16 replies to this topic

[brainslugged]

I realize that tolerance quickly builds to phenibut's sedative effects, but maybe we are wrong in thinking it tolerance builds to all of its effects.

http://onlinelibrary...1.tb00211.x/pdf
on page 4 suggests

Chronic administration of PB (50 mg kg i.p., twice daily for 5 days) promoted a tolerance to its sedative action on the last day of treatment while its nootropic effect was enhanced.

(the dosage here would be about 570mg in humans if injected. The bioavailability may not be good for phenibut orally, so the dosage would have to be adjusted accordingly)

and on page 5,

Discontinuation of chronic injections of PB to rats increases the density of GABA A and BDZ receptors in striatum while that of GABA B is decreased (38). Chronically administered BDZs have opposite effects.

would suggest that phenibut both Increases GABA-B receptor sites (while also binding to them) and decreases sensitivity of GABA-A (since the opposite of those happen on discontinuation). The wording is a bit odd, though, and the next sentence claims that "Chronically administered BDZs have opposite effects". I assume they mean the administration has the opposite effects from the discontinuation of phenibut? That is strange wording, but BDZs decrease GABA-A sensitivity with chronic use, right?

The difference between the two, though, is that phenibut possesses action at GABA-B receptors which would become more sensitive over time as the GABA-A receptors return to homeostasis.

Chronic i.p. administration of PB in mice antagonized the development of morphine dependence (5,6). BAC and sodium valproate had similar effects. PB also reduced naloxone-induced withdrawal effects in mice addicted to morphine (6).

on page 5 is also in line with the theory that GABA-B receptor action remains or increases with chronic use since GABA-B receptor agonists are known for decreasing drug dependence.

So, I think it is possible that phenibut possesses actual nootropic effects that we are overlooking by using it as a sedative. Although a crappy sedative due to swift tolerance, it could end up being a nice cognition/mood enhancer by acting on GABA-B receptors once the GABA-A receptors have downregulated to a homeostatic level.

I know it is only one paper, but do you think it is possible that phenibut exhibits nootropic effects through GABA-B receptors, and the initial effects that most people chase are only the effects on GABA-A receptors?

[lammas2]

Discontinuation of chronic injections of PB to rats increases the density of GABA A and BDZ receptors in striatum while that of GABA B is decreased (38).

I would say this is some kind of a compensatory mechanism - the body tries to compensate the excessive glutamate caused by downregulated GABA-B receptors by upregulating GABA-A and BDZ receptors. For benzodiazepines the body tries to compensate the excessive glutamate caused by downregulated GABA-A and BDZ receptors by upregulating GABA-B.

From personal experience with GHB/GBL/Benzos, I'm pretty sure that phenibut primarily binds to GABA-B receptors and only high doses result in some GABA-A activity. So yes - phenibut exhibits its nootropic effects through GABA-B agonism. The thing is - GABA-B agonism causes downstream dopamine release, which can also be 'nootropical'. But long-term use of phenibut has no nootropic benefits. It works great at first, but soon downregulation happens and you need to increase the dosage to feel the same effects. Fast forward few weeks and you need massive dosages just to avoid withdrawals - downregulated GABA-B and dopamine receptors cause massive anhedonia and anxiety.

All in all, for me phenibut is still my #1 supplement. Be careful with it though - GABA-B does not forgive nor forget.

[kenj]

Interesting. While I've initially sampled the 1-2 grams dosage a couple times, I take no more than 500mg/day now, but I do take it consistently throughout the week. Been doing this for a couple years now, with occasional breaks lasting weeks w/o any (perceived) withdrawal. YMMV.

[lammas2]

Do you still feel the effects? Are they less pronounced than in the beginning? What is the main reason for your daily phenibut usage?

[lourdaud]

Interesting. While I've initially sampled the 1-2 grams dosage a couple times, I take no more than 500mg/day now, but I do take it consistently throughout the week. Been doing this for a couple years now, with occasional breaks lasting weeks w/o any (perceived) withdrawal. YMMV.

