# Performance enhancing drugs for the soldier?



## Bigmac (17 Dec 2006)

I stumbled upon an article from Britain which states that the Ministry of Defense there is experimenting with drugs to enhance soldier's performance in combat. Many of the drugs are banned substances used by professional atheletes to build muscle and cardio endurance. They also want to use sedatives to help relax the soldiers or aid them in getting proper sleep and stimulants to keep them awake when needed. The era of the "super soldier" may be coming soon to a combat area near you. Maybe we will even be able to go the route of "Universal Soldier" or "Robocop" where we can recycle dead soldiers into cyborg killing machines?!
     Personally I think it is a bad idea as it can lead to addictions and a myriad of health problems, not to mention safety concerns. Do you really want to be fighting beside a steroid enhanced soldier gorked out on sedatives or hopped up on speed? Read the article in the link below and tell me what your opinion is.

http://www.timesonline.co.uk/article/0,,2087-2509065,00.html


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## reccecrewman (17 Dec 2006)

I find this rather humourous........... Imagine a government giving soldiers various substances to keep them calm and/or stimulated in battle......  There are several historical instances in which cocaine was used for precisely that. (Stimulated.......... not so much the calm and sedated thing)  Booze was also another favorite prior to entering battle. But as the original poster said, I see and agree with his opinion it's going to lead to problems down the road for the soldiers involved.  Look at the problem we have now. 

Cigarettes;

Given to the troops in both world wars for free (or sold for next to nothing)  The aim and purpose was to calm the men and steady the nerves.  Now there are thousands of vets who are hooked on nicotine and have no place to smoke.  Not even in their own Legions around the Province! For shame!  There was an article in the Ottawa Sun westerday in which a long term care facility in Ottawa has a group of 20+ war vets trying to raise $70,000 to turn over to the facility so they can have one room in the building converted to a smoke room that meets all Provincial & Federal guidelines so they don't have to go outside in the elements to satisfy an addiction the governemnt may well have helped nurture.  They had one elderly resident recently taken to hospital with a broken hip because of the rules of smoking 9m from an entrance and staff are not allowed to assist them.  This is one story from many most likely seen all over Canada.

Personally, I see nothing but bad news coming from the government handing out various stimulants/substances to enhance a soldiers performance.  I believe solid training and personal discipline and pride in being a soldier to be every bit as effective as some substance or stimulant.  My .02

Regards


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## Spring_bok (17 Dec 2006)

This really isn't much of a stretch.  We saw soldiers in Petawawa trialling a caffeine based chewing gum in very recent years.


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## Kilo_302 (17 Dec 2006)

The 82nd Airborne has used "stop" and "go" pills  (or red light, green light) for some time. My buddy who is currently in Baghdad with the US 2ID swears that they something in the Powerade during Basic and AIT that was supposed to calm everyone down and prevent fighting amongst the recruits. He said it was pretty much common knowledge.


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## aesop081 (17 Dec 2006)

Kilo_302 said:
			
		

> My buddy who is currently in Baghdad with the US 2ID swears that they something in the Powerade during Basic and AIT that was supposed to calm everyone down and prevent fighting amongst the recruits. He said it was pretty much common knowledge.



I taught AIT in the US......what you just said is pure BS


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## Michael OLeary (17 Dec 2006)

Kilo_302 said:
			
		

> The 82nd Airborne has used "stop" and "go" pills  (or red light, green light) for some time. My buddy who is currently in Baghdad with the US 2ID swears that they something in the Powerade during Basic and AIT that was supposed to calm everyone down and prevent fighting amongst the recruits. He said it was pretty much common knowledge.



So was "saltpetre in the food" 50 years ago, but never substantiated.

http://www.snopes.com/military/saltpetr.htm


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## Kilo_302 (17 Dec 2006)

> I taught AIT in the US......what you just said is pure BS



I'm not saying its true, just what he said.


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## Shamrock (17 Dec 2006)

Kilo_302 said:
			
		

> The 82nd Airborne has used "stop" and "go" pills  (or red light, green light) for some time. My buddy who is currently in Baghdad with the US 2ID swears that they something in the Powerade during Basic and AIT that was supposed to calm everyone down and prevent fighting amongst the recruits. He said it was pretty much common knowledge.





			
				Kilo_302 said:
			
		

> I'm not saying its true, just what he said.



