47 replies to this topic

[hawkie]

I just recently ordered some Modafil, because of the hype: How wonderful wouldn't it be to be able to be awake for 48 hours without this time-consuming sleep?

Now I've tried it, and I'm really disappointed. The only effect has been a racing heart and that I get more easily angry - not healthy in a relationship :-)

I've been using the herb Rhodiola for some time, and that is so much better than Modafil, it makes me both alert and happy, although it doesn't save me from the bed. I don't know - perhaps I've taken too little (400 mg) or perhaps Modafil doesn't work like the real (and expensive and patented) thing?

[theone999]

Hello, sorry to hear that Modafinil isn't working out for you. I agree that it perhaps is overhyped a bit, sometimes it can either make me "fuzzy" or "hyper". But it does what it says on the bottle, it keeps you awake. I dont' think it's supposed to act on your body in anyway. Even when i felt hyper, my BPM is normal. When you stay up for 24+, modafinil only makes my mind alert, it does nothing at all for my body as far as i can notice. As to the dosage, i think 400mg is more than enough. I take 2 x 100 mg 4 hrs apart, i find that's the best dosage personally.

[emerson]

I've actually been on both sides of the fence when it comes to modafinil. I used it a few times in my middle teen years, and was pretty underwhelmed by the experience. Throw another ten years onto me and there's all the difference in the world. The effects on me now are only a few steps away from feeling like a miracle in a bottle. While I don't know if I could comfortably go for 48 hours with no sleep on it, I gave a shot at going for only a two hour nap within that time frame and came out still chipper and productive at the end. Even better is just the feeling of waking up without an alarm clock, feeling rested, awake, and eager for the day. Of course that's the danger as well, because feeling rested and actually being so can be very different things. But that's also where the ability to still fall asleep on it can come in handy. It's not that difficult, for me at least, to wake up after three hours sleep on it and then make a decision that I 'need' to sleep for another two or three for the sake of both health and mental effectiveness the next day.

And speaking of mental effects, in my case the increased ability to concentrate on a task is almost unreal. While I'd heard occasional mention of that, it's the sleep angle which always seems to get the majority of the talking space. Which is somewhat a pity simply for the fact that the two aspects work so well together.

[doug123]

I have a prescription though...for 200mg a day... [thumb]

Edited by nootropikamil, 25 March 2007 - 03:44 AM.

[hormesis]

Is there anything that might be a good idea to take with Modafinil to prevent any negative side effects?

[doug123]

Is there anything that might be a good idea to take with Modafinil to prevent any negative side effects?

Not everyone will like modafinil's effects. No drug will work for everyone; it's usually best to weigh and consider possible side effects first.

Provigil AKA modafinil appears to be well tolerated in healthy subjects. That does not mean it will work for everyone.

See this paper, from which the following quote is taken:

‘Smart drugs’ are used by all sectors of society to improve the
functioning of the human mind. But there is now growing evidence,
particularly from the United States, that pharmaceuticals are being
both prescribed and illegally consumed by university students to
maintain supernormal levels of concentration in the run-up to
exams, with the suggestion that this trend will eventually encompass
younger children. How should society react to this increasing desire
by people to use smart drugs? What effects could their widespread use
have on our educational systems? Could children in the future face
blood or urine tests when sitting their A-level or GCSE exams?
Recent developments in drugs to improve memory and cognition
certainly raise the prospect of drug-testing regimes in schools similar
to those imposed on athletes. It is essential that educators in
particular think hard about the implications of such developments.
Are the smart drugs of the future more likely to be viewed as giving
an unfair advantage to pupils, or will they be embraced by parents
and teachers as a reasonable addition to the armament of selfimprovement
techniques designed to give children the best possible
start in life?
Until recently, psychotropic medications had significant risks that
made them attractive only when the benefits to the patient were
considered to outweigh the side effects. However, it is now becoming
possible to enhance cognition pharmacologically with minimal side
effects in healthy volunteers. For example, as part of a research
programme to identify cognitive enhancers for patient use, we
showed in our laboratory in Cambridge that a single dose of
modafinil (Provigil, a drug licensed for the treatment of narcolepsy)
induced reliable improvements in short-term memory and planning
abilities in healthy adult male volunteers.1 Improvements in
performance have also been shown in healthy young male students
after a single dose of methylphenidate (Ritalin).2 Some research has
indicated similar cognitive-enhancing potential with a group of
memory-modulating drugs called ampakines.3
Such drugs are typically developed to treat a medical condition,
but are proving to be safe enough for widespread use following
healthy volunteer studies. The list of agents, including nutraceuticals
and herbal enhancers, is also growing.4 More work is needed to
determine if these drugs will maintain their beneficial effects when
taken over a long period of time. Nevertheless, in the absence of
contrary advice, increasingly they will be used for indications other
than those they are licensed for.

