extraordinary pharmacology

[spectrasonic]

Hi all,
I'm new here and have just registered in order to transmit certain ideas that have been coming together for a while now. You may find the hyperbole a bit much but please bear with me. I'm no pharmacologist and this stuff isn't the easiest to write down. So here goes.....

Spectropharmacology as I call it, is basically Benveniste's "Digital Biology" (a misnomer if u ask me, perhaps Sonic Biology would be better). From digibio.com:

The Current Theory: "structural matching"


The presently dominant QSAR (quantitative structure-activity relationship) theory of molecular signaling claims that two structurally matching molecular objects exchange specific information by mere contact. (Sometimes also refered to as the Key/Keyhole interaction model). Specific molecular interactions happen after random collisions between partners on a trial-and-error basis, using electrostatic, short range (two to three times the molecule size) forces. But this kind of random encounter, amidst the bulk of molecules which are foreign to a given biochemical reaction, would give to these meetings statistically little chance of occuring. Thus, the simplest biological event might require a very long time to happen. This paradox is still unexplained by those adhering to this theory...
The shortcomings of this approach are best illustrated by the now widely-recognized failure of "drugdesign" to produce the expected volumes of new therapeutic substances.
In this context, it is worth noting that the words "molecular signal" are routinely used by biologists, yet receive no precise physical definition.


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The Proposed Theory: "electromagnetic signals"


Using various experimental protocols we are able to activate specific cell functions with the corresponding low frequency (<20kHz) electromagnetic waves. This prompted us to hypothesize that the molecular signal is composed of such low frequency waves and that the ligand coresonates with the receptor pretty much as the tuning of a radio device.
It is important to remark that these concepts do not violate any current biological or physical basic principle. It is well-documented that:
1) molecules emit specific frequencies;
2) a complex set of high frequency waves can produce low frequencies according to the "beat frequency" phenomenon,
3) all biological interactions occur in water, since, on the average, there are ten thousand molecules of water per molecule of protein.
Quantum electrodynamics calls for the existence of long range electromagnetic fields that can be transmitted by large - hundreds of angstroms - coherent domains present in water (adapted from E. Del Giudice & E. Preparata, 1994, Journal of Biological Physics, vol. 20, p. 105). Such long range EM fields would be capable of transmitting the EM message coming from molecules, thus generating a long distance specific attraction between two molecules with matching spectra, excluding non-resonating, unwanted random events. The field resulting from the aggregation of the two coresonating molecules would obviously exhibit a different frequency which would then coresonate with the next molecule or cluster of molecules which intervene in the next step of the biochemical reaction, and so forth and so on... The fact that small changes in the spectrum of a molecule (e.g. induced by a tiny structural change) would profoundly alter its resonating characteristics, would explain how minute changes (e.g. phosphorylation, replacement of an ion by a similar one, switching of two peptides...) radically modify the molecular tertiary structure and function.


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Summary


In summary, the current short range electrostatic theory of molecule interaction-recognition via random collision cannot help us understand how biological reactions really work. The key/keyhole and the structural matching are just cartoonesque descriptions of the exceedingly more sophisticated mechanism which is required to command the extraordinarily complex and rapid cascade of intricate biochemical reactions supporting life. By contrast, the EM interactions afforded by the capacity of water to support long range EM fields provide fascinating possibilities for understanding:
1) the specific and rapid long distance attraction of coresonating mates;
2) how the formation of aggregates with appropriate frequencies initiates the next step in the biochemical sequence;
3) how the steric structure of molecules can be altered or stabilized by subtle changes in their primary composition.

Next I am reminded of a quote from Shulgin:
“A psychedelic drug experience is a complex combination of many signals goingall at the same time. Something like the sound of an oboe playing the notes ofthe A-major scale. ...during the sounding of the note “A,” for example, there isa complex combination of harmonics being produced at the same time... Thismixture defines the played instrument as being an oboe.This analogy applies precisely to the study of psychedelic drugs and their ac-tions.... there are many components of a drug’s action, like the harmonics fromthe fundamental to the inaudible which, taken in concert, defines the drug. Withmuscial instruments, these components can be shown as sine waves on an oscilloscope.... But in psychopharmacology? There is no psychic oscilloscope....Certainly, any eventual definition of a drug will require some such dissection intocomponents each of which makes some contribution to the complex whole. The mental process may some day be defined by a particular combination of these components.”