Please tell me you're kidding.  I can see someone saying this, but I have a hard time believing anyone would believe it.  However, on my Snipercommandorangerninjapirate Course, we were all required to raise a puppy or kitten (personal choice) from day one and kill it with a spork on grad parade.


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## gaspasser (17 Dec 2006)

Shamrock said:
			
		

> Please tell me you're kidding.  I can see someone saying this, but I have a hard time believing anyone would believe it.  However, on my Snipercommandorangerninjapirate Course, we were all required to raise a puppy or kitten (personal choice) from day one and kill it with a spork on grad parade.


And the reason for killing a puppy or kitten for course grad was....?
That sound a tad inhumane and the animal rights people would be all over that in seconds.
However, I do agree that the military has used soldiers, etc, to test a myriad of drugs in the past and probably will continue in order to find that perfect balance between killer and "puppy lover".  In other words, the perfect soldier.
My 0.02$


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## Trinity (17 Dec 2006)

Did BYT just miss the sarcasm?

or did he forget to add the smileys in his post?!


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## gaspasser (17 Dec 2006)

Umm, maybe the snowbirds went over my head on that one.
Puppies and kittens were a loke, right? Oh, and I didn't see any smilies.  Was I supposed to add on?



Member of the Gullible Fools Club.


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## Kilo_302 (17 Dec 2006)

Maybe he thought "Snipercommandorangerninjapirate Course" was a course offered by the German Army.  ;D


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## a_majoor (17 Dec 2006)

The ancient Greeks usually had a final drink of wine before forming the Phalanx and marching into battle, so the use of mood altering substances is a very old tradition.

I have argued that modern sports medicine makes this very possible and even potentially benificial. Indeed, it may be easier and safer to use performance enhancing drugs, blood doping and other techniques on soldiers since this is done under control and in the the open, without the need for masking substances like Olympic atheletes need to use. Making PT resemble modern pentathelon training, and teaching memory enhancing techniques would also be very useful.

Every edge is needed, especially given the small numbers of soldiers available in the Western world.


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## Michael OLeary (17 Dec 2006)

N.B. Modern era performance-enhancing substances not to be confused with the Great War era apprehension-reducing substance Demerara.


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## Welshy (17 Dec 2006)

I remember reading somwhere that the German army during WW2 gave there soldiers methamphetamines  during the use of blitzkrieg. Also pilots in the US are given "go" and "stop" pills. Everyone remembers the Friendly Fire incident back during the first bit of A-stan, those guys where on "go" pills at the time.


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## JesseWZ (17 Dec 2006)

Welshy said:
			
		

> I remember reading somwhere that the German army during WW2 gave there soldiers methamphetamines  during the use of blitzkrieg. Also pilots in the US are given "go" and "stop" pills. Everyone remembers the Friendly Fire incident back during the first bit of A-stan, those guys where on "go" pills at the time.


I have never heard this before. Source please?


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## Shamrock (17 Dec 2006)

Pervitin, the wonder drug.  Key ingredient in tanker's chocolate.


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## zipperhead_cop (18 Dec 2006)

Interesting that this comes up.  I was in Pet for a week at the beginning of the month.  I was in the shacks and I think I was the only military person there.  There were, however, many civilians.  I ended up talking to one of them, and he was telling me that he was  from a vitamin company R&D division and they were there for some "work".  He was kind of vague about what he was there for, but he did tell me about a device they had that used a laser applied to the skin surface to do an analysis of the level of various vitamins in your system.  Technology was based around the spectrometer concept.  
It would be nice if the CF turned to naturalpathic concepts to provide energy/alert boosts for it's people.


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## Michael OLeary (18 Dec 2006)

Shamrock said:
			
		

> Pervitin, the wonder drug.  Key ingredient in tanker's chocolate.



http://www.erowid.org/ask/ask.cgi?ID=2952



> "Pervitin" is the name used for methamphetamine in the Czech Republic and other parts of Eastern Europe. The name "Pervitin" has been in use since 1938 when Temmler pharmaceutical in Berlin began producing methamphetamine and marketing it under that name. It quickly gained popularity among both the general population and the German military during World War II. Pervitin sales were restricted in 1941, but not before tens of millions of tablets were sold. Methamphetamine is still sold under the name "Pervitin" in Eastern Europe, including in liquid form (vials) for IM and IV use. It is also one of the slang names used for street methamphetamine (generally produced from ephedrine). There is some evidence that Pervitin/methamphetamine is being exported from the Czech Republic to other parts of Europe and Canada.


