• N&PD Moderators: Skorpio | thegreenhand

BEST Websites to Self-Educate Psycho-Pharmacology??

Proxies?

Pfff - just google free-proxy-list.

Follow this tutorial...



Again, given you ISP is blocking the site, not 100% it will work but, worth a try.
 
A few things.

I mean, there really is no "right" direction...

Psychiatry does a horrible job of explaining the relation of drugs to emotion and perception. It fits together on the surface (mostly), and seems pretty cogent, but dig a little deeper and there are a litany of contradictions.

Psychiatry can't really be understood except as an offshoot to neural correlates of behavior, which can't be all that well understood without more general neuroscientific knowledge. In fact, it's kind of a hazard. All kinds of absurd generalizations are made.

If you really want to know, take a class. Nothing will teach you better. A basic neuroscience class would give a lot of insight.

Wikipedia has actually gotten a lot better over the past few years. It's a decent resource imo.

An irony here is that clinical trials must be conducted so extensively and comprehensively because we don't have near enough scientific knowledge to approve a drug for human use based on its structure.

I'd question why you really want to know how this stuff works.
 
Pretty sure Sthal's 3rd/4th edition of essential psychopharmacology is available online to dowload in pdf form for free

Not that shit again, that book is way to simplified and generalised, eg 5ht2a blockade is good for anxiety, depression and causes da release and shit like that ppl spread online everywhere, its way more complicated then that.
 
Not that shit again, that book is way to simplified and generalised, eg 5ht2a blockade is good for anxiety, depression and causes da release and shit like that ppl spread online everywhere, its way more complicated then that.

Alright what's a good book then?

I'd like to get good insight into the factors affecting the potency of each drug, in addition to taking their binding profiles into consideration.
 
Amazon can be pretty good if you get lucky.

I got myself a copy of Kren&Kvac's 'the genus Claviceps for a bit less than $40, whilst I've seen it go secondhand for as much as £200 (GBP), although I'd not pay anything like that for a hardcopy. Perfect to take it places I can't take the computer, such as public transport, and of course, the lab (I've seen what the atmosphere in there at times has done to blocks of steel and iron, and whilst better ventilation is now sorted, have seen jam jar lids affected to the point where they were held together by the rims and the paint, disintegrating into chunky dust when touched with a fingertip, no WAY am I exposing the air intakes and circuitry of this computer to whats floating around in there before exiting the ventilation. Doubt they'd much appreciate sucking on a mixture of NOx, SOx, HCl, ammonia, chromyl chloride, sulfur, alkyl/acyl and phosphorus halides, acid anhydrides and iodine, amongst other...stuff.

In times past, leave an iron bar in there a week (clamp stand) the screws started to get corroded to the point where I had to switch to brass fittings, and give the steel rods a regular acid stripping, and both drill/tap some new boss heads and turn/knurl some all-brass screws to fit them. These, at least, have survived much better. Had to buy a new gas mask too. Not the filters, but a new actual mask because the rubber perished and disintegrated.

I thank any supernatural entities watching over that lab, to this day that I managed to get the $300 or so microscope evacuated before anything happened to it but a little bit of external corrosion on the sides of the stage, turning it green. Nickel or chromium or copper traces I presume. No harm done however, not that a bit of acid, lovingly applied and removed wouldn't get rid of. Thank FUCK, because I am not made of money, even if what I do have gets spent more on the lab than on the stomach.
 
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Change VPN, get access to library genesis.


Working my way through "essential pharmacology" by Stahl, and "molecular neuroscience" by some other author.

Covering only neurotransmission mechanics, and the chapters on anti-depressants.

Say I had all that material covered, speaking solely regarding knowledge on AD's, not mood stabilizers etc - how would that knowledge base compare to that of say, a consultant psychiatrist??
 
Well a psychiatrist is after all an MD, and they probably cover a much wider breadth of subjects, not just depression but normal physiology and normal hippocampal function and such. But I imagine their knowledge varies widely. There are good doctors and bad doctors.
 
So on the basis of them two books - I don't know are they considered "beginner" books, starter type books.

But on the strength of them, I could potentially have a greater berth of information, certainly than my GP, and possible than my consultant?

I ask because, I have very disenchanted with the quality of care they have provided so far, and the only reason I'm in as good a place as I am now (which still requires much improvement, even to get to the point of being able to hold down a part time job), is because of my own experimentation with various meds, and personal research as to what could be effective.
That information gives me confidence that I can achieve remission.... some day. How great would that be?

But at the hands of the doctors I'm attending, if I were to rely solely on their opinion - well - things would be grim.

