melatonin enhances opiates and reverses tolerance?

[Roxyanne]

I am having the inevitable insomnia issues that come with daily opiate use, so I recently bought some melatonin. I've never taken it before and was doing some research to make sure it can be taken with opiates, and I ran across this nifty article which makes me very happy. (since hydro/oxy/codeine metabolize to morphine this should apply to those as well) So.. I just took my first melatonin pill and I'm interested to see what happens.  Anyone got any experiences combining melatonin and opiates?   Will melatonin turn a bottle of shitty Cheratussin into a great buzz??   


Melatonin enhances the rewarding properties of morphine: involvement of the nitric oxidergic pathway.


Yahyavi-Firouz-Abadi N1, Tahsili-Fahadan P, Ghahremani MH, Dehpour AR.

Author information



Abstract



Melatonin has different interactions with opioids including the enhancement of the analgesic effects of morphine and also reversal of tolerance and dependence to morphine. The present study assessed the effect of melatonin on morphine reward in mice using a conditioned place preference (CPP) paradigm. Our data showed that subcutaneous administration of morphine (1-7.5 mg/kg) significantly increased the time spent in the drug-paired compartment in a dose-dependent manner. Intraperitoneal (i.p.) administration of melatonin (1-40 mg/kg) alone did not induce either CPP or conditioned place aversion (CPA), while the combination of melatonin (5-20 mg/kg) and sub-effective dose of morphine (0.5 mg/kg) led to rewarding effect. We further investigated the involvement of the nitric oxidergic pathway in the enhancing effect of melatonin on morphine CPP, by a general nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME). L-NAME (1 and 5 mg/kg, i.p.) alone or in combination with morphine (0.5 mg/kg) did not show any significant CPP or CPA. Co-administration of L-NAME (5 mg/kg) with an ineffective combination of melatonin (1 mg/kg) plus morphine (0.5 mg/kg) produced significant CPP that may imply the similarity of action of melatonin and L-NAME and involvement of the nitric oxidergic pathway in this regard. Our results indicate that pretreatment of animals with melatonin enhances the rewarding properties of morphine via a mechanism which may involve the nitric oxidergic pathway

 

[2earls]

@Roxyanne I hope you will be back to let us know what benefits you get from Melatonin  (if any). I'm always searching for the magic answer for my insomnia that doesn't involve taking on a new habit for pharmaceuticals.

I think I am going to try kratom even though I can't stand the taste. If it works well enough I suppose I can take the time to make capsules, but something less time consuming is preferable. 

Of course I have heard of Melatonin and that it helps you sleep and kind of dismissed it as something that didn't sound strong enough for my hardcore insomnia. Now that I see the info about opiates I'm interested because I am sure that is the basis of my sleeping issues. 

Thanks for posting 

 

[myalias]

I will be adding this to my regimen as well, I am curious how melatonin reacts with pks.

 

[alixjones2018]

Yes @Roxyanne please update us! I too suffer insomnia but have never tried to use anything for it. 

As I get older I get more frustrated with it and the only reason is because now it's just me.  For so many many years I used those hours as I raised 3 daughters on my own, worked full time, went to college, etc so I used it to my advantage to get more done. 

Now I really don't have much that needs that time devotion. So it's really "ticktock ticktock" screaming in my brain as I pad around my house looking for a time filler! 

SO!...please update us when you try it. I can't wait! 

 

[Roxyanne]

So I really dig the melatonin.  I've used it 4 nights in a row,  and all but one night I was able to sleep 7-8 hours without any residual grogginess.  It's a pleasantly-sleepy feeling and seems to interact quite well with (and even complement) the opiates.   I am taking a low dose (2mg) of the melatonin while those mice in the study were given a shit-ton, but I will say that I normally wake up in complete w/d (eyes running, sneezing, etc) and that hasn't happened.   In fact one night I cut my last dose in half and took it with the melatonin and there does seem to be some enhancement of the opiate effects and an easing of withdrawal (though subtle at this low dose);  Overall I highly recommend.  What it WON'T do:   It will not allow you to sleep when you eat two burritos and a bag of doritos chased with 7.5mg hydr0 at 8pm.  Your undigested food will fill up your chest and not allow you to lay flat until 2am, which is much more torturous when the melatonin is adding to your sleepiness.    So...no meals after 5pm, take your pk's at 8pm, melatonin at 10pm.  It's quite nice   

 

[Roxyanne]

I forgot to tag some folks in my update - see above!!    Also - last night I had a migraine (also made worse by chronic opi use) and the melatonin helped that as well. Didnt get rid of it completely but almost...and I was able to sleep it off.

