17 U.S. Code § 107 - Limitations on exclusive rights: Fair use
Notwithstanding the provisions of sections 106 and 106A, the fair use of a copyrighted work, including such use by reproduction in copies or phonorecords or by any other means specified by that section, for purposes such as criticism, comment, news reporting, teaching (including multiple copies for classroom use), scholarship, or research, is not an infringement of copyright. In determining whether the use made of a work in any particular case is a fair use the factors to be considered shall include—
(1) the purpose and character of the use, including whether such use is of a commercial nature or is for nonprofit educational purposes [all mirrored content falls under this clause, any ads present are mirrored from the original site, mirrored content earns me no revenue whatsoever];
(2) the nature of the copyrighted work [this is a unique resource for the mentally ill, and preservation of it can be argued to be incredibly important];
(3) the amount and substantiality of the portion used in relation to the copyrighted work as a whole; and
(4) the effect of the use upon the potential market for or value of the copyrighted work. [absolutely none whatsoever, as the original work no longer exists anywhere else (outside of whatever bits and pieces archive.org managed to capture) - the original site was intermittantly completely unavailable for a extended period of time before its SSL certificate expired (and was never renewed), and eventually the site went offline for good, then finally the DNS records were removed at some point prior to May 2018, so at this point it is well beyond the 'dead and rotting' stage]
The fact that a work is unpublished shall not itself bar a finding of fair use if such finding is made upon consideration of all the above factors.

This domain is not controlled by Jerod Poore, and I will NOT continue redirecting traffic from this domain to crazymeds.us [as I formerly did] while Jerod continues with his immature temper tantrum over adblock or continues to fail to maintain his site, fucking over his entire community and countless visitors in the process. [belated clarification: with specific regards to the adblock drama I was referring to Poore at one point replacing his entire site with a single page complaining about the amount of revenue lost to users with ad blocking active, which is something that I took extreme exception to because this affected ALL visitors to the site regardless of if or if not they were actually using ad blocking]
This mirror is unfortunately incomplete (and very slightly outdated), as /CrazyTalk/ was not included when I scraped the site (it was far too large to scrape given the site's extremely poor performance, my wish to avoid worsening the poor performance further, and other factors). If you're looking for a replacement forum, I suggest visiting https://www.crazyboards.org/forums/. There are issues with many of the mirrored pages, I am working on identifying and fixing them, but I do not have the time to address every single issue at this moment (although by now the majority of these issues have been resolved). Dynamic content is obviously completely broken (this is beyond my control), and the loss of /CrazyTalk/ is quite bad given how much good user-generated info was on there, but you have Jerod to "thank" for that. Maybe I'll bring it back online at some point, but it wouldn't be the same as before. For now, I suggest visiting CrazyBoards instead.
Note (Oct 9 2018): Infrequent additional updates regarding the status of this site will be posted on https://info.crazymeds.net

common mechanisms of action / pharmacodynamics

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Common and not-so common uses of Antidepressants | AD Topic Index | Antidepressant Dosage Equivalents

1.  It’s All About Chemistry, Baby. Maybe.

As with all crazy meds, if you look at the Clinical Pharmacology section of the PI sheet of any antidepressant (AD) you’ll see something along the lines of “The mechanism of action of Fixitol (panacea HCl) in humans is unknown, but is believed to be associated with its potentiation of neurotransmitter activity in the CNS.” In English: “We don’t know exactly how it works, but we think it has to do with making your brain juices work better.” This is better known as the Chemical Imbalance Theory of mental illness, which is incredibly easy to understand: you have too much or too little of something somewhere in your body. While the traditional chemical imbalance theory is based on neurotransmitters, especially, but not limited to, serotonin, norepinephrine, and dopamine, if you broaden it to include hormones, enzymes, and whatever else is produced by genetic expression triggered or suppressed by the meds in your brain, liver, and just about anywhere else the receptors affected by the drugs exist, it simplifies things greatly.

Unfortunately, most researchers don’t like the Chemical Imbalance Theory. They have all sorts of evidence to back them up.

There is a much easier, and probably more accurate explanation for psychiatric and neurological problems: The Communications Interference Hypothesis.

2.  Communications Breakdown

Your brain is the hub of the vast communications network that controls everything from abstract thought to keeping your heart beating. This network uses a combination of electrical and chemical signals to transmit messages to, from, and within your brain. The Communications Interference Hypothesis is: All psychiatric, neurological, and assorted other conditions treated with crazy meds are manifestations of disruptions in the network. It doesn’t care why there are disruptions. Not enough serotonin? Dopamine receptors that barely function? Too few neurons in your hippocampus?

