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Gabapentin / Lyrica linked to early onset of dementia ..

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Rampage St

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www.ncbi.nlm.nih.gov

The association between Gabapentin or Pregabalin use and the risk of dementia: an analysis of the National Health Insurance Research Database in Taiwan

Objective: Previous studies have shown that gabapentin or pregabalin use is associated with cognitive decline. Herein, we aimed to evaluate the association between gabapentin or pregabalin use and the risk of dementia. Methods: In this retrospective, ...
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

Personally I’ve abused gabapentin for the better half of the decade and I have felt a strong mental decline, almost like I’m in a permanent haze.

It is scary and the withdrawals are more scary. I fear.

Gabapentin is dangerous, I think they named it “Neuro - Rotting .. Neurotin for a reason.

Thoughts?
 
Doesn’t surprise me at all. I’m sure that ain’t be the last study showing those drugs ain’t that safer compared to benzos. Marketed so or not it seems hefty chunk of users are sure they are safer, and that might even be so but is it significant difference. I’m sure many people decided it’s better for them, well, mostly cuz high is better liked by most people.
 
Yeah gabapentin was just another non-addictive wonder drug for doctors to overprescribe, and now they are surprised that it has negative effects with overuse.

I think many drugs can increase propensity to get dementia. The discussion of that paper talks about how alcohol, opioids, antihistamines, tricyclic antidepressants, antipsychotics, anticonvulsants, anti-parkinson drugs, and proton pump inhibitors also all contribute to dementia.

The study found a hazard ratio of 1.45 overall which meant that the gabapentin group has a 1.45 x rate of dementia compared to the control group during the same interval of time for each group.

I'm slightly confused at the stratification by dosage, and generally how much gabapentin patients had received. I am under the impression that this study surveyed 90 day prescriptions, but I am just waking up and may have misread, as it is somewhat unclear.
 
Has gabapentin been around that long? I know the 2 discoverers (read 'lead developers') received a Nobel Prize for their work.

HOW did they hide the abuse potential and the withdrawal-syndrome?

Did you know that they have also developed 3-methyl pregabalin which is apparently 3 times more active? I wonder if this time the licencing authority demanded specific testing for the (totally unexpected) abuse/dependence liability ?
 
When I used phenibut daily for a few months it significantly dumbed me down, so I'm not shocked to hear this. I still wonder if there was any difference between the pregabalin and gabapentin groups, as it seems like they just lumped them together.
 
SpiralusSancti said:
$€£
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Peer review did take place. Maybe in animal models it doesn't show up? Even after a drug receives a ML, 'stage 4 trials' is termed pharmacovigilance i.e. IF a problem shows up, doctors are supposed to fill in a 'yellow card' which is sent to the MoH. Now THERE it could have been considered (for £) to be 'idiopathic'.

It did seem to take some years to become apparent - but maybe that was because doctors only used it on patients with serious disorders.

I don't know - but they should have the honour to give that prize back. And the money ;-)
 
AlsoTapered said:
Peer review did take place. Maybe in animal models it doesn't show up? Even after a drug receives a ML, 'stage 4 trials' is termed pharmacovigilance i.e. IF a problem shows up, doctors are supposed to fill in a 'yellow card' which is sent to the MoH. Now THERE it could have been considered (for £) to be 'idiopathic'.

It did seem to take some years to become apparent - but maybe that was because doctors only used it on patients with serious disorders.

I don't know - but they should have the honour to give that prize back. And the money ;-)
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It’s funny how there was already documentary about pragabalin abuse somewhere in UK while in other places like mine, where it was just getting some traction it was prescribed a lot and by many seen as a much safer, even less abusable alternative to benzos. I think here it first become know as “prison coke” (heard that expression for bupropion too). I think it still usually isn’t use outside circles of people using a lot of drugs or addicts as I know quite a few people who know for it, and know it’s pretty good but still didn’t get chance to try it. That’s cuz here there’s no “street pregabalin” so to speak but you have to get them prescribed or know someone who gets them prescribed. Maybe for the better given that diazepam is #1 prescription drug in my country (and benzos do exist on grey/black market too), enough time and it would get popular. For some even more as arguably it’s more recreational than most benzos and it can be snorted and that’s surely most popular ROI for some people when it comes to recreational drugs.
 
