Gabapentinoids The Lyrica (Pregabalin) Mega Thread v 2.0

[Regenesis2]

somebody in my family died and i ended up being the one who got given all the meds, there were a couple of pakets of this as well....

and...
well if you want to try it for some reason or another its not bad really. It's not as addictive and feels better than benzos IMO. It's kinda got like a light cannabis euphoria to it IMO.

 

[Katapult]

i did try 300. actually it hit me off guard and threw me into a dreamcoma on the sofa for 3 hours.dont know if thats a normal reaction but it was quite nice. had no tolerance to any meds or anything at the moment so it was quite intense...good though.

 

[MistaBoogeyman]

first time i took lyrica it were 2 75mgs , took em, half an hour later fell asleep for almost 20 hours.now when i take 1 300mg, it makes me feel my bupe , even though i get the same dose since 2 months and normally dont feel it.if i take a couple 300`s i get.....dont know how to describe it...maybe like couple benzos plus a couple beers?? yeah think that comes the closest. but still benzos are way better......and wayyyy less dangerous!!

 

[FPU4eva]

the withdrawls of using this for 6+months put me in a catonicn state that normal iv benzos did not work(ativan etc) and made it worse nearly died and have nerve damage still beware of detox i had a gram a day habit

 

[Katapult]

ok, had another try of this. I got the 150mg caps.
after 150mg I feel already a lot, slightly like being drunk and somehow it really reminds me of gbl, my speech and walking is quite affected.

when I take another 150mg the effects get much stronger and it literally puts me to sleep. I sleep very long after this and waking up is very difficult. am awake now for an hour and feel very smashed...

I like it as a recreational thing... still got a full pack of 64x150mg caps and that will last me for a long time...

 

[Janja]

Any thoughts on long-term adverse effects from using low to moderate doses of Lyrica for the treatment of fibromyalgia or other disorders? There has been some speculation about nerve damage and reduced cognitive function, but in terms of solid research, it seems that the jury is still out. Any articles on this subject would be welcome.

Also am interested.

 

[oneswtwld]

that shit fucked up my life, career and who knows what else it will do

 

[Katapult]

why that?

 

[SnrG]

that shit fucked up my life, career and who knows what else it will do

How so? How long were you on it and what were you taking daily? I use gbl in sessions of 500ml 24/7 and take a break after three weeks and take 1200 mg per day for a week to kill the g withdrawals.

I severed the big nerve just under the elbow when I almost lost my arm a few years ago, and although they could reconnect the nerve, it didntt join up as it should with the result that I have dead spots where I feel nothing on my arm, but around my wrist and for five inches above the pain response is much more acute than the othe arm, and if i pinch the skin its literally agony.

The pregabalin really reduces this hypersensitivity and also helps with my back pain (two discs removed) and every other pain. My knees are pretty shite, but with pregabalin, I can actually jog and get zero pain response from the knees or the back. Its very helpful for me in this regard. But I usually end up taking the whole 84 200 caps over a week as I like the high. But it is true that it dissipates after two days, so its only really usefulf for getting stoned for this period of time.

If I stick at the recommended dose for anxiety of 200mg x 3 times a day. I have no cognitive impairment. But if I take up to 800 per day as tolerance builds, I have massive cognitive problems and physical problems like shaking hands and slurred speech, and my legs feel like they are made of lead, literally. I find it difficult to walk - I also stagger like a drunk when I take up to 1200mg per day.

I was taking 1000 per day when I had panic attacks about starting a new job, and the result was that I remembered nothing from my handover and training. Absolutely nothing. So it fucked up that job so much, that I am now on sick leave for anxiety and depression, as my head went when my wife threw out my baclofen and lyrica so I couldn't tailor off as I normally do. I was seriously depressed, and was drinking a bottle of vodka a day at work to stop the anxiety. Wait, thats wrong. That was when I ran out of gbl and didnt have my lyrica to kill the gbl withdrawals.

But at high doses, it kills cognitive function, and if you mix in alcohol, it cabbages you.

Sn

 

[kanyeknievel]

Did not realize there was a mega thread for this

Okay so I got prescribed Lyrica, though I don't need it. So i decided to take a recreational does of 750mg at 11:20am.. I felt the peak and the most when i was in my college classes. I was like shakey, trying to write stuff but i wrote so slow, nod out half the time. But in both classes the teacher really liked me haha, i asked a bunch of questions n what no and it was pretty fun.

