Gabapentin losing its effect!?

[Jabberwocky]

anyone else take GABA for actual medical reasons!? such as seizures, like I do!? I also take Keppra for seizures on top of the GABA and have been doing so for quite a bit now and feel the GABA is no longer giving me any type of "feel".

I am scripted 1600MG/day and sometimes will take 3200/day to TRY and get a GOOOOOD feeling but always seem to fall short. havent felt any GOOD effects from the drug since I first started taking it.

also taking 8-12MG/bupe/day - so that always helps but at this point I feel the GABA is useless for personal pleasure and will continue to take at scripted dose for medical reasons.

anyone else feel the same about GABA after taking it for so long!? I get jealous when I see people who took 300MG and actually felt something/anything from it.

 

[dopamimetic]

The gabapentinoids are notorious for loosing the 'good' effects very quickly, mostly related to the relieving effect on mood, anxiety etc. with initial high doses of pregabaline being the most pronounced. The longer term effects are due to blockade of a subunit of calcium channels, as well as there is evidence for them to halt the formation of new synapses... which could be bad on the long run, leading to cognitive / memory impairment as well as even to depression, which seemed to happen to me.

I've been interested previously in what the mechanisms of the acute pregabalin experience are and how they could be reproduced without that rapid and long-lasting tolerance. Unfortunately that thread has disappeared. But it might be that it is some sort of downstream modulation in glutamatergic neurotransmission, maybe together with an increase in GABA synthesis and/or dopaminergic effects because this would fit the quality of the effects quite well.

Interestingly phenibut seems to be more similar to gabapentin / pregabalin in its overall effects than to the structurally very closely related baclofen, which is more of a pure GABA-B agonist and the structural similarity is (probably) why it has been said that phenibut works by that way too, but recent evidence shows that it is a comparatively weak GABA-B agonist and more potent of a α2δ ligand & a dopaminergic.

If my theory is correct, then the levetiracteam (Keppra) would even be counterproductive in regards of the beneficial effects of gabapentin on mood, when they are related to glutamatergic down regulation & the levetiractam shares the cholinergic / AMPA(?) positive allosteric modulation of it's parent molecule, piracetam. The racetams do strongly cancel out the nice effects of NMDA antagonists / dissociatives.

 

[EnlightenedOne1]

Like I've mentioned in numerous threads. Gabapetin's mechanism of action isn't even fully understood. I took it for 3 years at a beginning dose of 3,200mgs a day (800mg 2x per day), and the first 2 days, I thought I had found a miracle drug almost similar to the effects of GHB. Surprisingly, ALL of those effects diminished in days and I continued taking it until I tapered off. The withdrawal is pretty nasty but is EXTREMELY short lived. I went from 3,200 to 1,600 overnight and felt no withdrawals. It wasn't until I took 0mgs of Gababpentin that I had insomnia and brain zaps similar to SSRI wd but not as pronounced.

 

[dopamimetic]

Moved my theory over here into NSPD as it seems to fit more there and might get better suited responses

 

[Jabberwocky]

The gabapentinoids are notorious for loosing the 'good' effects very quickly, mostly related to the relieving effect on mood, anxiety etc. with initial high doses of pregabaline being the most pronounced. The longer term effects are due to blockade of a subunit of calcium channels, as well as there is evidence for them to halt the formation of new synapses... which could be bad on the long run, leading to cognitive / memory impairment as well as even to depression, which seemed to happen to me.

I've been interested previously in what the mechanisms of the acute pregabalin experience are and how they could be reproduced without that rapid and long-lasting tolerance. Unfortunately that thread has disappeared. But it might be that it is some sort of downstream modulation in glutamatergic neurotransmission, maybe together with an increase in GABA synthesis and/or dopaminergic effects because this would fit the quality of the effects quite well.

Interestingly phenibut seems to be more similar to gabapentin / pregabalin in its overall effects than to the structurally very closely related baclofen, which is more of a pure GABA-B agonist and the structural similarity is (probably) why it has been said that phenibut works by that way too, but recent evidence shows that it is a comparatively weak GABA-B agonist and more potent of a α2δ ligand & a dopaminergic.

If my theory is correct, then the levetiracteam (Keppra) would even be counterproductive in regards of the beneficial effects of gabapentin on mood, when they are related to glutamatergic down regulation & the levetiractam shares the cholinergic / AMPA(?) positive allosteric modulation of it's parent molecule, piracetam. The racetams do strongly cancel out the nice effects of NMDA antagonists / dissociatives.

English, please!?

why do you feel the levetiracteam is counterproductive? you feel combining the two would lead them to be less beneficial when it comes to mood!? what about the overall effect!? esp. when it comes to seizures!? because, in the end, that is really what I take them for.

phenibut and GABA are very much alike; those are two drugs I have taken quite often! even mixed them at different points and would end up w/ a heavy nod and find myself half asleep - gotta be careful when playing with a heavy dose. I havent touched phenibut in months since getting a steady script of GABA - very similar effect and no hassle w/ having to mix/weigh out powder.

