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Dear friends and fellow athletes,
"The development of modafinil brings to light a crucial social question. What would be the impediment for its use, if a compound such as modafinil is more like caffeine than amphetamine in terms of safety, and yet, as effective as the amphetamines?"
This quote is from an article published by the Aerospace Medical Association about the recently approved drug modafinil. It has come to my attention that many elite bodybuilders and athletes are using the drug modafinil in order to optimize their sleep cycles and obtain peak performance while they are awake. Modafinil is such an interesting drug, because it enables someone to remain awake for a very long time, say three or four days, with out needing sleep. And what makes Modafinil special, is that while it promotes a prolonged wakefulness, it is not stimulating in the way amphetamine, cocaine, or coffee are stimulating.
Modern society demands that we achieve peak performance and that our need to sleep not interfere with our ability to achieve. Some of you probably work out at the gyms called 24-Hour Fitness – where you can train day and night. Or perhaps you work the overnight shift. Or perhaps you need to stay awake for an extended period of time in order to prepare for an exam. Or perhaps you are an executive who has to be awake for both the Nikkei and the NASDAQ.
Controlling time has always been one of man’s driving forces – witness the proliferation of Starbucks on every corner. And with modafinil, science is close to making sleep unnecessary. Imagine if you will, how much you could accomplish if you only needed to sleep for say 8 hours twice a week. Well, this is not science fiction, but has in fact become a reality. After taking modafinil, users often remark, "I can't tell any difference." But many hours later, they realize that their attention and wakefulness are the same as much earlier and they experience no fatigue.
The armed forces needs soldiers that can resist fatigue for extended periods as well as maintain high levels of physical performance. Given this need, it is not surprising that the Armed Forces in general and the Air Force in particular are experimenting with modafinil for keeping troops and pilots alert for extended periods of time. The Pentagon cannot afford a soldier to make a single error as such a mistake could have devastating consequences. At the same time, the demands of service can necessitate that a soldier remain awake for an entire week without sleep.
In the recent American bombing missions, pilots have needed to fly from Missouri to Afghanistan without stopping. In the Persian Gulf War, pilots were frequently prescribed Dexedrine when flight durations were long. And in fact, in excess of 60% of pilots said that Dexedrine was “essential” to accomplishing their mission. This time around, modafinil has been studied and for pilots, it has shown to be effective at keeping them awake and focused.
Athletes have found modafinil to be particularly effective with their training. Especially athletes like bodybuilders who require a great deal of focus to achieve the desired results. Has any of this ever happened to you? You are mentally exhausted after a long day of work, but you have not done any physical activity at all. And so your training suffers. You began a workout, but became fatigued part way through. And so your training suffers. Some days, you are lacking in the mental focus necessary to train optimally. Your work or school schedule prevents training. Sometimes, you lack the physical energy necessary for an optimal workout. In all these situations, athletes have found modafinil to be helpful.
Modafinil is an eugeroic drug, (which simply means "good arousal"). While on modafinil, users typically feel focused and calm. And once the modafinil user ceases taking the drug, he is able to have a natural restorative nights sleep and awake refreshed in the morning. There are only two eugeroic drugs in existence at this time: the older adrafinil and the newer modafinil. Both drugs were developed by Lafon Laboratories of France.
Consider a normal day. For most of us, in the course of a normal day, you are either 100% awake or 100% asleep. Only about two or three percent of the time could you consider yourself to be in some state half way between sleeping and wakefulness. Most peoples’ sleeping and wakening cycles are like a light switch, either on (awake) or off (asleep).
About three years ago, scientists discovered the neurotransmitter orexin. Although its function was not initially known, they soon realized that this neurotransmitter is responsible for keeping our light switch in the on (awake) position. To discover what orexin does, the scientists altered mice so that they were missing this neurotransmitter. But except for missing the orexin transmitter, the mice were genetically identical to the control mice in the study in every other way. The mice without the orexin neurotransmitter behaved completely normally, with the sole exception being that they could not stay awake.
Narcolepsy is a disorder characterized by sudden and uncontrollable attacks of deep sleep. Extrapolating from the study of the mice missing orexin, the scientists postulated that the same neurotransmitter might be missing in narcoleptics. So, they did another study where they compared the hypothalamus of a narcoleptic with one from a normal individual. What they learned was that like in the mice, narcoleptics were indeed deficient in the orexin neuron.
