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Toxicology
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Gone with the Wind
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Post: #1
Toxicology
10-23-2009 8:18 AM

This thread is for the exploration of potential negative biological effects associated with pheromone testing. Here I'd like to collect experiences of actual negative physical or psychological effects, as well as theoretical speculation as to why some molecules may exhibit toxic effects.

Social effects, like getting beat up when wearing high doses of Androstanone, are beyond the scope of this thread.

Phillipus Auroleus Theophrastus Bombastus von Hohenheim (I love that name! Friends called him Paracelcus for short) expressed the fundamental idea in toxicology when he said this back in the 16th century.

Quote:Alle Dinge sind Gift und nichts ist ohne Gift; allein die Dosis macht, dass ein Ding kein Gift ist.

translation - "All things are poison and nothing is without poison; only the dose makes a thing not a poison."

Too much of anything is bad for you, and the essential question is how much is too much. A couple of examples. If you can eat a pound of salt and keep it down it will kill you. Similarly if you drink a few gallons of water it will upset your electrolyte balance and you will die. Mentally ill people have indeed done such things and died from it. However, both salt and water are essential to our survival, in appropriate doses.

It is normal for a dose-response curve to show beneficial effects at one level, and detrimental effects at another level. Most, and possibly all, chemicals exhibit these properties. One bit of falacious reasoning often used by politicians or policymakers is called the linear no-threshhold hypothesis. This hypothesis holds that if a lagre quantity of something produces a detrimental effect, a proportionally smaller quantity will produce a proprotionally smaller detrimental effect. Above I've given the examples of salt and water where this is not true. Policymakers think they are playing it safe by using this approach, but actually they are just being wrong.

One of the reasons the approach above is wrong is the presence of threshholds for many effects. Let's use the old practice of pressing witches to death for an example. You get a witch lay them down, and pile on bricks until the witch expires. Death is caused by the crushing of the ribs and inability to breathe. Say it takes 300 bricks to achieve this effect. Does this mean if you take 300 people and place 1 brick on each of their chests one of the 300 will die? We don't see that, because the threshhold where the ribs are broken and the lungs collapse is never even approached with a single brick.

Dose response curves vary from individual to individual. What is toxic for one individual may be fine for another. This is a major challenge in toxicology and product liability.

When considering pheromones, we need to consider both psychological and physical effects. For instance, if a smell causes an emotional response there are likely to be physiological indicators, like increased heart rate and respiration.

Intake pathways also bear consideration. It is possible for something to be completely harmless if you smell it, but if it is put onto the skin and absorbed into the blood it might be dangerous or cause other effects.

With that long winded introduction out of the way, here are a couple of observations to get us started.

From Diane in another thread.

(10-22-2009 7:39 PM)Diane999 Wrote:  Stess steroids are corticosteroids. They are released in the body only during periods of prolonged or intense stress. Some of these, if overused or overstimulated, can cause neuronal loss.

This is worth exploring. I experienced such effects during a time of emotional trauma, and looked into them at that time. The physiology of the brain does indeed change under long periods of stress, and the change can be permanent. PTSD and similar disorders are a manifestation of this effect. Questions for our exploration would be if smelling molecules induce similar long term stressors, or lead to heightened blood levels of corticosteroids. Another question would be if putting such chemicals on one's skin as a pheromone product could lead to direct absorption into the blood and potentially dangerous blood levels via that route.

Another tidbit from Diane

(10-22-2009 9:48 PM)Diane999 Wrote:  ...in my experience with some of the "mystery" chemicals, I don't feel some of them are safe at all to use if you have a heart condition or are prone to PTSD reactions. Now that is just my opinion, but also my reaction. P84, P100, P107 are three I can name off the top of my head that I would never use again at any concentration because my own physical reactions were so alarming.

Diane, can you list the observed reactions indiviually by putative? Would you care to speculate as to psychological components of the reaction?

