Context: This is a post apocalypse low fantasy, soft science world. In it megacorps have built a protected city for citizens to survive. The world outside the walls in dangerous, with toxic gas, radiation, deady evolved/mutated animals, and vengeful abandoned Androids intent on killing all humans.

Its dystopic in nature and in order to keep the population from realizing the CEOs dont care about them, and have no problem enacting draconian edicts under the guise of protecting them. I plan to have the new government continously drug them with sedatives to keep from revolting.

Question: Can humans can gain full immunity from constant drugging?

I know people tend to develop tolerances towards certain chemicals and additives, like drugs and medicine. But im curious if this is feasible or if people would develop an immunity too quickly to be effective.

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    $\begingroup$ Recent research on the rate of evolution has surprised some scientists. I can't find the original paper that I read about this, but a quick google revealed 2 related papers: royalsocietypublishing.org/doi/10.1098/rspb.2013.0211 , ncbi.nlm.nih.gov/pmc/articles/PMC2679939 . Echoing Kilisi, in a single generation, this is basically impossible -- however, depending on size and structure of the population, the rate at which people reproduce (pregnant at 15 or 30?) and the amount of mutagenic factors (radiation, chemical), there might be some interesting possibilities. $\endgroup$
    – Marco
    Sep 20, 2023 at 10:58
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    $\begingroup$ Why rely on a drug that needs to be constantly be reapplied? Use something that causes targeted neurological damage early on enough on the people(children), with the desired effects, and it will affect them for the rest of their life. Take Lead for example: It is believed to lower IQ and cause learning disabilities, if assumed true -and our desired effects of keeping the people stupid- You can just feed it to the pregnant mothers as supplement, and the children will have a life long to enjoy it. Now invent some drug that can be applied to damage aggression response, and Bob's your uncle. $\endgroup$
    – vinzzz001
    Sep 20, 2023 at 12:57
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    $\begingroup$ If the drug is alcohol, we've empirically proven that several millenia isn't enough to develop immunity. $\endgroup$ Sep 20, 2023 at 18:32
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    $\begingroup$ @Blueriver since alcohol inebriation reduces social inhibition, natural selection seems likely to -increase- it, not decrease it. Drunk people are more likely to have sex, and thus are more likely to reproduce. $\endgroup$
    – Ryan_L
    Sep 21, 2023 at 16:30
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    $\begingroup$ @Ryan_L you're right. And they're also more likely to forget about birth control, leading to an ever higher chance of reproducing. $\endgroup$ Sep 21, 2023 at 19:56

7 Answers 7


Full immunity is unlikely

Let's give an example of a drug used in copious amounts in current society. Alcohol!

With alcohol use you can see that people do get higher tolerances. They need more alcohol to get the negative effects. I went to a court once where the accused was found after an accident with a blood alcohol percentage well over what normally would be deadly. His survival was attributed to tolerance.

There are DNA differences as well, besides typical physical attributes. From a better way for the liver to break down the alcohol to simply having a larger size. All can influence the alcohol resistance.

But have you ever heard of someone never feeling the effects of alcohol?

The imperative word is resistance. At a certain moment the biology and tolerances reach a limit. You will get inebriated, you will eventually die from alcohol.

This isn't applicable to all drugs. Yet most will follow the alcohol example after a fashion. Even with some serious biological adaptations over generations it is unlikely to become immune. But the body might not feel the need for such adaptations. It is surviving. It is reproducing. It isn't being harmed, at least not on a short scale. The body could very well have a form of homeostasis that includes the drug.

So even with generations being drugged there is likely to be no tolerance response big enough to become for all intends and purposes immune.

And even if you find immunity, you can use a variant or different drug to start all over again.

  • 1
    $\begingroup$ I forgot people have different resistances to certain chemicals and drugs, I'll take into account this when the population has regular health checks and genetic screens to fine-tune doses. $\endgroup$
    – Saxionkin
    Sep 20, 2023 at 22:46
  • $\begingroup$ note that certain aspects of a drug can be eliminated or inhibited entirely, note alcohol flush reaction, something experienced by a lot of people in some areas where certain alleles are present, but not in others where enzymes are more efficient and can negate the effect. In that case there are very real effects of alcohol that have been removed or severely reduced by genetic factors $\endgroup$ Sep 21, 2023 at 14:52
  • $\begingroup$ @Saxionkin you do not need to finetune if they're dead. Removing them from the gene pool also allows lesser resistant people to survive better, making it easier to have a susceptible society. $\endgroup$
    – Trioxidane
    Sep 22, 2023 at 13:40

It depends on the drug

Let's take opiates (as an example). People who regularly use opiates build up a tolerance. It also becomes part of how their body functions (we'd call this a physiological, rather than psycological, addiction, though opiates show both of these). This is what leads to the shakes, hallucinations, rage, etc from quitting cold turkey.

