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How to Potentiate Modafinil


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#31 aLurker

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Posted 28 July 2010 - 03:52 PM

So what's good for IQ>140 then?

#32 Animal

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Posted 28 July 2010 - 06:14 PM

So what's good for IQ>140 then?


Regularly using it to it's full extent. I find it's too easy in modern society to settle into a routine and run on minimal brain power for an indefinite amount of time.

My suggestion is to join a high IQ society and befriend fellow members, participate in the IRC chat and physical meetings, read the monthly journal, join the network (in my case based on XING)and generally integrate yourself with people who can challenge or even surpass you intellectually. You'd think that all people do in high IQ societies is get together and have a circle jerk about how great they are, but in actuality most of the members of the Triple Nine Society I've associated with are modest and friendly, with many of them having been ostracised in some way because of their IQ's.

Seriously, meeting someone with an IQ above 170 is enlightening and humbling at the same time, and it encourages you to push yourself just so you can keep up with them in more abstract conversation. It's quite striking how eccentric individuals with IQ's over 170 seem to be, it's like a ceiling is hit where their cognitive processes appear to interfere with their ability to function effectively socially, very interesting people to talk to in my experience. The most intelligent (g wise) individual I've ever met had an IQ of 187, but he was an arrogant twat who thought the general populace were refuse that the planet should be cleansed of, as if IQ is the measure of a person. :dry:
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#33 NR2(x)

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Posted 29 July 2010 - 10:51 AM

Modafinil has negative effects on higher levels of intelligence; hardly significant tho.
I find it good because I have working memory deficits. I was assessed as a child to have a Verbal IQ of 182 but a performance IQ 100, I was not given an overall IQ.
Bang on animal; I definitly agree that hangout with people far smarter than you is the way to proceed, but feel that many High IQ societies will be filled with people in a losers routine, like you said.
Donepezil is a mixed bag, it makes you sleepy and this gets worse with time. Nicotine is more balanced.

#34 chrono

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Posted 31 July 2010 - 02:30 AM

I think I read somewhere that milk thistle decreases the enzymes that break down modafinil. Has anyone seen this somewhere?

Most discussion I've seen of this implies that milk thistle is good for protecting the liver from the possible (but rare) adverse effects modafinil might cause.

A mechanism for preventing tolerance was proposed in Milk thistle + modafinil = less tolerance, but I can't say if it's plausible or not.

#35 FunkOdyssey

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Posted 31 July 2010 - 01:46 PM

I think I read somewhere that milk thistle decreases the enzymes that break down modafinil. Has anyone seen this somewhere?

Most discussion I've seen of this implies that milk thistle is good for protecting the liver from the possible (but rare) adverse effects modafinil might cause.

A mechanism for preventing tolerance was proposed in Milk thistle + modafinil = less tolerance, but I can't say if it's plausible or not.


It wouldn't prevent CNS tolerance but it may prevent a reduction of modafinil bioavailability and/or half-life that would occur over time due to modafinil's induction of CYP3A4 which its also a subtrate of. Milk Thistle is a CYP3A4 inhibitor.

Its probably impossible to say what the net effect on CYP3A4 would be after combining them, or what dose of milk thistle would be effective.

edit: doesn't seem to be an effective CYP3A4 inhibitor in vivo-

Clin Cancer Res. 2005 Nov 1;11(21):7800-6.
Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan.

van Erp NP, Baker SD, Zhao M, Rudek MA, Guchelaar HJ, Nortier JW, Sparreboom A, Gelderblom H.

Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, the Netherlands.
Abstract

PURPOSE: Milk thistle (Silybum marianum) is one of the most commonly used herbal therapies, and its principal constituent silybin significantly inhibits cytochrome P450 isoform 3A4 (CYP3A4) and UDP glucuronosyltransferase isoform 1A1 (UGT1A1) in vitro. Here, we investigated whether milk thistle affects the pharmacokinetics of irinotecan, a substrate for CYP3A4 and UGT1A1, in humans. EXPERIMENTAL DESIGN: Six cancer patients were treated with irinotecan (dose, 125 mg/m(2)) given as a 90-minute infusion once every week. Four days before the second dose, patients received 200 mg milk thistle, thrice a day, for 14 consecutive days. Pharmacokinetic studies of irinotecan and its metabolites 7-ethyl-10-hydroxycamptothecin (SN-38), 7-ethyl-10-[3,4,5-trihydroxy-pyran-2-carboxylic acid]-camptothecin (SN-38-glucuronide), and 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin were done during the first three irinotecan administrations. RESULTS: Short-term (4 days) or more prolonged intake of milk thistle (12 days) had no significant effect on irinotecan clearance (mean, 31.2 versus 25.4 versus 25.6 L/h; P = 0.16). The area under the curve ratio of SN-38 and irinotecan was slightly decreased by milk thistle (2.58% versus 2.23% versus 2.17%; P = 0.047), whereas the relative extent of glucuronidation of SN-38 was similar (10.8 versus 13.5 versus 13.1; P = 0.64). Likewise, the area under the curve ratio of 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin and irinotecan was unaffected by milk thistle (0.332 versus 0.285 versus 0.337; P = 0.53). The maximum plasma concentrations of silybin ranged between 0.0249 and 0.257 micromol/L. CONCLUSIONS: Silybin concentrations after intake of milk thistle are too low to significantly affect the function of CYP3A4 and UGT1A1 in vivo, indicating that milk thistle is unlikely to alter the disposition of anticancer drugs metabolized by these enzymes.

PMID: 16278402


Edited by FunkOdyssey, 31 July 2010 - 02:31 PM.

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#36 chrono

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Posted 01 August 2010 - 02:55 AM

Thanks for clearing that up. Guess it might just be useful for putative liver protection if your dose is high/prolonged.

Piperine is probably a good CYP3A4 inhibitor [1] [2], so might be worth using if you're inclined to take an unquantified stab at the net effect.

#37 chrono

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Posted 04 August 2010 - 01:40 AM

A few abstracts on the correlation with intelligence:

Effects of modafinil on working memory processes in humans.
Müller U, Steffenhagen N, Regenthal R, Bublak P.
Department of Psychiatry, University of Leipzig

RATIONALE: Modafinil is a well-tolerated psychostimulant drug with low addictive potential that is used to treat patients with narcolepsy or attention deficit disorders and to enhance vigilance in sleep-deprived military personal. So far, understanding of the cognitive enhancing effects of modafinil and the relevant neurobiological mechanisms are incomplete. OBJECTIVES: The aim of this study was to investigate the effects of modafinil on working memory processes in humans and how they are related to noradrenergic stimulation of the prefrontal cortex. METHODS: Sixteen healthy volunteers (aged 20-29 years) received either modafinil 200 mg or placebo using a double blind crossover design. Two computerized working memory tasks were administered, a numeric manipulation task that requires short-term maintenance of digit-sequences and different degrees of manipulation as well as delayed matching task that assesses maintenance of visuo-spatial information over varying delay lengths. The battery was supplemented by standardized paper pencil tasks of attentional functions. RESULTS: Modafinil significantly reduced error rates in the long delay condition of the visuo-spatial task and in the manipulation conditions, but not in the maintenance condition of the numeric task. Analyses of reaction times showed no speed-accuracy trade-off. Attentional control tasks (letter cancellation, trail-making, catch trials) were not affected by modafinil. CONCLUSIONS: In healthy volunteers without sleep deprivation modafinil has subtle stimulating effects on maintenance and manipulation processes in relatively difficult and monotonous working memory tasks, especially in lower performing subjects. Overlapping attentional and working memory processes have to be considered when studying the noradrenergic modulation of the prefrontal cortex.