Finally, an observation of experience of Mrs. Gone with a314. I wear this quite a bit and neither I nor she experience negative reactions when it is on me. However, on a couple of occasions when we have applied a drop to her skin, she has experienced anxiety and increased heart rate. Since she does not experience this when she smells it on me I am led to believe that something absorbed through the skin creates this reaction. She finds it uncomfortable and thus does not wear a314 any more. Other than temporary discomfort, no other detrimental effects were observed.

Gone with the Wind

<p align="center">Gate, gate, paragate, parasamgate. Bodhi svaha!</p>
(This post was last modified: 10-23-2009 8:26 AM by Gone with the Wind.)
10-23-2009 8:18 AM
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Post: #2
RE: Toxicology
10-23-2009 8:48 AM

To all three of the molecules listed above I had amphetamine-like reactions and prolonged anxiety. P100 was the worst with a very small dose causing a rapidly overwhelming anxiety response that lasted about 4 hours.

I think that it isn't skin absorption as much as a olfactory receptor binding that is happening here. That would lead to a chain reaction in neurotransmitters in the brain.

For the skin absorption hypothesis, to get any effects like those I noted, you would have to not only absorb the substance through the skin, but also the element would have to pass the blood/brain barrier to get these kinds of anxiety effects. So that is a two level barrier to response. Whereas with a receptor binding element, the response can be almost instantaneous and barriers are not an issue.

Diane
(This post was last modified: 10-23-2009 11:12 AM by Diane999.)
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Post: #3
RE: Toxicology
10-23-2009 10:35 AM

I just checked in with Mrs. Gone on the duration of the anxiety/heart-rate effects she experienced with a314. She said it lasted a long time, perhaps 12 hours. The experiences are a few years old now and we didn't keep notes so take that as a subjective estimate.

The anxiety seems similar to what you are reporting with (possibly) different compounds. Again, the propriatary formulae prevent us from seeing possible commonality.

This leaves us with a puzzle. If, as you suggest, this is an olfactory effect, why does Mrs. Gone not experience it if she sleeps next to me while I'm wearing a314?

We may also consider that sexual dimorphism may play a role. It seems from my memory of reading reports of anxiety/increased heart rate that these effects are more often reported by females. Any speculation as to why this may be so?

This possibility is also at the heart of one of my reservations about blind testing. I am, for instance, reluctant to slather myself with estrogen metabolites and go about my daily life without an idea of what I put on, because the effects (social as well as toxicological) may be quite different on a male vs. a female.

PS - in order to prevent exponential growth in thread length, please trim any quotations to just the part of interest. Otherwize it gets very difficult to find new material in a thread.

PPS - I just thought of an experiment of interest. When I get back to my "lab" in a few days, I may try the 3 products you listed on myself and Mrs. Gone and note the reactions. She, a female who has experienced the anxiety effects before, but from different products, and me, a male who has not experienced such effects. What concentrations produced the observed effects? This experiment is dependent on convincing Mrs. Gone, who doesn't relish reliving the effects.

Gone with the Wind

<p align="center">Gate, gate, paragate, parasamgate. Bodhi svaha!</p>
(This post was last modified: 10-23-2009 10:49 AM by Gone with the Wind.)
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Post: #4
RE: Toxicology
10-23-2009 11:09 AM

I agree that the mystery is that she doesn't react that way when you wear A314, only when she does.

And you are right that there is no telling what is in that product or what exactly caused her reaction. The 12-hour bit sounds like androstanone neg effects, but since she doesn't react that way with you wearing it, who knows? I can't really speculate on that.

But I was referring only to my reactions to the three molecules I mentioned when talking about receptor binding vs. absorption through the skin.

Diane
(This post was last modified: 10-23-2009 11:11 AM by Diane999.)
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Post: #5
RE: Toxicology
10-26-2009 9:18 PM

(10-22-2009 9:48 PM)Diane999 Wrote:  ...in my experience with some of the "mystery" chemicals, I don't feel some of them are safe at all to use if you have a heart condition or are prone to PTSD reactions. Now that is just my opinion, but also my reaction. P84, P100, P107 are three I can name off the top of my head that I would never use again at any concentration because my own physical reactions were so alarming.


