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Know Your Gabapentinoids

The gabapentinoids are a class of drugs vaguely resembling the neurotransmitter GABA. Although they were developed to imitate GABA’s action, later research discovered they acted on a different target, the A2D subunit of calcium channels. Two gabapentinoids are approved by the FDA: gabapentin (Neurontin®) and pregabalin (Lyrica®).

Gabapentin has been generic since 2004. It’s commonly used for seizures, nerve pain, alcoholism, drug addiction, itching, restless legs, sleep disorders, and anxiety. It has an unusually wide dose range: guidelines suggest using anywhere between 100 mg and 3600 mg daily. Most doctors (including me) use it at the low end, where it’s pretty subtle (read: doesn’t usually work). At the high end, it can cause sedation, confusion, dependence, and addiction. I haven’t had much luck finding patients a dose that works well but doesn’t have these side effects, which is why I don’t use gabapentin much.

Pregabalin officially went generic last month, but isn’t available yet in generic form, so you’ll have to pay Pfizer $500 a month. On the face of things, pregabalin seems like another Big Pharma ploy to extend patents. The gabapentin patent was running out, so Pfizer synthesized a related molecule that did the same thing, hyped it up as the hot new thing, and charged 50x what gabapentin cost. This kind of thing is endemic in health care and should always be the default hypothesis. And a lot of scientists have analyzed pregabalin and said it’s definitely just doing the same thing gabapentin is.

But some of my anxiety patients swear by pregabalin. They call it a miracle drug. They can’t stop talking about how great it is. I can’t use it too often, because of the price, but I’m really excited about the upcoming generic version coming out so I can use it more often.

Still, I have to wonder – why am I sitting around waiting when I could just give people gabapentin? Confirmed pharmacodynamically-identical, generic, and cheap? The answer is, gabapentin doesn’t seem to work that well. I’ve never had patients with more than minimal anxiety happy on gabapentin alone. Am I imagining a difference betwee these two supposedly-similar medications? I don’t know. Although studies confirm pregabalin is great for anxiety, nobody has done the studies on gabapentin that would let me compare it. For now, the apparent difference between pregabalin and gabapentin is one of the great mysteries of life, one of the things that makes me doubt my own sanity.

One possibility is that we’re getting the doses wrong. UpToDate recommends treating anxiety disorders with gabapentin using a starting dose of 300 mg twice a day = 600 mg daily. But it recommends 100 mg three times a day = 300 mg of pregabalin. This dosing table suggests 1 mg pregabalin = 5 mg gabapentin, so 300 mg of pregabalin = 1500 mg gabapentin! So we’re starting gabapentin patients on less than half as much medicine as we start pregabalin patients on. If this forms a reference point in the doctor’s mind, then maybe what we think of as a “high dose” of gabapentin is the same as what we think of a “low dose” of pregabalin. Maybe all our gabapentin doses are just too low.

I usually avoid higher gabapentin doses because I feel like they have more side effects than low pregabalin doses. Is this just an illusion? Is it my bias? If a patient reports feeling dizzy on high-dose gabapentin, do I say “Yeah, you’re on a really high dose, I’m not surprised you feel that way, let’s back off?” And then if they feel the same thing on low-dose pregabalin, might I say “It’s a low dose, you’re just getting used to the medication, give it a few more weeks”? Might my biases even be affecting how patients report their own experiences?

Or might there be some obscure pharmacologic mechanism? This paper tries to compare the pharmacology of the two drugs. They say the body can easily absorb pregabalin, but has a limited ability to absorb gabapentin – the more gabapentin there is, the lower a percent gets absorbed:

With regard to the fraction of the dose absorbed, the lowest gabapentin dose studied (100 mg every 8 hours) is associated with absolute bioavailability of approximately 80%. This value was shown to decrease with increasing dose to an averageof 27% absolute bioavailability for a 1600 mg dose every 8 hours. In contrast, oral bioavailability of pregabalin averaged 90% across the full dose range of 75 to 900 mg/day studied

This doesn’t match the dosing table linked above, which suggests a 1:5 constant ratio between gabapentin and pregabalin dose. It also doesn’t really match the paper’s Figure 3, which shows a linear effect of gabapentin up to 1800 mg for nerve pain. It does match the paper’s figure 4, which shows little to no effect of gabapentin past 600 mg for seizures. I don’t really know what’s going on here. It would make some sense if the bottleneck were plasma -> CSF absorption, but that’s not what the paper’s saying. In any case, if the gabapentin/pregabalin relationship followed the same pattern for anxiety as for seizures, it would be impossible to ever get a dose of gabapentin as high as the starting dose for pregabalin, which would explain perceptions of pregabalin’s superiority. Try to increase gabapentin dose, and you just have extra gabapentin sitting around in the GI tract causing trouble. I don’t know if this is at all the right way to be thinking about this.

One more difference: gabapentin is not a controlled substance, but pregabalin is Schedule V, the designation the government uses for things that are technically addictive but that it’s not going to worry about too much. Why the difference? The government’s documentation of their decision doesn’t say. It could be total chance: both substances are right on the border, and a different bureaucrat got assigned to each case. But the decision doesn’t seem totally off-base to me. Although it’s theoretically possible to get addicted to gabapentin if you use a really high dose and try really hard, you’d have to be pretty desperate even by drug addict standards. I’ve seen a little more pregabalin addiction, though I agree with the FDA that it’s still pretty unusual (some people in the comments disagree). One likely culprit is the absorption rate: pregabalin gets absorbed in an hour or so, gabapentin takes three or four. Faster-acting substances are always more addictive; they peak higher and sooner, and it’s easier for the brain to associate stimulus (taking the drug) with response (feeling good). Could this also explain some of the efficacy difference? I don’t know.

Phenibut is not FDA-approved; it’s a common medication in Russia which gets sold as a supplement/nootropic/recreational drug in the US. The FDA occasionally asks people to stop selling it, but they’ve never gotten serious, and it’s still easily available on the open Internet.

Phenibut has the kind of approval ratings usually associated with North Korean dictators who kill anyone who disapproves of them – including the highest median rating on my nootropics survey. It’s phenomenal for social anxiety – not in the SSRI way of making you a little calmer, but more in the “getting just the right amount of drunk” way that turns you into a different, bolder, and more fun-loving person. Aside from this, it can give a hard-to-describe sense of tranquility and well-being.

(it also makes you feel like you’re wearing a hat even when you aren’t. I swear this is a real side effect.)

Needless to say, it’s potentially addictive and can seriously ruin your life. Conventional wisdom in the phenibut user community is that you can use 500 mg once every week (or maybe every two weeks) safely. Anything beyond that and you develop rapid tolerance. Increase the dose to fight the tolerance, and you start feeling worse on the days you don’t take it, using it more and more to compensate for the rebound, and eventually getting a withdrawal syndrome closely related to the delirium tremens that sometimes kills recovering alcoholics.

(does this mean that responsible phenibut use is a free way to have one great day per two weeks? depends how good your willpower is, I guess. see also this graph from this source)

The discovery of ketamine’s efficacy for depression was a mixed blessing. Ketamine such is a difficult medication to use – dangerous side effects, intolerable hallucinations, IV delivery – that it could never be a panacea, whatever its potential. But the discovery sparked a hunt for other ketamine-like chemicals that shared its efficacy but not its downsides. It also started a race to figure out how ketamine worked, with the hope that this would provide the key to what depression really was, deep down. Phenibut should inspire the same kind of interest. It’s too dangerous to use regularly, but it’s great enough that we should be looking into what the heck is going on.

Early research into phenibut focused on GABA, the main inhibitory neurotransmitter. The brain has two kinds of GABA receptors, GABA-A and GABA-B. Alcohol, Xanax, Valium, Ambien, barbituates, and the other classic sedatives all hit GABA-A. There aren’t that many chemicals that hit GABA-B, and the few that are out there tend to be kind of weird – one of them fell to Earth on a meteorite. But phenibut is a GABA-B agonist. This sounds like a neat solution to the mystery: a drug with unique anti-anxiety properties affects a unique inhibitory receptor. But another GABA-B agonist, baclofen, has minimal anti-anxiety effects. It is mostly just a boring muscle relaxant (there was some excitement over a possibility that it might cure alcoholism, but the latest studies say no). So probably GABA-B on its own doesn’t explain phenibut.

