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[P]
The Geek's Guide to Practical Brain Chemistry

By MK77 in Culture
Tue Feb 12, 2002 at 02:14:04 PM EST
Tags: Science (all tags)
Science

Billions of neurons work together to make your brain function. Chemicals known as neurotransmitters allow your neurons to communicate with each other. This complex system is an evolutionary wonder, but when something goes wrong in the land of neurotransmitters, serious mental illness can be the result. In the article below, we'll take a look at a few important neurotransmitters, how they can determine your mental health, how drugs -- both legal and illegal -- affect neurotransmitters, and which medications are available in the case of neurotransmitter pathology.


Neurons and Neurotransmitters

Your brain is a big bag of neuron cells -- nothing more, nothing less. Just as it isn't the electrons themselves, but rather their pattern of arrangement in your system's RAM which stores information in your computer, it isn't the neurons themselves which store information in your brain, but rather the connections between them which make you who you are. Each neuron has some number of dendrites, which are small appendages for receiving signals from other neurons, and some number of axons, which are longer appendages for sending signals to other neurons. You may already know that neurons aren't really physically touching each other. In fact, there is a small gap between the axon of a neuron sending a signal and the dendrite of a neuron receiving a signal. This small gap is the synapse. You've probably heard people talk about it before.

So, if the axon and the dendrite don't actually touch each other, how do they communicate across the synapse? Neurotransmitters. Each neuron has a small store of neurotransmitters which it can use for communication with other cells. Normally, When a neuron fires, it will release a neurotransmitter through its axons, the dendrites on the other side of the synapse will react to the presence of the neurotransmitter, and the message will have been delivered. After the message has been delivered, the neuron sending the message will reabsorb the neurotransmitter it originally emitted so that you don't have that chemical floating around in your brain, activating neurons it didn't intend to activate. The process of reabsorption of the neurotransmitter is known as reuptake. Reuptake is like garbage collection for your brain!

A Few Good Neurotransmitters

Most of what we know about neurotransmitters has been developed through observation about the amount of a particular neurotransmitter in the brain of a person or other animal and the condition of that person or animal. For instance, a high level of the neurotransmitter serotonin has been linked to positive moods, whereas a low level of the serotonin has been linked to depression and suicidal or agressive behavior. An increase of serotonin can make a person sleepy, where a decrease in serotonin can contribute to obsessive compulsive behavior.

How does serotonin get to your brain? Well, right now you have the amino acid called tryptophan in your bloodstream. Tryptophan competes with other amino acids in your bloodstream to enter your brain cells. When you eat a diet high in carbohydrates, your body naturally produces insulin, and the insulin clears amino acids other than tryptophan from your bloodstream, but doesn't interfere with the tryptophan, and the end result is that more tryptophan enters your brain cells where it is converted to 5-HTP (5-hydroxytryptophan) and finally to serotonin, which is sometimes called 5-HT in nutritional literature. If you've ever experienced a mood elevation from eating sweets, breads or pasta, it's probably because you've indirectly elevated your serotonin levels!

Dopamine is the critical neurotransmitter which regulates feelings of pleasure and pain. High dopamine levels are responsible for people with extremely active sex drives, and low dopamine levels cause sexual indifference. Dopamine also appears to be critical for smooth body movements, as Parkinson's disease is caused by a dopamine deficiency. Dopamine is also necessary for memory and reason, as individuals with low dopamine levels have trouble clearly remembering events and following a logical train of thought. A diet high in Vitamins E and C seems to increase the amount of dopamine in the brain, where Vitamin B6 and high protein diets seem to decrease the amount of the tyrosine amino acid entering the brain, and therefore reduce dopamine levels.

Norepinepherine, also called noradrenaline, is the neurotransmitter associated with alertness and orienting functions. Norepinepherine is actually produced from dopamine. Low norepinepherine levels have been linked with anxiety, lack of focus and fatigue. High norepinepherine levels are associated with the body's natural "fight or flight" reflex in stressful situations. The higher levels of norepinepherine seem to aid mental focus and increased muscle performance. The dietary strategies for increasing or decreasing norepinepherine seem to be similar to those helping in the control of dopamine, as the production of both neurotransmitters are closely linked.

An imbalance of neurotransmitters can cause a variety of unfortunate mental states. Decreased serotonin, particularly in combination with decreased dopamine, is a major cause of depression. People with schizophrenia have high levels of both serotonin and dopamine, though there is some question whether elevated amounts of both neurotransmitters is sufficient to induce schizophrenia or whether it is merely a symptom of schizophrenia itself. Finally, dopamine is the key in addiction. Any drug or process with affects dopamine levels to a significant degree, particularly those which increase dopamine levels, are likely to be addictive. From one point of view, there isn't much difference between the sex addict and the crack addict -- both are looking to boost the level of dopamine in their brains.

Neurotransmitters and Your Lifestyle

There is a strong feedback loop between the neurotransmitters in your brain, which affect the choices you make and the lifestyle choices you make affect the neurotransmitters in your brain. For instance, we see that alcohol not only causes an increase in dopamine, but also causes a burst in the serotonin released by your neurons. This serotonin burst accounts for the euphoric alcohol "buzz". However, once the buzz fades, your serotonin levels are lower than they were when you started drinking, leading you to drink again and again, forever seeking the heightened serotonin levels of that first drink. There are a few conflicting theories on the relationship between serotonin and alcoholism. Chronically low serotonin levels creates the chronic drinker who needs a drink every day to maintain a positive mood, but some people appear to not release serotonin at all when drinking, and this tends to create the binge drinker who doesn't know when to stop drinking because he can never get quite enough.

Caffeine, unlike alchohol, seems to lower serotonin levels somewhat, while at the same time significantly boosting dopamine. Furthermore, caffeine will decrease your appetite for carbohydrates, further cutting off your brain's source of serotonin. If your serotonin levels are already quite low, caffeine will only make your situation worse! Feeling down on days where you've had a few cups of coffee? You probably have less serotonin than you feel comfortable with.

Nicotine, as found in cigarettes, stimulates the release of all three neurotransmitters introduced above: serotonin, dopamine and norepinepherine. It's particularly interesting to note that the increase of serotonin associated with nicotine is the cause of smoker's decreased appetite, and the decreased serotonin levels encoutered during nicotine withdrawal is the cause of increased appetite amoung smokers who have recently quit smoking.

Marijuana, the mostly commonly used illegal drug in the United States, is just as effective as alcohol at causing a burst of serotonin to be released to your brain, and this serotonin burst followed by serotonin deficiency is the reason many depressed persons are attracted to marijuana and also the reason why marijuana can increase the severity of depression. Interestingly, marijuana seems to have no significant effect on dopamine levels, and this is the reason why many classify marijuana as a non-addictive substance.

Cocaine is an interesting drug, biochemically speaking. Not only does it cause a burst of serotonin and dopamine, it also blocks dopamine reuptake! As we discussed above, reuptake is the process responsible for cleaning out unwanted neurotransmitters from your brain and dopamine is the neurotransmitter active in the addictive process, so those of you who have never tried cocaine can imagine just how addictive a cocaine high could be. Cocaine is not a drug to be taken lightly.

One can think of Ecstacy as the anti-cocaine. Where ecstacy doesn't seem to affect dopamine levels much, it is the most effective narcotic for releasing serotonin. Ecstacy actually enters your serotonin containing neurons through the reuptake process and causes those neurons to release all of their serotonin at once. The intense euphoria of ecstacy is caused by the entire serotonin contents of your brain floating around, all activating your serotonin-sensitive dendrites at the same time. The down side of the ecstacy high is that you've depleted all of your serotonin in one burst, and you can experience depression due to decreased serotonin for as long as a week after the high. This is why ecstacy is particularly dangerous for those depressive individuals with naturally low serotonin levels. Because of the intense activity experienced by serotonin-containing brain cells under the influence of ecstacy, the functioning of these neurons may be permanently damaged.

In our love lives, dopamine will drive us to attraction, but a lasting relationship will tend to increase our serotonin levels. Interestingly, it seems that a series of short term relationships can decrease serotonin levels, but increase norepinepherine. You never know, the people you are attracted to might just be affecting your brain chemistry! Prayer and mediation will increase your serotonin levels. This is particularly interesting, because it actually shows a reasonable scientific basis for the healing power of prayer. This is related to the observation that patterns of positive thinking will cause a release of serotonin, where patterns of negative thinking will cause a release of dopamine.

Anti-Depressant Medications

Now that we've introduced a few neurotransmitters and their relationship with lifestyle, the question remains, what is a person to do if his or her neurotransmitters are out of balance? Well, by far, the biggest business of neurotransmitter adjustment -- aside from recreational drug use -- seems to be the treatment of depression.