http://www.demos.co....dia_public.aspx

[alexoverhere]

i have never had to take more than 200mg to feel the effects (within 10-15 mins.). i experienced euphoria the first day i took it, and anxiety after taking it for a long time without a break (now I cycle it). the only other side effect i notice is dry mouth when i bike, which is a bit annoying. but not falling asleep every afternoon makes it completely worth it for me.

[theone999]

alex, the time needed for modafinil to peak in plasma concentration is 2-4 hrs, and delayed up to one hour if taken with food. you sure it's not a placebo effect?
I've been taking it for a week now, and on no occasion did i feel any euphoria or anxiety at 200mg. If anything it can feel weaker than my 1st dose sometimes.

[doug123]

alex, the time needed for modafinil to peak in plasma concentration is 2-4 hrs, and delayed up to one hour if taken with food. you sure it's not a placebo effect?
I've been taking it for a week now, and on no occasion did i feel any euphoria or anxiety at 200mg. If anything it can feel weaker than my 1st dose sometimes.

I'm not Alex, though we're old friends...

Everyone reacts differently to drugs. That might be due to:

1) Your body weight. How much do you weigh?
2) Your metabolism.
3) Interactions with other medications you may be taking. For example, modafinil works on the same secondary messenger system as the active ingredient in Forslean..so if you are taking Forslean, you might want to reconsider stopping it as it may interfere with the effectiveness of Provigil.

There may be other factors too; I'm typing fast.

I can feel Provigil aka modafinil within about 20 minutes from when I take it on an empty stomach. It may have optimum plasma levels later, but I can still feel it pretty quick after I take it.

Edited by nootropikamil, 25 March 2007 - 03:45 AM.

[dopamine]

alex, the time needed for modafinil to peak in plasma concentration is 2-4 hrs, and delayed up to one hour if taken with food. you sure it's not a placebo effect?
I've been taking it for a week now, and on no occasion did i feel any euphoria or anxiety at 200mg. If anything it can feel weaker than my 1st dose sometimes.

I'm not Alex, though we're old friends...

Everyone reacts differently to drugs. That might be due to:

1) Your body weight. How much do you weigh?
2) Your metabolism.
3) Interactions with other medications you may be taking. For example, modafinil works on the same secondary messenger system as the active ingredient in Forslean..so if you are taking Forslean, you might want to reconsider stopping it as it may interfere with the effectiveness of Provigil.

There may be other factors too; I'm typing fast.

I can feel Provigil aka modafinil within about 20 minutes from when I take it on an empty stomach. It may have optimum plasma levels later, but I can still feel it pretty quick after I take it.

I take immediately after awakening -- on an empty stomach (it's quite a mouthful, but worth it):

250 mg Provigil
2.1 grams GeroNova ALCAR
900 mg GeroNova RLAMCT25
1 gram L-arginine HCL
800 mg oxiracetam
75 mg Atomoxetine HCL
4.5 mg Hydergine FAS

I weigh 90 kgs or 200 lbs.

Gets my morning a real jump start.