This led researchers to propose that phenibut might work as a gabapentinoid. It has the defining GABA backbone, and it has activity at the A2D calcium channel subunit. But its gabapentinoid activity is much weaker than gabapentin itself, so why should its effects be stronger?

Baclofen outdoes phenibut as a GABA-B agonist, and gabapentin outdoes phenibut as a gabapentinoid, but phenibut works better than either. This is the other big gabapentinoid mystery that keeps me awake at night.

Might it be a synergistic effect between the two different actions? If this were true, we would expect taking gabapentin and baclofen together to have phenibut-like effects. But these drugs are sometimes used for the same kinds of neuromuscular conditions and nobody has ever noticed anything out of the ordinary. I would love to see this studied but I don’t expect much.

Phenibut has two enantiomers, r-phenibut and s-phenibut. Both are decent gabapentinoids, but only r-phenibut has GABA-B activity. If both worked equally well, that would suggest phenibut worked on A2D; if r-phenibut worked better, that would implicate GABA. The best source I can find is this study, which says that only r-phenibut has effects on rats. Do the hokey tests they run rats through exactly correspond to treating anxiety in humans? Unclear, but this pushes me more in the direction of thinking GABA-B is an important part of phenibut’s effects. So does a passing resemblance between phenibut and GHB, an unusual drug that works on GABA-B among other things.

Overall I think phenibut is probably more GABA-B agonist than gabapentinoid, but I can’t explain why it’s so different from baclofen.

One fringe possibility: it isn’t. I’ve said that these two drugs are used for different indications, by different populations, and get different results. But the map isn’t the territory, and the way humans use and think about drugs doesn’t always reflect chemical reality. Everyone knew the second generation antipsychotics were totally different from the first generation ones, until we learned that they weren’t really, and the different effects we saw were a combination of using them differently plus having different expectations. And placebo alcohol can still get people pretty drunk. The only study I’ve found directly comparing phenibut to baclofen finds they work for similar indications, at least in rats (see bottom of page 476). And I can find a few comments on Reddit backing this up from experience.

My odds are against this theory – I think there’s probably some real difference between these drugs that we don’t understand. But constant vigilance never hurts.

[EDIT: commenter dtsund points out that baclofen has some issues with blood-brain barrier permeability; see here for more. Although some of it gets through, it could build up in the plasma much faster than in the brain, giving it disproportionately peripheral effects]

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101 Responses to Know Your Gabapentinoids

  1. The Nybbler says:

    Does anyone else feel an urge to go out and order some phenibut? And to put on a hat? Really, sounds like a pretty good substitute for alcohol in the “social lubricant” sense.

    • Radu Floricica says:

      Didn’t have time to read the article except very diagonally, but it’s probably not a bad idea to give my take cold. I’ve heard of phenibut from a bodybuilding context, where possibly because its anti anxiety effect it promotes recovery. I’ve taken it for maintenance insomnia, and I still consider it pretty damn good. It’s not a sleeping pill, but it did give me the occasional very good night. The first 3 uses or so gave probably the only nights this year that were completely interrupt-free, as measured by Oura ring. After that it was hit and miss, but still mostly hit.

      I’ve taken 0.5-1g, very occasionally. Not because I’m responsible, but because I bought powder and it’s sour as hell. Otherwise I’d probably have settled to 0.5g 2-3 times a week. At the moment I’m mostly feeling guilty because I’m not taking it more often – also I have another batch in the mail. To be compared with the 5mg of zolpidem I am taking 2-3 times a week because, well, I need it to function the next day if I wake up after 4 hours of sleep.

      My source.

    • Lambert says:

      The fact they had to make a separate r/quittingphenibut sub kind of gives me pause.

    • Elementaldex says:

      I did go out and order some phenibut a few months ago. I’ve taken 500 mg every 2-3 weeks and I think I notice an effect, but it is minor, at least at low doses I don’t think it can be considered an alcohol substitute.

      I was hoping it would help with sleep quality and given the data from my fitbit it does slightly increase what percent of my sleep is deep sleep. But again, pretty minor effect.

    • Nornagest says:

      FWIW, I tried it once and was kinda underwhelmed.

    • psmith says:

      As I recall, 600mg of phenibut pretty much felt like two beers.

      So, you know, it was nice, especially if you’re on a diet, but not exactly life-changing.

    • James says:

      How easy is it to get hold of?

    • The Nybbler says:

      (BTW, when I posted this there was no mention of alcohol in the second phenibut paragraph, but rather a more enthusiastic description)

    • Majuscule says:

      That sentence about the hat immediately reminded me of something a friend of mine said happened to her when she smoked some opium back in college. She described opium giving her a feeling “like wearing a warm hat that was slowly pulled down” until it covered her entire body.

      Is there some sort of “hat pathway”? A collection of nerves wired to encircle the body, emanating from the top of our heads? How could we study this?

  2. Paul Crowley says:

    Feel like this should have been titled “WTF, gabapentinoids, WTF?”

  3. Deiseach says:

    Feel like this should have been titled “WTF, gabapentinoids, WTF?”

    Come on, nobody thought Gabba Gabba Hey? 🙂

    Still, I have to wonder – why am I sitting around waiting when I could just give people gabapentin? Confirmed pharmacodynamically-identical, generic, and cheap?

    I honestly do think in vitro is very different to in vivo and generics/pharmacodynamically-identical really aren’t. I have a regular prescription for a particular medication and my chemist often gives me different versions (generic vs brand name or same drug, different manufacturer) depending on what they have in stock at the time. And I really do think some versions are less effective than others, I’ve noticed differences.

    Pharmaceutical plant A makes their version with just a tiny difference due to the process than Pharmaceutical plant B, and that difference isn’t enough to be picked up in QA testing (because it’s all chemical assays) but once it gets into a patient, that particular twist does make a difference when biology gets involved.

  4. rahien.din says:

    Gabapentin is already on the controlled or monitored substance lists of several US states. This seems to be because you can get a better kick from your opioid if you take it with a massive dose of gabapentin.

    I used to prescribe gabapentin for migraine prophylaxis, but stopped giving it after I came to suspect that one of my patients’ parents was diverting it. That was a really creepy feeling.

  5. simbalimsi says:

    Your dedication to your profession is really great. I wish your native language was Turkish so I could be your patient.

    About nootropics, I never see galantamine in discussions but makes me quite happy, focused and somewhat more intelligent I guess?.

  6. Freddie deBoer says:

    I take phenibut in 2000mg doses but only once every couple of months so I think I’m good.

    • hash872 says:

      How euphoric is 2000mg for you? It’s interesting how much phenibut tolerance seems to vary between people- some people get a lot out of just a few hundred milligrams, I personally need 1500 to have a good time

  7. dtsund says:

    Some quick Googling seems to say that Baclofen doesn’t cross the blood-brain barrier all that well; concentration in the brain is precipitously lower than in blood plasma. Perhaps it’s just that Phenibut crosses the barrier more effectively?

    Does Phenibut also have muscle-relaxant properties?

  8. algekalipso says:

    Thanks for writing about the differences between these gabapentinoids.

    I will take the chance here to say that perhaps more than finding a better drug in terms of acute anti-anxiety effects (which is great, don’t get me wrong), it would pay-off to invest time and energy on finding anti-tolerance drugs to keep the drugs we know are effective (e.g. phenibut!) working without generating tolerance, withdrawal, dependence, etc.

    The strongest lead I know of is Flumazenil, which upregulates GabaA recepors and seems to reverse long-term tolerance to benzodiazepines (which are famous for having a disproportionate long-term withdrawal effect relative to their benefits). I suspect that a flumazenil + phenibut combo or similar (as uncovered by future research) could be more groundbreaking for mental health than merely finding another drug that works like phenibut but isn’t bad in other respects. Tolerance, after all, is the main reason why nothing in psychiatric medicine is a panacea. In the long term, I envision a future where we’ve found safe, sustainable, and tolerance-free analogues (or combos) of MDMA. (see also: Utopian Pharmacology).

