Post: #11

I do see where you're going with your argument.

I see 2 major possiblities, and at this point don't necessarily believe either. But I do think both should be explored. The truth may even be a combination.

My personal explorations lead me to believe that there is more than placebo effect operating with pheromone responses. (I agree with you that probably most of us here do, or we wouldn't be wasting our time here.) It seems likely that there is both a psychological and a physical component to pheromone responses. For instance, take Androstanone response in human females. It seems to vary both with phase of the menstrual cycle (physical) and with the sexual experience of the woman (psychological).

One of the major impediments to pheromone research is the tendency of humans to reject hypotheses for ego-related reasons. That is why most researchers were reluctant for so long to admit any pheromone effects on humans, although they readily acknowledged the effects in other mammals. People did not want to believe that they were influenced in that manner. Many still don't, but the weight of evidence is starting to pile up and the scientific consensus is changing.

We shouldn't fall into the same errors of rejecting hypotheses based on ego instead of on evidence, especially in such an important consideration of negative toxicological, or other, effects.

As we learn more about the physiology of the brain and the endrocrine/neurotransmitter systems, the distinction between psychology and physiology becomes more and more blurred. For instance, "shell shock" was once thought to be purely psychological, possibly a character defect. Now PTSD is acknowledged to involve physical changes in the brain in response to trauma or long periods of stress. As our knowledge develops the term "psychological" may just boil down to a shorthand for distinguishing which responses are more shaped by environment and experience, as opposed to genetics.

Post: #12

Mrs. Gone applied 12.5 mcg p84 to her neck skin today and reports no anxiety response. This duplicates the dosage reported by Diane as producing the anxiety effects in her.

Mrs. Gone has experienced anxiety effects from a pheromone product before. Just not this one at this dose.

Post: #13

Many people have different responses to different pheromones. Some steroid pheromones studied seem to have a bimodal bell shaped curve regarding physical response which also seems to be dose dependent. Others seem to have opposite effects on different people. And some people have no response to some pheromones.

I think it is a dead end to try to fit limited data to a psychology reason. For one thing it is human nature for us to try to explain things in a way that makes sense to us personally and reduces anxiety about the unknown... even if there is no data to support it.

But, "It doesn't fit my personal experience, so it must be psychological" is akin to saying, "I don't know what the sun is, so it must be a god." It a comfortable trap that reduces anxiety about the unknown, but also deadens desire for any real research.

There is no data to support that every person will respond the same way to any pheromone, in fact the opposite is the case, and I'm certain you have seen evidence of this on the other forum. If you read the literature and look at the actual data breakdown you will see that there are is quite a lot of variation in response, even with pheromones that are well studied.

From the forum:

Warren is an example of a person who does very well with molecules that I have aversive reactions to, including P84. He finds P87 to be an empathogen, while I (and others) find the exact opposite to be true, and find the reaction to this one to be to turn off the emotions and leave a cold, clinical, reptilian signature.

Most people find P83 to be flirty and impatient. Others find it evokes aggressiveness and irritability, including explosive rage in a few reported instances.

Some people can't wear TAF at even low dose without getting a fight-or-flight response, and most can't tolerate a high dosage. But I've worn it at 60 mcg and higher many times with only good results. Xiphoid is another that finds high dosage of TAF to be beneficial.

Tisha loves to mix P74 with TAA and Androstenone. For me mixing the three together is an absolute disaster. I have little tolerance for TAA or Androstenone.

Some people find Beta Androstenol at high doses makes them too introspective and prevents sleep. Others find that high doses of Beta Androstenol shut off thought and leave one in a mystical state.

Tisha and a few others don't tolerate Methoxyestratetraenone well, and it gives her and them nightmares. Methoxyestratetraenone for many women is a very nice sensual molecule.

Gegogi gets very few self-effects from any molecules, but sees his pheromone usage affect others.

Personally, out of those that I've tested extensively, I find EST, Methoxyestratetraenone , TAF, TAC, Alpha Androstenol, Beta Androstenol, Androsterone, P78, P79, P80, P90, P102, and P103 to be my favorites and all very useful.

I don't tolerate TAA, Androstenone, P83, P84, P86, P87, P100, or P107 well at all, some at high doses, some at any dosage.

Out of all of these TAF, P84, P90, P100, and P107 are stimulatory. TAA and P86 hit the visual cortex and in a broad sense are stimulatory. P86 becomes definitely stimulatory for me at high dosage. It doesn't give me an anxiety response, but it does impart an amphetamine-like response for me at high dosage.