Let the people with impressive strings of letters after their names figure out the actual sources of the problems and develop better tools to fix them. All that matters is the tools we now have to correct the problem primarily work with the chemical signalling part of the network. If you have too few or marginally-functional serotonin receptors, raising the amount of serotonin they get is the functional equivalent of correcting how many receptors you have or how sensitive they should be, isn’t it? So if you have a screw loose you need a screwdriver, right? But if you don’t have a screwdriver or a dime, then a pair of pliers is better than a hammer or leaving the damn thing alone until the entire machine falls to pieces.

For a more detailed look at pharmacodynamics in general and the Communications Interference Hypothesis, see the page on Pharmacodynamics Basics.

3.  Methods to undo Madness

With a few exceptions every AD on the planet does the same thing: it enhances the effects of one or more neurotransmitters, thus strengthens the signal in the communications network. It does so in one or more of the following ways:

  • As a reuptake inhibitor, to increase the time, and often the amount of brain juice that stays on a neuron.
  • As an antagonist. To decrease excess neurotransmitters at “bad” neurons and focus them at “good” neurons.
  • As an agonist. To fine tune the sensitivity of a neurotransmitter receptor.

The biggest exception is Stablon (tianeptine), a reuptake enhancer, which speeds up the process of a neuron absorbing serotonin.

3.1  Quick on the Reuptake

All but a few antidepressants do some form of reuptake inhibition. Serotonin-Selective Reuptake Inhibitors (SSRIs), Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs), Norepinephrine-Selective Reuptake Inhibitors (NSRIs), Tricyclic Antidepressants, Serotonin Antagonist and Reuptake Inhibitors (SARIs - AKA trazodone and nefazodone), Wellbutrin (bupropion), Viibryd(vilazodone), along with some meds under development and some more available outside of the US all have some form of reuptake inhibition as part of their mechanism of action.

Reuptake inhibitors prevent a neurotransmitter from being absorbed further into the neuron, broken down and recycled. This allows your synapses to marinade in whatever the target brain juice is for a longer period of time, as well as increases the amount since the method of transporting the neurotransmitter is being slowed down. This enhances the transmission of the signal through the CNS’ communications network.

Monoamine oxidase inhibitors (MAOIs) create an effect similar to reuptake inhibitors, in that they slow down not the transportation mechanism, but the chemical that breaks down the neurotransmitter. This causes a build-up in all monoamine neurotransmitters, not just the ones listed below (except GABA, glutamate, and CRF, which aren’t monoamine neurotransmitters) to varying degrees, both within and on the surface of a neuron. In an oversimplified way (this is an overview after all), MAOIs have end results that are similar to reuptake inhibitors, with the most popular ones on the market acting like high-potency SNRIs.

An antagonist attaches itself (binds) to the receiving neuron’s receptors that soaks up the brain juice involved and reduces transmission of the neurotransmitter and decreases the strength, or volume, of the signal. How well it does so is called its affinity.

What an agonist does is on spectrum of functions1. As far as most crazy meds are concerned it’s just like the name implies, the opposite of an antagonist. It binds to a neuron’s receptor and enhances, or otherwise fine-tunes reception of the signal.

4.  Know Your Neurotransmitters

There are dozens of known neurotransmitters, perhaps hundred yet to be discovered, but the brain juices most crazy meds are thought to do the most work on are:

  • Dopamine (DA)
  • Serotonin (5HT)
  • Norepinephrine/Noradrenaline (NE)
  • Acetylcholine (ACh)
  • Glutamate (Glu)
  • Histamine (H)
  • Gamma-aminobutyric acid (GABA)
  • Corticotropin-releasing factor/hormone (CRF)
  • Melatonin (MT)

As far as antidepressants (ADs) are concerned the first three is where most of the action is. Acetylcholine (ACh) and melatonin (MT) are the targets of some new ADs. CRF has being recently studied as something responsible for why medications of many different classes work and, unfortunately, make you fat as well.

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4.1  Dopamine: Everybody’s Favorite Brain Juice

Dopamine, sweet, sweet, dopamine. While it is best known as the reward & pleasure neurotransmitter, the pleasure title really belongs to others, like the endorphins and oxytocin2. In addition to making us feel good about ourselves, dopamine also makes us feel energetic and helps us to think imaginatively. Anyone who has experienced, or has been around someone experiencing bipolar mania or the positive symptoms of schizophrenia can recognize how too much dopamine can explain things like over-inflated self-worth, not needing to sleep, and delusional behavior to the point of hallucinating.

To my knowledge five different dopamine receptors have been identified (D1 through D5). It’s an overabundance of dopamine, mostly at the D2 and D3 receptors, and particularly in the mesolimbic and mesocortical pathways3, that is suspected to be the likely culprit for many of the positive symptoms of schizophrenia and bipolar mania. The D1 and D4 receptors are involved as well, but as few meds work on those they are less studied. Other sections of the brain, as well as the liver, pancreas, and maybe other organs, use dopamine, and too little dopamine, whether naturally or as a result of taking APs, results in things like Parkinson’s (or the Parkinson’s-like movement disorders caused by APs) and unwanted enlargement of breasts.