Traditional drugs used to counter sleepiness have all been stimulants -- Dexedrine, amphetamine, cocaine, caffeine. The problem with these conventional amphetamine based stimulants is the numerous side effects. Such stimulants are highly addictive, can cause anxiety, jitteriness, irregular heartbeat, overconfidence, etc. Amphetamine also has a nasty rebound effect when it wears off -- meaning that sleep after using amphetamine is non-restorative and the user feels exhausted upon waking. What was needed was a drug that could enable someone to overcome sleepiness without the amphetamine like side effects.
Enter modafinil. Modafinil selectively activates the orexin neurons.
When we are awake, we can largely divide our state of wakefulness into two forms. The first form can be called vigilance. In the vigilance form of wakefulness, we are on guard -- hyper aware to threats around us. We are in this state of wakefulness when we sense we are in danger. Vigilance seems to be directly related to our levels of norepinephrine, serotonin, and dopamine. If we use a drug to stimulate norepinephrine, serotonin, or dopamine, we can chemically induce a state of hyperactivity or extreme vigilance.
The second form of wakefulness is a calm wakefulness. This calm wakeful state is characterized by one being attentive, engaged, and focused. You are hopefully in this state of wakefulness right now as you are engaged and focused on this issue of Elite Fitness News. It is believed that the histamine pathways control calm, focused wakefulness.
Conventional stimulants promote wakefulness with a shotgun approach. They stimulate the norepinephrine, serotonin, dopamine, and histamine pathways -- in other words, all the wakefulness pathways in the brain. Modafinil on the other hand promotes a more selective firing of the neurons primarily in the prefrontal cortex of the brain. The prefrontal cortex of the brain is where we believe many of the functions related to attention, engagement, and focus lie.
The use of modafinil in narcoleptics has produced very favorable results. Where as Dexedrine interferes with normal sleep leaving the users hung-over when they wake up, modafinil has no effect on the quality of the sleep that is obtained the night after the user stops taking it. In addition, unlike amphetamine, modafinil seems to have no potential for addiction.
Two studies directly compared the effects of modafinil and d-amphetamine on sleep. Both double blind controls involved about twelve individuals; one study was undertaken on individuals whose mean age was 68, the other on much younger volunteers. They utilized l00 mg or 200 mg of modafinil, or l0 mg or 20 mg of d- amphetamine or a placebo. All the drugs were administered orally and sleep scales, awakening quality and psychometric tests were completed in the morning.
The outcome of both tests showed that d-amphetamine caused a dose dependant impairment of sleep maintenance, but modafinil did not. Here in lies the problem for those who have difficulty staying alert and awake during the day. The use of "classic" stimulants such as amphetamines threaten to reduce total sleep time and REM sleep, this will ultimately mean higher and higher doses are required and a vicious circle ensues.
On the other hand, modafinil has not been shown to interfere with nighttime sleep. This would indicate that the two compounds operate by different methods.
Having almost no significant side effects has led doctors to experiment with modafinil to treat other disorders. Modafinil has been used to treat drowsiness and fatigue associated with depression, Parkinson’s, and multiple sclerosis. Further experiments are being conducted to study its effects on Alzheimer's disease, depression, attention-deficit disorder, age-related memory decline, idiopathic hypersomnia and everyday catnapping. Modafinil is even used to treat insomniacs as they frequently report low energy throughout the day.
A note worthy conclusion of one clinical trial compared modafinil to amphetamine and described amphetamine as "vigilance increasing" but modafinil as "vigilance promoting." This is an interesting comment because as we've seen, modafinil won't prevent a person from sleeping if they want to but if they wish to remain awake they will do so with a far greater alertness.
This vigilance promoting effect was demonstrated in a clinical trial where volunteers were subjected to 60 hours of sleep deprivation. During their continued wakefulness, their vigilance was assessed using questionnaires, analogue visual scales, and sleep latency tests.
The subjects received either 200 mg of modafinil or a placebo every 8 hours. The modafinil group sustained a satisfactory level of vigilance with an absence of sleep episodes. But the placebo group gradually declined and slipped into "micro-sleep" episodes, as would be expected after staying awake for longer than 24 hours.
A three year French study showed that modafinil reduced drowsiness in 83% of hypersomniac patients and 71% of narcoleptics. And Modafinil did not produce peripheric side effects, disturb night sleep, and it was never responsible for drug dependence.