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## Welshy (18 Dec 2006)

JesseWZ said:
			
		

> I have never heard this before. Source please?


The investigation done by the Canadian Board of Inquiry. It is not unusual for them to take "go" pills on the long missions. I read about it in the book call Friendly Fire.
http://en.wikipedia.org/wiki/Tarnak_Farm_incident

As with the German army thing, I cannot remember. It was so long ago.


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## TSKslover (18 Dec 2006)

Darpa Offers No Food for Thought

"Metabolic Dominance" or the "Peak Soldier"

http://www.wired.com/news/medtech/0,1286,62297,00.html

http://www.darpa.mil/dso/thrust/biosci/bs_human.htm


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## Steve 1 RNFLDR (18 Dec 2006)

Does anybody know when the army stopped issuing benzedrine?  The British paras at Arnhem had the stuff, don't know how widely available it was.


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## jollyjacktar (19 Dec 2006)

They were not the only ones to use Bennies, I remember my Dad saying they used to give it to the Commando's prior to ops as well.  I am sure there were other instances of better living through chemicals too.


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## zipperhead_cop (19 Dec 2006)

jollyjacktar said:
			
		

> I am sure there were other instances of better living through chemicals too.



Isn't that the short definition of the mess?   ;D


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## TN2IC (19 Dec 2006)

Kilo_302 said:
			
		

> Maybe he thought "Snipercommandorangerninjapirate Course" was a course offered by the German Army.  ;D




Scharfschützekommandoförsterninjapirat is the correct German Course Name... geee... I'll forgive you now...


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## Shamrock (20 Dec 2006)

zipperhead_cop said:
			
		

> Isn't that the short definition of the mess?   ;D



Sure, if you consider the evidence lock-up the mess.


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## fourninerzero (20 Dec 2006)

Shamrock said:
			
		

> Sure, if you consider the evidence lock-up the mess.



He IS a cop afterall...ya just never know ;D


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## zipperhead_cop (20 Dec 2006)

I count alcohol as a mood altering drug.


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## Cardstonkid (20 Dec 2006)

In a recent New Scientist magazine (sorry forgot which issue) I read an article about the coming pharmaceutical wonders. There are drugs right now that can keep you awake for days at a time with no side effects or diminished capabilities. (These are drugs used to treat sleeping disorders like narcolepsy) The potential for the military is obvious, but some of these drugs are being used in the drug/party culture. People who like drug parties can go for days and not sleep. I guess that way they can snort all of their parents money up their noses so fast that Mom and Dad can't send them to rehab before the money is all gone. 

Drugs of the future (the next ten years or so) may make sleep a thing of the past. Drugs will regulate the chemicals in the brain so that sleep is not needed. Furthermore, drugs such as Ritalin are now being used by healthy college kids to score better on tests, but new drugs will be specifically designed to enhance the performance of memory and problem solving. Not to mention controlling anxiety, stress, and a whole raft of other "normal" mental conditions.

Should be an interesting few years.


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## Sig_Des (20 Dec 2006)

Cardstonkid said:
			
		

> There are drugs right now that can keep you awake for days at a time with no side effects or diminished capabilities. (These are drugs used to treat sleeping disorders like narcolepsy)



Not questioning you, Cardstonkid, but I find it pretty unlikely that there'd be no side effects of diminished capabilities. I'd like to see more information on these "miracle" wake-up pills.

Who knows, maybe in a few years we'll each get an auto-injector IV in our initial issue.


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## zipperhead_cop (20 Dec 2006)

Cardstonkid said:
			
		

> Should be an interesting few years.



Like the current generation of X-box brats need any more incentive to not apply themselves.  Wait to see people get "decision chip" implants that will allow a processor to access the optic nerve impulses in order to make the best possible decision given pre-filled scenarios picked from situation recognition software.  
I can't (but should) believe how hard mankind is working to render itself useless.


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## George Wallace (20 Dec 2006)

Cardstonkid said:
			
		

> ...... There are drugs right now that can keep you awake for days at a time with no side effects or diminished capabilities.



Yes there are.  I heard a friend say how he had used them for a long drive home to Cape Breton from out West.  He stayed awake, taking those pills and drove safely all the way home for a long weekend.  It was great, until.........He stopped taking the pills and slept through the whole long weekend.  He said he'd never do that again.  Was a complete waste of his time and money.