4.2  Serotonin: The Answer to Everything

Serotonin, or 5-hydroxytryptamine (5HT)4, carries the signals for so many things in your brain, your gut, your cardiovascular system and elsewhere that it actually makes sense why drugs that affect it have contradictory side effects like constipation and diarrhea, insomnia and excessive drowsiness, or that serotonergic drugs like SSRIs can make depression worse. There are at least 20 5HT receptors in the human brain dealing with practically everything: anxiety, addictive behavior, appetite, cognition, hallucinations, impulsiveness, memory & learning, mood, nausea & vomiting, sleep, sociability, sexuality, and thermoregulation. To further complicate matters, serotonin regulates dopamine, which is one reason why too much serotonin can make you depressed.

4.3  Norepinephrine: I Can’t Decide

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4.4  Histamine: Heavy-Duty Sleep

4.5  Melatonin: Night-Night

This hormone you can buy OTC is used not only for sleep but also as an antidepressant.

4.6  Too Much is Never Enough

5.  Express Yourself

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Common and not-so common uses of Antidepressants | AD Topic Index | Antidepressant Dosage Equivalents

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6.  Bibliography

Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications (Essential Psychopharmacology Series) Third edition by Stephen M. Stahl © 2008 Published by Cambridge University Press.
Primer of Drug Action 12th edition by Robert M. Julien Ph.D., Claire D. Advokat, Joseph Comaty © 2011 Published by Worth Publishers.
Serotonin Receptors – From Molecular Biology to Clinical Applications M. PYTLIAK, V. VARGOVÁ, V. MECHÍROVÁ, M. FELŠÖCI PHYSIOLOGICAL RESEARCH 60: 15–25, 2011
”Serotonin Receptors” David E. Nichols and Charles D. Nichols Chemical Reviews, 2008, Vol. 108, 1614–1641 dx.doi.org/10.1021/cr078224o
”Overview on 5-HT receptors and their role in physiology and pathology of the central nervous system” Małgorzata Filip, Michael Bader Pharmacological Reports, 2009, Vol. 61, 761–777
1 Technically an antagonist is on the agonist spectrum, in the same slot as malfunctioning receptor, between partial agonist and inverse agonist.

2 You can also get both from sex and opioids, although the quantity and quality of those neurotransmitters from either source, especially the oxytocin, varies greatly from person to person. Which explains a shitload of things. In other people's lives as well I imagine.

3 Be honest with yourself, if I spelled out the exact neuroanatomical structures involved, would you know what the hell I was talking about? If you do, you can look it up. If you don't, just accept that people with an impressive array of letters after their names think the action is in specific, long-ass-named parts of the brain.

4 Yup, the same stuff you can buy in a vitamin store. And it will go to your brain. And it may be enough to fix what you have. Assuming what you buy is what the label claims to be. And you need more everywhere and not less in specific places.

How Antidepressants (ADs) Work by Jerod Poore is copyright © 2014 Jerod Poore

Last modified on Saturday, 13 June, 2015 at 19:29:05 by JerodPoorePage Author: Jerod PooreDate created: 11 March 2014

All drug names are the trademarks of someone else. Look on the appropriate PI sheets or ask Google who the owners are. The way pharmaceutical companies buy each other and swap products like Monopoly™ real estate, the ownership of any trademarks may have changed without my noticing.

Page design and explanatory material by Jerod Poore, copyright © 2003 - 2015. All rights reserved.
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Almost all of the material on this site is by Jerod Poore and is copyright © 2003, 2004, 2005, 2006, 2007, 2008, 2009, 2010, 2011, 2012, 2013, 2014, and 2015 Jerod Poore. Except, of course, the PI sheets - those are the property of the drug companies who developed the drugs the sheets are about - and any documents that are written by other people which may be posted to this site will remain the property of the original authors. You cannot reproduce this page or any other material on this site outside of the boundaries of fair use copying without the express permission of the copyright holder. That’s usually me, so just ask first. That means if want to print out a few pages to take to your doctor, therapist, counselor, support group, non-understanding family members or something like that - then that’s OK to just do. Go for it! Please. As long as you include this copyright notice and something along the lines of following disclaimer, I’m usually cool with it.

