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That Wacky Modafinil

pizzystrizzy said:
I'm not so sure -- I think psychiatrists would be happy to prescribe a drug that is not schedule II if it worked as well. Modafinil unfortunately doesn't really fit the bill. It certainly treats ADHD symptoms, but in terms of effect size, it isn't really much better than atomoxetine. It doesn't really compare to the effect sizes produced by the psychostimulants. http://www.medscape.com/viewarticle/461543

As far as regulatory matters are concerned, I think if no children had developed stevens-johnsons syndrome during the 2006 clinical trial, it probably would have been approved for ADHD.
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Those trials seemed really strange to me, I mean roughly 30% of the children reported rashes, and there were a couple possible cases of SJS that were not followed up for with biopsies. Also, with ~30000 off-label prescriptions in children as of 2007 and no reported cases of SJS and rashes being a rare side effect in the other populations... I'm not usually a conspiracy guy but I think there were some strings pulled to make atomoxetine the only "non-stimulant" ADHD drug on the market. Of the cases in younger individuals one had possible viral cause, one had other SJS causing medications and did not have a biopsy to confirm SJS (lamotrigine), and the last was on Zyprexa, Abilify, and Luvox (all known to have slight risks for SJS). Also, note how much is "unspecified" in the 15/M case.

http://www.fda.gov/Drugs/DrugSafety...afinilmarketedasProvigil:SeriousSkinReactions
 
pizzystrizzy said:
I'm not so sure -- I think psychiatrists would be happy to prescribe a drug that is not schedule II if it worked as well. Modafinil unfortunately doesn't really fit the bill. It certainly treats ADHD symptoms, but in terms of effect size, it isn't really much better than atomoxetine. It doesn't really compare to the effect sizes produced by the psychostimulants. http://www.medscape.com/viewarticle/461543.
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But contrary to atomoxetine modafinil is a stimulant, please refer to Ho-Chi-Minh's link above. The drug's promoters beating around the bush to avoid having it likened to other psychostimulants cannot hide the fact that it can and is being abused for similar reasons than methylphenidate. Also the manufacturer's claim that it has none of the side effects of methylphenidate may be true when therapeutic doses of modafinil are compared with abusive doses of methylphenidate but I can personally attest that modafinil taken at err, ... experimental doses carries a side effect profile that is difficult to tell from that of methylphenidate, the good and the bad. Taking into account that I'm strictly referring to oral MoA. One difference however is that modafinil is very long acting so you cannot repeatedly achieve the euphoric stage within a short period of time. This is a limiting factor for abuse but doesn't prevent it, and even prompts some users to engage in hazardous upper-downer cycles in order to be able to re-dose more often. Another claim that long onset prevents abuse is only valid as long as a user doesn't know what to expect. I know someone who sets her alarm at 4am to take the dose then goes back to sleep knowing the euphoric stage will wake her up at 6 and cut her appetite for breakfast so she can skip it. Absence of anorectic effect is also a mysth associated with the drug but it's not clear where it originates from considering the manufacturer admits appetite-suppressant effects.
 
Call it what you want, but the effect sizes are lower than those produced by amphetamine and methylphenidate, more on par with atomoxetine. In my experience, it mostly just made me wide awake. I'm sure it helps some people, but my experience matched with what the evidence suggests happens in the majority of cases.
 
Modafinil has very little to do with atomoxetine, what is known of its biochemistry (as per Ho-Chi-Minh's link, previously cited) and physiological action, both principal and side effects, draws a profile in close relationship with methylphenidate and dextroamphetamine. The main difference however is a much delayed onset and considerably longer duration. As with many other drugs of abuse this can subjectively affect the perception of potency, a good example being methaqualone vs strong but longer-acting benzo. Modafinil's patent holder no longer denies the drug's potential for abuse (evidence produced by and for the FDA to this effect is undeniable) but claims the longer duration of unpleasant side effects such as tachycardia and sleep-deprivation induced psychosis is an effective deterrent to abuse.