However, I would like to point out that extremes in childhood environments can and do change the physical nature of the brain on a micro and macro scale, as does single incidents of extreme trauma in adulthood. In this regard you could "loosely" attribute some physical responses to psychology. But the responses themselves would still be physical.

Diane

Post: #14

(10-28-2009 9:09 PM)Diane999 Wrote:  Many people have different responses to different pheromones...

If you read the literature and look at the actual data breakdown you will see that there are is quite a lot of variation in response, even with pheromones that are well studied...

I don't tolerate TAA, Androstenone, P83, P84, P86, P87, P100, or P107 well at all, some at high doses, some at any dosage.

I'm sold on the idea that there is considerable individual variation in response to pheromones.

The quote below led me to believe you thought some pheromone products had a greater chance of causing negative and possibly dangerous effects in others.

(10-22-2009 10:48 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.

Your warning implies that there may be a commonality of effects between what you experienced and what others may experience. To determine whether the warnings are warranted we should look into just how common the experience is. Or, if perfumes, sounds, pictures, etc., can create similar effects then one might consider the possibility the effect is information dependent, and since warnings against all information are not very feasible, approach the issue from a psychological perspective instead of a toxicological one.

Since Mrs. Gone experienced a similar reaction to the one you described, but to a different product, having her try the products you tried was of interest to us. If she reacted the same as you did, it would increase my faith in the applicability of your warning to members of the general population. The fact that she did not respond as you did (so far) does not indicate that your warning is incorrect or unwarranted. But my faith in it has not increased.

Post: #15

(10-28-2009 10:06 PM)Gone with the Wind Wrote:  The quote below led me to believe you thought some pheromone products had a greater chance of causing negative and possibly dangerous effects in others.

(10-22-2009 10:48 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.

Your warning implies that there may be a commonality of effects between what you experienced and what others may experience. To determine whether the warnings are warranted we should look into just how common the experience is. Or, if perfumes, sounds, pictures, etc., can create similar effects then one might consider the possibility the effect is information dependent, and since warnings against all information are not very feasible, approach the issue from a psychological perspective instead of a toxicological one.

I do believe that some substances should be used with extreme caution (and some shouldn't be tested at all) in some subset of users because of the potential for negative consequences. That doesn't mean that I believe every person would have the same risk factors.

I don't think that it is reasonable to put people at risk for potentially serious consequences without fair warning. Drugs are taken off the market every day because of a few serious adverse reactions in very few people.

I know that pheromones are not classified as drugs and we testers have to be very careful about bringing down the FDA's attention to this. But pheromones are psychoactive substances, and many are also produced in the body as neurochemicals.

(10-28-2009 10:06 PM)Gone with the Wind Wrote:  Since Mrs. Gone experienced a similar reaction to the one you described, but to a different product, having her try the products you tried was of interest to us. If she reacted the same as you did, it would increase my faith in the applicability of your warning to members of the general population. The fact that she did not respond as you did (so far) does not indicate that your warning is incorrect or unwarranted. But my faith in it has not increased.

My statement was a warning to a subset of pheromone users, not to the general population. I see that you took it as a blanket statement applicable to all, even though my quote above states, "if you have a heart condition or are prone to PTSD reactions."

If your wife is prone to PTSD-type reactions or if you had identified some commonalities between your wife and myself, such as ADD or some other factors, the premise for your logic might be more sound. But as it stands, I can't see how comparing her reaction and mine can give you any information except that our reactions are different. There isn't enough information to draw any conclusions.

And another issue here is the nature of these two specific substances... A314 and P84. Both are unknowns, but each is very, very different. I have never worn A314, so there is no bases there for a comparison of your wife's reaction to mine. If you want to compare her reactions to mine, here is a partial list of my reactions:

Androstenone - extreme muscle spasm and anxiety at any dose
Androsterone - mild euphoria and sensual feelings
Alpha Androstenol - giddiness and chattiness
Beta Androstenol - serentity, trust, relaxation
TAF - Focused and fine tuned, high dose promotes trust from others and high value for information from strangers
TAC - increases lower body tension, increases healthy muscle tension while decreasing neurotic muscle tension
P78 - extreme sensuality
P79 - random thoughts at light speed, random changes in emotions, interest
P80 - promotes feelings of strength and justice, powerful and energetic
P83 - pissy irritability, prone to thoughtless actions and speech
P84 - amphetamine like and caffeine overdose like
P86 - stimulates visual cortex and seems to dilate the eyes, at high dose is amphetamine like and akin to low dose LSD.
P87 - totally shuts off emotions and feelings of connection to others, lizardlike and analytical, cold
P90 - extremely motivational, organizational, and driven, almost compulsive need to get stuff done, causes sleeplessness
P91 - suppresses appetite, slows reaction times way down and causes some clumsiness, interferes with short term memory
P93 - motivational, not organizational
P100 - extreme caffeine overdose like reaction
P102 - hypnotic
P103 - hypnotic
P107 - fidgety, motivational but not organizational, restlessness and neck/shoulder muscle tension (painful), sleeplessness and difficulty focusing my eyes.
Instant Female Magic - no response

Diane

Post: #16

That is great data, Diane. You have been very dilligent in your note taking. You are also very responsive to these substances. I have noticed very few self effects, and the ones I did notice were very subtle and dissappeared after the first few usages. The effects were so minor in me that I was not inspired to take detailed notes.

Your data, and the widespread reporting of self effects on the AD forum, indicate that there are many people much more responsive than I am.

A key element as we consider the possible toxicology of pheromones is "what indicators do we use?" or when do we acknowledge toxic properties. I don't have a good answer but perhaps we should explore the issue.

As you note, potential new drugs undergo a much higher degree of testing. Usually on animals first, then on humans. Drug companies and researchers under their influence have been called on the carpet for misbehavior like excluding people with heart conditions from their research group, but not reporting that exclusion in their result. Predictably, when the drug in question hit the market, effects were seen in people with heart disease that were not seen in the preliminary study, because that element of the population was secretly excluded from the study.

There are a few differences between most pharmaceuticals and what we are investigating. One of the biggies is that we do not have the budgets or the resources of pharmaceutical companies. Another is that most drugs have chemical effects through getting in the bloodstream, either through the skin, inhalation, ingestion, or injection. Pheromones seem to work by triggering sensory neurons of some kind and sending specialized information to the brain for processing. Humans respond differently than pigs or insects, I believe, because of the involvment of cortical processing functions in addition to the lower functions found in insects and swine.

So, some big questions in front of us, and ones you personally may wish to confront quickly if you are going to distribute knowns or unknowns to people are:

1 - Do we need to be concerned with alergic reactions to either carriers or the chemicals in them?

2 - Do we need to be concerned with psychological reactions. (For instance, the agression response triggered in some males when wearing Androstanone. I've seen this one in others when I was wearing the Androstanone. There may be a chemical/physical basis in there somewhere, but it is easiest to talk about such responses as psychological, since they have a strong processing component to the high-level reaction.)

3 - If a single user reports reactions that could be dangerous to a subset of the population, how should that be dealt with? It could be a highly personal anomaly, or perhaps due to what was eaten for breakfast, or it could be a legitimate indicator of probable danger.

You make some very good points in your posts above, that lead me to believe that any type of precice toxicology is unlikely given our limited resources and the variability of response to pheromones. Given that perhaps another approach to protecting people should be considered.

1 - Warnings and acknowledgement of risk. Let people know that certain reactions like the ones in your list have been ovbserved, that research on the toxicology has not been done, and that the user must assume the risk of potential reactions. This would be a general warning for all products, not particular to one in which a reaction happens to have been observed. It may be good to document the acknowledgement and acceptance of risk. Both types of risk should be addressed. Physical effects on the user, like increased heart rate, and psychological reactions in others that could affect the user, like getting beat up or raped by a strongly responding individual.

2 - Exclusion of certain elements of the population from the experimentation with all pheromone products. Exclusion would be based on identification of conditions that might, in conjunction with possible reactions, increase risk to that subset of the population. You've noted PTSD and heart conditions. There may be others also. Perhaps we should brainstorm on other limiting conditions. This widespread exclusion might be justified based on the difficulty of even knowing that .01 % of the population is going to experience increased heart rate increase with a given unknown.

This approach acknowledges that risks may exist that have not been quantified, and takes a certain care to minimize the negative consequences and let people know what risk they are exposing themselves to.

There is a lot of value to a discussion of what is reasonable, given the potentials for risk and liability. Several perspectives are better than one. This is a much bigger issue for larger manufacturers and distributors of pheromone products, because they deal with larger populations and have deeper pockets. I don't see any of them addressing it.

