In the book He Drank and Saw the Spider, a poison is talked about in a metaphorical way: A person can be poisoned by putting a specific kind of spider into their cup, but the poison only works if you drink and then see the spider. If you don't see the spider, then nothing will happen.
The book used it as a metaphor, but how could a poison like that exist, where it only works if you know you've been poisoned?
The book is fantasy, with magic being a thing, but it is very rare in the universe.
When you are startled, it causes a physiological reaction. Make the effects of the startle reflex a necessary aspect. I know it can make your heart race, and probably dumps adrenaline or something.
So the ingested toxin, after it has time to get into the blood, but before it is cleaned out, needs the victim to have an adrenaline dump event. That’s why it’s associated with the empty cup — to get the timing right.
The toxin can be activated by adrenaline or other hormones associated with a fright, changing form and becoming the actual toxin; or it jams the receptors that are now in-use because of the startle, or any number of variations. So use one that’s properly metaphorical; e.g. by jamming the receptors he is literally scared to death.
It could be a drug developed for use in aversion therapy or extending the fight-or-flight reaction boost in soldiers. But overdosed or used on someone who is in less than ideal health, it’s fatal.
If you are looking for a purely mind-activated poison then you are not likely to succeed, no.
However, if you can make the subject think they have been poisoned by a particular substance, and this forces them to take an action to counter that poison, then you have a pretty much open playing field.
Two scenarios then...
Either the poison is a two component poison, and the antidote in combination with that which was ingested triggers the reaction.
Or the antidote is in fact toxic if an the actual toxin is not present. Some nerve agent antidotes can work this way.
Do note that in both cases it is not necessary that you have been truthful about what substance the victim has ingested, or even if they actually have ingested it or not. You only need to make them believe they have.
The spider secretes the poison, but contains the antidote.
If you drink the drink and see the spider, you're unlikely to decide to consume it. If you don't see the spider, you would most likely just consume the spider as well, ingesting both poison and antidote.
You are probably looking for a nocebo.
The nocebo effect is when a negative expectation of a phenomenon causes it to have a more negative effect than it otherwise would. A nocebo effect causes the perception that the phenomenon will have a negative outcome to actively influence the result. Mental states such as beliefs, expectations and anticipation can strongly influence the outcome of: disease; experience of pain; and even success of surgery. In the narrowest sense, a nocebo response occurs when a drug-trial subject's symptoms are worsened by the administration of an inert, sham, or dummy (simulator) treatment, called a placebo
I can confirm it works: when I was still at the university there was a fellow student who was paranoid about being poisoned by breathing organic substances we used in the lab.
One day, to play him a prank, we wrote on the whiteboard "organic cabinet has been opened" (it was normally under vacuum, as the organics we used where pretty reactive with oxygen and moisture) when he was in the testing room. As soon as he came out and read the whiteboard he started feeling sick and had to be accompanied to the ER, where despite we told the doctors it was only a prank and no substances were present in the lab he insisted in being unable to breathe properly.
The poison is lower density, and thus at the top of the cup. You drink this first.
The antidote is much higher in density, and thus sits at the bottom of the cup. This will only be drank if you finish the cup.
If you see the spider (wives tale or not), you aren't finishing that drink. You don't drink the antidote.
edit Just for fun, here is a picture of a cocktail I helped develop a few years back. The little balls are spherized chocolate liqueur. They are sitting on top of a dense white chocolate liqueuer, on top of which is a white spirit/liqueur mix, the higher alcohol content makes this much less dense. There is an invisible line (because they are both clear) that can only be seen if you have it at the correct angle, or if you rest tiny chocolate spheres in between the two liquids. The top mix is as clear as the bottom liqueur, but because we shake with ice, it creates condensation on that part of the glass if left in a warm room to take photos. Drinking does not mix the liquids. Stirring does.
This is not my photo, but it is the same drink.
JDługosz had a good idea by using the startle reflex to cause chemical changes in the body which make the poison potent. However, the startle reflex is a bit to broadband for this to be sufficient. Someone could simply sneak up behind you and pop a balloon to cause the startle, letting poison take effect.
