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Which receptors/enzymes to target for - drive, ambition,self-improvement?

motivation drive receptors enzymes ambition will dopamine serotonine goal self-improvement

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#1 chris106

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Posted 09 June 2013 - 03:39 PM


Ok, I'll try to keep the introduction short for once.
There are many threads on this board regarding motivation or fighting ahedonia. It's basically accepted that dopamine (for motivation) and serotonine ( for fighting anxiety and avoidance-behaviour, which indirectly cripple motivation) are involved.

However, reading through threads like the "(anticipatory) ahedonia" thread, or the "confidence and self-esteem" thread, there seems to appear a repeating problem when reading between the lines;

While many compounds that target serotonine (and to lesser extent dopamine and norepinephrine) and thereby decrease anxiety or avoidance-behaviour are highly supportive regarding social life and enjoying things more, they may have the tendency to make a person come to terms with it's current situation in life and decrease high-ambition and drive.

Now of course this can be a good thing - but not when, for example, pursuing a long term goal that is very ambitious and needs investment of determination and "blood and sweat" is the task at hand. Let me quote Galaxyshock, who put my point to words much better in the Anticipatory Ahedonia Thread:

...I've noticed mild anxiolysis, improved motivation, and mood elevation. There might be more curiosity, which is always a great sign - could be 5-HT2A upregulation or placebo. On the negative side, I could see how one could become content with a non-ideal situation - which could also be considered a positive depending on your perspective...



Getting to the point:
Because stimulants can make you feel "burnt out" after long term usage ( DA receptor downregulation), and anxiolytics
can make one become too comfortable and content with a "non ideal" life-situation -

I think instead of discussing which compounds are motivating (dopaminergic) or anxiolytic (serotonergic) in general, it would be interesting
to see if certain specific receptors or enzymes have shown to be involved in increasing what I would describe as:

- drive (more in a career-pursuing way)
- (will for) self improvement
- ambition (which in a way is the opposite of being satisfied with one's current situation)
- goal motivated behaviour ( without becoming an emotionless, anti-social prick, if possible :) )


I hope my point came across: There has to be a sweet spot between being overly stimulated by inducing stress and "fight- or flight mode" (which is how most stimulants operate), and beeing all flowers and butterflies about one's current circumstances, even when those are not ideal.

Now it may be naive to believe that what I call "ambition" can specifically be optimized trough targeting certain receptors or enzymes..
But after trying a lot of different nootropics/compounds in the last months, and sometimes temporarely hitting said sweet spot, I think there could be something to this theory...

So I'd love to hear your thoughts on this, and which compounds (or even better yet the specific receptors/enzymes they interact with) helped you in maintaining a healty level of ambition and goal motivated behaviour, without burning you out or overstimulate!

(Of course hormones, especially testosterone can play an important part in this too, so anecdotal experiences with them would be a welcome addition,too)

Edited by chris106, 09 June 2013 - 03:44 PM.


#2 daouda

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Posted 09 June 2013 - 04:14 PM

Anything that significantly raises Testosterone without allowing too much aromatization into estrogens will accomplish all this.
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#3 chris106

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Posted 09 June 2013 - 04:53 PM

Well, I guess Tongkat Ali comes to mind? I remember reading about a compound that could (partially) prevent Testosterone being aromatized into estrogen, but for the life of me, I can't seem to find it right now @_@'

Any examples of substances that accomplish this?

(I'm allready using DAA, Mucuna, high dose Vit-D and LO-Zinc, but even after a few weeks this combo does little to nothing in this regard. While I suspect low (free) Testosterone as a possible culprit, it seems I need to trigger other mechanisms to raise it...)

Also, has anyone here below the age of 35 tried DHEA with continous success? Is it possible to harm the bodies own ability of producing testosterone when starting supplementation with this at a too young age (I'm 28)?

Edited by chris106, 09 June 2013 - 04:56 PM.

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#4 Godot

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Posted 09 June 2013 - 05:34 PM

I think this is a most astute question to be asking. Addressing full neurotransmitter systems is a very diffuse, primitive approach. I don't know if there are answers to your question yet.