That's why I'm curious to compare the knowledge base I could attain myself, to their knowledge base - but specifically regarding depression.

My consultant did a masters in neuroscience - but again, I'm sure much of that entailed focusing on aspects outside of the depression spectrum.
 
A masters in neuroscience is good.

I think the important thing is up to date knowledge. It's okay if you got your degree 2-3 decades ago as long as you stay current and are genuinely interested but it seems like most doctors don't actually learn anything new after they get out of med school, even though there is continuing education type stuff I have heard a doctor friend speak of. But he said it was basically requiring him to relearn a bunch of old useless stuff instead of learning new useful stuff, he thought it was very stupid. He would learn so much more useful information if he just hopped on to PubMed and read some newer review articles for a few hours for a few days.

But psychiatry in particular is such a complex arena that I think current knowledge is important. What I'm trying to say is that even if your knowledge is much narrower in scope than a regular psychiatrists you still might have more useful and actionable knowledge about MDD if you have more recent information. They can have tons of knowledge but if it's outdated then that's no good. But psychology/psychiatry are big on diagnosing a condition based on Xyz criteria and then doing studies using different treatments with people diagnosed with that same condition and no other conditions (very controlled). The key point is that accurate diagnosis is important. I.e if someone thinks they have MDD and treats themselves as just having MDD it might be inaccurate to apply oneself to studies using MDD if you have ASD + MDD. The things that work for MDD may not work for ASD + MDD and vice versa, so accurate objective diagnosis (which is hard to do subjectively by oneself, and of course I think other medical professionals are probably fairly bad at it as well sometimes) is important. That's one of those things that psychiatrists will always have a leg up on us with - they're able to see things from a different point of view than what we see. MDD is often co-morbid so that's something to think about. But like I said there are good doctors and bad doctors. I'm sure there are plenty of psychiatrists and psychologists that are somewhere on the spectrum themselves and don't really know it.

But anyways, one important thing to examine is efficacy at X amount of time follow up. Being able to achieve X amount of reductions on a depression inventory score at 1 month is great but let's not be too short sighted. I'm sure many compounds could be used to that 1 month effect, but reversing hippocampal atrophy etc. and eventually at some point being able to taper off the drug and be in full remission unmedicated is the ultimate goal. I haven't examined the matter but my gut opinion is that dopaminergic drugs may not be the best at producing long term remission. Correcting the inflammation issues associated with MDD is a great therapeutic target for long term remission on the other hand, and fixing abnormal neuroplasticity with medications and CBT/mindfulness is important as well. But depending on the specific depression physiology, efficacy for different treatments is going to vary.
 
Well I suppose in terms of that diagnostic criteria - the doctors of medicine and PhD's that i've attending, have come up with such a broad range of diagnosis and, in my opinion - none of them truly correct.

This has hampered my treatment.

The main issue I aim to tackle is cognitive and executive dysfunction.
I know at it's lowest, this arises in tandem with very low mood, distress etc.
But that apart, a depressed "presentation", is certainty not a part of my condition.
That also being said, depressive symptomatology such as insomnia, gastric upset, reduced appetite, poor concentration, low energy etc - are all very much present.

So making a well defined diagnosis of MDD seems difficult.

There have been all sorts of co-morbid conditions speculated upon, such as ASD, schizoid PD, delusional disorder, OCD etc - but in my opinion, these are/were all just products of the severity of the MDD - social withdrawal, self induced delusions to incite an adrenal response and circumvent energy issues, albeit to a very minimal degree.

If my functionality in every capacity were to be restored, there would not be an issue.
There would not be complaints - period.


For this reason - I tend to overlook the doctors and consultants speculations as to my condition, and their proposed courses of treatment.
I'm not fully acquainted with neuroplasticity etc - but I am certain that talk therapies, including CBT, are entirely ineffective (for me).

I have concluded personally that this is purely an clinical/endogenous issue - of an a-typical nature, due to it's irresponsiveness to serotonergics.
Yet positive response to noradrenergics.

I personally think examination of executive function would be a much better condition indicator that psychiatric diagnosis, as far as my own situation is concerned.
But have not been presented with anything in the way of neurocognitive examinations/tests etc.


Anyways - the overall point being, my (well founded) contention that the medical focus should be purely focused on symptom relief, restoration of functionality - irrespective of diagnosis.
And the fact that, thus far, having been treated with anti-psychotics and serotonergics, I have proven responsive solely to noradrenaline implicators.