No signs of mineral depletion?

[kenj]

Do you still feel the effects? Are they less pronounced than in the beginning? What is the main reason for your daily phenibut usage?

The effects are the same as they were in the beginning: very subtle mind relaxation, but I found it to 'synergize' nicely with some of the racetams I were taking: aniracetam at first, and lately coluracetam.
It's difficult to describe/express the anecdotal 'nootropic' effects from it, so I'll just go with "very subtle mind relaxation". :-)

I've read about people swallowing GRAMS of this stuff for various reasons, and that's a no-go IME; I do get the "phenibut buzz" (kinda like being drunk), but basically cognitively nonfunctional if I exceed 1.5-2 grams, so I don't do that.

Interesting. While I've initially sampled the 1-2 grams dosage a couple times, I take no more than 500mg/day now, but I do take it consistently throughout the week. Been doing this for a couple years now, with occasional breaks lasting weeks w/o any (perceived) withdrawal. YMMV.

No signs of mineral depletion?

Which minerals?

[vali]

I'm going to second the phenibut + racetam synergy. While I use phenibut only very rarely, when I do I always take some piracetam or aniracetam with it. The effect is very nice.

[Dreamy]

I definitely notice a nootropic effect from Phenibut, but it seems to be dose dependent. At around 750-1000 mg I notice an increase in physical and mental energy. At my old job I was completing work tasks much quicker and more efficiently, and my ability to interact and socialize with people was greatly improved. The only problem now is I don't seem to have an effect from that dosage anymore, and anything over 1200 mg seems to nullify the nootropic effect.

I decided to take a small break and combine it with 400 mg of oxiracetam and 200 mg of caffeine before class today. I'll report back after class.

[spookytooth]

I took Phenibut 4-5 times in the last few weeks at doses ranging from 750mg to around 2g. The effect was great and incredibly helpful in social situations but after the last two times taking it during which I dosed around 2g each time my cognition was shot. Horrible short term memory und extremely fuzzy thinking.
I should add that I do not possess a healthy brain to begin with so this might not happen to a "normal" user.
Loved the way it made being a "people-person" easy though...

Edited by spookytooth, 27 August 2013 - 10:42 PM.

[brainslugged]

I have been taking ~1g/day for the past 2 days, and it has been amazing. Much better than 500mg which didn't do much.

I was extremely at ease and positive but not benzed up like I am on 2g+. Keep in mind I am taking this with d-amp and racetams, so that may counter some of the GABA-A effects, and it is too early to tell if these effects are primarily due to GABA-A or B

I would say this is some kind of a compensatory mechanism - the body tries to compensate the excessive glutamate caused by downregulated GABA-B receptors by upregulating GABA-A and BDZ receptors. For benzodiazepines the body tries to compensate the excessive glutamate caused by downregulated GABA-A and BDZ receptors by upregulating GABA-B.

But that doesn't make as much sense in the context of changes after discontenuation of the drug. If Benzos downregulate GABA-A receptors to form tolerance, you would expect discontinuation of benzos to cause the receptors to upregulate, or at least not downregulate even more.

The wording is tricky.

From personal experience with GHB/GBL/Benzos, I'm pretty sure that phenibut primarily binds to GABA-B receptors and only high doses result in some GABA-A activity. So yes - phenibut exhibits its nootropic effects through GABA-B agonism. The thing is - GABA-B agonism causes downstream dopamine release, which can also be 'nootropical'. But long-term use of phenibut has no nootropic benefits. It works great at first, but soon downregulation happens and you need to increase the dosage to feel the same effects. Fast forward few weeks and you need massive dosages just to avoid withdrawals - downregulated GABA-B and dopamine receptors cause massive anhedonia and anxiety.

All in all, for me phenibut is still my #1 supplement. Be careful with it though - GABA-B does not forgive nor forget.

Thanks. What dosage do you use and how often?

Also, the goal would be to remain at a level where the effects aren't strongly feelable, but there, similar to stimulants after the initial semi-euphoric stage where they no longer provide the feeling that they initially did, but they retain concentration benefits. So, I will not ever be increasing dosage in pursuit of its "good" feeling effects.