Combining Hydergine and Modafinil (Provigil) may be slightly counterproductive, as the former acts as an alpha-1 receptor antagonist (J Pharmacol. 1985;16 Suppl 3:1-17.) while Modafinil works on the same receptor as an agonist (Pharmacol Biochem Behav. 2002 Nov;73(4):971-8).

[doug123]

[quote name='da_sense'][quote name='theone999']
alex, the time needed for modafinil to peak in plasma concentration is 2-4 hrs, and delayed up to one hour if taken with food. you sure it's not a placebo effect?
I've been taking it for a week now, and on no occasion did i feel any euphoria or anxiety at 200mg. If anything it can feel weaker than my 1st dose sometimes.[/quote]

Bad side of modafinil is it needs at least 1 h to start feeling it...slow onset, everyone i know experienced this. I even tried sublingual but didn't help much.
[/quote]

The time it takes a drug to exert its effect is not a side effect.

[quote name='http://www.medterms.com/script/main/art.asp?articlekey=5489']Definition of Side effects

Side effects: Problems that occur when treatment goes beyond the desired effect. Or problems that occur in addition to the desired therapeutic effect.

Example -- A hemorrhage from the use of too much anticoagulant (such as heparin) is a side effect caused by treatment going beyond the desired effect.

Example -- The common side effects of cancer treatment including fatigue, nausea, vomiting, decreased blood cell counts, hair loss, and mouth sores are instances of side effects that occur in addition to the desired therapeutic effect.

Drug manufacturers are required to list all known side effects of their products. When side effects of necessary medication are severe, sometimes a second medication, lifestyle change, dietary change, or other measure may help to minimize them.[/quote]

I have been taking Provigil aka Modafinil (or adrafinil) for about 4 years, and my metabolism must be pretty quick; when I take 200mg on an empty stomach I can feel it within 20 or 30 minutes.

[doug123]

Combining Hydergine and Modafinil (Provigil) may be slightly counterproductive, as the former acts as an alpha-1 receptor antagonist (J Pharmacol. 1985;16 Suppl 3:1-17.) while Modafinil works on the same receptor as an agonist (Pharmacol Biochem Behav. 2002 Nov;73(4):971-8).

That is an astute observation. I have been taking this combination for a while and experienced no particularly negative side effects; maybe that is because Hydergine is a weak antagonist?

Have these effects been confirmed in vivo? I'd check the references but got to get studying for a quiz I have at 10am.

[dopamine]

This is a different study than the one referenced, but attempts to show the in vivo effect of co-dergocrine mesylates on alpha-adrenoceptors

Eur J Pharmacol. 1983 Sep 30;93(3-4):159-68.

Interaction of ergot alkaloids and their combination (co-dergocrine) with alpha-adrenoceptors in the CNS.

Markstein R, Closse A, Frick W.

Co-dergocrine (Hydergine), composed of four dihydrogenated peptide ergot alkaloids (dihydroergocornine, dihydroergocristine, dihydro-alpha-ergokryptine and dihydro-beta-ergokryptine), has been reported to interact with alpha-adrenoceptors. The effect of the combination and its individual components on alpha-adrenoceptors subtypes in the rat brain was investigated in the present study. All five ergot drugs displaced [3H]rauwolscine, [3H]clonidine and [3H]WB 4101 from specific binding sites in membrane preparations from rat and bovine brain at nanomolar concentrations. In rat cerebral occipital cortex slices, the ergot drugs inhibited 1-noradrenaline-stimulated cyclic AMP formation (alpha 1-adrenoceptor test) and facilitated electrically evoked noradrenaline release (alpha 2-adrenoceptor test) at nanomolar concentrations. The results from the functional tests suggest that the ergot drugs have a slightly higher affinity to alpha 2-adrenoceptors which are antagonised in a competitive manner. The alpha 1-adrenoceptors are antagonised by the ergot drugs in a non-competitive manner. The relative order of potency at both receptor types was similar in that dihydroergocornine, dihydro-alpha-ergokryptine and dihydro-beta-ergokryptine were equipotent, whereas dihydroergocristine was less potent. The effect of the combination of the ergot alkaloids at both alpha-adrenoceptors appears to reflect the summation of the contributions of its components. The differences seen in the functional tests were less pronounced in the binding tests.

