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lyrica's (pregabalin's) real mechanisim

allthegoodjwh's

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Could a more experienced bluelighter than I please have an answer for this before the Wikipedia page said it converted glutamate into Gaba through glutamate acid decarboloxye forgive my spelling but now that information has been removed from the pharmacology and all it says is that it lowers noreadrenaline substance p and a couple of other neurotransmitters but that doesn't explain its very real sedative euphoric ans anxiolytic properties as well as a hallucinogen this deffinatly have a dissociative feel to them and if mixed with vyvance (lisdexamphetamine) and it can be a borderline overwhelming dissociation where as the effects are strong enough your stuck in the trip and of course the disinhabitions like a graceful drunk where you bear your sou while looking complely sober but yeah of there already an answer please post the link and close this thread if there is I apologize I've been trying to find the answer for two days so if someone could explain in detail how it produces all those effects whether its downstream receptor activitey or an entirely new mechanism of action to produce its effects thank you in advance
 
I suspect a drug rep or two has been editing the wiki. Lyrica simply gets into the blood faster and has a faster onset of action then gabapentin. Whereas gabapentin's bioavailability and absorption seem to depend on what is in your GI Tract when the gabapentin is there, pregabalin does not. It is likely that fact and that fact only which leads to people feeling different effects from lyrica and gabapentin... just as those who shoot heroin feel much different than those who swallow a morphine sulfate extended release. Its sedative/anxiolytic and at higher doses dissociative effects are likely due to (much the same as gabapentin) it's main action as an NMDA antagonist. It also, just like gabapentin, causes reduction of transmission of voltage gated calcium channels with chronic use, and appears to bind to the channels regardless of length of use. It is no different in any way shape or form in its affects than gabapentin and no studies that weren't funded by Pfizer found it to be superior to gabapentin in any measure or to have any significantly different pharmacological action. It's a cheap patent extension that "feels different subjectively" because it gets into your body faster and lower doses are more potent. When lyrica goes off patent you can bet Pfizer will have another knockoff ready.. infact they've already begun trials and it's called "atagabalin". Though some research has shown very bad side effects of gabapentin/pregablin/atagablin.. like for example, causing cancer in vitro and in mice.
 
that is quite interesting could you site your source for lyrica being an nmda antagonist, it would explain the dis-inhibition anti-depressant and dissociative effects
as i read that nmda antagonists that bind to the PCP2 site on the nmda receptor it causes through an unexplained (at least to me) an unknown mechanism

i mean since it decreases glutamate via gaba synthesis it could cause a possible downstream antagonisim of nmda receptors

is that the only known effect it has i feel like it hits multiple receptor sites and has a very extensive downstream activity path

if it truly is an nmda antagonist it would explain both stimulant potentiation in my case 60mg of vyvance a day, and how normally while vyvance is particularly resistant to tolerance due to the lysine attatchment which allows it to be abosrbed in the gut and not altered by stomach ph and food content meaning a stable dose each time and spread through out the day so while it doesnt have that heavy rush that stimulant users crave it keeps you in a nice euphoric cloud. anyway case in point lyrica when taken with the vyvance allows the vyvance to keep going hard every day
because one week i wasnt able to get a script brecause the doctors office was closed (fucking scheduled drug laws) and noticed a significant drop of effects through out the week, but the next week there was no decline of effects (with lyrica) and actually significant potentiation

honestly lyrica in higher doses feels like a weak dro high mixed with a kolonopin and a 15mg hydrocodone
like its the best anti-anxiety drug out there except........ ED this thing makes sex a nightmare
and that was a little side reason i was trying to figure out the pharmacology
figure out the cause of the problem then you can figure out a solution

but in reality there should be one person out there (with sources) that can provide a detailed if not complete pharmacology of this next gen drug i just cant shake the feeling it has a novel euphoric action or extensive standard pharmacodynamics
maybe its just me because it metioned that the euphoric feeling can go away but for me its very consistent no stronger or weaker
a drug that doesnt have any major tolerance issues (unless its just me) seems something a lot of people would be interested as i am
 
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Like gabapentin, pregabalin binds to the α2δ (alpha2delta) subunit of the voltage-dependent calcium channel in the central nervous system. Pregabalin decreases the release of neurotransmitters including glutamate, noradrenaline, substance P and calcitonin gene-related peptide

decrease of calcitonin gene related peptide is thought to stop migraines and some forms of pain in people that are succesptable to those ailments

