Opiates and Sleeping

[Enlitx]

I just started grad school to obtain my PhD in pharmacology, so my knowledge is limited at this point, but there is one question that has been bugging me for a while. I used to use opiates extensively before I realized that they were not compatible with a successful career. During the early days of my use, they would induce a heavy sleep. After I became addicted, and from that point forward, they would prevent me from obtaining even a few hours of sleep. I would literally get one or two hours of sleep if I was lucky, even if I dosed twelve hours before I went to bed. To my knowledge, opioids are generally inhibitory agonists. Although it was grossly simplified, my medical pharmacology course stated that generally opioids decrease cAMP and thus decrease signal transduction. I realize that they stimulate the release of dopamine in the nucleus accumbens, but what role does that have in the sleep/wake cycle? I would think that they would promote sleep, not prevent it. Why did sleep deprevation only become pronounced after I suffered from addiction? Also, why do they cause such intense and severe nightmares? This would seem counter intuitive. I realize that these questions are quite broad, but if anyone knows certain pathways in the brain that may play a role, or biochemical mechanisms that may be responsible, I would love to put this question to rest.

 

[Epsilon Alpha]

It more has to do with rebound CREB activity in the locus coeruleus (think massive NE increases) than anything else as far as I know, they also suppress REM and royally rape your sleep architecture. As for the role each individual mechanism of action plays I don't know.

My current pharmacology prof is a pain specialist so I'll see what else he has to say on this when classes start.
-EA

 

[Nagelfar]

My simple understanding would be with continued use, dopamine becomes increasingly a reinforcer, with higher levels the more & longer you become habituated.

However my experience personally is different. At first, I could sleep 1 or two hours, wake up feeling like I had the best rest of my life, realize it was only a couple hours sleep, shrug my shoulders go about my day, and usually nod out some time therein. Three years of near continuous use later I sleep normally (it didn't take nearly this long but this was my time of use / situation at the end of my last habit) but awake in slight withdrawal that helped me actually get out of bed (have had a psychologically hard time getting out of bed my entire life) with motivation to get more opioids (at least).

However, unlike many people, I can sleep in the beginning of withdrawal, even on a three bag a day habit, I usually sleep heavily the first three days of discontinuation. The fourth & fifth or fifth & sixth day is when I am vomiting and can't sleep well, and the sleep I do get I don't remember, cold sweat and cramps, feels like my heart is beating too fast & painfully, I even try to hold my breath until I pass out it's so miserable.

 

[BananasAndOranges]

Tolerance and dopamine like said by another poster. Once your body gets adjusted its kinda like a rush of dopamine and thats what makes you feel good. Shit I make no sense lol.

 

[whippa craka]

Because you were addicted, and withdrawls can start creeping up quickly and quietly. Im sure you know symptoms of opiate withdrawals include RLS, cold sweats and inability to sleep. Dosing 12 hours before sleep would be terrible, you would be going through withdrawals, whether mild or severe, before you go to bed. Dosing right before sleep would have been the best thing to do.

The answer to your question is: Withdrawals.

 

[Biovail]

For a while I was taking oxycodone. If I took it within the 3 hours before I went to sleep, I would have very intense nightmares before I was even fully asleep. It seems like nightmares normally only occur in REM sleep, when your brain is capable of "imagining" hypothetical situations. In NREM sleep your brain is simply repeating brainwave patterns you experienced throughout the day.

But when on oxycodone one of two things was happening. Either I was somehow having nightmares in the very early stages of NREM sleep, or I was entering REM sleep immediately and not cycling like a person normally does, but without the normal body paralysis that accompanies it. The result was very scary and would often make me not want to go back to sleep. Though I would be dreaming and having nightmares, I would still be fully concious of my body laying in bed. It's very hard to describe. Normally upon waking from a dream, you're aware that you were dreaming and can say to yourself "wow, that was a scary dream". But on oxycodone, I would wake up, and my dreams wouldn't have the same sense of "difference" from the real world. As if some important part of my brain wasn't able to distinguish between dream and reality like it normally should.

Very scary.

 

[tyrael]

.....
At first, I could sleep 1 or two hours, wake up feeling like I had the best rest of my life, realize it was only a couple hours sleep, shrug my shoulders go about my day, and usually nod out some time therein.
.....