However, the startle reflex is only one of many reflexes we have, and some of them are far more nuanced than a mere startle.
It's known that digestion starts with the eyes and the nose. As you see and smell food, you actually start prepping the digestive enzymes needed to digest it. You'll generate the correct set of digestive enzymes for the particular foods you smell. This effect could be used to generate a particular cocktail of enzymes which you only produce once you know what you're getting.
A similar pattern appears in bee stings as well. If you are allergic to bee stings, the first sting is not all that dangerous. You puff up a bit, but it's not all that bad. However, the second sting can be very fatal because your body now knows what it's responding to and has hyper-attuned itself.
Some effect between these two extremes is probably what you are looking for.
The nocebo effect is documented to work through a reduction in dopamine and endogenous opioid levels in the brain's pleasure centers. This could be used to trigger a poison -- the poison only works on, say, a dopamine receptor type if the dopamine levels are depleted by some other external factor. In a sense, it'd be the opposite of a "silent antagonist" where the antagonist only works if the receptor is binding a ligand.
While this requires complex biochemistry understanding to pull off, it'd be fairly reliable (compared to relying on the nocebo effect alone) and would allow for a broader range of effects as well, especially if the change from the receptor+ligand+poison complex to receptor+poison causes the chemical lysis of part of the poison, releasing a much more toxic fragment such as a superoxide, hydroxyl, or 1,4-didehydrobenzene radical that can go on to do severe damage.
There is no poison! Or there is!
Basically, there is no such poison. You just make everyone think there is.
Think about it. You have a poison that never works if you don't know you were poisoned, but always works when you have been poisoned. The only way to know FOR SURE that you were poisoned is to be dead.
So, how does someone get this myth going. Simply, you claim that you have such a poison, and then use some real poison of some individuals. Make sure, after they have been poisoned, that they realize it (make it easy, or obvious, or use a whole lot of discrete suggestion), then get these events some publicity.
If anyone later thinks that they were poisoned, just tell them that you didn't poison them, and they therefore survived.
When you want to use this poison, simply make sure that it is noticed.
So, basically, IT IS A SHAM. There is not a spider in every cup. Those who never realize they were poisoned never were. You just have to make sure that every real victim gets enough publicity to the fact that they realized they were poisoned for your fantastic story to continue. Ultimately, dead men tell no tales, live men must not have realized or not have been poisoned. It is up to you, as the man behind the curtain, to decide which!
It isn't really the knowledge that kills you, although it appears that way:
The drink contains one component of a compound poison, the other component is released from the spider the moment it is exposed to air (ie., you have emptied the cup and the spider is plain to see) and needs then to be inhaled - your nose needs to be directly above the cup, so you see the spider.
If you just drain the cup on the floor, the second component is released too far away from your nose and dilutes too much - hence the appearance as if the look at the spider kills you.
Don't use this on a blind person, or you'll spoil the trick.
Psychoactive drugs can work in quite specific ways. For example, the parasitic fungi Ophiocordyceps unilateralis and Toxoplasmosis gondii alter the behaviour of infected ants and cats in ways that benefit the parasite; mescaline and LSD each cause humans to visualise distinctive, recognisable types of image.
So I don't think it would be impossible to believe that a spider's venom could be more or less harmless, yet cause you to have a fatal seizure / apnea / heart attack / suicidal compulsion on seeing the spider's specific pattern of markings.
As always with those questions: If someone knew how to make it, someone would make it. There have been a couple of answers around placebo-like effects and panic attacks and such (which also was my initial thought), but the obvious problem would be that those do not even need the substance itself and the image alone might be enough to kill. So we have to get pretty sci-fi here:
We know nothing about our brain. But if we did, this would be a possible task. Let's take your spider example. We have a memory of a spider - if we see it, something in our brain is activated and it has been theorized that it comes down to a singular cell - or something like that. If we had a highly targeted drug that could infiltrate a single, specific cell (or area or whatever you need) and if that cell is triggered does X - this could be enough. X could be deadly on its own or you take a mix that becomes deadly once X has happened. Maybe this could be done with a specific image, maybe just any spider or even thinking about a spider (for example the word "spider" could trigger the response) would be the only option. It could be done in theory, but maybe our grand-grand-children will be murdered like that.