PMID: 15221200 [PubMed - indexed for MEDLINE]


This one suggests that, in addition to the measure of sustained attention only increasing in the low IQ group, they were also the only ones to suffer a reduction in speed:

Cognitive effects of modafinil in student volunteers may depend on IQ.
Randall DC, Shneerson JM, File SE.
Psychopharmacology Research Unit, King's College London

The results of two previous studies on the effects of modafinil, a selective wakefulness-promoting agent, in healthy university students were combined in a retrospective analysis. This allowed determination of whether the effects of modafinil were dependent on IQ and whether the larger sample size (n=89) would reveal more cognitive benefits. A battery of cognitive tests was completed 2-3 h after dosing. In the whole sample, modafinil (200 mg) significantly reduced the number of missed targets in a test of sustained attention (RVIP). However, interestingly, several interactions between modafinil and IQ emerged. Modafinil (100 and 200 mg) significantly improved target sensitivity in the RVIP test, but only in the group of 'lower' IQ (mean+/-sem=106+/-0.6), not in the 'higher' IQ group (mean+/-sem=115.5+/-0.5). Furthermore, there were significant modafinil x IQ interactions in two further tests. Modafinil significantly reduced speed of responding in a colour naming of dots, and in clock drawing, but only in the 'lower' IQ group. Thus, the cognitive benefits of modafinil seem particularly marked in tests of vigilance and speed, in which sleepiness would be an important factor. Furthermore, the results indicate that high IQ may limit detection of modafinil's positive effects.

PMID: 16140369 [PubMed - indexed for MEDLINE]



#38 chilp

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Posted 04 August 2010 - 07:26 AM

Thanks for these studies chrono.

#39 Neuronic

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Posted 07 August 2010 - 08:22 PM

I am very interested in this topic myself. I found modafinil to be losing it's effects after a few months. I started taking deprenyl in addition and I found modafinil to work great. It brightened my mood and was great. The effects lasted the whole 5 months I took it. I have only taken modafinil for 2 months and it barely work now.
So Animal is right on deprenyl, you just have to wait a good 2 weeks to see.

If I knew it was safe to take it with GHB I would start taking it again.

#40 soulfiremage

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Posted 30 September 2010 - 05:01 PM

I'm using modifinal 200mg with 100mg caffeine and 8mg galantamine in the morning.


My first day gave me euphoria, mild jitters etc-however that may be caffeine in concert. I'm getting powder shortly, so will have modifinil only. I was concerned about tolerance after a few days, however it seems that other experience tolerance after much longer usage, so my weekend break will help.


I have a major problem with IQ scores. They seem to measure something way too ephemeral to be useful as a real measure and predictor of individual intelligence. They don't take into account multiple aspects of any one mind, the different personalities etc. I've had all kinds of scores until I learnt to stop bothering with them-they were more about ego satisfaction and security than any reality. I accept that certain tests can establish a temporary context for the study of drug affects, though it's an artificial baseline. These scores are too varient with mood and even recent experience. If I spend a week programming, something that I'm a novice at, the work involved will jump up any scores on all kinds of tests. The same, in reverse, goes for a week on the drink or similar.

A property so seemingly labile, to me, seems illusionary. Anyway that's a whole other debate.

The galantimine and modifinal enhance my attention quite pointedly, until quite late at night. This combo is highly useful to me. Whether I try more than 200mg, is another matter!
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#41 longevitynow

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Posted 30 September 2010 - 09:34 PM

My modafanil experience is limited, just a few samples from my doc. But to post from my limited experience, I did find Piracetam to enhance the effect. I tend to feel mentally alert but a little physically tired with modafanil. The physical tiredness was lessened with Piracetam, as well as the duration of my focus (taking 3-4000 mg Piracetam at the same time as Modafanil and another 2-3000 mg 5-6 hours later). Caffeine seemed to help also, but for me tea more than coffee as coffee makes me wired/antsy/not able to sit still. DHEA and adrenal glandulars seem to help also (I imagine the modafanil is draining some stimulant neurotransmitter pathways and the DHEA and glandulars help replenish them--would imagine Tyrosine and Phenylalanine would also, but didn't try those).

#42 someidiot

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Posted 08 November 2010 - 03:12 PM

Betahistine? Just a conjecture...