Increased levels of CGRP have been reported in migraine and temporomandibular joint disorder patients as well as a variety of other diseases such as cardiac failure, hypertension, and sepsis.[14][15][16][17][18][19]
Preclinical evidence suggests that, during a migraine, activated primary sensory neurons (meningeal nociceptors) in the trigeminal ganglion release CGRP from their peripherally projecting nerve endings located within the meninges.[20] This CGRP then binds to and activates CGRP receptors located around meningeal vessels, causing vasodilation, mast cell degranulation, and plasma extravasation.[7][20][21][22] Human observations have further implicated the role of CGRP in the pathophysiology of migraine. Activation of primary sensory neurons in the trigeminal vascular system in humans can cause the release of CGRP. During some migraine attacks, increased concentrations of CGRP can be found in both saliva and plasma drawn from the external jugular vein.[7][20][21][22] Furthermore intravenous administration of alpha-CGRP is able to induce headache in individuals susceptible to migraine.[23]
The source of CGRP in migraine (and other pain conditions) is largely thought to derive from the peptidergic peripheral innervation where alpha-CGRP is the predominant isoform produced by sensory neurons. It is the alpha-CGRP isoform that is presumed to be the primary contributor to pain mechanisms. However, more recent evidence demonstrates that CGRP is expressed among keratinocytes of the epidermis where it is predominantly the beta form.[24] Furthermore, CGRP expression in keratinocytes is substantially increased in certain human chronic pain conditions and animal models of induced chronic pain conditions, whereas the alpha-CGRP containing peptidergic innervation is decreased in painful skin sites.[24] Therefore, keratinocyte-derived beta-CGRP may have an important role in chronic pain mechanisms, as well as other dermatologic disorders known to involve changes in CGRP levels, such as psoriasis. Although very little is known about the functional differences between these two isoforms, research has demonstrated that the beta-CGRP is also expressed among enteric neurons of the gut, and CGRP has been implicated in mechanisms of visceral pain disorders, such as irritable bowel syndrome.



hmmm so for all those haters on pregabalin it may and probably will if that information is correct help prevent "a variety of other diseases such as cardiac failure, hypertension, and sepsis.[14][15][16][17][18][19]" the cancer thing is a stretch its possible but the receptor capable of doing it is several levals downstream so i dont find it likely unless someone can provide sufficent evidence to prove otherwise
 
I'm glad you're interested in the pharmacology... more than a lot of people around here. But you are WAAAAY oversimplifying the mechanisms of NMDA and what an antagonist or agonist could cause down stream. Some antagonists have completely different effects when bound to the same exact site on NMDAR's that other antagonists bind to. It isn't that simple. NDMA and glutamate in general are such basic and broad transmitters that they aren't easily predictable, ever. And to theorize that pregablin can fix all these problems because an nmda antagonist should downstream activate x and y which have been implicated in some cardiac problems doesn't mean it will. hell x and y could be implicated in cardiac problems as a side effect downstream from something else's feedback loop. Unfortunately we're just beginning to scratch the surface of glutamatergic potential. It has the ability to cause sedation/dissociation/hallucination/anxiolysis/amnesia/anesthesia/and even psychosis that mimics 100% schizophrenia all from JUST antagonists. It's such a main component of our system and it's wired and connected to so much of our CNS that we just can't make speculations like that because while they could be right, they are more than likely wrong.

Gabapentin Pregabalin Atagabalin and all the other gabalins seem to cause carcinoma's. They did in vitro and they did in mice in vivo. Why? I have no idea. The current theory is they may actually work by also stopping new cells and nerves from growing/forming connections and they don't even know if that's true how it causes that. Could it interfere with apoptosis, maybe? Could something messing with our cells basic control loops cause cancer, absolutely. But it's only speculation at this point. What isn't speculation is that it does seem to cause cancer. There are many studies on it. Infact, gabapentin extended release was tried to be brought on patent and the FDA denied it specifically because of it's carcinogenic potential. It wasn't a special molecule it was just an extended release version of gabapentin. But gabapentin was approved. Why? Because sometimes the drug companies get their way, but I like to think the FDA wised up. Had gabapentin been brought out now it would be denied. It was approved as an adjunct and last line of treatment for seizures that don't respond to anything else, and the data showed it really didn't help seizures anyways. But it was touted as a wonder drug, research started appearing saying it was good at curing pain nerve pain fibromyalgia, anxiety, insomnia everything it was a miracle. And that's why Pfizer got hit with that enormous 430 million dollar (and now another 141 million) settlement/lawsuit. The research on gabapentin was falsified by pfizer. They realized they were going to make no money on the drug when the fda approved it as an adjunect to other seizure meds, and they had marketing teams type up research papers and publish them as fact, the pushed it off label for everything and doctored their market-made research publications to reflect that gabapentin worked wonders for every single problem. They got in a LOT of trouble. 90% of the research on gabapentin is under scrutiny and what has been looked at by investigators (the FDA research given to the FDA by Pfizer with data on their drug) which was used to get the drug approved, turned out to be so scientifically flawed that there was no way it had ever actually been done. It literally was made up in a board room and then some doctor was paid to put his name on it.