@alixjones2018  @myalias  

@2earls

 

[Sunrise81]

Thank you so much @Roxyanne, for finding this and letting our awesome community know about it. I’m also one who had insomnia (didn’t know it was from oPi’s) and the mEd I take is m0rF so I’ll def try this!! I’ve had insomnia for years and avg about 1-3 hours a night. I’ve done that for many, many years. But it makes sense now b/c I’ve been on pk’s (severe chronic pain) for many years. I’ve been told, in the past, to try it but I figured that since most rX sleeping aids either make me so groggy the next day or just don’t work at all, that it wouldn’t help me. Now that I know that it works well with what I take, I will definitely be trying it. And I’m also like you, in that I wake up in full w/d’s which sucks each and every morning so I’m really hoping that it helps me with that as well. Thank you again for this very valuable info!!! 

Oh, and if you notice that it also helps keep your tolerance down or even reverses it, please update on that or send me a PM. I would be very grateful! 

 

[Roxyanne]

Y'all -  I gotta give yet another plug for the melatonin.  I'm in a newish relationship, and every time I spend the night at dude's house I can't sleep (he snores, his pillows are horrible, the room is too hot, he wants to spoon, etc etc).  Literally I can't sleep more than about two hours and it takes me three days to recover.  So last night I brought the melatonin with me... and OMG:   I passed out immediately and slept for 7 hours despite a huge meal, two glasses of wine, prob 15mg hydr0, acid reflux and the loudest snoring you've ever heard.   By the time I woke up, he had been up for two hours and commented "you were sleeping so hard I was almost worried.."  YAY!  I've continued researching, and its pretty magical stuff:  lowers blood pressure, improves brain function, curbs anxiety...tons of stuff on PubMed, and I haven't seen any dangers or bad side effects.  Seriously anyone w/insomnia  needs to go get some ASAP.     @Sunrise81 I also resisted trying it for years because I don't like the hangover I get from sleep aids (I also figured it was mostly hype anyway).   I can't tell that its done anything for my overall tolerance, but when you take it at night with the opi's it defintely enhances the euphoria.   And my morning w/d symptoms are wayyy better! 

 

[alixjones2018]

OMG @Roxyanne! I am so excited about this finding! I am like you that I have avoided it just because of that hangover feeling from the one time I have ever tried anything for sleep. 

I know this is going to sound crazy but I want to make sure I duplicate exactly what you are using. Could you share the brand of melatonin you are using? And I think you said it was 2mg right? A couple hours after your last dose of pain medication? You don't take them together, correct? 

This will be a game changer for me if it works even half as well as you are experiencing!

Thank you again for sharing! 

 

[myalias]

Even if it didn’t enhance or reverse tolerance I would recommend melatonin to anyone with any type of trouble sleeping as the very first thing to try.  All it does is make the chemical in your brain that says its sleep time to say its sleep time. Zero impact otherwise, no morning hangovers, no residual effects(no noticeable effect whatsoever other than to help sleep!).

It is truly a supplement and not a drug.

The positive impact on opioids is pretty awesome considering its complete lack of noticible effects other than an easier time initiating sleep.

 

[jmo4114979]

Hi.  There is a site devoted to problems sleeping and one of the things they talk about is melatonin.  The site is cantsleep.org  http://www.cantsleep.org/   I was on ambien 10 mg for 10 years until my children noticed a change in my mood and behaviors.  I could sleep and nap 10-12 hrs a day no problem.  Now I am on Belsomra but wake every night after only 7 hours.  I am no expert but where ambien works on the basis of hypnotic state, Belsomra works on the arousal state, and melatonin works with the bodies natural body rhythyms.  Anyway, My Dr with 50 yrs in the field says that more and more are going to melatonin and with success.  He is trying to get me to try it, but at least for now i favor 7 hrs of sleep over 0 hours sleep.  Following is a bit of the article.  Interesting how it points out that insomnia gets worse with age.

"Melatonin is a very important hormone that is secreted naturally by the human body. It's primary function is helping to keep our circadian rhythms - or body clocks - in check. When those clocks get out of whack, insomnia is a common result. Many people who struggle with insomnia find themselves eager to try sleep aids - natural sleep aids that include melatonin have been effective in managing the symptoms of insomnia.

The link between melatonin and insomnia seems to become stronger and stronger with every passing years, as more and more studies show a connection between the two. Interestingly, insomnia is much more common in older people - and levels of melatonin naturally begin to decline with age. If you suffer from insomnia, you should definitely look into melatonin and find out more about what it can do for you.."

Jack

 

[Sunrise81]

I completely agree @myalias!! Living with insomnia for years really takes a toll on the brain and the body. I got some and am going to try it. I’m praying it works for me. Thank you all for your input!! 

 

[Roxyanne]

 @alixjones2018 i bought Nature's Bounty 1mg tablets. ive been taking mostly 2mg, (but have also tried 1mg and it was pretty effective as well).  i take my last major dose of hydr0 usually around 8 pm and take the melatonin about 930 so i can be asleep by 11.  this weekend i took them together: took big dose of hydr0 and 2mg melatonin about 1am and stayed up till 3am partying- it was a great combo.  im continuing to experiment w the evening hydr0 dose. and of course its all much better on an empty-ish stomach. the melatonin seems to last about 7hrs in the system, so time your dosing accordingly!! and do let us know how it works for you! 