Yup!  You will be able to stay awake for days, but guess what......your body needs the rest and once you do go to ground, you may sleep through several days.  Talk about confused when you do wake up.


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## tomahawk6 (20 Dec 2006)

Red Bull or Bawls for all !!! ;D


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## a_majoor (21 Dec 2006)

This has been discussed here in some detail:

http://forums.army.ca/forums/threads/23394/post-222064.html#msg222064



> Re: Infantry of Tomorrow
> « Reply #97 on: May 31, 2005, 12:01:08 » Quote
> 
> --------------------------------------------------------------------------------
> ...


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## Cardstonkid (21 Dec 2006)

The next step is the "Sleep pills" that will allow a person to sleep for 8 hours after having been awake for days and then when awake feel as if they had fully recovered from the long wake period. In the New Scientist article I believe it mentioned these drugs were in the clinical drug trial phase and are quickly approaching the application for approval stage. 

If I remember correctly the trick of these drugs is that they do for our brain what sleep does. It keeps all the chemicals in balance. Like I said it should be an interesting next few years.


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## zipperhead_cop (22 Dec 2006)

Yeah, funny thing that brain chemistry.   :-\
I'm no bio major, but I think I will content myself with cramming vitamins and chugging Timmies when I have to do some sleep deprivation tasks.  Once you start messing around with your brain soup, if something jumps the rails it seems pretty tricky to get it right again.  
Balance of brain chemistry seems to be the big issue with many mental health patients and it seems like many of them never get it right.  I would hate to see people messing with a perfectly good balance, then wrecking it when the body loses its ability to regulate itself.


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## Nemo888 (22 Dec 2006)

The Army could use this to ensure reenlistment. No more drugs if you quit!


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## George Wallace (22 Dec 2006)

Cardstonkid said:
			
		

> The next step is the "Sleep pills" that will allow a person to sleep for 8 hours after having been awake for days and then when awake feel as if they had fully recovered from the long wake period. In the New Scientist article I believe it mentioned these drugs were in the clinical drug trial phase and are quickly approaching the application for approval stage.
> 
> If I remember correctly the trick of these drugs is that they do for our brain what sleep does. It keeps all the chemicals in balance. Like I said it should be an interesting next few years.



Only a few posts above yours I gave an example of a person who took drugs to stay awake to make a long trip.  When he stopped taking the drugs, his body shut down and he slept for two days.  That being the case, and backed up by ZC's post, there would be no requirement to now induce sleep with another drug.  The body and brain would automatically be doing that anyway.  ZC's post also points out other serious consequences of throwing the Brain and Body's natural 'scheduling' off.

I love it when people post and don't read what was already posted.....if you thought of it, don't you think others may have too?


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## Cardstonkid (22 Dec 2006)

I agree with what you have said, my point was the drug companies may be able to offer products that will let a person choose if and when they want to sleep. _IF_ that is possible it will have far reaching implications for the military and for society. Personally I am leery of the long-term consequences of chemical tinkering with the human brain. I won't be volunteering for any test groups of the new drugs.


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## Sig_Des (22 Dec 2006)

Cardstonkid said:
			
		

> Personally I am leery of the long-term consequences of chemical tinkering with the human brain. I won't be volunteering for any test groups of the new drugs.



Hey, here's an idea. Why don't we volun-force first-time failers of drug testing into one of these test groups?  >

"Sorry, Pte. Bloggins, we've identified Cannabis in your urine. So you won't be going over with the TF. However, you're in luck...we'll be sending you someplace else..."


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## Shamrock (22 Dec 2006)

Cardstonkid said:
			
		

> If I remember correctly the trick of these drugs is that they do for our brain what sleep does. It keeps all the chemicals in balance. Like I said it should be an interesting next few years.



Sleep does more for the brain and body than maintain chemical balance.  When we're asleep, our brains undergo various changes.  New synapses are formed, existing synapses are maintained or removed.  This allows us to form stronger memory bonds of the day's activities among other benefits.  REM sleep seems to be the state whereby this happens -- persons who learn something and undergo REM sleep are better able to retain it than those who learn it and remain awake during that time (yes, it has been postulated that blocking occurs from new things learned during the time of wakefulness).  

Even nonsomniacs (people who don't require considerable amounts of sleep -- about an hour to two a night; these people are different than insomniacs, who still require a more "standard" 8 hours but have difficulty falling asleep) require REM sleep to keep their thinkers thinking.