Anyway look up the cancer thing no joke there.
 
Regarding pregabalin and a possible action as NMDA antagonist i dont think pregabalin is an NMDA antagonist, because however i cannot produce the source anymore i did read that pregabalin is less active in company with an NMDA antagonist like for example methadone is one.

Maybe very maybe this explains why i do better on 900 mg pregabalin then the 600 mg whom are listed as possibly delvering highest therapeuthical effects, because i always take 160 mg methadone with pregabalin, but there is no way for me to say if pregabalin acts less well together with methadone as i dont know what to expect with pregabalin only.

I find methadone becoming more potent combined with pregabalin so that is an effect you better know about before pregabalin and methadone are combined. I think its reasonable to assume that pregabalin combined with methadone strengthens pregabalin no matter the NMDA antagonism from methadone.

Before pregabalin tolerance hit hard i would feel euphoric with those 900 mg, but it took about three hours before this effect became pronounced and a reason i suspect for the long time for it to act every single day again is that pregabalin relies onto lowering certain neurotransmitter amounts, because it only takes an hour for oral pregabalin to reach it's max bloodlevel only it's bloodlevel does not correspondend with it's effects atleast not for me. I did read about people who report an effect within the hour and i suppose this is possible before tolerance hits, but also in spite of tolerance development and since i learned to respect my max dose the 900 mg work also against depression.

At first i would dose pregabalin guided by tolerance development so only days later i would take as highest amount 3 grams, but that is madness, because effects disappeared with 3 grams until i kept it to 900 mg for a little while and eventually the effects were mine again, except for this true euphoria feeling. Not taking pregabalin for about 3 days and by day 4 taking the 900 mg again resulted in feeling good, but i think not taking it for about a week might reproduce that initial euphoria again i find myself unable though not to take it for a week.

Combining a benzo with pregabalin will potentiate this benzo bigtime so since i like to take 75 mg oxazepam with it makes that benzo quite feelable while it's potency can be compared with the one from librium with the difference that oxazepam can produce sort of buzz whereas librium dont. Librium is lovely to deal with benzo withdrawals, except if you have a xanax habit librium is too weak to properly substitute for that one.

I always talk too much my whole point was to mention that i read that pregabalin is less effective when combined with an NMDA antagonist if this is true or not is something else. Further based on how pregabalin affects me does not make me think it hits certain known receptorsites, because if it would do this then it wouldn't take 3 hours before i can say the effect is max it would be feelable much sooner like within one hour. Lowering the production of certain neurotransmitters like glutamate is probably the most important one, but less noradrenaline is maybe less wanted, because more of this neuro has an anti depressant effect then less substance P is probably feelable, but the combined effects from pregabalin on neurotransmitter release are in my opinion responsible for most of it's effect.

About the chance that pregabalin and related can cause cancer i had no idea about this so this is concerning, but i dont think i would stop taking it, because of the cancer chance.
 
Well the cardiac protection and other mischalenious sorry for the spelling on my mobile phone that refuses to spell check
but it had nothing To do with nmda or glutamate it was that other action of lyrica the decrease of that calcium peptide and it litterally states word for word that an increase of that peptide could not does but could be resposible for those health problems and that's why I said it may because it was mostly in theory but if that source I sited is correct than it Would for sure infill then its just speculation based on a few promising patient outcomes and sparse results