I love pregabalin as a mild recreational drug/day enhancer. It's one of my all-time favorite substances and I've come to prefer it over phenibut, due to it being more stimulating and clear-headed. Gabapentinoids are among the best pain medicines too. I've used them for chronic gastritis pain that neither opioids or NMDAr antagonists would touch, and I've also used them for muscle strains.
 
As a pain medication they are likely a better option than many. I was tried on gabapentin and pregabalin. But giving someone on crutches a drug that caused unsteadiness proved to be a mistake.

Taking them for fun seems ill-advised as they do produce an abstinence syndrome i.e. cause physical dependence and if people enjoy the psychotropic effects, psychological addiction is an issue. Unfortunately I'm stuck with oxycodone for severe chronic pain. Fortunately the only psychological response is anxiety so it's not something I enjoy.

Yet another GABAgenic drug shown to be addictive. People don't seem to learn from history. From sulfonmethane to now, every generation is hailed for it's safety and utility.
 
Yeah, the withdrawal from gabapentinoids is not fun, and ranges from major depressive symptoms to psychotic symptoms and parasomnias. Thankfully most of the withdrawal symptoms can be avoided even with fairly rapid tapers. That's been my experience at least.

Although there's no conclusive evidence to support the notion that gabapentinoids are GABAergic. From various reviews..
Evidence suggests that pregabalin, although structurally related to GABA, is not functionally related, and as such does not act via the GABAergic system. Pregabalin itself is inactive at GABAA, GABAB, and benzodiazepine receptors, and is not converted metabolically into GABA or a GABA agonist. In addition, clinically effective concentrations of pregabalin have no effect on GABA uptake or degradation. Furthermore, experiments conducted in the rat forebrain and in the rat optic nerve demonstrate that pregabalin does not elevate GABA levels acutely in these tissues. [ref]
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and
Despite its structural similarity to GABA, GBP does not bind to GABA receptors, is not converted metabolically into GABA, and is neither a substrate for, nor a direct inhibitor of, GABA transport. [ref]
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and
conventional binding studies failed to demonstrate an interaction between GBP and the GABAB receptor [ref]
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and a study of brain GABA levels in humans
Despite significantly increased ratings of fatigue and tiredness within the GBP group, we failed to find any statistically significant changes in our MRS or TMS measures of GABA. [ref]
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The primary binding site of GBP and pregabalin is alpha2delta subunit of voltage-gated calcium channels [ref], and this activity can explains their analgesic efficacy (alpha2delta is upregulated in dorsal root ganglion in several animal models of pain). It might explain how they impair cognition, as the protein thrombospondin interacts with alpha2delta subunit to mediate cell-cell interactions necessary for synaptogenesis, and gabapentin (and presumably other gabapentinoids) impair this interaction. [ref]

Phenibut was inferred to be a GABA-B agonist in functional assays, but its potency in this assay was orders of magnitude lower than both its alpha2delta affinity and the GABA-B potency of baclofen and F-phenibut. [ref]

In short, the evidence indicates that primary target of GBP, pregabalin, and phenibut is alpha2delta subunit of VGCCs, whereas baclofen and f-phenibut appear to function as GABA-B agonists. Subjectively, GBP, pregabalin, and phenibut (and also 4-methylpregabalin) feel fairly similar to me. Baclofen and f-phenibut feel quite different, although I've only tried them at lower doses (up to 10mg and 150mg, respectively). Baclofen is somewhat dissociating and dysphoric, whereas f-phenibut feels like a staticky mild sedative, but neither of them produced the hypomanic effects that I've come to associate with alpha2delta antagonism. GBP has a bit of f-phenibut's staticky feeling and phenibut has a bit of dissociation and sedation, which is why I prefer pregabalin and its clear-headed hypomania and anxiolysis.
 
Baclofen isn't fun. There are many cases where baclofen could have been prescribed but... Pfizer did a LOT of PR with doctors to ensure it was a blockbuster.
 
If I would try to explain someone who didn’t try either, how different are pregabalin and phenibut I would say about as different as some more uplifting and some more relaxing weed strain. As dose gets bigger so does the difference too.
 
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