my opinion, what ultimately killed both of them).
And this persistence was while he was going through three marriages, dozens of jobs, and non-stop alcoholism. Some of this is documented (poorly) in the move “Barfly” but I think a better movie about Bukowski is the indie that Matt Dillon did about his novel, “Factotum” which details the 10 years he was going from job to job, woman to woman, just trying to survive as an alcoholic in a world that kept beating him down.
He wrote his first novel in 19 days. Michael Hemmingson who I write about below, wrote me and said Bukowski had to finish that novel so fast because he was desperately afraid he was going to be a failure at being a successful writer and didn’t want to disappoint John Martin, who had essentially given him an advance for the novel.


(a tattoo of the epitaph on Bukowski's tombstone)
3)      Survival. When I think “constant alcoholic” I usually equate that with being a homeless bum. Bukowski, at some deep level, realized that he needed to survive. He couldn’t just be a homeless bum and kill himself, no matter how many disappointments he had. He worked countless factory jobs (the basis of the non-fiction novel, “Factotun”) but even that wasn’t stable enough for him. Finally, he took a job working for the US Government (you can’t get more stable) working in the post office for 11 years. He didn’t miss child support payments (although he constantly wrote about how ugly the mother of his child was), and as far as I know he was never homeless or totally down and out from his early 30s ’til the time he started having success as a writer.
And despite writing about the overwhelming poverty he had, he did have a small inheritance from his father, a savings account he built up, and a steady paycheck. The post office job is documented, in full, in his first “novel”  called, appropriately, “Post Office”. Many people think that’s his best novel but I put it third or fourth behind “Ham on Rye” and “Factotum” and possibly “Women”.  He also wrote a novel, “Hollywood” about the blow-by-blow experience of doing the movie “Barfly”. All the names are changed (hence its claim to be fiction) but once you figure out who everyone is, its totally non-fiction. Like all of his other novels (not counting “Pulp”, which was the worst American novel ever written and published).
[See, 33 Unusual Ways to Be a Better Writer – many tips I got from reading his books.]
4)      Discipline. Imagine working a brutal 10 hour shift at the Post Office, coming home and arguing with your wife or girlfriend, or half-girlfriend, half-prostitute that was living with you, finishing off three or four six-packs of beer and then…writing. He did it every day. Most people want to write that novel, or finish that painting, or start that business, but have zero discipline to actually sit down and do it. If there was any talent that Bukowski had that I can’t actually figure out how he got it, its that discipline.
When he was younger (early 20s, late teens) he spent almost every day in the library, falling in love with all the great writers. The love must have been so great it superseded almost everything else in his life. He had to write like them or he really felt like he would die. He had to “put down a good line” as he would say. And every day he would try. And good, bad, or ugly, he probably ultimately ended up publishing (many posthumously) everything he ever wrote. I try to match that discipline. Even when I don’t post a blog post I write seven days a week, every morning. At least 1000 words and a completed post. I used to do this in my 20s when I was trying to write fiction. My minimum then was 3000 words. I did that for five years.
It adds up. The average book is 60,000 words. If you can write 1000 words a day then you’ll have 6 books by the end of the year. Because poetry books are much smaller, Bukowski probably had around 80 or so books published by the time he was dead and I bet there are more coming.



(his first novel at age 49. You're never too old).
5)      His “literary map”. He was inspired by several writers and he inspired many more. Some of my favorite writers come from both categories. He was probably most inspired by three writers: Celine, Knut Hamsun, and John Fante. I highly recommend Celine’s “Journey to the End of the Night”.  Celine is almost a more raw version of Bukowski. He was constantly angry and trying to survive and do whatever it took to survive. The thing about Bukowski, as opposed to many other writers, is he didn’t concern himself with flowery images or beautiful sunsets. He totally wrote as if he were speaking to you and Celine does that to an extreme but he’s so raw and smart that the way he “speaks” is like an insane person trying to spew out as much venom as possible. 600 pages later his first book is a masterpiece and I often use it in my pre-writing hour every morning when I read stuff to inspire myself to write.
John Fante wrote the underappreciated “Ask the Dust” which was completely forgotten until Bukowski’s publisher republished it and all of Fante’s books. (I also recommend the movie  with Colin Farrell and a naked Salma Hayek).


