Michael J Fox's Parkinson's Disease may have been caused by amphetamine use and/or sleep deprivation

Important Foreword:
1. I'm a fan of his: Back to the Future is probably one of my top-5 favorite movies.
2. I interned for a neurologist my senior year of high school and saw how widespread Parkinson's Disease is among older people, so I think it's awesome that he's raising awareness of PD and helping to find a cure.
3. I don't have any preconceived disdain for drugs; I'm very open minded. I have many wonderful friends who've used drugs and are just fine. I'm not an anti-drug crusader.
4. If I'm right about how Michael got PD, it was just an accident: he didn't know that this would happen to him as a result of amphetamine use. If he knew, he wouldn't have used them [again, assuming he used them]. These kinds of accidents have happened in the past with other things (like cigarettes) and will probably continue to happen in the future (eg people are worried about the long-term effects of cell phone radiation).
5. Half of the reason I'm writing this up is that I like solving problems, and a lot of people wonder how Michael got Parkinson's at such young an age (I wondered this myself).
6. The other half of the reason I'm writing this up is that I think it's important for people to know that using drugs & not getting enough sleep might lead to problems down the road; I'm open to the idea that for some people the benefits of drug use / sleep deprivation may outweigh the costs, but I think people should know what the costs might be (eg cigarettes). I'm not a fan of hidden costs. There are a lot of people taking Adderall and skimping on sleep nowadays and I doubt many of them know that there's some evidence that it might lead to Parkinson's Disease.

With that said, here's my thinking:

[Update: Since people seem to be arriving at this page via Google, I just wanted to say that my current thinking (as of 2019) is that Michael's Parkinson's was most likely a result of accidentally-toxic drugs that he was given while working on a TV show in Vancouver in the late '70s, possibly aggravated by later amphetamine use / sleep deprivation.  Towards the bottom of the page I have a link to a NYT article called "Parkinson's 'Clusters' Getting a Closer Look" and some excerpts from the article that seem to me to be pretty strong indicators that this is what happened.  If I had to guess, I'd guess the drugs Michael took were cut (diluted) with something toxic.  This seems to be extremely common with black-market/illegal/unregulated drugs.  Society is seeing this exact thing happen right now with other drugs.  In Europe they're dealing with fake/cut ecstasy killing people, and in the US we're dealing with fake/cut prescription opioids killing people (cheap fentanyl from China is used as a cutting agent for prescription opioids).  And again, I love Michael as an actor, so please don't take this as a condemnation of him.  Accidents happen; two years ago I gave myself permanent (slight) hearing damage after a night spent dancing at a club to very loud music.]


Contents:


Related Page: Sleep Deprivation May Be a Factor in Developing Parkinson's Disease

1. Michael's family does not have a history of Parkinson's Disease

2010 Interview with Sanjay Gupta of CNN:
http://www.youtube.com/watch?v=la63uShbtsc

Michael: It's often said with Parkinson's that genetics holds the gun and environment pulls the trigger. I mean, why has no one in my family ever had Parkinson's? It's not necessarily that we don't all have the risk, it's just that I ran into whatever that trigger was.

I just saw this interview the day I created this page (2012/04/01), and this was the thing that made everything "click" for me. When I heard that he didn't have a family history of PD I suddenly remembered several other bits of information that I had picked up in the past few years but had never considered all at the same time. Those bits of information are below.


2. Many drugs are known to cause permanent changes to the brain over time

I was a psychology / philosophy double-major in college, and I took a bunch of classes on the workings of the brain. One of those classes was specifically on the pharmacology of popular drugs (caffeine, cocaine, marijuana, etc.). We looked at a bunch of different drugs and I remember that at least a few of them seem to cause permanent changes in your brain after a while.

2a. Ecstasy:
The top half of the below picture shows a regular person; the bottom half shows the brain of a long-term ecstasy user. Brighter-light is good; it means more brain activity. The stuff really does seem to rot your brain.
Image
Update: apparently ecstasy may not rot your brain after all:
http://www.huffingtonpost.com/2011/02/2 ... 25704.html
http://www.erowid.org/chemicals/mdma/md ... ity1.shtml

3. Amphetamine use can lead to permanent changes to the brain that cause Parkinson's Disease

Wikipedia: Amphetamine is a psychostimulant drug that produces increased wakefulness and focus in association with decreased fatigue and appetite.