  9. Nostranoodle says:

    Fibromyalgia patient here – I find pregabalin to be magic stuff. My psych agreed with you; he found gabapentin just didnt work as well, and so we never tried it. PK seems very important, i.e. trying to keep plasma levels fairly constant, which is hard with a drug with such a short halflife. I take it 4 times a day, with a double dose at bedtime; the sedative effect of the latter seems genuinely helpful. Not sure if Pfizer intends to register the extended release formula here, but I would be keen to try it.

    Of course since I am in Australia, I get each months supply for ~AUD28, with the rest paid by the govt. I only get that price since my “neuropathic pain is non-responsive to other treatment” (duloxetine didnt do much, and desvenlafaxine made me feel terrible).

    The most interesting side-effect Ive noticed seems to be a reduced desire for coffee. I used to “need” to drink a lot of coffee, in that way that people joke about in workplaces. Now I often forget to get a coffee and dont notice, or am busy with something at my desk and cant be bothered with the interruption, or get a coffee and leave it untouched (which never ever happened before pregabalin).

    • Robert Beckman says:

      How well does it work for you compared to high dose opiates?

      I used to rely on duloxetine (tradename: cymbalta) but it stopped working for me a year ago and we haven’t found any combination of anything that reliably lets me walk (or even sit to be able to work again – and I was very high income previously), and after I had acute kidney failure this spring I had to stop the indomethacin (and all other NSAIDs) so right now it’s just high dose opiates (slowly increasing) and 4000mg/day of paracetamol.

      MD and I experiment every month with something new, but everything has been a miss thus far.

      • Nostranoodle says:

        I never tried opiates, seemed like Pandora’s box. TBH one of the reasons I feel like pregabalin is having a genuine effect, is that the outcomes were different to expectations. I was expecting less pain, and its moderately effective there, but mostly I just feel better, and have fewer days off work.

        Speaking of opioids, I did consider low-dose naltrexone (i.e. below the dose that hits opiate receptors, but enough to affect immune cells) but immunology is hard, and all the fibromyalgia trials are in women, who use different immune cells in their pain pathways, and it just didnt seem well-understood enough to risk it. Instead Im currently trying metformin on the basis of another very small trial, but since metformin is such a safe drug it seemed less risky. Good luck with your experiments!

  10. Moorlock says:

    FWIW: personal experience with gabapentin.

    I was on between 900-1800 mg/day of gabapentin for a pinched nerve in my neck. It worked very well for me: Kept the pain at bay for several years until the pinched nerve suddenly got much worse and I needed surgery.

    When first going on gabapentin I was troubled by extraordinarily vivid and lengthy (and sometimes disturbing) dreams… they were realistic to the point where they started intruding on my waking memories (“did that actually happen, or did I dream it?”) in a way that was a little worrisome. That subsided after a few weeks.

    Other than that, no side effects worth noting. I did find myself having increased alcohol cravings when I was withdrawing from gabapentin, which seems worth noting to people going through that process.

    • USB_qsd says:

      Similar to my experiences. Very low alcohol use prior to Gabapentin, genuinely disliked and avoided alcohol. No substance use other than tea. Prescribed Gabapentin for bulging and thinning disk L4/L5(also have a history of seizures which are in remission), took it very sparingly and noticed no effects for a few years, then returned to it daily for 1 year, 3 pills a day. Stopped, and then the alcohol use just spiked massively. Never felt a dependance on the gabapentin, I honestly just took it “just cause”… never noticed any effects. But yeah, almost right after stopping Gabapentin I began drinking moderately and have not stopped, something like 6-7 months now.

  11. SCPantera says:

    Do you not have access to any pharmacist resources? Sounds like you’d benefit a ton from access to say Micromedex or Facts & Comparisons. Do you have a pharmacy department who could hook you up? (cough are they hiring cough)

    There’s usually pretty good fast info on kinetics which might be helpful, eg:

    (Gabapentin)
    Bioavailability
    Inversely proportional to dose due to saturable absorption:
    Immediate release:
    900 mg/day: 60%
    1,200 mg/day: 47%
    2,400 mg/day: 34%
    3,600 mg/day: 33%
    4,800 mg/day: 27%
    Extended release: Variable; increased with higher fat content meal

    (Gabapentin ER is only available as brand Gralise)

    Trivia: Gabapentin is actually Schedule V in ND where I went to school, tramadol was a controlled substance there before it caught on everywhere also

    • perlhaqr says:

      Do you not have access to any pharmacist resources?

      Hrm. If he doesn’t, my ex-wife now lives in the Bay Area, and is a trauma pharmacist, and also kind of a nerd who might be willing to and be interested in discussing drugs with Scott.

      Scott: If you want an intro, email me at my username at gmail.

      • Garrett says:

        > trauma pharmacist

        Thank you for introducing me to that term and sending me down a research rabbit hole.

        • perlhaqr says:

          You’re welcome. 🙂 It’s a pretty cool field. It was fairly new when she was doing her residency back in the early 2000’s, but it’s much better established now.

          It was kind of amusing when I was doing the EMT thing. “I brought you a present, honey!”

  12. hash872 says:

    I’ve taken around 1500mg of phenibut once a week, most weeks for getting close to a year. Tolerance is definitely real (I am disciplined about not taking more every time), but I’ve had zero issues with wanting more or withdrawals- if I skip a week or two for whatever reason, I don’t notice anything and don’t even really think about the phenibut. It’s a highly effective way of basically forcing yourself to have a good day. (It does take astonishingly long to kick in- like no other drug I’ve ever taken. A minimum of 3 hours and more like 4).

    Interestingly, from the few times that I’ve been on it and also had random conversations with other people, it does not seem to reduce my anxiety at all (and like with every drug I’ve ever done, it slightly garbles my mouth and makes communication a bit difficult). I take it solely for the euphoric effects. It also doesn’t have that much effect on my sleep, contrary to what everyone else says- I do sleep deeper, but I wouldn’t say the sleep quality is overall any better. Sex is definitely superior

    • g says:

      Perhaps if I knew more about phenibut the answer to this question would be obvious, but: Does the last sentence mean “sex is definitely more effective than phenibut in promoting good sleep” or “phenibut definitely improves sex”?

  13. ddreardon says:

    Is there any research you are familiar with in regards to patient satisfaction comparing gabapentinoids and other anxiety reducing medication such as benzodiazepines? My girlfriend is currently taking benzodiazepines with pretty phenomenal results, but with moderate side effects.

    • Scott Alexander says:

      No research, but I think everyone likes benzos better than gabapentin. Not enough pregabalin or phenibut experience to compare.

    • Deiseach says:

      May I ask how your girlfriend is getting a prescription for benzodiazepines, or is it time-limited? I’m curious because I was flatly refused when I tried asking my GP for a repeat prescription due to addiction potential concerns.

      (It may just be that I am pheonomenally unlucky when it comes to medication: I couldn’t get anti-depressants despite presenting with suicidal ideation and a list of symptoms off this, I was refused benzos for the addiction concerns, and I have to kick up an unmerciful fuss in order to get any complaints taken seriously and not dismissed as “ah it’s just your imagination”. I think in part this is due to the outward shell of functionality I have been taught from childhood on to project; while internally I am having a screaming breakdown, externally I am reasonably normal appearing*. I think if I did the whole ‘floods of tears, irrational ranting and raving, collapsing on the floor in hysterics’ thing that I genuinely feel like doing but am suppressing, I might possibly get taken seriously about not being able to function, but who knows?

      Or there’s always the “cry for help fake suicide attempt” which probably would work, the problem there being if I ever get to that point, I’m not going to fuck around with fake attempts, I’ve got a real attempt that will really work because I looked it up on the Internet and yep, it’ll kill ya.)

      *EDIT: You lucky darlings get the incoherent irrational ranting and raving, screaming, tears and the rest of it. Thank you for being my support system, I love you all! 🙂

      • perlhaqr says:

        Given how docs like to hand out antidepressants like candy most of the time I’m shocked to hear that you’ve had trouble getting them. The benzo thing is less surprising.

        FWIW, I got my long term scrip for them when I showed up at my psychiatrists office pretty much uncontrollably crying. But I also had a standing diagnosis of PTSD, and was pretty clearly having a panic attack, so… I dunno. It was also an office that was fairly, ah… generous, with scrips for stuff. YMMV.

      • Rand says:

        In the US, very few GPs will prescribe benzodiazepines (especially on an ongoing basis), which many states are tightening controls on. If they feel you need them, they might give you a one-time prescription (but more likely something less dependence-inducing) and refer you to a psychiatrist.