But, be that as it may, it only applies to the extent that the user won't counter the side effects by stacking with an appropriate CNS depressant/muscle relaxant 'suppressant'. Clonazepam is the drug of choice for this, but etizolam, oxazepam and even an ethanol/opiod combo are often used. All in relatively small dosage so that Modafinil blocks out recreational effects of the downers. What the abuser seeks is to be able to enjoy the positive effects of modafinil without having to pay the price on the short term. After individual calibration this allows users to abuse modafinil on a regular basis, leading to addiction.

I am 50 years old, I have been using uppers (all of them) for the purpose of work performance enhancement and, on occasion, for recreation for 35 years. I may not be a scientist but I consider myself an educated guinea pig. I can tell a real stimulant from a pseudo-stimulant like atomoxetine or buproprion. Even on paper it's obvious they won't get anyone euphoric. But modafinil can, and does for a majority of people. But some individuals are resistant, maybe you are. This can be due to natural brain chemistry, or use of other drugs, sometimes even trivial drugs like NSAID's or even certain foods can interfere with the psychoactive properties of a drug on one individual and not the next. To use myself as an example, cannabis has very little effect on me. I don't know why, but I know it's the same for certain other people.

I am not here to argue with you, if modafinil had no euphoric effect on me I would in large part share your opinion. But as the OP stated, modafinil is whacky.
 
Kilfer said:
Modafinil has very little to do with atomoxetine, what is known of its biochemistry (as per Ho-Chi-Minh's link, previously cited) and physiological action, both principal and side effects, draws a profile in close relationship with methylphenidate and dextroamphetamine.
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Perhaps we are having a miscommunication here. I am not suggesting that its mechanism of action or its pharmacological profile in general is at all similar to atomoxetine. The only similarity I have pointed out, and the only one that really seems all that relevant to me, is that they have very similar *effect sizes* in terms of their efficacy vis-a-vis adhd symptoms. In other words, I'm not saying that it works *like* atomoxetine, simply that it only works as well as atomoxetine. The effect sizes for both are substantially lower than those seen with methylphenidate or amphetamine. That doesn't mean that they don't work -- they do. And so does bupropion, and desipramine, etc. Modafinil appears to work better than those two, but worse than methylphenidate and amphetamine. I'm not sure if I can make this point in any other way.

I can tell a real stimulant from a pseudo-stimulant like atomoxetine or buproprion. Even on paper it's obvious they won't get anyone euphoric. But modafinil can, and does for a majority of people. But some individuals are resistant, maybe you are.
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I don't disagree with this. I'm sure it is more euphoric than bupropion and atomoxetine, as the latter two score lower on measures of 'liking' than caffeine. I could even concede that it is as euphoric as amphetamine (I don't think it is, but whether and to what extent it produces euphoria is neither here nor there). Methcathinone is a very euphoric stimulant, but I wouldn't consider it an effective treatment for ADHD.

That's really my only stake in this discussion. The few times I tried it, I took a low dose (200 mg IIRC) and my goal was not recreational. I found it to be similar to caffeine without the anxiety. That's not bad -- I like caffeine and find it helpful, so caffeine that doesn't produce anxiety and lasts 12 hours is impressive in my book. But it isn't amphetamine. Perhaps if I had taken a larger dose it would have seemed more similar. But at the doses tested in clinical trials, the effect sizes were smaller than those produced by d-amphetamine or methylphenidate, and nothing in my experience contradicts those findings.
 
pizzystrizzy said:
Perhaps we are having a miscommunication here. I am not suggesting that its mechanism of action or its pharmacological profile in general is at all similar to atomoxetine. The only similarity I have pointed out, and the only one that really seems all that relevant to me, is that they have very similar *effect sizes* in terms of their efficacy vis-a-vis adhd symptoms.
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Ah well, that changes the perspective. For my commentary was not about efficacy in treating ADHD, but abuse potential as a CNS stimulant. I admit limited knowledge about therapeutic benefits of modafinil in treating ADHD, outside of data published by various but not necessarily authoritative sources. I do not have ADHD, I was diagnosed with narcolepsy but that was back when the term included hypersomnia and chronic fatigue syndrome, conditions for which modafinil is deemed equally effective as MPH and dextro. I alternate MPH with modafinil but resist -not always successfully- taking downers with modafinil knowing it will inevitably lead to addiction.