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## Cardstonkid (22 Dec 2006)

I found the New Scientist article I was referring to. A good read if you are interested and have the time.

http://www.newscientist.com/channel/health/mg18925391.300-get-ready-for-24hour-living.html

Get ready for 24-hour living
18 February 2006 
NewScientist.com news service 
Graham Lawton 




A good night's sleep SO MUCH to do, so little time. 

Between a hectic work schedule and a thriving social life, Yves (not his real name), a 31- year-old software developer from Seattle, often doesn't have time for a full night's sleep. So he swallows something to make sure he doesn't need one. "If I take a dose just before I go to bed, I can wake up after 4 or 5 hours and feel refreshed," he says. "The alarm goes off and I'm like, let's go!"

Yves is talking about modafinil, a stimulant that since its launch seven years ago has acquired a near-mythical reputation for wiring you awake without the jitters, euphoria and eventual crash that come after caffeine or amphetamines. Yves has been popping modafinil on and off for the past three years and says it is "tremendously useful". "I find I can be very productive at work," he says. "I'm more organised and more motivated. And it means I can go out partying on a Friday night and still go skiing early on Saturday morning."

Modafinil is just the first of a wave of new lifestyle drugs that promise to do for sleep what the contraceptive pill did for sex - unshackle it from nature. Since time immemorial, humans have structured their lives around sleep. In the near future, we will, for the first time, be able to significantly structure the way we sleep to suit our lifestyles.

"The more we understand about the body's 24-hour clock the more we will be able to override it," says Russell Foster, a circadian biologist at Imperial College London. "In 10 to 20 years we'll be able to pharmacologically turn sleep off. Mimicking sleep will take longer, but I can see it happening." Foster envisages a world where it's possible, or even routine, for people to be active for 22 hours a day and sleep for two. It is not a world that everyone likes the sound of. "I think that would be the most hideous thing to happen to society," says Neil Stanley, head of sleep research at the Human Psychopharmacology Research Unit in the University of Surrey, UK. But most sleep researchers agree that it is inevitable.

If that sounds unlikely, think about what is already here. Modafinil has made it possible to have 48 hours of continuous wakefulness with few, if any, ill effects. New classes of sleeping pills are on the horizon that promise to deliver sleep that is deeper and more refreshing than the real thing. Further down the line are even more radical interventions - wakefulness promoters that can safely abolish sleep for several days at a stretch, and sleeping pills that deliver what feels like 8 hours of sleep in half the time. Nor is it all about drugs: one research team even talks about developing a wearable electrical device that can wake your brain up at the flick of a switch.

To some degree, we are already adept at controlling sleep. Most people in full-time work deprive themselves of sleep during the week, deliberately or otherwise, and catch up at the weekend. We often augment our sleep-suppressing powers with caffeine, nicotine or illegal stimulants such as cocaine and amphetamines. We are also highly dependent on substances that help us sleep. According to some estimates, 75 per cent of adults suffer at least one symptom of a sleep problem a few nights a week or more. In 1998, a team from the Henry Ford Health Sciences Research Institute in Detroit, Michigan, published a study revealing that 13 per cent of adult Americans had used alcohol to help them get to sleep in the previous year, and 18 per cent had used sleeping pills (Sleep, vol 21, p 178).

Despite the enormous resources that we pour into getting good sleep and wakefulness when we want them, most of the drugs at our disposal are crude instruments at best. The vast majority of sleeping pills - known in the business as hypnotics - are simply "knockout drops" that put you in a state almost like sleep but without its full restorative properties. "Hypnotic-induced sleep is better than no sleep, but it isn't natural sleep," says Stanley. With their addictive nature, the drugs we use to keep us awake, such as coffee and amphetamines, are even worse. In combination with our clock-watching lifestyles, these sleep and wake aids are driving ever more people into what Foster calls the "stimulant-sedative loop" where they need nightly help getting to sleep and daily help staying awake.

Modafinil has changed the rules of the game. The drug is what's known as a eugeroic, meaning "good arousal" in Greek. It delivers natural-feeling alertness and wakefulness without the powerful physical and mental jolt that earlier stimulants delivered. "There are no amphetamine-like feelings," says Yves. And as Yves' way of taking it shows, being on modafinil doesn't stop you from falling asleep if you want to.