The effects are the same as they were in the beginning: very subtle mind relaxation, but I found it to 'synergize' nicely with some of the racetams I were taking: aniracetam at first, and lately coluracetam.
It's difficult to describe/express the anecdotal 'nootropic' effects from it, so I'll just go with "very subtle mind relaxation". :-)

This may be the same result as I have been getting for the past few days. I would describe it as a "cool" mood. A general decrease in neuroticism, maybe,

I've read about people swallowing GRAMS of this stuff for various reasons, and that's a no-go IME; I do get the "phenibut buzz" (kinda like being drunk), but basically cognitively nonfunctional if I exceed 1.5-2 grams, so I don't do that.

Yeah, high doses help me sleep for an eternity, but that is about it. I don't understand the attachment to the phenibut "high". To me, it makes me feel dizzy and like I am in a dream-state. Over 3 grams, and I feel like I have brain damage.

I decided to take a small break and combine it with 400 mg of oxiracetam and 200 mg of caffeine before class today. I'll report back after class.

I'm interested to know results.

I took Phenibut 4-5 times in the last few weeks at doses ranging from 750mg to around 2g. The effect was great and incredibly helpful in social situations but after the last two times taking it during which I dosed around 2g each time my cognition was shot. Horrible short term memory und extremely fuzzy thinking.
I should add that I do not possess a healthy brain to begin with so this might not happen to a "normal" user.
Loved the way it made being a "people-person" easy though...

I've had good results from this dosage (1g) in the past, during my HS graduation. It doesn't make me a "people-person", but does act as a very nice social lubricant and make me be able to work in groups better, like Dreamy's experience. Less overload from being around more than one person. Also reduced inhibitions. During graduation, I wasn't specifically more social, but I didn't get the normal "holy fuck so many people moving everywhere and doing infinite things" feeling that I get at events with a lot of people, and I didn't spaz out when people talked to me, although I was still quiet and reserved. It also synergized with alcohol nicely afterwards

High doses affect my cognition in the same way as you, though. Fuzzy thinking is a good description for it.

[mrnootropic]

People say no dont use it long term, I would say the same. I would cycle it.

I didnt cycle it , i didnt experience any side effects even when i took it everyday.

People menton some horrible side effects, i would just cycle it 5 days on 2 days off just to be safe.

[spookytooth]

What I meant to say was that after I had taken it and the effect had worn off my cognition was influenced for the negative. I didn't mind the slightly fuzzy thinking during the higher doses. It took me about a week to recover and get back to baseline. I get that with most drugs (incl. alcohol) though which is the reason why I don't normally consume any. I had hoped to find something in phenibut that I may enjoy from time to time easing social situations like dating etc without those cognition crushing effects afterwards.

Edited by spookytooth, 29 August 2013 - 10:27 PM.

[brainslugged]

Well, used it every day for the past week (5 days in a row). Wow. Great effects and no signs of them slowing. I have been SO at ease during (physics) lab and everything. I am very functional. I talk to people and everything, just like a normal person :D

Mood has been good. Haven't been overloaded during lab, which is very, very nice. Very aware and focused yet calm. Reading comprehension under pressure is better. Just generally in a very, very good mood. In class, the calming effect of the phenibut synergizes very nicely with the d-amp. On tests, I am focused, yet without needing anxiety to be focused (as before d-amp) and without the schitzy feel from d-amp elevating my anxiety on tests.

Also, increased libido and increased enjoyment of activities.

Very good results so far, but it has only been 5 days. I hope it keeps on like it has been. This could end up being a very valuable drug for long term use as long as dosage isn't raised to seek the euphoric effect. Will just have to wait and see.

What I meant to say was that after I had taken it and the effect had worn off my cognition was influenced for the negative. I didn't mind the slightly fuzzy thinking during the higher doses. It took me about a week to recover and get back to baseline. I get that with most drugs (incl. alcohol) though which is the reason why I don't normally consume any. I had hoped to find something in phenibut that I may enjoy from time to time easing social situations like dating etc without those cognition crushing effects afterwards.