 

[Jabberwocky]

brain zaps are never good when you have a brain tumor, like myself.. which is why I am scripted the gaba/levetiracteam . 1600/MG/gaba and 3000/MG/levetiracteam! I use the 1600/MG in the AM rather than space throughout the day; I use the 3000MG/levetiracteam twice throughout the day in 1500/MG doses (AM/PM). I still feel the GABA had an effect early on even when using w/ the levetiracteam

 

[dopamimetic]

I've tried to explain my theory over here

I could be totally wrong of course concerning the gabapentin & levetiracetam. That they have both a protective effect against seizures and do not cancel out each other. But it could be that they do not interact as well together as they should and using a different combo involving the unfortunately seldom used tiagabine (Gabitril, available in France - an anti epileptic that works by inhibiting GABA reuptake, so doing very roughly the same as the suggested increase in GABA synthesis of pregabalin/gabapentin, as well as the NMDA antagonist memantine that showed anti convulsive effects in studies too and as I can tell works to prevent or alleviate brain zaps from SSRI withdrawal).

Dual effects of gabapentin and pregabalin on glutamate release at rat entorhinal synapses in vitro.
But then again, Felbamate but not phenytoin or gabapentin reduces glutamate release by blocking presynaptic NMDA receptors in the entorhinal cortex.

lyrica's (pregabalin's) real mechanisim
And so on. Sorry for flooding you with information, I have yet to read through all these interesting new references and then I might be able to come up with a more accurate theory

 

[Stargazer]

I take 800mg 3x day-Neurontin. It was prescribed for nerve pain, but didn't do much for that. However, it helps with anxiety tremendously for me. I've been taking it about a year now...it still helps.

If I don't take it, anxiety and panic comes back pretty much. I understand taking it in large doses-it produces the feeling that I get sometimes w Lyrica. Being the gabapentin is a weaker analog than pregablin...why not get an Rx for Lyrica? Due to your situation, it seems you could. I'm actually surprised your Dr. didn't prescribe Lyrica/Pregablin for you.

Taking it in in large quantity for those "good, trippy feelings" can only be done occasionally, then you have to keep taking higher doses, and you go through your script really fast. Lyrica is a better bet if that's your desire.

Don''t take it everyday....if your condition allows, take it every other or every two days, and you'll get the feeling you want. To clarify, I'm talking about Lyrica/Pregablin. Hope you're well Brown.

 

[Jabberwocky]

I go to MGH - mass general hospital and I am in the neurology center - they have some of the best doctors in the world. I was originally scripted the 3000MG of leve/day but brought up the gaba for my own personal reasons; the Dr. was cool w. it and felt it would only be a PLUS to what I was already taking - didnt feel it had any type negative effect to go along w/ the leve.

 

[dopamimetic]

Okay, then this aspect has been wrong. Sorry, I am just an amateur interested in neuroscience & highly speculating on these topics which always comes with the high possibility for false conclusions etc ... I don't want to say that I am anywhere near to being a professional at all (which I am not) but at least some of my theorized thoughts have been amazingly accurate regarding newly found studies, papers & research ... so at least I am not totally wrong about everything.

This includes the beneficial effects of dissociatives (NMDA antagonists) on some mood disorders, therapy resistant refractory depression etc. which is now very interestingly being extensively researched in the regards of the unique effects Ketamine showed.
And no doctor would have believed me if I'd have tried to talk about this back in 2005.

 

[Stargazer]

- nothing wrong with trying to help others

 

[Jabberwocky]

I take 800mg 3x day-Neurontin. It was prescribed for nerve pain, but didn't do much for that. However, it helps with anxiety tremendously for me. I've been taking it about a year now...it still helps.

If I don't take it, anxiety and panic comes back pretty much. I understand taking it in large doses-it produces the feeling that I get sometimes w Lyrica. Being the gabapentin is a weaker analog than pregablin...why not get an Rx for Lyrica? Due to your situation, it seems you could. I'm actually surprised your Dr. didn't prescribe Lyrica/Pregablin for you.

Taking it in in large quantity for those "good, trippy feelings" can only be done occasionally, then you have to keep taking higher doses, and you go through your script really fast. Lyrica is a better be if that's your desire.

Don''t take it everyday....if your condition allows, take it every other or every two days, and you'll get the feeling you want. To clarify, I'm talking about Lyrica/Pregablin. Hope you're well Brown.

why do you feel Lyrica would be better for me!? I am going to bring it up next time I see him but I am having a hard time figuring out why Lyrica may be a better script!? Lyrica I consider for pain; I am NOT in pain; however, I do have a tumor and seizures are something I have to put up w/ in life. The leve works but I added on the gaba for my own personal use; all things still are working out just fine but I def. lost that good "feel" I once had w/ the gaba.