Therefore - focusing purely on treatment using anti-depressants - my query would be, given the study of two such aforementioned books, as well as review of clinical trial/pubmed data - should I theoretically establish a significant enough knowledge base to rival that of my consultant (again, with the focus being PURELY on MDD treatment - with the aforementioned outlines factors specific to my own case)?
 
The whole idea behind neuroplasticity is essentially that neurons that fire together wire together and "use or lose it". It's the idea that the brain is constantly making and trimming connections through processes like long term potentiation (LTP) and long term depression (LTD). Altered neuroplasticity is associated with MDD.

I personally think the people that are neurally capable of inciting positive emotions/inciting energy with their cognition (maladaptive day dreaming essentially) have something going on before they ever start using their cognition in that manner. Simply put, they might have an overactive and ruminating type mind.

Has bipolar type II been discussed? Any signs of slight hypomania in previous years? The sodium channel antagonists like lamotrigine have been used with success in bipolar depression.

Anyways, I suspect that the same neuroplasticity/neurophysiology that lends itself to being able to induce positive feelings/energy with the mind by imaging artificial scenarios and such is probably a mind that's more vulnerable to depression because of years of activation of the default mode network, and lack of de-activation of the default mode network when one is task positive is heavily associated with cognitive dysfunction. Those mind wandering circuits are supposed to shut off one when is task positive (that is to say that normally the default mode network is engaged when one is task negative) but when it doesn't, cognitive dysfunction ensues. This is where I think mindfulness can really help, which has proven effective for depression, especially ruminating depression.

I think some people won't be helped by typical counseling type therapies unless it helps lead them to a more mindfulness-like mental state. But that's usually not the focus of most psychologists.

But as to your question, I imagine your knowledge would begin to rival that of your consultant if you studied the aforementioned sources carefully, a neuroscience text or two to give you the basics, Wikipedia where you need it, and then PubMed where the wheels hit the pavement (and there are great review articles on there as well). PMC is similar to PubMed but features full articles.

But earlier my point was that getting at the root cause is important and that it's hard to figure out what your root cause is on your own. For example, if one has insomnia all their life and then gets depressed, you wouldn't necessarily tunnel vision on the depression if the depression is a result of the insomnia - you would treat the primary insomnia. If your current state is because of abberrant thought patterns that have been occurring long before you had depression, it would be important to address that. In that scenario, all the knowledge in the world about depression might not be as helpful as someone else who can connect the dots and treat the insomnia and see if the depression begins to resolve.
 
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The whole idea behind neuroplasticity is essentially that neurons that fire together wire together and "use or lose it". It's the idea that the brain is constantly making and trimming connections through processes like long term potentiation (LTP) and long term depression (LTD). Altered neuroplasticity is associated with MDD.

I personally think the people that are neurally capable of inciting positive emotions/inciting energy with their cognition (maladaptive day dreaming essentially) have something going on before they ever start using their cognition in that manner. Simply put, they might have an overactive and ruminating type mind.

Has bipolar type II been discussed? Any signs of slight hypomania in previous years? The sodium channel antagonists like lamotrigine have been used with success in bipolar depression.

Anyways, I suspect that the same neuroplasticity/neurophysiology that lends itself to being able to induce positive feelings/energy with the mind by imaging artificial scenarios and such is probably a mind that's more vulnerable to depression because of years of activation of the default mode network, and lack of de-activation of the default mode network when one is task positive is heavily associated with cognitive dysfunction. Those mind wandering circuits are supposed to shut off one when is task positive (that is to say that normally the default mode network is engaged when one is task negative) but when it doesn't, cognitive dysfunction ensues. This is where I think mindfulness can really help, which has proven effective for depression, especially ruminating depression.

I think some people won't be helped by typical counseling type therapies unless it helps lead them to a more mindfulness-like mental state. But that's usually not the focus of most psychologists.

But as to your question, I imagine your knowledge would begin to rival that of your consultant if you studied the aforementioned sources carefully, a neuroscience text or two to give you the basics, Wikipedia where you need it, and then PubMed where the wheels hit the pavement (and there are great review articles on there as well). PMC is similar to PubMed but features full articles.

But earlier my point was that getting at the root cause is important and that it's hard to figure out what your root cause is on your own. For example, if one has insomnia all their life and then gets depressed, you wouldn't necessarily tunnel vision on the depression if the depression is a result of the insomnia - you would treat the primary insomnia. If your current state is because of abberrant thought patterns that have been occurring long before you had depression, it would be important to address that. In that scenario, all the knowledge in the world about depression might not be as helpful as someone else who can connect the dots and treat the insomnia and see if the depression begins to resolve.

I'm just after seeing that pubmed and pmc are both seemingly run through the site ncbi.gov, with the pubmed articles having only abstracts and, as you said, the pmc articles containing full reviews.

