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Opioids Can Benadryl (Diphenhydramine) higher my hydrocodone tolerance?

brownsound

Greenlighter
Joined
Apr 18, 2008
Messages
14
I've been getting prescribed norco (10/325) from my doctor (and getting a few extra on the side every month).


I've also had trouble sleeping, or had extremely restless sleep, so I turned to Benadryl for help. It worked like an absolute charm, except for one thing: It seems as if when I'm regularly using Benadryl to help me sleep, my hydrocodone tolerance goes up. Now don't get me wrong, I know that diphenhydramine is usually used to potentiate the effects of the hydrocodone, but I'm not talking about dosing them together, as I only need the Benadryl to help me sleep.

Within lies the problem---every time I start taking Benadryl to help me fall asleep, I notice a pretty large difference in my tolerance. If this was just a one-time thing, I wouldn't have even given it a second thought, but the funny thing is that there are three distinct times that I can remember where I've stopped taking Benadryl (but continued with the hydrocodone), and after one or two days of no Benadryl, it takes me only about 50% of a normal dose of hydrocodone to reach the same high as usual.


I'm absolutely 100% positive that this is what is happening, but I have researched and still haven't come up with anything, so I thought I'd ask here =)


Thanks for the help everybody!
 
Diphenhydramine can have a slight "hangover" effect.

Also, how long have you been taking hydrocodone? How often do you take it? What kind of doses do you take? It is possible it's just regular opiate tolerance but I'm not sure.

Using multiple sedatives can decrease the effectiveness of any one downer, but overall I am not sure what's going on here. Maybe some other people will have some more insight.
 
Diphenhydramine can have a slight "hangover" effect.

Also, how long have you been taking hydrocodone? How often do you take it? What kind of doses do you take? It is possible it's just regular opiate tolerance but I'm not sure.

Using multiple sedatives can decrease the effectiveness of any one downer, but overall I am not sure what's going on here. Maybe some other people will have some more insight.

I was also thinking it was a regular tolerance, but it's just too much of a coincidence that the three or four times that I stopped taking Benadryl regularly (about a month's break each time) my hydrocodone tolerance greatly decreased.

As far as hydrocodone doses, I take about 30mg. And I definitely know what you're talking about with the whole "hangover" effect of Benadryl, sometimes when I wake up I'm really groggy...maybe that is why? Another strange thing I noticed is that every night once the Benadryl kicks in, I'll get slight chills every now and then (which I would otherwise absolutely NEVER get---besides when I'm withdrawing from hydrocodone).

It is also important to mention that I take quite a bit of the Benadryl to get me to sleep, usually about 150-200mg (I've grown quite a tolerance to it).


Well thank you for that oh so insightful response, chief.
 
I am actually not sure why you have experienced this.

I don't have a lot of benadryl or diphenhydramine hcl experience, I don't really like it as much as doxylamine succinate or hydroxyzine hcl.

Maybe other people could offer some insight. :)
 
Please don't bump your own thread.

Many people who take antihistamines such as diphenhydramine and other sedating ethanolamines find that unless they use opioids (or MORE opioids) that they'll be restless and uncomfortable and they won't get the effects in this regard that they normally experience or expect from opioids alone.

Whether that theory is correct for you or not I don't (and can't) know, but I do know that your opioid receptors don't magically down regulate from introducing anticholinergic drugs (drugs that work on acetylcholine, not opioid receptors) and then magically up regulate when you stop taking them.

I can understand believing your tolerance to be going up and down but it just doesn't work like that in the brain with these substances.
 
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I used to take a ton o f benadryl, used to trip of tylenol simply sleep, then I stopped breathing one day, and never again.

Now i almost puke if I even think of them, and I've taken them a few times after, and just makes me feel like shit.

There shouldn't be a cross tolerance, antihistamine and opiates. So I'd say most likely your drop in tolerance is more so you need more to feel good, but it's not really changing your tolerance. The benydryl can make you feel shitty, but it's not going to do anything to your opiate receptors. Hope that makes sense
 
^spot on.

The only thing I'd quibble with (and its pretty much just semantic) is that what he is experiencing isn't a change in tolerance but a *perceived* change in tolerance.

Thanks for adding the akathisia link, C.H.

Ironically, anticholinergic drugs are used to treat extrapyramidal effects (such as akathisia) caused by taking neuroleptic medication however these drugs like diphenhydramine alone can cause symptoms similar to akathisia/RLS.
 
^spot on.

