![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 6 to 30 of 30. Go back in thread:
Posted by Janice on May 8, 2000, at 11:14:50
In reply to Re: Drugs for Creativity? - Cam , posted by Greg on May 8, 2000, at 10:05:35
Hello DC,
I am manic depressive (working hard to get rid of it). And from my experience, there seems to be only a short period of time when I could be especially creative--at the beginning of a mania. I believe many manic depressives are creative not necessarily during their mania, but because they are manic depressive.
Jazz music induces creativity in me. It seems to hypnotize the petty part of my brain used for daily living, and leaves the rest to be fully creative. I'd look for something like this.
Janice
Posted by Janice on May 8, 2000, at 14:37:42
In reply to Drugs for Creativity? , posted by DC on May 8, 2000, at 7:06:44
hi Dc,
I forgot to respond to your part about stimulants. Of course, we are all different, but I found stimulants either prevented or decreased my mania. I'm not positive, but I believe they would more often than not prevent rather than induce mania (for me anyway). Janice
Posted by Noa on May 8, 2000, at 17:30:01
In reply to Re: Drugs for Creativity? , posted by Janice on May 8, 2000, at 14:37:42
I would think stimulants would bolster the more linear thinking you described as academic. For creative expression, what you are trying to access is the non-linear, the part that eludes you if you try too hard to grasp it. What about trying something like meditation, to learn to let go of the ambitious part of your brain and allow the creative recesses to come forward as they will?
Posted by medlib on May 8, 2000, at 19:56:03
In reply to Drugs for Creativity? , posted by DC on May 8, 2000, at 7:06:44
> Out of curiosity--has any one here experimented with higher doses of stimulants? I'm a creative writer and I'm wondering if taking a higher dose now and then might put me in a different, perhaps more creative, zone. What about other drugs? Is there any safe way to boost creativity?
> I came across a word recently on a website about career aptitude testing. The word was "ideaphoria", which, as I understand, is basically the ability to think of many, many ideas quickly. People who have this onrush of ideas tend to have a knack for creative writing. It's different than the "critical" thinking of academia. It sounds a bit like Mania--and it's no secret that many great artists were manic-depressives. So maybe my question is: how can I induce mania?------------------------------------
DC--
I lived in LA during the late 60s, 70s. IMO, Timothy Leary left his fine mind down the rabbit hole-and a lot of others jumped in after it; we never saw their valuable selves again.
Drugs can't make you into someone or something more or different. Some make you *believe* that they can (stims). Others (mj, hallucs) make you believe that they *have*, or that it doesn't matter, anyway.
I lived in a canyon with a lot of creative types and carpooled with 2 writers. Creativity and I have never met (I scored a "D" on Johnson O'Conner's Ideaphoria test). So, when I expressed my natural awe of their craft, I was surprised when they responded similarly. Each said that structure, discipline and persistence were the most important factors. One said that writing was her job; that her confidence came from working hard at that job consistently; that producing something she was proud of was the bonus, and geting something published was a matter of "fate and a good agent." I remember thinking that that would be good for *any* job. I guess this is not news to you, but it sure was to me.
BTW, I, my ex, and both our kids have taken the J. O'C. tests, so, if you're interested in them, I'd be happy to answer questions, if I can.
Best wishes--medlib
Posted by PeterJ on May 8, 2000, at 20:00:23
In reply to Re: Drugs for Creativity? , posted by Janice on May 8, 2000, at 14:37:42
> hi Dc,
>
> I forgot to respond to your part about stimulants. Of course, we are all different, but I found stimulants either prevented or decreased my mania. I'm not positive, but I believe they would more often than not prevent rather than induce mania (for me anyway). JaniceYour observation is backed up by several studies and case reports showing that amphetamine reduces manic symptoms On the other hand there are reports of amphetamine inducing mania as well and certainly the effects of amphetamine can mimic manic symptoms. It would seem that many bipolar individuals react to amphetamine in a ways similar to people with ADHD and find the stimulant calming. Here are some references.
Peter
Case study: antimanic effectiveness of dextroamphetamine in a brain-injured adolescent.
Max JE; Richards L; Hamdan-Allen G
University of Iowa, Department of Psychiatry, Iowa City 52242-1009, USA.