But, if you keep using opiates, it takes a higher and higher dose to get high. What is interesting is that your non-lethal dose also goes up - your body works around the high level of opiates. This is a massive problem when people get clean for a while, and then relapse, they'll often take the same dose as they were taking just before they got clean. However, without the tolerance, the dose is high enough to be fatal.

So, applying this to your fictional drug - your government is going to need to target individuals precisely - variations in bodyweight and so forth mean you can't roll out a single dose for everyone. If they're doing that, the government can ramp up the dose of this fictional drug as it works less well for people.

This is kind of an interesting entrypoint, if this has been happening for many years - people might just start dropping dead, as their drug doses get too high. You might see strange effects at higher doses, which would be realistic for a drug. You might see people cycled through "detoxing" - the government could take people off it, in a controlled (prison-like?) environment, then could start their doses lower again.

The point is, it's not a "dump it in the water supply and sedate everyone" kind of situation. It's a dynamic, somewhat chaotic and desperate move - the government now can't stop the drugs, because you'd have a raging, insane populace pretty much instantly. But the status quo would be collapsing as drug doses get too high to tolerate, or the effectiveness of the drug decreases.

  • $\begingroup$ Good point, it's important for the government to keep a stable population and there is no one dose fits all, so I'll have to have them give individual doses to people based on weight and age, as well as have more common health checks to make sure they aren't overdosing. $\endgroup$
    – Saxionkin
    Sep 20, 2023 at 22:45
  • $\begingroup$ @Saxionkin - you'll also have to ramp up doses as tolerance builds up, which is going to be tricky. It'd be less "do they build up resistance?" and more "is there a stable place where they're drugged enough, but the drug is not killing them?" $\endgroup$
    – lupe
    Sep 20, 2023 at 22:50

Not in a single generation. People can and do develop a tolerance for a drug after prolonged usage. This means that the drug has less effect at the original dosage.

Whether this would be an issue in the next generation is unknown. All drugs taken by a pregnant female are passed to the infant, and some while breastfeeding. But of course an infant is a LOT smaller than the mother so the effects can be horrific and/or life-threatening.

  • $\begingroup$ Important to note this is an adaptation - your genetics have already evolved to be able to adjust their tolerance to drugs, within a certain range, just like you genetically have the ability to learn to understand languages, and then you learn to understand English. You can learn to understand Spanish, but you can never learn to understand bats because our ears genetically can't even perceive those sounds. Likewise you may build up a tolerance to some toxins, but not others. $\endgroup$ Sep 20, 2023 at 12:37
  • $\begingroup$ I don't see how drug tolerance will be passed between generations, either, unless drug tolerant individuals reproduce at different rates resulting in natural selection over the course of millennia. What you describe here is merely passing the drug itself onto the next generation, not any kind of tolerance. $\endgroup$ Sep 20, 2023 at 14:42
  • $\begingroup$ This makes sense, I'll have to take into account how generations would change, even if they aren't affected genetically by the drug. $\endgroup$
    – Saxionkin
    Sep 20, 2023 at 22:49
  • $\begingroup$ @NuclearHoagie Epigenetic inheritance is a thing, and might come into play. Alternatively, it's fœtal exposure. $\endgroup$
    – wizzwizz4
    Sep 20, 2023 at 23:02

There's room to do (almost) whatever you want

Drugs (psychoactive or no) vary extremely widely in terms of:

  • whether or not they ever induce tolerance and how fast they do if so
  • whether they have an obvious withdrawl syndrome
  • how debilitating or dangerous the withdrawal is, if any
  • whether or not it's realistically possible to overdose and how easy it is if so

The drug ziconotide is sometimes used in hospitals in place of morphine because it's a strong painkiller that appears not to induce any obvious tolerance even after months of constant use. In line with this, someone can stop using it abruptly "without any concern for the development of withdrawal symptoms." (The main problem with it is that it has to be given via spinal tap.)

Drugs that actually induce dependence, not just tolerance, often take a while to do so, like a month of daily use. There are some drugs out there that induce tolerance within a few days (tachypylaxis), although this doesn't necessarily come along with a withdrawal syndrome if the person stops taking the drug at that point.

If a drug does cause withdrawal, the symptoms vary widely between drugs, both in terms of their severety and how long the withdrawal lasts. I've gotten the impression that drug withdrawal tends to take sometime between a few days and a few weeks for most drugs. Some come with relatively mild symptoms, like caffeine, which causes grogginess and headaches; others come with more severe symptoms, like SSRIs, which can cause intense nausea and vomiting during the withdrawal. Even worse, a drug I take every day for migraine prophylaxis, propranalol, has a black box warning telling you not to stop taking it abruptly because it can cause dangerous heart palpitations and even heart attack. Alcohol withdrawal is also infamous for its danger—it can involve seizures that can lead to brain damage and death.

As for overdose, some relatively popular recreational drugs are non-toxic enough that you would struggle to chemically injure yourself even if you took doses thousands of times larger than is recreationally common. Other popular recreational drugs are remarkably toxic, like nicotine—about 0.5–1 g of nicotine, taken orally, is enough to kill most adults. Smoking a cigarette only gives 2 mg or so, though, so nicotine overdose isn't very common. A more serious case of active vs. toxic dose comes up with acetaminophen, i.e. Tylenol, where a common over-the-counter dose of 0.5–1 g is worrisomely close to the maximum recommended 24-hour dose for an average adult, 4 g. Hundreds of people die from accidental Tylenol overdose every year in the U.S. alone. Perhaps we're fortunate that it doesn't come with a pleasant high.

All of this is to say that I think you have room to have your mind-control sedative have whatever properties you please as far as tolerance goes. There's definitely room to have it never induce tolerance. You could also have it induce tolerance very slowly, ramping up gradually over months or years, or have it induce tolerance very quickly, over the course of a few days. You could give it a viciously unpleasant or even deadly withdrawal syndrome, a mildly uncomfortable withdrawal syndrome, or no withdrawal syndrome. You could have it be highly toxic, so that it's scarily easy to overdose on, or have the toxic dose be so far away from the psychoactive dose that overdose is unknown in the medical literature, or anything in-between. The human brain is famously complicated.

One thing I will say is that the medical reality rather favors the government in your setting, I think. There are lots of drugs that keep working to some extent as you keep taking them, but you do develop a dependence, and they can be deadly to stop taking suddenly (again propranalol is such a drug). If the sedative was like this, people might be afraid not to take it once they had gotten started on it. You can wean yourself off of drugs like that by gradually reducing the dose, but if the only way to get the drug was to go to a government clinic and have them administer it or something, you wouldn't necessarily have that much control over the dose. That could keep people in thrall to the sedative just out of grim necessity.

Alternatively, you could have the drug not induce tolerance, be quite non-toxic, and very pleasant. I don't think you would need to try very hard to coerce people to take a drug like that—just make it widely, freely available and present it as a healthy habit. Soma in Aldous Huxley's Brave New World is perhaps the "textbook" example of this in English-language fiction.

To be honest, I think that might be only realistic way to have a drug keep people from revolting without also intensely disabling them. If it makes them happy, they'll put up with a lot. If they're just sedated, it wouldn't necessarily make them not want to revolt, so you would have to sedate them enough that they were too sleepy to drive or work or anything too. I think it would be hard to keep the society going that way. So, a drug that makes everyone happy and satisfied seem more plausible to me as a way of preventing revolt. We don't really know of any drugs that are true "mind control agents," in terms of making people pliant and suggestible but otherwise capable of acting normally (the CIA and KGB looked very hard for things like that during the Cold War…). I suppose we don't know of anything quite like soma, either, but somehow it seems more plausible to me, if nothing else because we do know of many drugs that induce various flavors of euphoria.

I think the only thing that's not likely is to have it so that people develop complete tolerance that never goes away after taking it for a while. Generally, if someone stops taking a drug that induces tolerance, their tolerance dissipates gradually. If the drug was dangerously toxic, though, I suppose it's possible that enough people would die from taking it to exert selective pressure on the population over time. If some people are genetically immune to the drug, they won't be at risk of overdose (or at least not in the same way), so they would be more likely to live and pass their genes on. For this to result in widespread immunity, either the gene would have to be very easy to inherit once the mutation arose somewhere or a lot of non-immune people would need to die off in a short timespan (like if the government introduced the sedative widely in a reckless fashion).

"Pratical" complete tolerance is more feasible, though. If the drug has a toxic dose near the active dose and induces tolerance over time, it could get to the point that the active and toxic dose were practically overlapping as someone kept taking it. At this point, a non-toxic dose wouldn't have much of an effect on the person in psychological terms, and a toxic dose might kill them, so the only thing they would get out of taking it is staving off withdrawal. In the "forcing everyone to take it to prevent deadly withdrawal" scenario, this kind of effect could throw a wrench in the government's plans once enough people got to that point, especially if nobody really noticed what was happening at first.


You don't need drugs. Control food and water.

Keep soldiers and police well-fed and content so that they stay loyal to you, and eliminate all dissidents as soon as possible. Keep everyone else starving and thirsty. Only give food and water if they work, and only so much that they can work.

Starving people don't usually have any energy to revolt, so most of trouble is eliminated that way, and if they happen to display any discontent, they are no match for well-fed police and army. They cannot even fortify anywhere if they don't have anything to eat, so all revolts die out quickly when already starving people don't get any food until they work again.

That is basically how they do it in North Korea.

Of course, you can add drugs to this. When you use them as an addition, not as the primary tool, tolerance is not necessarily a problem.

  • $\begingroup$ This is a fine idea, but i want the populous to think their situation is better than it is, so they have freedoms like being vegan, choosing from multiple clothing styles, and having breaks. So the government needs to be more subtle, kind of like Vault tech; where everyone thinks they're good, only for characters to discover later its dystopic. $\endgroup$
    – Saxionkin
    Sep 22, 2023 at 1:23
  • $\begingroup$ What if you add in heavy propaganda + give them those treats occasionally: regularly to those who are deemed loyal, dissidents never get them, others now and then to keep their interest up. If you want everyone to think that the government is good, it's hard to avoid heavy propaganda anyway, and rewards that are withdrawn can be more addictive than rewards that you get all the time. $\endgroup$ Sep 22, 2023 at 5:38

Genetic adaptation takes time

What's your timeframe? If that's "near future" after centuries or a few millenia, then you should expect no adaptation, as we can see that even for single gene benefits like lactase persistence (ability to process lactose) a mere 10 000 years isn't enough to fully spread across population, so in the absence of explicit artificial selection/breeding (which still would take hundreds of generations) you shouldn't expect to see major changes in tolerance unless your timeframe is approaching 100 000 years.

  • $\begingroup$ The whole story is around 700-1000 years from current 2023, so I know there won't be any genetic or evolutionary changes, I mean in the short term of personal immunity. I was going to use this information to decide how to approach government drugging in the story, and I couldn't find any info on if people can gain full immunity. $\endgroup$
    – Saxionkin
    Sep 22, 2023 at 1:27
  • $\begingroup$ Genetic adaptation doesn't always take very long. In fact, it can happen in seconds: if you have a population of bacteria in a petri dish, and you introduce a potent toxin into the dish that kills all but the 2% of those bacteria with a genetic resistance to it, you will be left with a (smaller) population of bacteria where genetic resistance to the toxin is common, just like that. This is just as true with humans, but it's rare that anything that bad happens to a large human population, fortunately. Maybe it's a bit beside the larger point, but I just think it's worth noting. $\endgroup$ Sep 22, 2023 at 20:35

Coercion Unnecessary

I don't know why you think the corps need to force people to take drugs. It should be sufficient to offer them for free, and people will self-medicate. You just need to make their lives sufficiently unpleasant, and they will seek out the drugs themselves. Now, you might say that not everyone takes drugs, but that's only partly true. Almost everyone in rich societies partakes in caffeine, and a good portion partake of alcohol and nicotine, all without any external coercion. And with legalization, cannabis will become very popular as well.

Pretty much every natural psychoactive substance has been available for thousands of years, and seem to be as effective today as when they were first discovered (besides caffeine, alcohol and tobacco, we also have peyote, amanita, ayahuasca, iboga, ad nauseum). The body would only build up an immunity if the effects were strictly negative/harmful. Since people take these substances recreationally or to self-medicate, the body only needs to restrict the most negative effects of the substances, such as disturbances to heart rate, metabolism, etc.

When people build up a tolerance, it is because they are taking the drug at high doses. You don't want a drug that lets people get too high. Caffeine is a model drug for your purposes: it provides stimulation, it creates psychological dependence, but overdosing is an unpleasant experience that few people seek out, so it almost never happens.

So the perfect drug is one which becomes less effective or downright unpleasant at increasing concentrations, thereby discouraging overuse. You want it to make people happy/pacified, but not fiends. You could also engineer the drug to cause vomiting/diarrhea at high doses to further discourage excessive consumption. "Training" consumers to partake at the optimal dose will effectively guarantee that they do not become habituated to it.


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