The high is undescribable, i don't even know how to compare it or explain the feeling.


But to people that have taken this, how long does it last? I do feel I'm coming down and not nearly as bas as before. Its currently 7:22. Its not freakin me out its just im a bit tired of it and just want it to kinda stop and go away.

Will i be back to baseline soon? Or am I gonna feel it somewhat until i go to sleep?

 

[scientist]

I have experience Lyrica twice now. Once yesterday (300mg) and once today (450mg.)

I obtained the tablets from my girlfriends mother who has lots of back pain issues and nerve damage, but she doesn't like to take them for some reason.

The high is rather indescribable. There's a feeling of euphoria but its unlike anything else.. The loss of balance and coordination is also pretty strange. I find its very similar to GHB as the feeling is your head is kinda "tight" but "floaty." I have not had such affects as Mr. Tambourine Man has but I have had the slight dissociative feeling (only comparing to mushies / high doses of nitrous oxide.) I noticed a somewhat introspective feeling aswell, as I was walking to the park with my girlfriends niece yesterday I was thinking alot about the trees and things like that. It was very enjoyable.

I'm rather keen to keep experimenting with these capsules, but if I take 600mg tomorrow, would I get less of an affect considering I've had it for 2 days already?

 

[nervousone]

Did not realize there was a mega thread for this

Okay so I got prescribed Lyrica, though I don't need it. So i decided to take a recreational does of 750mg at 11:20am.. I felt the peak and the most when i was in my college classes. I was like shakey, trying to write stuff but i wrote so slow, nod out half the time. But in both classes the teacher really liked me haha, i asked a bunch of questions n what no and it was pretty fun.

The high is undescribable, i don't even know how to compare it or explain the feeling.


But to people that have taken this, how long does it last? I do feel I'm coming down and not nearly as bas as before. Its currently 7:22. Its not freakin me out its just im a bit tired of it and just want it to kinda stop and go away.

Will i be back to baseline soon? Or am I gonna feel it somewhat until i go to sleep?

please research drugs before you take them. there is absolutely no reason a drugs duration should surprise you. this is the stuff to look up BEFORE you take a drug.

 

[likeakite]

I take The 50 mg Lyricas, about 3 at a time then re-dose as needed. It makes me feel pretty good. Sometimes I still feel it the next day, my body is numb, kinda like Barbs. Lyrica goes well
with Hydro also. Overall a good drug if you have nothing else.

 

[DiRtYjErZ]

Has anyone noticed a marked difference in empty stomach vs full and how eating after dosing decreases effects rapidly?

 

[Vaya]

Has anyone noticed a marked difference in empty stomach vs full and how eating after dosing decreases effects rapidly?

"Pregabalin oral bioavailability is estimated to be greater than or equal to 90% and is independent of dose. The rate of pregabalin absorption is decreased when given with food resulting in a decrease in Cmax by approximately 25 to 30% and a delay in Tmax to approximately 2.5 hours. Administration with food, however, has no clinically significant effect on the extent of absorption."

From a damn good datasheet on pregabalin

~ vaya

 

[Vaya]

Any thoughts on long-term adverse effects from using low to moderate doses of Lyrica for the treatment of fibromyalgia or other disorders? There has been some speculation about nerve damage and reduced cognitive function, but in terms of solid research, it seems that the jury is still out. Any articles on this subject would be welcome.

I'd LOVE to see someone produce some articles on these topics.

~ vaya

According to the book Psychiatric Issues in Epilepsy: A Guide to Diagnosis and Treatment, "There are no formal cognitive studies of pregabalin using formal neuropsychological measures." (p. 86)

Also, the transcript from a presentation archived on medscape entitled "Long-term tolerability of neuropsychiatric disorders in women: Cosmetic, metabolic and cognitive adverse effects" :

There's been concern over the last few years (and we finally started paying attention to the fact) that some of the AEDs can cause fairly significant interference with cognitive function. This sort of cropped up as we started getting a hold of these newer medicines that had actually less effect on cognitive function, and we began to notice this.

But in terms of thinking of the cognitive effects of these drugs, one of the things that's very important to do is to separate sedation from the cognitive effects. It's not necessarily easy, but there is a difference between medicines that make people sleepy and medicines that actually interfere with the ability to process information and to think clearly. On a simplistic level, one of the ways of thinking about it is that for many patients, hopefully most, sedation is an effect people become tolerant to over a period of time. Now, that isn't always the case, but one hopes that after a period of time, patients will be less sleepy from their medicine.