J Am Acad Child Adolesc Psychiatry 1995 Apr;34(4):472-6
ABSTRACT:
A relatively enduring and counterintuitive antimanic response to dextroamphetamine in a brain-injured
adolescent who had failed trials involving divalproex, lithium, haloperidol, and carbamazepine is
described. This finding combined with data from previous reports of antimanic effects of test doses of
stimulants imply that such a pharmacological probe may prove relevant for the prediction of treatment
response of mania to dextroamphetamine and perhaps for subclassification of bipolar disorder.Treatment of mania with dextroamphetamine [letter]
Clower CG
J Clin Psychiatry 1988 Jul;49(7):283Dextroamphetamine treatment of mania.
Garvey MJ; Hwang S; Teubner-Rhodes D; Zander J; Rhem C
Department of Psychiatry, Veterans Administration Medical Center, Iowa City, IA 52242.
J Clin Psychiatry 1987 Oct;48(10):412-3
ABSTRACT: Five of six acutely manic patients treated with dextroamphetamine experienced a 50% or greater
reduction in their mania severity scores. Side effects were noted in only one patient. The treatment
results suggest that dextroamphetamine might be useful in the treatment of mania.[Proceedings: D-Amphetamine in manic syndrome (author's transl)]
D-Amphetamin beim manischen Syndrom
Beckmann H; Heinemann H
Arzneimittelforschung 1976;26(6):1185-6
ABSTRACT:
Six manic patients were acutely treated with 30 or 50 mg d-amphetamine, respectively. There was no
intensification in any of these patients of gross manic behavior or single manic symptoms. Conversely,
there was sedation and considerable reduction of manic symptomatology in all of them. This effect
lasted for 1 to 3 h only. The clinical subgroup "elated-grandiose" was significantly, the subgroup
"paranoid-destructive" was not significantly influenced. "Drive" and "mood" were similarly reduced.
There was, however, no complete recovery from mania.
Posted by JohnB on May 8, 2000, at 21:17:24
In reply to Drugs for Creativity? , posted by DC on May 8, 2000, at 7:06:44
The issue of artists and drugs is a complex one.. Since the beginning of humankind shamans, artists, and healers have been using herbs as well as other techniques such as fasting in pursuit of the "vision quest". But it was usually done within a the framework of beliefs and tribal culture. I personally knew an Indian shaman or "medicine man" who would supervise groups in the desert.
Many of the shamans are in fact what we might call "strong, grounded, realistic minded personalities". If they wanted to break though to the other side, they might need strong medicine.
But many creative people are already THERE, ie., they are already highly sensitive, or possibly even have problems such as this board deals with. For them taking drugs for creative or other reasons can be risky. For every artist who got some benefit from an altered state, there are probably 20 sensitive souls who were harmed, or possibly even in a few cases spiraled down the tubes because of drugs; not to mention the 5,000 "normal" non-artists drinking or drugging recreationally who probably shouldn't be. So the question is; are you strong, grounded, smart, educated, knowledgeable and humble? And if you're posting on this board you have to ask yourself- "how lucky do I feel?".
Yeh, Picasso was taking opium when he broke through to Cubism, and Kerouac took and drank a lot, but these were major league players, both tough-as-nails, who were already totally immersed in their fields. And in the case of Kerouac, who I think was a depressive, the drink consumed him.
So the idea I would suggest is this. Become totally immersed in whatever it is you want to write, and you will probably find the ideas will come.
To quote Dennis Miller; "Of course that's just my opinion - I could be wrong."
Posted by quilter on May 9, 2000, at 0:29:06
In reply to Re: Drugs for Creativity? , posted by JohnB on May 8, 2000, at 21:17:24
>
>My experience with creativity is that drugs enhance it only because they get my depression enough better to allow thought about other things than the illness. There is a book, "The Artist's Way" by J. Cameron that helps unblock or enhance your creative process through different exercises. Not as fast or easy as your idea but certainly safer and probably better at allowing you to access the skills you acquire any time or place.
