Can a substance be more lethal in smaller doses?

Question

Yes, I realize this question is a bit ridiculous, and there are no cases of it in reality (that I can find), but with a bit of truth twisting, could it theoretically be possible?

In my fantasy world I want a poison, which has an antidote - that antidote being itself.

Here's my theory: the substance is very closely related to something in the human body, like a bacteria or something, but has one tiny difference, which is what makes it lethal, and it kills you pretty fast. If a bunch of this stuff is released into your body, would your body recognize it faster, and since its so similar to your body in the first place, could it be easier to neutralize a larger dose, while a tiny drop would kill you faster?

Also this is in medieval period before antibiotics.

Answer 1

Related to cmaster's solution:

The "poison" is actually harmless A.

The body converts A to B, also harmless.

The body converts B to C, deadly.

Once the A->B path has saturated you get an A->D path.

D blocks the B->C reaction.

B is eliminated from the body faster than D.

While I am not aware of anything with this behavior there are things that exhibit part of it. I don't know if it's still the case but the treatment for methanol poisoning is ethanol. Saturate the reaction path with the ethanol and the methanol doesn't kill you.

Also, consider acetaminophen. With the usual dose the preferred pathway produces a chemical that is of little threat. However, there's a second pathway that produces N-Acetylimidoquinone which is a nasty customer. While this is always produced it is usually in small quantities and quickly neutralized. However, the primary pathway can saturate, once it does all the remainder gets converted to the N-Acetylimidoquinone which destroys your liver and thus kills you if you don't promptly get a liver transplant.

It occurs to me that if such a chemical actually exists it probably would be unknown. After all, why would you test above the dose that kills all your test animals? And in humans such exposure would be extremely rare. Even if there is a case of unexpected survival it's unlikely they would spend the effort to figure out why.

Answer 2

What you're looking for is an emetic - a substance that induces vomiting. This is the specific reason why, as @Alberto Yagos already stated in his answer, suicide-by-pills doesn't always work - many pills are coated in a small amount of emetic so you'll throw them up if you take too many.

In the case of your poison, a large enough dose would cause you to throw it all back up, thus saving your life. A small enough dose, however, would just slowly digest in your stomach, and once it's in your bloodstream, it's lethal.

A cursory search hasn't found me any real-life emetics that would kill you if you didn't take enough of them. The closest I can find is copper sulfate, but it only becomes dangerous way past the point at which it makes you throw up, and doesn't seem to do anything below that threshold. The good news is, this means you can invent your own emetic poison, and tweak the numbers (how long it sits in the stomach for, how much is required to induce vomiting) until they're just right for your story.

Answer 3

This is perfectly possible, and I guess it could be readily done with modern technology. For less technical settings, you just need to say that some plant happens to produce the poison, it's believable enough.

So how does it work?
Your poison needs to be a drug (let's call it P) that targets two different compounds in the human body (call them A and B). Think of a large molecule with two different functional groups, each of which are responsible for one of the two reactions. Such molecules should be quite easy to produce with modern methods.

• Compound A is rare in the human body. P strongly interacts with A to produce the evil, deadly compound E.

• The evil compound E needs some time to do its destructive work, though.

• Compound B is abundant in the human body, but P only weakly interacts with it to form some other compound R.

• When compounds E and R meet, the E is destroyed for good.

With these traits and reactions, you would get the following behavior:

• A low dose of P will mostly interact with A to form the evil E, killing the victim.

• A big dose of P will quickly interact with all the A that's available to form E. Once the reservoir of A is depleted, no more E can be formed. The rest of the dose of P then interacts with B instead, forming large quantities of R. The R proceeds to eliminate the E before it can do too much harm.

• After a large dose of P, the body will be flooded with R, granting immunity to P for a limited amount of time.

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If you want to optimize, you may also skip the compounds B and R, and have P directly inhibiting E. In this case, the toxicity of small doses would rely on P turning A into E more quickly than it can eliminate the produced E. The non-toxicity of large doses would rely on P quickly depleting A, so it destroys the produced E instead.

The two path reaction seems easier to explain to me, though.

