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Guanfacine seems nootropic

guanfacine

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#1 protoject

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Posted 04 July 2013 - 05:18 PM


Hey guys,
haven't been posting much or involving myself too much in discussion here recently so I apologize for that.
Just kinda rudely pokin my head in here.
I hope you guys have been doing swell,
and won't mind me mentioning that I've been having some success with guanfacine for ADHD.

However, not at doses regularly perscribed by a doctor.

I think the doses they perscribe are 0.5mg up to 4 mg and even 8 mg sometimes. I will detail my dosage in a minute...

Some people say guanfacine is the opposite of a nootropic and it dumbs them down.

I disagree- I find it helps me focus without causing much for negative side effects. It also appears to be enhancing my memory (both imprinting and recall)- particularly if I try to remember.

However the dosage I use for this has been converted from a rhesus monkey study into a human dose, rather than using what's regularly perscribed to a human.

0.0015 mg per kg
in rhesus monkey would be
0.000486486486486486486486486486486
in human. . . .
per kg.

x 66 kg (my weight)

=0.03 mg

Dissolving powdered guanfacine (pure) into distilled water and using a dropper to dose.

My dropper:
dropper= 1 mg per mL
5 drops per 0.25 ml
meaning 1 divided by 20
=0.05 mg .

So I'm using about the same dosage as the monkey.

But why use this dosage, you say?
Because I found that 0.25 mg of guanfacine and anything above that causes too many side effects.
The side effects are- depressive mood swings, worsened insomnia , clouded mind and, it's almost actually bordering on this wierd half awake/half asleep psychotic kind of symptom which is hard to describe.

I decided going down to that super low dosage was reasonable because it works to enhance a monkey's memory and attention, and is mostly side effect free for me. (well, not 100%, but it's to a point where the benefits exceed the side effects). I'm also under the impression that I'm building up the levels of guanfacine in my blood day by day and helping maintain an effect while combatting any tolerance, since it's half life is 17 hrs, though I am not sure if this would actually translate into my brain still being under effect of whatever guanfacine has already been metabolised from the previous day.

Problems:
- I haven't objectively measured attention and memory. I've simply noticed that on the days of dosing guanfacine, I am able to recall song names, album names, artists names and sounds for songs. Usually I can remember the sound if it starts playing, but with guanfacine I can actually take multiple points of data, remember them and tie them together and if I remember one thing, it cascades into the other memories that were imprinted.

It is also easier to focus on one task and get lost in doing it, rather than becoming bored and giving up.
It hasn't cured all ADHD symptoms but has made it easier to focus and take an interest in what I am doing.
At times it is easier to organize categories of information; seperate them into specific functions and then relate them together.
I would also say it is different than amphetamines in the sense that it is more subtle.
Also, although it's said that guanfacine shouldn't be motivating but only calming, it is actually motivating to some degree. Because you feel like you want to pursue your interests due to this new found mental ability, and you feel more confident that you can actually complete a task.

Anyway thought anyone curious about that or with interest would consider, hypothetically, that this dosage might work if other dosages haven't turned out well for them, due to side effects or comorbid disorders.

I have also taken a lot of nootropics over the years and I'd say most of them didn't work out for me, but guanfacine works better than those for me personally.

Edited by protoject, 04 July 2013 - 05:22 PM.

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#2 KoolK3n

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Posted 04 July 2013 - 07:47 PM

How did you obtain the pure powder?

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#3 brainslugged

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Posted 04 July 2013 - 08:01 PM

Interesting. I was looking at Guanfacine yesterday night some, and had all but given up on it. It is a frequent source of confusion for me. It is interesting to read an anecdote and about the study. http://www.ncbi.nlm..../pubmed/2903226

So I guess this is going right back on my watch-list of drugs. I was disappointed by the claims that it reduced memory and reduced cAMP, but this gives it new hope. I was unaware of the subtypes mentioned in the studies. It would be interesting to see if other people have the same results at this dose.