Prozac and other SSRIs (Selective Serotonin Reuptake Inhibitors) are the biggest news in depression treatment in the last ten years. As you might guess from the SSRI descriptor, these drugs block the reuptake of serotonin, just as cocaine blocks the reuptake of dopamine, such that a patient ends up with free-floating serotonin in their brain, activating serotonin sensitive neurons much more freely than naturally occurs. Some have argued that SSRIs are, well, pathological in that the reuptake process is a necessary part of normal brain function, but others find it a very useful treatment for some forms of depression, particularly in individuals where reuptake happens too soon. (If you'll remember the garbage collection metaphor above, think about using Java with the garbage collector turned off as a fix for a buggy garbage collector which frees objects when there are still references pointing to those objects). In recent news, August of 2001 was the month that the patent on Prozac expired, making way for many cheaper Prozac alternatives which work just as Prozac. One unfortunate side-effect of SSRIs is a decrease in dopamine levels. Patients on anti-depressants who complain of decreased sex drive, problems with memory or fuzzy thinking are often reporting a decrease in dopamine.

MAO inhibitors (Monoamine oxidase inhibitors) are an older treatment for depression, but they work by decreasing the body's MAO, which is responsible for the breakdown of serotonin and norepinepherine. When the MAO decreases, serotonin and norepinepherine activate serotonin or norepinepherine sensitive dendrites for a longer period of time, causing more brain activity in those neurons. Interestingly, MAO is also responsible for the breakdown of dopamine, so a patient on MAO inhibitors can actually experience an increase in dopamine activity coincident with the increase in serotonin and norepinepherine lifetime.

One over-the-counter "herbal" remedy which has recently been gaining in popularity is 5-HTP. When we introduced serotonin above, we mentioned that 5-HTP is the immediate chemical precursor to serotonin. One wouldn't find pills containing serotonin very effective because serotonin itself won't cross the blood/brain barrier, but since 5-HTP will, it can be a useful means of increasing your neurons' stores of serotonin. 5-HTP is legel to sell as an herbal medicine in the United States because it can be extracted from the African Griffonia Simplicifolia plant, but other countries require a perscription or don't have 5-HTP available at all.

On a purely personal note, I've had several severe suicidal depressive episodes in my life, and I'm currently taking one-hundred milligrams of 5-HTP every morning. I've found it to be quite effective in treating my depression.

Awareness is Critical

Hopefully now you have a slightly better understanding of neurotransmitters and how they can affect your life. If you think that you might have a neurotransmitter imbalance, the first step is to try and clearly identify the problem. A visit to the doctor is always a good idea if you suspect something is wrong. Tests can be run, and the problem can be verified.

Understanding what is wrong is the first necessary step toward fixing the problem.

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The Geek's Guide to Practical Brain Chemistry | 78 comments (67 topical, 11 editorial, 0 hidden)
5-HTP and tryptophan (3.71 / 7) (#4)
by jabber on Tue Feb 12, 2002 at 12:41:53 PM EST

5-HTP is legal because it can be extracted from a plant? So can cocaine and heroin.. There must me more to legality than ease of derivation. Why else is something that is a potential 'mood-lifter' so easily available? Seems 'unamerican' in today's drugs == terrorists context.

As for tryptophan, from carbos, resulting in a mild high.. Maybe, but not in my experience.. I tend to get a feel-good sensation from rare steak. Not protein, mind you, because fish, chicken, or any other white meat just doesn't do it.. But bloody beef makes me all sorts of giddy, and mentally sharp. I'd be curious to know why..

Great article.

[TINK5C] |"Is K5 my kapusta intellectual teddy bear?"| "Yes"

5-HTP != coke (2.00 / 1) (#17)
by Gluke on Tue Feb 12, 2002 at 02:35:19 PM EST

You should try taking 5-HTP. It's not a "mood lifter". It's about as good of a mood lifter as eating lots of turkey.

[ Parent ]
5-HTP and tryptophan (3.50 / 2) (#18)
by ouroboro on Tue Feb 12, 2002 at 02:40:09 PM EST

I can vouch for the "carbo high". I can get a nice satisfying low level buzz from a carb heavy meal. Mind you nothing like a few bears or good sex, but still a very pleasant feeling.

[ Parent ]
Re: 5-HTP and tryptophan (4.00 / 5) (#26)
by dnaworks on Tue Feb 12, 2002 at 03:54:00 PM EST

Mind you nothing like a few bears

You're a far braver man than I ... after just one bear, I'm far too scratched to handle another :-)

[ Parent ]

"supplements" (3.00 / 1) (#21)
by persimmon on Tue Feb 12, 2002 at 02:46:19 PM EST

5-HTP is sold as an herbal supplement, like stevia (an herbal sweetener) and Saint John's Wort. If it's fairly non-toxic you can sell almost anything as a supplement, but if you want to call it a medication or a food (as SJW or stevia, respectively, are actually used), that requires special FDA finger-shaking and studies.

So 5-HTP is availible over-the-counter because they don't call it a "mood enhancer" or some such on the bottle.
--
It's funny because it's a blancmange!
[ Parent ]

My bottle says: (3.00 / 2) (#27)
by MK77 on Tue Feb 12, 2002 at 04:18:02 PM EST

5-HTP offers you the ideal, complementary blend of 5-HTP with Vitamin B-6. Together, these ingredients interact to increase your body's production of the calming neuro-transmitter serotonin.* 5-HTP will help you feel more relaxed, sleep better and enjoy a more positive outlook.*

* These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

(Yes, that asterisk disclaimer is on the bottle).


--
Mmm... rageahol
[ Parent ]

what it doesn't say (4.00 / 3) (#32)
by persimmon on Tue Feb 12, 2002 at 05:28:02 PM EST

It doesn't say it has an anti-depressant effect. It doesn't compare itself to drugs commonly in use to treat similar conditions. You can cover a lot of ground for supplements with that umbrell--er, I mean little disclaimer. Accordingly, it also doesn't list side effects, apropriate dosage, effectiveness statistics or possible drug interactions in the package, like "real drugs" do.

My bottle says "Promotes balanced serotonin levels" with the same disclaimer.
--
It's funny because it's a blancmange!
[ Parent ]

5-HTP is not well tested (3.00 / 1) (#34)
by MK77 on Tue Feb 12, 2002 at 05:47:13 PM EST

You're absolutely right. I haven't been able to find any serious studies on the effects of 5-HTP on depression, or mixed with other drugs, or otherwise -- only anecdotal evidence.

I can say that 5-HTP has helped me with depression, though I am not certain whether it is more increased serotonin levels, or largely placebo which causes me to be able to manage. However, my scientifically untested belief is that there is something to it.


--
Mmm... rageahol
[ Parent ]

serious studies (5.00 / 2) (#38)
by persimmon on Tue Feb 12, 2002 at 07:01:31 PM EST

For non-anecdotal evidence, try searching the National Library of Medicine's PubMed for abstracts of articles and papers. You can often get articles through your affiliated University for little or no cost, they don't have them in archived periodicals or a fulltext article database.

My dad (a pediatrician) recommends the following web sites for researching alternative medical systems and treatments: http://altmed.nccam.nih.gov/nccam/, herbmed.org, http://cpmcnet.columbia.edu/dept/rosenthal/, medscape.com.
--
It's funny because it's a blancmange!
[ Parent ]

Thanks for the links (none / 0) (#65)
by farmgeek on Wed Feb 13, 2002 at 03:32:16 PM EST

My wife is heavily into the herbal thing, while I am an eternal sceptic (I refuse to spend money on something until I've seen several credible studies).

Looks like there may be some credible info here.

[ Parent ]
That act from 1994... (3.50 / 2) (#39)
by Scandal on Tue Feb 12, 2002 at 07:31:16 PM EST

In 1994, Congress passed the Dietary Supplement Health and Education Act (see a synopsis here at the FDA's web site) which basically requires the FDA to allow any substance for sale which is available naturally but which isn't already classified as an illegal or controlled substance. So, basically, if you can find it in a plant or animal (or man, for that matter), and it isn't already illegal or controlled, then you can provide it legally. The FDA must prove that the substance is particularly harmful in order to have it removed from the market.

Thus, cocaine and opium are still illegal.


*Scandal*


[ Parent ]
Seriously? (1.23 / 26) (#7)
by czth on Tue Feb 12, 2002 at 01:02:55 PM EST

This complex system is an evolutionary wonder ...

You don't seriously believe that, do you? If so, I have some land in Florida I'd like to sell you. Try this experiment: take a watch apart. Throw it in a washing machine. Set it on high. Let me know how long it takes until your watch comes back out (or, hey, even something that can keep time[1], I'm not picky). You can up the number of washing machines a few orders of magnitude if you like, I still feel it's a pretty safe bet. And this evolutionary experiment already has all the parts available and no outside interference.

[1] Using it as a sundial doesn't count.

czth

Another experiment (4.61 / 13) (#14)
by zakalwe on Tue Feb 12, 2002 at 01:58:38 PM EST

Take your watch apart. Put it on a table, and pray for it to be recreated. This is a much more fair experiment, since its at least something God is supposed to be capable of. Evolution by contrast has absolutely nothing to do with random assembly of watches so calling this an "evolutionary experiment" is a complete strawman.