One thing that I have found to be quite stimulating of drive and feelings of personal power is the pheromone molecule androsterone (administered via olfaction.)

Here's a summary of its effects: http://pheros.net/di...drosterone-rone

Field tests of this pheromone molecule on its own have shown that wearers of small amounts, generally around 2.5mcg, enjoy an elevated social status and are treated with a higher level of respect than normal. Users also report a feeling of confidence and of increased masculinity. At higher doses, androsterone seems to incite confrontational thought and behavior in the wearer and others, unless buffering molecules such as alpha androstenol or epiandrosterone are added.


Also, if you're looking to manipulate T levels, you could try grapeseed extract as an aromatase inhibitor and stinging nettle to increase free T.

Edited by Godot, 09 June 2013 - 05:34 PM.


#5 chris106

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Posted 09 June 2013 - 06:08 PM

One thing that I have found to be quite stimulating of drive and feelings of personal power is the pheromone molecule androsterone (administered via olfaction.)


Well I admit I have experimented with Pheromones in the past, even though 'd have to check if they really contained androsterone. So am I getting this right - the wearer only "feels" personally empowered because others (especially females) treat him differently? I think this approach would be very prone to placebo, I remember feeling more empowered and confident just because I approached people more to see if the pheromones really worked - out of sheer curiosity.

Don't know how to phrase it, but this approach seems a little too "indirect" for me, even though it could be kinda like the "cherry on the cake" so to say, if other things work out as well.

However, the part about grapeseed extract and stinging nettle seems most interesting. Guess I'll have to do a little more digging on the whole (pro)-hormone topic, before I can make any educated decissions on what to try...

Also,I learned a new word today - astute. Yay! :)

EDIT: According to examine.com, grapeseed extract may not be bioavailable enough to to reach noticeable aromatase inhibition...

The Procyanidins themselves have very potent effects in vitro (especially anti-inflammatory and aromatase inhibiting) but the apparent poor bioavailability of GSE makes these pathways most likely either underpowered or less significant than the in vitro leads us to believe.


Maybe a combination of Tongkat Ali (even though it's aromatase inhibiting properties are not proven) and DHEA would be promising?

Edited by chris106, 09 June 2013 - 06:19 PM.


#6 Godot

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Posted 09 June 2013 - 07:08 PM

One thing that I have found to be quite stimulating of drive and feelings of personal power is the pheromone molecule androsterone (administered via olfaction.)


Well I admit I have experimented with Pheromones in the past, even though 'd have to check if they really contained androsterone. So am I getting this right - the wearer only "feels" personally empowered because others (especially females) treat him differently? I think this approach would be very prone to placebo, I remember feeling more empowered and confident just because I approached people more to see if the pheromones really worked - out of sheer curiosity.


On the contrary, many people find that the effects on the wearer are more powerful than the effects on others -- which makes sense, considering that the wearer is exposed at closer range for a longer period of time.

Everyone that has tried more than 5 micrograms or so of androsterone on its own without anything to buffer its effects has reported finding themselves thinking and behaving aggressively. At lower doses, the self-effect could be in line with what you're looking for.

#7 chris106

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Posted 09 June 2013 - 07:51 PM

Well, makes sense I guess - maybe I'll give it another try sometime after all...

Not to derail the topic, but I just found a ridiculously cheap source for 200:1 Tongkat Ali extract.
Now after extensive research on Longecity I'm aware that only Pasak Bumi aka "Indonesian Eurycoma Longfolia" is the real deal, and that it's extremely rare to find a reliable source that doesn't sell scam.

That being said - I have ordered from Indigoherbs many times before, and can vouche for at least their Rhodiola Rosea, Jiaogulan and Mucuna being the real deal.
Still, 18€ (or 21$) for 25g of "real" 200:1 extract seems just impossible...

Long story short, I'll be the guniea pig here, since I allready ordered. Their shippments usually arrive in Germany via 2-4 days, so I guess I'll soon be able to tell you all if this stuff is legit!