Answer 4

There is one possibility: your lethal substance is an ingested poison. With a low dose, it goes into the bloodstream and kills you. In a large dose, it is so harmful your stomach immediately throws it up, saving your life.

It isn't pretty, but it is reason some suicides with pills failed. And as another example, Napoleon tried to kill himself during his exile and he took so much poison he threw it up and survived (to be murdered by another poison later).

Answer 5

What you're proposing is certainly possible, although I don't know of a case that demonstrates this exactly. The behavior of biologically active molecules (drugs or toxins) can be very complex (see pharmacokinetics on Wikipedia). Many poisonous substances are detoxified or made toxic by enzymes in the body (drug metabolism). For instance, ethanol, the active component of beer, is converted by the liver enzyme alcohol dehydrogenase to acetylaldehyde (more toxic than ethanol) and then by the enzyme acetaldehyde dehydrogenase to acetic acid (nontoxic and naturally occurring in the body).

Drugs that can cause the body to make more of an enzyme are called enzyme inducers. Interestingly, some drugs can induce their own metabolism (for example, the anti-epileptic carbamazepine). This is called autoinduction of drug metabolism, meaning that the drug upregulates the same enzyme that degrades it. In fact, this is one mechanism for developing a tolerance to drugs.

So your poison could be a toxin that upregulates its own metabolism. The biological activities of drugs can be very nonlinear, so it is possible to have a situation where the toxic effects of your molecule are fatal at low concentration, while, at high concentrations, it highly upregulates the enzyme that metabolizes it, making it nontoxic before its effects are fatal. I don't know of any molecule that acts this way off the top of my head, but I wouldn't be surprised if something like this exists.

Answer 6

Homeopathy is the real world, but very, very mistaken, idea that "like cures like". An infinitesimal amount of a poison can cure the poison's symptoms. For example, mandrake root can cause hyperactivity and hallucinations, so a homeopathic "doctor" faced with a patient with such symptoms might produce a tincture of extremely diluted mandrake root. The more diluted the tincture, the more powerful the cure.

In reality this is hogwash. Homeopathic tinctures are so diluted statistically they often contain not even a single molecule of the original substance. Homeopathy "theorizes" that the alcohol or water retains the "memory" of the original substance, also hogwash. Homeopathy "worked" because doctors at the time would do more harm than good, and the "medicine" came with a long required list of healthy habits the patient must practice. Now it's just a placebo.

But in a fantasy world, why not?!

Homeopathy was developed in the 18th century, but "like cures like" goes back to Hippocrates so the concept would be around for a medieval setting.

Take the same approach as homeopathy, but now it's like kills like. In Homeopathy, diluting a poison is supposed to turn it into a cure. In your world, diluting a cure turns it into a poison! A large amount will save you, but an infinitesimally small amount will kill you. Perhaps the substance itself is the cure, but the diluted "solution" (in quotes because there's nothing of the original substance left) retains the "memory" of the disease it's meant to cure.

Answer 7

You're missing a couple of elements here.

Effects vary depending on delivery method.

If the substance isn't readily digested, you might need large quantities to get any of it into the victim's system. In the extreme case, it might be completely ineffective that way. Taken in some other form - injected into the bloodstream, for the most obvious example, but more recently using coated microcapsules - you can get that substance to where it works.

Effects vary depending on surface area.

A bit of gravel stuck in a nostril is an annoyance. The same rock ground to a fine powder and inhaled over time gives you silicosis. Nanoparticles appear to have different characteristics to larger bulk stuff.

So smaller amounts can be more effective - but you'll need to use it differently.

Answer 8

Drugs.

We already have what you describe. When you're addicted to some substances, you can't simply "just stop", that'll kill you as your heart will fail. You will need to get close to the average dose of a person and slowly lower the dosage.

In you case, the drug could be with less/no additional effects, but when stopped, you die because your body no longer produces whatever is in the drugs. You could make it a food suplement, or as assasin introduce it slowly into the waterstream and threaten to stop.

Answer 9

One possibility is that the substance binds to itself in large amounts but not so well in smaller amounts. Since it doesn't bind as well in small amounts it's able to interact with the body more so in those small amounts. It's poisonous in both situations, but significantly more so in small amounts.