Would ncbi be the main source, through different "subsections", as it were, of academic information in that case?
I've spent a lot of time going through different sites that was ultimately a time sink - so having a reliable base of information would certainly be helpful.


I suppose when I say cognitive impairment - I mean, energy reduced to the point where it's extremely difficult to focus or concentrate.

This can be temporarily circumvented by a kind of, "enthusiastic" response in certain situations, perhaps that "enthusiasm" giving rise to somewhat of an adrenal response which improves concentration in them situations.
Such situations would be - reading information here, reading new articles that pertain to my situation and potential remission.
Thus, I can spend time, or have the concentration to read these responses and write responses, study mechanisms of action - as that's all pertinent to my recovery - something which incites, an "adrenal" response, an enthusiasm.

That level of cognitive function would not be present if I were to be studying, something not relevant to my condition.

By a similar condition - when I meet with my doctor or consultant, a therapist, whatever - that same enthusiasm or "adrenal response" becomes apparent, and I feel gives rise to a hindrance in terms of their ability to evaluate or observe my true level of dysfunction - fatigue, cognitive impairment, executive dysfunction - and thus, their insufficient treatment approach with me - despite my forcefully outlining this phenomenon.

So - self evaluation - not ideal as you said, but in my case, ultimately necessary.

Mania?
I wish. That would allude to an energy surplus - which I could definitely make use of.
No, strictly fatigue

In terms of rumination and your logic regarding how cognitive impairment might arise:
I certainly don't ruminate. Ironically, there's no real "sadness", or grievances at it were.
Aside from when my functionality dips so low, then distress comes about, and social withdrawal - but again, as a result of personal hygiene and presentation suffering due to low energy - not a product of social inability.

The governing point being - it's not cognitive impairment as a result of "mind wandering/day dreaming" etc.
It's just purely, not enough energy to concentrate.
By example - I wouldn't have enough energy to implement a "mindfulness" approach.
My carers over the last 2.5 years have had a very difficult time comprehending this.
How can a guy who doesn't present the least bit depressed - have such extreme depressive symptoms?
And my doctors and consultants, unfortunately for me - fall into the same bracket.
They assess my presentation - not depressed.

They tell me, "force yourself to do things. Engage socially etc".
I'd imagine, somewhat of a similar underlying principle to your own contention regarding modifying neuroplasticity.

But the reality is - the energy - simply isn't there, to do those things..... when I'm not being treated with noradrenergics, that is.

Though the other poster - bandet something - seemed to be onto something regarding "euphoriants" raising executive function.
His contention was, like I had said, "nail on the head".

And that is the problem overall.
Not enough energy, to do anything.

Before noadrenergics - take a five minute walk over to the shop - not possible.

So - I don't know - a very a-typical form of depression, you would imagine.
 
Pfff - how many weeks did I spend sifting through pubmed articles, without the background info.

Now it's all available by simply setting the search filter to PMC, instead of pubmed....
 
Can anyone recommend a book that clarifies in detail this spoken of "downstream" mechanism of action?
The "downstream" effects of AD's, that take places weeks after commencement of initial dosing?
 
Just progressing through Stahls book more, he seems to allude to - if I've gathered this correctly - a signal transduction cascade, the end of which, in terms of long term late gene product effects, being what he would refer to as, the "downstream" effects.

Does that sound right at all?

There also seems to be some information on g-protein binding, coupling with post synaptic receptors, and the resulting cascade thereof - again alluding to what is known as downstream activity...?
 
I gotta say - working more and more through Stahls book - and it's answering so many of my questions.
Fantastic.
I have a lot more to go however, and can only take in so much at a time, especially with my level of cognitive impairment.

But I fuckin' love finally getting answers to my questions, and true insight into the approach to this illness.

Essential Pharmacology - to get a true grasp on this topics, would the studying of many more such books be necessary - or should I have certainly the bones of it from this book alone?

Cause I have a meeting with my consultant in two weeks - and I wish to be unfalteringly clear as to what approach I wish to adopt, so I can't leave any room for error.
 
The signaling cascades important for depression are related to neurotrophins like BDNF and the receptor TrkB (which can signal through mTOR) see for example http://www.nature.com/mp/journal/vaop/ncurrent/full/mp2016145a.html

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4012208/ - BDNF signaling dysfunction is implicated in MDD.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4360225/ - here is a great study. You'll notice this study is examining the morphological component of depression. How the signaling cascades relate to cellular morphology is important - it's not just about how a neurotransmitter might alter neurotransmission in the short run.
 
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