        Among psychiatrists, attitudes seem to range from “not in a million years” to “here have some benzos!” (Both are pretty worrisome).

      • ddreardon says:

        She sees an actual psychiatrist, not a GP, with follow up every few months. She didn’t need to behave in any sort of erratic manner, but I expect that the willingness to write a prescription for them varies. She just described the symptoms of her anxiety and her psychiatrist was willing to write her a prescription.

  14. dpm96c says:

    Just logged in to say that these drug/psychiatric-overview posts are probably my favorite SSC genre and I always get excited when I see one pop onto the RSS feed.

  15. RKN says:

    It does match the paper’s figure 4, which shows little to no effect of gabapentin past 600 mg for seizures.

    That’s a little surprising given Goodman and Gilman indicate gabapentinn is effective for seizure control at doses of 900-1800/mg daily, and in some patients at twice that dose.

  16. SEE says:

    Anecdatum:

    Gabapentin seemed to work wonders on my anxiety for about four weeks, and then I became very agitated and irritable, which ended as soon as I discontinued the gabapentin.

  17. Purplehermann says:

    1 mg pregabalin= 5 mg gabapentin
    300 mg pregabalin=1800 1500 mg gabapen

  18. queldado says:

    It seems I have a different (better) experience with gabapentin than everyone else. While on vacation in an unnamed Asian country where a prescription is more of a nice-to-have than a requirement, I got ahold of some gabapentin from a pharmacy and started experimenting with it.

    I followed the protocol of taking 300 mg every 30 minutes. This staggering of doses is supposed to be necessary in order for it to be absorbed properly. Eventually, after 1,5 hours or so, I started to feel a nice buzz (I ended up taking 1200 mg in total this first time). All of my baseline anxiety disappeared and I started to feel mildly euphoric, similar to the euphoria you feel after 4-5 beers. Unlike beers, however, gabapentin didn’t make me dumb or dull my senses to any significant degree. Compared to benzodiazepines, gabapentin was more euphoric and pro-social (based on my limited experience with benzos they mainly cause apathy and anhedonia).

    The next day I tried the same dosing regimen again, but it was very apparent that tolerance to the recreational and anxiety-reducing effects of gabapentin is built up very quickly – I had to roughly double the dose in order to get the same euphoria/pro-social effects, which also caused more alcohol-like side effects (reduced intelligence/dulling of senses). After this I waited a few days before taking gabapentin again, which was enough to reduce the tolerance to an imperceptible level.

    I took gabapentin a few more times on the same vacation, and enjoyed it very much. It’s not a mind-blowing drug, but as a better replacement for a few drinks of alcohol it’s great. However, I eventually discovered that gabapentin more than anything else is useful as a sleep aid. Unlike benzos and zolpidem, which have negative effects on my sleep quality and cause severe sleep inertia in the morning, gabapentin made me sleep better than ever and ready to jump out of bed in the morning (I’m usually a heavy user of the snooze function on my alarm clock). When I got back to my home country, I tried getting it prescribed as an occasional sleep aid, without success (while it’s not yet scheduled where I live, it seems doctors are catching on to the fact that it has potential as a drug of abuse). As an anxiolytic I don’t think it would work quite as well because of how quick tolerance builds up, although I admittedly don’t have any experience with chronic use.

  19. Murphy says:

    Weird thought number 1221… something….

    The talk about phenibut made me think of something I used to wonder about.

    Motivation is hard. Lots of people have things they’d love to make themselves do… but we’re human.

    I’d love to rewire my brain a little so that I get as much enjoyment from a bowl of salad as I do from a nice steak. Or to actually get the “runners high” that some people seem to get.

    But I don’t have root access to my own brain.

    Part of the problem with drugs is that our brains respond to reward and there’s a clear line of cause and effect from a syringe full of heroin and the reward.

    We’re gradually moving into a time when quite a lot of people have implants or similar to dispense some medical drug.

    So.

    Bob decides he should exercise more but motivation is his issue and he knows this.

    So Bob gets something like one of those little chips that can slowly dispense a drug, but it’s filled with some kind of recreational substance and set up to be triggered remotely.

    Bob’s gym activity is monitored somehow and whenever he hits some kind of milestones he’s set for himself it doses him a little with the timing a bit fuzzed to try to build an association between the activity and the reward. Intellectually he may know it’s the implant… but his lizard-brain is getting rewarded whenever he exercises and eats right.

    presumably any such system would also handle very gradual tapering of doses and/or avoiding doses that could cause tolerance or physical addiction.

    It’s straight out of a dystopian scifi where the government sets all the milestones and all the milestones are “supports Dear Leader” but lots of things have potential for evil dystopian governments.

    And I could kind of imagine some people going for it.

    Though it might be amusing to try to get a clinical trial run. If it turned out well I could see half the doctors in the NHS supporting it to treat obesity and smoking.

    It would just need some kind of catchy and jokey acronym for the trial.

    • Radu Floricica says:

      If you have a moderate-to-high risk tolerance, all you need is already available. Use nicotine vaping as a reward.

      It apparently does take a non-trivial amount of discipline to only use it as a reward, but if you manage that it should work pretty well. On the plus side, worst case scenario is you get addicted to the same substance as probably half the population.

    • perlhaqr says:

      But I don’t have root access to my own brain.

      It’s funny you mention this, and it occurred to me that this is possibly the place I should bring this idea up, because I’ve had it before.

      I feel like the ketamine infusion sessions give some level of root access to my brain. Which is why playing songs with good lyrics works so well in improving my self-disposition.

      I’d really like to do some sort of work to figure out if there’s a way to do good programming type stuff with this technique, but I’m pretty sure that no study would allow that sort of cowboyism. 😉

    • noyann says:

      CCT. Cyborg’s Clicker Training.

      Hypnosis might also be working to make the reward system you came with fire on a predetermined achievement.

  20. perlhaqr says:

    1.) Heh. I came here to ask if you’d read this study. I guess so. I just found out about it this morning.

    2.) Anecdata: I was on 2400 mg of gabapentin for about 1.5 years, and it never seemed to actually do very much for me. I didn’t have the side effects either though, except when I was ramping to a new dose, and that only for a couple of days. Also, when I quit taking it, I pretty much quit all at once, and didn’t have any side effects from that either.

    3.) You touched on the one thing I’m kind of a fanatic proselyte about, ketamine. (*chorus of angels*) Ketamine saved my godsdamned life. Seriously. 365 days ago, I was in the depths of preparations for my own suicide, which was scheduled for the 4th of August. On the 2nd, unfortunately*, my housemate (who is a substance abuse counselor) found clear evidence of my plans, and got me to hold off for a bit. Late September, I had my first ketamine infusion, and basically instantly regained hope that my depression was treatable. Just getting “caught” didn’t change my mind about self-termination, it just put me into a state of “I guess I’m going to have to wait until various people have been satisfied that this really isn’t fixable and will get out of the way.” Ketamine changed my mind. I went from “lying on the couch watching Netflix and not really even enjoying it but it made time pass” to “going out and doing things I used to enjoy again” in one session. My regimen is 2 sessions in the span of a week, usually Monday and Thursday, at roughly 10 week intervals. (8 to 12, depending on how life is going.) In fact, I have one scheduled for later today, and then again on Monday. If you’d like to chat about ketamine treatment, email username at gmail, and I’d be happy to talk your ear off about it. 😉

    * In retrospect, not that unfortunate. But I was kinda irritated at the time.

    • anchpop says:

      Does it need to be infused? I have a depressed friend who I wouldn’t mind giving some ketamine to if it would make her feel better but I don’t have any way of infusing it

      • Freddie deBoer says:

        If we’re talking black marker here ketamine can be snorted.

        • Garrett says:

          From what I can tell, the infusions are done over a long period of time. If that’s the case you’d want to try and slow down the absorption rate. Snorting is one of the fastest routes of absorption. Of course, the S-ketamine nasal spray is absorbed nasally. This is where you really want a pharmacist to comment.

      • perlhaqr says:

        ObIAmNotADoctor: I kinda think it does, actually. The feeling I get from talking to people who have used K recreationally, versus the people who have used it therapeutically, is that the extended period of influence, combined with the slower onset and slower drop off, is part of what makes it so effective.