Do you know how stable it is in water? It could be very cost-effective to buy 2mg tabs and dissolve them.

EDIT: Oh, didn't see that you bought a powder. I 2nd KoolK3n's question.

Edited by brainslugged, 04 July 2013 - 08:03 PM.


#4 sparkk51

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Posted 05 July 2013 - 01:27 AM

Interesting. I was looking at Guanfacine yesterday night some, and had all but given up on it. It is a frequent source of confusion for me. It is interesting to read an anecdote and about the study. http://www.ncbi.nlm..../pubmed/2903226

So I guess this is going right back on my watch-list of drugs. I was disappointed by the claims that it reduced memory and reduced cAMP, but this gives it new hope. I was unaware of the subtypes mentioned in the studies. It would be interesting to see if other people have the same results at this dose.

Do you know how stable it is in water? It could be very cost-effective to buy 2mg tabs and dissolve them.

EDIT: Oh, didn't see that you bought a powder. I 2nd KoolK3n's question.


I can't give you a source, but I'm pretty sure reduced cAMP would increase prefrontal cognition, as cAMP inhibits it. This is part of the reason Guanfacine is good for ADHD.

Edited by sparkk51, 05 July 2013 - 01:27 AM.


#5 KoolK3n

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Posted 05 July 2013 - 01:38 AM

Interesting. I was looking at Guanfacine yesterday night some, and had all but given up on it. It is a frequent source of confusion for me. It is interesting to read an anecdote and about the study. http://www.ncbi.nlm..../pubmed/2903226

So I guess this is going right back on my watch-list of drugs. I was disappointed by the claims that it reduced memory and reduced cAMP, but this gives it new hope. I was unaware of the subtypes mentioned in the studies. It would be interesting to see if other people have the same results at this dose.

Do you know how stable it is in water? It could be very cost-effective to buy 2mg tabs and dissolve them.

EDIT: Oh, didn't see that you bought a powder. I 2nd KoolK3n's question.

I was extremely interested in getting my hands on some Guanfacine, but was fairly disappointed with the reviews online. Even when the drug worked as in improved focus, concentration, memory, etc it typically resulted in blunted emotion aka zombie effect. But regardless I still wanna try it but probably at the dose protoject uses. Found this interesting wiki page that explains how it works: http://en.wikipedia...._Nervous_System. I think increased cAMP keeps the HCN channels open leading to weaker signaling.

Edited by KoolK3n, 05 July 2013 - 01:40 AM.


#6 Default8

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Posted 05 July 2013 - 03:12 AM

I can't give you a source, but I'm pretty sure reduced cAMP would increase prefrontal cognition, as cAMP inhibits it. This is part of the reason Guanfacine is good for ADHD.


:/ I think you have that the wrong way around. I could find lots of articles on this but I'll leave you with one from the 80's on the beloved Piracetam.

http://www.ncbi.nlm..../pubmed/6311225

During investigations of 2-oxy-pyrrolidine-acetamide (piracetam, Nootrop) the influence on the cyclic adenosine monophosphate (cAMP) level was measured. 20 guinea pigs (inbred albinos) were used for the investigations. 6 animals served as a control group, 14 animals were treated daily for 16 days with 35 mg piracetam/kg b.w. The cAMP concentration was determined in the frontal brain and intestine. The animals treated 16 days with piracetam showed an increase of cAMP in the frontal brain of 134% compared with untreated animals. In the intestinal tissue, the difference between the control group and the piracetam-treated animals ranged around 84%.


If that is not enough look up "Inhibition of Cyclic AMP Phosphodiesterase (PDE4) and cognition"

Edited by Default8, 05 July 2013 - 03:13 AM.


#7 KoolK3n

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Posted 05 July 2013 - 04:13 AM


I can't give you a source, but I'm pretty sure reduced cAMP would increase prefrontal cognition, as cAMP inhibits it. This is part of the reason Guanfacine is good for ADHD.