In fact, its effects are so subtle that many users say they don't notice anything at all - until they need to. "I wouldn't say it makes me feel more alert or less sleepy. It's just that thoughts of tiredness don't occur to me," says Yves. "If there's a job at hand that I should be doing, I'm focused, but if I'm watching a movie or something, there is no effect."

People who take modafinil for medical reasons usually take just enough of the drug in the morning to see them through the day, but it also seems to be able to deliver sustained wakefulness - for a couple of days at least. "The military has tested sequential dosing," says Jeffrey Vaught, president of R&D at Cephalon, modafinil's Pennsylvania-based manufacturer. "It works for 48 hours or so, but eventually you need to sleep."

Perhaps the most remarkable thing about modafinil is that users don't seem to have to pay back any "sleep debt". Normally, if you stayed awake for 48 hours straight you would have to sleep for about 16 hours to catch up. Modafinil somehow allows you to catch up with only 8 hours or so. Well before Cephalon took an interest in the drug, French researchers discovered this effect in cats back in the early 1990s (Brain Research, vol 591, p 319), and it has since been found to apply to humans too.

“I wouldn't say it makes me feel more alert or less sleepy. It's just that thoughts of tiredness don't occur to me”So how does modafinil work? "No one really knows," admits Vaught. He says that Cephalon thinks it understands the drug, but is keeping the details under wraps. What is clear is that, like other stimulant drugs, modafinil prevents nerve cells from reabsorbing the excitatory neurotransmitter dopamine once they release it into the brain. The difference is that it somehow does so without producing the addictive highs and painful crashes associated with most stimulants. A number of independent studies suggest that this might be because it also interferes with the reuptake of another neurotransmitter, noradrenalin.

However it works, modafinil is proving hugely successful. Since it hit the market in 1998, sales have been climbing steadily - from $25 million in 1999 to around $575 million in 2005. Cephalon insists that the drug is for treating "medical" sleepiness caused by diseases such as narcolepsy and sleep apnoea.

Even so, it's clear that modafinil is becoming a lifestyle drug for people like Yves who want off-the-peg wakefulness. "At first I got it from a friend, and then I got diagnosed as a narcoleptic online," says Yves.

All the indications are that modafinil is extremely safe. The drug can have side effects, most commonly headaches, but up to now there have been no severe reactions, says Vaught. In fact, it is hard to find anyone with a bad word to say about modafinil, except that there may be unseen problems down the line as the drug becomes more widely used. "I think it's unlikely that there can be an arousal drug with no consequences," says Foster. In the long run, it is possible that casual users might have to keep upping their dose to get the same effect. Stanley has similar worries. "Is it a potential drug of abuse?" he asks. "Will it get street value? We'll see."

Cephalon does not seem to be worried. Modafinil's success has spurred it to develop a successor, armodafinil. The company is also developing other eugeroics - one experimental drug called CEP-16795 switches off the H3 histamine receptor, which appears to be one of the molecular switches that controls the sleep-wake cycle. However, Vaught claims that the original will be a tough act to follow. "Modafinil is very effective and very safe," he says. "How do you beat it?"

There are ideas as to how. Last year, Sam Deadwyler of Wake Forest University in Winston-Salem, North Carolina, reported the results of an experiment with a drug called CX717. The findings suggest that modafinil won't have the field to itself forever.

Deadwyler kept 11 rhesus monkeys awake for 36 hours, throughout which they performed short-term memory and general alertness tests (Public Library of Sciences Biology, vol 3, p 299). At that level of sleep deprivation, a monkey's performance would normally drop to the point where it could barely function at all, but Deadwyler found that CX717 had remarkable restorative powers. Monkeys on the drug were doing better after 36 hours of continual wakefulness than undrugged monkeys after normal sleep. When Deadwyler imaged their brains with functional magnetic resonance imaging, (fMRI), he found that the drug maintained normal activity even in severely sleep-deprived individuals. The results build on those of an earlier, small-scale trial on 16 men that found CX717 could largely reverse the cognitive decline that comes with 24 hours of sleep deprivation (New Scientist, 14 May 2005, p 6).

Soldiers get high
CX717 belongs to a class of drugs called ampakines, which subtly ramp up brain activity by enhancing the action of its main excitatory neurotransmitter, glutamate. Cortex Pharmaceuticals of Irvine, California, which developed CX717, originally saw the drug as a cognitive booster for people with Alzheimer's, but it is its potential to counter the effects of sleep deprivation that is attracting the most attention.

