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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 10 of 10. This is the beginning of the thread.
Posted by Polarized on September 1, 2012, at 10:56:05
I have recently started Nuvigil.
I was put on 150 mg, the smaller of the 2 standard doses (the other is 250 mg). I am "medication sensitive", meaning that it takes less medication for me to achieve the desired effect.
150 proved to be to much for me. The main effect was a very elevated sense of energy, especially physically but also psychologically. There was also the sense of euphoria that is mentioned in the Pharmaceautical company's publication.
I then cut down to 50 mg, which was fine and achieved the desired effects, but within 2 weeks was up to 75 mg. 75 mg had a relatively strong effect, but now 3 weeks later that has also subsided. I should be able to stay on 75, but it's not the same as it was 3 weeks ago.
Here is my question: did anyone with experience with this medication feel an almost immediate increase in tolerance?
What's your experiences? Tolerance build-up? Euphoria?
Thanks.
Posted by rjlockhart37 on September 2, 2012, at 0:01:59
In reply to Nuvigil / Provigil Effects, posted by Polarized on September 1, 2012, at 10:56:05
Nuvgil is more fo wakefulness....this defeintly is not a proven fact but I heard provigil is better for the mood....i've read articles of how its mood bringtner....i mean the only diffrence with that is nuvgil is one isomer from provigil.
But still yes it can have a wakefulness feeling that increases NE and some dopamine...it would increase much if you started Nemanda.
rj
Posted by AlexCanada on September 2, 2012, at 15:18:31
In reply to Nuvigil / Provigil Effects, posted by Polarized on September 1, 2012, at 10:56:05
provigil would keep building tolerance for me. usually giving it a break for a few days would help in this regard. mood brightening? i think a bit. it helped more with energy, feeling alert, improvement to cognition but appeared to produce a bit of a crash in late evening where i'd feel empty and quite procrastinated.
> I have recently started Nuvigil.
>
> I was put on 150 mg, the smaller of the 2 standard doses (the other is 250 mg). I am "medication sensitive", meaning that it takes less medication for me to achieve the desired effect.
>
> 150 proved to be to much for me. The main effect was a very elevated sense of energy, especially physically but also psychologically. There was also the sense of euphoria that is mentioned in the Pharmaceautical company's publication.
>
> I then cut down to 50 mg, which was fine and achieved the desired effects, but within 2 weeks was up to 75 mg. 75 mg had a relatively strong effect, but now 3 weeks later that has also subsided. I should be able to stay on 75, but it's not the same as it was 3 weeks ago.
>
> Here is my question: did anyone with experience with this medication feel an almost immediate increase in tolerance?
>
> What's your experiences? Tolerance build-up? Euphoria?
>
> Thanks.
>
Posted by Polarized on September 2, 2012, at 17:02:50
In reply to Re: Nuvigil / Provigil Effects, posted by AlexCanada on September 2, 2012, at 15:18:31
> provigil would keep building tolerance for me. usually giving it a break for a few days would help in this regard. mood brightening? i think a bit. it helped more with energy, feeling alert, improvement to cognition but appeared to produce a bit of a crash in late evening where i'd feel empty and quite procrastinated.
Thanks Alex for the advice. I think I'll try cutting down to 50 mg on weekends, then back to 75 during the week.
Has anyone with a tendency toward mania has any issues with Nuvigil/Provigil and mania?Supposedly the medication does not induce it, and my Dr. said it doesn't based both on knowledge of the medication as well as his clinical experience with it, but the Pharmaceautical company's documentation lists it as a possible side effect.
Posted by pedr on September 3, 2012, at 15:15:20
In reply to Nuvigil / Provigil Effects, posted by Polarized on September 1, 2012, at 10:56:05
I've only tried Provigil but I gather it's very similar to nuvigil. I experience very rapidl acclimation to it. After taking it for a week or two, it makes me more tired rather than more awake.
Pete
Posted by phidippus on September 3, 2012, at 22:14:56
In reply to Nuvigil / Provigil Effects, posted by Polarized on September 1, 2012, at 10:56:05
I did not experience any kind of tolerance with Nuvigil. I was taking 250 mg and lovingg it. I did get euphoria, but other than that I enjoy its energizing quality.
Unfortunately, Nuvigil triggered a mixed state and I decided to stop the drug.
What's funny is no one seems to know how this drug works.
Eric
Posted by SLS on September 3, 2012, at 23:05:23
In reply to Re: Nuvigil / Provigil Effects » Polarized, posted by phidippus on September 3, 2012, at 22:14:56
> I did not experience any kind of tolerance with Nuvigil. I was taking 250 mg and lovingg it. I did get euphoria, but other than that I enjoy its energizing quality.
>
> Unfortunately, Nuvigil triggered a mixed state and I decided to stop the drug.