Posted by FP on May 9, 2000, at 11:23:08
In reply to Drugs for Creativity? , posted by DC on May 8, 2000, at 7:06:44
> Out of curiosity--has any one here experimented with higher doses of stimulants? I'm a creative writer and I'm wondering if taking a higher dose now and then might put me in a different, perhaps more creative, zone. What about other drugs? Is there any safe way to boost creativity?
> I came across a word recently on a website about career aptitude testing. The word was "ideaphoria", which, as I understand, is basically the ability to think of many, many ideas quickly. People who have this onrush of ideas tend to have a knack for creative writing. It's different than the "critical" thinking of academia. It sounds a bit like Mania--and it's no secret that many great artists were manic-depressives. So maybe my question is: how can I induce mania?DC:
Enough people have posted about the dangers of inducing mania, and other, safe methods that may enchance creativity.
Reading between the lines, I'd have to guess that you're "blocked." I mean, no one decides they want to be a creative writer unless they already ARE (or WERE) creative - do they?
I know that at the peak of my creative writing years, the ideas came so fast and thick I couldn't write them all down. The imaginary was real, and insistent that its stories be told.
Then, around the age of 23-24, it stopped. I could force it, to some extent, but it lacked the "'I MUST be written down' authority" of the old stuff.
Fortunately, by then I had discovered the photography of Lee Friedlander and William Eggleston, and discovered that creativity could also mean just looking at the things around you without judging "ugly" or "beautiful." I've been doing that, pretty much continuously, for the last 15 years. That period coincides with some of my heaviest drug use ever, and also with my sobriety - and you can't tell from the pictures which were taken when.
So, in conclusion:
1. The only thing that's every bought back my creative writing impulses (briefly) was binge drinking. Not reccomended.2. If you are, in fact, blocked at writing, try something else for awhile. Convince yourself it's only temporary - that you'll put down the camera / paintbrush / dance classes / saxophone lessons as soon as you feel the need to write again.
3. To deal with being blocked in you "back up" creative outlet, you should have other activities you enjoy. For the past couple of years I've been making and selling stereo loudspeakers, during my photgraphic down time.
4. I wish you well .... my feeling is that the kind of creativity needed for writing exists only under certan special conditions (lonely, miserable childhood, mild psychosis, ailienation, daily daytime drinking, etc.)
However, creativity will always find an outlet. Just don't worry and don't try to force it.
Straight from the horse's orifice to your ear:
FPPS: If you found this helpful in the slightest, you can always e-mail.
Posted by Adam on May 9, 2000, at 17:12:40
In reply to Drugs for Creativity? , posted by DC on May 8, 2000, at 7:06:44
My impression of creative people and drugs is that, especially with hallucinogens,
it gave them some interesting experiences to apply their creativity to. At most,
they were inspired by what they felt or saw, just as many other things inspired them.
I don't think drugs ever did anything to make them more creative or interesting.The only possible approach I could think of might be to use a nootropic. I believe
that if something could improve your memory, then you might retain more of your
creative thoughts, and hence the juices might flow more easily. At best, such an
approach would keep you from losing good ideas. It wouldn't give them to you. I
don't think anything of that sort would.Unfortunately, there's little convincing evidence that nootropics do all that much
for the unimpaired. Piracetam might be something to try. It appears to be very safe
and tolerable, even at absurdly high doses, and it's relatively cheap and easy to get
from overseas. Some even say it can generate "flashes of creativity". I guess one
would have to judge the quality of their experiences on piracetam for themselves.A combination of piracetam and a choline supplement might be a marginally effective
memory/cognative booster, and there's plenty of anecdotal information out there on
the Internet to help you mix such a coctail. If you have some expendable income, and
aren't expecting the heavens to open and pour out inspiration, what the heck.
Posted by JohnB on May 9, 2000, at 17:51:22
In reply to Re: Drugs for Creativity? , posted by FP on May 9, 2000, at 11:23:08
FP-
Re William Eggleston; Now there's a name I didn't expect to see. I had a book of his work, but can't seem to find it now. I think it had on its cover the picture of the red ceiling with the extension cords coming out of the light fixture. He knew color.