Another French study conducted with 149 patients over a period of 2 years, was treating patients with narcolepsy-cataplexy at 200 mg to 400 mg daily. The patients were then asked to score the benefit of modafinil themselves from 0 (no affect) to 3 (excellent affect), 64.1% of the subjects scored it as excellent.
The safety of Modafinil is well established too. Blood and pulse rates usually remain unchanged at normal therapeutic doses. In fact, the relative safety of modafinil was further demonstrated by a suicidal 21 year old female who ingested 4500 mg of the drug. Her side effects were limited to tachycardia, excitation and insomnia .
As is common with most drugs, modafinil should not be used by those with serious liver disorders, nor those women who are pregnant or nursing. The official insert for the modafinil package remains unclear as to the precise drug contraindications, but as it is an alpha-adrenergic agonist, those drugs that represent alpha-adrenergic antagonists should be avoided. These include prazosin, phentolamine or beta-blockers such as propranolol (Inderal). Furthermore, drugs that enhance norepinephrine activity (such as yohimbine) should only be used with care, as there may be a synergistic affect.
Adrafinil, a first generation drug similar to modafinil, is noted as contraindicated with epilepsy and has been shown to enhance the potency of anti-epileptic drugs such as phenytoin (Dilantin/ Epanutin). Although this contraindicated isn't mentioned in any of the modafinil literature, it is best being advised to take note of.
As for effective dosages, there appears to be little difference in the effectiveness of different doses. What seems more important is maintaining regular administration of the dose. Those who simply wish to remain awake and alert will benefit from a single l00 mg dose. To remain on call all day, l00 mg in the morning and another l00 mg in the afternoon is probably all that is required. For those wishing to remain awake during the night, then another l00 mg in the late evening would be taken. Basically, the drug exerts its effect for 8 hours, at which time the user should repeat the dosage or sleep. Dosages for those suffering from narcolepsy, hypersomnia and catoplexy are 100-200 mg morning and afternoon. Some of the doses in trials have been as high as 600 mg to 700 mg daily although doses over 500 mg daily can cause euphoria, slight motor excitation, or even insomnia.
All this brings me back to the original quote from the Aerospace Medical Association.
"The development of modafinil brings to light a crucial social question. What would be the impediment for its use, if a compound such as modafinil is more like caffeine than amphetamine in terms of safety, and yet, as effective as the amphetamines?"
So, would it be harmful to us if we only slept two nights out of seven?
Studies involving rats that were kept awake for 5 to 30 days showed that rats would get sepsis and die from the presence of pathogenic organisms or their toxins that would form in the blood or tissues. But surprisingly, there is almost no data that indicates that prolonged sleep deprivation has any serious impact on humans at all. And the research on humans showed very little changes in basic bodily function in studies where subjects were kept awake for four days or even longer.
In summary, we all know that both food and sleep are important, but where there is a great deal that is known about the role nutrition plays in humans, comparatively little is known about the role sleep plays. In the future, drugs will exist that will be even more effective than modafinil at selectively targeting orexin and we will be able to stay awake ever longer with even fewer side effects.
And, the next generation of sleeping pills will likely be orexin blockers that would have the ability to induce an immediate, deep, intense REM sleep. This REM sleep would be both highly restorative and able to induce the production of significant amounts of growth hormone by those taking it. Of course there might be a few side effects from an orexin blocker sleeping pill. Two that come to mind would be intense dreams and the possibility of an eight-hour erection.
In future issues of Elite Fitness News, I’ll share with you a bit more about next generation sleeping pills. And as always, I appreciate your comments and feedback about modafinil, orexin, or anything else right on the boards.
References
1. Lamberg L "Narcolepsy researchers barking up the right tree" JAMA Sep. 96, 11 276 (10) 765-766.
2. Jouvet M, Albarede JL, Lubin S, Meyrignac C "Noradrenaline and cerebral aging" Encephale May 1991 17 (3) 187-195.
3. Saletu B, Frey R, Krupka M, Anderer P, Grunberger J, Barbanoj MJ "Differential effects of a new central adrenergic agonist- modafinil and d-amphetamine on sleep and early morning behaviour in elderly" Arzneimittelforschung Oct 1989 39 (10) 1268-73.
4. Nicoladis S, DeSaint, Hilarre Z "Nonamphetamine awakening agent modafinil induces feeding changes in the rat" Brain Res Bull 1993 (32) 2 87-90.
