I’ve been on Adderall for several years, 20 mg. XR with an occasional 5 or 10 mg non-XR later in the day, but not too late, maybe 2:00 or so.

I’ve not experienced problems falling asleep and staying asleep until the past several months. The usual melatonin and Benadryl to solve the problem is no longer working.

Now I find myself taking .50 mg of Xanax to sleep and am concerned that this will become a habitual need for decent sleep.

Any thoughts or suggestions would be greatly appreciated. I do se my Psychiatrist in a few weeks.

Thank you so much!

Do you exercise on a frequent weekly basis (at least 30 minutes 3 times a week)? If not, the sedentary lifestyle can produce troubles getting a good nights sleep.

Also, one thing to note is that the typical duration of effects for extended release amphetamine salts is ~ 8 hours, and for the instant release is ~ 3-4 hours. One thing that I noticed that you are taking is Benadryl. Benadryl, or diphenhydramine HCL, is scientifically known to inhibit the cytochrome p450 substrate (2D6) that metabolizes amphetamine. The extent of inhibition is unknown, but it is known to have varying intensities of inhibition in people. This is alot like grapefruit juice interaction (except grapefruit is with the 3A4 substrate) with other various drugs.

This basically means that if you take diphenhydramine, it will block the 2D6 substrate from metabolizing and deactivating the amphetamine salts. This causes a rise in absorbtion rate, and thus a higher blood serum concentration (basically like taking more medication than you would have normally).

Did that last paragraph make sense? It's like saying taking adderall is fine, lets say you take one pill. But, if taken with diphenhydramine, it is like taking 2 or 3 pills instead (or even more depending on the severety of the inhibition).

Here is where I got that information from if you were curious in reading up on it(an .edu site): http://www.medicine.iupui.edu/Flockhart/table.htm

Thank you ECU20! Fascinating!

I'm not so sure that is 100% correct ecu20. From that chart:

Inhibitors compete with other drugs for a particular enzyme thus affecting the optimal level of metabolism of the substrate drug which in many cases affect the individual's response to that particular medication, e.g. making it ineffective.

Since they are competing for the same enzyme, wouldn't it make more sense that the amphetamine has used up most of this during the day and the diphenhydramine is what is not metabolizing well and thus having no effect (not helping with sleep in this case)? That's what it seems like to me.


What you describe seems vaguely possible if taken the other way, say you had a bunch of diphenhydramine and then a couple hours later amphetamines which would not immediately metabolize due to the enzyme being depleted from the diphenhydramine... I still don't think this would build up to "2 or 3 doses", I think that it would just not kick in till later when more of the enzyme is available, so if you took a regular scheduled dose 4 hours later and your original dose is still in your system it would be like taking a double makes sense. Do you have any citation for the 2 or 3 dose type of thing?

To clarify, I agree that you should probably avoid mixing the two as neither will have it's optimal effect due to enzyme depletion.

also do/did you take any of the following:

yohimbine
caffeine
baking soda
alka seltzer
tums
MAO inhibitor
tricyclic antidepressant

?

I'm not so sure that is 100% correct ecu20. From that chart: ...
Since they are competing for the same enzyme, wouldn't it make more sense that the amphetamine has used up most of this during the day and the diphenhydramine is what is not metabolizing well and thus having no effect (not helping with sleep in this case)? That's what it seems like to me.
...

Do you have any citation for the 2 or 3 dose type of thing?

Just to clarify what i am answering, referring to your quoted bold or underlined text.

To address the bold portion, I think you may have substrate and inhibitors confused. In that chart, amphetamine (adderall) is a substrate of CYP450-2D6, and diphenhydramine (benadryl) is an inhibitor of CYP450-2D6 (unknown to what extent being a powerful or weak inhibitor).

A substrate is "a molecule upon which an enzyme acts."

With that definition, all inhibitors can technically be defined as substrates. BUT-

An inhibitor "competes with other drugs for a particular enzyme thus affecting the optimal level of metabolism of the substrate drug."

This means that an inhibitor is relatively selective and actively competes against the substrate in being metabolized, thus more of the inhibitor is metabolized than the substrate; theoretically.


To answer the second part, no I do not have a citation for the 2 or 3 dose type of "thing." I was simply attempting to put it into layman's terms so the majority of people would understand, that it will potentate and greatly increase serum blood levels of amphetamines (like everything else in this world, everybody is different, as is the same with drug metabolisms and dosage efficacy).

As for the diphenhydramine, depending on how quickly the original posters body could metabolize and excrete it plays a part in if it was the culprit.

----------------------
Cite for info below: http://www.druglibrary.org/schaffer/Misc/driving/s13p5.htm

A study that shows graphs of peak serum levels of diphenhydramine of a 22 year old male who injested 100mg of diphenhydramine peak in 2-3 hours at 0.2 µg/ml. At 10 hours late, there was still serum levels of 0.075 µg/ml 10 hours after injestion. The graph is below:

http://www.druglibrary.org/schaffer/Misc/driving/figure/s13p5f3.gif

Depending on how much the original poster took, and how much time was in between that throughout the night into the next morning when the OP stated they took their adderall dosage. They still possibly would have (probably DID) have a serum level of diphenhydramine that could potentially interact with assisting a greater absorbtion and bioavailability of adderall.

