Psycho-Babble Medication Thread 886706

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Providgil Could Be Additive Study Says

Posted by Phillipa on March 23, 2009, at 19:22:15

According to this study providgil could be additive. Phillip

Study Flags Potential for Abuse and Dependence With Modafinil


March 20, 2009 A pilot study has found that modafinil (Provigil, Cephalon), a wake-promoting agent used to treat narcolepsy, blocks dopamine transporters and increases dopamine in the nucleus accumbens, actions that suggest the potential for abuse and dependence, researchers say.

The finding should highlight the need for heightened awareness of the potential for abuse in vulnerable individuals, the authors conclude.

"Modafinil is a very beneficial medication, and this particular finding in and of itself should not affect the way it is prescribed for the treatment of narcolepsy or even for the treatment in some instances off-label for [attention-deficit/hyperactivity disorder] ADHD or off-label for cognitive impairment in patients with schizophrenia, because under those conditions, the patient is being monitored properly," lead author Nora D. Volkow, MD, director of the National Institute on Drug Abuse, told Medscape Neurology & Neurosurgery.

"However," she added, "it is directly pertinent to the concept of the misuse of modafinil, which is increasingly being utilized by healthy individuals with the expectation of improved cognitive performance." In this unsupervised setting, the drug may not be as safe as previously thought, Dr. Volkow said.

The study, using positron emission tomography (PET) scanning, is published in the March 18 issue of the Journal of the American Medical Association.

Abuse Potential?

Unlike classical stimulant medications like methylphenidate (Ritalin, Novartis Pharmaceuticals), modafinil has been thought to produce its wake-promoting effects independent of dopaminergic actions, Dr. Volkow said. Although the Physician's Desk Reference does suggest there are some dopaminergic effects, including psychoactive and euphoric effects, she noted, "this was dismissed on the fact that the affinity of modafinil for the dopamine transporter was very low."

However, a series of animal studies, particularly in knockout mice, have suggested that the dopaminergic system might after all be crucial to the alerting properties of modafinil. For example, knockout mice for the dopamine transporter do not respond to modafinil, she noted.

To look more closely at the acute dopaminergic effects in humans of modafinil at doses used clinically, the researchers PET scanning to measure the effect of 200 mg and 400 mg of modafinil on extracellular dopamine and dopamine transporters in 10 healthy male subjects.

Scans were done over an 8-month period, using 2 tracers: [11C]raclopride, a D2/D3 ligand sensitive to changes in endogenous dopamine, and [11C]cocaine, a dopamine transporter radioligand, to measure changes in dopamine D2/D3 receptor and dopamine-transporter availability measured by changes in binding potential after modafinil or placebo.

They found that modafinil decreased the mean [11C]raclopride-binding potential in the caudate, putamen, and nucleus accumbens, reflecting increases in extracellular dopamine. "The magnitude of the change was actually equivalent to what we have previously reported for oral methylphenidate or Ritalin," Dr. Volkow said.

Mean (Standard Deviation) Decrease in [11C]raclopride Binding Potential With Modafinil Region Mean (SD) Decrease (%) 95% CI P
Caudate 6.1 (6.5) 1.5 10.8 .02
Putamen 6.7 (4.9) 3.2 10.3 .002
Nucleus accumbens 19.4 (20) 5 35 .02

Modafinil also acted to decrease [11C]cocaine-binding potential in the same brain structures, reflecting occupancy of dopamine transporters. "We showed that at the doses used clinically, you are occupying more than 50% of the dopamine transporters" with modafinil, Dr. Volkow noted. "Even though the medication may have, in an in vitro experiment, relatively low affinity, at the doses you are using, its availability which must be relatively high is producing a significant level of transporter blockade."

Mean (Standard Deviation) Decrease in [11C]cocaine Binding Potential With Modafinil Region Mean (SD) Decrease (%) 95% CI P
Caudate 53.8 (13.8) 43.9 63.6 < .001
Putamen 47.2 (11.4) 39.1 55.4 < .001
Nucleus accumbens 39.3 (10) 30 49 .001

"Awareness of this as a potential complication should enable us to manage the utilization of this medication in a safer way," Dr. Volkow concluded. Although dependence on medications such as stimulants is rare, it does happen, she added. "By alerting the physician and the patient to this possibility, they can recognize the symptoms for addiction if they start to emerge."