At the moment my hypothesis is that taking amphetamines for an extended period of time is like driving your car at its highest RPMs for an extended period of time (like, years): after a while you're going to start causing more wear and tear on your car than you would have if you'd kept things at the lower RPMs. And doing all this while cutting back on sleep seems like it's analogous to driving around without changing the oil. It seems like it would make a bad thing even worse.

3a. Parkinson's Disease is a result of decreased dopamine levels in the brain.

Dopamine is a chemical in your brain; your brain uses it to do stuff. If you don't have it, it's like being vitamin-deficient: you see problems. The idea that PD is connected to reduced dopamine levels is uncontroversial in the scientific community. You can read about it on wikipedia:http://en.wikipedia.org/wiki/Parkinson%27s_disease

3b. Amphetamine use can lead to fewer dopamine-producing neurons.

From a Michael J Fox-foundation-funded website: Stimulants May Up Parkinson's Risk
http://www.pdonlineresearch.org/news/20 ... nsons-risk

Patients who abuse methamphetamine and other related stimulants may be increasing their chances of developing Parkinson's disease, researchers have found.

Those hospitalized in California for methamphetamine or other amphetamine-related conditions had a significantly greater risk of developing the neurological condition than those admitted for appendicitis or cocaine use, Russell Callaghan, MD, of the University of Toronto, and colleagues reported online in Drug and Alcohol Dependence.

The findings "support the long-hypothesized notion, based on animal data, that meth/amphetamine exposure might lead to enduring damage of brain dopamine neurons in humans," Callaghan and colleagues wrote.

[me: the studies he's alluding to are below, I gathered them from Callaghan's article:]
Fibiger and McGeer '71 - Effect of acute and chronic meth treatment on tyrosine hydroxylase activity in brain and adrenal medulla
Seiden '76 - Long-term meth induced changes in brain catecholamines in tolerant rhesus monkeys
Ricaurte '84 - Further evidence that amph produce long-lasting dopamine neurochemical deficits by destroying dopamine nerve fibers
Ryan '90 - Histological and ultrastructural evidence that D-amphetamine causes degeneration in neostriatum and frontal cortex of rats

For the graph below, red is good; it means more brain activity.

(I need to find the image again)

American Academy of Neurology Press Release November 2011: Using Amphetamines May Increase Risk of Parkinson’s Disease [via minderbinder, below]
http://www.aan.com/press/index.cfm?fuse ... elease=904

Using Amphetamines May Increase Risk of Parkinson's Disease, Study Suggests [via minderbinder, below]
http://www.sciencedaily.com/releases/20 ... 193013.htm

More info: Could Clinical Use of Stimulant Medications Increase Risk for Parkinson’s Disease or Other Neurological Sequelae? A Review of the Evidence


4. People with very demanding lifestyles often use amphetamines to stay alert

4a. Truck drivers have a very demanding lifestyle and often use amphetamines to stay alert:

2010.01 Sexual and Drug Use Risk Behaviors of Long-Haul Truck Drivers
http://www.publichealthreports.org/cphc ... _52-60.pdf

Some participants in the study reported that the drugs of preference for truck drivers were methamphetamine and cocaine. The harsh working conditions were said to promote the use of drugs that allow truck drivers to remain awake and focused for long periods of time. According to [prostitutes], stimulants such as methamphetamine and crack cocaine were used by drivers while driving, with [prostitutes] during sex, and during parties. For example, when asked if the truck drivers used any other drugs besides crack, a 30-year-old Hispanic male [prostitute] responded: 

"Mostly crack. But there are methamphetamines there. Once in a while there’s heroin, but that’s kind of a rarity to the truckers. It’s mostly the [prostitutes] that are heroin addicts."