Posted by DC on May 9, 2000, at 23:32:55
In reply to Re: To FP; -William Eggleston , posted by JohnB on May 9, 2000, at 17:51:22
Thank you all for your thoughts and advice. I guess I must have some talent because I got into one of the top creative writing programs in the country--I'll be going in the Fall. But I having a really hard time with it. I don't spend enough time writing and when I do write I often don't like it. Some of this has to do with depression I think. I'm not planning on taking any illicit drugs. If I could get myself to do it every day and establish a habit I'm sure that would help. Thanks again.
Posted by boBB on May 10, 2000, at 0:04:48
In reply to Re: creativity, posted by DC on May 9, 2000, at 23:32:55
I can't beleive this site has self-selected for people who do not know the use of stimulunts pervades creative circles. There are other ways, to be sure, like NOT WRITING, because CREATIVITY IS AN ADDICTION, and if humans would just CREATE LESS we would leave a lot more room for the rest of life to express itself.
Anyway, creativity is the product of fluid thought. Stimulants basically jump start NOR-E networks, often along lines not usually realized in response to external experiential stimulus. The anecdotal experiences posted here read more like a homework assignment for a fifth grade DARE class than like research. Lets see some objective studies about the creative effect of stimulants and other neurotropics. And lets do away with the culturally biased "licit/illicit" labels and deal with them as what they are - stimulants, amenergic agents, Sympathamemetics, whatever.
P.S. I write for a living. What a waste of a good mammal's life!
Posted by boBB on May 10, 2000, at 0:31:41
In reply to Yess, Virginia, Hollywood toots Coca, posted by boBB on May 10, 2000, at 0:04:48
Darn. There was at least one good line in the post that got lost when my browser crashed.
(lots of JAVA error messages in the new system. Whassup wit dat?)Anyway .... deleted was a bunch of prattle about creativity and drugs and some equal but opposite anecdotes about enhanced creativity under the influence. Let me put it this way. If i come to your house and sit down to the piano and you can't get me up, and your guests are leaving on account of my stilted renditions - try sharing some illegal smile and see if thing improve.
But the good line that got left out was my profound opinion that addiction, whether to heroine, cocaine, tobbacco, money, chocolate, sex, academic acheivement, creativity or PsychoBabbling - all addiction has a similar neurological footprint having to do with upregulation of dopaminergic neurons.
And that's the truth, Blthlthlthlthblthl!
Posted by bob on May 10, 2000, at 0:37:47
In reply to Yess, Virginia, Hollywood toots Coca, posted by boBB on May 10, 2000, at 0:04:48
> P.S. I write for a living. What a waste of a good mammal's life!
... but aren't you assuming that you're a GOOD mammal? Hmm?
(good to see you back!)
bob
Posted by FP on May 10, 2000, at 11:36:44
In reply to Re: creativity, posted by DC on May 9, 2000, at 23:32:55
> Thank you all for your thoughts and advice. I guess I must have some talent because I got into one of the top creative writing programs in the country--I'll be going in the Fall.
Congratulations!
>But I having a really hard time with it. I don't spend enough time writing and when I do write I often don't like it. Some of this has to do with depression I think.
First thought: writer's block often means you've encountered a technical problem you don't know how to solve. In my case, the writing in college that bought attention was surreal - After awhile I convinced myself I "should" write in a more realistic vein, and got stuck.
Re: Depression. Maybe, Maybe. Since your first post said "INCREASE my dose of stimulants" (emphasis mine) I wondered if you were already being treated for ADD or something similar. All big life changes cause stress, which can trigger depression.
OR it could be plain old FEAR. Maybe in college there was no question (at least in your own mind) that you were the best writer around - now you'll be facing some real competition, and be judged by some of the best. Hopefully, you're going for the right reasons - some (at least one) on the faculty has a view of fiction like yours, and you hope they can mentor you, and to network and make contacts generally.
Another form of fear: have your parents or others talked about the financial hardships of being a writer? Have you gotten the lecture about how aweful the market for fiction is in this country? (Except for works that are "narrowcasted" at specific demographic groups?) I know that stuff began to get to me, too.
>I'm not planning on taking any illicit drugs. If I could get myself to do it every day and establish a habit I'm sure that would help.
Yes! Writing everyday really helps (I think it's essential), as do all those stupid tricks they tell you, like creating biographies for your characters, etc. Or maybe fragments of dialogue of action pop into you head; write'em down somewhere - eventually they may start assembling themselves.