In your personal case as you make decisions on manufacture or distribution and how you deal with these issues, decisions are entirely up to you. Any discussion here can be taken for what it is worth. These considerations affect all of us us to a greater or lesser degree as we involve others in our own personal experimentations.

Post: #17

I just want to address one part of this at this time. This will be lengthy... my apologies.

(10-29-2009 8:05 AM)Gone with the Wind Wrote:  [...]Another is that most drugs have chemical effects through getting in the bloodstream, either through the skin, inhalation, ingestion, or injection. Pheromones seem to work by triggering sensory neurons of some kind and sending specialized information to the brain for processing. Humans respond differently than pigs or insects, I believe, because of the involvment of cortical processing functions in addition to the lower functions found in insects and swine.

We don't know that what you have stated above is fact. And even if it is the case that these only bind/stimulate receptors, that does not rule out the possibility for negative consequences.

Understand that the neuronal surface cell receptors in the olfactory canal are part of the nervous system. They are expressed on the surface of the olfactory mucosal surface (and on the epithelial surface of the lungs), and are therefore not protected by the blood/brain barrier, but rather are exposed and vulnerable to the outer environment. Yet their neuronal bodies are in communication with and affect neurons that are protected by the blood/brain barrier.

The definition of a receptor is a molecular structure in a cell or on the surface of a cell that allows binding of a specific substance that causes a specific physiologic response. In the case of nerve cell surface receptors, the specific physiologic response will be either inhibitory on the nerve or excitatory on the nerve, inhibiting or enabling the release of specific neurotransmitters from that nerve cell, which in turn changes the "state" of nerve cells with which it is in communication (which are many).

AMPA receptor is one such neuronal receptor found in the olfactory passage - This is an ionotropic receptor. It binds ozone and other ionic substances. In people with allergic disease the binding of ozone results in an increased activity of sensory nerves in the upper airways with a subsequent increased release of neuropeptides. In addition to the known ozone-induced release of proinflammatory mediators, these mechanisms may explain the increased responsiveness of patients with hypersensitive airways.

AMPAr binds 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine which is an anticonvulsant drug. It binds certain axiolytic drugs which act as modulators on this receptor. It binds certain diuretic and antihypertensive drugs. Certain modulating compounds which bind to this receptor have memory and cognitive effects (both positive and negative).

AMPAr also binds Glutamate, which is the main excitatory neurotransmitter released by nerve cells. AMPAr also is inhibitory on Glutamate release under certain conditions. In the nose AMPAr binds ionic substances like ozone, volatile fatty acid butyrate and propionate, and free protons (H+).

NMDA receptor is another neuronal receptor expressed in the olfactory passage. It is also an ionotropic glutamate receptor. The loss of NMDA receptors through aging is implicated in the characteristic chronic anxiety and restlessness seen in Alzheimer's disease. In the nose NMDAr binds the antagonist (inhibitory) hallucinogens and anesthetics and dissociative recreational drugs, causing the inhibition of glutamate release.

Over activation of either of these receptors with glutamate or a glutamate analog (such as aspartate) on these receptors causes excitotoxicity which in turn causes all the post synaptic nerve cells to be damaged or destroyed. Any substance that strongly increases the release of glutamate in neuronal tissue can have this affect if it binds to either of these two receptors.

nACh (Nicotinic acetylcholine) receptors express on the surface of the bronchial epithelium. These are activated by nicotine, where it is mainly excitatory on these neurons.

G-Protein Coupled Receptors (GPCRs) are the main receptors involved in odor detection. They are "slow" activators of neurological response either through cAMP or phosphatidylinositol pathways. They have binding affinity to pheromones, hormones, and neurosteroids. Most classes of these surface receptors mainly bind axiolytic and anti-halucinogenic substances which down-regulate NMDAr and AMPAr excitability, but certain subtypes of this class of receptor are excitatory on NMDAr and AMPAr. GPCRs also bind serotonin, GABA, Bombasin, Dopamine, epinephrine, norepinephrin, oxytocin, and Glutamate. (Serotoin and bombesin are components of vaginal fluid from secretions via the Bartholin's gland.) These receptors are involved in immune and allergic response as well. Blood pressure, heart rate, and digestive processes are controlled through nervous system transmission via GPCR pathway regulation of both the sympathetic and parasympatheic nervous systems. GPCRs down regulate when they are overexposed to their activating substances and that produces desensitization to the activating substances.