I belive the euphoria comes from the glutamate acid decarboxyle or however you spell it action sue to it biding to that subunit of the voltage gated calcium channel after a couple hours it could build up a serious Gaga concentration especially at high doses but my guess is it takes a little bit of tims and I have read in more than one source that people have combined xanax and methadone to produce a heroin like effect
And as lyrica makes large Gaba concentrations it can technically act as a weak benzodiazapine
also because it turned all that glutamate into gaba the glutamate in the brain is much less acting as technical Antagonisim (this last lack of glutamate is more of a hypothesis then fact) so it could also potentiate methadone in that way as well I remember jwh-018 no one beloved it was an nmda antagonist (downstream of course) but it was dissociative as fuck I would combined high doses of both 018 and dxm and I would be outtta there

but one last item on my agenda for the moment

lunesta and ambien both gabaA agonists not Pam and also gaba-rho (C) agonists and can produce dissociation and hallucinations
benzodiazapines do not bind to gaba-c and do not. Produce those effects
another example is mucimol from both panther caps and Amanita muscaria
lyrica increases gaba which can Bind to gaba-c
But oh ho it gets better according to the page on gaba-c gaba binds to c over a in a 10:1 ratio Ye users
creating a model sedative hallucination
that can reach hqllucinatory binding levals at c wtihout riddiculous sedations and or prodrug induced Brian lesions

but that really makes sence to me at least lol
 
I'm extremely skeptical of the claim that the only differences in MOA between gabapentin and pre-gablin is absorbtion/metabolism.I know this can profoundly change subjective experience, but the effects feel categorically different to me. Just a small example, lyrica is a pretty strong stimulant for me and the opposite is true of gabapentin. But it goes way beyond that. Of course I have no hard evidence of this whatsoever.
 
I'm extremely skeptical of the claim that the only differences in MOA between gabapentin and pre-gablin is absorbtion/metabolism.I know this can profoundly change subjective experience, but the effects feel categorically different to me. Just a small example, lyrica is a pretty strong stimulant for me and the opposite is true of gabapentin. But it goes way beyond that. Of course I have no hard evidence of this whatsoever.

I can’t get high off gabapentin for shit... Lyrica is definitely more potent.
 
Lotta experience with both. Sure, gabapentin is actively transported across the gut ,and the transporter gets saturated quick and easy. Nuke has made several good posts on this subject., and she has given good advice. Search for em, I can't be bothered ;)

Pregabalin is distinctly different in it's effects. Night and day. Well, maybe, sunset and night ;) I ain't buying absorption as the culprit for well, shit.
 
I'm glad you're interested in the pharmacology... more than a lot of people around here. But you are WAAAAY oversimplifying the mechanisms of NMDA and what an antagonist or agonist could cause down stream. Some antagonists have completely different effects when bound to the same exact site on NMDAR's that other antagonists bind to. It isn't that simple. NDMA and glutamate in general are such basic and broad transmitters that they aren't easily predictable, ever. And to theorize that pregablin can fix all these problems because an nmda antagonist should downstream activate x and y which have been implicated in some cardiac problems doesn't mean it will. hell x and y could be implicated in cardiac problems as a side effect downstream from something else's feedback loop. Unfortunately we're just beginning to scratch the surface of glutamatergic potential. It has the ability to cause sedation/dissociation/hallucination/anxiolysis/amnesia/anesthesia/and even psychosis that mimics 100% schizophrenia all from JUST antagonists. It's such a main component of our system and it's wired and connected to so much of our CNS that we just can't make speculations like that because while they could be right, they are more than likely wrong.

Gabapentin Pregabalin Atagabalin and all the other gabalins seem to cause carcinoma's. They did in vitro and they did in mice in vivo. Why? I have no idea. The current theory is they may actually work by also stopping new cells and nerves from growing/forming connections and they don't even know if that's true how it causes that. Could it interfere with apoptosis, maybe? Could something messing with our cells basic control loops cause cancer, absolutely. But it's only speculation at this point. What isn't speculation is that it does seem to cause cancer. There are many studies on it. Infact, gabapentin extended release was tried to be brought on patent and the FDA denied it specifically because of it's carcinogenic potential. It wasn't a special molecule it was just an extended release version of gabapentin. But gabapentin was approved. Why? Because sometimes the drug companies get their way, but I like to think the FDA wised up. Had gabapentin been brought out now it would be denied. It was approved as an adjunct and last line of treatment for seizures that don't respond to anything else, and the data showed it really didn't help seizures anyways. But it was touted as a wonder drug, research started appearing saying it was good at curing pain nerve pain fibromyalgia, anxiety, insomnia everything it was a miracle. And that's why Pfizer got hit with that enormous 430 million dollar (and now another 141 million) settlement/lawsuit. The research on gabapentin was falsified by pfizer. They realized they were going to make no money on the drug when the fda approved it as an adjunect to other seizure meds, and they had marketing teams type up research papers and publish them as fact, the pushed it off label for everything and doctored their market-made research publications to reflect that gabapentin worked wonders for every single problem. They got in a LOT of trouble. 90% of the research on gabapentin is under scrutiny and what has been looked at by investigators (the FDA research given to the FDA by Pfizer with data on their drug) which was used to get the drug approved, turned out to be so scientifically flawed that there was no way it had ever actually been done. It literally was made up in a board room and then some doctor was paid to put his name on it.