But even given that, some patients will continue to experience persistent disturbances with their thinking. It's also difficult to assess and to evaluate some of the literature that's out there, because measurement of cognitive effects is a very complex process. Some of the older literature that looked at this, when we've gone back and evaluated it very carefully, we realize that what was being measured was really more motor reaction speed rather than cognitive function, and we've had to rethink some of our conclusions about cognitive effects of the drugs on that basis.

It's also very important that when we compare these medicines, we're comparing reasonable nontoxic doses of the medicines. There was a classic case of a comparison of carbamazepine and phenytoin's cognitive effects, and it came out looking like one of the drugs was worse than the other; it turned out that with the drug that looked worse, if I remember correctly I believe it was phenytoin, actually the majority of patients who were assessed with cognitive disturbances were on higher doses with higher blood levels and actually were closer to being intoxicated on medicine. So, making sure we're comparing apples to apples is very important. Next slide, please.

Thinking about just sedation for a minute, this is an attempt to just try to line up our AEDs in terms of their sedative properties, and I think many people would agree with this particular categorization. I'm sure there are some people who wouldn't agree with some of the choices in terms of the pigeonholes that we've put them in, but clearly, some of our older AEDs are quite sedating -- things like phenobarbital, phenytoin, and even carbamazepine, as well as some of our newer medicines, like topiramate. And then we get down to some of our newer medicines that actually aren't very sedating at all. Again, with gabapentin, many patients do get very sedated on that initially, but there seems to be a fair amount of tolerance that develops with gabapentin. Pregabalin has probably the same sort of effect, and lamotrigine of course is not tremendously sedating at all. If we can then, we can go to the next slide.

Thinking about actual cognitive effects of these medicines separate as much as possible from their sedative effects, we can start thinking about a couple of things. One of them is that epilepsy itself may influence cognitive function, depending on the type of seizures a person has, or what the etiology of the seizure disorder is. For example, with traumatic brain injury or stroke, there may be effects of the underlying cause of the seizure disorder on cognitive function.

In terms of our AEDs, it's also kind of important to remember that these medicines exist to tone down or dampen the function of neurons and synapses, and on that basis, we need to anticipate that almost any of these medicines if they're given in high-enough doses, or in combinations, certainly can impair cognitive function. So, it's probably part of what we're working with with these medicines.

A great deal of attention, mentioned a few minutes ago, has been paid over the years to comparing especially the older antiepileptic drugs with each other. There's been a lot of anecdotal information and some very nicely done studies; and if we put all this together, trying to differentiate cognitive effects of things like carbamazepine and phenytoin, it's very difficult to make firm conclusions. On average, the differences between these medicines at clinically useful doses that are not toxic is probably small, on average. That doesn't mean that we don't want to pay attention to individual patients and how they respond to medicines.

Certainly, if we take a good hard look, the best evidence out there says that long-term effects of benzodiazepines, barbiturates, and probably topiramate, one of our newer antiepileptic drugs, the long-term effects of these drugs can be significant on cognitive function. Some of our newer AEDs have been evaluated carefully. If we can go to the next slide, please.

This is just a summary of a couple of studies that were done looking specifically at, in one case, a comparison of gabapentin, lamotrigine, and topiramate. This was in a small group of healthy young adults, so it certainly isn't the most definitive thing out there, but we were looking at clinically useful, clinically appropriate doses of these medicines, and when these people were compared, the cognitive effects of lamotrigine and gabapentin were certainly less than were seen with topiramate.

Topiramate is fairly well established in having some significant ability to interfere with cognition. And the bottom bullet on that slide is just a synopsis of a second study where gabapentin, lamotrigine, and levetiracetam were compared; in that particular study, both comparing them against carbamazepine and comparing the patients against their own baseline, all 3 of those medicines had no discernable negative cognitive impact.

So, it looks as though some of our newer AEDs may have some advantage for us in terms of the potential for causing less cognitive disturbance.

Pertinent accompanying slides:

AEDs and Sedation

Adverse Cognitive Effects

Newer AEDs and Cognition

 

[Regenesis2]

Search for an article called "Lyrica and neurontin are death sentence to new synapses"
I just saw it the other day.
This is news to me and if it is accurate it would make it a really shitty choice to help someone get through benzo withdrawals or other addictions.

 

[Cane2theLeft]

^Yeah there's interesting research on how gabapentin and pregabalin prevent thrombospondin from binding to the receptors thus inhibiting new synapse formation.