[ Parent ]
Ha!!! (1.50 / 4) (#16)
by Ranma on Tue Feb 12, 2002 at 02:28:49 PM EST

You have a rather fundementalist idea of God, don't you? I think a serious agnostic would be upset by your assumptions.

[ Parent ]
I'm sure you don't intend this as a non-sequitur (2.33 / 3) (#20)
by SIGFPE on Tue Feb 12, 2002 at 02:43:39 PM EST

Nonetheless I can't see any connection with the subject in hand. Maybe you should explain what you mean using less subtle metaphors so idiots like me can understand what you're talking about.
SIGFPE
[ Parent ]
I can't believe it's not logic! (4.66 / 3) (#35)
by autonomous on Tue Feb 12, 2002 at 05:48:52 PM EST

Your example is not valid. Your assumption is that a complex chemical system could never come from an uncontrolled series of chemical reactions because there is no screwdriver involved. If you placed the watch into a system capable of assembling small watch parts the same way nature is capable of assembling proteins you might have a fair comparison.
-- Always remember you are nothing more than a collection of complementary chemicals worth not more than $5.00
[ Parent ]
Read a bit of Dawkins. (none / 0) (#47)
by afree87 on Tue Feb 12, 2002 at 08:57:37 PM EST

Maybe you might get something meaningful out of it.
--
Ha... yeah.
[ Parent ]
Read a bit of Hume as well (4.50 / 2) (#77)
by solri on Sat Feb 16, 2002 at 11:29:44 AM EST

Oh god, that tired old watch analogy again. I thought David Hume put that one to rest centuries ago. Here's an alternative analogy (modernising an example from Hume). Think of your computer, and all the amazingly complex parts that makeup its hardware. Could one person have possibly constructed all of that? Obviously not - it has to be the work of thousands of people. Now consider the universe, which is, of course, much more complex than a mere PC. How could this possibly be the creation of a single being? Obviously, to create something so huge and complex, there have to be zillions of gods. Analogies are fun, but prove nothing.
"Nice philosophy may tolerate unlikely arguments" - John Ford
[ Parent ]
It's oversimplification day! (4.00 / 1) (#55)
by CaptainSuperBoy on Wed Feb 13, 2002 at 12:30:25 AM EST

What's worse: Oversimplification of evolution theory by creationists who want to discredit it? Or oversimplification of evolution theory by people who want to explain how I was once a monkey that didn't get eaten?

--
jimmysquid.com - I take pictures.
[ Parent ]
Yummy monkey (none / 0) (#73)
by isdnip on Wed Feb 13, 2002 at 10:41:01 PM EST

When you were a monkey, you did get eaten! By a very large cat.

But you had time to reproduce beforehand.

And some people still think cats are cute.

[ Parent ]
I did not get eaten! (none / 0) (#74)
by CaptainSuperBoy on Thu Feb 14, 2002 at 10:37:46 AM EST

I didn't get eaten when I was a monkey! I was India's infamous "monkey man!" I ate babies!

--
jimmysquid.com - I take pictures.
[ Parent ]
Watches are too simple. (none / 0) (#56)
by xriso on Wed Feb 13, 2002 at 12:48:11 AM EST

Seriously. Watches cannot self-reproduce or do anything very self-useful. They are mostly a collection of gears and an easily consumed power source. No, a better analogy would be far more complex.

But hey, simple monocellular lifeforms had 100 million (or was it 10 million?) years and a lot of space to come into existance, so we can't exactly rule it out. I believe the latest fad for abiogenesis is the RNA World theory, but maybe that's changed already.
--
*** Quits: xriso:#kuro5hin (Forever)
[ Parent ]

One small point. (5.00 / 2) (#57)
by Alfie on Wed Feb 13, 2002 at 04:49:17 AM EST

Keep in mind that abiogenesis is technically separate from the theory of evolution. It is possible, for example, that god or an asteroid or what-have-you planted the beginnings of life and everything evolved from there.

Much, much more information can be found at the talk.origins Archive. Of special interest to this discussion is the FAQ entry regarding abiogenesis.



[ Parent ]
you've given no evidence whatsoever (4.33 / 3) (#15)
by alprazolam on Tue Feb 12, 2002 at 02:25:10 PM EST

Chronically low serotonin levels creates the chronic drinker who needs a drink every day to maintain a positive mood

many depressed persons are attracted to marijuana...and also the reason why marijuana can increase the severity of depression.

Prayer and mediation will increase your serotonin levels.

Please provide evidence to back up the preceding claims, if you have any.

auto-suggestion (3.83 / 6) (#24)
by adiffer on Tue Feb 12, 2002 at 03:37:24 PM EST

The bit about prayer and meditation is largely the result of auto-suggestion. It is pretty well known that if you concentrate on achieving a particular emotional state AND you actually want to get there, you can often do it. Since some of these states are directly linked to the type and quantity of certain hormones in your bloodstream, your mental focus does the work for you.

This may sound hokey to some people, but a lot of people can do it if they bother to try. The externalization of the 'Power of Prayer' can be viewed as a misunderstanding of the internalized 'Power of Auto-Suggestion.'
-Dream Big. --Grow Up.
[ Parent ]

A few links (3.00 / 1) (#30)
by MK77 on Tue Feb 12, 2002 at 04:58:20 PM EST

I don't have hard references -- most of the research for this article was done through web searches. But here's some of the things I found:

serotonin and alcohol: http://open-mind.org/News/AA/6.htm

serotonin and marijuana: http://www.lacbc.org/brain.html -- though on second review, my comments about marijuana are unsubstantiated by this. I'll try and figure out where I got that in my notes.

serotonin and meditation: http://unstress4less.org/transcendental_meditation-tmresearch-biochemistry.htm


--
Mmm... rageahol
[ Parent ]

Not very conclusive (4.33 / 3) (#33)
by Mr Fred Smoothie on Tue Feb 12, 2002 at 05:32:07 PM EST

While there is too much hard medical evidence of a link between serotonin and alcohol to even bother posting links (do a search on "alcohol," "serotonin" and "abstract" to see what I mean), this is misleading to an extent because alcohol is a "broad-spectrum" drug in its effects on the brain and there are implications in both causality and treatment of the dopaminergic, norepiphrinergic, and GABA systems as well as the serotonin system -- and the degree of the involvement of the various systems seems also to vary by "type" of drinker.

Even the open-mind.org link you post is not persuasive; read the last paragraph. The author of the study cited in the link explicitly acknowleges the ambiguity of the results, in particluar the lack of clarity WRT the direction of causality.

The tm article is interesting and is the only "prayer/meditation is good" type article I've seen anywhere which actually documents real controlled studies; most of the "prayer is good" style of announcements I've seen are in explicitly religous publications which make vague reference to studies which turn out to be either anecdotal, or conducted by biased researchers who don't make any attempt to control for other factors (full disclosure: I'm a practicing Christian and do believe prayer is beneficial, I just haven't seen persuasive scientific evidence to that effect).

[ Parent ]

Ecstasy neurotoxicity (4.90 / 21) (#19)
by SvnLyrBrto on Tue Feb 12, 2002 at 02:41:52 PM EST

First off, a slight correction. Ecstast is NOT a narcotic. Nor is it a psychedelic, as some people assume (If you're hallucinating on E, you probably got MDA, a common adulterant in fake pills, or maybe your MDMA was laced with acid). Ecstacy, rathar, is actually a phenylthylamine.

As for ecstacy being the anti-cocaine, you're more right than you seem to know. Not so much because of the way each makes you feel, but because taking both together is what really will "fry your brain". (Well, nothing so dramatic as that. You're more likely to cook your brain by getting fake pills containing PMA, and overheating. But MDMA plus cocaine is a quick way to MAXIMIZE the harm that MDMA will do to your brain.

The problem of seratonin depletion and depression is actually pretty easily dismissed. All it takes is some moderation and waiting a while to let seratonin replenish. And 5-HTP is helpful in this regard, as is SAMe. I use both as part of my post-load, and I NEVER get the cracked out feelings the day after, nor do I get the "suicide tuesday" effect.

You do sort of lead to the REAL problem WRT/ MDMA induced neurotoxicity, but you don't quite get there. The problem is the breakdown of dopamine when it comes into contact with monoamine oxidase (MAO).

MAO, as you mention, is there to break down excess seratonin delivered by the reuptake transporters. MAO breaks down seratonin harmlessly. But when one does MDMA, there is a ridiculous excess of seratonin to be taken up and broken down. So the reuptake transporters go into overdrive. And when you run out of free seratonin, they don't shut down immediately. They get confused and start to suck up dopamine.

MAO was never meant to come into contact with dopamine. Where seartonin breaks down harmlessly, dopamine breaks down into hydrogen peroxide!!! Yup, same stuff as in hair bleach... and none too good for your grey matter.

A more detailed explination (but still in laymans terminology) of this can be found in the slideshow at DanceSafe.

This is why Ecstasy and cocaine mix so badly. MDMA releases some, but not too much, dopamine. Cocaine, as you say, releases a LOT of dopamine, and prevents its normal reuptake. More dopamine when the seratonin runs out == more hydrogen peroxide.