But suppose Shulgin's wrong and there is a psychic oscilloscope.

Stay tuned.
Much more to come.

 

[Refluxer]

Can you please expand on the proposed theory? :D EM Messages?

What kind of spectras are you talking about? There's nothing new about the idea that small molecular changes also changes absorption spectras and other properties. If you're actually trying to explain something you believe is novel, you'll have to expand your explanation in a meaningful way.

I also don't get what's so mysterious about how molecules reaches their targets.

BTW The key-lock theory was once challenged and the induced fit theory was added to the repertoire.

 

[LuxEtVeritas]

I believe he is sayibng that components in the body communicate with each other over distance that occurs before mere engagement of "key into keyhole"

is this what you are saying in a nutshell?

certainly resonance of some atomic nature that produces a basic 'language' and all that is very feasible

 

[spectrasonic]

OK
To recap: not "locks and keys" but spectropharmacology.
We should be thinking of Spectroscopy-Activity Relationships (SpAR) rather than SARs
Have you ever wondered how a plant like cannabis, for example, is able to contain hundreds of active compounds which function "harmonically" in conjunction with each other, when ingested?
Could it be that they are indeed harmonic in a literal sense both in the plant and the body?

Now let me introduce a different topic: "Wetware hacking"/Cranial Electro-Stimulation (CES)/ Trans Neural Magnetic Stimulation (TMS).
A Dr Patterson did lots of work with CES in the 70s, particularly helping people kick addictions (Pete Townsend). I recall seeing the frequencies for serotonin and catecholamines.
Now what if this frequency was in fact a resonant frequency of the molecule(eg serotonin) itself? Accordingly each (psychoactive) compound's molecular signature would be reproducible by a chord, and each note would correspond to a particular property.
I've seen no work on multiple-frequency CES but it seems to me it would be viable via a soundcard for no more than a few quid.
I can also "see" simple open-source software able to lower spectroscopic data by X octaves and adjust individual frequency components.
I've seen mention online of Hans Cousto's work where he gives resonant frequencies for THC, LSD, and MDMA but I've seen no mention of them used for CES.

A couple of other bits and pieces:

I would expect conformational restriction to result in the removal of certain vibrations. Thus the result would be a subset of the experiential/spectroscopic frequencies. From what I've read 2C-B-fly relative to 2C-B seems to bear this out.

A G-Protein receptor is a coil with 7 turns, so I imagined it was an antenna.

So the two main practical goals of all this info would be the soundcard CES detailed above, but more importantly to this forum:
The designing of molecules so that they possess unique spectroscopic properties.

Stay tuned.
Much more to come.

 

[Ham-milton]

I just can't imagine that any of this will pan out.

And you're taking a lot of stuff that's true, applying a metaphor, and then taking the metaphor as truth, like the g-protein receptor shape actually being an antenna.

Also, another problem with your theory is that it just doesn't make sense compared to the things that we do know about structure activity relationships and receptor binding. I mean, everything we've learned about how the shape of a compound effects it's ability to bind (As in how you can have amphetamine variants that are inactive as DARIs because the substitutents cause it to bend in a way that prevents it from fitting in the receptor) would be rendered false if this were true, though I doubt that.

I also don't know that it's true that these compounds are constantly emitting any sort of frequencies.

What you're talking about with CES and TMS involves radio-type waves, and 2C-B and the other drugs aren't emitting radio waves. If they were, it'd be a hell of a lot easier to detect drugs.

 

[Acyl]

I suppose its a unique way to look at the interaction, but can you really see this revolutionize the process of drug design? (is that your goal?) It seems like a way to just further understand how something that we already can accomplish works. Ofcourse understanding the mechanism of action would be beneficial, but will it change how we go about makin drugs?

How would designing a molecule with "unique spectroscopic properties" be any different from designing ones with unique structural properties? All work done in these fields is based on structure-activity relationships, so really, they are already designing molecules with diff spectroscopic properties by simply changing the structure. We just look at it from a different angle. The structure theory seems to already incorporate what you're proposing.

I like what you mentioned about the conformation of molecules though, could this perhaps be a way to 'rule out' certain analogues?