        But then, the FDA has also approved an IN administered esketamine formulation, so maybe I’m talking out my ass.

        But I also wanna say that (for me, at least) music is a huge part of the therapy. I have a playlist (actually, several very similar playlists) that I listen to on my MP3 player while I’m getting my infusion (which lasts about 45 minutes) and *significantly* influences what the experience is like. So I have a number of “uplifting” songs in there. Which are actually, like, heavy metal music, but with positive messages. Motorhead’s “Ridin’ With the Driver” (“No force on Earth can stop me now, I’d like to see ’em try!”) and “Stand” (“Stand! You can make it! Stand! You can take it! Stand! Realize that nobody can break you if you stand!”), A Dark Halo’s “Unbreakable”, Manowar’s “Black Wind, Fire, and Steel”, etc. But the list is set up to match my own experience of onset, peak, trail, in terms of what’s playing when, and how it ramps me up as the drug is coming on, and how it’s going as I come down. Slower stuff at the beginning and end, with heavier stuff at the beginning and gentler stuff at the end, and then really hard and fast stuff in the middle.

        I dunno if that information helps you or not. FWIW, my dosing is 1mg / kg, over that 45 minute period. Theoretically, some people can get a benefit from 0.5 mg / kg, but I know people who are much smaller than I am who needed 2.0 mg / kg before they got any benefit.

        It’s becoming a more common treatment option, though. I know of two places here in Albuquerque that have opened up since I started getting my treatments, and that was only 10 months ago. Google, to see if you can find a treatment center near you. Also, be aware that prices vary wildly. I’ve seen anywhere from $100 – $600 per session, here. I have no idea what prices are like elsewhere, except in Germany, oddly enough, which is probably useless for you, since their system is utterly different from ours.

    • broblawsky says:

      Thank you for sharing your experience. If I may ask: was your friend’s ketamine acquired via a prescription, or via alternative means? Because I recall from the previous discussions of prescribed ketamine isomers (s-ketamine) that their effectiveness was in doubt. Please don’t feel compelled to answer if you don’t feel safe in doing so.

      • perlhaqr says:

        Oh, no. Uh. I *think* I understand what you’re asking, but if I answer the wrong question, feel free to try again.

        The ketamine wasn’t administered by my housemate. He just caught wind of my plans and called in the troops. My father showed up on my doorstep before the weekend was over. He’s the one who ran me all over town talking to people about treatments I hadn’t tried yet.

        I go to a clinic that’s run by an anaesthesiologist, in order to get my treatment sessions. It’s very above board. I’m pretty sure this is just straight, old school, been off patent for forever ketamine. Comes in a bulk bottle, the doc pulls as much as is appropriate for your dose out of the bottle, puts in in the infusion syringe (which is very large) then draws saline out of the IV bag to dilute the ketamine so that it can by run into the IV line via an infusion pump. Apparently it’s made in Puerto Rico, because my first set of sessions was very expensive, due to having to have the ketamine made up to my dose at a local compounding pharmacy, but now that the doc can get it in bulk again, the price has dropped significantly.

        Was that the question you were actually asking, or did I misunderstand?

        If there’s something in particular anyone wants to know, I actually have a session later today, and I can try to remember to ask the doc…

      • broblawsky says:

        Yeah, you understood. Sorry if I was a bit obtuse: I was primarily asking if you were getting street ketamine or esketamine (rather than regular ketamine) from a clinic, and asking someone if they’re committing a crime is a little tricky, etiquette-wise.

        Please ask your anesthesiologist if he knows anything about esketamine.

        • perlhaqr says:

          He said basically the same thing Scott did in the other post about ketamine. Well, he was actually *more* cynical than Scott was, in that he said that the whole thing was a setup between the hospitals and the pharma companies to make sure they got a bunch of money.

          Also, having read into the comment thread there, I’m kinda glad I didn’t catch that one. I’m not sure I could have remained polite, and therefore, remained a commenter. 😉

          Side note: I’m not sure Unsong was the right thing to feed my brain right before a ketamine session. 😉

          • broblawsky says:

            Thank you for asking him. I suspect he’s right about that, although it might be worthwhile if esketamine works as well for other people as regular ketamine works for you. Whether it does is an important question.

          • Deiseach says:

            I’m interested in that you describe getting it via IV, whereas I’ve recently seen stories that esketamine is available as a nasal spray, and being fair to the FDA they’ve permitted it despite some opposition.

            It would seem that the “only administered under doctor/hospital supervision” is to monitor for side effects but mostly to catch and prevent abuse, and I have to say – being cynically inclined – I think the abuse potential is definitely there. Setting it up so any doctor just prescribing the inhaler version that you can take at home or as needed is going to end up with abuse, and the equivalent of pill mills.

            It’s definitely a pain in the arse for legitimately depressed people to have to jump through the hoops, but given the kinds of consequences that would occur if abuse was facilitated (“Something Must Be Done! Ban this method and this treatment and this drug now!” and then nobody who needs it can get it, the same way the opiod abuse crisis is interfering with legitmate pain management for chronic pain sufferers), it’s no harm to err on the side of caution now so that a useful treatment isn’t strangled in the cradle.

          • perlhaqr says:

            @Deiseach

            Yeah, my doc is one of those cowboy anaesthesiologists Scott talked about in his last ketamine post. It’s definitely a very off-label, grey market use of the stuff, but holy fuckballs, it works so goddamned well. Like I said in my upthread post, I was going to kill myself. And there wasn’t going to be any of that “cry for help” BS, either, I had a method that would be guaranteed 100% effective, and non-messy. My goal was basically to be the politest suicide I could possibly be.

            And just “getting caught” beforehand didn’t change my mind on any of that. If anything, I was sufficiently convincing that half the people I talked to were on my side afterwards. (Not my mom, but, well, one can only expect a certain number of miracles.) But I agreed to let them try new things on me, and basically come to agree with my conclusion that nothing was actually going to work… and it turned out I was really, really wrong.

            It was like flipping a godsdamned switch.

            I rent a shop space, where I (theoretically) work on my car projects. Mid-January, 2018, I put a car in the garage, with the intent of stripping it down and rebuilding it. Between January and mid-September, I got as far as: Putting it on jack stands, removing the wheels, and removing the driveshaft. And that’s it.

            Mid-September, I had my first k infusion session. The very next day, I went to the shop, and pulled the engine out of the car. And the day after that, I went back, and removed the rear suspension. And so on. I hate using the term, but frankly, it was kinda miraculous.

            @broblawsky

            The big issue being, apparently it doesn’t. :-/ Not only because it appears to be the wrong… isomer? I think that’s the right term, but I’m not really a chemist. But also because the route of delivery is non-optimized for therapeutic use.

            The closest I can come to describing it is that the sessions are like rebooting my brain, and getting to use music to update things at a slightly deeper level than I normally have access to. Which is why I pick the lyrical content of the stuff I listen to so carefully during sessions.

            But I think that process requires the 45 minute infusion process, with the 10 minute onset, the 35 minute peak, and the 30 minute comedown after the infusion pump has stopped, while I’m just metabolizing the drug. A fast bump up the nose isn’t going to have the same sort of mental plasticizing effect, I don’t think.

            Though, I suppose I should actually try it, and see what the experience feels like from the perspective of someone who has been on this therapy regimen for a while now. Hrmmmmmm.

          • broblawsky says:

            @perlhaqr Having first-hand experience on esketamine vs conventional ketamine would be valuable, but please don’t do anything to screw up your treatment. Discuss this with your doctor first.

          • perlhaqr says:

            @broblawsky

            Ha ha, oh, GODS yes. 😀 No, there’s no way I’m going to risk the progress I’ve made.

            But, today is the second session of my usual 2 session treatment at 10 week intervals (which is the other thing about the esketamine dosing schedule, it’s 3x weekly, and more expensive, but since it’s now FDA approved, insurance will cover it…) so, I’ll ask the doc what he thinks when I see him this afternoon.