The best description I can think of is this; a thin layer of metal isn't very strong when stressed (like a chemical in a body would be) so it breaks with very little force into small pieces compared to a thick layer of that metal. It's been too long since chemistry class, so I can't say how accurate this description is.

Answer 10

Napoleon's attempted suicide by Arsenic comes to mind, legend has it that he thought himself so great a man that he took several times the lethal dose for a man his size; instead of dying he puked it back up and lived to tell the tale. It's not that arsenic is necessarily less poisonous in very large doses but the body is better at realising it's in trouble and rejecting the material. The Calabar and Castor Bean can both appear more lethal in small doses because if swallowed whole they don't release their toxins but if chewed, especially the Castor Bean, they can be deadly.

Answer 11

I'm going to go with a different answer and say disease.

There is a phenomenon in the bacterium kingdom in which an action can be executed collectively by all bacterium once a certain population is attained. the big example is luminating:

Theoretically the smaller the dose of a deadly bacteria that one ingests, the longer it would take to die, and thus be harder to track, and harder to treat early.

Answer 12

Two other solutions, but with some statistic :

1. A plant which produce 2 kinds of berry : one is a powerful but slow poison; the other is a an antidote which is more powerful than the poison: one antidote berry is enough to cure two berries of poison. You can't differentiate between them with medieval technology. So, statistically speaking, the more you eat the fruit, the more chance you have to find a cure for the poison you ingest.
2. The fugu is a fish delicious if we'll prepared but deadly if a mistake is made. You can create a fish which is its own antidote if well prepared. And same thinking as the solution above, you have more chance to live the more you eat the fish.

Answer 13

Maybe oxygen?

With a limited amount of oxygen it is definitely more lethal, but it doesn't really fit into the poisons part.

Unless you consider the part where some say it is actually just killing us very slowly. And how some consume antioxidants to keep their skin youthful, etc

Answer 14

Take some kind of bacteria that only clumps together when reaching a critical concentration. Clumping together will disable their ability to enter the hosts cells.

Answer 15

Another version of the throw up poison might be something your body is able to detect and treat similar to an infection. This compound must be built on proteins that interact similarly like some poison of an animal. In low quantities it just shuts down vital organs and muscles but in higher quantities, your body detects it and produces a fever which destroys the protein (which just happens to have its breakpoint at the human body heat level at fever times)

Answer 16

Suppose that pills are coated with emetics so that someone who takes an overdose will vomit them up and maybe survive. Suppose that someone injects deadly poison or maybe an overdose of the medicine into the pills of their intended victim.

If the target takes the normal amount of pills, the poison or extra medicine will kill him. But if he accidentially takes an overdose, the high level of emetics will cause him to vomit and perhaps vomit enough to survive.

So this has taking more of the specially sabotaged pills having less of a probability of death. But it does work only by having the pills contain two or three different drugs with different effects, not one single drug.

Answer 17

For a slightly different twist, that may still stay compatible with your world.

A plant can contain multiple poisons.

The deadly poison in small doses is undetectable, It's medieval time, there is no bloodtests, just showing symptoms, you show 0 symptoms until it's too late, then you die, but it takes a long period to metabolize.

In larger dosages, you start to process the well rumored hallucinogens well before your body has time to metabolize the poison. You recognize the legends / rumors / specific hallucinogens that are related with this plant, and know that you must remove it from your body ASAP to have any chance of survival.

It's not that a larger dose is necessarily an antidote, but is the only way to know that you have ingested it and take action consciously.

The fact that small doses are still lethal and undetectable, is probably a secret known only to assassins.

Answer 18

The two best voted answers gave me the idea of using a catalyst...

Catalyst C quickly converts all available Vitamin Q (found in fruit H consumed widely in the land) to deadly Poison P. In large amounts however, the catalyst sits on the receptors and blocks Poison P from acting, until they both are safely removed from the system. This works because P is eliminated faster from the body than C.

An interesting side effect is of course that your skin turns a bright shade of green while P is still in your system. Now, you need to be very careful not to eat any of that tasty fruit H until you're back to your usual shade of beige. This trick of turning vivid green is widely used by the tribes in gaba-gooba land to help them with hunting and stealth attacks on rival tribes. However, vitamin Q deficiency is wide-spread, leading to short statures and a tendency to wiggle uncontrollably when sleeping.