#43 Orajel

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Posted 16 May 2012 - 06:51 PM

Have you tried bergomottin? I'm not sure how expensive it is in supplement form, but it's a relatively powerful CYP3A4 inhibitor

#44 Junk Master

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Posted 16 May 2012 - 10:07 PM

"The stimulating action of modafinil was increased by chlorination, but decreased by methylation."



http://www.ncbi.nlm....pubmed/15005110

#45 Cephalon

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Posted 17 May 2012 - 01:11 PM

In my experience Noopept enhances Modafinil alot, but I don't know how safe the combo is. No idea if they share similar methods of action. Both should have impact on Glutamate receptors I guess.

Otherwise Caffeine is my number one Modafinil stack - but if that lost effect for the OP I can just come up with Noopept. ..

#46 zeropoint

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Posted 19 May 2012 - 06:34 PM

I am very interested in this topic myself. I found modafinil to be losing it's effects after a few months. I started taking deprenyl in addition and I found modafinil to work great. It brightened my mood and was great. The effects lasted the whole 5 months I took it. I have only taken modafinil for 2 months and it barely work now.
So Animal is right on deprenyl, you just have to wait a good 2 weeks to see.

If I knew it was safe to take it with GHB I would start taking it again.


Those tolerance effects make taking modafinil everyday a waste of money....haven't tried the deprenyl addition so that may be a good suggestion.
I get insomnia about once a week and using modafinil after a poor night sleep is where it really shines, sleep deprivation causes lowered mental performance and memory that is helped significantly. Just taking modafinil after a good night's sleep most times doesn't seem to do much, no matter what dose.


#47 Junk Master

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Posted 20 May 2012 - 03:42 PM

Modafinil fell out of favor with the military because of rapid tolerance. There's just such a huge difference between the first time you take 400 mg and the second day.

#48 Ampa-omega

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Posted 20 May 2012 - 05:13 PM

Modafinil fell out of favor with the military because of rapid tolerance. There's just such a huge difference between the first time you take 400 mg and the second day.


that really really sucks, anyone know what the mechanism is of modafinil tolerance?
does it have something to do with orexin histamine receptors becoming downregulated?

maybe taking histamine receptor antagonist at night increase the receptor sensitivity in the day ?

Edited by Ampa-omega, 20 May 2012 - 05:26 PM.


#49 zeropoint

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Posted 20 May 2012 - 06:11 PM

"The stimulating action of modafinil was increased by chlorination, but decreased by methylation."



http://www.ncbi.nlm....pubmed/15005110


Is this chlorination in vivo? or in vitro? I,m assuming in vitro.

#50 Isochroma

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Posted 19 March 2013 - 01:14 AM

Found this on Erowid:

Hard to Completely Give Up
Adrafinil (Olmifon) & Milk Thistle
by jetgirl
Citation: jetgirl. "Hard to Completely Give Up: experience with Adrafinil (Olmifon) & Milk Thistle (ID 74830)". Erowid.org. Apr 22, 2009. erowid.org/exp/74830

DOSE: oral Adrafinil oral Milk Thistle
BODY WEIGHT: 150 lb

First I'd like to mention, that at least in my experience, milk thistle, when taken in concert with *anything* causes it to have a much longer tail. In other words, taking milk thistle causes any drug to stay around in my system for a period of several days, instead of the hours that would be experienced by the average user.

So, I've discovered that combining milk thistle with olmifon allows me to take only the tiniest fragment of a pill and still reap the benefits as if I'd taken the whole thing.

Like most stimulants, it gets me to gladly engage in tedious work, like programming or sorting things or cleaning the apartment. But unlike other stimulants, it doesn't interfere *as much* with falling asleep. However, unlike other reports, maybe because of the milk thistle, I find I don't sleep as well as I would like. In fact, after stopping it, I find I need to sleep heavily for several days afterwards, like 20 hours a day heavily. But there's nothing like a deep sleep with snoring and deep deep slow breathing, so it's okay.

About 3 hours after taking it, I notice that my eyes and nose feel cold. I don't like that feeling, I can counteract it a bit with a decoction of warming herbs like ginger and cinnamon. That feeling goes away after 6 hours.