Again, although these findings should not change how modafinil is used in the clinical setting under a physician's supervision, it does have implications for the possibility of diversion of the drug for nonmedical use as a cognitive-enhancement agent.

The belief has been that modafinil, because it does not have dopaminergic effects, is safe in this application, she said. "These findings suggest that we need to be cautious about the potential that modafinil has reinforcing effects in the human brain, and therefore one of the potential side effects could be its addictiveness," she added.

Cognitive Enhancement

A Commentary published online December 7, 2008 in Nature brought this issue of cognitive enhancement for healthy individuals to the forefront, Dr. Volkow pointed out. In the commentary, Henry Greely, from Stanford Law School, in California, and colleagues discussed the "responsible use of cognitive-enhancing drugs by the healthy," a trend brought forward first among students using drugs such as Adderall (Shire US) or Ritalin to achieve higher grades (Greely H et al. Nature. 2008;456:702-705). They propose a path toward helping society to "accept the benefits of enhancement, given appropriate research and evolved regulation."

They refer to modafinil in the article, suggesting that because prescriptions are not common, diversion is rare. However, anecdotal evidence suggests that adults "sometimes obtain modafinil from their physicians or online for enhancement purposes."

The concept of cognitive enhancement in healthy people "theoretically, in my view, is not negative, provided that the medications don't have any side effects," Dr. Volkow said. If modafinil had not had dopaminergic effects, it would have been "transformative, because it would have given us a medication that is wake-promoting without the potential negative effect of reinforcement and addiction. It didn't turn out like that, so as of now, cognitive-enhancing medications for healthy people should be viewed with a lot of caution."


Extent of Diversion Uncertain?

Asked about these new findings, Mark Mahowald, MD, a sleep expert at the University of Minnesota, in Minneapolis, commenting on behalf of the American Academy of Neurology, called this an "interesting and important article," because it provides more much-need information on the precise mechanism of action of modafinil.

However, he said, "I don't think there's good evidence that modafinil use frequently results in chemical dependence as we conventionally think of it." An informal poll of colleagues at his own institution since publication of this article, Dr. Mahowald added, showed that none have seen dependence in patients treated with modafinil. "I'm not saying it doesn't happen, but if it does, it certainly isn't often."

He also questioned how great the diversion of modafinil really is, since studies have suggested cognitive enhancement with this agent is not substantially different than that of caffeine, at a cost of about $10 per tablet.

"It does improve alertness, there's no question about that," Dr. Mahowald said. "How much it truly improves cognition, I think, remains to be seen."

Dr. Volkow agreed on the point that modafinil is expensive, which is likely to price it out of the hands of students in high school, for example. However, college students might be able to afford it, and the drug is expected to go off patent in 2012, which could substantially reduce the price.

The National Institute on Drug Abuse conducts a survey of high school students in the United States, asking them about their patterns of drug use, including illicit drugs and psychotherapeutics such as oxycodone (Oxycontin, Purdue Pharma) or Ritalin without a prescription.

"We've never had a question about modafinil, and as a result of this particular finding, I'm already speaking with my grantees to evaluate what it would take to start evaluating this question," Dr. Volkow said.


The study was carried out at Brookhaven National Laboratory under contract from the US Department of Energy, with infrastructure support from its Office of Biological and Environmental Research. Support was also provided by the National Institutes of Health, the National Institute on Alcohol Abuse and Alcoholism intramural research program, the National Institute of Biomedical Imaging and Bioengineering, and the General Research Clinical Centers. The authors report no relevant financial disclosures.