The only thing I'd quibble with (and its pretty much just semantic) is that what he is experiencing isn't a change in tolerance but a *perceived* change in tolerance.

Thanks for adding the akathisia link, C.H.

Ironically, anticholinergic drugs are used to treat extrapyramidal effects (such as akathisia) caused by taking neuroleptic medication however these drugs like diphenhydramine alone can cause symptoms similar to akathisia/RLS.

So you are saying that he's experincing a percieved change? If so that's the same thing I was saying.

If we consider tolerance as number or opiate receptors, there would be no change from taking diphenhydramine, however, continued opiate use would increase them, and likewise tolerance. So any tolerance changes may manifest as real, but have no basis from the opiod receptors
 
So you are saying that he's experincing a percieved change? If so that's the same thing I was saying.

If we consider tolerance as number or opiate receptors, there would be no change from taking diphenhydramine, however, continued opiate use would increase them, and likewise tolerance. So any tolerance changes may manifest as real, but have no basis from the opiod receptors

I think what might be happening is that diphenhydramine is overpowering a certain part of the opiate experience.

Kind of like if you take benzos on top of buprenorphine and pass out, you will be asleep and not really get to appreciate the mildly stimulating nature of buprenorphine.

I don't know if that makes much sense to you or not, but I hope it does.
 
^that's a really good comparison.

Jam- I was more so quibbling with phrasing, I thought we were on the same page. I think we're probably even on the same paragraph!
 
I don't know if this might help with the groggy hangover of diphenhydramine, I used to take it when I worked till 2.00am then had to be up for 7.00am, it took me a while to wind down after work.
I used to wake up feeling like crap, then I realised it'd better to take it only if you can have around 8 hours of uninterupted sleep..I know this isn't always possible but it does help.

As for the other thing, I take around 300mg of DHC a day, and often take about 80mg of diphen and it never affects me either way.
 
^that's a really good comparison.

Thanks Cane! I was hoping it made sense to someone. :)

I do believe though, that's the difference between enjoyable and dull drug combos. If you choose one drug that's going to mask the effects of the other (MDMA and cocaine for instance), then the combo is probably not going to be as fun as when the other drug will amplify/blend with the other (heroin and cocaine, as an example).

And such an effect can vary from person to person (like amphetamine and benzos, for me the benzos would kill amphetamine's effects so I wouldn't bother combining these, but some people actually like to combine these regularly or occasionally).

I don't know if this might help with the groggy hangover of diphenhydramine, I used to take it when I worked till 2.00am then had to be up for 7.00am, it took me a while to wind down after work.
I used to wake up feeling like crap, then I realised it'd better to take it only if you can have around 8 hours of uninterupted sleep..I know this isn't always possible but it does help.

As for the other thing, I take around 300mg of DHC a day, and often take about 80mg of diphen and it never affects me either way.

I agree, at times when I needed to wake up early, antihistamines are always a bad choice just because I would wake up not refreshed at all.
 
So far these responses have been extremely insightful for me, thanks.

Cane, I do understand what you're saying about how the strength hasn't changed in any way due to the diphenhydramine, that it just feels like it has, but the thing that I don't get about that is this:

Those times after stopping diphenhydramine abruptly, what an 80mg dose did for me (in terms of analgesia, euphoria, sedation), would now only take 40mg. I took an 80mg dose after I stopped the diphenhydramine, and I was nodding, feeling almost like puking, and super constipated for almost 2 or 3 days. I don't really take them for recreation or to feel like that, so it was a bit offsetting.

Could it be that maybe the diphenhydramine that had been in my system constantly (every night I dosed to go to sleep) was the reason why I could handle an 80mg dose without puking/nodding? I know that diphenhydramine is an antihistamine and as such it would help with puking and the like, but I'm still kinda confused.
 
The other posters seem to be focusing on the pharmacodynamic interaction between these two drugs. First, your doctor should know you are taking diphenhydramine while concurrently taking hydrocodone. In your first post, you mention that taking diphenhydramine makes feel like your hydrocodone tolerance goes up. The potential for this interaction could be due to diphenhydramine's potential(moderate) to inhibit hepatic microsomal enzyme CYP2D6. Hydrocodone is partially a prodrug which needs CYP2D6 to metabolize into its more potent form hydromorphine. Therefor, if you take a CYP2D6 inhibitor with
Hydrocodone then you are less likely to feel the very potent effects of the more active metabolite. That said, you would still receive therapeutic benefit from the drug itself and other metabolites. You should speak to a pharmacist about this and most should be able to confirm this and give you better treatment advice.
 
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