5. Ferraro L, Tanganelli S, O’Connor WT, Antonelli T, Rambert F, Fuxe K "The vigilance promoting drug modafinil decreases GABA release in the medial preoptic area and in the posterior hypothalamus of the awake rate; possible involvement of the serotonergic 5-HT3 receptor" Neuro Sci Lett 1996 Dec 6 220 (1)
6. Gold LH, Balster RL, "Evaluation of the cocaine like discriminative stimulus effects and reinforcing effects of modafinil" Dept of Phar & Tox, Med Coll VA, USA.
7. Maffont F, Mayer G, Minz M, "Modafinil in diurnal sleepiness, a study of 123 patients" Expl Fonct Neuro CHU Parid France. Sleep 1994 Dec 17 (8) 5113-115.
8. Billiard M, Besset A, Montplasir J, Laffont F, Goldenberg F, Weill JS, Lubin S "Modafinil, a double blind multicentric study" Sleep 1994 Dec 17 (8) 5107-112.
9. Bastuji H, Jouvet M "Successful treatment of idiopathic hypersomnia and narcolepsy with modafinil" Prog Neuro Psy Pharm 1988 12 (5) 695-700.
10, Saletu B, Frey R, Krupka M, Anderer P, Grunberger J, Barbanoj MJ "Differential effects of a new central adrenergic agonist- modafinil and d-amphetamine on sleep and early morning behaviour in young healthy volunteers" Int J Clinical Pharm Res 1989 9 (3) 183-185.
11. Lagarde D, Batejat D, Van Beers P, Sarafian D, Pradella S "Interest of modafinil, a new psycostimulant during a sixty hour sleep deprivation experiment" Fund Clin Pharmacol 1995 (9) 3- 271-9.
12. Broughton RJ, Fleming JA, George CF, Hill JD, Kruger MH, Moldofsky H, Montplasir JY, Morehouse RL, Moscovitch A, Murphy WF "Randomised double blind placebo controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy" Neurology 1997 Aug (49) 2 P444-451.
13. Basset A, Chetrit M, Carlander B, Billard M "Use of modafinil in the treatment of narcolepsy, a long term follow up study" Neurophysiol Clin 1996 26 (1) 60-66.
14. Arnuff I, Homeyer P, Garma L, Whitelaw WA, Derenne JP "Modafinil in obstructive sleep apnea hypopnea syndrome, a pilot study in 6 patients" Respiration 1997 64 (2) 159-161.
15. Boivon DB, Montplisir J, Petit D, Lambert C, Labin S "Effects of modafinil on symptomatology of human narcolepsy" Clin Neuropharmacol 1994 Fed 16 (1) 46-53.
16. Lyons TJ, French J "Modafinil the unique properties of a new stimulant" USAF School of Aerospace, Brooks TX (Science News Note 1991, 62 432-5).
17.Laffont F, Cathala HP, Kohler F "Effect of modafinil on narcoleptic and idiopathic hypersomnia" 5th Euro Cong sleep research, Copenhagen 1987 586.
18. Laffont F,Cathala HP, Waisbord P, Kohler F "Effect of modafinil on narcoleptic patients" 9th Euro Cong sleep research, Israel 1988; 26.
19. Bastuli H, Jouvet M "Traitement des hypersomnies per la modafinil" La Press Medicale 1986 15 (28) 1330.
20. Goldenberg F, Weil JS, Van Frenkeel R, "Effects of modafinil on diurnal variation of objective sleepiness in normal subjects" 5th Int Cong Sleep Research 1987 (149).
21.Saletu B; Saletu M; Grunberger J; Frey R; Zatschek I; Mader R, "On the treatment of the alcoholic organic brain syndrome with an alpha-adrenergic agonist modafinil: Double-blind, placebo-controlled clinical, psychometric and neurophysiological studies. Prog Neuropsychopharmacol Biol Psychiatry, 14(2):195-214 1990.
22. Brun J; Chamba G; Khalfallah Y; Girard P; Boissy I; Bastuji H; Sassolas G; Claustrat B, "Effect of modafinil on plasma melatonin, cortisol and growth hormone rhythms, rectal temperature and performance in healthy subjects during a 36 h sleep deprivation" Journal of Sleep Research, 1998 Jun; 7(2): 105-14.