(maybe Hayek's best role)
Bukowski was almost afraid to admit how much Fante directly influenced him. He wrote in one “short story”, “I realized that admitting John Bante had been such a great influence on my writing might detract from my own work, as if part of me was a carbon copy, but I didn’t give a damn. It’s when you hide things that you choke on them.”
Note he spelled “Fante” as “Bante”. That’s the extent of Bukowski’s fiction. Another interesting thing is the last line. Nothing flowery, nothing descriptively beautiful, yet a line like that is what made Bukowski unique and one of the best writers ever, getting at the hidden truth of what was really happening in his head, rather than telling yet another boring story filled with flowery descriptions like most books and stories are.
Then there’s the authors Bukowski influenced. Michael Hemmingson wrote an excellent review of Bukowski in the book “The Dirty Realism Duo: Bukowski and Carver” which I highly recommend. Raymond Carver comes from the same genre of down-and-out, oppressive relationships that were beyond his ability to cope with them, and realist, simple writing that was mostly autobiographical (although that’s a little less clear in Carver’s case). I’d also throw Denis Johnson’s book of short stories (Jesus’ Son) in that category (Johnson studied with Carver) and more recently, books like the above-mentioned Michael Hemmingson’s  “Crack Hotel”, “The Comfort of Women”,  “My Date(Rape) with Kathy Acker” and other stories.  I’m dying to find other writers in this category.


(I haven't seen the movie. Is it good?)
I read how Denis Johnson needed $10,000 to pay the IRS. So he threw together some vignettes he had forgotten about, called the collection “Jesus’ Son” and sent it off to Jonathan Galassi and said, “here, you can have these if you pay the IRS”. So I Facebook-friended Galassi and asked him if he could tell me one author in Denis Johnson’s league but I’m still waiting for a response.
I wish I could find more writers like these. Perhaps William Vollmann who wrote “Butterfly Stories” but his bigger fiction is too difficult for me to read (anecdote: he wrote the afterward to the recently re-published Celine’s “Journey of the Night” so all of these writers tend to recognize their common lineage.)
6)      Poetry. I really hate poetry. When I open up the New Yorker (blecch!) and read the latest poems in there I can’t understand them, they all seem like gibberish to me, they all seem too intellectual. And yet, out of all the poets I’ve read, the only ones I really like are: Bukowski, Raymond Carver, and Denis Johnson. Poetry allowed them to master making each word in a sentence effective and powerful. It was this training that allowed them to destroy the competition when they sat down to write their longer pieces. It makes me want to try my hand at poetry but even the word “poetry” sounds so pseudo-intellectual I just have no interest in doing it.
Bukowski: Alcoholic, postal worker, misogynist (there’s a video you can easily find on Youtube where he must be almost 60 and he literally kicks his wife in anger while he’s being interviewed.), anti-war, anti-peace, anti-everything, hated everyone, probably insecure, extremely honest, and he had to write every day or it would kill him.
In his own words, words which I hope to live by: “What a joy it must be to be a truly great writer, even if it means a shotgun at the finish”.
————————
Suggested Reading:

Biographical:
–          Michael Hemmingson:  The Dirty Realism Due: Charles Bukowski  and Raymond Carver
–          Howard Sounes: “Charles Bukowski: Locked in the Arms of a Crazy Life
Bukowski’s Writings (that I recommend):
  • –          “Ham On Rye”
  • –          “Factotum”
  • –          “Women”
  • –          “Post Office”
  • –          “Hollywood”
  • –          “Portions from  a Wine-Stained Notebook”
  • –          “Absence of the Hero”
  • –          “The Last Night on theEarth”(poems)
  • (I don’t recommend “Pulp” – don’t read it).
Other fiction in the “Dirty Realism”category:  
  • –          Celine, “Journey to the End of theNight”
  • –          Fante, “Ask the Dust”
  • –          Raymond Carver, “Cathedral”
  • –          Denis Johnson, “Jesus’ Son”
  • –          William Vollmann,  “Butterfly Stories”
  • –          Michael Hemmingson, “This  Other Eden”
  • –          Junot Diaz, “Drown”
  • –          Jerzy Kosinski, “Steps”
Poem:
“You Don’t know What Love Is (an evening with Bukowski)” by Raymond Carver.
Article: John Fante, father of LA Literature:
Movies:
“Factotum”

If anyone  can think  of  anybody else in this specific “dirty realism” category, please put it in the comments. I’d also like to read women in this category but I think it’s a particularly male category. Jack Kerouac falls somewhere in there but he’s more “beat” which I think is different. And Chad Kultgen’s recent books (“The Average American Male”, for instance) are also somewhat in the realism category but not quite “dirty” enough.  





