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See, that’s what the app is perfect for.

Sounds perfect Wahhhh, I don’t wanna
nostalgebraist

themodernsound asked:

So while we're talking about bupropion; to my knowledge every Serotonin-Dopamine Reputake Inhibitor yet researched has been shelved as a potential anti-depressant because of abuse liability. Why, in your estimation, would this be any different than combining bupropion with an SSRI (discounting NRI activity of course but that would really only further highlight my curiosity/confusion)?

slatestarscratchpad answered:

It shouldn’t be. The serotonin should be irrelevant. The interesting question is why bupropion doesn’t have abuse potential.

(it sort of does - there are people who will abuse bupropion - but it’s not that common and you have to be desperate)

The answer is “nobody knows anything about any of this”. Sinemet is Literally Dopamine, and you can take it and recover from hypodopaminergic disorders, yet it’s not addictive. Pramipexole is a great dopamine agonist and it’s not addictive either.

My guess is this stuff has to do with where in the brain it increases dopamine, how quickly, how much, by what method, etc. But that’s all just a guess.

nostalgebraist:

We totally know about this!  Some dopamine “reuptake inhibitors” bind to the dopamine transporter when it’s in the “open configuration” and others when it’s in the “closed configuration,” and the difference maps onto abuse potential: cocaine and methylphenidate are on one side (”binds to open DAT”), bupropion/hydroxybupropion and modafinil are on the other(”binds to closed DAT”), and there are some more esoteric/research-type chemicals on each side which also fit the pattern.  Here is a paper about it, and here’s another.

The latter paper speculates, at the end, that the DAT is just more frequently in the open configuration than the closed one (at least I think that’s what they’re saying).  So drugs that bind to open DATs get more chances to bind than those that bind to closed DATs, all else being equal.

Of course, all else isn’t ever equal, and this is presumably just one (important) contribution to the overall effect, along with the usual ones like binding affinity and rate of delivery to the brain.  Bupropion is particularly complicated because it is largely a prodrug to the metabolite hydroxybupropion when taken orally (you end up with way more hydroxybupropion than bupropion in plasma), and hydroxybupropion is a much weaker dopamine reuptake inhibitor than bupropion.  As @wirehead-wannabe mentioned, people do (ab)use bupropion recreationally by insufflating it (or injecting it), which bypasses first-pass metabolism, so you get more actual bupropion as opposed to hydroxybupropion in your brain (and of course it is delivered way faster).  It makes sense that this would be more reinforcing, although one would think the “binds to closed DAT” thing would still mean it isn’t all that reinforcing.  (Which seems likely to be true: if snorted bupropion produced a high anywhere near comparable to cocaine, you’d think it would get really widely abused and be made a controlled substance.)

(N.B. the first paper linked above is about modafinil, which is apparently a “binds to closed DAT” reuptake inhibitor, like bupropion.  From what I have read, e.g. this paper, it looks like that is probably all modafinil is; the fancy hypotheses about histamine and orexin don’t explain anything that dopamine reuptake inhibition wouldn’t.  So modafinil is probably a much “cleaner” example of what you get from “binds to closed DAT” inhibitors, without all the bupropion-specific weirdness discussed above.)

Anyway, I don’t know anything about SDRIs, but if the ones mentioned by the anon asker were the “binds to open DAT” kind of DRI, that would explain everything nicely.

Thanks, I didn’t know that (and must have missed the past few times you’ve blogged about it).

I’m a little confused, though. You have the positive effects of stimulants and you have the abuse potential. If modafinil has fewer opportunities to bind than amphetamine, it sounds like you would need a higher dose in order to get the same level of positive effects. But wouldn’t that also increase the abuse potential? Ie why does the open/closed thing change the effectiveness/abuse ratio?

nostalgebraist Source: slatestarscratchpad

Anonymous asked:

Would you consider writing more reviews of fiction books? Your review of "On The Road" was hugely entertaining. Also, what is your favorite fiction book or some of your favorite fiction books?

Thanks. I do read fiction sometimes, but I don’t think most of it would be as entertaining to review as “On The Road”. That one worked out because it was a well-known cultural touchstone, it had interesting implications, and I had strong opinions on it. I think most fiction wouldn’t be as interesting for me or for my readers.

Anonymous

goodnightmoonvale asked:

Out of curiosity, do you have any examples of experiences that made you realize not everyone was as trustworthy as you initially assumed? Or what you meant by "a different relationship with the truth" (that may not actually be what you said; I forget the exact phrase you used)?

The one I remember was a guy who came in with PTSD. Told us a lot about his time in Vietnam, how he saved some people’s lives, how friends died in his arms, etc. Seemed like a nice guy, very sincere.