Later this year, the Defense Advanced Research Projects Agency (DARPA), based in Arlington, Virginia, will put CX717 through its paces as a wakefulness promoter for combat. In an experiment designed to mimic the harsh demands of special ops, investigators will push 48 volunteers to the limit - four consecutive nights of hard work with only 4 hours of recovery sleep in between. "They'll go from being tired to exhausted to crashing," says Roger Stoll, Cortex's chief executive. For some of them, however, the ordeal will be softened by regular doses of CX717. DARPA hopes the drug will counteract the sleep deprivation.

The trial should help answer some outstanding questions about CX717's potential. "We don't know yet if it eliminates feelings of sleepiness," says Stoll. "The early signs are that people function better, their brain is a little more hyped. But we haven't tested sleepiness directly." As with modafinil, the evidence suggests that people struggle to tell if they're on the drug or not, and that hasn't turned out to be much of a problem for modafinil.

Whatever the outcome of the DARPA trial, CX717 won't be the last word on eugeroics. Stoll says Cortex has similar but more powerful molecules up its sleeve. Thought they are being developed mainly as memory enhancers, some may turn out to be powerful wakefulness promoters too. Industry giants GlaxoSmithKline and Eli Lilly have ampakine programmes of their own, and at least one other company, Arena Pharmaceuticals of San Diego, California, has declared an interest in wakefulness promoters, though it hasn't released any details of its research.

When and if those drugs come through, the US military is sure to be interested. DARPA is one of the most active players in the drive to conquer sleep, setting up and funding much of the basic research on wakefulness. The army and air force have research programmes too.

It's easy to see why DARPA is interested. "We make the assumption that soldiers are going to be sleep-deprived," says DARPA neuroscientist Amy Kruse, who runs the agency's sleep-deprivation research programme. "We want to know what we can do to bring them back up to the level they would be at if they had a good night's sleep."

When DARPA talks about sleep deprivation, it really means it. Soldiers on special ops sometimes have to be awake, alert and active for 72 hours at a stretch with only minimal rest. That's like starting work on Monday morning and not stopping until Thursday. "Three days, that's when they really start hurting," says Kruse.

The military has a long history of using caffeine and amphetamines to get its people through. It has now added modafinil to the list, and is clearly interested in CX717. And Kruse says she is confident that there is lots of room for further improvement.

Last year, a DARPA-funded team led by Giulio Tononi at the University of Wisconsin Madison discovered a strain of fruit flies that gets by on just a third the normal amount of sleep. The "minisleep" mutant carries a change to a single gene, encoding a protein involved in potassium transport across cell membranes. Intriguingly, defects in potassium channels are associated with reduced sleep in humans, particularly in the autoimmune disease Morvan's syndrome, one symptom of which is chronic sleeplessness. What that suggests, says Kruse, is that new drugs designed to latch onto potassium channels in the brain could radically alter the need for sleep. There are also likely to be other molecular targets in the brain just waiting to be exploited, she says.

“I'm the guy who puts sleep-deprived pilots in a plane, gives them drugs and says, did it work?”DARPA is meanwhile pursuing other strategies to conquer sleep deprivation. At Yaakov Stern's lab at Columbia University in New York, DARPA-funded neuroscientists have used fMRI to image the brains of sleep-deprived people, to find out which regions are affected when you are very tired. Then they used a transcranial magnetic stimulation (TMS) machine - routinely used to switch localised brain regions on and off - to switch off those areas and see if that reversed the effects.

"This is all proof of concept," says Stern. "It's hard to imagine a sleep deprived pilot using TMS," not least because the machines are too bulky to fit in a cockpit. "The next step is to apply TMS before or during sleep deprivation to see if it blunts the effect. That has more of a shot at a lasting effect." Stern says his team is also looking into a new technique called DC brain polarisation, which has similar brain-boosting effects to TMS but uses DC current instead of magnetism. The beauty of this "poor man's TMS" is that the equipment is significantly smaller and cheaper - it could even be incorporated into headgear that gives you a jolt of wakefulness at the flick of a switch. And then there's always neurofeedback - training people to activate the brain regions that get hit by sleep deprivation, effectively willing themselves awake.