The article you mentioned is interesting but in my mind loses credibility with unsubstantiated claims such as...

Neurontin and its newer more potent version, Lyrica, are widely used for off-label indications that are an outright flagrant danger to the public. These blockbuster drugs were approved for use even though the FDA had no idea what they actually did in the brain. A shocking new study shows that they block the formation of new brain synapses1, drastically reducing the potential for rejuvenating brain plasticity – meaning that these drugs will cause brain decline faster than any substance known to mankind.

...

However, such uses can no longer be justified because the actual mechanism of the drugs is finally understood and they are creating a significant long-term reduction in nerve health.

Here is the abstract from the study -

Gabapentin receptor alpha2delta-1 is a neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis.

Eroglu C, Allen NJ, Susman MW, O'Rourke NA, Park CY, Ozkan E, Chakraborty C, Mulinyawe SB, Annis DS, Huberman AD, Green EM, Lawler J, Dolmetsch R, Garcia KC, Smith SJ, Luo ZD, Rosenthal A, Mosher DF, Barres BA.

Duke University Medical Center, Cell Biology Department, Durham, NC 27710, USA. [email protected]

Abstract

Synapses are asymmetric cellular adhesions that are critical for nervous system development and function, but the mechanisms that induce their formation are not well understood. We have previously identified thrombospondin as an astrocyte-secreted protein that promotes central nervous system (CNS) synaptogenesis. Here, we identify the neuronal thrombospondin receptor involved in CNS synapse formation as alpha2delta-1, the receptor for the anti-epileptic and analgesic drug gabapentin. We show that the VWF-A domain of alpha2delta-1 interacts with the epidermal growth factor-like repeats common to all thrombospondins. alpha2delta-1 overexpression increases synaptogenesis in vitro and in vivo and is required postsynaptically for thrombospondin- and astrocyte-induced synapse formation in vitro. Gabapentin antagonizes thrombospondin binding to alpha2delta-1 and powerfully inhibits excitatory synapse formation in vitro and in vivo. These findings identify alpha2delta-1 as a receptor involved in excitatory synapse formation and suggest that gabapentin may function therapeutically by blocking new synapse formation.

And here is the accompanying press release from the researchers (provided on the same site as and in contradiction to the above article)... its long so I put it in NSFW tags. Its very SFW.

NSFW:

Researchers at the Stanford University School of Medicine have identified a key molecular player in guiding the formation of synapses — the all-important connections between nerve cells — in the brain. This discovery, based on experiments in cell culture and in mice, could advance scientists’ understanding of how young children’s brains develop as well as point to new approaches toward countering brain disorders in adults.

The new work also pinpoints, for the first time, the biochemical mechanism by which the widely prescribed drug gabapentin (also marketed under the trade name Neurontin) works. “We have solved the longstanding mystery of how this blockbuster drug acts,” said Ben Barres, MD, PhD, professor and chair of neurobiology. The study shows that gabapentin halts the formation of new synapses, possibly explaining its therapeutic value in mitigating epileptic seizures and chronic pain. This insight, however, may lead physicians to reconsider the circumstances in which the drug should be prescribed to pregnant women.

The paper, to be published online Oct. 8 in the journal Cell, looks at the interaction between neurons — the extensively researched nerve cells that account for 10 percent of the cells in the brain — and the less-studied but much more common brain cells called astrocytes. Much work has been done on how neurons transmit electrical signals to each other through synapses — the nanoscale electrochemical contact points between neurons. It is the brain’s circuitry of some 100 trillion of these synapses that allow us to think, feel, remember and move.

It is commonly agreed that the precise placement and strength of each person’s trillions of synaptic connections closely maps with that person’s cognitive, emotional and behavioral makeup. But exactly why a particular synapse is formed in a certain place at a certain time has largely remained a mystery. In 2005, Barres took a big step toward explaining this process when he and his colleagues discovered that a protein astrocytes secrete, called thrombospondin, is essential to the formation of this complex brain circuitry.

Still, no one knew the precise mechanism by which thrombospondin induced synapse formation.

In this new study, Barres, lead author Cagla Eroglu, PhD, and their colleagues demonstrate how thrombospondin binds to a receptor found on neurons’ outer membranes. The role of this receptor, known as alpha2delta-1, had been obscure until now. But in an experiment with mice, the scientists found that neurons lacking alpha2delta-1 were unable to form synapses in response to thrombospondin stimulation.