In other words, I'm not saying that it works *like* atomoxetine, simply that it only works as well as atomoxetine. The effect sizes for both are substantially lower than those seen with methylphenidate or amphetamine. That doesn't mean that they don't work -- they do. And so does bupropion, and desipramine, etc. Modafinil appears to work better than those two, but worse than methylphenidate and amphetamine. I'm not sure if I can make this point in any other way.
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I get your point, I assure you. Maybe modafinil is the the proof that not all scheduled stimulants are indicated for the treatment of ADHD. I mean, not all stimulants outside of cocaine and (with one exception I think) cathinone analogs, which apparently are not useful for ADHD either, although I'm not sure why. Too short acting maybe?

I don't disagree with this. I'm sure it is more euphoric than bupropion and atomoxetine, as the latter two score lower on measures of 'liking' than caffeine. I could even concede that it is as euphoric as amphetamine (I don't think it is, but whether and to what extent it produces euphoria is neither here nor there). Methcathinone is a very euphoric stimulant, but I wouldn't consider it an effective treatment for ADHD.
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Trust me, once untoward side effects are suppressed modafinil high is barely distinguishable from amphetamine high, and lasts longer. But not as intense as coke. But therein lies the danger: modafinil side effects area easier to control. You can almost tailor the high to your liking... until sleep deprivation effects set in, and those cannot be suppressed. Personally I always keep on hand some chloral hydrate to knock me to sleep after 48 hours if I'm still up. And I don't drive after 24 hours without sleep regardless of how alert I feel.

That's really my only stake in this discussion. The few times I tried it, I took a low dose (200 mg IIRC) and my goal was not recreational. I found it to be similar to caffeine without the anxiety. That's not bad -- I like caffeine and find it helpful, so caffeine that doesn't produce anxiety and lasts 12 hours is impressive in my book. But it isn't amphetamine. Perhaps if I had taken a larger dose it would have seemed more similar. But at the doses tested in clinical trials, the effect sizes were smaller than those produced by d-amphetamine or methylphenidate, and nothing in my experience contradicts those findings.
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200mg is like 5mg of methylphenidate, not enough to experience euphoria.
 
WTF is Kilfer talking about? Germany actually UNSCHEDULED Modafinil because it was proven not to be abusable. Every study looking at it's effects in humans show it to be a non-abusable psychostimulant.

The fact that it binds to the dopamine transporter and inhibits reuptake is meaningless when you look at actual human studies.

The FDA scheduled it based on very bad studies (none of which actually found it TO be abused, but only that it shared characteristics that in their opinion made it likely to be abused- similarities which are meaningless in the absence of actual abuse cases). I don't believe that there is even one case study published for modafinil abuse to date- yet I can find them for quetiapine and sulbutiamine! lol.

There are long-onset long-duration psychostimulants with low potential for abuse which still produce definite euphoria and addiction- lisdexamfetamine being one of them.

Modafinil is not a recreational drug and never will be. It is great for getting work done, and has black-market value as a productivity enhancer- but not as a recreational drug.
 
Hammilton said:
WTF is Kilfer talking about? Germany actually UNSCHEDULED Modafinil because it was proven not to be abusable. Every study looking at it's effects in humans show it to be a non-abusable psychostimulant.

The fact that it binds to the dopamine transporter and inhibits reuptake is meaningless when you look at actual human studies.

The FDA scheduled it based on very bad studies (none of which actually found it TO be abused, but only that it shared characteristics that in their opinion made it likely to be abused- similarities which are meaningless in the absence of actual abuse cases). I don't believe that there is even one case study published for modafinil abuse to date- yet I can find them for quetiapine and sulbutiamine! lol.

There are long-onset long-duration psychostimulants with low potential for abuse which still produce definite euphoria and addiction- lisdexamfetamine being one of them.

Modafinil is not a recreational drug and never will be. It is great for getting work done, and has black-market value as a productivity enhancer- but not as a recreational drug.
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I got a definite mood boost out of it, not "euphoric" per say, but I definitely felt pretty damn good on it. Granted I could take up to 400mg a day and it wouldn't change from the effects I got at 50mg. It has a lot of research as an atypical antidepressant so that might be what we're feeling.