OR, maybe your batteries just need recharging. Presumably you've been going at this pretty hard for awhile, and you're just plain exhausted. Kick back, relax, meet new people, and do new things - that might be the ticket.
> Thanks again.
Anytime. Hate to sound like Pres. C., but "I feel your pain." You'll work this out, one way or another. Trust me.
FP
PS: OMIGOD! I just realized that - by admitting my biggest writing phase (college) coincided with lots of drug taking, I'm, on some level, agree-ing with boB(B)! Who woulda thunk it?
Posted by Janice on May 10, 2000, at 12:18:13
In reply to Yess, Virginia, Hollywood toots Coca, posted by boBB on May 10, 2000, at 0:04:48
stimulants only increase linear type thinking for me, maybe because I use them for ADD and bipolar. I am too lazy to look up any papers. Sorry.
and my writing is at, at least, a grade 6 level.
I find, probably like many others, that if I'm not really precise with my writing on this board, people can misinterpret what you say.
Janice
Posted by SLS on May 10, 2000, at 15:37:17
In reply to Amphetamine Treatment of Mania, posted by PeterJ on May 8, 2000, at 20:00:23
> > I forgot to respond to your part about stimulants. Of course, we are all different, but I found stimulants either prevented or decreased my mania. I'm not positive, but I believe they would more often than not prevent rather than induce mania (for me anyway). Janice
> Your observation is backed up by several studies and case reports showing that amphetamine reduces manic symptoms On the other hand there are reports of amphetamine inducing mania as well and certainly the effects of amphetamine can mimic manic symptoms. It would seem that many bipolar individuals react to amphetamine in a ways similar to people with ADHD and find the stimulant calming. Here are some references.
> Peter
Peter,Other than in those cases of brain-injury patients, have all the instances of amphetamine-induced improvement of manic symptoms you encountered been extremely transient?
I guess I just like to brainstorm this stuff, but couldn't the acute pouring-out of dopamine effected by amphetamine produce a temporary state of accommodation (continual depolarization) of dopaminergic neurons, thereby decreasing neural activity in the culprit regions and temporarily ameliorating manic symptoms, this phenomenon only to diminish once presynaptic stores are partially depleted or postsynaptic receptor sensitivity reduced?
(I must catch my breath)
Perhaps the consequence of these changes at the synapse is a prophylactic effect against mania in certain individuals.
I feel like I'm reaching.
- Scott
Posted by PeterJ on May 13, 2000, at 4:20:26
In reply to Re: Amphetamine Treatment of Mania, posted by SLS on May 10, 2000, at 15:37:17
> > > I forgot to respond to your part about stimulants. Of course, we are all different, but I found stimulants either prevented or decreased my mania. I'm not positive, but I believe they would more often than not prevent rather than induce mania (for me anyway). Janice
>
> > Your observation is backed up by several studies and case reports showing that amphetamine reduces manic symptoms On the other hand there are reports of amphetamine inducing mania as well and certainly the effects of amphetamine can mimic manic symptoms. It would seem that many bipolar individuals react to amphetamine in a ways similar to people with ADHD and find the stimulant calming. Here are some references.
>
> Other than in those cases of brain-injury patients, have all the instances of amphetamine-induced improvement of manic symptoms you encountered been extremely transient?
>
> I guess I just like to brainstorm this stuff, but couldn't the acute pouring-out of dopamine effected by amphetamine produce a temporary state of accommodation (continual depolarization) of dopaminergic neurons, thereby decreasing neural activity in the culprit regions and temporarily ameliorating manic symptoms, this phenomenon only to diminish once presynaptic stores are partially depleted or postsynaptic receptor sensitivity reduced?
>
> (I must catch my breath)
>
> Perhaps the consequence of these changes at the synapse is a prophylactic effect against mania in certain individuals.