Answer 19

Put things in a bottle that DO not properly mix (eg oil and water bound substances). Make sure whatever is carrying the poison rises to the top with the antidote pooling below... Mind liquid levels and where the spout on the container is!

Answer 20

A Little Learning

^{by Alexander Pope}

A little learning is a dangerous thing;
Drink deep, or taste not the Pierian spring:
There shallow draughts intoxicate the brain,
And drinking largely sobers us again.
      ︙

 (goes on for another 14 lines)

^{Copied from Poets’ Graves.}

Sorry; I couldn’t resist.

Answer 21

Yes, the question is ridiculous! But it's fun all the same. Really, the answer to your question (and its sub parts) is "No".

All substances have the potential to be lethal in some way or other given the right combination of nature of substance, amount of substance, size of subject, health of subject, constitution of subject and route of substance administration.

First, we'll look at your actual question, thinking about it logically:

Can a substance be more lethal in smaller doses?

• A bullet is made of (usually) lead. You can safely hold it in your hand and not die. If it's injected using a standard bullet injecting device (aka a gun), it'll be lethal. A small bullet, properly injected, is no more lethal than a large one. In fact, lethality decreases with ammunition size and power. If you get shot with the smallest size bullet available (a 7 cal pinfire round), you're not going to die as a direct result of being shot. A 95 cal JDJ round. Yeah, that'll be a fatality when properly injected.

• A few grammes of bronze make a nice pendant to be safely worn on a necklace. An irate girlfriend could hurl the object at your head, probably in conjunction with a tirade about diamonds and high carat gold, and won't even hurt you. A few tonnes of bronze falling on your head will crush you dead.

• A relatively low concentration of gaseous oxygen is nice and refreshing to breathe. Jumping into a pool of highly concentrated & refrigerated liquid oxygen will turn you into a block of ice pretty quick!

• Even well known poisons operate the same way. A single molecule of ricin can kill a single cell. A single cell!? It takes a number of castor beans to obtain enough toxin to kill a person.

Building from my original answer:

• What we can see here is that smaller amounts of substances are far less deadly than larger amounts.

• We can also see that any amount beyond this perfectly deadly dosage, again properly administered, is no more deadly than the smaller, adequately deadly dosage.

• Finally, that there is a (variable) sweet spot where a substance becomes deadly. Goldilocks all over again.

Conclusion: every substance has a particular set of circumstances in which it is adequately deadly. Too much of that substance is no more deadly. Too little is not deadly enough. No amount of truth twisting of semantic games will make a substance more deadly at smaller dosages.

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Next, we'll take a look at the subquestions:

• In my fantasy world I want a poison, which has an antidote - that antidote being itself. -- Let's take a look at the definition of antidote: it is some substance that counteracts the effect(s) of another poisonous substance. You're asking for an illogical tautology. If a substance is its own antidote, it can not have had any kind of poisonous effect whereby an antidote would be desired. If a substance has a poisonous effect, it's a poison, not an antidote to the poison. So, +1 for recognising the ridiculousness of the question. I would state, however, that you do leave yourself an out by working within the realms of Fantasy. In Fantasy, there is nothing stopping you from simply declaring any number of poisonous substances, magical or otherwise, to be their own antidotes for reasons.

• Here's my theory: the substance is very closely related to something in the human body, like a bacteria or something, but has one tiny difference, which is what makes it lethal, and it kills you pretty fast. -- This makes sense. There are beings & substances already in the body that work this way. If you become infected with group A streptococcus and develop necrotizing fasciitis, you'll die pretty quickly. There are many bacteria and viruses that can kill relatively quickly.

• If a bunch of this stuff is released into your body, would your body recognize it faster, and since its so similar to your body in the first place, could it be easier to neutralize a larger dose, while a tiny drop would kill you faster? -- No. This is not how the human body works. The immune system works by immune cells recognizing chemical signatures of foreign invaders that differ from the chemical signatures of your own cells. (This is why autoimmune diseases are so nasty -- your immune system recognises your own body as foreign and begins attacking itself.) Once an immune cell recognises an invader, that cell releases a chemical signal that basically says "Oi! There's an invader!" Other immune cells respond by "eating" the invading bacteria, "sequestering" infectious matter or by cells increasing their own resistance to infection. You get responses like swelling, heat and pain as the body tries to lay siege to the local infection.