Oh, please be aware that this could differ from human to human. Maybe that poison has to be designed for each target specifically. Maybe this is even more awesome. I think so
Also note from the comments: For pseudoscience / handwaving in a story, one could look into “NLP"
The poison is made up of microscopic robots.
These robots are all linked up to each other in a hive mind and when they are drank they scan the brain to see if it knows that what was drank is poison. If the brain knows that poison was drank these robots start attacking the nerves and killing them but if the brain doesn't know that what was drank is poison these robots pass harmlessly through the digestive system.
The spider is aquatic (these exist naturally so its not a stretch to have that). Its exoskeleton (or something naturally on or released onto its exoskeleton) becomes oxidised upon exposure to air. An old nurses tale says that this spider comes to judge good and bad people, and to quickly drink a glass of ale and swear allegiance to god, so that if it's death the spider brings, then they die in a state of grace.
Unfortunately the oxidised compound is highly soluble and dissolves in the last of the drink, thereafter reacting in the stomach with ales made from a particular process or crop, and becomes fatal even in microscopic doses. (Also plausible - cross reference ricin, ergot - I think - and other spoiled wheat/barley toxins).
This allows a slightly different scenario from the rest, where it's the combination of seeing the spider, and traditional folk belief (with their usual grain of truth) which is fatal. Enough people die - and enough don't - to sustain the nurses tale. But someone who has worked it out would be able to check (or ensure) the ale to hand when the victim called for ale, was the kind which wouldn't be survived (assuming it isn't the same beverage that was in the cup). The spider being aquatic is not commonly seen and maybe even a bit mythical if very hard to find, but provided it can cope with the beverage in place of water, this explains why the spider is okay in the drink as well. It could even be that the spider is imagined to magically appear, and the idea that it was put there by an individual would be sacrilege or "beyond the pale".
The main "hard science" stretch is whether enough can oxidise and dissolve in the short time available at the end of a drink. An alternative might be that the toxin doesn't need to oxidise. Instead it's a little denser than water and tends to accumulate in the bottom of the drink, where the spider has been exuding it, and the tiny dose is mostly concentrated in the last dregs of the drink. So it isn't seeing the spider that does it. Its the fact that only a person who sees the spider, has also just drained the last part of the drink in their cup (which exposes it to their sight).
Variations on these ideas allow quite a flexible range of scenarios.
What about a reverse cause and effect?
The spider, wary of this person who's rocking its current residence all of a sudden, will consider itself hidden and out of harm's way, until a direct look is cast by the drinker, in its direction.
As long as the drinker minds his own business, so will Spidey. He's just a photo-shy guy spider.
If and when he gets stared at - Spidey panics and, outraged at the indignity of it all, attacks.
Of course, you'll need a certain amount of intelligence/conditioning/valid evolution for a don't-look-at-me spider, but there are plenty of examples in the animal kingdom.
Did you hear about the placebo effect? Well, it's almost the opposite.
Placebo effect is when a doctor (or shaman) gives you an aspirin (or "magical water") to heal you from a sickness, wound or pain when they are fake (flour aspirin or normal water) but your wound, sickness or pain are healed (this effect is more common with pain). This works because our brain think that you are healing and it removes the pain or forces your body to heal that.
Nocebo is the opposite. When you take an aspirin (real or fake), it has a written secondary effect (e.g: stomach pain) and you have them, even if these secondary effects are false is called nocebo. This work in a very similar way that placebo but with the opposite effect.
A real example was tested with a prisoner:
I have no idea when it was, where or with who but it's real.
Edited: It was done by a scientific of Phoenix in the penitentiary St. Louis, Missouri. More Info (Warning: Spanish).