I did have a seizure a few months back after taking an Adderall during the day and having a HARD TIME sleeping at night; didnt sleep till around 5AM and ended up having a seizure in my sleep around 8AM - I ALWAYS have seizures in my sleep - thats WHEN/IF I even have a seizure.

nowadays I am taking quetiapine/seroquel to sleep; it always worked for me so I went back to it.

any advice on how to go about getting lyrica/prega would be great, ha.

 

[dopamimetic]

If gabapentin works for you, then pregabalin could always be worth a try as it has a similar profile of effects but a better bioavailability and more linear pharmacokinetics afaik.

While quetiapine gets used widely for sleep in low doses and seems to work quite well, this effect is because of its histamine H1 antagonism and possibly adrenergic blockade. One of its metabolites afaik is a norepinephrine reuptake inhibitor and this could make things worse, as well as the dopamine antagonism does (even just 50mg make some people restless including me & my girlfriend before the sedation takes over, and >100mg are highly dysphoric and anxiogenic to me). Clonidine can make a good sleep aid at 75-150mcg, as well as the OTC antihistamine doxylamine which in the right dosage (sometimes even below the usual 25mg - 12.5mg or even less can be enough) mimics the sedative effects of quetiapine quite well afaik.

Your bad reaction to Adderall / amphetamine might be related to the norepinephrine which I feel is counter-productive in many. The unfortunately currently RC-only isopropylphenidate is a much better alternative and even has been patented for ADHD. Low dose (ami)sulpride might also do the trick.
But then again it could be that dopamine itself is pro-convulsive, I really don't know, but I'd bet that the norepinephrine is much worse in this aspect as it intensifies things like brain zaps & inner tension which I attribute to be related to pro-convulsive mechanisms at a sub-seizure threshold. If this is true, then the quetiapine would be possibly bad.

There is the (possibly wrong) speculation that norepinephrine is helpful for ADHD. This might be true for part of the individuals, or it might be from the beneficial effects of atomoxetine (Strattera) which is a NRI. It has recently been shown that it does antagonize NMDA glutamate receptors, and the related reboxetine which is only a NRI but probably does not affect glutamate does not share the beneficial effects and has even been suggested that it should been withdrawn from the market as an anti depressive because of lack of efficiency. On the other side the NMDA antagonist memantine has repeatedly shown positive effects for ADHD as well as anti-convulsive & anti-depressive / anxiolytic effects and after the brain adjusted to its nACh antagonism, also pro-cognitive effects.

Seroquel just gets used so widely because Big Pharma is pushing it.

 

[Jabberwocky]

any catch one of the last Drugs, Inc!? they show the dude pushing Seroquel in prison; I remember back in my prison days (04/05) is when I first heard of Seroquel; some dude, my roomie, would always get it for sleep. there would be times he would give me his dosage and I'd use it for sleep. at the time I thought it was such a big deal and I was "getting away" w/ so much; now I look back and realize I was a 21yr old fool w/o a clue! ha. just funny thinking back.

anyway, the pregabalin seems to be pushed more-so for pain than anything else; I cant imagine a neurologist scripting it for seizures but lets see what happens; I have no problem bringing it up and giving it a try! after all, I've known the guy for a bit now and he knows I am always updated in the pharma game, so maybe, just maybe, he'll go w/ my decisions rather than his.

 

[chrisincville]

Yeah, you're definitely not going to get the euphoria from gabapentin forever, but it should still be helping pain. I have nerve pain and am scripted 3600mg/day. I still feel it helping the nerve pain when I have lost any recreational benefit.

Pregablin is a lot more potent and doesn't have the atrocious BA that gabapentin has. There is also an extended release version of gabapentin that is now available (gabapentin encarbil) which supposedly fixes the BA to a more acceptable(? ) rate.

 

[Stargazer]

^^^ Brown the above posters have the scientific backup info down better than I can explain.

Lyrica/Pregablin, I believe, in Europe where its sold over the counter, was first used for generalized anxiety disorder and seizures. So, it's become a dual diagnosis medication. It is as Chrisin said, a lot more potent than Gabapentin...That feeling many people seem to like from gaba, comes from the Pregablin in it.

The reason I think Pregablin would be better for you, is it will give you the feeling that you say you are trying to get from Gabapentin...it's really Pregablin that you like. You can also build a tolerance to Pregablin....that's why I suggested, if your condition allows, if you get an Rx for it, you skip a day in between your meds, and you will get that feeling. It's better than taking all your gabapentin, and maybe if you're lucky...you'll get that feeling. Like- Monday...take Pregablin....Tues and Weds....skip it....Thurs-take it. I guess it's staggering it, in a different way than is suggested for gabapentin.