Additionally, one [prostitute] discussed being offered drugs in exchange for sex. When asked, “One of the things we are trying to learn about truck drivers is drug use, and we have been told by some other sex workers that drug use is high. Can you tell me what your experience has been with that?” a 45-year-old Hispanic female [prostitute] responded, “Yeah, they’ve come up to me and said they have speed and coke with them sometimes, and they’ll even offer that to me instead of money.” Another interviewee was asked, “Out of maybe 10 truck drivers, how many do you think that you come across are using drugs?” The 38-year-old white male [prostitute] interviewee answered, “Out of 10, I would guess half. Some smoke pot and all that, but it’s mostly crack and crystal meth to stay awake.”

1988 - Drug Use by Tractor-Trailer Drivers
http://rzbl04.biblio.etc.tu-bs.de:8080/ ... al#page=54

Truck drivers often spend long hours on the road and have to deal with fatigue, loneliness, boredom, and uncomfortable driving conditions. There is considerable informal information that many truck drivers use drugs as a means of coping with their difficult working conditions.Alcohol, marijuana, cocaine, and amphetamines generally are mentioned as drugs used. In a 1977 mail survey (Wyckoff, 19791, stimulants such as “bennies, goofballs, and copilots” were the most common drugs reported by men truck drivers, with 14 percent saying they used such drugs occasionally or regularly to stay awake while driving.
4b. Students may have demanding lifestyles and often use amphetamines to stay alert

2011.11 - Adderall Abuse: Smart Pill or College Crack?
http://www.myfoxdc.com/dpp/news/investi ... ack-110111

It is a growing epidemic across college campuses. Students are popping pills to get an academic edge. The drug is Adderall, a prescription drug that is illegally abused by many students to study. Only the consequences can be deadly.

The pill gives college students the ability to pull all-nighters, study for days with only a few hours of sleep. It is a stimulant that makes the heart pound, blood rush and can provide a feeling of euphoria.

"It's pretty common nowadays," said Devon Fehn, a junior at the University of Maryland.

Adderall has been successfully used to treat attention deficit hyperactivity disorder or ADHD. It has also been abused: snorted like cocaine or mixed with alcohol and a cocktail of other drugs. But on college campuses, it is most often used to help students concentrate on studying. Students call it the smart drug or steroids for the brain.

"Adderall, yeah, it's very popular, everyone uses Adderall," said one student who did not want to be named.


4a. Musicians may have a very demanding lifestyle and may use stimulants to stay alert:

Apparently The Beatles used stimulants:

Phenmetrazine is a stimulant drug that was previously used as an appetite suppressant, but has since been withdrawn from the market. Phenmetrazine was taken by The Beatles early in their career. Paul McCartney was one known user. McCartney's introduction to drugs started in Hamburg, Germany. The Beatles had to play for hours, and they were often given "Prellies" (Preludin) by the maid who cleaned their housing arrangements, German customers, or by Astrid Kirchherr (whose mother bought them). McCartney would usually take one, but John Lennon would often take four or five. Hunter Davies asserted, in his 1968 biography of the band, that their use of such stimulants then was in response to their need to stay awake and keep working, rather than a simple desire for kicks.

Source: http://en.wikipedia.org/wiki/Phenmetrazine

5. Michael was living a very demanding lifestyle from the '70s to the '90s


This point is a big part of my argument; Michael had a strong motive to use amphetamines.

Michael's rise to fame created a huge demand on his time; the clearest example of this was Michael's insane work schedule while filming Back to the Future in 1985:
http://en.wikipedia.org/wiki/Back_to_th ... Production

Michael J. Fox was the first choice to play Marty McFly, but he was committed to the show Family Ties. Family Ties producer Gary David Goldberg felt that Fox was essential to the show's success. With co-star Meredith Baxter on maternity leave, he refused to allow Fox time off to work on a film. [...] Fox's schedule during weekdays consisted of filming Family Ties during the day, and Back to the Future from 6:30 pm to 2:30 am. He averaged five hours of sleep each night. During Fridays, he shot from 10 pm to 6 or 7 am, and then moved on to film exterior scenes throughout the weekend, as only then was he available during daytime hours. Fox found it exhausting, but "it was my dream to be in the film and television business, although I didn't know I'd be in them simultaneously. It was just this weird ride and I got on."[16] Zemeckis concurred, dubbing Back to the Future "the film that would not wrap". He recalled that because they shot night after night, he was always "half asleep" and the "fattest, most out-of-shape and sick I ever was".