Once upon a time there was a prisoner with a death sentence in the electric chair. He would be killed in a few days but a scientist proposed an experiment with the prisoner. The scientist would try to kill the prisoner with a lethal bleeding but there was a chance of survival, the prisoner accepted (he has a chance of survival and if it wasn't true he would at least die painlessly).
He was tied to a chair and the doctor made a little cut in their wrists (this cut was so little that it didn't cut their veins or arteries -doesn't bleed- but the prisoner didn't know) but he said to the prisoner that he will start to bleed. To make this more real he put a serum bag, dropping the serum (drop by drop) into a metal cube so the prisoner could "hear the sound of his own blood dropping into the cube" (this was fake so he put the bag and cube outside the visual range of the prisoner).
Every 10 minutes the scientific approached the prisoner ("checking the status of the patient") and closed the serum bag a little (making each time fewer drops).
Almost 2 hours later he closed the bag completely (so, no more drops) and a minute later the prisoner fell unconscious and his heart stopped beating. This is because his brain thought that he lost all his blood.
You can convince your victim that they will die with a poison. To make this more realistic you could put non-lethal poison (something that makes you feel sick so they would think that there are poisoned).
Your poison could work with a chemical reaction.
It depends on what You exactly mean by "exist" and "works".
There are very real and very strong psychosomatic effects in our real world.
You can think something like "placebo effect" inverted. Knowledge about being "poisoned", if you are deeply convinced, can make you contact an illness or shock you to death.
Of course reliability of such a method can be questioned ;) ... unless you rely heavily on magic of some sort.
Quantum mechanics allows for particles to simultaneously be in two different states at the same time. This can be thought of as being in two places at once, or travelling two different paths at the same time. It is not until an observation event occurs that the particle must decide one or the other. See the links for more details and pretty pictures on the specifics how this was proven to be true, even though we still don't know why, or how, exactly.
In any case, given that particles, and atoms can exist in such a state, it should be theoretically possible for a molecule to also achieve such a state, namely, a poison molecule.
Now, this molecule could have the particular property of being non-poisonous in when it is still in a dual quantum superposition state, but poisonous should it leave said superposition state and enter into one of the non-superposition states.
This would achieve the desired affect scientifically, even if the development, storage, and deployment of such a substance is well beyond current scientific capability and is purely a theoretical exercise.
Example
Going back to the story cited in the question, the act of observing the spider triggers awareness or knowledge of the presence of the poison, which could very well suffice as the "observation" event needed to collapse the quantum superposition substance into an actual particle/molecule, and thus poison the person upon observing the triggering object.
It's a very plausible idea that a drug could have different effects depending upon how the brain responds to changes.
For example; Heroin drug users are often at risk of overdosing if they take the drug in a different environment. There have been many cases where users have died from overdoses after taking the same amount after moving to a new home.
There are many papers on the subject:
https://www.sciencedaily.com/releases/2000/10/001012074704.htm
There are also many different kinds of ways drugs activate. Not all drugs trigger different responses at different doses.
Some drugs have no effect until you reach a specific dose amount, and taking any more after that has no further effects.
Some drugs reverse their effects when you overdose. For example; some sleeping pills will act like a stimulus if you overdose. Keeping you awake and hyper.
Some drugs reach a high point of effectiveness at higher doses, but taking more resets the effect back to zero. You have to take even more to increase the effect again.
So it's possible. Using these facts about drugs that you could create a designer drug that "appears" to work like magic.
Maybe you keep giving a person a drug in secret with a tea cup. They build a tolerance to the drug as you slowly increase the dosages over time. One day you introduce the spider to the cup. At first they drink the tea with the drug and not see the spider, but one day they see the spider. This triggers a change in environment and they loose their tolerance for the high dose of the drug.
They overdose as a result.
To everyone else. This looks like strange magic.
This may work this way: the poition makes your heart very vulnerable to any stress, so it stops at any panic or fast movements.
If the person does not know he was poitioned, he is relaxed and everything goes as usual. But if he sees the spider he comes under immediate stress and his heart stops.