Granted I have some weird neuro-chemistry going on... I find opioids make me anxious a hell. Caffeine helps me sleep. Nicotine is also one of the most euphoric things I've ever touched. I'm also the guy that prefers the subjective effects of pseudoephedrine to amphetamine (if it wasn't for that damn vasoconstriction...)
 
Actually it means less than nothing. he's basing his moronic opinion on the same study that everyone else here is basing them on- the fact that modafinil raises dopamine levels by binding to DAT. However, modafinil has an affinity weaker than bupropion which i don't see anyone claiming to be abusable (I found it incredibly dysphoric and only took two doses before I had to give up).

It's not self administered by animals, blind administration doesn't result in any liking effects- it's not a recreational drug in humans.

The fact that people use it to accomplish goals doesn't mean anything.

Millions use caffeine every day to stay up late and get work done. The incidence of caffeinism is extremely low. We don't have any case studies for modafinil addiction, in fact, we have hundreds describing caffeine addiction, though.

It's far less addictive than caffeine or THC. That's saying something.
 
Hammilton said:
Actually it means less than nothing. he's basing his moronic opinion on the same study that everyone else here is basing them on- the fact that modafinil raises dopamine levels by binding to DAT. However, modafinil has an affinity weaker than bupropion which i don't see anyone claiming to be abusable (I found it incredibly dysphoric and only took two doses before I had to give up).

It's not self administered by animals, blind administration doesn't result in any liking effects- it's not a recreational drug in humans.

The fact that people use it to accomplish goals doesn't mean anything.

Millions use caffeine every day to stay up late and get work done. The incidence of caffeinism is extremely low. We don't have any case studies for modafinil addiction, in fact, we have hundreds describing caffeine addiction, though.

It's far less addictive than caffeine or THC. That's saying something.
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Oy! The number of things you assume!

Because caffeine has been mainstream for thousands of years?

And do a damn search, there are plenty of people who find WB abusable, me included.
 
WB? Is this some moronic slang for wellbutrin? I can't find any case studies confirming addiction to this drug either. I'll look a bit more after the children are in bed, but I doubt I'll find much.

The availability of a compound certainly has an impact on the number of people who will become addicted, but the fact that after millions of prescriptions we don't have even one case study of someone actually addicted to the drug- when drugs like sulbutiamine (far less available) have already seen cases published of actual addiction.

The fact that you claim to find some euphoria from it is relatively meaningless. If you were unable to control your use of it and became addicted to it, it would be far more meaningful. Lots of drugs are known to cause transient euphoria in some people, it'll be listed on all sorts of drugs in the single digit % of side effects. However, there are still zero reports of addiction to a drug.

And what exactly am I assuming?
 
WB? Is this some moronic slang for wellbutrin? I can't find any case studies confirming addiction to this drug either. I'll look a bit more after the children are in bed, but I doubt I'll find much.
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As was mentioned earlier, buproprion induces fewer reports of "liking" than caffeine in studies (but that's something...it's not neutral or dysphoric). I see how it could get 'addictive' in that after months to years of a daily regimen, there could be some clear withdrawal symptoms (the incidence being less frequent and the severity milder than with SSRIs it seems though).

ebola
 
Just to be clear, when I'm referring to something being addictive, i'm not in any way considering the liability to produce physical dependence. That's a feature shared by a whole host of non-psychologically addictive compounds. I'm referring only to a drugs ability to produce the effects and behaviors associated with psychological addiction. I don't see anyone lying, cheating and stealing to acquire modafinil (or bupropion for that matter) or ridiculous ramping up of dose- features used in the clinical definition of addiction and present with all truly addictive drugs, the amphetamines, cocaine, opiates, etc.

If modafinil were actually addictive you'd see people forging scripts and stealing money to support their modafinil habits. Doesn't happen- and it's not because it's so available that's its unnecessary.
 
Doesn't this just suggest that "addictive" is a vague and nebulous concept, in need of clarification when used? I concur that mere physical dependence is not enough to anchor the concept (nor is it even a necessary condition for addiction to manifest). . .and turning the discussion back toward modafinil again, I haven't seen any indications that it's addictive in any sense.

ebola
 
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