 

Re: Providgil Could Be Additive Study Says

Posted by kenny6 on March 23, 2009, at 19:32:03

In reply to Providgil Could Be Additive Study Says, posted by Phillipa on March 23, 2009, at 19:22:15

Great post. This is nothing against you at all for I've actually been posting here a while and know who you are but Provigil really, really, really sucks. "Oh no but the kick isnt artificial..." yeah, no its a psychotropic kick all right. Just as good as a cup of tea! (i took 200mgs on Nardil before moving up...) I know it's a hot commodity...So who wants to buy two 200mg sample packs (no medication inside of course) right from the reps! Perfect condition!

 

Re: Providgil Could Be Additive Study Says kenny6

Posted by Phillipa on March 23, 2009, at 21:28:01

In reply to Re: Providgil Could Be Additive Study Says, posted by kenny6 on March 23, 2009, at 19:32:03

Kenny no sure what you men how bout babbling explain? Love Phillipa

 

Re: Providgil Could Be Additive Study Says

Posted by desolationrower on March 24, 2009, at 0:41:22

In reply to Re: Providgil Could Be Additive Study Says, posted by kenny6 on March 23, 2009, at 19:32:03

the study provides some useful information, but 'provogil is addictive' headline is exactly the kind of dumb brain-picture study conclusion that gives brain scans such a bad reputation

-d/r

 

Re: Providgil Could Be Additive Study Says

Posted by bleauberry on March 24, 2009, at 18:02:35

In reply to Providgil Could Be Additive Study Says, posted by Phillipa on March 23, 2009, at 19:22:15

Here is the important part of the article that needs to be highlighted, and avoid reading into anything that isn't there...

"Again, although these findings should not change how modafinil is used in the clinical setting under a physician's supervision, it does have implications for the possibility of diversion of the drug for nonmedical use as a cognitive-enhancement agent."

God forbid. It works on dopamine? It makes suffering people feel better? Oh no, we can't have that. Let's write an anti-provigil article.

Honestly, if someone who is perfectly healthy uses it to be a top achiever at the workplace or to get an A on an exam, sounds fine with me.

As far as getting hooked, I personally never felt any addiction to it in the 3 years I took it. In contrast, I was highly addicted to Paxil or Zyprexa or Prozac and even ST Johns Wort.

If one is concerned about being "hooked" on a drug, any drug, then they should probably not ever start it. Try stopping Luvox after taking it for years and you'll know what "hooked" is.

Cheers to Modafinil/Provigil. I think it is an unsung hero helping to fight chronic bedridden disaster illnesses worldwide. If someone else wants to abuse, I could care less.

 

Re: Providgil Could Be Additive Study Says

Posted by metric on March 26, 2009, at 12:29:15

In reply to Providgil Could Be Additive Study Says, posted by Phillipa on March 23, 2009, at 19:22:15

It's long been known that modafinil is a DRI. The significance of this property has been downplayed by its manufacturer for good reasons -- clearly a wise decision.

As long as mood-elevation is viewed as an adverse drug effect, it shouldn't come as a surprise that none of the "antidepressants" work (except the old unselective MAOIs, which are plagued with so many side-effects that they're useless in all but the most desperate cases).

Modafinil is probably the closest thing we have to an "antidepressant" in the U.S. Of course it's only used off-label for that purpose, because only non-mood-elevating "antidepressants" are permitted; how silly is that? "Antidepressants" are extensively screened prior to marketing to ensure they lack "abuse potential". A drug has "abuse potential" if it elevates mood. The contradiction is irreconcilable. Think about it.

A shift in public attitude -- and attendant change of laws -- is sorely needed in order for effective pharmacological management of depression to become routine.

 

Re: Providgil Could Be Additive Study Says

Posted by Zana on March 26, 2009, at 14:51:14

In reply to Re: Providgil Could Be Additive Study Says, posted by metric on March 26, 2009, at 12:29:15

I agree with metric. Provigil gives me a lift that nothing else does. I don't experience it as nearly as SSRIs or benzos. I'm sure there is plenty of room for abuse, but just because it makes you feel good doesn't make it a bad thing. It is stupid.
Zana

 

Re: Providgil Could Be Additive Study Says metric

Posted by bleauberry on March 26, 2009, at 17:49:43

In reply to Re: Providgil Could Be Additive Study Says, posted by metric on March 26, 2009, at 12:29:15

Brilliantly worded, metric. So true.