23. Groopman, Jerome, "Eyes Wide Open" The New Yorker, 2001 December 3: 52 - 57
Dear friends and fellow athletes,
"The development of modafinil brings to light a crucial social question. What would be the impediment for its use, if a compound such as modafinil is more like caffeine than amphetamine in terms of safety, and yet, as effective as the amphetamines?"
This quote is from an article published by the Aerospace Medical Association about the recently approved drug modafinil. It has come to my attention that many elite bodybuilders and athletes are using the drug modafinil in order to optimize their sleep cycles and obtain peak performance while they are awake. Modafinil is such an interesting drug, because it enables someone to remain awake for a very long time, say three or four days, with out needing sleep. And what makes Modafinil special, is that while it promotes a prolonged wakefulness, it is not stimulating in the way amphetamine, cocaine, or coffee are stimulating.
Modern society demands that we achieve peak performance and that our need to sleep not interfere with our ability to achieve. Some of you probably work out at the gyms called 24-Hour Fitness – where you can train day and night. Or perhaps you work the overnight shift. Or perhaps you need to stay awake for an extended period of time in order to prepare for an exam. Or perhaps you are an executive who has to be awake for both the Nikkei and the NASDAQ.
Controlling time has always been one of man’s driving forces – witness the proliferation of Starbucks on every corner. And with modafinil, science is close to making sleep unnecessary. Imagine if you will, how much you could accomplish if you only needed to sleep for say 8 hours twice a week. Well, this is not science fiction, but has in fact become a reality. After taking modafinil, users often remark, "I can't tell any difference." But many hours later, they realize that their attention and wakefulness are the same as much earlier and they experience no fatigue.
The armed forces needs soldiers that can resist fatigue for extended periods as well as maintain high levels of physical performance. Given this need, it is not surprising that the Armed Forces in general and the Air Force in particular are experimenting with modafinil for keeping troops and pilots alert for extended periods of time. The Pentagon cannot afford a soldier to make a single error as such a mistake could have devastating consequences. At the same time, the demands of service can necessitate that a soldier remain awake for an entire week without sleep.
In the recent American bombing missions, pilots have needed to fly from Missouri to Afghanistan without stopping. In the Persian Gulf War, pilots were frequently prescribed Dexedrine when flight durations were long. And in fact, in excess of 60% of pilots said that Dexedrine was “essential” to accomplishing their mission. This time around, modafinil has been studied and for pilots, it has shown to be effective at keeping them awake and focused.
Athletes have found modafinil to be particularly effective with their training. Especially athletes like bodybuilders who require a great deal of focus to achieve the desired results. Has any of this ever happened to you? You are mentally exhausted after a long day of work, but you have not done any physical activity at all. And so your training suffers. You began a workout, but became fatigued part way through. And so your training suffers. Some days, you are lacking in the mental focus necessary to train optimally. Your work or school schedule prevents training. Sometimes, you lack the physical energy necessary for an optimal workout. In all these situations, athletes have found modafinil to be helpful.
Modafinil is an eugeroic drug, (which simply means "good arousal"). While on modafinil, users typically feel focused and calm. And once the modafinil user ceases taking the drug, he is able to have a natural restorative nights sleep and awake refreshed in the morning. There are only two eugeroic drugs in existence at this time: the older adrafinil and the newer modafinil. Both drugs were developed by Lafon Laboratories of France.
Consider a normal day. For most of us, in the course of a normal day, you are either 100% awake or 100% asleep. Only about two or three percent of the time could you consider yourself to be in some state half way between sleeping and wakefulness. Most peoples’ sleeping and wakening cycles are like a light switch, either on (awake) or off (asleep).
About three years ago, scientists discovered the neurotransmitter orexin. Although its function was not initially known, they soon realized that this neurotransmitter is responsible for keeping our light switch in the on (awake) position. To discover what orexin does, the scientists altered mice so that they were missing this neurotransmitter. But except for missing the orexin transmitter, the mice were genetically identical to the control mice in the study in every other way. The mice without the orexin neurotransmitter behaved completely normally, with the sole exception being that they could not stay awake.
Narcolepsy is a disorder characterized by sudden and uncontrollable attacks of deep sleep. Extrapolating from the study of the mice missing orexin, the scientists postulated that the same neurotransmitter might be missing in narcoleptics. So, they did another study where they compared the hypothalamus of a narcoleptic with one from a normal individual. What they learned was that like in the mice, narcoleptics were indeed deficient in the orexin neuron.