Interestingly, this study shows that Hydergine also antagonizes the alpha-2 receptor, which when stimulated decreases the release of norepinephrine. So the substance itself has somewhat contradictory effects on the monoaminergic system. The best description of Hydergine's activity, IMO, is in the following study -

J Pharmacol. 1985;16 Suppl 3:1-17.

Hydergine: interaction with the neurotransmitter systems in the central nervous system.

[Article in English, French]

Markstein R.

Hydergine (co-dergocrine, ergoloid mesylates, dihydroergotoxine) is an ergot preparation which has been shown to be of value in the treatment of senile mental impairment. Results from biochemical in vitro investigations suggest that Hydergine interacts directly with subtypes of alpha-adrenoceptors, dopamine and serotonin receptors. For instance, in slices of rat cerebral cortex, it blocked noradrenaline-induced increase of cyclic AMP content and facilitated electrically evoked noradrenaline release which is consistent with antagonistic properties at postsynaptic alpha 1- and presynaptic alpha 2-adrenoceptors. Furthermore, Hydergine had mixed agonist/antagonist properties at postsynaptic D1 receptors mediating stimulation of adenylate cyclase, and at pre- and postsynaptic D2 receptors mediating inhibition of evoked dopamine and acetylcholine release in the rat striatum, respectively. Hydergine had also mixed agonist/antagonist properties at the serotonin-sensitive adenylate cyclase in the rat hippocampus and the presynaptic serotonin autoreceptors present on nerve terminals in the rat cortex. Based on these in vitro data, it is suggested that Hydergine influences central monoaminergic systems in a dualistic manner. On the one hand, it can compensate for a transmitter deficit in dopaminergic and serotoninergic systems, but at the same time, counteract a possible hyperactivity in the same transmitter systems. The noradrenergic systems may be affected in a similar way but by a different mechanism. In this latter system, Hydergine increased evoked noradrenaline release by blocking presynaptic alpha-adrenergic autoreceptors, but by a simultaneous blockade of postsynaptic alpha 1-adrenoceptors sets a ceiling effect to the noradrenergic stimulation. Thus, Hydergine might be able to counteract and prevent disturbances in the interplay between monoaminergic and other transmitter systems in the central nervous system. It is proposed that these multiple effects of Hydergine are in part responsible for its beneficial effects in senile mental impairment.

So, in effect, Hydergine serves as a limiting factor for noradrenergic neurotransmission, setting the essential boundaries for how much stimulation is "allowed" in the affected regions of the brain. My guess would be that, if the Modafinil is producing noradrenergic stimulation above the ceiling effect which Hydergine produces, then the stimulatory effects of Modafinil will be proportionally decreased via competition with the alpha-1 receptor.

[doug123]

I take several drugs that have conflicting receptor antagonistic/agonistic profiles. It's just a question of extent. Caffeine has been shown to antagonized by theanine (mg for mg!) in rats, and I take both... Hydergine, for what it's worth, appears to be very mild. I've been taking Hydergine FAS for about two and a half years along with my Provigil, no problems thus far. However, bromocriptine is another ergot I learned should not be messed with. It's a POTENT Dopamine 2 receptor agonist, not just any old agonist...

Peace out...
http://www.ncbi.nlm....l=pubmed_docsum

Biosci Biotechnol Biochem. 2000 Feb;64(2):287-93. 

Inhibiting effects of theanine on caffeine stimulation evaluated by EEG in the rat.

Kakuda T, Nozawa A, Unno T, Okamura N, Okai O.