  Releasing a whole load of infectious agents will not speed up the recognition process or the chemical response time. In fact, the only effect a larger quantity of a deadly infectious agent will have is to swamp the subject's immune system. Sure, it may recognise an infection is present, and will mount a defense, but too much will simply overpower the reaction.

  NB: Also, if the proposed substance is already sufficiently identical in chemical signature to your own tissues, your immune system will not be triggered by it. This is molecular mimicry. The small "dose" of bacterial infection or whatever, will kill your subject adequately.

• Also this is in medieval period before antibiotics. -- This of course, is a red herring. Even with modern antibiotics, it is still possible to die from sepsis.

Answer 22

I don't know if this qualifies, but a considerably smaller dose of some drugs (I think heroin) could result in lethal withdrawal symptoms, if the user is already addicted to bigger doses.

How do you cure drug addiction? With a big dose, but split in a controlled way in a long period.

Answer 23

Ketamine has very different effects at different doses. At a high dose it is an anesthetic that knocks you out and if that dose is not too high, doesn't kill you. At lower doses it can induce a trance-like state and cause hallucinations.

If you put someone in an environment where being knocked out is safe, but wandering around without having full command of your faculties is dangerous (e.g. a mine field, a busy intersection, scaffolding at a construction site, in a trench on a battlefield), a low dose could be deadly, while a high dose is merely incapacitating.

Answer 24

It's not unheard of for a herb or such to have opposite effects when taken in small doses versus large doses. As an anecdotal example (most examples for this sort of thing are probably anecdotal), white mulberries can make me more depressed if I eat a bunch, but if I just eat a few, they make me less depressed than had I not eaten any.

Or, it might treat the symptom while you're taking it, but cause the symptom after you stop, or treat it for a period of time and eventually cause it (even if you're still taking it). The same thing that can treat a problem can often cause the same problem. However, making it reliably do the same thing for every person is perhaps the hard part. If it's just one person's physiology, you may be in luck. People often respond differently to stuff that doesn't just intensify the effect based on dosage.

So, I think what you're asking is definitely possible. Getting a solid explanation for it and the science behind it might be tougher, though, if you need that.

It sounds like maybe an addictive substance with severe withdrawal symptoms may fit your need. The withdrawal symptoms might include death. You might need more of the drug (not a larger amount) to ease off of it over a period. This idea has probably been done before, just for the record. I know similar ones have been done.

As an alternative, you could have an essential nutrient. Extremely low doses of it could be fatal, while higher doses could be healthy.

Low doses of a substance might cause microbes/parasites to produce a toxin, while a higher dose might kill the parasites (thus evading their toxic reaction).

Answer 25

A real life example: here in Russia stray dogs are a big problem: they kill and maim up to 100 people every year (and those are only registered cases). And our animal control is fake: they do nothing. Country folks get rid of stray dogs by using a drug called "izoniazid", which is almost harmless for humans, but for some reason is deadly for dogs. They say that a correctly calculated doze makes the stray dog just lie down and die, small overdoze would produce agony, but a doze too big will make the dog to throw up, survive, and even become partially immune to poison. So the kind of poison you are asking about definitely exists in real world. But are there drugs that affect a human - I don't know.

Answer 26

Strictly speaking, this is technically not an answer to the letter of the question, but I believe that it addresses the spirit of the question:

A syringe (with a hypodermic needle) containing a lethal dose of any poison, pathogen, or whatever — specifically, one that is fatal when injected into the bloodstream.

Normally (in the hands of somebody with the technical skill to poke a needle into a blood vessel), this can, of course, be used to kill somebody.  But replace the needle with a piece of pipe with a thickness (diameter) greater than, say, one centimeter (0.4 inches), and it doesn’t work so well.  Sure, depending on how sharp it is, it can be used to cut the victim (like a knife) or cause blunt force trauma (like a club), but it won’t be able to inject a toxin into a blood vessel.