Here's a part of a documentary from 1987 that shows how hard he was working:
http://www.youtube.com/watch?v=8ug8G1QUwSg#t=12m32s

Narrator: The worst thing about their son's celebrity is that there are so many demands on his time, they don't get to see him as much as they'd like to.
Father: We were down there two weeks and we might have seem him nine hours.
Mother: He gets up in the morning, and from the minute that he comes out of his bedroom, his assistant is there with the list of things that are happening today, and what he's gotta do before he even leaves for work, and then what he has to after work, what's required of him. [As the assistant:] "You know, you have to come straight home because I've got a car picking you up because you have a photo shoot" or whatever it might be, and it's...it's tough. It's a young man's game, I'll tell ya.


6. Michael has been aware of the benefits of amphetamines since at least 1983

In 1983 Michael was in an episode of "Family Ties" about how speed (amphetamines) could be used to enhance performance if someone was living a very demanding lifestyle. In the episode, Michael's character started using speed to study for finals, so it was probably something Michael would remember. The show depicts amphetamines (unrealistically afaik) as being capable of making a person far smarter than they otherwise would be: for example, Michael's character writes a term paper that is so persuasive it converts his Democrat-leaning professor to a Republican. The only bad side-effects of amphetamines shown in the episode are 1) using them illegally is "[morally] wrong", 2) psychological dependence, 3) disagreeable personality, 4) working too much (painting your room, waxing the floor). There is no mention of possible permanent physical effects (like Parkinson's Disease).

If Michael started using amphetamines in r/l and didn't experience substantial negative symptoms, he may have concluded that he'd be fine. As I said at the beginning of this page, it's the same problem that cigarette smokers faced before it became widespread knowledge that smoking lead to cancer: you see some negative side-effects up front and don't find them that bad, but you end up blindsided by later side-effects that are much worse.

As a side-note, this demonstrates one of the problems I have with TV shows and movies: a person will watch TV shows and movies and have an instinctual tendency to use these episodes to inform his view of the world, when in fact it's just not necessarily true that these things are accurate. I suspect this may have screwed me up for a long time because my idea of how dating / relationships / marriage worked was influenced by all the TV / movies I'd seen growing up, and it just wasn't a very accurate depiction of reality. Nowadays I don't like watching TV / movies for this very reason: it just isn't a true view of the world. It presents a view of the world that can cause you problems if you act on it.

Examples:
1 - Television / movie depictions of drowning make people terrible at actually being able to tell when someone is drowning.

Family Ties - Speed Trap
Season 2 - Original Airdate: November 9th, 1983
Part 1 - http://www.youtube.com/watch?v=kcT5bT7dyeM
Part 2 - http://www.youtube.com/watch?v=I_1X2t1Qt2I
Part 3 - http://www.youtube.com/watch?v=1ShY_344gpk

Update: It may even be possible that the episode was written in response to the writers' knowledge or suspicion of Michael's pre-existing use of amphetamines. Although I find that a little far-fetched because it would seem to be risk a backlash from Michael.z


Objections I've heard and my responses

1.
One big objection I can think of is, "Surely there are lots of people using amphetamines a lot; why don't we see more people with these symptoms?"

Another way of saying it is, "If amphetamines are likely to cause PD, why didn't the study of amphetamine abusers find a larger effect? It said it found a 76% increased chance of PD; that isn't that big of an increase. Smoking increases your odds of lung cancer by something like 1000-2000%."

Here's the quote from the study:

We found that meth/amphetamine users had a 76% increased risk of developing PD in comparison to a matched population-proxy control group. Based on our findings, this means that if we followed 10,000 meth/amphetamine users (at least 30 years of age) and 10,000 people of similar age, race, and sex from a California-population-based sample for 10 years, we would expect approximately 21 cases of PD in the methamphetamine group and approximately 12 in the population group.