What concentrations caused these effects? Right now the only one I have is p84 @ 2.5 mcg/sp. I'd like to experiment a bit with the doseages you used to see if I can pin some things down. I'll put in an order after I get a bit of info.

Gone with the Wind

<p align="center">Gate, gate, paragate, parasamgate. Bodhi svaha!</p>
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Post: #6
RE: Toxicology
10-26-2009 11:43 PM

(10-26-2009 9:18 PM)Gone with the Wind Wrote:  What concentrations caused these effects? Right now the only one I have is p84 @ 2.5 mcg/sp. I'd like to experiment a bit with the doseages you used to see if I can pin some things down. I'll put in an order after I get a bit of info.

P84 gave me adrenaline response with one spray at 12.5 mcg/spray. It wasn't nearly as bad as P100.

This is from my journal 2/5/09:

Quote:5:34 "“ sprayed one spray P84 to chest. No other pheromone.

Soon I get a rapid consciousness shift, feels like someone has grabbed my consciousness and given it a rapid pull to the side, sort of like out of body stuff.

I get a lot of adrenaline body reactions, a rapid exhaustion of epi/norepi, and a bit of a shocky response, feels like glucocorticoid flooding, some mild dissociation, followed by relaxation. My fingers and toes are really cold.

This makes me feel the same as I feel after an unexpected explosive argument, relieved its over, but still suffering from the adrenaline overload. What happens in the body after the emergency is over? This is what P84 feels like.

Mild headache.

As a general rule, I don't do well with anything that garners any kind of adrenaline or amphetamine response. As you may recall, I have ADD. They tried me on Ritalin. I was a total basket case, shaky, uncomfortable, jittery. I get the same sort of response with these few pheromone putatives. TAF, on the other hand, which some people find gives them fight or flight at higher doses, just calms me down and helps me filter out extraneous information.

Diane
(This post was last modified: 10-26-2009 11:53 PM by Diane999.)
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Post: #7
RE: Toxicology
10-27-2009 6:33 AM

Do you remember the dosages you used for p100 and p107?

We should consider the possibility that these physiological reactions are not inate but may be based on previous experiences. That may account for a variability between people.

Most of us are quite aware of the potential for smells to evoke conscious memories. It is not a big jump to hypothesise that they may trigger unconscious memories and unconscious physiological responses. This could be a result of a powerful experience which resulted in "reprogramming" of some neural circuits. Anxiety is often reported, which could be consistent with an earlier traumatic experience. This hypothesis would suggest that the anxiety response would be hard to predict, as it would be based on individual experience. We would expect less uniformity in response than say, response to amphetamines, which work on an inate physiological mechanism. Some degree of commonality could be possible if certain traumatic events shared certain smells. For instance, the rape experience may be charachterised by certain smells and a number of previous rape victims might exhibit an anxiety response to that particular stimulus.

Gone with the Wind

<p align="center">Gate, gate, paragate, parasamgate. Bodhi svaha!</p>
(This post was last modified: 10-27-2009 6:34 AM by Gone with the Wind.)
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Post: #8
RE: Toxicology
10-27-2009 5:32 PM

(10-27-2009 6:33 AM)Gone with the Wind Wrote:  Do you remember the dosages you used for p100 and p107?

We should consider the possibility that these physiological reactions are not inate but may be based on previous experiences. That may account for a variability between people.

Most of us are quite aware of the potential for smells to evoke conscious memories. It is not a big jump to hypothesise that they may trigger unconscious memories and unconscious physiological responses. This could be a result of a powerful experience which resulted in "reprogramming" of some neural circuits. Anxiety is often reported, which could be consistent with an earlier traumatic experience. This hypothesis would suggest that the anxiety response would be hard to predict, as it would be based on individual experience. We would expect less uniformity in response than say, response to amphetamines, which work on an inate physiological mechanism. Some degree of commonality could be possible if certain traumatic events shared certain smells. For instance, the rape experience may be charachterised by certain smells and a number of previous rape victims might exhibit an anxiety response to that particular stimulus.