Our medical professionals, as advanced as they are compared to 100 years ago, are riddled with gigantic flaws.

 

Re: Providgil Could Be Additive Study Says

Posted by garnet71 on March 26, 2009, at 19:19:38

In reply to Providgil Could Be Additive Study Says, posted by Phillipa on March 23, 2009, at 19:22:15

I, too, agree that was a very fitting response by Metric.

It's BS. Anytime I hear a drug *could be* addictive, I immediately think 'it must work'!

Of course, I'm very opinionated/biased after being traumatized when doctors let me have a 3 to 4 day long panic attack and no sleep for 4 days, while I almost completely lost my mind--because they wouldn't prescribe me 7 days' worth of Xanax while I awaited my PDoc appointment. If I hadn't been resourceful enough to go out and drink 2 whole bottles of wine to supress my nervous system, I would have had a complete breakdown and probably would have been given a chemical lobatamy at the mental hospital like they did to my sister. Instead, I remained half-drunk until the PDoc appt. and fully recovered due to self-medicating. Of course, that's now in my medical record, so I could be considered to be an alchohol abuser and *drug seeker* from that incident. lol

Maybe I'll ask for Provigil next time if the Adderall doesn't work out for me.

 

Re: Providgil Could Be Additive Study Says

Posted by desolationrower on March 27, 2009, at 2:47:44

In reply to Re: Providgil Could Be Additive Study Says, posted by garnet71 on March 26, 2009, at 19:19:38

yeah, the conflation of pleasure=addiction is very typical biological/behavioralist model. i think a large part of the problem is most doctors never have any liberals arts classes, and also most doctors are overachiever types (this relates both to how they see what is good in life, and reduced amount of time b*llsh*tt*ng and thinking about things).

-d/r

 

Re: Providgil Could Be Additive Study Says

Posted by bleauberry on March 27, 2009, at 15:17:15

In reply to Re: Providgil Could Be Additive Study Says, posted by desolationrower on March 27, 2009, at 2:47:44

> and also most doctors are overachiever types (this relates both to how they see what is good in life, and reduced amount of time b*llsh*tt*ng and thinking about things).
>
> -d/r

I'm not sure what you meant here, but I just wanted to, in a friendly polite opinionated way, say I totally completely disagree with any statement that most doctors are overachievers.

They obviously had to have some above-average stick-to-it-ness to get through school and residency.

But in actual clinical practice, my experience with over a dozen GPS and specialists tells me they are huge underachievers. When some idiot like me from pbabble can discuss common normal things many of us here know about drugs, and the doctors give me a blank stare because I am more educated than they are, well, it is sad. I mean, this sick guy has the time to do maybe 30 minutes of research online each evening, but they the specialists don't? Come on.

A high achiever would be on top of the game. Very few are. It's almost like they spent their energy getting there, and now that they are there, it is just a well paid job. The overachieveness part of it is gone. All used up.

My own view.

From 1992 untill now, with 3 GPs, a dermatologist specialist, and about 12 psychiatrict specialists, and one Lyme Literate specialist, of the whole bunch there has only been ONE overachiever.

When you see an overachiever, you will know it. They are astounding at what they do.

 

Re: Providgil Could Be Additive Study Says bleauberry

Posted by Garnet71 on March 27, 2009, at 19:26:48

In reply to Re: Providgil Could Be Additive Study Says, posted by bleauberry on March 27, 2009, at 15:17:15

When I read what d/r said, I partially agreed. I picture some doctors, before they get their MDs, needing to go prove themselves, so they do it via their achievement in becoming a doctor--only to realize after that time they hate the job. Then they realize after they became a doctor that they are the same empty person inside who still needs to prove themselves, so they will find another way to go at it again...the cycle continues.