This can be battled in a handful of ways.

First off, is to maximize the amount of seratonin available, while reducing the amount of dopamine. 5-htp has been found to reduce MDMA induced neurotoxicity, for this reason. Pantothenic acid also helps, as it aids your brain in absorbing 5-HTP. Of course you also want to avoid increasing dopamine levels, which means avoiding cocaine, DLPA, and L-Tyrosine. I, presonally take 5-HTP before (400mg) and after (100mg).

Second, a little chemistry knowledge can help. Both the breakdown into hydrogen peroxide and the damage that the perodide will do, are oxidizing reactions. So you counter that with antioxidants (which are good for you for other reasons anyway). In fact, one of the stronger antioxidants, alpha lipoic acid, was found (in rats) to completely ELIMINATE MDMA's neurotoxic effects. Alpha lipoic acid also has the advantage of a synergistic effect when combined with other antioxidants. That is, the total protection afforded is greater than the sum of the parts (kind of like mixing alcohol and barbituates, only good for you). I perfer a nice mix of alpha lipoic acid, vitamin C, vitamin E, and taurine.

The third option comes into play if you have access to fluoxetine. Fluoxetine (Proxac) has a greater affinity for your seratonin transporters than MDMA, dopamine, and even seratonin. Thus, takint it six hours after MDMA will block dopamine from entering the reuptake transporters and coming into contact with MAO. This has also been shown to be effective in mitigating MDMA induced neurotoxicity. One thing to remember, tho, is that because SSRIs bind to the seratonin transporters so much more easily than anything else, they will actually prevent MDMA from affecting you at all, if they're in your system BEFORE Ecstasy.

Then, of course, there's the obvious: keep hyderated, don't overheat, and make fucking sure you know what you're taking!!!

Feh... and bush and co. would have you think that ravers are nothing but a bunch of drugged out ignorami who have no idea what they're putting in their own bodies. Most of the above I researched myself over time. And I got quite a few helpful pointers from other ravers.

'Tis funny... I can (and have... on numerous occasions) sit down and have a talk about seratonin, MDMA, and the esoterica of neurochemistry... It'll make sence, we'll have references, and we'll both learn something. The best the medical profession can do, OTOH, is put some quack on oprah, who will show me a blue and purple blob, and expect me to take him at his word (without any supporting data... not even so much as a legend to show me what the colors on his blob mean!!!) that Ecstasy "eats holes in your brain". Is it any wonder that no one believes or trusts them or their republican puppetmaters?

cya,
john

Imagine all the people...

dehydration vs. hyponatrea (4.88 / 9) (#23)
by bumdass on Tue Feb 12, 2002 at 03:17:57 PM EST

A little note about hydrating yourself:

MDMA is also anti-dieuretic, meaning it will actually PREVENT your body from removing water from the bloodstream. This is why users generally will not need to urinate while under the influence.

Because MDMA is an amphetamine, it increases the body temperature and heart rate of the user, which can drain water from the body. Most ecstacy overdose deaths are caused by dehydration from excessive dancing.

Hence, users are told to "drink water".
However, some people take this too far, and they drink water excessively. This dilutes the blood to such an extent that cells begin to die. Other ecstacy overdoses are caused by this condition, called hyponatrea (literally, low salt). This happens much more rapidly than it normally would because of the anti-dieuretic effect, and a normal amount of water as low as a few liters can be fatal for someone with a low body weight.

So, the moral of the story is: drink Gatorade or Powerade or some other drink with a good electrolyte balance. These drinks contain enough salt and water to prevent either condition from occurring.

[ Parent ]
What I do... (4.50 / 6) (#29)
by SvnLyrBrto on Tue Feb 12, 2002 at 04:41:53 PM EST

Good tip. As a matter of fact, this is an important thing to remember even if you're going to be sober. Hyponatremia (commonly called water intoxication) is known to affect all kinds of people. Outside of the rave/nightclub scene, it most commonly occurs in distance runners!

Since most parties (and even most clubs) don't carry sports drinks, I usually bring in a few salt packets (like from a fast food place). One or two in your water bottle won't affect the taste, and it'll keep your electrolytes up.

This is impoprtant for ME especially. My family has a history of LOW blood pressure. So if my salt level gets low, hello dizzyness and naseua! Before I had it figured out, I even passed out from low BP a few times.

If you're at a bar or club, the tomato juice in a bloody mary usually has plenty of salt. And Red Bull has 200mg of salt per can (along with a nice assortment of antioxidants and B-compled vitamins). Payday bars are good too, if you can bring candy in, or buy it there; a nice sugar rush, protien from the peanuts, and a healthy layer of salt on top of it all.

There's a pretty good discussion of this where I provided some useful links over at the DanceSafe E-Board.

cya,
john

Imagine all the people...
[ Parent ]

Research notes... (5.00 / 1) (#36)
by Signal 11 on Tue Feb 12, 2002 at 05:57:07 PM EST

I've done similar research and concluded the risk is minimal, provided reasonable precautions are taken. The use of MDMA is no more dangerous than an imbalanced diet, properly managed. The problem is, far, far, too many people do not research drugs. Nobody reads the labels on tylenol bottles and wind up dying every year from one of the most well-known drug reactions on the planet: Tylenol + alcohol = you frag. *shrugs*

If you have additional information about this, could you please forward it to me? I've been researching this drug quite a bit, and have probably over a hundred pages of texts on the matter. However, you surprised me with your very detailed and concise explanation, as well as bringing up a few points I had not considered - specifically your explanation of why dopamine manages to connect to seratonin uptake sites makes a lot of sense.

Thanks!


--
Society needs therapy. It's having
trouble accepting itself.
[ Parent ]

A lot of it is hardcopy... (5.00 / 2) (#43)
by SvnLyrBrto on Tue Feb 12, 2002 at 07:48:20 PM EST

Some of the best sources are the actual research papers I linked to. Unfortunately, PubMed only posts the abstracts, and in most cases you have to pay to download a PDF.

However, if you have access to a decent university library, you should be able to get hardcopies of your own. I've a file folder full of the things.

Another excellent resource, probably the best one available these days, is: Ecstasy : The Complete Guide : A Comprehensive Look at the Risks and Benefits of MDMA, by Julie Holland M.D. It was only published last year, so it has most of the up to date research included. A big plus with this book is that, unlike most books about drugs, this one is written from neither the "counterculture" NOR the war on (some) drugs point of view. Rathar, Dr. Holland tries to present factual information as objectively as possible and allow the reader to draw his own conclusions.

For the sake of doing research, I'd skip, for now, titles such as Ecstasy: The MDMA story, and Ecstasy, Dance Trance and Transformation. Both are good books, but focus more on the culture surrounding the drug than MDMA itself. Plus, they are somewhat dated and don't have data as up to date as Dr. Holland's book.

So far as what is available online, take a lot of it with a grain of salt, and don't believe any single source. But there ARE a few gems in the garden. Erowid is an obvious and excellent resource, as the Alchemind Society. One feature of alchemind.org is the Ask Dr. Shulgin section, where Dr. Alexander Shulgin himself answers questions periodically. A valuable part of the aforelinked DanceSafe E-board is the Theraputic Benefits section, where Ann Shulgin and Sue Stevens post and answer questions. The E-boards in general are pretty good. But get a feel for who knows what they're talking about before taking anyone at face value.

Over all, your very best bet (short of tracking down those PubMed articles in the library) for good, factual, up-to-date information, with a minimum of bias, is Dr. Holland's: "Ecstasy : The Complete Guide : A Comprehensive Look at the Risks and Benefits of MDMA".

cya,
john

Imagine all the people...
[ Parent ]

Goddamit (none / 0) (#58)
by axxeman on Wed Feb 13, 2002 at 05:01:02 AM EST

Why oh why can we only rate comments up to 5?

Desperately need Egyptologist. Can you help?
[ Parent ]

errata (3.33 / 3) (#67)
by supruzr on Wed Feb 13, 2002 at 04:55:27 PM EST

I'm happy that you get your information from erowid.org and Shulgin's literature, but I wish you'd at least check yourself for accuracy before you "repeat" it. Yes, MDMA is a "phenylthylamine" (phenethylamine), but stating terms that nobody recognizes does little to clarify. Most directly, MDMA is an amphetamine. I'd think the chemical name would give that away. As such, most of the adverse effects associated with amphetamines apply to MDMA. In addition, yes, there is a very hazy area of study dealing with the neuropharmocology of MDMA. Unfortunately, there aren't nearly as many facts as you claim, and the bottom line is: everyone claims to know how MDMA affects the brain, and everyone seems to disagree. In the years and years MDMA has been studied in the brain, the only really concrete fact that every researcher agrees on is that it affects seratonin. It MAY do a whole slew of things on top of that, such as impair mitochondrial production of adenosine, which would lead to cell death:

Cellular energy exhaustion or impairment may cause MDMA neurotoxicity. Normal activity of the neuron cause a certain degree of oxidative stress. A sustained increase in neuronal activity would therefore be expected to increase oxidative stress. More importantly, increased neuronal activity is accompanied by increased energy consumption that could eventually lead to a depletion of neuronal energy sources. This can impair the energy-requiring mechanisms that maintain and repair neurons. Furthermore, the most important source of cellular energy, mitochondria, can be impaired by oxidative stress (Crompton, 1999).