Maybe I'll open a single Thread for this though, so back to the topic! :)

Edited by chris106, 09 June 2013 - 07:53 PM.

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#8 magniloquentc0unt

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Posted 10 June 2013 - 10:00 AM

I'm happy you're opening this thread, as i'm in your exact situation: been fighting what has eben recently nailed down to disthimia with negative schizo symptoms. been on Tianeptine the last 2 months, with partial success, and im not happy yet. I had my hormones checked a year ago and everything scored fine: but the "fine" range is so wide....

Edited by magniloquentc0unt, 10 June 2013 - 10:14 AM.


#9 magniloquentc0unt

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Posted 10 June 2013 - 10:14 AM

I can maybe add my 2 cents in the form of anectodes regarding a couple of points:
I have tried a couple of substances: Fluoxetine (Prozac), Tianeptine (Stablon), Methylphenidate (Ritalin), Modafinil (Provigil).
I did not respond to the Ritalin and the Modafinil.

- drive :
Fluoxetine game me good drive, i was literally doing things i wouldve never done otherwise, i just had energy and motivation
Tianeptine gives me some drive, but not even remotely near as the fluoxetine
- (will for) self improvemen
Fluoxetine made me learn a ton of new stuff while i was on it: was curious and motivated to learn things. it was rewarding. I believe its not only due to the energy levels.
Tianeptine is, as of now, second month im on it, not really affecting my behavious in this aspect.
- ambition - goal motivated behaviour
None of the substance changed anything in regards to this, i believe this trait might be more related to the personality of the individum

anyhow, for me fluoxetine wasnt worth it, left me with emotional numb personality and "who cares its all fine" actitude that im trying to revert with tianeptine, i would not suggest you take it, but maybe its useful for research purposes, you know, checking what receptors it touches etc.

#10 chris106

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Posted 11 June 2013 - 01:38 PM

Thanks for your insight on your experiences it's very much appreciated! Especially the part about Ritalin and Modafinil not affecting you, I allmost can't imagine that :)
Just goes to show again that everyone's brain-chemistry is different, I guess It's pretty safe to say that your problem isn't dopaminergic in nature :)

- ambition - goal motivated behaviour
None of the substance changed anything in regards to this, i believe this trait might be more related to the personality of the individum


Very interesting point! That's pretty much why I opened this thread! I have high ambitions in some areas of my live, and in those i desperately want to improve and make the most out of me. And on some days this feeling/mindset is very strong. So I guess it is somewhere in my character - otherwise It wouldn't make me feel so angry when I feel like this ambition/feeling is often burried under a layer of shit, anxiety and brainfog so I just can't access it on other days - even though it was clearly there just before...


Anyhow, I think you are also following the anticipatory ahedonia thread, but I forget - have you tried SJW and Panax yet? Or Rhodiola? The right adaptogens combined can have quite the powerfull effect, if taken for a long enough period of time. What about Sam-e?

Regarding hormone tests I pretty much agree with you. The standard for what is conscidered to be the "normal" range in those is very questionable. I belive there should rather be an "optimum" range. Also you'd have to dive deep into the topic to be able to determine if really all the important parameters are checked, or if the test is just on a superficial level...
have you looked into possible thyroid issues,too? Or maybe a sleeping disorder or apnea being the possible root for your issues?

Sadly, the list of possible culprits is sheer endless, but It's allways worth pursuing the search of the root of one's problems!

Edited by chris106, 11 June 2013 - 01:49 PM.


#11 Thorsten3

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Posted 11 June 2013 - 09:53 PM

The best thing I have found for drive/motivation is polyrachis ant. It stimulates ATP and I find it extremely energizing. It's also quite adrenergic, but, not overly so like tongkat or HGW - so is suitable for day to day use. It's never spoken about and is very unheard of in most parts.

I wouldn't say it motivates me with long term planning or career goals, but it kicks my ass in to gear for nailing tasks, day to day. It just energizes you and doing things that are boring don't become tiring or exhausting. I mean, it apparantly is a highly anti-inflammatory compound. So, this might explain this effect. I notice the same anti fatigue effects from schizandra, he shou wu, reishi, chaga and anything else that is highly anti-inflammatory.