Anyway look up the cancer thing no joke there.

That's scary as I am a frequent pregabalin user. I think what your referring to is prgabalins denial of thrombospondin secretion. I find it affects my cognition significantly. You can drive on the same path 20 times and still not remember the way. Same for names, telephone numbers, and learning new behaviors. It also drives the user into complete empathy, where if your partner is sad, you are too, if your partner is happy so are you. It's almost an instantaneous switch of feelings based on those around you. I have to say, without alcohol of or a benzodiazepine it can get tiring at times. Just my opinion.

A question I've always wondered is what's behind the water retention and the weight gain?

Anyways, heres a study on thrombospondin:

Neurontin and Lyrica are Highly Toxic to New Brain Synapses

Byron's Comments:

This study inadvertently proved the extreme danger of several blockbuster drugs.

Study Title:

Gabapentin Receptor α2δ-1 Is a Neuronal Thrombospondin Receptor Responsible for Excitatory CNS Synaptogenesis
Study 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 α2δ-1, the receptor for the anti-epileptic and analgesic drug gabapentin. We show that the VWF-A domain of α2δ-1 interacts with the epidermal growth factor-like repeats common to all thrombospondins. α2δ-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 α2δ-1 and powerfully inhibits excitatory synapse formation in vitro and in vivo. These findings identify α2δ-1 as a receptor involved in excitatory synapse formation and suggest that gabapentin may function therapeutically by blocking new synapse formation.

From press release:

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.”

Study Information:

Çagla Eroglu, Nicola J. Allen, Michael W. Susman, Nancy A. O'Rourke, Chan Young Park, Engin Özkan, Chandrani Chakraborty, Sara B. Mulinyawe, Douglas S. Annis, Andrew D. Huberman, Eric M. Green, Jack Lawler, Ricardo Dolmetsch, K. Christopher Garcia, Stephen Gabapentin Receptor α2δ-1 Is a Neuronal Thrombospondin Receptor Responsible for Excitatory CNS Synaptogenesis Cell 2009 October
Stanford University School of Medicine.

Link:

http://www.wellnessresources.com/st...yrica_are_highly_toxic_to_new_brain_synapses/
 
That's so odd in reference to the last post those things happen but only when om off of it....like a withdrawal effect but I do get a crude ecstasy trip when mixed with vyvance a very empathetic loved up kinda trip it also has most if not all of marijuanas effects minus the time dilation of course but I'm pretty damn sure it doeant directly effect the cannabinoid cb1 but either directly hits downstream targets or shares some other pharmacological link to it
 
The euphoric effect comes from the GABA alpha activation and the GHB in which the GABA is metabolized.
The supposedly hallucinations you claim may be due to GABA rho (is that how they call it now?) activation.
The activation of that receptor at the voltage gated calcium channel, stops the formation of synapsis.
Regards!
 
Since pregabalin turns glutamate into gaba and gaba metablolises into ghb then ghb receptors release dopamine glutamate and I belive alter k+ channels as well but the rise in glutamate levals would lead to more gaba and so on and on I proposed this months ago and no one took me seriously but a sedative euphoriant dissosiative hallucinogen is worth having a look at because for me at least it seems like a mix of mRNA high dose dxm or a little k two ambien a hydrocodone and a couple bowls of hydro sprinkled on a 4 bar almost is like a little of every type of drug and again this is in my opinion not fact lol some people if not most don't feel lyrica the way I do
 
Dumb question, but how similar is phenibut to neurotin (I have experience with) and lyrica (I have no experience with sadly). From what I have heard/read about Lyrica, I feel like I would really enjoy and benefit from it.
 
Phenibut is quite different than lyrica. Phenibut is the dirty promiscuous cousin of Baclofen. Phenibut Can share some similarities to like extra extra extended release GHB, but still has it's own way of dosing things. Atdoses high enough to get "high" (4-5 grams) it certainly feels hard on the body.