On the other hand:

One study found that ATP levels were unaltered up to three hours after MDMA administration (Hervias, 2000).

And yes:

...some of the dopamine released by MDMA *MAY* be transported by SERT into serotonergic axons (Faraj, 1994) and subsequently oxidized (Nash 1990; Schmidt, 1990; Sprague and Nichols 1995b). The oxidation of dopamine can form hydrogen peroxide which, in turn, may produce hydroxyl radicals.

However:

There is currently little direct evidence to support a role for dopamine metabolites in MDMA neurotoxicity. Some dopaminergic drugs alter MDMA neurotoxicity, but it is not clear that this is due to increasing or decreasing dopamine release. Many dopaminergic drugs are now thought to affect MDMA neurotoxicity through nonspecific mechanisms such as altering body temperature (Colado, 1999a; Malberg, 1996) or scavenging free radicals (Sprague and Nichols 1995a; b; Sprague, 1999). However, dopamine release does seem to play a poorly understood role in MDMA neurotoxicity (Nash and Brodkin 1991; Schmidt, 1990; Shankaran, 1999b; Stone, 1988).

Other people here have been talking about the ridiculousness of 'folk-pharmocology' and this does nothing to dispel it. This may be hard for you to believe, but dancesafe is not a reliable source of psychopharmocology. You know how to determine that? They don't provide the sources of their information. Slide 19 in that nifty slideshow you link to is the first instance of a scientist being credited by name, and "Researchers say" is not a valid citation. I can shit in a box and call it MDMA research, if you want. For that matter, you aren't citing sources either. Not citing sources generally leads to misplaced credibility.

The best the medical profession can do, OTOH, is put some quack on oprah, who will show me a blue and purple blob, and expect me to take him at his word (without any supporting data... not even so much as a legend to show me what the colors on his blob mean!!!) that Ecstasy "eats holes in your brain". Is it any wonder that no one believes or trusts them or their republican puppetmaters?

No, the best the medical profession can do is Alexander Shulgin, whose book PiHKAL you yourself have cited. Maybe you should stop watching Oprah if you don't want to be exposed to pseudomedical crap. Just a thought. If you've ever heard someone qualified to speak on the subject say that "ecstacy eats holes in your brain" you probably weren't paying attention to the context. DXM is commonly sold as ecstacy, and yes, DXM *can* eat holes in your brain. It's called NMDA antagonist neurotoxicity. I'm in a somewhat unique position to speak on that subject, because I have it.

Now I know your heart was in the right place, providing all this wonderful information, but you're taking as gospel data that is very poorly understood, and could very well be wrong. If you want well-supported data and a complete listing of possible chronic effects of MDMA, I recommend to you the book _Ecstasy: The Complete Guide_ edited by Julie Holland, ISBN 0892818573. The neurotoxicity section of the book can be found in synopsis form online at http://www.erowid.org/chemicals/mdma/mdma_neurotoxicity1.shtml

[ Parent ]
Sources... (4.00 / 1) (#69)
by SvnLyrBrto on Wed Feb 13, 2002 at 07:25:42 PM EST

>Yes, MDMA is a "phenylthylamine" (phenethylamine),
>but stating terms that nobody recognizes does
>little to clarify. Most directly, MDMA is an
>amphetamine.

Well, if you want to be pedantic about misspellings, that's your affair. I'm sure somewhere I've spelled it as ecstacy instead of ecstasy as well. Care to flame me about that too?

I daresay, though, that you are far out of your league for challanging Dr. Shulgin's classification (and inclusion in PIHKAL) of MDMA as a phenethylamine in the first place.

MY main point there, however, is that MDMA is NOT, by any streach of the imagination, a narcotic. (Well, I did meet one cop once who insisted otherwise. But, then, they are not exactly known for knowing what they're talking about. If they had any intelligence or creativity, they'd be doing something constructive with their lives, instead of preying upon harmless members of soceity.)

Now, I won't argue that there is a bit of contradictory research. But when you make baseless accusations like:

>I can shit in a box and call it MDMA research,
>if you want. For that matter, you aren't citing
>sources

... I have to call it the bullshit that it is. If you mean I'm not citing sources in a nice, little MLA style bibliography, okay then. But did you follow any of the links I provided? I cited several articles from PubMed (All of which I have the full text... in some cases annotated by a friend who's a medical student and translated some of the more hardcore doctorese for me), PiHKAL itself, and another book, which we'll get to later.

>DXM is commonly sold as ecstacy,

Which is why we gets our pills tested before we takes them.

>DXM *can* eat holes in your brain. It's called
>NMDA antagonist neurotoxicity. I'm in a somewhat
>unique position to speak on that subject,
>because I have it.

I'm sorry to hear about your condition. But there is something to remember:

DXM is not Esctasy, it is an adulterant.
DXM is NOT Esctasy, it is an adulterant.
DXM is NOT Esctasy, it is an adulterant.

Nor is MDA Ecstasy... nor MDE. Amphetemine is definately not Ecstasy, nor is speed+acid, despite what some stupid people may tell you. All of these (including DXM) are adulterants. MDMA IS Ecstasy (er... Rather, Ecstasy is MDMA). And may the people who sell fake pills rot in drug dealer hell.

There are reasons that pill testing services exist.

>If you want well-supported data and a complete
>listing of possible chronic effects of MDMA, I
>recommend to you the book _Ecstasy: The Complete
>Guide_ edited by Julie Holland

Ah, yes... the book. You mean the book I praised a lot and highly recommended to Signal 11 in another post, in this very thread, a good day before you decided I needed to be flamed for not citing any sources and knowing nothing of which I talk? The book which I had on pre-order from Amazon months before it was published? The book which arrived at my doorstep well before it showed up in the local library or bookstores? The book that was my main reading material for a good month, and now sits on my bookshelf right next to PiHKAL and TiHKAL?

Thanks for the recommendation. It is an excellent book.

cya,
john

Imagine all the people...
[ Parent ]

errata #2 (none / 0) (#75)
by supruzr on Thu Feb 14, 2002 at 03:09:00 PM EST

I daresay, though, that you are far out of your league for challanging Dr. Shulgin's classification (and inclusion in PIHKAL) of MDMA as a phenethylamine in the first place.

I suggest you reread my post, because I challenged no such thing.

If you mean I'm not citing sources in a nice, little MLA style bibliography, okay then. But did you follow any of the links I provided? I cited several articles from PubMed (All of which I have the full text... in some cases annotated by a friend who's a medical student and translated some of the more hardcore doctorese for me), PiHKAL itself, and another book, which we'll get to later.

Yes, and among those, PiHKAL is the only primary source. Maybe you don't see a problem citing as "sources" websites that cite OTHER websites and studies as sources, but I do. We can use this method of inventing credibility to daisy chain websites in an infinite loop, if you want.

DXM is not Esctasy, it is an adulterant.

I'm happy you're capable of stating the obvious, but I'd rather call DXM a disassociative anesthetic. By your leave, of course.

Ah, yes... the book. You mean the book I praised a lot and highly recommended to Signal 11 in another post, in this very thread, a good day before you decided I needed to be flamed for not citing any sources and knowing nothing of which I talk?

Yes, that book. Get something straight, kid. I'm not your biographer, and I don't care about the content of your other posts. I'm replying to THIS one. Now, since you've done a good job of ignoring the point I tried to raise in my original reply, I'll state it very clearly here: you're not an expert on psychopharmocology just because you go to these sites. You're repeating data that is by no stretch of the imagination scientifically verified. I have been studying and working with the substances in question going on five years now. I'm sorry if that bruises your ego. Am I flaming you? If you think so, you don't have a clear understanding of what a flame is. If you don't expect someone to call you for being careless, then you're going to get "flamed" a lot. I may be a slashdot refugee, but I'm certainly not a troll.

[ Parent ]
DXM the adulterant, and PubMed articles. (4.50 / 2) (#76)
by SvnLyrBrto on Thu Feb 14, 2002 at 06:11:17 PM EST

>I'd rather call DXM a disassociative anesthetic.
>By your leave, of course.

Sure, now that you've admitted that it is not the same thing as ecstasy.

But you DO know why DXM finds its way into pills (and thus, into the bodies of incautious drug users), yes?

Well, aside from actually being legal, which, so long as MDMA is illegal, is unfortunate, because DXM's legallity only encourages the sleazy to make fake, adulterated pills; and having a psychoactive effect that the very inexperienced MIGHT mistake for the real thing...

... DXM would stand a fair chance of fooling the old Marquis reagent field test for Ecstasy. See, both DXM and Ecstasy (and chemically similar drugs, like MDA and MDEA) have the same color change reaction then exposed to Marquis Reagent. They both react to turn the reagent a dark purple to black. The way to tell the difference, was by the time. MDMA would turn black in five seconds or less, and DXM would take ten seconds or more... in theory. In reality, other factors, such as the fillers and binders in the pill scraping, and the temprature at which the test was done, made distinguishing the two annoyingly imprecise (short of sending a pill into the lab for gas chromatography).