Traditional drugs used to counter sleepiness have all been stimulants -- Dexedrine, amphetamine, cocaine, caffeine. The problem with these conventional amphetamine based stimulants is the numerous side effects. Such stimulants are highly addictive, can cause anxiety, jitteriness, irregular heartbeat, overconfidence, etc. Amphetamine also has a nasty rebound effect when it wears off -- meaning that sleep after using amphetamine is non-restorative and the user feels exhausted upon waking. What was needed was a drug that could enable someone to overcome sleepiness without the amphetamine like side effects.
Enter modafinil. Modafinil selectively activates the orexin neurons.
When we are awake, we can largely divide our state of wakefulness into two forms. The first form can be called vigilance. In the vigilance form of wakefulness, we are on guard -- hyper aware to threats around us. We are in this state of wakefulness when we sense we are in danger. Vigilance seems to be directly related to our levels of norepinephrine, serotonin, and dopamine. If we use a drug to stimulate norepinephrine, serotonin, or dopamine, we can chemically induce a state of hyperactivity or extreme vigilance.
The second form of wakefulness is a calm wakefulness. This calm wakeful state is characterized by one being attentive, engaged, and focused. You are hopefully in this state of wakefulness right now as you are engaged and focused on this issue of Elite Fitness News. It is believed that the histamine pathways control calm, focused wakefulness.
Conventional stimulants promote wakefulness with a shotgun approach. They stimulate the norepinephrine, serotonin, dopamine, and histamine pathways -- in other words, all the wakefulness pathways in the brain. Modafinil on the other hand promotes a more selective firing of the neurons primarily in the prefrontal cortex of the brain. The prefrontal cortex of the brain is where we believe many of the functions related to attention, engagement, and focus lie.
The use of modafinil in narcoleptics has produced very favorable results. Where as Dexedrine interferes with normal sleep leaving the users hung-over when they wake up, modafinil has no effect on the quality of the sleep that is obtained the night after the user stops taking it. In addition, unlike amphetamine, modafinil seems to have no potential for addiction.
Two studies directly compared the effects of modafinil and d-amphetamine on sleep. Both double blind controls involved about twelve individuals; one study was undertaken on individuals whose mean age was 68, the other on much younger volunteers. They utilized l00 mg or 200 mg of modafinil, or l0 mg or 20 mg of d- amphetamine or a placebo. All the drugs were administered orally and sleep scales, awakening quality and psychometric tests were completed in the morning.
The outcome of both tests showed that d-amphetamine caused a dose dependant impairment of sleep maintenance, but modafinil did not. Here in lies the problem for those who have difficulty staying alert and awake during the day. The use of "classic" stimulants such as amphetamines threaten to reduce total sleep time and REM sleep, this will ultimately mean higher and higher doses are required and a vicious circle ensues.
On the other hand, modafinil has not been shown to interfere with nighttime sleep. This would indicate that the two compounds operate by different methods.
Having almost no significant side effects has led doctors to experiment with modafinil to treat other disorders. Modafinil has been used to treat drowsiness and fatigue associated with depression, Parkinson’s, and multiple sclerosis. Further experiments are being conducted to study its effects on Alzheimer's disease, depression, attention-deficit disorder, age-related memory decline, idiopathic hypersomnia and everyday catnapping. Modafinil is even used to treat insomniacs as they frequently report low energy throughout the day.
A note worthy conclusion of one clinical trial compared modafinil to amphetamine and described amphetamine as "vigilance increasing" but modafinil as "vigilance promoting." This is an interesting comment because as we've seen, modafinil won't prevent a person from sleeping if they want to but if they wish to remain awake they will do so with a far greater alertness.
This vigilance promoting effect was demonstrated in a clinical trial where volunteers were subjected to 60 hours of sleep deprivation. During their continued wakefulness, their vigilance was assessed using questionnaires, analogue visual scales, and sleep latency tests.
The subjects received either 200 mg of modafinil or a placebo every 8 hours. The modafinil group sustained a satisfactory level of vigilance with an absence of sleep episodes. But the placebo group gradually declined and slipped into "micro-sleep" episodes, as would be expected after staying awake for longer than 24 hours.
A three year French study showed that modafinil reduced drowsiness in 83% of hypersomniac patients and 71% of narcoleptics. And Modafinil did not produce peripheric side effects, disturb night sleep, and it was never responsible for drug dependence.