Giving dad some backchat.


Psychedelics




Hallucinations. Vivid images. Intense sounds. Greater self-awareness.
Those are the hallmark effects associated with the world's four most popular psychedelic drugs. Ayahuasca, DMT, MDMA and psilocybin mushrooms can all take users through a wild mind-bending ride that can open up your senses and deepen your connection to the spirit world. Not all trips are created equal, though – if you're sipping ayahuasca, your high could last a couple of hours. But if you're consuming DMT, that buzz will last under than 20 minutes.


Still, no matter the length of the high, classic psychedelics are powerful. Brain imaging studies have shown that all four drugs have profound effects on neural activity. Brain function is less constrained while under the influence, which means you're better able to emotion. And the networks in your brain are far more connected, which allows for a higher state of consciousness and introspection.
These psychological benefits have led researchers to suggest that psychedelics could be effective therapeutic treatments. In fact, many studies have discovered that all four drugs, in one way or another, have the potential to treat depression, anxiety, post-traumatic stress disorder, addiction and other mental health conditions. By opening up the mind, the theory goes, people under the influence of psychedelics can confront their painful pasts or self-destructive behavior without shame or fear. They're not emotionally numb; rather, they're far more objective.
Of course, these substances are not without their side effects. But current research at least suggests that ayahuasca, DMT, MDMA and psilocybin mushrooms have the potential to change the way doctors can treat mental illness – particularly for those who are treatment-resistant. More in-depth studies are needed to understand their exact effects on the human brain, but what we know now is at least promising. Here, a look at how each drug affects your brain – and how that's being used to our advantage.


AyahuascaAyahuasca is an ancient plant-based tea derived from a combination of the vine Banisteriopsis caapi and the leaves of the plant psychotria viridis. Shamans in the Amazon have long used ayahuasca to cure illness and tap into the spiritual world. Some religious groups in Brazil consume the hallucinogenic brew as religious sacrament. In recent years, regular folk have started to use ayahuasca for greater self-awareness.
That's because brain scans have shown that ayahuasca increases the neural activity in the brain's visual cortex, as well as its limbic system – the region deep inside the medial temporal lobe that's responsible for processing memories and emotion. Ayahuasca can also quiet the brain's default mode network, which, when overactive, causes depression, anxiety and social phobia, according to a video released last year by YouTube channel AsapSCIENCE. Those who consume it end up in a meditative state.
"Ayahuasca induces an introspective state of awareness during which people have very personally meaningful experiences," says Dr. Jordi Riba, a leading ayahuasca researcher. "It's common to have emotionally-laden, autobiographic memories coming to the mind's eye in the form of visions, not unlike those we experience during sleep."
According to Riba, people who use ayahuasca experience a trip that can be "quite intense" depending on the dose consumed. The psychological effects come on after about 45 minutes and hit their peak within an hour or two; physically, the worst a person will feel is nausea and vomiting, Riba says. Unlike with LSD or psilocybin mushrooms, people high on ayahuasca are fully aware that they're hallucinating. It's this self-conscious tripping that has led people to use ayahuasca as a means to overcome addiction and face traumatic issues. Riba and his research group at Hospital do Sant Pau in Barcelona, Spain, have also begun "rigorous clinical trials" using ayahuasca for treating depression; so far, the plant-based drug has shown to reduce depressive symptoms in treatment-resistant patients, as well as produce "a very antidepressant effect that is maintained for weeks," says Riba, who has studied the drug with support from the Beckley Foundation, a U.K.-based think tank.
His team is currently studying the post-acute stage of ayahuasca effects – what they've dubbed the "after-glow." So far, they've found that, during this "after-glow" period, the regions of the brain associated with sense-of-self have a stronger connection to other areas that control autobiographic memories and emotion. According to Riba, it's during this time that the mind is more open to psychotherapeutic intervention, so the research team is working to incorporate a small number of ayahuasca sessions into mindfulness psychotherapy.
"These functional changes correlate with increased 'mindfulness' capacities," Riba says. "We believe that the synergy between the ayahuasca experience and the mindfulness training will boost the success rate of the psychotherapeutic intervention."


DMTAyahuasca and the compound N,N-Dimethyltryptamine – or DMT – are closely linked. DMT is present in the leaves of the plant psychotria viridis and is responsible for the hallucinations ayahuasca users experience. DMT is close in structure to melatonin and serotonin and has properties similar to the psychedelic compounds found in magic mushrooms and LSD.
If taken orally, DMT has no real effects on the body because stomach enzymes break down the compound immediately. But the Banisteriopsis caapi vines used in ayahuasca block those enzymes, causing DMT to enter your bloodstream and travel to your brain. DMT, like other classic psychedelic drugs, affect the brain's serotonin receptors, which research shows alters emotion, vision, and sense of bodily integrity. In other words: you're on one hell of a trip.
Much of what is known about DMT is thanks to Dr. Rick Strassman, who first published groundbreaking research on the psychedelic drug two decades ago. According to Strassman, DMT is one of the only compounds that can cross the blood-brain barrier – the membrane wall separating circulating blood from the brain extracellular fluid in the central nervous system. DMT's ability to cross this divides means the compound "appears to be a necessary component of normal brain physiology," says Strassman, the author of two quintessential books on the psychedelic, DMT: The Spirit Molecule and DMT and the Soul of Prophecy.
"The brain only brings things into its confines using energy to get things across the blood-brain barrier for nutrients, which it can't make on its own — things like blood sugar or glucose," he continued. "DMT is unique in that way, in that the brain expends energy to get it into its confines."
DMT actually naturally occurs in the human body, and is particularly present in the lungs. Strassman says it may also be found in the pineal gland – the small part of the brain associated with the mind's "third eye." The effects of overly active DMT when ingested via ayahuasca can last for hours. But taken on its own – that is, smoked or injected – and your high lasts only a few minutes, according to Strassman.
Although short, the trip from DMT can be intense, more so than other psychedelics, Strassman says. Users on DMT have reported similar experiences to that of ayahuasca: A greater sense of self, vivid images and sounds and deeper introspection. In the past, Strassman has suggested DMT to be used as a therapy tool to treat depression, anxiety and other mental health conditions, as well as aid with self-improvement and discovery. But studies of DMT are actually scarce, so it's hard to know the full extent of its therapeutic benefits.
"There isn't much research with DMT and it ought to be studied more," Strassman says.


MDMAUnlike DMT, MDMA is not a naturally occurring psychedelic. The drug – otherwise called molly or ecstasy – is a synthetic concoction popular among ravers and club kids. People can pop MDMA as a capsule, tablet or pill. The drug (sometimes called ecstasy or molly) triggers the release of three key neurotransmitters: serotonin, dopamine and norepinephrine. The synthetic drug also increases levels of the hormones oxytocin and prolactin, resulting in a feeling of euphoria and being uninhibited. The most significant effect of MDMA is the release of serotonin in large quantities, which drains the brain's supply – which can mean days of depression after its use.
Brain imaging has also shown that MDMA causes a decrease in activity in the amygdala – the brain's almond-shaped region that perceives threats and fear – as well as an increase in the prefrontal cortex, which is considered the brain's higher processing center. Ongoing research on psychedelic drugs and the effects on various neural networks has also found that MDMA allows for more flexibility in brain function, which means people tripping on the drug can filter emotions and reactions without being "stuck in old ways of processing," according to Dr. Michael Mithoefer, who has studied MDMA extensively.
"People are less likely to be overwhelmed by anxiety and better able to process experience … without being numb to emotion," he says.
Last year, the U.S. Food and Drug Administration granted researchers permission to move ahead with plans for a large-scale clinical trial to examine the effects of using MDMA as treatment for post-traumatic stress disorder (PTSD). Mithoefer oversaw the phase-two trials – backed by the Multidisciplinary Association for Psychedelic Studies (MAPS), an American nonprofit founded in the mid-1980s – that informed the FDA's decision. During the study, people living with PTSD were able to address their trauma without withdrawing from their emotions while under the influence of MDMA because of the complex interaction between the amygdala and the prefrontal cortex. Since the phase two trials had strong results, Mithoefer told Rolling Stone in December that he expects the FDA to approve the phase three trial plans sometime early this year.
While research into MDMA's use for PTSD treatment is promising, Mithoefer cautions that the drug not be used outside of a therapeutic setting, as it raises blood pressure, body temperature and pulse, and causes nausea, muscle tension, increased appetite, sweating, chills and blurred vision. MDMA could also lead to dehydration, heart failure, kidney failure and an irregular heartbeat. If someone on MDMA doesn't drink enough water or has an underlying health condition, the side effects can be life threatening.


Psilocybin MushroomsMushrooms are another psychedelic with a long history of use in health and healing ceremonies, particularly in the Eastern world. People tripping on 'shrooms will experience vivid hallucinations within an hour of ingestion, thanks to the body's breakdown psilocybin, the naturally-occurring psychedelic ingredient found in more than 200 species of mushrooms.
Research out of the Imperial College London, published in 2014, found that psilocybin, a serotonin receptor, causes a stronger communication between the parts of the brain that are normally disconnected from each other. Scientists reviewing fMRI brain scans of people who've ingested psilocybin and people who've taken a placebo discovered that magic mushrooms trigger a different connectivity pattern in the brain that's only present in a hallucinogenic state. In this condition, the brain's functioning with less constraint and more intercommunication; according to researchers from Imperial College London, this type of psilocybin-induced brain activity is similar to what's seen with dreaming and enhanced emotional being.
"These stronger connections are responsible for creating a different state of consciousness," says Dr. Paul Expert, a methodologist and physicist who worked on the Imperial College London study. "Psychedelic drugs are a potentially very powerful way of understanding normal brain function."
Emerging research may prove magic mushrooms effective at treating depression and other mental health conditions. Much like ayahuasca, brain scans have shown that psilocybin can suppress activity in the brain's default mode network, and people tripping on 'shrooms have reported experiencing "a higher level of happiness and belonging to the world," according to Expert. To that end, a study published last year in the U.K. medical journal The Lancet discovered that a high dose of mushrooms reduced depressive symptoms in treatment-resistant patients.
That same study noted that psilocybin could potentially treat anxiety, addiction and obsessive-compulsive disorder because of its mood-elevating properties. And other research has found that psilocybin can reduce the fear response in mice, signaling the drug's potential as a treatment for PTSD.
Despite these positive findings, research on psychedelics is limited, and consuming magic mushrooms does comes with some risk. People tripping on psilocybin can experience paranoia or a complete loss of subjective self-identity, known as ego dissolution, according to Expert. Their response to the hallucinogenic drug will also depend on their physical and psychological environment. Magic mushrooms should be consumed with caution because the positive or negative effect on the user can be "profound (and uncontrolled) and long lasting," Expert says. "We don't really understand the mechanism behind the cognitive effect of psychedelics, and thus cannot 100 percent control the psychedelic experience."
Correction: This article has been updated to clarify that Dr. Jordi Riba's work is supported by the Beckley Foundation, not MAPS. 


Source: http://www.rollingstone.com/culture/what-psychedelics-really-do-to-your-brain-w471265


Saturday, February 25, 2017

Parkinson's linked to gut bacteria



Thursday, 1 Dec 2016 | ETCNBC.com



Sherbrooke Connectivity Imaging Lab | Getty Images
 Coronal view of a human brain in Parkinson's disease



Parkinson's linked to gut bacteria

Robert Ferris | @RobertoFerris



For the first time, researchers have found a functional link between the bacteria in the gut and the onset of Parkinson's disease, one of the world's most common debilitating brain disorders.

A team of scientists from several institutions in the United States and Europe showed how changing the bacteria in the guts of mice affected the manifestation of Parkinson's symptoms — even including bacteria taken from the guts of humans with the disease.

The findings suggest a new way of treating the disease: The best target for treatment may be the gut, rather than the brain. The researchers hope the new information can be used to develop "next generation" probiotics, more sophisticated than the sort of probiotics found on the shelves of health food stores today.

"One can imagine one day, maybe in our lifetimes, patients will be prescribed drugs, and in the pills will be the bacteria that protect them from disease or even maybe treat their disease symptoms," said Sarkis Mazmanian, one of the researchers on the team and professor of microbiology at the California Institute of Technology.

The scientists published their findings Thursday in the journal Cell.

Parkinson's disease is a neurodegenerative disorder where brain cells accumulate excessive amounts of a protein called alpha-synuclein and then die off. Patients lose motor function, experience tremors and shaking, and suffer other physical and mental effects. One million people in the U.S. and up to 10 million worldwide suffer from the condition. It is considered the world's second most common neurodegenerative disease after Alzheimer's.

It is not usually the result of genetics, most often, it seems to be influenced by environmental factors.

Previous research has suggested connections between gut bacteria and Parkinson's, as well as other diseases such as multiple sclerosis. But no research has shown exactly how the two might be related.

The researchers performed three different experiments that showed the link between the germs in the gut and the disease in the brain.

First, the team acquired two sets of mice that had been genetically modified to overproduce alpha-synuclein — the protein that is the hallmark of the disease. One set of mice had a complete microbiome — the collective name for the bacteria in the gastrointestinal tract. The other set had no bacteria in their guts — they were germ-free.

The germ-free mice were still overproducing alpha-synuclein, but their brain cells were not accumulating the protein. The germ-free mice showed fewer symptoms and performed better on a series of motor skills tests meant to model the kinds of tests given to human patients.

However, the mice with the complete microbiome did begin accumulating the protein in their brain cells, and began showing brain damage in the regions that one would expect for a Parkinson's patient.

Next the team fed both types of mice certain short-chain fatty acids that are commonly produced by bacteria in the gut. In other words, they were looking to see if even germ-free mice would show symptoms if the researchers mimicked gut bacteria activity.

And this time, the germ-free mice did show symptoms of the disease in the brain when fed the chemicals.

This suggested that the chemicals certain types of gut bacteria produce worsen conditions in the brain.

Finally, the team did a third experiment where they took samples of gut bacteria from human Parkinson's patients and from healthy human controls and transplanted them into the germ-free mice that overexpressed alpha-synuclein. Remarkably, the mice began to exhibit symptoms. However, only the bacteria from the Parkinson's patients caused symptoms in the mice. The germ-free mice given samples from healthy humans did not produce symptoms

In some ways, Mazmanian finds the third experiment most telling.

"At first pass, what this tells you is that it is not the presence or absence of bacteria that matters, it is the types of bacteria that are there," he said.

In other words, it could mean that the guts of Parkinson's patients have certain bacteria that contribute to the disease, or that they lack certain beneficial bacteria that could help protect against the disease.

Samples of gut bacteria in Parkinson's patients render this possible. They tend to have certain kinds of bacteria not found in healthy people, and they also lack others that are found in healthy people, Mazmanian noted.

Moving forward, Mazmanian said the team would like to identify specific bacteria that are helpful or harmful and understand how they might contribute to or prevent the disease, and what kinds of treatments might produce the microbiome that best protects against the disease.




Robert Ferris Science Reporter

Link: http://www.cnbc.com/2016/12/01/parkinsons-linked-to-gut-bacteria.html?__source=newsletter%7Ceveningbrief


More from Modern Medicine:

Why microbiome science is booming

Chinese first to test CRISPR gene editing in humans

A new drug is slowing memory loss in Alzheimer's patients



Richard Burton talking about alcohol addiction with Dick Cavett

Wednesday, February 22, 2017

Tuesday, February 21, 2017

Bing Crosby-Mister booze



  
Uploaded on Dec 27, 2011
mister booze by bing crosby

send movie request to jimmy_spanjo@hotmail.com



Tuesday, September 27, 2016

Olivier Ameisen wrote "The End of My Addiction"



Good descriptions of anxiety and alcohol cravings ....

I read his book years ago.  It was about a drug MS,ers take to prevent muscle cramps that he used to end his alcohol addiction.  He took huge doses of the drug, Baclofen to halt his cravings for alcohol...

http://faith-seeking-understanding.org/tag/olivier-ameisen/

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

Posted in Addiction & Recovery | Tagged ,






The End of Alcoholism? Part 2




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






Tag Archives: Olivier Ameisen

10/5/15

The End of Alcoholism? Part 3



 
© 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







Source: http://faith-seeking-understanding.org/tag/olivier-ameisen/