Your more shadey pill manuefacturers would take advantage of this weakness, and use DXM instead of MDMA. And thus, people, unfortunately, would wind up taking adulterated pills even if they were careful to test.

Fortunately, there are two new reagents in use now that will foil the peddlers of DXM. The Mecke Reagent will turn two distinct colors depending on DXM vs. Ecstasy, making it much easier to screen out that adulterant. Simons Reagent will even screen out MDA, foiling the more advanced adulterers. (MDA would fool the Marquis reagent even IF you were sure that the pill was not DXM.

Like I said. I'm sorry you would up with so many bunk pills and got exposed to so much DXM. But there ARE resources available to people to help keep that from happening.

(ugh... like I said, may people who sell adulterants rot in drug dealer hell)

>PiHKAL is the only primary source. Maybe you don't
>see a problem citing as "sources" websites that
>cite OTHER websites and studies as sources,

>You're repeating data that is by no stretch of
>the imagination scientifically verified.

Not quite. You obviously don't understand what PubMed is.

PubMed is NOT a site that references other sites for medicial information. PubMed is a searchable archive of the abstracts of published, and peer-reviewed articles that have appeared in legitimate scientific journals. PubMed points you directly to the original research, by the scientists who DO the original research in the first place!

I'll spell it out even simpler, useing one of the examples I had in the top-level post: The article from Neuroreport, published 26-NOV-1999: Alpha-lipoic acid prevents 3,4-methylenedioxy-methamphetamine (MDMA)-induced neurotoxicity.

This article was published, in the aforementioned Neuroreport journal, by Dr.'s Aguirre, Barrionuevo, Ramirez, Del Rio, and Lasheras of the Department of Pharmacology, of the University of Navarra.

Dr.'s Aguirre and co. did NOT just do a web search on ALA and MDMA, summarise the results, and write up a paragraph to be posted on PubMed. That's not what PubMed is about.

They conducted a study useing the scientific method. They got a bunch of rats, dosed them with ALA and MDMA, and recorded the results against a control group. They did this enough times to have a valid, repeatable, statistical sample. Then they wrote up their results, and submitted them to the peer-review process, in order to get them published in the appropiate scientific journal. After the article passed its peer-review, it was published in Neuroreport.

Now, and only now, does PubMed enter the picture. They collect the abstracts of articles that have already passed the peer-review process and been published in medical journals. They put these abstracts in a searchable database, and in many cases provide a link to a service that will, for a fee, let you download a PDF of the full article.

If you balk at paying for the download, or if the particular artilce isn't online, you go to any decent university library and print or photocopy the thing for .05 per page.

And now you have a copy of the ORIGINAL, peer-reviewed, repeatable, scientifically verified research that other sources, such as erowid, summarise. And hey, you don't even have to go around cutting open rats yourself!

cya,
john

Imagine all the people...
[ Parent ]

outstanding post/a few corrections (none / 0) (#70)
by Shpongle Spore on Wed Feb 13, 2002 at 09:15:16 PM EST

One thing I've learned the hard way from writing about drugs is not to assume that what you read, your personal experience, or your friends' experience are the whole story. In particular, MDMA will cause visual hallucinations in some people and under some circumstances, such as taking overly large doses or being in an environment with a lot of visual "noise" like a forest at night with lots of shadows everywhere. I've known of this to happen with pills that were unmistakably the real thing.

Also, contrasting phenethylamines with psychedelics isn't right, since lots of phenethylamines are psychedelics (mescaline, anyone?)

But all bitching aside, your post was very informative and had a lot of information that was new to me, even though I've been actively studying up for years. Bravo!
__
I wish I was in Austin, at the Chili Parlor bar,
drinking 'Mad Dog' margaritas and not caring where you are
[ Parent ]

Couple of comments... (none / 0) (#78)
by adrade on Tue May 14, 2002 at 08:31:10 PM EST

1. Dopamine is metabolized by MAO, as is serotonin, though serotonin is metabolized selectively by MAO-A in the axon and has no such extracellular method.

2. MDA is a metabolite of MDMA. In fact (and of this, I am not completely sure), I believe it is the most common metabolite of MDMA detected in urine analyses.

3. In terms of legal classification, I believe most states classify MDMA as a narcotic, but then again, so classified also is marijuana.

4. Again, dopamine is supposed to be broken down by MAO, and I believe most selectively by MAO-B(just not in the 5-HT axon terminal). Increased extracellular dopamine seems to potentiate free-radical formation and lipid peroxidation of the 5-HT axon terminal ("pruning the axon field"). This is supported by seemingly increased damage with co-administration of l-Dopa, a precurser of dopamine.

5. MAO-B seems also to be implicated in the toxicity, since inhibition seems to attenuate toxicity (though deprenyl, and I think one other that was tested, scavenges for free-radicals, so the true neuroprotective route is unknown).

6. You are quite right in suggesting that people stay hydrated and cool. Increased ambient temperature has been associated with increased free-radical formation in general, and with MDMA, potentiates toxicity.

7. Lipoic acid in high doses in rats has been shown to eliminate MDMA-associated toxicity, as has ascorbic acid. I would recommend both, but for the former a time-release mechanism, since ALA (TA) is readily absorbed but is fastly eliminated from your blood. You should be safe at least up to 1,200 mg. (300 mg SR, www.jarrow.com)Vitamin C quickly reaches its maximum absorption level and does not in its common form pass the blood-brain barrier. It's oxidised form dehydroascorbic acid, however, does. Vitamin C, interestingly, is found in the brain at a 10x higher density than in plasma and is quickly eliminated (as is a-tocopherol) after MDMA admin.

8. 5-HT has also been shown to scavenge for free-radicals and is the immediate precurser for serotonin. Lack of serotonin has been implicated also in potentiating toxicity. For these two reasons, this chemical may also help. l-Tryptophan is also a free-radical scavenger, though it may not as drastically increase 5-HT levels after MDMA since tryptophan-hydroxylase, the enzyme that converts this to 5-HTP, is inhibited by MDMA.

I apologize in advance for any inaccuracies in my post. To the best of my knowledge, the information above is supported by rigerous scientific studies. If anyone is interested in a reference for anything above, feel free to email me: adam-k5h@adrade.com, and I'll get right on it. I'm no scientist, just a student.

Best to all,
  -Adam

[ Parent ]

The Geek's Guide to Practical Brain Chemistry? (2.33 / 3) (#22)
by deefer on Tue Feb 12, 2002 at 03:10:10 PM EST

Is it just me, or should this have been written by spiralx? :)


Kill the baddies.
Get the girl.
And save the entire planet.

I don't know... (none / 0) (#37)
by rusty on Tue Feb 12, 2002 at 06:27:09 PM EST

...but I do know that it should be memorized by the whole London Kabal. ;-)

____
Not the real rusty
[ Parent ]
Nah... (3.00 / 1) (#42)
by deefer on Tue Feb 12, 2002 at 07:45:17 PM EST

With our short term memories, we'd only forget it within 5 minutes! :)




Kill the baddies.
Get the girl.
And save the entire planet.

[ Parent ]

Other tidbits (4.55 / 9) (#25)
by Wondertoad on Tue Feb 12, 2002 at 03:38:35 PM EST

- Our understanding of brain chemistry is really moving along very quickly right now. Scientists say that we've gotten as much understanding of the brain in the last decade as we've gotten throughout all of history.

- Marijuana's main effect is not on serotonin, but what it actually does is mimic an entirely different neurotransmitter: the anandamides. Cannabinoids take up the anadamide receptors. This is similar to what the opiates do in taking up the receptors that react to pain. The difference is that there are no receptors for cannabinoids/anadamides in the areas of the brain that control involuntary activities. (That makes it remarkably safe.)

- Anandamides have also been found in chocolate, but only certain ones and not the ones that produce a "high". But this is part of chocolate's mystery: it actually can produce a brain chemistry change that leads one to a greater sense of well-being.


Psychoactives in chocolate: (4.60 / 5) (#31)
by SvnLyrBrto on Tue Feb 12, 2002 at 05:23:12 PM EST

>But this is part of chocolate's mystery: it
>actually can produce a brain chemistry change that
>leads one to a greater sense of well-being.

Chocolate has a whole collection of psychoactives. Chocolate even has its own entry in erowid!!!

Here's a short list, taken from a link on erowid:

Neurotransmitters:

-- Serotonin
-- Histamine

Methylxanthines:

-- Theobromine
-- Caffeine

Tetrahydroisoquinolines:

-- Salsolinol
-- Methyltetrahydroisoquinoline

Amines:

-- Phenylethylamine
-- Tele-methylhistamine
-- Spermidine
-- p-tyramine
-- 3-methyloxytyramine
-- Tryptamine
-- Spermine



cya,
john

Imagine all the people...
[ Parent ]

No cannabinoids in involuntary actions involved (5.00 / 1) (#59)
by Teukels on Wed Feb 13, 2002 at 05:40:00 AM EST

>The difference is that there are no receptors for cannabinoids/anadamides in the areas of the brain that control involuntary activities. (That makes it remarkably safe.)