Hmm. That seems odd. Especially with piracetam, I don't ever withdraw from anything, it seems. Even d-amp, with piracetam, there is little to no change from baseline when I take a break (from the d-amp). Have you tried piracetam in combination with it?

People say no dont use it long term, I would say the same. I would cycle it.

I didnt cycle it , i didnt experience any side effects even when i took it everyday.

People menton some horrible side effects, i would just cycle it 5 days on 2 days off just to be safe.

Side effects from long term usage? I've never heard of them unless the person keeps increasing the dosage. I may do 5 on, 2 off, though, if I start to feel tolerance. At the same time, by one line of thought, it would be bad to take a day off if the nootropic effects really do have reverse tolerance. You would be setting the tolerance back.

[lammas2]

You are really playing with fire here. Ofcourse I can understand you, the honeymoon period of phenibut is heaven on earth. But it won't last forever. Phenibut is a strong GABA-B agonist, your receptors WILL downregulate. 2 days off is nowhere near enough to reverse tolerance. The effects will start to fade sooner or later, withdrawals very likely, even at low dosages (first hand experience). When you get there, don't quit cold turkey, do a slow taper.

http://www.mindandmu...enibut-casualty

Kinda related to this topic: I once did a mathematical analysis exam while under the influence of GBL (GABA-B agonist). Got the highest score possible. GABA-B agonists (in the right dose) definately have a nootropic property.

Edited by lammas2, 31 August 2013 - 12:01 AM.

[123apk]

Interested to hear if any of you guys went through with this long term use of Phenibut?
As other people have mentioned though, the social lubricant effects do go unfortunately.

[brainslugged]

Not to resurrect a thread but I have been taking it daily (about 1g/day) still since I made these posts. And I still get effects.

• A slight phenibut wave of relaxation and mood boost *still* occur about 2-3 hours after taking it.
• The effects on my ability to socialize and not get overwhelmed still stands. I don't know if its because I have learned to get over my anxieties and to deal with social situations better during the initial effects or if it is still due to the effects of phenibut.

I haven't really noticed any negative side effects. Of course its possible that they do exist and have just become normal to me after over 3 years. But I am far happier and more functional than I was in 2013, and while phenibut is only a small part of that, it is still a part that I feel is significant. It certainly hasn't caused my life to get worse. And I haven't died or anything.

 

Its just one anecdotal report. Maybe I'm a unicorn. But I think that more attention should be given to phenibut and it should be demonized less. Like every drug that has the potential to induce euphoria, it does have dangers and abuse potential. And it does build tolerance and have withdrawal effects. But its important to remember that tolerance isn't always (or even normally) complete tolerance, and that substances with potential for abuse can certainly have potential for responsible and beneficial use as well.

 

I am certainly not suggesting that everybody go out and buy some phenibut and take it every day or that it can't be addictive and dangerous. But I do think that it has potential as a mood-boosting and anxiety-reducing medicine with relatively few side effects

[Ben]

The problem I have with phenibut is the effect I sense that it has on BDNF. After taking it for a while I get the opposite effect of lions mane (less motivation, lower mood).

 

I don't really know how to interpret these papers, but another (better known in the west) GABAb agonist, baclofen, has some evidence for BDNF inhibition:

 

https://www.ncbi.nlm...ubmed/21930121:

 

 

 

Baclofen (10mg/kg, i.p.), but not THIP (10mg/kg, i.p.) or flunitrazepam (10mg/kg, i.p.), administration resulted in significant inhibition of BDNF mRNA expression in the cornu ammonis 3 and dentate gyrus but not in the cornu ammonis 1 region of the hippocampus.

 

 

Baclofen prevents the elevated plus maze behavior and BDNF expression during naloxone precipitated morphine withdrawal in male and female mice.

 

 

However: For alcohol patients receiving a high dose of baclofen, there were no changes versus control for serum BDNF (I wonder if serum measurement isn't effective)