The military isn't just interested in wakefulness. It also has a keen interest in the other side of the coin. John Caldwell works at the US Air Force Research Laboratory in San Antonio, Texas. He has spent most of his career testing the effects of stimulants, including modafinil, on pilots. "I'm the guy who puts sleep-deprived pilots in a plane, gives them drugs and says, did it work?" he says. He has also done a handful of studies on sleep aids - testing the best way to help night pilots sleep well during the day, for example. In recent months Caldwell has become aware that there is a quiet revolution going on in sleep medicine. "There's a new idea out there," he says. "Drugs that change sleep architecture."

Sleep researchers have known for over 50 years that sleep isn't merely a lengthy period of unconsciousness, but consists of several different brain states (see Diagram). How those states are put together to build a full night's sleep is called sleep architecture.

Catching the slow waves
In the past, says Caldwell, sleeping pills were designed not to mess with sleep architecture, although they generally do, suppressing the deepest and most restorative "slow-wave" sleep in favour of shallower stage 2 sleep. Now, though, modifying sleep architecture is seen as the way forward. There are two new drugs in the offing that significantly increase the amount of slow-wave sleep. One of them, gaboxadol, made by Merck, is in phase III clinical trials and could be on the market next year. To Caldwell these drugs hold out the promise of a power nap par excellence. "Maybe you can make a short period of sleep more restorative by filling it with up with slow-wave sleep," he says.

Much like modafinil, gaboxadol and the other slow-wave sleep promoter - Arena Pharmaceuticals' APD125, currently in phase II - are the start of something bigger. For more than 35 years, sleeping pills have been a one-trick pony. If you wanted to send someone to the land of nod, there was only one way of doing so - targeting the neurotransmitter GABA, which is the brain's all-purpose dimmer switch. Old-fashioned hypnotics such as barbiturates and benzodiazepines work by making neurons more sensitive to the soporific effects of GABA. It's also why alcohol makes you sleepy. Even the newer, cleaner sleeping pills, such as the market leader Ambien, work through the GABA system.

Manipulating the GABA system is a sure-fire way of putting people to sleep, but it has its problems. One is that the brain adapts to the drugs, which means that most cannot be taken for more than a few days without losing their potency. The effects often linger well into the morning, making people feel groggy and hung over. Many are also addictive.

What's more, sleep quality has rarely been considered. "In the past we would take a hypnotic and say, does it put you to sleep?," says Stanley. "That's a pretty inexact way of dealing with it. In that respect, alcohol is a good hypnotic." Now, however, there is a recognition that there is much more to sleep than the GABA system. Last year the first non-GABA sleeping pill came onto the market - the first new class of hypnotic for 35 years. Rozerem, made by Japanese firm Takeda, mimics the effects of the sleep-promoting hormone melatonin. Nor is it the only one. There are at least three other new classes of hypnotic that don't go anywhere near the GABA system. And though gaboxadol works through GABA, it hits a type of receptor that has never been targeted by drugs before.

According to Stanley, there is even more scope for improvement. "It is possible that pharmaceuticals will allow you a condensed dose of sleep," he says, "and we are not that far away from having drugs that put you to sleep for a certain length of time." He predicts you could soon have tablet combining a hypnotic with an antidote or wakefulness promoter designed to give you a precise number of hours' sleep. "A 4, 5 or 6-hour pill."

We seem to be moving inescapably towards a society where sleep and wakefulness are available if not on demand then at least on request. It's not surprising, then, that many sleep researchers have nagging worries about the long-term impact of millions of us using drugs to override the natural sleep-wake cycle.

Stanley believes that drugs like modafinil and CX717 will tempt people to overdose on wakefulness at the expense of sleep. "Being awake is seen to be attractive," he says. "It's not cool to be asleep." Foster has similar worries. "It seems like that technology will help us cope with 24/7, but is coping really living?" he asks. Others point out that there are likely to be hidden health costs to overriding our natural sleep-wake cycles. "Pharmaceuticals cannot substitute for normal sleep," says Vaught.

Still, even the doubters admit that to all intents and purposes we are already too far down the road of the 24-hour society to turn back. For millions of people, good sleep and productive wakefulness are already elusive, night work or nightlife a reality, and the "stimulant-sedative" loop all too familiar. As Vaught puts it, "We're already there." So why not make it as clean and safe as possible?

From issue 2539 of New Scientist magazine, 18 February 2006, page 34


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## Trinity (23 Dec 2006)

OKAY

if you read that entire last post...  you need a break

I found some ...  um.. NON performance enhancing drugs 
tested on soldiers

This is quite funny

http://www.youtube.com/watch?v=eliP1Ji1CQ0&mode=related&search=


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