If you like neurontin you will like lyrica. Cleaner, more refined. Both seem to increase synaptic GABA and thus can rightfully elicit comparisons to both GABA-A and GABA- B agonists. Almost no one ige intrdocuced doesn't enjoy lyrica once they got the dose right.. It varies tremendously, and I don't think it is actively transported just straight up absorbed and straight forward pharmacodynamics. I'm a hard head for GABA anything (3O mg etizolam gets me out of bed, no amnesia, or slurring unless combined with another downer, even kratom) and even with Nukes staggered dosing method (my version consisting of 300 mg every half hour, with a couple 600 substations thrown in there) and im still not "morontonized" ( it actually makes me sharp, funny and smart FWIW) I need like 2600 to be satisfied. 600 mg of pregabalin. Is my max, spins, and circles and even barfing above that. YMMV

Bored of the GABAergics now. Take Gabaoentin and Baclofen for legit medical issues, and have for eight years but gonna try tapering off of these once my etizolam taper is done. One at a time, but ANY GAbaergics have a terrible effect on my cognition. Got on the etizolam like 6-8 weeks ago once I found the police thousands of miles have unfinished business with me, and this is r doing time, jumping through hoops, etc. Stressed. But time to deal with it now, just like this etizolam binge.
 
Yeah, I am a gaba hard head myself. I have to be very very careful with them (I learned my lesson several times over). I would like to try to get ahold of lyrica someday.

A close relative of mine is on Neurontin daily for nerve issues, he was shocked when I told him that if he stopped suddenly he would likely face some withdrawals. Apparently, his doctor never mentioned it to him.

30 mgs of etizolam is quite a bit my man. Please be careful.
 
I am currently on baclofen daily for muscle spasms and nerve issues as well, i think this would probably go nicely with it. I will have to ask my doc to throw this into my cocktail next time around, see what he says.
 
Lyrica caused cancer in one species' of mice, and studies show pregabalin did not cause nor catalyze the onset of tumor growth in rats.

A mouse's body functions differently from a human or even a rat's body; although a human is not a mouse, the findings of Pregabalin causing cancer in mice certainly raises suspicion of gabapentin and lyrica being carcinogenic in humans.

Limited studies have been done and at this point in time speculation is speculation. Until more research has been done, it is probably safe to assume lyrica and gabapentin are no more carcinogenic than tobacco/nicotine and alcohol. I mean people smoke and drink daily even though those two substances cause cancer, and there are multiple factors contributing to promotion of cancerous tumor growth such as age, weight, genetics, ect.....

I'm not going to stop taking lyrica or gabapentin , and frankly i am quite fond of pregabalin's synergism with opiates and.benzodiazepines
 
charles said:
The euphoric effect comes from the GABA alpha activation

No, this has been ruled out experimentally.

some good jwhs... said:
Since pregabalin turns glutamate into gaba and gaba metablolises into ghb then ghb receptors release dopamine glutamate and I belive alter k+ channels as well but the rise in glutamate levals would lead to more gaba and so on and on

This doesn't follow. Pregabalin facilitates synthetic conversion of glutamate to GABA (I'm guessing by some sort of enzymatic induction or inhibition), yes, but it's unclear whether this effect is is particularly dramatic, and it certainly wouldn't follow the time-course of pregabalin-inebriation. Synthesis of GHB from GABA involves a metabolic intermediate, succinic semialdehyde, and while pregabalin should boost this pathway via suppression of catabolism of GABA into glutamate, we should expect this effect to be relatively minor due to how indirect it is and because GHB serves as a precursor for GABA in some anatomical regions. Similarly, the magnitude of 'dopamine rebound' following increased levels of GHB is in question.

Now GHB agonism does seem to increase glutaminergic release, but further conversion to GABA would depend on continued activity of pregabalin. However, looking back to the first step, insofar as pregabalin facilitates conversion of glutamate to GABA, there should be a reduction in the amount of glutamate available, limiting pregabalin's efficacy in increasing GABA synthesis.

Basically, when you have such a convoluted chain of neuro-chemical events, with the significance of some of these events in doubt, it becomes unlikely that a feedback loop as you describe could sustain itself.

a sedative euphoriant dissosiative hallucinogen is worth having a look at because for me at least it seems like a mix of mRNA high dose dxm or a little k two ambien a hydrocodone and a couple bowls of hydro sprinkled on a 4 bar almost is like a little of every type of drug and again this is in my opinion not fact lol some people if not most don't feel lyrica the way I do

I really don't understand the rest of what you're saying. :P

ebola
 
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