Central Research Institute, Itoen Ltd., Shizuoka, Japan. ITN00527@nifty.ne.jp

In this study, the inhibiting action of theanine on the excitation by caffeine at the concentration regularly associated with drinking tea was investigated using electroencephalography (EEG) in rats. First, the stimulatory action by caffeine i.v. administration at a level higher than 5 micromol/kg (0.970 mg/kg) b.w. was shown by means of brain wave analysis, and this level was suggested as the minimum dose of caffeine as a stimulant. Next, the stimulatory effects of caffeine were inhibited by an i.v. administration of theanine at a level higher than 5 micromol/kg (0.781 mg/kg) b.w., and the results suggested that theanine has an antagonistic effect on caffeine's stimulatory action at an almost equivalent molar concentration. On the other hand, the excitatory effects were shown in the rat i.v. administered 1 and 2 micromol/kg (0.174 and 0.348 mg/kg) b.w. of theanine alone. These results suggested two effects of theanine, depending on its concentration.

    PMID: 10737183 [PubMed - indexed for MEDLINE]

Edited by nootropikamil, 25 March 2007 - 03:45 AM.

[doug123]

I said bad side as something that is not positive about it, not as side effect, another bad thing is that it's half life is 12-15h...

I see.

But a 12 hour half life is, in my opinion, a positive aspect of modafinil's chemical properties. When I first starting taking adrafinil four years ago (1200 mg a day), I found the solution to my lack of motivation and got out of bed without grumbling about it. I would wake up and get right up out of bed; which is not something I could do before -- ever -- normally (unless a young woman happens to be in bed with me).

Recently, this effect has disappeared. This might be due to the fact that I work out really hard and that might make me more tired in the morning. Or maybe because I am not all obsessed with setting curves in all of my classes anymore. Maybe next quarter this effect will re emerge...

[theone999]

Hey, after 2 nights of very short sleep being boosted on modafinil, i was hungry and ate a kitkat and drank a can of red bull. That was 4 hrs after 100mg of modafinil. Then an hour later, I assumed that the caffeine would make me hyper, but it had the exactly opposite effect. i was sitting on the sofa and nearly fell asleep. i was very relaxed and the best word i can think of is "warm" i felt warm, not that i was physically hot. Then after a while i felt slightly nauseous when i ate dinner. My BMP was 80 and pressure 130-90. Doenst' seem to be particularly high.
Felt weird... certainly didnt' expect 2 stimulants to react like this.

Any one else consuming caffeine on modafinil have similar effect?

[doug123]

I wouldn't take your experience from one day to translate across the rest of the days. You might want to see a qualified health care profesional to see if you might have ADD.

[debu]

I thought Modafinil was an off label treatment for ADD? I was diagnosed with ADD a long time ago, and I also don't respond well to Modafinil anymore. It gives me a cloudy thought process, and makes me feel a sort of dirty anxious focus. However I react much better to Modafinil if I take hydergine, maybe because of the counter effects?

[exigentsky]

Modafinil is no miracle and still relatively primitive compared to what I think a stimulant should be. It keeps me awake and functioning as if I was on 8 hours of sleep when in reality I had less than two. Very useful for procrastinators! However, I can't say it helps in any other area. In the end, nothing is better than sleep and no drug will replace this primal need. All modafinil does is delay the symptoms of sleep deprivation.

[debu]

just to add some anecdotal stuff...I soaked in some epsom salts last night (magnesium) after a workout, this morning I took some Modafinil and seem to be tolerating it a lot better. Anyone experiencing anxiety or bad effects from it might try to supp Magnesium and see if this helps.

[alexoverhere]

alex, the time needed for modafinil to peak in plasma concentration is 2-4 hrs, and delayed up to one hour if taken with food. you sure it's not a placebo effect?
I've been taking it for a week now, and on no occasion did i feel any euphoria or anxiety at 200mg. If anything it can feel weaker than my 1st dose sometimes.

Bad side of modafinil is it needs at least 1 h to start feeling it...slow onset, everyone i know experienced this. I even tried sublingual but didn't help much.

theone999: I suppose it could be a placebo effect, but I feel it quickly every time I take (always on an empty stomach). Do you have any references about the time to actual onset of action?

The first time I ever took modafinil, I experienced extreme euphoria. It went away quickly (i.e., lessened dramtically on the second day and disappeared on the 3rd day), but I felt euphoria again for when I took modafinil after not taking it for ~3 weeks. Provigil's manufacturer, Cephalon, claims that modafinil might produce euphoric effects, and I've read of isolated reports of euphoria in summaries of clinical trials. Most of the current literature, however, seems finds no support for such effects (e.g., http://ajp.psychiatr...ull/163/6/1109), so it's probably something most people don't have to be concerned about.

[emerson]

Modafinil is no miracle and still relatively primitive compared to what I think a stimulant should be. It keeps me awake and functioning as if I was on 8 hours of sleep when in reality I had less than two. Very useful for procrastinators! However, I can't say it helps in any other area. In the end, nothing is better than sleep and no drug will replace this primal need. All modafinil does is delay the symptoms of sleep deprivation.

To be sure, sleep is the best way to go. I think getting eight hours sleep a night might be among the most powerful performance enhancing strategies available to the average westerner. That said, a fairly sizable chunk of the population winds up forcing themselves into the unfortunate position of being sleep deprived on a fairly regular basis. The student who also works full time, the rotating shift worker or even the most damned of the damned - employee at a startup. Taking some of the agony of the normal week away from them might not seem miraculous to some, but I'm betting to many of them it'd be little different than Jesus riding down on a talking dinosaur to lay his hands on them to remove the discomfort. Personally, I've been in my share of accidents. None of them horrors, but certainly times of suffering. And bad as they were, I would take any single one of them over the time I was juggling a full academic load, work, and a social life in the midst of a sleepless haze. And to shift a bit to metaphor, I don't think anyone would argue that continual use of aspirin is better than going to a doctor to have the cause of the pain cured. But if the cures a long time in the wait, I can really see someone mistaking their particular little pill for the hand of god.

[theone999]

hmm, emerson, have you heard of a drug currently in development called "Gaboxadol" made by Merck which could come on to the market as soon as sometime next year. That is supposed to make you need less sleep as it puts you in the deep stages of sleep for longer and quicker.

well that's a very short description anyway. try googling the term. There was also a big story about it in New Scientist 18th Febuary 2006 if anyone reads it.

[psy333che]

I would like to add that I am taking provigil (100mg. to 200mg)a day and one of the wonderful benefits I have found is that it keeps me awake and alert all day and I am having normal night sleeps finally which is why it was prescribed

I think that if anyone is having problems sleeping from it it is because they are taking later in the day and taking more then they need
The initial feeling is euphoric (first day only)when taking it but the effects are really subtle and beneficial
You are just more alert and don't feel tired during the day and my sleep pattern seem much better since I have been taking them

From what I have read here from many different types and variables of provigil that many are taking here and what seem to be very large amounts and all times of the day

Most are taking it incorrectly and are expecting it to be like an amphetamine.
It really is an incredible drug
People are different in the way it effects you and I know quite a few people who take it

200mg is really the most you can take in a day for it to have a beneficial effect
if you are expecting anymore then this is not a drug for you
June

[emerson]

hmm, emerson, have you heard of a drug currently in development called "Gaboxadol" made by Merck which could come on to the market as soon as sometime next year. That is supposed to make you need less sleep as it puts you in the deep stages of sleep for longer and quicker.

well that's a very short description anyway. try googling the term. There was also a big story about it in New Scientist 18th Febuary 2006 if anyone reads it.

I caught this one a bit late! Gaboxadol's been on the periphery of my awareness for a while now, stuck in a limbo of "check on in a more in-depth manner when time permits." Time, it seems, is often very stingy with that notebook of permission slips.

From what I've heard in a kind of off-hand, tiny google input, occasional blurb among a larger text here, it definitely sounds interesting for a number of reasons. Not even just for potential benefit, but also for the fact that it's great all around for any new experimental evidence of the human brain's hidden gears and motors.