I could probably second this. Although even now I feel like I sleep like a baby - nod quickly, very "sound" sleep - but the next day I'm often more tired then if I hadn't!

Because you were addicted, and withdrawls can start creeping up quickly and quietly. Im sure you know symptoms of opiate withdrawals include RLS, cold sweats and inability to sleep. Dosing 12 hours before sleep would be terrible, you would be going through withdrawals, whether mild or severe, before you go to bed. Dosing right before sleep would have been the best thing to do.

The answer to your question is: Withdrawals.

Yes, qft! Not specifically saying this is your case Nagelfar! But you are very much spot on re being symptomatic due to withdrawals! Classic signs!

 

[Psychedelic Jay]

Sleep is beautiful until you get dependent... Then it is completely destroyed.

 

[Coolwhip]

It isn't just withdrawls.

I can't explain it either. But I know what not going to sleep because of WD feels like and that is not what the OP is talking about.

I think he is talking about how when you take a high dose you get the nods, and if you want can fall into a warm, deep, lovely sleep. But if you take a low dose you get energetic, you are UP, you can't sleep, you want to clean, to dance, to go out, etc. if you take the dose in afte evening you will be up all night.

I think he is associating it with length of habit instead of size of dose as I am, because of tolerance.

The same doses which used to sedate him, are now only low doses, and he doesn't have the money to waste on a dose high enough to put him to sleep.(or didn't I know he is off them now)

 

[Deleted member 137730]

I just started grad school to obtain my PhD in pharmacology, so my knowledge is limited at this point, but there is one question that has been bugging me for a while. I used to use opiates extensively before I realized that they were not compatible with a successful career. During the early days of my use, they would induce a heavy sleep. After I became addicted, and from that point forward, they would prevent me from obtaining even a few hours of sleep. I would literally get one or two hours of sleep if I was lucky, even if I dosed twelve hours before I went to bed. To my knowledge, opioids are generally inhibitory agonists. Although it was grossly simplified, my medical pharmacology course stated that generally opioids decrease cAMP and thus decrease signal transduction. I realize that they stimulate the release of dopamine in the nucleus accumbens, but what role does that have in the sleep/wake cycle? I would think that they would promote sleep, not prevent it. Why did sleep deprevation only become pronounced after I suffered from addiction? Also, why do they cause such intense and severe nightmares? This would seem counter intuitive. I realize that these questions are quite broad, but if anyone knows certain pathways in the brain that may play a role, or biochemical mechanisms that may be responsible, I would love to put this questi
on to rest.

opiates release NE and dopamine in the mPFC which can cause stimulation in the same way certain stimulants do. Amphetamine and opiates share a similar reward pathway, and locomotor stimulation in drug addicts and rats is shown. Besides the extra dopamine release which can lead to more NE sythesized on its own from dopamine b hydroylase, opiates also release histamine which causes wakefulness. Provigil causes wakefulness from histamine inducing properties along with orexins, so you can see histamine can be a potent stimulant. Also antihistamines cause drowsiness.

so extra histamine + extra dopamine/ne release in certain areas of the brain equals= no sleep and or slight stimulation from opiates. Also opiates derived from thebaine have more stimulant properties, buprenorphine and oxycodone are the opiates most directly derived from thebaine. Both have a reputation for being speedy. The morphine class is more sleepy than the codone class, the morphine class effects serotonin more than the codones class.

I think it would be the extra NE release and dopamine release in the reward pathway and mPFC that causes the stimulation the most with histamine being a secondary cause. Most people dont realize that although opiates do block the LC and opiates inhibit adrenaline, NE is released in some areas. Of course histamine is also often ignored as the itchyness goes away, however itchyness only shows up at very high levels of histamine release IIRC.

 

[whippa craka]

opiates release NE and dopamine in the mPFC which can cause stimulation in the same way certain stimulants do. Amphetamine and opiates share a similar reward pathway, and locomotor stimulation in drug addicts and rats is shown. Besides the extra dopamine release which can lead to more NE sythesized on its own from dopamine b hydroylase, opiates also release histamine which causes wakefulness. Provigil causes wakefulness from histamine inducing properties along with orexins, so you can see histamine can be a potent stimulant. Also antihistamines cause drowsiness.

so extra histamine + extra dopamine/ne release in certain areas of the brain equals= no sleep and or slight stimulation from opiates. Also opiates derived from thebaine have more stimulant properties, buprenorphine and oxycodone are the opiates most directly derived from thebaine. Both have a reputation for being speedy. The morphine class is more sleepy than the codone class, the morphine class effects serotonin more than the codones class.