And when the researchers grew neurons in a dish that were bioengineered to overexpress this receptor, those neurons produced twice as many synapses in response to stimulation with thrombospondin than did their ummodified counterparts.

The new discovery about alpha2delta-1’s key role in synapse formation carries important implications for understanding the cause of pain and of epilepsy and developing improved medications for these conditions.

It was already known that alpha2delta-1 is the neuronal receptor for gabapentin, one of the world’s most widely administered medications. Gabapentin is often prescribed for epilepsy and chronic pain, and its off-label use for other indications is widespread. Up to now, the molecular mechanism of gabapentin’s action — what, exactly, it’s doing to counter seizures or chronic pain — was unknown. But both syndromes may involve excessive numbers of synaptic connections in local areas of the brain.

In their new study, Barres and his colleagues found that when gabapentin was administered in developing mice, it bound to alpha2delta-1, preventing thrombospondin from binding to the receptor and, in turn, impeding synapse formation. Likewise, by blocking thrombosponin, gabapentin may reduce excess synapse formation in vulnerable areas of the human brain.

Barres noted that he and his colleagues found that gabapentin does not dissolve pre-existing synapses, but only prevents formation of new ones. That greatly diminishes gabapentin’s potential danger to adults. In mature human brains, astrocytes ordinarily produce very little thrombospondin, and adult neurons don’t form many new synapses, although some new synapses do continue to be formed throughout life — for example, in a part of the brain where new memories are laid down and at sites of injury to neurons, such as occurs after a stroke.

But the new findings raise questions about gabapentin’s effect in situations where synapse formation is widespread and crucial, most notably in pregnancies. The vast bulk of the brain’s synapses are formed during gestation and the very early months and years after birth. Because gabapentin easily crosses the placental barrier, it could potentially interfere with a fetus’ rapidly developing brain just when global synapse formation is proceeding at breakneck speed.

“It’s a bit scary that a drug that can so powerfully block synapse formation is being used in pregnant women,” Barres said. “This potential effect on fetal brains needs to be taken seriously. Right now, doctors have the view that gabapentin is the safest anticonvulsant. There is no question that pregnant women with epilepsy who have been advised by their neurologists to continue their anticonvulsant treatment with gabapentin during their pregnancy should definitely remain on this drug until instructed otherwise. But there is no long-term registry being kept to track gabapentin-exposed babies. Our findings are saying that we need to be following up on these newborns so that their cognitive performance can be studied as they grow older.”

 

[Regenesis2]

Hmmm, so if it blocks excitability synapses and over expressed ones then it sounds like a good thing for those seeking neurontin type benefits and maybe underlies it's less addictive characteristics.
Thanks for showing the source study!

 

[Vaya]

"Always cite your sources"

I've always been a bit concerned about what it is that makes pregabalin compromising to male fertility, and whether or not it was reversible. From the same datasheet cited a few posts above (and also, below), I found this information, which I found, as a human male, rather comforting:

Fertility: Preclinical data: In male rats, oral administration of high doses of pregabalin resulted in reversible decreased sperm
motility and fertility. These were not observed at exposures (plasma AUC) up to 11 times the expected human exposure at the
maximum recommended clinical dose of 600 mg/day. There were also no drug-related effects on sperm parameters in a long
term monkey study with exposures up to 8 times the expected maximum human exposure. In female rats, oestrus cycles were
prolonged by high oral doses of pregabalin, but fertility was unaffected, and an increase in post-implantation loss also occurred.
No adverse effects were seen at an exposure approximately 50 times the expected maximum human exposure.
Human data: In a double-blind, placebo-controlled clinical trial to assess the effect of pregabalin on sperm motility, 30 of 46
healthy male subjects were exposed to pregabalin at 600 mg/day for 3 months. Pregabalin did not exhibit detrimental effects on
the reproductive function of healthy male subjects, as measured by semen analysis.
Teratogenesis: Pregabalin was not teratogenic in mice, rats or rabbits. Fetal developmental toxicity was not observed after
treatment of pregnant mice and rabbits with oral doses that resulted in respective pregabalin exposures that were 30 times and
17 times the expected human exposure at the maximum recommended clinical dose of 600 mg/day. Increased fetal skeletal
variations were seen in rats at oral doses resulting in exposures = 17 times the expected maximum human exposure, but lower
doses were not tested in a full study.

datasheet on pregabalin

~ vaya