 

[alixjones2018]

Thank you @myalias for that! I don't have the tolerance issue, its purely a sleep thing for me. My pancreas has come to a hard stop on producing insulin for me and I can certainly tell that sleep impacts my "brittle" diagnosis.  The swings are less when I do get a good night's sleep.

@Roxyanne thank you so much! I will let you know! I think I am going to wait until Friday just because I would die from "shame" if I overslept for work!

 

[Handsley]

I took melatonin for years but have stopped 2 years ago when the benzos took over that department, but it worked so good.  I took two 2 mg per night and I slept really well.   I think it's time to get my bottle out again.  I did a lot of research when I first started taking it and here's what I know.  There's a wide variety in the quality.  I've found a really good one that seems to help my son and I.  He suffers from Tourette's syndrome and took it quite frequently when he was younger.  It's safe for children. Kids with Tourette's have a pretty hard time sleeping.  Now that he is a teenager, sleep comes easy, though.  It's the waking up that's hard.   But he has it next to the bed just in case.  

Source Naturals is the one I think is the best.  It's sublingual and they make an orange one that's pretty tasty.  You can get them online at A.  they have dissolving ones and also liquid.  What is recommended is that you need to take it about an hour or 2 before you go to bed.  It enhances your natural sleep hormones, which need darkness and quiet to activate.  So don't expect to fall asleep if you have the lights on and the TV blaring.  A study I read said up to 10 mg per day is considered safe.

I, too, have to set my alarm, take my meds an hour before I get up and suffer till they start to work and God help me if the alarm doesn't go off and I have to get ready without them.  I am absolutely thrilled to hear they might have an effect on my tolerance.  Thank you so much for posting this and starting this discussion.  The times I've had to go off of opiates, one of the worst things is not being able to sleep and the melatonin helped me quite a bit then as well.  When you're at that stage, getting a few hours is better than none.  

 

[Handsley]

I’ve been taking the melatonin and you are right, it does help with that morning crap feeling.  If you are taking benzos too, take less because they work so fast now.  I’ve fallenasleep at my desk, on thetoilet, in a chair.  So don’t take it 1-2 hours before or you’ll be waking up with your pants down doubled up staring at the tile floor.  

 

[Sunrise81]

I finally got some a couple weeks ago. I started by taking one 5mg (I also take 2 benadryls...I have severe insomnia and severe anxiety), but did nothing. Then I started taking two 5mg’s and helped a little. I got some 10mg’s and I take 1.5 so it equals to about 15mgs. That dose helps me actually fall asleep and stay asleep. I get about 7hrs straight sleep whereas before the melatonin, with just 2 benadryls, I was getting 1-2 hrs of very broken up (10 mins here, 15 mins there) sleep. It’s been a tremendous help!! I guess I have to take such a high dose because my insomnia & anxiety are so out of control (which my lovely drs don’t help with either of those). But I’m very glad this thread was started because it has been my saving grace!!! Seriously!!! 

 

[Gracie5]

Something my doctor told me about Melatonin, which I have used for many years, is that you should take it about 30 minutes before you plan to fall asleep, and make sure you are resting and really ready to sleep for it to be effective. It’s also safe for children, according to my son’s doctor (son is 15, so not a young child).

Another natural sleep aid is L Tryptophan. Tryptophan is part of the reason you feel so tired after eating Thanksgiving dinner. 

I’ve always struggled with falling asleep, so I use these in combination with Magnesium. Magnesium is something in the body that can be depleted by stress, and it helps relax the body. It’s also in Epsom salts, so a nice bath with Epsom salts helps with relaxation and muscle aches.

 

[Chicago]

Y'all -  I gotta give yet another plug for the melatonin.  I'm in a newish relationship, and every time I spend the night at dude's house I can't sleep (he snores, his pillows are horrible, the room is too hot, he wants to spoon, etc etc).  Literally I can't sleep more than about two hours and it takes me three days to recover.  So last night I brought the melatonin with me... and OMG:   I passed out immediately and slept for 7 hours despite a huge meal, two glasses of wine, prob 15mg hydr0, acid reflux and the loudest snoring you've ever heard.   By the time I woke up, he had been up for two hours and commented "you were sleeping so hard I was almost worried.."  YAY!  I've continued researching, and its pretty magical stuff:  lowers blood pressure, improves brain function, curbs anxiety...tons of stuff on PubMed, and I haven't seen any dangers or bad side effects.  Seriously anyone w/insomnia  needs to go get some ASAP.     @Sunrise81 I also resisted trying it for years because I don't like the hangover I get from sleep aids (I also figured it was mostly hype anyway).   I can't tell that its done anything for my overall tolerance, but when you take it at night with the opi's it defintely enhances the euphoria.   And my morning w/d symptoms are wayyy better! 

Thanks for all the great info! Better send him to buy those ‘My Pillows’ - those are killer pillows! Woot has them on sale every so often.  Anyway, read your post and went out for some melatonin. Thx again!