I think it would be the extra NE release and dopamine release in the reward pathway and mPFC that causes the stimulation the most with histamine being a secondary cause. Most people dont realize that although opiates do block the LC and opiates inhibit adrenaline, NE is released in some areas. Of course histamine is also often ignored as the itchyness goes away, however itchyness only shows up at very high levels of histamine release IIRC.

I have had sleep issues and have personally found opiates to help. You are picking out a couple of possibly very well, thousands of side effects and interactions between the human body and oxycodone. I know it helps with sleep

 

[Psychedelic Jay]

I have had sleep issues and have personally found opiates to help. You are picking out a couple of possibly very well, thousands of side effects and interactions between the human body and oxycodone. I know it helps with sleep

I'm sorry, but, I totally disagree with this statement.

Blocking production of GABA while simultaneously releasing norepinephrine and dopamine and vast amounts of histamine... This is a wreak on your sleep mechanism.

You ever noticed how we like to "ride out" the opiate high? It is just too damn rewarding to go to sleep. IMHO If I re-dose at 3 in the morning, best believe I'm going to be up till 7 or 8.

 

[Enlitx]

opiates release NE and dopamine in the mPFC which can cause stimulation in the same way certain stimulants do. Amphetamine and opiates share a similar reward pathway, and locomotor stimulation in drug addicts and rats is shown. Besides the extra dopamine release which can lead to more NE sythesized on its own from dopamine b hydroylase, opiates also release histamine which causes wakefulness. Provigil causes wakefulness from histamine inducing properties along with orexins, so you can see histamine can be a potent stimulant. Also antihistamines cause drowsiness.

so extra histamine + extra dopamine/ne release in certain areas of the brain equals= no sleep and or slight stimulation from opiates. Also opiates derived from thebaine have more stimulant properties, buprenorphine and oxycodone are the opiates most directly derived from thebaine. Both have a reputation for being speedy. The morphine class is more sleepy than the codone class, the morphine class effects serotonin more than the codones class.

I think it would be the extra NE release and dopamine release in the reward pathway and mPFC that causes the stimulation the most with histamine being a secondary cause. Most people dont realize that although opiates do block the LC and opiates inhibit adrenaline, NE is released in some areas. Of course histamine is also often ignored as the itchyness goes away, however itchyness only shows up at very high levels of histamine release IIRC.

That was the answer I was looking for. Just to be certain, by mPFC you mean medial prefrontal cortex? What do you mean by LC? I do realize that dopamine can be converted to noradrenaline, but what percentage is actually converted to noradrenaline as opposed to a seperate metabolic pathway? We have these very helpful charts that quantify the percentage of some chemicals that undergo phase I and phase II metabolism (simpe polarization such as hydroxylation of a molecule as opposed to conjugation with large molecules such as glucorinic acid). I do not have such a chart for dopamine though, I suspect since we are studying foreign molecules as opposed to endogenous ligands. If you stimulate the nucleus accumbens with dopamine/NE, is there an intrinsic stimulation of other areas of the brain while the areas that control fear and anxiety are dampened? Do opiates dampen the activity of the amygdala? I never thought about the histamine aspect, even though I knew histamine was released by opiates.

I have the basic information I wanted though. No one has answered why opiates cause nightmares though. That seems very odd to me. Opiates induce euphoria in waking hours but the complete opposite reaction in sleep? Very odd. The only explanation that I can come up with is that the actual reward pathway is no longer stimulated during sleep and therefore the areas responsible for fear exhibit a rebound effect during sleep and thus causes intense feelings of fear. It seems like these questions would be extensively researched given the popularity of opioid painkillers available on the U.S. market.

 

[Nagelfar]

I think it would be the extra NE release and dopamine release in the reward pathway and mPFC that causes the stimulation the most with histamine being a secondary cause.

Interesting, Oxycodone if I recall correctly has less histamine release, but is that much more wakeful, then, because of mPFC? I didn't know this, though from personal experience would venture guessing Oxycodone both causes less histamine release & is more 'wakeful' than morphine classes. Maybe the serotonin affinity of morphine also makes it more 'drowsy' as in the manner of a pure molly MDMA nod.