:/ I think you have that the wrong way around. I could find lots of articles on this but I'll leave you with one from the 80's on the beloved Piracetam.

I don't think the mechanism is fully understood and I don't think you read my post. cAMP keeps HCN channels open. Open=Bad. Guanfacine works by indirectly closing the channels. Closed channels=Good (in the prefrontal cortex).
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#8 Default8

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Posted 05 July 2013 - 05:46 AM

No I didn't, got a bit excited. Any references for cAMP keeping HCN channels open? Don't worry found it.

Alpha2A-adrenoceptors strengthen working memory networks by inhibiting cAMP-HCN channel signaling in prefrontal cortex.

We report that alpha2A-AR stimulation strengthens working memory through inhibition of cAMP, closing Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels and strengthening the functional connectivity of PFC networks.


Interesting... will read the full thing when I have the time

Edited by Default8, 05 July 2013 - 06:27 AM.


#9 Default8

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Posted 05 July 2013 - 07:38 AM

From that "Alpha2A-adrenoceptors..." article

In hippocampus, high levels of cAMP are essential for long-term potentiation and memory consolidation, leading to long-lasting changes in synaptic architecture (cAMP also plays a beneficial role when hippocampus interacts with Pre-Frontal Cortex (PFC) under conditions when delay lengths are very long, see (Runyan and Dash, 2005). In contrast, the WM operations of the PFC depend on the transient activation of microcircuits that are disrupted by high levels of cAMP. Thus, cAMP-HCN signaling may play an especially important role in PFC.



So we are both right :P

According to wikipedia the α2A adrenoceptors that Guanfacine act on are localised on the pre-frontal cortex. So OP might be on to something here.

In the article it talks about Guanfacine application of 5 nA to 50 nA. What kind of units are these?

Edited by Default8, 05 July 2013 - 07:39 AM.


#10 brainslugged

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Posted 05 July 2013 - 08:27 AM

According to wikipedia the α2A adrenoceptors that Guanfacine act on are localised on the pre-frontal cortex. So OP might be on to something here.

Damn, your right. Here I was worried about hippocampal cAMP. I've been making this kind of mistake a lot recently. Guess I need more nootropics so that I can research nootropics, ha ha.

I was extremely interested in getting my hands on some Guanfacine, but was fairly disappointed with the reviews online. Even when the drug worked as in improved focus, concentration, memory, etc it typically resulted in blunted emotion aka zombie effect. But regardless I still wanna try it but probably at the dose protoject uses. Found this interesting wiki page that explains how it works: http://en.wikipedia...._Nervous_System. I think increased cAMP keeps the HCN channels open leading to weaker signaling.


Yeah, I am not wanting the blunting effect either, but lower doses may be able to help with that. I didn't realize that it was only pfc cAMP that it reduced.

I don't know if this is good or bad for amphetamine sensitization. A few weeks ago, it seems like I found a study saying that cAMP reduces sensitization, but I can't find it now, only stuff contrary http://scholar.googl...t=0,11&as_vis=1 so it may be beneficial to amp use.

I don't know, and don't want to derail the thread with that, just throwing it out there.
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#11 joostus

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Posted 05 July 2013 - 09:34 AM

I think only the extended release version is really working for Guanfacine. While it has an half-life of 15 to 18 hours the peak plasma rises to quick with the IR Guanfacine. Rising and falling blood-sugar levels probably lead to the side effects Protoject is witnessing. While micro-dosing might be a solution, I was interested in taking this for ADHD, because I don't have much luck with the stimulant medication. The dose for ADHD is 4mg of the extended release, it's too bad that the price for the extended release is 20 times higher the the generic IR version. If I find a cheap source for the extended release I will most certainly try it.

On a side note don't take this medication in combination with the traditional ADHD medication (stimulants like methyl-phenidate and amphetamines) because it puts a dangerous strain on your body.

#12 brainslugged

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Posted 05 July 2013 - 10:31 AM

On a side note don't take this medication in combination with the traditional ADHD medication (stimulants like methyl-phenidate and amphetamines) because it puts a dangerous strain on your body.


How so? What are the subjective effects? Is there a pharmacological reason not to do it? I thought it was fairly common in psychiatry.

#13 Default8

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Posted 05 July 2013 - 11:53 AM

Be interesting to try Guanfacine and GEBR-7b (provided it's safe)/Rolipram together. May decreases cAMP in the pre-frontal cortex and increase it in the hippocampus

Edited by Default8, 05 July 2013 - 12:07 PM.


#14 KoolK3n

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Posted 05 July 2013 - 10:58 PM

Be interesting to try Guanfacine and GEBR-7b (provided it's safe)/Rolipram together. May decreases cAMP in the pre-frontal cortex and increase it in the hippocampus

The two should work together but a higher dose of Guanfacine would probably be needed to counteract the elevated cAMP.

#15 KoolK3n

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Posted 08 July 2013 - 12:24 AM

I don't know if this is good or bad for amphetamine sensitization. A few weeks ago, it seems like I found a study saying that cAMP reduces sensitization, but I can't find it now, only stuff contrary http://scholar.googl...t=0,11&as_vis=1 so it may be beneficial to amp use.

I found some really interesting info on Agmatine and its inhibition of NOS. http://examine.com/s...ments/Agmatine/. Tell me what you think of it.
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#16 KoolK3n

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Posted 08 July 2013 - 12:40 AM

Be interesting to try Guanfacine and GEBR-7b (provided it's safe)/Rolipram together. May decreases cAMP in the pre-frontal cortex and increase it in the hippocampus

I think I got it! The use of Trental SR, Clonidine or Guanfacine (preferable), and other hypotension preventive treatments (lots of water and salt intake with exercise) http://www.ncbi.nlm....les/PMC2888469/. Trental is a potent nonselective phosphodiesterase inhibitor that significantly boosts cerebral blood flow and intracellular cAMP levels. Clonidine has been reported to reduce blood flow maybe because of its potent hypotensive action http://www.ncbi.nlm....les/PMC3087273/. So the two could synergize. Both Clonidine and Trental SR are available off of Nobledrugstore.com. I had no problems with them so far and the Clomid I ordered was of good quality. But anyways, what do ya'll think so far? Increased cAMP and decreased Clonidine/Guanfacine side effects.

#17 Major Legend

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Posted 08 July 2013 - 12:41 AM

interesting...how long did it take to stark working? and isn't there risk of fainting standing up and stuff on this kind of medication?

#18 brainslugged

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Posted 08 July 2013 - 03:10 PM

I don't know if this is good or bad for amphetamine sensitization. A few weeks ago, it seems like I found a study saying that cAMP reduces sensitization, but I can't find it now, only stuff contrary http://scholar.googl...t=0,11&as_vis=1 so it may be beneficial to amp use.

I found some really interesting info on Agmatine and its inhibition of NOS. http://examine.com/s...ments/Agmatine/. Tell me what you think of it.

Holy fuck. BRB while I order a lifetime supply of that :|o

I didn't know that Agmatine had all those properties. Really, that is an amazing finding for tolerance. I am getting giddy now. It is so available, too. Decrease in nNOS, inhibition of calcium channels, NMDA inhibition... that's the top 3 mechanisms, all in one substance, holy cow. Then the fact that it decreases opiate tolerance is consistent with the memantine pattern, so this looks to be a very promising substance (and safe/nootropic too).

The (possible) anti-nictonergic effects are a bit worrying, and it does say that it may increase cAMP (although I am not sure where in the brain), but the substance is still promising.

This is really exciting. Thank you so much. I will buy some and test it if I can get a script for an amp next psych visit (end of the month). I don't want to hype it too much in my mind, but it looks good.

I also didn't know that examine was so information-rich. Last time I looked at it, it seemed like it was just a paragraph summary. Either it improved a ton or I got unlucky and had viewed a crap example in the past (or I just didn't pay attention enough).

Edited by brainslugged, 08 July 2013 - 03:12 PM.

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#19 KoolK3n

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Posted 08 July 2013 - 03:43 PM

Holy fuck. BRB while I order a lifetime supply of that :|o

That's exactly what I was thinking!! lol. But sadly, I found it's implicated in schizophrenia: http://www.ncbi.nlm....pubmed/23664672 and http://www.ncbi.nlm....pubmed/21989253. I think the response is definitely U-shaped dose dependent curves. Most of the benefits, antidepressant, anxiolytic, and cognitive enhancing effects were noted roughly between 3mg/kg-10mg/kg in humans. For me, that could be 250mg/d-1000mg/d. I doubt it will cause mental illness but this certainly warrants more research. Agmatine levels decline as you age so how would that be an adequate biomarker for schizophrenia when a lot of times doesn't develop until middle age? It's all very complex. Anyways, I think the most reliable source would be USP Labs off of Amazon. It's one of the more expensive brands but I think the quality is legit. HardRhino is selling a kilo for $45 but they run a shady business. According to my dosage, I would be spending $20 a month for 1000mg/d of Agmatine from USP Labs. If I stick with a low 500mg/d. Price would cut in half.

Edited by KoolK3n, 08 July 2013 - 04:02 PM.


#20 BieraK

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Posted 24 November 2017 - 12:21 AM

https://www.ncbi.nlm...ubmed/21883531/

If someone is interested here is the study. I was experimenting with a similar compound this year, clonidine, with very low microdoses 25 mcg disolved in 7 - 8 ml of water, then one ml of that solution. The first day effects where notorious, a sense of confidence and motivatión. The nexts days the drug started to give me a very relaxed but not sedated sense of body, I was in the present moment "here right now" less interna world focused, relaxed and with confidence. The last dosage of the drug was combined with Polygala, that was one of the most profound effects of a nootropics I was very focused and calm, reading a book of linguistic theory, a friend was close to me and I not see it, then he sit in a chair very close to me and I not see it until he tell "hello, wow you are so concentrated, what are you reading?". I only read 45 minutes but the experience was so profound I remember very well until today some of the ideas of the book. Another excellent effect was a reducción in pain and better sleep, my body was fully relaxed in the morning. I think that these drugs go very well with classical stimulants because counteracts anxiety and body tensión. I ordered Guanfacine today I hope that I could repeat that experience, because was very joyful, peaceful and productive. If this works well I will stack it with a phenidate or amphetamine.

Edited by BieraK, 24 November 2017 - 12:24 AM.

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#21 jack black

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Posted 24 November 2017 - 05:10 PM

BieraK,

Thanks for posting. I have access to both and I tried regular doses and it was too sedating. I may need to try the low dose method.



#22 BieraK

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Posted 27 November 2017 - 08:02 PM

Yes, try low doses, regular dosage of clonidine gives me a sedating sense of body and send me to sleep.

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#23 gamesguru

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Posted 27 November 2017 - 08:32 PM

I was disappointed by the claims that it reduced memory and reduced cAMP, but this gives it new hope. 

 

cAMP is a double edged sword anyways.  there was recently a thread tying it together with glutamate and alzheimers.  that means less can be better

 

you can even find some supporting evidence along those lines

α2A-Adrenoceptors Strengthen Working Memory Networks by Inhibiting cAMP-HCN Channel Signaling in Prefrontal Cortex

http://www.sciencedi...092867407003443

 

too often though people look at an interesting substance and think, how can i get my hands on that?  really though they are more often than not useless in practice and useful only as something to appreciate, to further our awareness.. an academic tool.  like imagine if everybody all the time thought about how to get their hands on some good lsd, we would lose some respect for it inevitably and not do ourselves any favors in the process.  better to let the academicians be the pioneers, the barriers to research are being slowly lifted and they sadly are not to be found in your basement with you hamster wheel


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