            Side note: The intervals aren’t perfectly consistent. The first one I did was 12 weeks, but both myself and my housemate agree that was too long. The next several were 10 weeks, and that seemed to be working well. This last interval was 9 weeks, but I was a bit “overdue” by the time I had my session last Friday. I think that’s probably due to the distilled stress I’ve been mainlining the last couple of months, though…

          • jameverywhere says:

            perlhaqr,

            Do you think there’s a possibility that your ketamine treatment effects could be permanent if you did this mental reset thing, then also completely reset your life as well? As in, did the treatment and changed your life for the better in dramatic and significant ways, rather than returning to the daily grind?

            I ask for my own personal situation. I’m about to dramatically change my life to try and cure my depression and I wonder if ketamine might be able to cement the change. I don’t want to rely on ongoing treatments, however.

          • perlhaqr says:

            @broblawsky

            Doc said that trying the esketamine therapy would not have any deleterious effects, and that having the comparison data might be pretty useful, so, I should go for it.

            @jameverywhere

            Hrm. I dunno. My depression, at least in part, stems from the fact that my body and brain just kinda make the wrong chemicals. But I don’t know enough about that to know if it’s fixable or not. I am working towards that “reset your life” thing though.

            My planned suicide was scheduled for a date approximately 8 months after I had lost the last job I had (which was a very, very horrible job as a systems administrator for a person who may be genuinely sociopathic: she seemed to make efforts to drive people to the edge, and make efforts to set people up for failure so she’d have an excuse to yell at them) which… in retrospect, I’m *glad* I lost the job, because I hated it. But I bring it up because I’ve recently completed a semester at the local trades school, which has granted me a CDL. I’m going from being a computer jock to truck driving. This is actually my fourth attempt to leave computing, I have also gone to the same trades school to learn welding, machining, and to get my EMT license. (Which I no longer have, because in the midst of working the horrible job 60 hours a week and going through my divorce, I just didn’t have the spoons to bother with the needed continuing ed classes to maintain it.) But I’m going to make a concerted effort to go be a trucker.

            Which seems like a fairly hefty reset, although I would also have to admit that there are lots of aspects of my life that I haven’t made any alterations to. For instance, I’m still a fairly horribly disorganized slob. But at least now it’s because I’m out doing things and just so busy that dealing with the mess is just a very low priority, as opposed to my simply not caring about anything at all any more.

            In my decidedly non-expert opinion with only one real data point (myself), I don’t think that it is likely that it’s possible to permanently cure depression with just one set of ketamine sessions. While it does seem to make the brain (the mind?) vastly more plastic than normal, I don’t think it makes it quite plastic enough for that. But I do think that it’s possible that if a person were to make a lot of other changes in their life (and it’s great for giving a depressed person a big leg up out of the “depression rut”), and to work on the “reprogramming” aspect in a more systematic way, that a person might be able to use it “for a while” and then not need it any more.

            ——

            Not Even Particularly “Scientific” Wild Ass Guess Time: I suspect that part of what causes systemic depression to hit some people so hard is the depression spiral aspect of things. People who are prone to depression, if they hit a big enough stumbling block, or enough smaller ones in series, start spiraling downwards, and the further down the spiral you go, the more downward momentum you pick up, and the easier it is for even smaller things to cause you to stumble and spiral faster. Between various chronic pain problems, various relationship problems, and a number of other things in my life and with my body and brain, by “the end”, I was at a point where I was just laying on the couch all day, smoking lots of weed, drinking lots of beer, and watching Netflix. I actually exhausted my queue. But I was pretty much at rock bottom, and breaking out the pick-axe, sledgehammer, and drills.

            The ketamine certainly didn’t “cure” me, but it lifted me enough that I could go do things again, and had some motivation to do so. Which I admittedly then used to go accomplish work on my fairly silly hobbies, but at least I was doing something again. And after a bit, I had enough motivation to go back to school again, too, and I’m working on making improvements in my life over time.

            So I think the ketamine therapy can help a person who is biochemically prone to depression break out of the downward spiral, and get back on steady ground. I hope that can eventually be permanent But I don’t want to make too many claims for the stuff, or give you any sort of false hope, because I simply don’t know. Which doesn’t mean you should get false, uh, “disillusionment”, either. Because I simply don’t know. I mean… I’ve only been doing this for 10 months. I’ve had a grand total of five therapy treatments, consisting of two sessions each. So I’m still pretty new at it, but I can’t help but proselytize about the “It made me not want to kill myself any more” part. 🙂

            But the downward spiral to that point was 30 years in the making. If it “only” took me five years to get back out of it on a mostly-permanent basis, I’d consider that pretty darn good. I mean… I basically already lost that much time (and more) to the black hole of depression. At least I’m doing things I care about while I’m fighting my way back out. And to be clear, I feel like I’m making progress, even if I’m not “fixed” yet.

            And on the gripping hand, it sounds like you might not be as far down the spiral as I was last year. For one thing, judging from your statement, you have enough motivation and available spoons to make alterations in your life before the ketamine therapy. So who knows? Maybe you can get away with just one treatment. Still, if it turns out you need a couple of touch-ups afterwards, don’t let that get you down. (ha ha) Concentrate on the fact that your efforts to make changes in your life are working, and take the treatments as you need them, if you need them.

            Best of luck, friend. 🙂 Let us know how it goes?

  21. nupi says:

    Long time lurker, first time poster.

    Timely post. Lately had stronger than usual anxiety, fatigue, weird (possibly neuropathic) pains, worse than usual sleep and balance issues. Seeing a neurologist in early August (GP was entirely helpless) and already thought pregabalin might be worth a try as a combined anxiolytic and analgesic (please don’t suggest Duloxetine as the other on the list, I tried it as an antidepressant years back and felt really odd, obsessed about all kinds of things). For people who already used, how bad are the side effects?

    • noyann says:

      Not too bad with 375…450 mg/d on a ~70…80 kg person (for post-zoster neuralgia).

      Mostly drowsiness and a kind of vertigo-lightness that feels like I was not fully in my body, but not unpleasant. Perception and emotion were not as intense as usual. (It could be tried on hypersensitive persons or sensory processing disorder, IMO.) Peaking shortly after intake. (ETA: Half life is 6…7 hrs, I had changed from 3 x 150 mg to 4…6 x 75 mg, halving the tablets, to have a more even, erm, experience.)
      Appetite (a permanent desire for snacks) and weight increased.

      Taking it with or soon after a meal slows uptake and the peaks of (side) effects were noticeably lower and broader then. Drinking much increases its renal elimination; pains did set in again earlier than expected in high-pee times.

      • noyann says:

        Remembered more: Sometimes difficulty finding and pronouncing words.
        Pregabalin stabilizes the neuronal membranes, so they trigger less easily. I guess the more prominent side effects are in the body systems/functions where they are easier to notice.

    • icodestuff says:

      Don’t remember what my dosage was, but probably similar to @noyann, as it was for the same thing and we’re about the same weight. My experience couldn’t have been more different. I had to discontinue after just a few doses each of pregabalin and gabapentin. Gabapentin gave me surprise projectile vomiting after maybe 2 or 3 doses. “Surprise” as in I had no clue it was about to happen until about two seconds before it happened, barely even enough time to think “something is wrong, bathroom now!” let alone get out of bed to get there. No heaving, just mouth-open-vomit-out. I had barely enough time to turn my head away from my feet and avoid anyone else. “Projectile” as in the entire contents of my stomach were suddenly several feet across the room in one or two reverse peristalsis contractions. No nausea or dizziness to go with it.

      A few days later I was given pregabalin instead. That was fine for about 2 days (although I don’t remember it working well), and then I got the scariest migraine of my life. Now, I’ve had migraines before. They’d only ever involved headache and hypersensitivity. No flashing lights or anything, so it took a while to recognize what was going on. I started seeing what I thought at first was an afterimage – I’d been reading on a bright phone in a dark car, but it turned into spots all over my visual field. But they were small so I figured it was just afterimages again from some cars that had just turned on their lights in the parking lot. So I started driving. About 2 blocks later, I realized something was very wrong with the left side of my visual field. It wasn’t making sense. I quickly pulled over and turned the rear view mirror so I could see my eyes. I looked left and then immediately my eyes snapped back to center. But my brain was insisting my eyes were pointing left, so it was filling in my visual field with what it had briefly seen on the left plus the actual forward gaze, all jumbled together. But my brain insisted I was looking left, even though I could clearly see two eyes forward in my rear view mirror. Tried a few more times, same result. No issues looking right. Quickly checked for face drooping or uneven arms because I was worried I was having a stroke. Nothing, thank God. Put on hazard lights and drove extremely slowly back to the parking lot (I was not stopped in a legal parking spot) before calling someone to pick me up. Hypersensitivity hit about 10 minutes later, headache around 20 minutes after that, and all the effects lasted all night. I’m just glad I’d decided to keep reading the article I was in the middle of after getting in the car; if I’d left straight away, I would have been on the freeway when the migraine hit and probably hit someone.