I agree on its apparent safety. However not having receptors for those in areas of the brain that control the sympathetic nervous system does not prove it cannot have influence that. Research and possibly own experience tells us a different story since increased heartrate, jagging movements (sometimes) are felt, things which are no part of my voluntary movements.

Nevertheless things probably would have been worse when there actually were receptors in the sympathetic nervous system for those.



[ Parent ]
Intriguing... (3.60 / 5) (#28)
by Remus Shepherd on Tue Feb 12, 2002 at 04:33:52 PM EST

Dopamine also appears to be critical for smooth body movements, as Parkinson's disease is caused by a dopamine deficiency.
Cocaine is an interesting drug, biochemically speaking. Not only does it cause a burst of serotonin and dopamine, it also blocks dopamine reuptake!

So has anyone thought of using cocaine (or a safer derivative) as a treatment for Parkinson's?

Any drug or process with affects dopamine levels to a significant degree, particularly those which increase dopamine levels, are likely to be addictive.
patterns of negative thinking will cause a release of dopamine.

Thinking negatively is addictive??

Fascinating information, thanks for sharing it. As someone who has never taken drugs, and been alcohol and caffeine free for 7 years, I sometimes wonder how my brain functions differ from everyone else. :)


...
Remus Shepherd <remus@panix.com>
Creator and holder of many Indefensible Positions.

So, what then? (2.00 / 1) (#41)
by deefer on Tue Feb 12, 2002 at 07:42:52 PM EST

As someone who has never taken drugs, and been alcohol and caffeine free for 7 years, I sometimes wonder how my brain functions differ from everyone else.

So what do you do for kicks then?

Not trolling, just genuinely interested in what you use as a substitute...


Kill the baddies.
Get the girl.
And save the entire planet.

[ Parent ]

Clean livin' :-) (3.00 / 1) (#44)
by Remus Shepherd on Tue Feb 12, 2002 at 08:32:04 PM EST

Sex when I can get it. :) Haven't had a girlfriend for about a year, though.

Music relaxes me and makes me feel happy. I play music in the car, at work, in the shower, and whenever there's nothing good on TV.

And computer games are good for improving my mood. I wonder what effects adrenaline has on brain chemistry.


...
Remus Shepherd <remus@panix.com>
Creator and holder of many Indefensible Positions.
[ Parent ]
Gaming (2.50 / 2) (#53)
by Souhait on Wed Feb 13, 2002 at 12:17:26 AM EST

Gaming just drains me. If I'm feeling negative then that emotion is gone, but if I'm happy that pretty much leaves me, too. It's a lot like watching TV, in some respects. Well, some games are... Diablo II is pretty much like that, but starcraft was fairly intense and much more enjoyable, if not quite as addictive, which is funny.

[ Parent ]
parkinsons / addiction (3.00 / 2) (#45)
by iGrrrl on Tue Feb 12, 2002 at 08:34:47 PM EST

So has anyone thought of using cocaine (or a safer derivative) as a treatment for Parkinson's?
L-DOPA, a precursor to dopamine, is one of the standard treatments for Parkinson's. Cocaine does too many other things to be useful in this regard.
Thinking negatively is addictive??
Just about anything can be addictive. The trick is stimulation of the reward pathways, which are not always simply affected by a drug. The addiction pathways that go through the nucleus accumbens (I think, at least in rats...) are not entirely understood. This thought is different, of course, from the mechanisms that underlie opioid (heroin) addiction, for example, although the reward pathways also come into play there.

--
You cannot have a reasonable conversation with someone who regards other people as toys to be played with. localroger
remove apostrophe for email.
[ Parent ]

L-DOPA, a precursor to dopamine (none / 0) (#60)
by Teukels on Wed Feb 13, 2002 at 05:59:28 AM EST

>L-DOPA, a precursor to dopamine, is one of the standard treatments for Parkinson's.

True. "L-Dopa taken as a daily pill reaches the brain where neurons convert it to dopamine" Dopamine itself won't cross the blood brain barrier. "Allthough it alleviates the symptoms, L-Dopa does not halt the death of neurons and eventually the loss is to large to relieve. The other limitation is that L-Dopa does not only enter the cels that need extra dopamine but also others and cause harmful side effects that include nausea, stereotyped movements, hallucinations and delusions. These effects can be counteracted with some other drugs or by various slow release devices." (Kalat, J. W., Biological Psychology, 1998)

Another helpful drug for Parkinsons patients is Deprenyl, it slows the loss of neurons and decreases the need for L-Dopa and prolonges the life in Parkinson's patients (and also in aged but otherwise normal rats.)

Other ways:

- Blocking Monoamine oxidase B which changes good stuff into evil stuff.

- Nicotine (Smoking people suffer less Parkinsons)

- Use of fetus to make enthousiastic undamaged fresh neurons.

(All information comes from the same source mentioned, pages 136, 137)

[ Parent ]
Smoking People (none / 0) (#64)
by farmgeek on Wed Feb 13, 2002 at 03:18:56 PM EST

"Smoking people suffer less Parkinsons"

You can imagine the wonderful image floating in my brain from this particular sentence.



[ Parent ]
i can certainly attest to that (none / 0) (#49)
by goosedaemon on Tue Feb 12, 2002 at 09:13:41 PM EST

maybe i'm just odd (i certainly am in other ways) but i find that, though at the same time abhorring it, i get some jollies out of negative, depressed thinking. the word "addictive" never came to my mind, though, but i certainly thought it was self-perpetuating.

[ Parent ]
Casey Jones, you'd better watch your speed (4.00 / 2) (#51)
by pietra on Tue Feb 12, 2002 at 10:13:02 PM EST

Cocaine is a fabulous treatment for Parkinson's for the first hour or so. Afterwards, you have both Parkinson's and a cocaine addiction. Theoretically, if you were a fabulously wealthy Parkinson's sufferer and had an unlimited source of coke, you'd be pretty much okay. A few people actually tried this in the '70s, and wound up becoming interesting footnotes in my college introductory psychobiology text. Needless to say, they did not do well--yet another example of why self-medication is not a good idea.

[ Parent ]
cocaine derivatives for Parkinson's (none / 0) (#71)
by Shpongle Spore on Wed Feb 13, 2002 at 09:26:20 PM EST

So has anyone thought of using cocaine (or a safer derivative) as a treatment for Parkinson's?

I imagine there are people constantly trying to find safer versions of illegal drugs. Trying surfing over to Chemfinder and comparing Paxil to ecstasy or Wellbutrin to amphetamine. The similarities are overwhelming, at least to me.
__
I wish I was in Austin, at the Chili Parlor bar,
drinking 'Mad Dog' margaritas and not caring where you are
[ Parent ]

Intriguing cultural phenomenon (4.33 / 9) (#40)
by SIGFPE on Tue Feb 12, 2002 at 07:40:55 PM EST

I'm used to folk psychology but I think we're seeing something new nowadays: folk pharmapsychology. People go to parties these days and talk about their dopamine levels and serotonin levels and prozac as if they actually know what any of these things do. It's scary the way what was once hardcore neuroscience jargon is now used in the most ignorant ways by ordinary people. "This drug raises my serotonin levels", "that drug lowers my dopamine levels". People don't have the faintest clue what they are talking about but these statements seem to get repeated so often that they eventually come to be taken as gospel truth. If you actually pick up papers on these subjects the relationships are often presented in a very guarded manner with speculations about causality between different neurotransmitter phenomena clearly labelled as such. But these speculations get unreliably copied from paper to pop science mag to women's magazines to party conversation and now I see them reproduced in a K5 article as something scientific. Amazing!
SIGFPE
How primative our understanding is... (none / 0) (#66)
by thesync on Wed Feb 13, 2002 at 04:09:12 PM EST

Saying that some psychological condition is the case of "too much neurotransmitter" is a very large simplification. We really have no true idea about the real causes of most of these conditions, but we have some scientific evidence of using drugs that change neurotransmitter amounts can reduce symptoms.

It is much like saying "Oh, your computer isn't working right, try giving it a higher voltage on the +5V line" as opposed to swapping out a bad RAM chip. Sure, it might help a bit, but it isn't a cure.

We are only at the beginning of understanding these conditions - they probably have much more to do with "wiring" than they do with brain-wide neurotransmitter levels.

That said, please take your meds! They help.

[ Parent ]
I'm a fan of the neuroleptics (none / 0) (#46)
by MFS on Tue Feb 12, 2002 at 08:55:29 PM EST

antipsychotics, and the atypical antischitzophrenics

of course, that's what I do for a living...


Nope, not me. I must be someone else.