All rights reserved. No warranty is expressed or implied in this information. Consult one or more doctors and/or pharmacists before taking, or changing how you take any neurological and/or psychiatric medication. Your mileage may vary. What happened to us won’t necessarily happen to you. If you still have questions about a medication or condition that were not answered on any of the pages you read, please ask them on Crazy Talk: the Crazymeds Forum.
The information on Crazymeds pertains to and is intended for adults. While some information about children and adolescents is occasionally presented (e.g. US FDA approvals), pediatric-specific data such as dosages, side effects, off-label applications, etc. are rarely included in the articles on drugs or discussed on the forum. If you are looking for information regarding meds for children you’ll have to go somewhere else. Plus we are big pottymouths and talk about S-E-X a lot.
Know your sources!
Nobody on this site is a doctor, a therapist, or a pharmacist. We don’t portray them either here or on TV. Only doctors can diagnose and treat an illness. While it’s not as bad as it used to be, some doctors still get pissed off by patients who know too much about medications, so tread lightly when and where appropriate. Diagnosing yourself from a website is like defending yourself in court, you suddenly have a fool for a doctor. Don’t be a cyberchondriac, thinking you have every disease you see a website about, or that you’ll get every side effect from every medication1. Self-prescribing is as dangerous as buying meds from fraudulent online pharmacies that promise you medications without prescriptions.
All information on this site has been obtained from the medications’ product information / summary of product characteristic (PI/SPC) sheets and/or medication guides - which is all you get from sites like WebMD, RxList, NAMBLA NAMI, etc., the sources that are referenced throughout the site, our personal experience and the experiences family, friends, and what people have reported on various reputable sites all over teh intergoogles. As such the information presented here is not intended as a substitute for real medical advice from your real doctor, just a compliment to it. You should never, ever, replace what a real doctor tells you with something from a website on the Internet. The farthest you should ever take it is getting a second opinion from another real doctor. Educate yourself - always read the PI/SPC sheet or medication guide/patient information leaflet (PIL) that comes with your medications and never ever throw them away. OK, you can throw away duplicate copies, but keep at least one, as that’s your proof of purchase of having taken a med in case a doctor doubts your medical history. Plus they take up less space than a bottle, although keeping one inside of a pill bottle is even better.
Crazymeds is not responsible for the content of sites we provide links to. We like them, or they’re paid advertisements, or they’re something else we think you should read to help you make an informed decision about a particular med. Sometimes they’re more than one of those things. But what’s on those sites is their business, not ours.
Very little information about visitors to this site is collected or saved. From time to time I look at search terms used and which pages they bring up in an effort to make the information I present more relevant. And the country of origin, just because I’m geeky like that. That’s about it. Depending on how you feel about Schrodinger, our privacy policy should either assuage or exacerbate your paranoia.
Crazymeds is optimized for ridiculously large screens and browsers that don’t block ads. I use Firefox and Chrome, running under Windows 72. On a computer that sits on top of my desk. With a 23 inch monitor. Hey, at least you can make the text larger or smaller by clicking on the + or - buttons in the upper right hand corner. If you have Java enabled. Like 99% of the websites on the planet, Crazymeds is hosted on domain running an open source operating system with a variety of open source applications, including the software used to display what you’ve been reading. As such Crazymeds is not responsible for whatever weird shit your browser does or does not do when you read this site3.
No neurologists, psychiatrists, therapists or pharmacists were harmed in the production of this website. Use only as directed. Void where prohibited. Contains nuts. Certain restrictions may apply. All data are subject to availability. Not available on all mobile devices, in the 12 Galaxies Guiltied to a Zegnatronic Rocket Society, or in all dimensions of reality. Hail Xenu!

‘Everything is true, nothing is permitted.’ - Jerod Poore

1 While there are plenty of books to help you with hypochondria, for some reason there’s not much in the way of websites. Then again, staying off of the Internet is a large part of curing/managing the disorder.

2 Remember kids, Microsloth operating systems are like TOS Star Trek movies with in that every other one sucks way, way more. With TOS Star Trek movies you don’t want to bother watching the odd-numbered ones. With Microsloth OS you don’t want to buy and install the even-numbered ones. Anyone who remembers ME and Vista knows what I mean.

3 Have I mentioned how open source operating systems for commercial applications is one of the dumbest ideas in the history of dumb ideas?* I don’t even need my big-ass rant any more. Heartbleed has made my case for me. And that’s just the one that got all the media attention. The very nature of an open source operating system makes security as much of an illusion as anonymity on teh Intergoogles. Before you flip out too much: the domain Crazymeds is hosted on uses a version of SSL that is not affected by the Heartbleed bug. That’s one of the many reasons why I pay a lot of money and keep this site on Lunarpages.

* Yes, I know I’m using open source browsers. I also test the site using the now-defunct IE and Safari browsers. Their popularity - and superiority - killed IE and Safari, so that’s why I rely on the open source browsers. It’s like brand vs. generic meds. Sometimes the generic is better than the brand.

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