      On the other side of things, I’ve used baclofen after some bad muscle spasms, and never had any side effects from it. No addiction, no neurological effects at all. It did take a couple days to start working though.

      • noyann says:

        Pregabalin must be ramped up slowly (gabapentin probably too). Omitting that may have caused your reactions.

        My prescription stepped up every 3 days, adding 1/2 of 75mg x 2/day; then from 2 x 75mg x 2/day to the max of 3 x 150mg with permission to go full 600mg/day, if needed.

        Abrupt withdrawal can be serious, up to epileptic seizures. I think the body gets used to the reduced excitability of the neurons (yeah, we learn to be thick!) [*] and then has to re-adapt to being clean, and then reactions may overshoot (at first) and we are hyper-excitable.

        [*] E.g. my slight dizziness/vertigo/not-really-in-my-body got better, after ~6 weeks I felt safe enough for everyday cycling.

        ———————–
        Who will read that now? A future archeologist?

        • icodestuff says:

          Wow, did not know they had to be ramped, and apparently the doctor and/or nurse when I was in the hospital didn’t either (where I was given the gabapentin, and prescribed the pregabalin). That’s kinda scary to think about, but at least I know I don’t need to avoid them forever, as long as I have a doctor who knows what they’re doing.

  22. Squirrel of Doom says:

    a lot of scientists have analyzed pregabalin and said it’s definitely just doing the same thing gabapentin is.

    Maybe the difference is “Price Placebo”?

    If I’m being treated with a $500/month drug, I’ll probably trigger a higher placebo response that for a $7/month one.

    We all know you get what you pay for, and the brain’s Placebo Center may also apply that heuristic.

    • noyann says:

      Anecdatum: I had to pay <6€ for 100 x 150 mg with my insurance plan and Pregabalin worked well on an anxiety it was not prescribed for, I only learned about that effect looking pg up after treatment started.

  23. MereComments says:

    This is somewhat orthogonal to the main post, but are the doctors/psychiatrists who prescribe gabapentin aware of its main use amongst opioid addicts? The current trend among people that might have been on methodone a few years ago is to mix gabapentin with their suboxone medications (used to treat opioid addiction). Suboxone on its own (allegedly) doesn’t produce the euphoria of opioids, but mixing it with gabapentin blocks whatever part of suboxone that prevents the user from actually getting high. Here’s one article about it. This is common knowledge among addicts and the people around them, but I’m not sure how much the medical community is aware of this issue. Users can doctor shop or trade drugs at NA meetings to get this combination, which they then often take with other drugs like klonopin or xanax because, hey, why not? Just thought this should be mentioned in an post about gabapentin (before this post I had only ever heard of it in the above context).

    • Scott Alexander says:

      I wasn’t until just now (I vaguely knew addicts used it, but I’d forgotten exactly for what).

      I’m confused about how it would potentiate opioids, and I’m really skeptical of the article’s claim that it jailbreaks suboxone by kicking naloxone off of receptors. The naloxone in suboxone is irrelevant to its hard-to-abuse-ness unless it’s being injected. So you’re not going to accidentally get high off suboxone just by taking gabapentin along with it.

  24. slovakmum says:

    What is Vigabatrin / Sabril ? Is it the same group of pills as gabapentin and pregabalin ?

    • Scott Alexander says:

      According to Wikipedia, “an irreversible mechanism-based inhibitor of gamma-aminobutyric acid aminotransferase”. That means it prevents the enzyme that breaks down GABA from working, leading to more GABA. That’s different from the gabapentinoids, which have GABA in the name but really work on calcium channels.

      I agree this is annoying and confusing.

    • Kinkkisyyksia says:

      Unlike different GABA receptor agonists, vigabatrin increases GABA concentration in the synapses and thus should activate GABA-A and GABA-B receptors roughly equally (at least in principle, couldn’t find good data about this with a quick literature search).

      However, vigabatrin has a habit of making you blind in the long run, which pretty strongly discourages using it in anxiety, as well as abuse. It’s also why it’s nowadays used almost solely (at least in my country) in treatment of most severe and treatment-resistant paediatric epilepsies.

  25. I’m a bit late with this comment, but I really wanted to say I loved both this article’s content and its presentation. I was giggling all the way through the introduction of phenibut.

    Thanks for sharing your thoughts on this! (And thanks to everyone else who commented with theories or shared anecdata; part of what I love about Slate Star Codex is the high information density in the comments. Y’all are awesome.)

  26. Orion says:

    I think that patients who feel like a drug is helping them will describe the side-effects as mild or even choose not to talk about them, whereas patients who don’t feel like a drug is doing anything will describe equivalent side effects as more severe or more troubling. You don’t actually get “raw” data on how much nausea or fatigue a medication causes, only weighted data about the ratio of fatigue and nausea to perceived benefit. This is partly because happier people will genuinely be less upset by the side-effects, and partly because patients make strategic decisions about how to report side-effects and whether to report side effects based on what prescription they want to receive. I also suspect that people with uncontrolled anxiety disorders would experience more side effects from a placebo than people with well-controlled anxiety disorders would.

    I’m going to guess with 50% confidence that if you doubled the dose of gabapentin (from 600 to 1200) that reported side effects would fall to Pregabalin-like levels. I know some people say that a 50% prediction isn’t a real prediction, but I would argue that “increasing the dosage reduces reports of side effects” is a surprising claim that has a <50% prior.

  27. app says:

    Just a random note about dual-prescribing baclofen and gabapentin – I am a clinical psychologist in a rehabilitation medicine department, and the PM&R docs do plenty of prescribing these two in tandem for patients with spinal cord injury, who often need baclofen for spasticity management and gabapentin for neuropathic pain management.

  28. Strawman says:

    Possibly somewhat related to the phantom hat effect of phenibut: Nearly a decade ago I was briefly prescribed zolpidem (Ambien) as a sleeping aid, and on the occasions I remained awake long enough to experience its hallucinogenic effects – which I remember as pretty enjoyable, but otherwise unremarkable and in no way life changing (wholly without any of the sense of meaningful revelation one can get from, say, an lsd trip, *cough* or so I’ve heard) – I also remember having the sensation of wearing not quite a hat, but more of a helmet.
    I have no experience with phenibut, so I can’t tell how similar this feeling was, I just thought it might be worth mentioning as I haven’t seen that particular effect of zolpidem described anywhere else (not that I’ve been looking, haven’t thought about it for years until this post reminded me).

  29. hopaulius says:

    Every consideration of the efficacy of a drug that influences mood should begin with the placebo effect. The null hypothesis should be: patient expected a better outcome with drug B, and thus experienced it (although I’m aware that this isn’t a great null-hypothesis formulation). You ended with a mention of placebo alcohol. That’s the starting place. So the lowering of efficacy over time isn’t necessarily an addictive response, just ennui.

  30. Stuart Buck says:

    I don’t know much about gabapentin per se, but I know it’s one of the poster children for bad clinical trial reporting/evidence. See, e.g.:

    https://www.nejm.org/doi/10.1056/NEJMsa0906126

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3439687/

    https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001378

  31. nameless1 says:

    Baclofen is definitely fixing my alcoholism! Just because one study contradicts the experience of many doctors and patients, does not write it off. There are many kinds of alcoholism with different underlying reasons.

    Dr. Olivier Ameisen used drink to cope with anxiety. I too, but I am not consciously anxious, it just manifests in super tight upper trapezius muscles. You know, the same back shoulders that everybody likes to get massaged because everybody stores stress there. But for me, they were like concrete. I got never drunk, but I used alcohol as a medicine to get more relaxed and after 25 years of doing so every day I needed like two bottles of wine.