Polyrachis, also, apparantly, increases strength/endurance, stamina (like rhodiola, which also increases ATP) and sexual drive. Of which, I can definitely confirm! It doesn't necessarily increase libido, per se, but it has resolved my erectile function issues - to the extent, where I can literally shag like a rabbit. No longer being 'Mr 30 second man' is a such a relief!

Do I have studies? No. I'm not even aware of any, to be honest in our Western world. However, I do trust the thousands of years of research that has gone behind such compounds in Chinese medicine. Polyrachis is a revered herb and one of the all time greats - alongside reishi, schizandra and ginseng. It isn't some obscure compound that even Chinese medicine doesn't even recognize.

There isn't anything euphorically mood enhancing, about it. So, for me, there isn't any distractions whilst using it (hedonistic persuit and all activities/distractions that lead towards it, for instance).

It's ideal for my needs and I don't go a day without it.

Edited by Thorsten2, 11 June 2013 - 10:00 PM.

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#12 Tom_

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Posted 11 June 2013 - 10:44 PM

Dopamine, Noradrenaline, reduced global GABA, AMPK glutamate receptors, adrenaline, lowered Ach, corticosteroids

#13 chris106

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Posted 12 June 2013 - 10:59 AM

The best thing I have found for drive/motivation is polyrachis ant. It stimulates ATP and I find it extremely energizing. It's also quite adrenergic, but, not overly so like tongkat or HGW - so is suitable for day to day use. It's never spoken about and is very unheard of in most parts.


Sounds interesing, but this stuff seems very hard to come by, and information about it is sparce. Do you have asource for it? Seems like the kind of compound that would be rather expensive, I guess...

#14 tunt01

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Posted 12 June 2013 - 11:22 AM

Those who worked the hardest had higher levels of dopamine in two areas of the brain known to be important in reward and motivation. The areas are the striatum and ventromedial prefrontal cortex.
That finding wasn't a surprise. Another was: Treadway found that those not willing to work hard for the reward had high levels of dopamine in another brain area involved in emotion and risk perception. This area is the insula.
"The folks with relatively more striatal dopamine were focused on the reward," Treadway says. "The folks with more insular dopamine were thinking about how tired their pinky was. They were focused on the costs."


dopamine in the striatum = reward and motivation.

http://www.webmd.com...rs-slack?page=2


and cdp-choline increases density of dopamine receptors of the striatum

http://www.longecity...ptor-densities/

Edited by prophets, 12 June 2013 - 11:24 AM.

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#15 chris106

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Posted 12 June 2013 - 02:34 PM

and cdp-choline increases density of dopamine receptors of the striatum


True. Oddly enough it's also the only form of choline that doesn't make my Brainfog worse. That being said I can only take 500mg/ day max of CDP, or I'll get too wired/ unfocussed. Plus having ADD-PI, this only slightly helps me...

Edited by chris106, 12 June 2013 - 02:36 PM.


#16 socialpiranha

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Posted 13 June 2013 - 04:28 AM

comt
mao-a and b
phosphodiesterase
enkephalinase
endorphinase

cyclicAMP(cAMP)
nitric oxide

The nucleus accumbens, an area within the striatum is implicated in most reward issues, creb induced dynorphin expression seems to be the bad signal vs dopamine being the good to be simplistic about it.
http://perspectivesi...012005.abstract
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#17 chris106

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Posted 13 June 2013 - 08:26 PM

comt
mao-a and b
phosphodiesterase
enkephalinase
endorphinase

cyclicAMP(cAMP)
nitric oxide

The nucleus accumbens, an area within the striatum is implicated in most reward issues, creb induced dynorphin expression seems to be the bad signal vs dopamine being the good to be simplistic about it.


Now that's what I'm talking about! Thanx for this great post, will read up on all of this as as soon as I can! Definetely should help in finding specific supplements to help in this regard!





Also tagged with one or more of these keywords: motivation, drive, receptors, enzymes, ambition, will, dopamine, serotonine, goal, self-improvement

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