I take Lyrica for nerve pain. It's the only med, out of the hundreds I've been prescribed that actually helps. I don't take it everyday, even though I'm supposed to. I take it more PRN....I worry it won't help for pain anymore if I take it daily..I've been through too much w this condition. Anyway, I stay on Gapapentin because it stabilizes anxiety and panic attacks for me. As I said, more by accident I found it to help for the anxiety. It was supposed to be for nerve pain. I'm sure you know that gabapentin is also a dual diagnosis med.

Funny you mention Seroquel and Drugs, Inc lol you're funny....I didn't hear of it until I was locked up. I was about the only person that wasn't taking it. And I was having trouble sleeping (?)...anyway, I took some about 2wks ago, when having a lot of difficulty sleeping (I have to get my Amitryptilline-sp? Rx filled)....It was not a good experience. I felt drugged-like my head weighed 200lbs. and sand bags were on my legs...but I still couldn't sleep It lasted the entire next day. Everyone is different that's for sure.

Hope that helps Brown. And you have very intelligent people helping out ^^^ Hope you're well.

 

[razordesignz]

It's amazing the lengths some users go to in explaining things scientifically and in a pharmaceutical sense. Gabapentin effects die off very fast hence why the mgs increase so greatly to such high numbers quickly. Just like all drugs you need more and more and more. Try getting to the root of the problem. If it is a deeper medical need seek out a specialist. Almost no medication works long term without bad things being included unless you hit good with something that builds in your system. Like (gross) ssri's or anti depressants etc. And even they due quite strange things to your mind over time things which are generally close to impossible to reverse long term.

 

[Stargazer]

Chrisin...yes, if your nerve pain gets worse, Pregablin is a Godsend.

I mentioned skipping days with Pregab was in reference to getting the feelings of well-being Brown is asking about. If it is taken everyday, a tolerance builds quickly, and as with Gaba, those feelings will no longer be felt. I have been told by friends in the UK that they can purchase Pregab over the counter. And at first, it was prescribed for GAD and seizures. The reason it Pregab came up is one of my friends is unable to take it, due other meds he is on. I said "I believe", not "In Europe" Just wanted to clarify

I certainly am not as scientifically informed as you are, and am speaking from personal experience. I guess I wasn't able to convey that as well as I thought...

The cost of Lyrica is outrageous....and Gaba isn't cheap either, you aren't kidding.

 

[chrisincville]

Chrisin...yes, if your nerve pain gets worse, Pregablin is a Godsend.

Oh, I'm sure..I've taken pregablin plenty of times in the past, and have had it scripted twice. One of the main reasons I kept switching back to gabapentin is that I am able to make a month's supply of gabapentin last nearly 3x longer than that of what strength/dose the docs put me on.

I mentioned skipping days with Pregab was in reference to getting the feelings of well-being Brown is asking about. If it is taken everyday, a tolerance builds quickly, and as with Gaba, those feelings will no longer be felt. I have been told by friends in the UK that they can purchase Pregab over the counter. And at first, it was prescribed for GAD and seizures. The reason it Pregab came up is one of my friends is unable to take it, due other meds he is on. I said "I believe", not "In Europe" Just wanted to clarify

*thumbsup*

I certainly am not as scientifically informed as you are, and am speaking from personal experience. I guess I wasn't able to convey that as well as I thought...

No worries! Actually, it's probably me that's slipping, LOL. And I'm no doctor, scientist, pharmacist, or any other type of medical professional..just a patient/addict that has a fascination with meds in relation to science and the effects drugs have on the human body. Although, sometimes I feel like I am more informed than the med people I deal with, haha.

Plus, I've done many hours of research out of pure fascination..[/quote]

The cost of Lyrica is outrageous....and Gaba isn't cheap either, you aren't kidding.

Yep and the same pharmaceutical company owns the patents to both..

 

[pally pete]

Chrisin...yes, if your nerve pain gets worse, Pregablin is a Godsend.

I mentioned skipping days with Pregab was in reference to getting the feelings of well-being Brown is asking about. If it is taken everyday, a tolerance builds quickly, and as with Gaba, those feelings will no longer be felt. I have been told by friends in the UK that they can purchase Pregab over the counter. And at first, it was prescribed for GAD and seizures. The reason it Pregab came up is one of my friends is unable to take it, due other meds he is on. I said "I believe", not "In Europe" Just wanted to clarify

I certainly am not as scientifically informed as you are, and am speaking from personal experience. I guess I wasn't able to convey that as well as I thought...

The cost of Lyrica is outrageous....and Gaba isn't cheap either, you aren't kidding.

Pregabalin is not available over the counter here in the UK.

Prescription only.