    So maybe anxiety -> tight muscles -> drinking, and thus Baclofen fixes the intermediate reason. But I used to have panic attacks when I had no alcohol at home and now every time I have a craving I flip a 10mg pill and it goes away for 3-4 hours.

    Don’t diss it. Dr. Ameisen got the idea from random people who were already using it for this reason and there are tons of people using it, often without a prescription just buying it online and it works in many, many cases.

    How does one calculate abstinence rate? In the first 2 days taking 15 mg a day I did not drink and suffered. Next 3 days I drunk. Next 3 days taking 40 mg a day not drinking. This is where I am now. I could even go into a music club and dance without drinking, that is a big deal as of course places like that are huge drinking triggers and excuses.

  32. ksvanhorn says:

    I’m undergoing ketamine therapy myself right now, and I’m puzzled by this statement:

    Ketamine such is a difficult medication to use – dangerous side effects, intolerable hallucinations, IV delivery

    Dangerous side effects? From my reading on the subject it’s one of the safer anesthetics, as it doesn’t suppress your respiratory system. Untrained soldiers administered it to the injured in the Vietnam War. They give it to injured children in the ER. Ketamine abuse can cause trouble, but even there, consider the case of John Lilly: really over-the-top overuse of ketamine, to the point where he had a hard time finding a place to inject, and yet he lived to 86. That seems to argue against a high level of toxicity.

    IV delivery? Some providers use that method, but mine uses intramuscular injection. One shot in the shoulder and done.

    Intolerable hallucinations? The hallucinations/altered state lasts only 45 minutes, all in a comfortable, secure environment under medical monitoring, and they’re completely over by the time you leave the office. Based on my experience, intolerable is certainly not the word I would use. Yes, the sessions can be quite bizarre. Yes, if nobody told you what to expect it would be pretty alarming. But it doesn’t last long, and when you know to expect a pretty strange altered state, it’s just weird, not scary.

  33. Anthony says:

    I take 100mg Gabapentin daily, in the mornings. My prescription says “up to 3x daily as needed”.

    I was prescribed it after noticing that while Bupropion was lifting my depression, it seemed to be increasing my anger, as well. When I got the first bottle, I’d had a really shitty commute home and was really angry. I took one capsule and felt the anger melting away over the next 10 minutes, in a way that coming down off anger without chemical assistance didn’t.

    Since I started taking it daily (mornings before leaving for work), I’ve noticed a lot less anger. I will sometimes supplement with an additional capsule if I’m facing a particularly stressful situation, but not as often as perhaps I should.

  34. Majuscule says:

    I’m intrigued by how many folks have tried some of these medications, either prescribed or self-administered. I’m also curious if any of you with anxiety get routine thyroid checks? I never had any overt symptoms of hypothyroidism but my numbers indicated treatment, and once I started treating my thyroid I realized I was much less anxious. I’d been experiencing long bouts of anxiety and depression for most of my life that were pretty unpleasant but never felt “serious” enough for me to seek treatment. In hindsight, I probably should have seen someone about it. But since I started regulating my thyroid about a decade ago I haven’t had more than a few days at a time of feelings and insomnia that went on for months in my teens and twenties. This is purely anecdotal, but I suspect treating even a mildly dysfunctional thyroid might be as effective as some psychoactive medications. Note that thyroid issues may be cyclical so you might need to get tested repeatedly over a long period of time to get diagnosed. Did anyone’s psychiatrist or neurologist order a thyroid panel before prescribing antianxiety or depression meds?

  35. Are you familiar with the Works of Thomas Szasz?
    If so have you written about him? if not what are your thoughts?

  36. Kinkkisyyksia says:

    In Europe, generic pregabalin (along with gabapentin) has been available for some time, and is relatively cheap. In Finland, it’s widely used to potentiate different substances of abuse, and reportedly fetches a high price on the streets. This may be at least partly due to liberal prescribing of pregabalin for (suspected) neuropathic pain and anxiety at a time when attitudes towards benzodiazepines were becoming ever stricter. Nowadays, many experts here advise physicians to be as cautious prescribing pregabalin to patients with suspected substance abuse problems as with BZDs. According to the addicts I’ve worked with (as a PC / emergency doctor), pregabalin goes pretty well with practically every sedative (booze, benzos, opioids, muscle relaxants, etc.), suggesting (I think) direct pharmacodynamic synergism rather than something like counteracting naloxone. It’s notable that gabapentin seems to be much less popular for this purpose; among those who have tried both, attitudes towards gabapentin range from “nice but not in the same league as pregabalin” to “utterly useless”. This is probably due to the pharmacokinetic factors discussed by Scott. When used as adjuvant sedatives, most common pregabalin doses seem to be in the range of 300 mg. According to the data presented in the post, this would equate to 1500 mg of gabapentin, most of which wouldn’t be absorbed quickly or at all.

  37. Kinkkisyyksia says:

    In Europe, generic pregabalin (along with gabapentin) has been available for some time, and is relatively cheap. In Finland, it’s widely used to potentiate different substances of abuse, and reportedly fetches a high price on the streets. This may be at least partly due to liberal prescribing of pregabalin for (suspected) neuropathic pain and anxiety at a time when attitudes towards benzodiazepines were becoming ever stricter. Nowadays, many experts here advise physicians to be as cautious prescribing pregabalin to patients with suspected substance abuse problems as with BZDs.

    Apparently, pregabalin goes pretty well with practically every sedative (booze, benzos, opioids, muscle relaxants, etc.), suggesting (I think) direct pharmacodynamic synergism rather than something like counteracting naloxone. It’s notable that gabapentin seems to be much less popular for this purpose; among those who have tried both, attitudes towards gabapentin range from “nice but not in the same league as pregabalin” to “utterly useless”. This is probably due to the pharmacokinetic factors discussed by Scott. When used as adjuvant sedatives, most common pregabalin doses seem to be in the range of 300 mg. According to the data presented in the post, this would equate to 1500 mg of gabapentin, most of which wouldn’t be absorbed quickly or at all.

  38. Jan_Rzymkowski says:

    It’s super wierd because in Poland pregabalin costs lunch money and it had been like that for at least 3 years (600mg/day cost me less than 15 dollars a month) in which I was taking it.
    As for me, it treated my back pain nicely, but at the expense of a debilitating aboulia that forced me to leave a PhD program in chemistry. Not sure if it had that effect on its own or only with combination with SSRIs — to my knowledge my case wasn’t described in literature nor any of the psychiatrists I’ve been to heard about such an adverse effect.

  39. paulbali says:

    Do the hokey tests they run rats through exactly correspond to treating anxiety in humans?

    I’m not sure ‘hokey’ is the right word, Scott, for the Forced Swim Test a.k.a. the Behavioural Despair Test.

    Other h-words like hellish, horrific, and humanist come to mind.

    I agree there’s something ludicrous in the scene: white-coated pros, gathered round to scrutinize the agonized animal, disinterestedly. What’s ludicrous is several contradictions & contrasts: the bully’s outsizing of the tiny victim; the labworkers’ cool manner & the victim’s expressive anguish; and the act’s putative ethical justification [the animal is fit to be abused, since psychologically unlike us] conjoined with the act’s scientific justification [the animal is a relevant model of human anxiety, since psychologically like us].

    I wonder by what future year a Moral Asterix will be appended to our citings of this research to acknowledge crimes against life committed.

  40. elderpedal says:

    Dealing with a relative taking Gabapentin initially prescribed to preclude heart flutters that would often interrupt her sleep. Additional 411 is that she’d been, for roughly four years, on a steady dose of Xanax (daily, half a pill, she states). I’ve read that side effects from long term use of Xanax include deterioration of short-term memory, particularly among the elderly population (to include said relative) AND heart flutters. We’ve worked her off Xanax (because I feared that continued use would further impair her memory) and would like to work her off the Gabapentin for alike concerns. I realize this is probably not the forum to help me resolve my angst… but I am interested in learning as much as I can about Gabapentin use and effects.

  41. 2irons says:

    I would caution that doctors prescribing more pregabalin and gabapentin and those drugs interacting with street drugs has been blamed for Scotland’s rise back to the top of the per capita drug death tables. The majority of overdoses involve polydrug use.

    Why are these drugs in particular being abused? They enhance opioid euphoria and they trade for way more than lots of other drugs in prison because they’re undetectable in routine urine tests.

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