>
> I feel like I'm reaching."Oh that a man's reach should exceed his grasp,or what's a Heaven for?" --Robert Browning
Not that I'm implying you don't grasp the subject, but I thought the quote was apropos :-)
I don't know what the literature says about the duration of the effect. I do know that the effectiveness of stimulants against Attention Deficit Disorder (ADD) does not wear off after time. Occam's razor suggests to me that since ADHD and mania share many symptoms that the mechanism of stimulants in treating both may be similar. On the other hand the refractory, kindling-like aspects of mania suggest the possibilty that some treatments may lose effectiveness.
It is often assumed that stimualants are inherently...well, stimulating. This is not necessarily so. A 1974 Science article by Joseph Tecce and Jonothan Cole showed that 13 of 20 adults were less alert the first hour after amphetamine, although all subjects were more alert at 2 and 3 hours.
With hyperactive individuals the initial de-activating effect is prolonged and their is usually no stimulant effect.
Their are a lot of theoretical explanations for the effectiveness of stimulants in AD(H)D. Some suggest a reduced dopamine activity due to some kind of auto-inhibition. Other theories suggest DA inhbition of NE. Still others suggest a focusing effect of DA on the frontal lobes. Any of these could potentially apply to mania.
My own personal observations is that amphetamine initially sedates me, with delayed stimulation after a few hours. Other dopaminergic drugs are almost invariably sedating and de-activating to me. These include ritalin, pemoline, bromocriptine, diethylpropion, bupropion, l-dopa, and isocarboxazid. For example, if I take ritalin, I have to lie down, and am virtual immobile for several hours. All the other drugs in the list produce similar effects.
This sedating effect of DA drugs may have something to do with the fact that I have several relatives with ADD. I don't have it myself, but may have some neurochemical similarities.
But then you can't judge much by my personal drug responses. I seem to have odd or paradoxical responses to many drugs. Dr. McCoy would blame it on my green vulcan blood I'm sure :-)
Peter
Posted by PeterJ on May 13, 2000, at 4:36:44
In reply to Yess, Virginia, Hollywood toots Coca, posted by boBB on May 10, 2000, at 0:04:48
There's creativity in Hollywood? I hadn't noticed. :-)
I have no beef against using drugs to enhance creativity. It's not my thing, but it works for some people. Live and let live.
But If the government insists on regulating drugs, I think they should find out what John Travolta was on when he made "Battlefield Earth" and ban it (Schedule I)!
Peter
Posted by SLS on May 13, 2000, at 9:03:43
In reply to Re: Amphetamine Treatment of Mania, posted by PeterJ on May 13, 2000, at 4:20:26
> My own personal observations is that amphetamine initially sedates me, with delayed stimulation after a few hours. Other dopaminergic drugs are almost invariably sedating and de-activating to me. These include ritalin, pemoline, bromocriptine, diethylpropion, bupropion, l-dopa, and isocarboxazid. For example, if I take ritalin, I have to lie down, and am virtual immobile for several hours. All the other drugs in the list produce similar effects.
This appears to be similar to a low-dose apomorphine effect. Under a microscope, your presynaptic autoreceptors probably resemble tiny membrane-bound Arnold Schwarzeneggers.
My reactions to amphetamine and bromocryptine are the reverse. I experience an improvement in energy and mood from amphetamine within an hour. This effect disappears after a few more hours, whereafter I lose the improvement and get sleepy and irritable. When last I tried bromocryptine, it was in combination with Parnate and desipramine. I experienced an improvement within the first day. Unfortunately, as seems to be always the case, I lost it after three days. It's as if my gas-tank is near empty, and is quickly drained after the engine starts up and runs for a little while.
I don't see Provigil in your list.
One study I came across indicated that modafinil produces an increase in the release of dopamine in the nucleus accumbens. (I also found a glucose-utilization study representing regional brain activity that contradicted this). I would interpret this to be an indicator of a downstream net effect representing the increased activation and the elevations in mood and motivation produced by this drug. It is proposed that this is accomplished through an inhibition of GABAergic neurotransmission, most likely controlled via noradrenergic pathways that are influenced by the NE alpha-1 agonist actions of modafinil. Other structures important for wakefulness and activation are also stimulated, but not by direct action at the dopamine synapse. As a matter of fact, neuroleptics apparently are unable to reverse modafinil-induced increases in behavioral activity in lab animals. (I am suspicious that the technicians are sometimes placed in this category). Modafinil is much more selective as to which pathways are stimulated when compared to the shotgun blast of amphetamine.