GPR30 is a G-Protein Coupled receptor that is expressed in the nasal passage. This receptor binds 17b-Estradiol in the presence of a fixed concentration of progesterone, which causes a 3-4 fold increase in the release of LH. LH increases progesterone and testosterone production. R-carvone, a component of spearmint essential oil, when binding to this receptor increases LH release by 1000 fold.

GABAA receptors are found in the olfactory nasal mucosa. GABA is the main inhibitory neurotransmitter in the central nervous system. In addition to binding GABA, GABAA receptors also bind benzodiazepines, nonbezodiazapines, barbiturates, ethanol, inhaled anaesthetics, and neuroactive steroids. Binding of these substances to GABAA receptor produces either anti-anxiety effect or sedation.

Androstandiol (5a-androstan-3α-ol-17b-ol) also binds and positively modulates GABAA receptors (Frye et al., 1996) with potent anxiolytic (anti-anxiety) and anticonvulsant activity (Frye and Reed, 1998; Reddy, 2004ab), and Androsterone has similar activity (Kaminski et al., 2005)..

Allopregnanolone (5a-pregnan-3a-ol-20-one) and allotetrahydrodeoxycorticosterone (5a-pregnane-3a,21-diol-20-one) are also positive modulators of GABAAr (Puia et al., 1990) and have anticonvulsant (Rogawski and Reddy, 2004) and anxiolytic (Rodgers and Johnson, 1998; Bitran et al., 1991; Finn et al., 2003) activity. Alpha Androstenol is a positive modulator of GABAA receptors comparable to the ones mentioned above (Rafal M. Kaminski, Herbert Marini, et al 2006).

Pregnenolone sulfate and DHEA sulfate also bind to GABAA where they act to block and inhibit the action of this receptor. Blocking and inhibiting this receptor may cause anxiety and restlessness.

There are many, many other surface receptors, some involved in cell repair, some involved in immunologic response, some involved in sensory modulation. The point is each of these, when activated, start chain reactions that grossly affect the whole person.

And we've just begun to classify all the receptors found on the mucosal surface of the nasal cavity and the lung. Over 400 have been identified in the nose. Most of these identified receptors are still considered orphans, meaning the binding substances have yet to be found and of course their activity is unknown.

Diane

Post: #18

Wow! Thanks for the education Diane. That was a lot of work to type.

That is just a glimpse of an incredibly complex model. People working from a model are at a great advantage when choosing hypotheses to test. People blindly grabbing things and testing are unlikely to stumble upon the correct questions, much less their answers.

We shouldn't lose track of the fact that they are models though. I think it will be beneficial to shift between the molecular level receptor theories you've expressed here, and other models. Different models may point to different questions of interest. And once something has been discovered, it may have implications for multiple models. For instance, if you figure out humans are sensing something, you may start looking for the receptor mechanism. You'll continue to see me referencing psychology, evolutionary biology, information type models, etc. Please don't interpret that as discounting a favored model.

I'm convinced no model is "right." We can make accurate predictions with quantum mechanics. But as the systems get more complex, the calculations get harder, and finally impossible. But we can look at another level and use rules of chemistry. For other phenomona we may wish to use a gravitational model, which neither chemistry or quantum mechanics address.

Those preliminaries aside, what you've written is very interesting. You've given some indication of references, which I don't have time to follow up even if they were complete. Has this research been done on humans? It's looking like there are some strong pointers towards molecules of interest. Also intriguing is the possibility that other chemicals may enhance an effect they don't themselves produce.

As far as toxicology goes, do we have indications of strengths of effects? For instance, aromatherapy people will affirm that some smell has a calming effect, but the effect is likely very subtle and may not calm a highly agitated individual the way an injection of a sedative would. I wonder if there are feedback loops limiting the strength of effects produced through these neural mechanisms. It is very possible that effects from stimulation of the nervous system and subsequent activation of natural bodily systems would have such evolved negative feedback loops that would be entirely bypassed by injecting chemicals into the blood, etc. This could tend to make effects produced by neural stimulation less hazardous than many pharmaceuticals.

I've been very busy this week and only able to snatch moments in the morning and evening for this interaction. I've been looking forward to those moments.



PS - is this a typo?

(10-29-2009 3:48 PM)Diane999 Wrote:  (Serotoin and bombesin are components of vaginal fluid from secretions via the Bartholin's gland.) ...

Post: #19

It wasn't much of an education if you still think this is just a model or a theory. That is what they do in "soft" sciences (yeah) like psychology. I have serious issues with psychological studies and the science behind them, especially when they are not backed up with hard evidence of biologic functioning.