However, I disagree with both of you--I don't think MOST doctors are either (okay maybe half..lol); but I have to say I do think there are many crummy ones out there. I've had quite a few myself. I do think some get into the field for the wrong reasons-for example, as I stated above.

I've worked with those people that need to prove their worth through their jobs/careers--it's awful working with those types. Those are the kind of people that have attacked me for achieving w/o trying to achieve, which was much to their discontent as those types of people often are used to being the best, #1, at everything while trying to prove their 'worth'. When someone else matches that, especially w/o trying as hard as they, it puts a huge hole in their ego and they feel very threatened and attack. I have seen that predator look in their eyes and their extreme uncomfortablness.

Just the words of an observor of human behavior and former frequent abuse survivor. (has a ring to it like frequent flyer miles). lol

 

Re: Providgil Could Be Additive Study Says Garnet71

Posted by bleauberry on March 27, 2009, at 20:23:54

In reply to Re: Providgil Could Be Additive Study Says bleauberry, posted by Garnet71 on March 27, 2009, at 19:26:48

I agree with you. I would only add that in my opinion those doctors you are talking about are not high achievers. There are some egostistical things involved there, and empty efforts to prove themselves, but those things do not make high achievers. High achievers are the ones that are still at their computer studying or writing even though everyone else in the office went home 2 hours ago. They can't wait to get to work in the morning because they love it so much. They accomplish significant successes with their patients that other doctors could not or would not. They have discovered on their own certain tricks of the trade they did not learn from a school, a book, or anyone else, something they noticed and perfected in their own practice. They dream of writing their book of fascinating successes and stuff when they retire. Those are high achievers.

The ones you are talking about are the opposite...losers...and that is why they have to try to prove themselves, and why they are easily intimidated.

> When I read what d/r said, I partially agreed. I picture some doctors, before they get their MDs, needing to go prove themselves, so they do it via their achievement in becoming a doctor--only to realize after that time they hate the job. Then they realize after they became a doctor that they are the same empty person inside who still needs to prove themselves, so they will find another way to go at it again...the cycle continues.
>
> However, I disagree with both of you--I don't think MOST doctors are either (okay maybe half..lol); but I have to say I do think there are many crummy ones out there. I've had quite a few myself. I do think some get into the field for the wrong reasons-for example, as I stated above.
>
> I've worked with those people that need to prove their worth through their jobs/careers--it's awful working with those types. Those are the kind of people that have attacked me for achieving w/o trying to achieve, which was much to their discontent as those types of people often are used to being the best, #1, at everything while trying to prove their 'worth'. When someone else matches that, especially w/o trying as hard as they, it puts a huge hole in their ego and they feel very threatened and attack. I have seen that predator look in their eyes and their extreme uncomfortablness.
>
> Just the words of an observor of human behavior and former frequent abuse survivor. (has a ring to it like frequent flyer miles). lol
>
>

 

Re: Providgil Could Be Additive Study Says

Posted by desolationrower on March 28, 2009, at 21:25:28

In reply to Re: Providgil Could Be Additive Study Says Garnet71, posted by bleauberry on March 27, 2009, at 20:23:54

bb, i use the word 'overachiever' in the social sense, that people highly value markers of success, and being recognized as superior, etc. not anything about their effectiveness or committment to patients' health.

-d/r

 

Re: Providgil Could Be Additive Study Says metric

Posted by Neal on March 31, 2009, at 15:02:52

In reply to Re: Providgil Could Be Additive Study Says, posted by metric on March 26, 2009, at 12:29:15

_


"As long as mood-elevation is viewed as an adverse drug effect, it shouldn't come as a surprise that none of the "antidepressants" work (except the old unselective MAOIs, which are plagued with so many side-effects that they're useless in all but the most desperate cases)."

We still live in a Puritan society, my friend. Until their fingers can be pried off the levers of power, we all have to live under this kind of enforced piety. Never mind that Mexico has been turned into a semi-narco state because of American demand for all the stuff made illegal in the good ole US.

There are some things that could help some very depressed people feel a little better, but that can't happen in the "pull yourself up by your own bootstraps" society.

_


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