12.5 mcg/spray - 1 spray ea.

Smell? These had no discernable smell, and no.. this was a purely physical response to the chemicals, not an emotional or "evoked" response.

Occam's Razor... sometimes a cigar is just a cigar.

Diane
(This post was last modified: 10-27-2009 5:35 PM by Diane999.)
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Post: #9
RE: Toxicology
10-27-2009 9:06 PM

Thanks for the dosage information. I just placed an order to get the p100 and p107.

Mrs. Gone applied 5 mcg p84 to the skin of her neck today and there was no discernable anxiety response. She'll try a higher dose tomorrow.

By smell I meant any chemical input through the nose. Some of the stimuli I called smells may not be consciously perceptible.

It is not always easy (or perhaps sometimes even always possible) to distinguish between responses with a psychological component and purely physical responses. Hence double blind experiments with placebo controls. If psychological responses could be easily sorted out experimenters wouldn't have to go to all that trouble. The presence of feedback loops between our chemestry and our psyche also complicates things. A psychological change can cause a chemical change which can then cause a physical change in the brain, which may affect our psychological state, which...

Gone with the Wind

<p align="center">Gate, gate, paragate, parasamgate. Bodhi svaha!</p>
(This post was last modified: 10-27-2009 9:20 PM by Gone with the Wind.)
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Post: #10
RE: Toxicology
10-27-2009 11:51 PM

(10-27-2009 9:06 PM)Gone with the Wind Wrote:  Thanks for the dosage information. I just placed an order to get the p100 and p107.

Mrs. Gone applied 5 mcg p84 to the skin of her neck today and there was no discernable anxiety response. She'll try a higher dose tomorrow.

By smell I meant any chemical input through the nose. Some of the stimuli I called smells may not be consciously perceptible.

It is not always easy (or perhaps sometimes even always possible) to distinguish between responses with a psychological component and purely physical responses. Hence double blind experiments with placebo controls. If psychological responses could be easily sorted out experimenters wouldn't have to go to all that trouble. The presence of feedback loops between our chemestry and our psyche also complicates things. A psychological change can cause a chemical change which can then cause a physical change in the brain, which may affect our psychological state, which...

I'm not sure why you are splitting this this way. Do you believe that any or all pheromonal response is no more than conditioned psychological response, or is it that you believe only my response is conditioned? And what would you base this theory on? Many people do believe that all pheromone response is nothing more than placebo effect. Those people don't wear pheromones.

But let's assume that pheromones do work on a physical system state. You do understand that people have different chemical reactions to things that affect the physical systems of the body? That is why there is a response curve to medications and such. Pheromones, if the pheromones are receptor binding and activating substances, would behave the same way.

Take copulins for example. My theory is that they are mainly ionic-type AMPA receptor binding molecules that begin neurochemical cascades in the body, which turn on Nitric Oxide production, and glutamic acid release, and which also stimulates GABA-A release. To my knowledge no one has done the research on copulin fatty acids on humans, but the animal studies are full of very exciting information, which clearly shows these system changes with increased blood flow, increased excitement, and increased production of testosterone (in males) and progesterone in females, increased LH production, etc..

But, for example, if someone had a faulty NO production pathway, inhaling copulins all day long won't have any effect on NO levels in the body, hence no increased in erection strength (or in erections), no increased blood flow, no increased excitement levels, no increase in LH production and testosterone, etc. These people would tend to be diabetic or have kidney disease or erectile dysfunction, high blood pressure of unknown origin, or some other condition affection NO production capability, including medications which block this or associated substance binding receptors.

There are also variabilities in receptor structure based on genetic variability, hence our individual differences in response to antidepressant medications, etc.

Do you see where I'm going here? All this variability and taking medications potentially affects the way that an individual responds to receptor binding substances, or even if a substance binds at all or creates a response if it binds.

Diane
(This post was last modified: 10-28-2009 12:12 AM by Diane999.)
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