I feel this is a premiere stimulant with none of the irritability or negativity caused by caffeine. But it does have the same soul-sucking side effects of other stimulants that causes me to feel emotionally hollow. After several days of using it I become quite wound up so that an unexpected random noise will cause me to be startled and shiver deeply. Social relationships get strained without me being aware of why. Ultimate I wind up too tense to relate to anyone naturally, but it is so great for tedious tasks as mentioned, that it's hard to completely give it up.


Exp Year: 2008 ID: 74830 Gender: Female Age at time of experience: Not Given Added: Apr 22, 2009

Edited by Isochroma-Reborn, 19 March 2013 - 01:15 AM.

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#51 noot_in_the_sky

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Posted 10 May 2013 - 08:08 PM

Interesting finding isochorma, I wounder if anyone else here have felt a similar effect?

In other matters, some people in other forums have claim to had used pramipexole(.5mg) together with modafinil.

bdog527 said:

I think at lower doses you are preferentially hitting autoreceptors thereby reducing DA output.I've worked up to .5mg b.i.d. and it is working quite well for mood and anxiety. It combines very well with modafinil, in my opinion there is a definite synergy between the two. The modafinil attenuates the somnolence and the pramipexole ameliorates the anxiety and overfocus that I can get from the former.As an aside I've noticed a leaning and hardening effect on my physique yet my weight has gone up. It can't be in my head because my pants fit are fitting looser.

For me personally, the combination of pramipexole and modafinil is simply awesome. It's like Adderall without the anxiety. I've never taken d-amp before but what I'm feeling is pure mental energy and enthusiasm for my work and hobbies and no physical discomfort. If anyone here plans to try pramipexole I highly recommend procuring some modafinil or even adrafinil and try running them together.

Oh I also set a 1 rep and 5 rep max on my bench last night and it was ridiculous how easily it went up. My bench is my toughest lift to improve so I am very pleased. My neurons must be in perfect synchronicity.


http://www.mindandmu...-mirapex-3.html

Edited by noot_in_the_sky, 10 May 2013 - 08:08 PM.


#52 soulfiremage

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Posted 11 May 2013 - 12:04 AM

Serious scientists still come out with IQ scores? Thought that singular measure was discredited. Don't get me wrong, I've a personal reason for wanting it to be valid-I got a decent score years ago but I just have skepticism of the score and the idea we can prove a cut off point for a drugs improvement using this.

Damn bed time ipad posting is painful!

I did consider importing a kg of moda as my source has quit selling.

Tried real grapefruit juice?

Or instead tdcs :)

I am uk based and just got one from http://www.trans-cranial.com/. Works well.

#53 blueinfinity

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Posted 15 May 2013 - 06:46 PM

Modafinil fell out of favor with the military because of rapid tolerance. There's just such a huge difference between the first time you take 400 mg and the second day.

Modafinil fell out of favor with the military because of rapid tolerance. There's just such a huge difference between the first time you take 400 mg and the second day.


that really really sucks, anyone know what the mechanism is of modafinil tolerance?
does it have something to do with orexin histamine receptors becoming downregulated?

maybe taking histamine receptor antagonist at night increase the receptor sensitivity in the day ?


I would also like to know, I want modafinil, where can i get this in the US (california)

and it seems most people that have tried still have it and use it, any cons/negatives?

#54 FocusPocus

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Posted 05 July 2013 - 08:07 PM

I wish the OriginalPoster would come back here since he disappeared a year back; and tell us how the red pill (Modafinil and Donepezil) worked for him!

Wishful thinking ;) :sad: that is!

Edited by tarsuc, 05 July 2013 - 08:12 PM.


#55 machete234

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Posted 07 July 2013 - 06:21 PM

Whats with this combination of forskolin and artichoce extract?
I heard on a podcast that it comes somewhere close to modafinil.

#56 norepinephrine

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Posted 07 July 2013 - 07:44 PM

See chemically-induced long-term potentiation thread.

See chemically-induced long-term potentiation thread.

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#57 machete234

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Posted 07 July 2013 - 10:18 PM

See chemically-induced long-term potentiation thread.

See chemically-induced long-term potentiation thread.


Exactly, you could maybe use that combination to lower your modafinil intake with a similar wakefulness.





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