Another French study conducted with 149 patients over a period of 2 years, was treating patients with narcolepsy-cataplexy at 200 mg to 400 mg daily. The patients were then asked to score the benefit of modafinil themselves from 0 (no affect) to 3 (excellent affect), 64.1% of the subjects scored it as excellent.
The safety of Modafinil is well established too. Blood and pulse rates usually remain unchanged at normal therapeutic doses. In fact, the relative safety of modafinil was further demonstrated by a suicidal 21 year old female who ingested 4500 mg of the drug. Her side effects were limited to tachycardia, excitation and insomnia .
As is common with most drugs, modafinil should not be used by those with serious liver disorders, nor those women who are pregnant or nursing. The official insert for the modafinil package remains unclear as to the precise drug contraindications, but as it is an alpha-adrenergic agonist, those drugs that represent alpha-adrenergic antagonists should be avoided. These include prazosin, phentolamine or beta-blockers such as propranolol (Inderal). Furthermore, drugs that enhance norepinephrine activity (such as yohimbine) should only be used with care, as there may be a synergistic affect.
Adrafinil, a first generation drug similar to modafinil, is noted as contraindicated with epilepsy and has been shown to enhance the potency of anti-epileptic drugs such as phenytoin (Dilantin/ Epanutin). Although this contraindicated isn't mentioned in any of the modafinil literature, it is best being advised to take note of.
As for effective dosages, there appears to be little difference in the effectiveness of different doses. What seems more important is maintaining regular administration of the dose. Those who simply wish to remain awake and alert will benefit from a single l00 mg dose. To remain on call all day, l00 mg in the morning and another l00 mg in the afternoon is probably all that is required. For those wishing to remain awake during the night, then another l00 mg in the late evening would be taken. Basically, the drug exerts its effect for 8 hours, at which time the user should repeat the dosage or sleep. Dosages for those suffering from narcolepsy, hypersomnia and catoplexy are 100-200 mg morning and afternoon. Some of the doses in trials have been as high as 600 mg to 700 mg daily although doses over 500 mg daily can cause euphoria, slight motor excitation, or even insomnia.
All this brings me back to the original quote from the Aerospace Medical Association.
"The development of modafinil brings to light a crucial social question. What would be the impediment for its use, if a compound such as modafinil is more like caffeine than amphetamine in terms of safety, and yet, as effective as the amphetamines?"
So, would it be harmful to us if we only slept two nights out of seven?
Studies involving rats that were kept awake for 5 to 30 days showed that rats would get sepsis and die from the presence of pathogenic organisms or their toxins that would form in the blood or tissues. But surprisingly, there is almost no data that indicates that prolonged sleep deprivation has any serious impact on humans at all. And the research on humans showed very little changes in basic bodily function in studies where subjects were kept awake for four days or even longer.
In summary, we all know that both food and sleep are important, but where there is a great deal that is known about the role nutrition plays in humans, comparatively little is known about the role sleep plays. In the future, drugs will exist that will be even more effective than modafinil at selectively targeting orexin and we will be able to stay awake ever longer with even fewer side effects.
And, the next generation of sleeping pills will likely be orexin blockers that would have the ability to induce an immediate, deep, intense REM sleep. This REM sleep would be both highly restorative and able to induce the production of significant amounts of growth hormone by those taking it. Of course there might be a few side effects from an orexin blocker sleeping pill. Two that come to mind would be intense dreams and the possibility of an eight-hour erection.
In future issues of Elite Fitness News, I’ll share with you a bit more about next generation sleeping pills. And as always, I appreciate your comments and feedback about modafinil, orexin, or anything else right on the boards.
References
1. Lamberg L "Narcolepsy researchers barking up the right tree" JAMA Sep. 96, 11 276 (10) 765-766.
2. Jouvet M, Albarede JL, Lubin S, Meyrignac C "Noradrenaline and cerebral aging" Encephale May 1991 17 (3) 187-195.
3. Saletu B, Frey R, Krupka M, Anderer P, Grunberger J, Barbanoj MJ "Differential effects of a new central adrenergic agonist- modafinil and d-amphetamine on sleep and early morning behaviour in elderly" Arzneimittelforschung Oct 1989 39 (10) 1268-73.
4. Nicoladis S, DeSaint, Hilarre Z "Nonamphetamine awakening agent modafinil induces feeding changes in the rat" Brain Res Bull 1993 (32) 2 87-90.
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