Im probably overlooking a bunch of stuff that could infact make this theory more useful, though.

 

[Acyl]

He was using the radio wave tuning as an example. All molecules resonate... this is what makes nuclear magnetic resonance and IR spectroscopy work.

 

[spectrasonic]

OK. Next installment.
Funny thing is I've been sitting on these ideas for over a year, and what I've just written is about the sum total of my thoughts on the matter. Then, just yesterday, googling g-protein receptors, I came across the most incredible addition to all of this. This guy, Luca Turin has beaten me to it with much of this stuff, has written massively technical studies on it, (most of which goes right over my head), but, his work is strictly involved with the phenomenon of smell/perfumes/odorant compound design (which is also a g-protein receptor affair) I suggest all you pharmacological types should check out his writings at flexitral.com, then apply these same ideas to psychedelic pharmacology. I would have cut-and-pasted something but its hard to find a good introduction. Apparently there has also been a popular book or two and a BBC documentary on his ideas. (Google "Vibration Theory of Olfaction").

 

[Ham-milton]

Both of those techniques involve inducing resonance by adding energy either with IR or high powered magnets, exciting the compounds to do something they wouldn't normally do.

And re: the spectroscopic properties of compounds- I assume you're talking about the IR spectroscopic readouts like the first on this page. These readouts aren't showing something these compounds are doing all the time, these emissions are induced via special techniques, and so they're not showing you something they're doing in your brain, rather it's just showing you what the compound is. I'm not real good at reading these, but I'm getting the hang of it. They just tell you where things are located, what substitutents are on the structure, and so forth.

I can't find any difference between "unique spectroscopic properties" and "unique structural properties."

My point about molecules not admitting radio waves was that if they're not admitting radio waves (I'll use that term to include all frequencies, which is technically incorrect, since depending on temperature, they're going to admit some radiation no matter what, but the emissions aren't unique based upon what molecule we're talking about)- that there's nothing else for them to emit.

I mean, there's only so many different types of radiation that they can emit, and they've got to emit something for this theory to work.

edit: some of this may be incorrect, I might be a little stoned, and physics isn't something I know tons about. I did take a semester course about particle physics (gluons, muons, electrons, quarks, etc- spin, color, and so forth), but this this sort of thing, I dunno

 

[Ham-milton]

I've actually read Turin's theory a couple years ago, it was interesting, but there wasn't *anything* about it that made me say "yeah, this makes sense" and really, there wasn't even a whole lot that was technical about it- I mean, the guy never even conducted the experiments he said would prove it.

Read Keller and Vosshall, 2004 for a really good explanation of why Turin's hypothesis doesn't make sense.

oh, actually I just found an editorial that talks about how when they actually ran the series of experiments that Turin proposed and claimed would prove his theory true. I didn't finish reading the editorial, and it's been a year since I read the initial paper, but as I recall, not one of the experiments went in his favor.

His theory has been roundly dismissed for a lot of reasons- not least because it doesn't fit with what we already know, and because there's absolutely nothing about it that's been proven.

It's not even a theory, it's a hypothesis with no support.


edit: An addition about a comment made earlier:

Have you ever wondered how a plant like cannabis, for example, is able to contain hundreds of active compounds which function "harmonically" in conjunction with each other, when ingested?

First, Cannabis sativa or Cannabis indica don't contain hundreds of active chemicals. Where do you get this information from??? Cannabis contains a few active chemicals (is it 2 or 3?) and less than a hundred inactive cannabinoids. They don't function "harmonically" each active compound acts on whichever receptor it binds to, as either an agonist, antagonist or partial agonist. In this case, they're weak agonists. Each compound exerts it's effect when it binds- say, a mild psychedelic or mild depressant effect- they're both sent through your CNS, and by the time you can feel it, they've both blended them.

You're taking a metaphor again, and pretending that the metaphor is actually what's happening in order to forward you ideas, but with all the millions of dollars and the technology that's been put into learning what we know today, do you really think that you're going to upset the world of psychopharm with a disproven hypothesis applied to another field where it makes equally little sense?

 

[Acyl]

Both of those techniques involve inducing resonance by adding energy either with IR or high powered magnets, exciting the compounds to do something they wouldn't normally do.