The studies conclusions also could help explain why when you take diphenhydramine for an OTC sleep aid, you sometimes still wake up the next morning still drowsy/sleepy and groggy ;).

No I havent had the alkaline products....I know they can greatly enhamce the effects of amphetamine.
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I'm sorry, but i'm just not sold on melatonin being an effective sleep aid. 0.3mg is about how much of that hormone our body produces, and most people take 1-3mg if not more at a time, which is more than our body will ever produce at one time. I took it at 1mg, and did not notice it helping. Diphenhydramine did more for me at 100mg ;)

I'm sorry, but i'm just not sold on melatonin being an effective sleep aid. 0.3mg is about how much of that hormone our body produces, and most people take 1-3mg if not more at a time, which is more than our body will ever produce at one time. I took it at 1mg, and did not notice it helping. Diphenhydramine did more for me at 100mg ;)

What is the bioavailability of melatonin taken orally? Another thing to consider is that if you're not sleeping well in the first place, then your natural melatonin being secreted is not actually being secreted (due to not enough darkness), or is not doing it's job effectively.

I used to get a significant effect from melatonin supplements (3mg), though lately I seem to not be affected at all. It's hard to believe that I could have a tolerance to it, especially since I've stopped using for over a year, so I'm wondering if there's a factor that is inhibiting it's absorption. Also, I've found that not all melatonin supplements are equal in effectiveness (at least for me). I have yet to determine the difference (though I know I wasn't comparing apples to oranges either, as I was comparing 1 3mg tablet to 3 1mg tablets of differing brands, but it's still interesting that the 3 1mg tablets were totally ineffective).

Another note:

Amphetamine is the active ingredient of Adderall. Diphenhydramine is the active ingredient of some sleep aids. These ingredients don't need to be converted to something else to actually make them active. Rather, the enzymes are used to make them inactive. The main thing that is in the way of effectiveness is absorption. If anything, taking one is going to potentially prolong the exposure to the other. However, a significant portion of Amphetamine is excreted unchanged, so actual metabolism has less of an impact on the duration of effect compared with other drugs (which are mostly excreted in metabolite form).

Now I find myself taking .50 mg of Xanax to sleep and am concerned that this will become a habitual need for decent sleep.

Any thoughts or suggestions would be greatly appreciated. I do se my Psychiatrist in a few weeks.

Thank you so much!


The Xanax will be nothing but trouble if you start relying on it for sleep, your concerns are very valid. Benzo addiction is no joke, look up some of the withdrawal effects - people can die from coming off these meds if they are on high doses for long periods.

My advice - make sure you get enough exercise every day (20 minutes of intense cardio work) cut out any caffeine. Lower your dose of adderall or take your last dose earlier in the day.

Yesterday was my first day on adderall. It was effective but even though my last dose was around 4 pm, I couldn't sleep and barely got any sleep all night. I'm exhausted today and I have class.

Okay, I think I understand now... thanks HighFunctioning and ecu20. Just to clarify:

Amphetamines and diphenhydramine are already active and don't need to metabolize to be effective, however, as they metabolize less is available and their effects decrease.

Taking both together would, thus, make less enzyme available causing both to metabolize slower and there would be more of both drugs in your system than normal.

http://74.125.45.104/search?q=cache:usT4HSCyCLEJ:gsm.about.com/compact/showmono.asp%3Fmonotype%3D%26cpnum%3D2220%26r%3D60 78%26match%3DF+melatonin+bioavailability&hl=en&ct=clnk&cd=1&gl=us
Melatonin bioavailability is: 30-50%, unstated whether it is male or female.


http://www3.interscience.wiley.com/journal/73504060/abstract
Females melatonin bioavailability is 3x the amount of men (3 fold).


Unsure about how much, but the minimum is 30% (.9mg). Women are 3 fold though, and the 30-50% does not state men or women.

Hi Carriie. I've never known (personally) Benzo's (Xanax) to be reliable in the long run for obtaining a quality sleep. I too suffer from sleep depravation after being on adderall for a long period of time. I also don't help matters by consuming caffiene while taking adderall as ecu20 and others suggest. I hit a point where I am thinned out, ill tempered, and quite frankly...more ADD than without the medication. It's frightening how this mode of being creeps up on me without being fully aware. My only remedy to date has been to take a brief vacation from the adderall and catch up on sleep. One of the benefits of Adderall is that it's not a substance that has to build up in your system over time to gain effectiveness, and allows a little more flexibility than most other psychotropic medications. I am not saying this is necessarilly what you should do, and I certainly would not suggest anyone attemting such without the advice of their doctor. I'm only telling you what has seemed to work for me thus far. I just came off a 3 day vacation period today which is the longest I have taken in the last several months. I slept rougly two whole days away in the 3 day period. I go through various stages of mild depression and anxiety while doing this but I keep reminding myself that I am comming off the meds, and I just try to remain relaxed. Once I feel a sense of normalcy, I go back on the meds and I am good for another month or so before I have to do it all over again. If only I (stupid) would give up the coffee! :-) I might not have as much sleeping issues, but I just love it too much.