Response:
I haven't thought of an answer to this one yet that I'm totally comfortable with. One possible response is that if he was using it a LOT, way more than what other people do, then he may have suffered the consequences sooner than other people, just like how some people who smoke a lot get lung cancer sooner than others (Christopher Hitchens is a good example). My understanding is that it's hard for smokers to just smoke 1 cigarette a day; the withdrawal from nicotine compels them to smoke about a pack a day, with heavier smokers going beyond that. But if meth/amphetamines don't cause that same kind of withdrawal, it might be easier for people labelled "users" to not use the drug heavily enough to see symptoms in 10 years, just as light smokers' chance of cancer after 10 years may not be drastically higher than nonsmokers [the link says a 50% higher risk of dying of any cause for light smokers].

Here's what the study says about their amphetamine-users sample:

Our investigation cannot provide information on age of initiation, frequency, dose, or duration of drug use. Nevertheless, it is reasonable to assume that the drug users in our study were, for the most part, “moderate to heavy” stimulant users having clinically significant problems as indicated by a formal hospital diagnosis of a meth/amphetamine-use disorder. In this regard, 96% of individuals in our meth/amphetamine cohort had received an inpatient diagnosis indicative of either meth/amphetamine abuse or dependence at their index admission. Here we emphasize that the clinical relevance of our findings might be limited to high dose meth/amphetamine users


So I guess the question is, "What exactly does 'moderate-to-heavy' mean in that quote?" If the people in that study were considered moderate users if they used amphetamines every week on Saturday nights, they may not be anywhere near someone who uses amphetamines every day to stay awake for work. That would in turn mean that the 76% increase underestimates the risk for people who use it every day.

2.
from a random person on the internet:

too much of your argument is dependent on the Family Ties connection

Response:
I don't think so; even if that episode didn't exist I still think the argument would be very strong, because Michael would still have had an incentive to use amphetamines b/c of his demanding career.

3.
from a biopsychology / cognitive psychology professor with an interest in neuroscience and memory:

MJF's PD could be linked to ingesting tainted drugs. There are cases of neurotoxins that produce PD.

Response:
This sounds plausible. I think I read online that there were some other people who worked with Michael on a movie(?) before he was really famous and also developed Michael's symptoms, so it may be that they all took tainted drugs.

Potentially-relevant info: Studies of drug clinics have shown a connection between amphetamine use and PD, so if tainted drugs are the only cause (and not the amphetamines themselves) then it would need to be a fairly common kind of problem w/ the drugs (although their being tainted may explain the severity of the symptoms Michael experienced without ruling out the amphetamines themselves as a contributing factor). And scientists have done lab studies w/ rats in which they inject untainted amphetamines and saw problems. I'll need to read those studies carefully to make sure they were problems connected w/ PD.


Here's a page where I had a back-and-forth with someone about my hypothesis:
http://news.ycombinator.com/item?id=4276328


Related links:

  • 2002.05.14 - NYT - Parkinson's 'Clusters' Getting a Closer Look
    • This specifically talks about the MJF cluster.
    • So the cluster involved 1) the main star of the show, 2) the director of the show, and 3) the script supervisor of the show, as well as a cameraman. Arguably three of the most-demanding positions on the show.
    • Excerpts:
      • Mr. Fox, it turns out, was one of four people who worked on a production crew at a television studio in Vancouver, British Columbia, in the late 1970's and developed Parkinson's disease. Given that only 125 people worked on the crew in those years -- including actors, directors, writers, production people and technicians -- the number of cases seems extraordinary.
      • Typically, Parkinson's disease afflicts one in 300 people. In people as young as Michael J. Fox, 30 when the disease was diagnosed in 1991, the illness is much rarer. Fewer than 5 percent of Parkinson's patients develop symptoms before age 50, said Dr. Caroline Tanner of the Parkinson's Institute. The Vancouver cluster includes Mr. Fox and a woman who learned she had Parkinson's at age 38.
      • Dr. Donald Calne, director of the neurodegenerative disorders center at the University of British Columbia, estimates that the odds of the four cases occurring at the same time in such a small group of people are less than 1 in 1,000.
      • Mr. Fox said he was curious about the cluster, out of both empathy for the people he worked with and because, as he put it, ''the beginning of my career and the end of my career being tied in a single event is pretty cosmic or weird to me.'' But whether the cluster should be investigated, he said, is a question he leaves to the judgment of scientists.
      • Don S. Williams, who directed Mr. Fox in two Canadian situation comedies beginning when the actor was 16, and who also has Parkinson's, tried to get in touch with Mr. Fox soon after reading the news. ''But I couldn't get past his handlers,'' he said. Mr. Williams learned of his illness nine years ago, when he was 55.
      • Sally Gardner, whose Parkinson's was diagnosed when she was 38, in 1984, had been a script supervisor in the late 1970's, and had worked with Mr. Fox and Mr. Williams.
      • The fourth member of the cluster, a cameraman who has kept his identity secret, was recently found by Jerry Thompson, writer and director of a Canadian television documentary about Mr. Fox and Parkinson's disease. The cameraman's diagnosis came at age 54. Thompson's documentary, ''The Parkinson's Enigma,'' which was broadcast last month, publicized the cluster's existence.
      • ''If this is a genuine cluster and not a statistical fluke,'' said Dr. Oliver Sacks, a neurologist and writer, ''it would certainly suggest an environmental agent at work.''
      • Parkinson's does not seem to be primarily a genetic disorder. It runs in the families of only about 10 percent to 15 percent of patients, Dr. Tanner of the Parkinson's Institute said. A large study she conducted indicated that the identical twins of Parkinson's patients are no more likely to have the disease than fraternal twins -- a sign that the disease is not largely genetic.
      • ''It is important to look for infectious as well as toxic agents,'' Dr. Sacks said.
      • Dr. Calne suspects a virus may indeed have caused the Parkinson's cases in Vancouver. ''In many areas of medicine it is fully accepted that there are several types of cause for one type of disorder,'' he said.
      • Toxins can also set off parkinsonism, as doctors learned in 1983, when seven young adults in the San Francisco Bay Area suddenly developed symptoms. Dr. Langston examined this cluster of patients and learned that they all had injected themselves with a synthetic form of heroin that contained the toxic molecule MPTP. The MPTP killed large numbers of the victims' dopamine-producing cells.
  • 2007.09.13 - IntMath - Michael J. Fox and the Parkinson’s cluster



4.
A response from Michael Rae, an associate of Aubrey de Grey:

This is an intriguing hypothesis. While the reliance on case series data from hospitalized patients in the original laying-out of the argument was evidentially rather weak, the *prospective* study reported at the 2011 Annual Academy of Neurology meeting, on which a press release was posted by one of your commenters, substantially strengthens it. Even there, however, I note that it is now over three years later, and this report has not appeared in any peer-reviewed journal, putting a wobble in even that leg of the stool.

I would say that the main weakness in the argument is the simple lack of any actual evidence whether Mr. Fox actually used amphetamines -- and yes: as soon as I read your 'headline,' my mind immediately leapt back to that episode of Family Ties  . Also, I thought of the film "Bright Lights, Big City," which I've never seen, but I know (and the Wiki and IMDB entries confirm) involves Fox's character having his life torn apart by drugs (cocaine, in particular) amongst other problems; interestingly, perhaps, per the Wikipedia page "McInerney claims that Cole wrote all the drugs out of the script while Cole claims that he did this on instructions from Pollack, who was worried that the film would hurt Fox's wholesome image with audiences. " These were apparently restored at some point, because all the plot synopses do feature Fox's character being an addict. This *tends* to argue against the idea that Fox would think amphetamines harmless, but (a) cocaine is not, of course, actually an amphetamine, and (b) this was several years after the Family Ties episode.

Moreover, while it's not impossible that he might have had an amphetamine habit go on for an extended enough amount of time as to substantially increase his PD risk, I would have expected that in the celebrity-obsessed tabloid media circus in which we live, if there were even strong hints in his life that he might have been using amphetamines at the height of his public visibility, we very likely would have heard about it.


Response:
I've underlined his main ideas. This essay argues for a fairly weak hypothesis (that there's "reason to believe" that this may be what caused his situation), and I don't think the points he brought up are strong enough to show that this weak hypothesis cannot be true.