My attending did a side job at the VA and treated a lot of Vietnam vets, so he knew a lot about military “culture” and how they talked about stuff. He became really suspicious that my patient was never actually in Vietnam, and checked a VA database which confirmed my patient wasn’t a veteran. After a while my patient started telling more and more stories about various heroic things he did in various situations both during and after the war, and we realized he was just narcissistic and a compulsive liar.

goodnightmoonvale

Anonymous asked:

Could polyamory be harmful for naturally monogamous people? Are there any psychological risks associated with reducing jealousy and attachment in people who seem hardwired for strong jealousy, romanticism and attachment?

If by “harmful” you mean “it will make them really upset”, and by “naturally monogamous people” you mean “people who get really upset by polyamory”, well, there’s your answer.

I’m not sure how else to define those terms so I’m not really sure what you mean.

Anonymous

Anonymous asked:

If prestigiousness of residency doesn't affect the kind of job you're likely to get, what does?

I’m a little confused by this myself. It’s not that all psychiatrist jobs literally pay the same salary. But the salary differences are based on things like “Do you have to live in an unpopular area?” or “How much work do you have to do?” rather than better psychiatrists being paid more.

If you want to do academic research, then you might want to have completed a prestigious residency. But even there I’m not sure that’s true. A couple of people from my (non-prestigious) residency have gotten fellowships at Ivy League colleges, mostly just by asking for them - there’s not always a lot of competition for fellowships in certain areas.

I think prestigious residencies help for becoming President of the APA or something. They might help a little for being Professor of Psychiatry at Harvard, although it might also be that you just need to get a regular residency, then a good fellowship, then do good research. I don’t think they help for making money, or living in a nicer city, or treating richer vs. poorer people, or anything like that.

I wasn’t going for anything ambitious, so I might be very wrong about this.

Anonymous

Anonymous asked:

How far are we from human wireheading and safe "paradise engineering" through pharmacology, nanotechnology, genetic engineering or finely-tuned neural stimulation?

“Safe” doesn’t seem like the right word for this area. I think the brain surgery is already safe, insofar as brain surgery ever is. But you will never have a life again, and you’ll probably deliberately injure your brain stimulating it too much, which barely matters because you would never use it again.

If you want something better than this, I think the questions tend more towards philosophy and neuroscience, not engineering.

Anonymous

Anonymous asked:

if the time-dependent sensitization hypothesis (Antelman et. al) may be entirely or partially true in case of SSRIs, and we still don't have accurate pharmacogenomic tests to personalize the drug choice, would it make sense to conduct RCTs with patients taking single or few doses of few different SSRIs and then wait a couple of weeks for effects?

Why does this always happen to me? “Hey, I was wondering about the implications of an obscure 1988 psychopharmacology study known only to a few subspecialists, and I happened to be reading your Tumblr, what do you think?”

So, having gone and read Antelman, I think I deflect the question. Antelman’s theory is so different from existing mainstream belief that if it were true, interesting ways of testing stuff would be the *least* of our problems.

My guess is that it isn’t true. Antelman’s experiments all suggest that drugs start exerting their actions immediately, but SSRIs (and tricyclics) take weeks before they kick in. That alone to me discredits a lot of what he says about antidepressants. I know experiments in the 80s were notoriously bad, and he mentions in a footnote that other labs can’t replicate his results.

I haven’t finished the paper yet, and I don’t know anything about this area, but that would be my guess. Also, it’s been thirty years and nobody has done anything he suggested, which makes me think the experts weren’t impressed either.

Anonymous

Anonymous asked:

What kind of improved treatments for various anxiety disorders and somatic symptoms should we expect in the next decade?

Judging by the past decade, a bunch of things that are basically SSRIs+Buspar, and which the pharmaceutical companies will say don’t have sexual side effects and then pretend to be surprised when they inevitably do.

Oh, you were expecting optimism? Sorry, we’re all out of optimism here.

On the other hand, the patent for Lyrica may expire next year, and I think that will get more of a (well-deserved) place in anxiety treatment once it’s affordable.

Anonymous
millievfence

Anonymous asked:

_Nickel and Dimed_ did for me pretty much what you hope books-about-being-poor would do for people at large. It is intellectualized rather than tearjerking, and about voluntary rather than inherited poverty, leaving predictable angles of attack for those concerned with purity, but IMO it is a candidate.

slatestarscratchpad answered:

I read that too and it was really good, and I was thinking about it when I wrote that. Then I made the mistake of looking for commentary about it online, and found various people who tried the same experiment with opposite results, and everyone telling everyone else they were doing it wrong or spinning it dishonestly or whatever.

millievfence:

She was also horribly condescending and refused to listen to actual poor people.

It’s been a long time since I read the book; remind me what you mean?
millievfence Source: slatestarscratchpad