It's not quite a poison, it is really far-fetched and it's not really reliable, but one possibility would be to trigger an epileptic seizure, if your victim suffers from epilepsy. And flickering light is known to trigger seizures, so you can make your spider shiny and flickering (and the adrenaline would likely contribute to the seizure).
But more reliable would be to just put flashing magical LED light at the bottom of the cup, activated by air.
I especially like the answer using the 'observer effect' within quantum mechanics, but unfortunately non-determinism applies to both actors in this scenario so there would be no quantum mechanical way to be 'sure' the target was poisoned (independent of any action or inaction on their part).
I would suggest the method used by illusionists regularly which is to use misdirection to effectively poison the target by their own actions (I'm not suggesting Illusionists poison anyone, rather they simply encourage the audience to assist in the act of creating the illusion for themselves).
In a relevant example, one could add a precursor or uncatalyzed poison to the drink. If the drinker does not see the spider then the poison passes harmlessly through the biological system and is excreted. Yet if the drinker sees the spider, some cultural-ethnic-habit-superstition-religious action (the action being completely normal, acceptable, predictable, and normally harmless) causes the activation of the poison compound and thus ultimately their fatal poisoning is the result of their own actions. Refer to the practice in some ancient cultures of using a silver implement to eat one’s food in the house of a stranger… the cultural belief being that if the unknown hosts are trying to poison the guest, the silver would turn black. Similarly, If one were to poison the cup with the spider being seen by the target, then they would reasonably not eat the meal which ironically contains the deactivating antidote… conversely, a scenario where the target sees the spider in the cup causes the target to rush outside in search of wood-mushrooms which in his/her culture are medicinal, yet in this land they are very much fatally poisonous.
To me it is very suggestive of a Poe classic: ‘The Cask of Amontillado’ (oldie-but-goody)
It is the most well known "poison" historically speaking.
Sin/Evil
Now this is technically a tad bit subjective, but let us consider this:
many religions say that sin is the ultimate cause of mortality (as in the ability to die and stay dead)
One cannot accidentally sin. Most things tend to emphasize that the perpetrator actually does something wrong and knowingly so. After all, that is the dictionary definition of the word.
I think this qualifies. It is a bit of a stretch and isn't a physical poison. However, a mental poison that has a 100% mortality rate with no known cure to prevent death (nobody says anything about staying dead) is certainly a reasonable thing to look into.
Also, it is worth noting that without the presence of this poison already in place no other poison will be successful. They will always fail.
So in a roundabout way this means that this is the only poison that actually will work and requires one to know they have been poisoned... and willingly accept the poison.
Maybe it's a kind of a nocebo effect (negative placebo). Think of it that way: The person who takes the drink and does not see the spider, doesn't loose a thought on being poisoned neither. Thus, everything will be just fine. But if that person sees the spider, the person starts to worry about the possibility that someone just poisoned her. This leads to a physical reaction and the activation of the "poison" which now causes real physical symptoms.
Maybe, similar to other answers, the poison in the cup is actually benign until mixed with another substance. The person drinking the "poison" is led to believe, or perhaps comes to know through faulty research (or maybe even deceit), that the antidote is a certain chemical. However, the "antidote" is what activates the poison and kills them. Hence, if they know they're poisoned, they will seek out a cure, but the cure kills them. If they are oblivious to the "poison" nothing happens as it is benign.
In a real world situation this would have some real benefits and quite possible with the upcoming nanotechnology. The body could encapsulate any unwanted drugs so they would not be absorbed by the stomach unless confirmed with the Host. In the stomach would have be a form of communication device where the host could deny or allow certain chemicals to be absorbed into the body. This would definitely prevent any date rape drugs.
A poison typically works independent on whether you know about it or not. If it shall only work if you know about it, it would have to be able to literally read the mind (nocebo effects or cheating by faking the poisoning and then waiting for the person to make a mistake are not very specific and might easily fail).
The usual chemical compounds cannot do that, so either you have to use advanced technology (like the nanorobots of Anders Gustafsons answer) or magic.
A magical solution could for example be:
