# What does half life really mean?



## BusterBluth (Sep 21, 2009)

I understand that it's supposed to be the period after which a substance loses half of it's availability/effects (or something close-- I'm not all that interested in the definition, more about what this means practically speaking).

The reason I raise this question is because I was reading about adderall and, though I didn't see a half life specific to adderall, I saw that amphetamine was reported to have a half life of ~12h and the same for dextroamphetamine. If the half life is, relatively, long, why is it that many people report the effects of IR being gone after 4-6hrs?

Methylphenidate's half life seems to make a bit more sense. It is reported to be 2-4hours, which is more consistent with the duration of its reported IR effects.

If I am missing something basic in the pharmacology of adderall, which is probably the case, correct the error. Otherwise, why do people often have the short-lasting experiences with amphetamines/adderall if the half life is supposedly half a day?


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## Ehsan (Mar 21, 2009)

i have a similar question.
cyproheptadine's half life is claimed to be 1-4 hours.
but its sedative effect starts after 4-5 hours and drowsiness remains for a long time.

maybe that's because drugs' effect is highly nonlinear versus plasma level of drug. there are many drugs that are known to work differently at various dosages for example amisulpride.
human's brain is very complicated. there are many drugs that have unknown mechanism of action after many years of use!


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## JayDontCareEh (Jul 16, 2007)

I think it just means how long the drug stays in your system. 

I could be way off though.


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## martyboi (Sep 18, 2009)

the half life and how long the drugs effects lasts are not necessarily the same. For example the half life of THC can range from 1-10 days even though the effects only last like 2.5 hours...the duration of the effects has more to do with how long it takes your brain to regain control of itself after the drug has been in control.


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## Ash09 (Apr 27, 2009)

The half life refers to the blood plasma concentration, many drugs bind to plasma proteins such as albumin, obviously when bound to these proteins the drug doesn't have any psychoactive effect because it's not binding to any receptors in the CNS. So a drug with a high rate of protein binding like diazepam will remain in the blood plasma a long time after it has been displaced from receptors in the CNS, drugs with lower protein binding like morphine will largely be eliminated from the plasma before it has been displaced from the CNS giving it a longer duration of action than it's half life. Some drugs have low lipid solubility so take a long time to be absorbed into the bloodstream and then the CNS, this means a drug can take longer than it's half life to exert a psychoactive effect. Drugs can also undergo recirculation due to various factors such as being absorbed into tissues like fat and muscle which complicate matters of half life.


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## pharmSAD (Jan 9, 2010)

Half life refers to the length of time following the taking of a drug that it takes for half of the drug to be excreted by the body. e.g. let's say you take 30 mg of drug X, which has a half life of, say, 8 hours. Eight hours after taking that 30 mg of drug X, only 15 mg (i.e. half of 30 mg) will be left in your body. However, half life is just one more thing that varies from person to person and can vary from day to day in one person. This is also simplified, as half life usually has to do with plasma (blood) concentration. Nevertheless, that is at least the idea of half life.

As you can see, it has nothing to do with how long it takes for a drug to become active; in fact, if anything, it refers to the opposite: how long it takes for a drug to lose its effect.

And it's further complicated because of the accumulation of dose. e.g. let's say you take 30 mg of drug X (same drug as in the previous example) every 8 hours. After your first 8 hours, only 15 mg of drug X will be left in your system; however, you then take another dose (of 30 mg), so you now have 45 mg in your system. Eight hours from then, you'd have half of 45 mg left in your system - so 22.5 mg, but now you take another dose: you have 52.5 mg in your system. After another 8 hours and another dosing, you have (52.5/2) + 30 = 56.25 mg in your system; after another, you have 58.125 mg in your system; after yet another, you have 59.0625 mg; and so on... Eventually, you'd have 60 mg in your system, which is when you're said to be in "steady state" (because 8 hours after taking your last dose, you'd have excreted 30 mg, but then you'd take another dose of 30 mg, so you'd be back at 60 mg).

This is sometimes why it takes a while for a drug to take action. e.g. let's say you need 50 mg of drug X in your system for it to take action; well, you would need to take three doses of it before it reached those levels.


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## UltraShy (Nov 8, 2003)

Half life is simply how long it takes for half of a drug to leave your body. It's a pretty poor indicator of therapeutic effect in some cases. Take Valium, for example. Valium, counting all its active metabolites has a half life of up to 200 hours. Anybody who's taken it can assure you that Valium doesn't remain in effect for 8 days, perhaps 8 hours.


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## John_in_SF (Mar 1, 2009)

Most drugs don't maintain their therapeutic effect for long, at least on a single administration. So half-life isn't very useful infomation except for titration, _e.g._ getting off a drug which has discontinuation effects.


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## pharmSAD (Jan 9, 2010)

UltraShy said:


> Half life is simply how long it takes for half of a drug to leave your body. It's a pretty poor indicator of therapeutic effect in some cases. Take Valium, for example. Valium, counting all its active metabolites has a half life of up to 200 hours. Anybody who's taken it can assure you that Valium doesn't remain in effect for 8 days, perhaps 8 hours.


This kind of goes with what I said.

Here's the idea: let's say you need 100 mg of valium for you to get 100% effect.

If you were to take 10 mg of valium, you'd have absolutely no effect.
If you were to take 30 mg of valium, you'd have maybe 5% effect.
If you were to take 50 mg of valium, you'd have maybe 15% effect (even though you are taking 50% of the dose that gets you 100% effect).
If you were to take 70 mg of valium, you'd have maybe 30% effect.
90 mg of valium, you'd get maybe 60% effect.

Not everything is linear. That is, if you have 50% of the drug in your system, doesn't mean that the drug is at 50% of its max effect. A lot of the time, if you have 50% of the drug in your system, you can barely feel the effect of the drug; however, if you double the dose, you might absolutely feel the effect of the drug. It can even be more specific than that, where 80% of the drug in your system = a little bit of effect, but increase the dose just a bit, and you get a lot of effect.

Thus, if the half life is say 200 hours, it might take just a few hours before you lose 20% of the drug (half life is also non-linear), such that 80% of the drug is in your system. As I said before, oftentimes 80% of the drug in your system may only produce a small effect compared to having 100% of the drug in your system. So excreting only a bit of the drug might totally reduce the effect of that drug. Small reduction in amount of drug (which doesn't take long to occur) ---> big reduction in the effect of that drug.

Does this make sense?


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## BusterBluth (Sep 21, 2009)

I'm glad so many people decided to continue to define half life even though that was understood and not the question being asked... jk-- all responses are always welcomed and appreciated. 

But basically what I am hearing is that half life is not a good indicator of how long you will experience the effects of a certain substance-- this is good information. So why then do so many people say things like 'oh, well XYZ has a half life of #hrs so you _definitely _need to dose every 24 hours on the hour."?


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## pharmSAD (Jan 9, 2010)

BusterBluth said:


> So why then do so many people say things like 'oh, well XYZ has a half life of #hrs so you _definitely _need to dose every 24 hours on the hour."?


This is likely the most commonly used phrase in pharmacology: it depends. It depends on several things, most notably the half-life and the drug's effect on you. The shorter the half life, the more important it is that you take the drug on schedule; the more powerful the drug's effect on you, the more important it is that you take the drug on schedule.

Why? If it takes 4 hours for half of the drug to be eliminated from your system, then missing a dose by an hour is pretty significant (one hour is 25% of 4 hours). If it takes 200 hours for half of the drug to be eliminated from your system, then missing a dose by an hour is pretty INsignificant (one hour is 0.5% of 200 hours).

If the drug has a strong effect on you, then having a small amount of it in your system (which is what would happen if you missed a dose by an hour with a drug that has a half life of 4 hours), would mean that the drug would have very little effect, and you might also experience withdrawal symptoms. If the drug only has a small effect on you, then you won't likely know the difference between 50% effect (taking it on schedule) and 35% effect (taking a drug with a half life of 4 hours an hour after schedule). Think of it this way: it's easy to tell the difference between 50 pounds and 70% of 50 pounds, which is 35 pounds; however, it is quite a bit more difficult to tell the difference between 5 pounds and 70% of 5 pounds, which is 3.5 pounds.

And don't forget that people sometimes say things that aren't totally true.


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## OKdOut (Feb 22, 2008)

*half life*

In practical terms, half-life is important for 3 different reasons.

1. effectiveness
2. toxicity
3. bioavailability

1. Effectiveness 
For all drugs, there is a concentration where one can expect the drug to work, and there is also certain concentrations when a drug will not work at all. There is a certain percentage of the receptors in the body that needs to come in contact with the drug, in order for the body to respond to the drug.
Drugs are generally titrated to a 105 lb 5'5'' female and a 160 lb 5'10'' male, or the average of the two. If you are larger or smaller than those figures, the concentration of the drug will therefore be higher or lower, and the effect will last longer or shorter correspondingly. Also, if your body is used to the drug, you will also need a higher concentration in order to get the same effect, or the effect will last much shorter than normal.

2. Toxicity
All of the above assumes that the person has a healthy liver and kidney.
Half-life also refers to the time it takes for the liver to convert dangerous chemicals into harmless chemicals.There is a certain point of concentration of a drug in which the liver just can not handle it and the liver will fail. In alcohol for example, if you reach that point, the liver will begin to fail, and the full strength of the alcohol will remain in the body, and eventually reach the brain. At that point, the person will have alcohol poisoning, meaning the concentration of the alcohol is greater than the liver can handle.
So you would want to know the half life of a drug, in order to space the dosage so that the concentration of the drug never gets higher than the liver can handle.
Similarly, our kidneys remove drugs from the blood. Their is a certain concentration at which our kidneys can not handle, and they will fail. So we also want to know the half life in order to space the dosage so that the concentration in the body never exceeds what the kidneys can handle.

3.bioavailability
The 3rd reason we need to know the half life of a drug, is to know how long we can expected it be active in the body. This is much more complicated than the other 2 reasons. Some drugs will only work at certain concentrations and will not work at all at other concentrations. In addition to that, drugs can interact with other drugs if their concentrations is high enough, and drugs can trigger allergic or other defense behaviors from the body. Water soluble drugs like Vitamin C, will dissolve in water and can easily leave the body. LSD on the other hand, is a fat soluble drug. The drug can remain in the fat cells, as long as those cells are alive. 
If a person is about to change drugs,like from benzodiaprines to _MAOIs_, you need to know the half life of the previous drugs in order to ensure that the body has elinmated enough so that the two drugs will not react with each other. This is why one needs to wait a certain period of time before changing to different class of drugs, or changing between different times of drugs.

So we want to know the half life of a drug, in order to know the concentration of the drug at any point in time, even months after the person originally took the drug. In this way, dosages are set so that the concentration is high enough for the body to respond to it, but not high enough for the drug to overwhelm the body.


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## meyaj (Sep 5, 2009)

omg... all this misinformation in this thread is making my head hurt. I'm too tired now to really address anything, but I'll make one little exception



OKdOut said:


> LSD on the other hand, is a fat soluble drug. The drug can remain in the fat cells, as long as those cells are alive.


LSD is HIGHLY water soluble and actually insoluble in fats, and is quite rapidly eliminated from the body, with a half-life of (at most) a few hours.


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## OKdOut (Feb 22, 2008)

meyaj said:


> omg... all this misinformation in this thread is making my head hurt. I'm too tired now to really address anything, but I'll make one little exception
> 
> LSD is HIGHLY water soluble and actually insoluble in fats, and is quite rapidly eliminated from the body, with a half-life of (at most) a few hours.


I was wrong and you are correct. LSD is water soluble. I was thinking of something else.

And there are a few other incorrect details there too. But I wasn't into fine details, just the overall idea.


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## John_in_SF (Mar 1, 2009)

pharmSAD said:


> This is likely the most commonly used phrase in pharmacology: it depends.


My candidate is, "The exact mechanism of XXX is unknown." (But XXX sure makes a hell of a lot of money!)


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## millenniumman75 (Feb 4, 2005)

^Wow.....Triple X! :lol


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## spazitude80 (Jun 24, 2013)

BusterBluth said:


> I understand that it's supposed to be the period after which a substance loses half of it's availability/effects (or something close-- I'm not all that interested in the definition, more about what this means practically speaking).
> 
> The reason I raise this question is because I was reading about adderall and, though I didn't see a half life specific to adderall, I saw that amphetamine was reported to have a half life of ~12h and the same for dextroamphetamine. If the half life is, relatively, long, why is it that many people report the effects of IR being gone after 4-6hrs?
> 
> ...


In order for you to understand the half life you have to understand bioavailibility. You see depending on the route taken oral IV IM ect drugs have a differant BA percentage the BA is going to be much lower orally than IV the drug in question Adderall actually has a rather high Oral BA I think about 80 percent that means if you take 10 mg IR your body is only using 8 MG of it food usually effects BA but not in the case of adderall. IV your going to be getting 100 percent of 10 mg's of the drug. Thats why the med you get in your IV tube is much less than what you would take orally for instance you might take 20 mg morphine than get admitted to the hospitol and get 15mg with the same effect because its going in your vains. That being said half life has nothing to do with effects it has to do with the amount of drug in your system like others before have said if adderalls half life is 12 hours than if you take it now in 12 hours half will be out of your system 12 more hours half more and so on until its undetectable Well the reason adderall only last 6-8 hours is because with this drug spacifically you want to take the lowest possible theraputic dose and with a low dose you may have what is called "end of dose failure" Many people only use it for work/school so they only need it to work for a short period of time so they take a small enough dose to where it doesn't work the full 12 hours but you have end of dose failure. Also depends on tolerance, metabolism and theres other things that can mess with Adderall. I hear that grape juice has a synergestic effect on Adderall but I'm not certain. Sorry I probably confused everyone more.

and PS. Acid is most definatly water soluable


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