>
> What's funny is no one seems to know how this drug works.
>
> Eric
Is it different from Provigil?I don't know what the latest is on Provigil, but it does increase orexinergic flow from the hypothalamus, eventually activating histaminergic neurons. I have also read that it increases dopamine as well, but I don't know how it accomplishes this.
- Scott
Posted by phidippus on September 3, 2012, at 23:50:45
In reply to Re: Nuvigil / Provigil Effects » phidippus, posted by SLS on September 3, 2012, at 23:05:23
I have no idea how it differs from Provivgil-I haven't looked into it.
This is pretty typical about what I find on Nuvigil:
"Mechanism of Action and Pharmacology
The precise mechanism(s) through which armodafinil (R-enantiomer) or modafinil (mixture of R- and S-enantiomers) promote wakefulness is unknown. Both armodafinil and modafinil have shown similar pharmacological properties in nonclinical animal and in vitro studies, to the extent tested.
At pharmacologically relevant concentrations, armodafinil does not bind to or inhibit several receptors and enzymes potentially relevant for sleep/wake regulation, including those for serotonin, dopamine, adenosine, galanin, melatonin, melanocortin, orexin-1, orphanin, PACAP or benzodiazepines, or transporters for GABA, serotonin, norepinephrine, and choline or phosphodiesterase VI, COMT, GABA transaminase, and tyrosine hydroxylase. Modafinil does not inhibit the activity of MAO-B or phosphodiesterases II-IV."
A long list of what it doesn't do.
HOWEVER, plenty of literature points to it effecting dopamine somehow.
Eric
Posted by SLS on September 4, 2012, at 6:07:43
In reply to Re: Nuvigil / Provigil Effects » SLS, posted by phidippus on September 3, 2012, at 23:50:45
> A long list of what it doesn't do
A hypothalamic orexinergic/histaminergic pathway is involved in the pharmacology of modafinil.
I would say that this study helps to elucidate what modafinil does do. I am not sure how important dopamine reuptake inhibition is at clinically relevant concentrations. It is rather low in potency at the DAT.
- Scott
------------------------------------------------
Neurosci Lett. 2010 Oct 15;483(3):193-6. Epub 2010 Aug 7.
Modanifil activates the histaminergic system through the orexinergic neurons.
Ishizuka T, Murotani T, Yamatodani A.
SourceDepartment of Medical Science and Technology, Graduate School of Allied Health Sciences, Faculty of Medicine, Osaka University, Japan. ishizuka@cc.osaka-dent.ac.jp
AbstractModafinil is a drug used to treat hypersomnolence of narcolepsy. We previously reported that modafinil increases hypothalamic histamine release in rats but did not increase locomotor activity in histamine-depleted mice, suggesting that modafinil-induced locomotor activity involves the histaminergic system. Modafinil is also thought to express its effect through the orexinergic neurons, and orexin increases hypothalamic histamine release. These findings led us to investigate whether modafinil activates the histaminergic system via the orexinergic system. In the present study, we performed in vivo microdialysis and c-Fos immunohistochemistry to investigate whether the orexinergic system mediates the activation of the histaminergic system by modafinil using orexin neuron-deficient mice. Two hours after the injection, modafinil (150 mg/kg) caused a significant increase of histamine release compared to the basal release in wild type mice. However, modafinil had no effect on the histamine release in orexin neuron-deficient mice. By immunohistochemical study, we found that there was no neuronal activation in the tuberomammillary nucleus where the cell bodies of the histaminergic neurons exclusively exist in orexin neuron-deficient mice. These findings indicate that modafinil-induced increment of histamine release requires intact orexinergic neurons.
Posted by phidippus on September 4, 2012, at 15:41:02
In reply to Re: Nuvigil / Provigil Effects » phidippus, posted by SLS on September 3, 2012, at 23:05:23
Provigil and Nuvigil are both based on the drug Modafanil, so have similar modes of action.
Modafinil induces wakefulness in part by its action in the anterior hypothalamus. Its dopamine-releasing action in the nucleus accumbens is weak and dose-dependent.
Modafinil has central alpha 1-adrenergic agonist effects i.e. it directly stimulates the receptors. Modafinil also inhibits the reuptake of noradrenaline by the noradrenergic terminals on sleep-promoting neurons of ventrolateral preoptic nucleus (VLPO). More significant, perhaps, is its ability to increase excitatory glutamatergic transmission. This reduces local GABAergic transmission, thereby diminishing GABA(A) receptor signalling on the mesolimbic dopamine terminals.
Orexin neurons are activated by modafinil. Orexinergic neurons are found exclusively in the lateral hypothalamic area. Their activation is associated with enhanced pleasure-seeking and motivation as well as arousal. Orexinergic fibers project to the entire central nervous system.
Eric
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