This is hard core, down to it, basic human biology. A lot of very well trained scientists worked very hard and are continuing to work very hard to elucidate the function of of these and other receptors. And the information I provided, none of those receptors are theorized to function in those ways. They were shown to function in those ways. There is a difference. I specifically did not include any receptors that have not been elucidated.

All this information is about human beings. I specifically did not go to any animal references because I know you believe that biological processes in "animals" are not relevant to humans, even though many of them are identical in every way.

I tried to simplify the information to make it easily understandable. I guess I didn't do such a good job there.

I may spend some time to try to give you a basic neurology lesson later if I can find the time. I think if you understand better how nerves in the central nervous system work, you will better understand the function of these neuronal surface receptors and how they work when stimulated with an agonist, antagonist, or partial agonist or partial antagonist, or how their function is different when different binding sites are stimulated. But even a simplified lesson is quite complex. Add to that that these systems work in tandem or opposition and modulate each other in complex ways and it can become confusing if you don't have the background.

Meanwhile, you can look up any of this information in the human genome library for each class of olfactory mucosa receptors. Or just google any of them and you should come up with about 56,000 hits for each one. Wikipedia, although often wrong, does usually list a ton of papers at the bottom of each article. Search wiki for each of these receptor types and you will find some of the information you are asking about.

Go find them if you want the references. They are as easily accessible to you as they were to me. I've already spent a huge amount of time to just search and compile the (partial) list for you. And I really don't have the time to do this further for you right now.

Serotonin and bombesin are components of human vaginal fluid via excretion from the Bartholins gland. No that is not a typo. These may have only local tissue effects, but considering there is a fully functional receptor for these substances in the nasal mucosa of humans, they may also play a role in chemical phero-signaling. No research that I know of has been done on this subject in humans to date.

The Bartholins Gland is actually an endocrine gland, the only one ever discovered that is also an exocrine gland. It produces Serotonin, Bombesin, and Calcitonin.






etc.

If there is a pheromonal function to these substances, they would function to shut off hunger in those exposed to them.

In animals studied to date (I know... gasp, huh?) exposing an organism to these substances causes them to seek out others of their species for mating. All energy that was formerly spent in searching for food now goes into producing young. If you google search serotonin + pheromone you will find studies where animals ranging from flat worms to fish were experimented on all giving the same results. Expose an organism to exogenous serotonin (in the environment) and they will stop eating and start mating.

Serotonin is one of those substances that if you overexpose a human at too high a dosage would cause excitotoxicity and death. This is called serotonin feedback syndrome, or serotonin syndrome, or serotonin storm, or serotonergic syndrome. Google any of those to find information on the mechanisms of action.

Diane

Post: #20

A few points.

1 - I look at all human conceptualization as modeling. I used examples from the "hard" sciences like physics and chemistry to try to illustrate this. People accept that the simple Netownian law of gravitation is just a model with limitations, but as we build more and more complex models often everyone loses sight of the fact that they are models and not reality. This limits flexibility of viewpoint and often prevents people from seing beyond the limitations of the model. I'm all for conceptual models, I just like to see them recognized for what they are. My thoughts on this have been heavily influenced by meta-model that was fleshed out in .

2. I consider any time you spend in this interaction as a gift. Please don't get too pissy about time spent. Just give what you want, and take what you want. I appreciate whatever appears, as I find your thoughts quite interesting.

3. Many of your guesses or declarations about what I think are wrong. If you want some thoughts clarified, your easiest approach is to ask me about them. [ie. "I know you believe that biological processes in "animals" are not relevant to humans"]

4. Thanks for clarifying your typo. I thought you were probably trying to type "serotonin." You may want to go back and fix the spelling error as I think many people may be using your post above as a reference, and they could be confused by that inadvertant slip of the fingers. I make lots of spelling errors. I bring this particular one to your attention because misnaming the molecule may misrepresent your intended meaning.

5. My thoughts about negative feedback loops were inspired by considering various self-limiting processes in our bodies, like the production of natural opiates in the system when running. People don't OD from these like they do from opiates injected into their blood. Thanks for the information on serotonin storms. Are you claiming that such storms can be precipitated just by stimulating olfactory nerves? One could do it by snorting cocaine but that is changing blood chemistry in a gross manner, as opposed to initiating a natural process by stimulating receptors primarily in the mucosa of the respiratory tract.