A very mixed and mixed-up bag (4.89 / 19) (#48)
by iGrrrl on Tue Feb 12, 2002 at 09:11:55 PM EST

It's amazing, really. The mix of correct information and half-understood overinterpretations makes this piece difficult for me to dissect. It would take too long to pull it entirely apart, and probably wouldn't interest anyone but me to do so. I'll try to limit my remarks.
Your brain is a big bag of neuron cells...
The brain is not a big bag of neurons (to call them "neuron cells" is redundant). Neurons in the brain are highly organized. The connections, the layering, etc. etc, make up a complex architecture with specific local function. It would be like saying a chip is jut a bunch of silicon lines. If I hit you in exactly the right place, I could make you lose the ability to understand tones of voice. In another place, you would lose the color aspect of vision. If I separate your frontal lobes from the rest of the brain, I take away your personality.

No, not a bit bag.

In fact, there is a small gap between the axon of a neuron sending a signal and the dendrite of a neuron receiving a signal. This small gap is the synapse.
No, that small gap is the synaptic cleft. The connection between a neuron and its target is called a synapse. Some synapses are chemical, requiring neurotransmitter release from the pre-synaptic cell. Other synapses are electrical, and are the result of direct electrical coupling between cells. Most of the neuronal connections in the mammalian brain are through chemical synapses.

And here is where most of the article and other "Pop Psychopharmacology" goes wrong. (Thank you for the phrase SIGFPE.) Through the rest of this article, neurotransmitters are discussed as if they slosh around in a spongy brain. While there are some cases of "squishy" transmission (Noradrenaline terminals from the locus coeruleus, Dopamine in the striatum), most neurotransmission in the brain is pretty much point to point.

What the re-uptake inhibitors do in large part is keep the neurotransmitter in the synaptic cleft for longer periods. The architecture is such that if transmitter does leave the cleft, it does not diffuse very far away. There is very little purely fluid space in the brain -- even the synaptic cleft is not clear space. There are extracellular matrix molecules, among other proteins.

There's a lot more to bring to task in this article. The two points above are only in response to the very first section. I am not nit-picking. The two mistakes are fundamental and in part they underlie the rest of the problems in the piece. Please don't take this article as gospel -- it isn't.

--
You cannot have a reasonable conversation with someone who regards other people as toys to be played with. localroger
remove apostrophe for email.

Certainly not gospel (none / 0) (#50)
by MK77 on Tue Feb 12, 2002 at 09:42:52 PM EST

Yes, I've comitted the following sins while writing this article:
  • Not knowing much about brain biology before I started
  • Being rigorous about neither my sources nor my conclusions
  • Getting a mishmash of information from Google searches and what I can pick up in the psychology section at Barnes and Noble
  • Writing with an aire of authority I really don't have

That said, I think it is useful for the average person to understand a little bit about brain chemistry -- and as flawed and misleading as the article may be, I think it's at least a starting point. Is there anything in particular you would recommend reading to get it right? Dry, academic texts are okay. Links to Amazon are wonderful.


--
Mmm... rageahol
[ Parent ]

books.. (4.00 / 1) (#52)
by krkrbt on Tue Feb 12, 2002 at 10:35:23 PM EST

You might start with Allen Hobson's The Chemistry of Conscious States or Candace Pert's Molecules of Emotion, for an introduction to peptide chemistry. Peptides are molcules that carry information throughout your body. There are molecules associated with every emotion - happy molecules, sad molecules, angry molecules, ecstatic molecules. Candace Pert was the researcher who isolated the opiate receptor in the mid-70's (which is what allows drugs like Heroin to work their magic). I've only read the latter, and I think it is worth reading for anyone interested. It probably clashes with many K5'ers belief systems, though ("science" & skepticism are a belief systems too).

[ Parent ]
An excellent book. (none / 0) (#61)
by minra on Wed Feb 13, 2002 at 08:08:42 AM EST

An excellent book on the brain, with emphasis on consciousness is:

Enchanted Looms by Rodney Cotterill

It synthesizes a theory of consciousness out of contemporary (1998) knowledge of brain topology, neural networks, neurochemistry, and some behavioral psychology.

This book gets my highest recommendation. If you're seriously interested in the phenomenon called 'consciousness', you must read it. :-)

[ Parent ]

Author recommendations (none / 0) (#62)
by iGrrrl on Wed Feb 13, 2002 at 08:47:46 AM EST

Anything by Joeseph Ledoux. I've read The Emotional Brain, and thought it was very good -- accessible for the non-neuroscientist yet says nothing to make a neuroscientist cringe. His newest one (The Synaptic Self) should be similarly excellent, but I've not read it.

Anything by Damasio is considered controversial at best.

Michael Gazzinaga has a new popular book out that I haven't read. He's more cognitive than chemist, but his credentials are solid, his basic research better than good, and his conclusions more than a little interesting. He's best known for his work with split brain patients -- people who have had their corpus callosum cut to treat intractable epilepsy.

On my website is an essay I wrote for the PSYCHE-D list addressing issues of the supposed neurochemistry of consciousness. Although I originally posted it for another reason, you might find the brief discussion of receptor types and subtypes interesting.

Of your "sins," Writing with an aire of authority I really don't have strikes me as potentially the most embarrasing.

--
You cannot have a reasonable conversation with someone who regards other people as toys to be played with. localroger
remove apostrophe for email.
[ Parent ]

Serotonin Syndrome (4.00 / 1) (#54)
by CaptainSuperBoy on Wed Feb 13, 2002 at 12:22:47 AM EST

This is a decent article, a brief introduction to brain chemistry. Of course this is all very simplified, but we're not exactly reading a neuropharmacology journal here.

One thing that should be mentioned is serotonin syndrome, a serious condition that can result from an abnormally high level of serotonin in the brain. This is most often caused by combining two drugs that act on serotonin, such as an MAOI and an SSRI. If you're taking an MAOI then you already know the dangers, but even if you're not using one there is still a risk. dextromethorphan (DXM) is a cough suppressant that can also get you high. Combining DXM with an SSRI or other serotonin-related drug could cause serotonin syndrome. Since cocaine and amphetamines (including MDMA) can increase serotonin, they can also put you at risk.

This is a potentially serious condition. There are mental symptoms such as confusion and restlessness. There are also muscular reactions, such as twitching and clumsiness. It's rare, but you can die from serotonin syndrome.

I don't pretend to know a lot about it, I just didn't see it mentioned and it is important to know about if you're going to be taking drugs that affect serotonin levels. If someone knows more, please correct me or fill in the blanks.

--
jimmysquid.com - I take pictures.

Not quite right.... (5.00 / 1) (#63)
by bumdass on Wed Feb 13, 2002 at 01:21:38 PM EST

AFAIK, DXM does not affect the serotonin system directly. Instead, it acts on NMDA receptors, overstimulating the cells. The neurons actually begin rupturing and spilling all sorts of oxidants into the brain, so another chemical (sorry, can't remember the name offhand) shuts down the overheating neurons, which causes a waterfall effect, including hallucinations and severe intoxication. This may affect serotonin levels somewhere else in the brain, but DXM does not act upon the serotonin receptors at all.

It takes about a week or so for the neurons to completely heal from this damage. If another dose is taken before the damage is healed, the cells can die. Over time, this can cause serious problems. Mice that are given massive repeated doses of DXM and other dissociative anesthetics develop Olney's lesions (think small swiss cheese-like holes...generally a bad thing to have in your noodle).

While it's not currently fashionable to give massive repeated doses of DXM to humans and then dissect their brains, what is clear is that longtime DXM addicts (all dissociatives are slightly addictive) start exhibiting symptoms of brain damage (forgetting words or grammatical structures, etc).

So, be careful with dissociatives. While you probably have millions of neurons to spare, killing off a few can have SERIOUS consequences later in life. For example, recovery from a stroke occurs when neurons reroute messages around dead neurons, but this depends on the number of working neurons. Kill a few too many, and you're likely to spend the rest of your days as a vegetable (or at least severly disabled).

[ Parent ]
Antipsychiatry (3.50 / 2) (#68)
by acheon on Wed Feb 13, 2002 at 06:57:58 PM EST

http://www.antipsychiatry.com/

SAMe vs. 5-HTP (1.00 / 1) (#72)
by Shpongle Spore on Wed Feb 13, 2002 at 09:39:30 PM EST

You mentioned 5-HTP but not SAMe, which seems to be very similar. It's a smaller molecule than 5-HTP, kind of suggestive of both serotonin and dopamine modulecules, and I imagine your brain will turn it into a little of each. Supposedly it has a very wide range of other biological functions, but I'm no biochemist so I won't go there.

In terms of effect I think it's like non-drowsy 5-HTP, or 5-HTP mixed with Wellbutrin. It's more expensive than 5-HTP (about $1 per 200mg pill), so I use it as a supplement to my 5-HTP intake. It might be a better all-around choice for some people, though.

Damn, I have supplements to my supplements. How sad is that?
__
I wish I was in Austin, at the Chili Parlor bar,
drinking 'Mad Dog' margaritas and not caring where you are

The Geek's Guide to Practical Brain Chemistry | 78 comments (67 topical, 11 editorial, 0 hidden)
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