Yeah, you're right.

 

[Refluxer]

Best thread in ADD in a long time.

Hamilton: In NMR the strong magnetic field orient particles, then energy is added with EM radiation (radiowaves).

 

[Ham-milton]

Hamilton: In NMR the strong magnetic field orient particles, then energy is added with EM radiation (radiowaves).

I should have clarified further, you're right, what I said is technically incorrect and incomplete.

This isn't something I know tons about, but isn't the magnetic field and em radiation inseperable? I mean, I assume those magnets aren't permanent magnets are they, and how do you seperate between electromagnets and other forms of em radiation?

Is this a really dumb question? Maybe I should do some more reading about.

Best thread in ADD in a long time.

agreed, lol

 

[vecktor]

my understanding of luca turins theory was that electrons would tunnel through the molecule sitting in the receptor. so the theory is not a huge diversion from lock and key because the molecule still has to be able to get into the active site. this could quite conceivably happen in vivo. electrons definately tunnel through molecules depending on the presence of the correct groups in the molecule which lose the energy to enable tunneling. I haven't bothered looking at the evidence for Lucas theory recently. however he now has a company designing unorthodox fragrances based on his theory and from what I have heard they seem to work.
the electron tunneling energies correspond to the kinds of energies associated bending flexing and other vibrations that we see with IR spectroscopy.
I am not convinced either way but it is very interesting all the same

 

[Ham-milton]

There's an explanation of it here.

It's a wikipedia link and it's awfully biased, probably one of the more biased science-related (excluding creationism!) pages I've seen. Not so much in what it says, but what it neglects to say. The "challenges" section has a one liner that boils down to "some people say this "theory" is false." Even the title of the section is misleading, it's not a theory, it's just a hypothesis.

The biggest flaw in the whole theory, and that makes it laughable, is that it's all based on energies that are emitted under unique conditions, and makes not attempts to explain that flaw.

It's all just based upon IR spectroscopy readouts, right? Okay, now with IR spectroscopy, you're using IR radiation to induce IR emissions. These compounds aren't pumping out IR radiation all the time.

Can anyone explain this? I mean, this guys a biophysicist right, he can't be that big of a moron, can he?

 

[Acyl]

When you look at people through nightvision goggles.. what do you see?

 

[Ham-milton]

I see them giving off IR radiation due to their inherent body temperature (assuming they're alive).

If every molecule was giving off the sorts of spectra associated with the readouts we're discussing, IR spectroscopy would be a hell of a lot easier.

All it'd require would be a set of nightvision goggles.

 

[Acyl]

If every molecule was giving off the sorts of spectra associated with the readouts we're discussing, IR spectroscopy would be a hell of a lot easier.

...what are you talking about? Most molecules vibrate in the infrared range.

All it'd require would be a set of nightvision goggles.

Thats redarded, nightvision goggles simply tell you that something is emitting EMR in the infra-red region. How is that good for analytical purposes? I dont even understand what your post is trying to say ...

 

[Ham-milton]

...what are you talking about? Most molecules vibrate in the infrared range.

And I can't think of a single molecule that doesn't. The issue is why they're emitting ir radiation. It's because they're warm. The warmer they are, the frequency if the emissions increases. It's not some innate property of the molecule.

Thats redarded, nightvision goggles simply tell you that something is emitting EMR in the infra-red region. How is that good for analytical purposes? I dont even understand what your post is trying to say ...

It was a joke, if you couldn't get that, well... enough said.

Let me maybe simplify this: Under normal conditions molecules aren't emitting the spectra you see on the readouts. They're emitting a frequency in the IR range as a function of their temperature- so, at the proper temperatures, two vary different substances may emit the same frequencies. If sort of ir-emission spectra theory of psychopharm was accurate, well, two very different substances could induce the same buzz if they were at the right temperature.

With spectroscopy, most importantly absorbtion spectroscopy, conditions are manipulated in a way that doesn't happen all the time.

I still can't figure out what I'm missing here that makes this theory remotely plausible.

 

[Acyl]

Didnt sound like a joke :s


You cant change the number of vibrational modes of a molecule by increasing the temperature.

And how much can the temperature of your body vary? Not enough to do anything like that I would hope.. and not nearly enough to change the characteristics of a C=O stretch.