Perhaps Provigil would accomplish your mission by not depending on dysregulated dopaminergic synapses, and by not stimulating those pathways that may produce counterproductive effects that are idiosyncratic to your condition.
I just wanted to fill up a page. I'm sure you've already tried it.
- Scott
-------------------------------------------------------------
Neuroscience 1998 Dec;87(4):905-11 Related Articles, Books
Brain regional substrates for the actions of the novel wake-promoting agent modafinil in the rat: comparison with amphetamine.Engber TM, Dennis SA, Jones BE, Miller MS, Contreras PC
Department of Pharmacology, Cephalon, Inc., West Chester, PA 19380, USA.
Modafinil is a novel wake-promoting compound for which the mechanism and sites of action are unknown. We examined the neural substrates in the brain for the actions of modafinil using 2-deoxyglucose autoradiography and compared the findings to those obtained with amphetamine. Modafinil showed a relatively restricted pattern of changes in brain regional metabolic activity, while amphetamine altered glucose utilization in a wide variety of brain regions. Both modafinil and amphetamine increased glucose utilization in all subregions of the hippocampus (subiculum, CA1-CA3 and dentate gyrus) and in the centrolateral nucleus of the thalamus. Modafinil also increased glucose utilization in the central nucleus of the amygdala, but amphetamine had no effect in this region. Brain structures in which amphetamine increased metabolic rate but modafinil had no effect included regions of the basal ganglia, other nuclei of the thalamus, the frontal cortex, the nucleus accumbens, the ventral tegmental area and the pontine reticular fields. These findings suggest that, while both modafinil and amphetamine promote wakefulness, they act via distinctly different mechanisms. Modafinil appears to act on a specific subset of brain pathways which regulate sleep and wakefulness, whereas amphetamine affects a greater number of cerebral structures involved in the regulation of these behavioral states. Modafinil also lacks the pronounced effects on the extrapyramidal motor system which are characteristic of amphetamine and other psychomotor stimulants, implying that the effects of modafinil are not mediated by the dopamine system and that modafinil may selectively increase wakefulness with fewer side effects.
PMID: 9759978, UI: 98430778
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6 : Eur J Pharmacol 1996 Jun 13;306(1-3):33-9 Related Articles, Books
The vigilance promoting drug modafinil increases dopamine release in the rat nucleus accumbens via the involvement of a local GABAergic mechanism.Ferraro L, Tanganelli S, O'Connor WT, Antonelli T, Rambert F, Fuxe K
Institute of Pharmacology, University of Ferrara, Italy.
The present in vivo microdialysis study demonstrated that the subcutaneous injection of modafinil (diphenyl-methyl-sulfinyl-2-acetamide) in doses of 30-300 mg/kg dose dependently increased dopamine release from the intermediate level of the nucleus accumbens along the rostro-caudal axis of the halothane anaesthetized rat. The effect of modafinil in a dose of 100 mg/kg was counteracted by the local perfusion in the nucleus accumbens with the GABAB receptor antagonist phaclofen (beta-p-chlorophenyl-gamma-aminopropyl-phosphonic acid) (50 microM), the GABAA agonist muscimol (3-hydroxy-5-aminomethyl-isoxazolol) (10 microM) and the neuronal GABA reuptake inhibitor SKF89976A (4,4-diphenyl-3-butenyl-nipecotic acid) (0.1 microM), whereas it was increased by the GABAB receptor agonist (-)-baclofen [beta-(p-chlorophenyl-gamma-aminobutyric acid)] (10 microM). In addition, the modafinil-induced increase of dopamine release was associated with a significant reduction of accumbens GABA release. These results suggest that the dopamine releasing action of modafinil in the rat nucleus accumbens is secondary to its ability to reduce local GABAergic transmission, which leads to a reduction of GABAA receptor signaling on the dopamine terminals.
PMID: 8813612, UI: 96408605
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Posted by PeterJ on May 13, 2000, at 23:17:42
In reply to Re: Amphetamine Treatment of Mania - PeterJ, posted by SLS on May 13, 2000, at 9:03:43
> > My own personal observations is that amphetamine initially sedates me, with delayed stimulation after a few hours. Other dopaminergic drugs are almost invariably sedating and de-activating to me. These include ritalin, pemoline, bromocriptine, diethylpropion, bupropion, l-dopa, and isocarboxazid. For example, if I take ritalin, I have to lie down, and am virtual immobile for several hours. All the other drugs in the list produce similar effects.
>
> This appears to be similar to a low-dose apomorphine effect. Under a microscope, your presynaptic autoreceptors probably resemble tiny membrane-bound Arnold Schwarzeneggers.Terminator autoreceptors. That could well be. I like the image, anyway. "Hasta la vista, Dopamine.!" Maybe I should try (ami)sulpiride to negate these guys.
> My reactions to amphetamine and bromocryptine are the reverse. I experience an improvement in energy and mood from amphetamine within an hour. This effect disappears after a few more hours, whereafter I lose the improvement and get sleepy and irritable. When last I tried bromocryptine, it was in combination with Parnate and desipramine. I experienced an improvement within the first day. Unfortunately, as seems to be always the case, I lost it after three days. It's as if my gas-tank is near empty, and is quickly drained after the engine starts up and runs for a little while.Have you tried l-dopa? If the gas tank is the presynaptic catecholamine store, it might help (in combination with a stimulant) On the other hand, you could be experienceding tachyphylaxis due to a downstream effect. Either the DA receptors down regulate quickly or the cells stimulated by DA (or the cells they affect...and so on) become refractory to more stimulation.
> I don't see Provigil in your list.
I haven't tried Provigil (Modafinil) however I have tried a close cousin Olmifon (Adrafinil) which I ordered from France a few years ago. It is used there for fatigue and depression. My reasons for trying it were just what you suggest--that it produces stimulation by a different mechanism. I even spoke with the inventors of modafinil/adrafinil when they visited the U.S. for a conference.
However, much to my disappointment, a brief trial of adrafinil produced similar sedating effects to those of all the DA drugs I had tried. Not quite as severe, but definitely sedating and not stimulating.
Caffeine does stimulate me, BTW, but not in a good way. I become very nervous.
Yohimbine also was mildly sedating, too.
Peter
Posted by Adam on May 16, 2000, at 18:39:39
In reply to Re: Yess, Virginia, Hollywood toots Coca, posted by PeterJ on May 13, 2000, at 4:36:44
The man clearly was abusing crack cocaine.
Of course Scientology forbids that.
So is it then a GOOD thing, or a BAD thing?
> There's creativity in Hollywood? I hadn't noticed. :-)
>
> I have no beef against using drugs to enhance creativity. It's not my thing, but it works for some people. Live and let live.
>
> But If the government insists on regulating drugs, I think they should find out what John Travolta was on when he made "Battlefield Earth" and ban it (Schedule I)!
>
> Peter
Posted by john bower on July 15, 2001, at 20:02:03
In reply to Re: Amphetamine Treatment of Mania - PeterJ, posted by SLS on May 13, 2000, at 9:03:43
What nutritional supplements help in bipolar mania / depression / cycling.
GABA, L-Taurne, L-Glutamine, Choline and inositol, L-Tryphtophan, if needed --- for rapid cyclers ?? - 500 m.g. phenylalanine.
Posted by SalArmy4me on July 19, 2001, at 0:40:20
In reply to GABA in treatment of mania/nutritional supplements, posted by john bower on July 15, 2001, at 20:02:03
Why not just turn to a professional doctor to treat such a difficult problem as rapid-cycling?
> What nutritional supplements help in bipolar mania / depression / cycling.
>
> GABA, L-Taurne, L-Glutamine, Choline and inositol, L-Tryphtophan, if needed --- for rapid cyclers ?? - 500 m.g. phenylalanine.
Posted by Elizabeth on July 19, 2001, at 11:30:15
In reply to Re: GABA in treatment of mania/nutritional supplements, posted by SalArmy4me on July 19, 2001, at 0:40:20
> Why not just turn to a professional doctor to treat such a difficult problem as rapid-cycling?
That seems wise. I'd also add that GABA is probably not very effective because it's metabolised extensively before it makes it to the CNS.
-elizabeth
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