Does oxycodone cause GABA receptors to down-regulate?

[Valthinking]

After augmenting on Mirapex, my doctor tried many meds (gabapentin, pregabalin, horizon, tramadol, Tylenol #3) and clonazepam. Then I was given oxycodone, which worked. However, it took me six months to get off of clonazepam and it's taken another year to climb out of that hell. For some reason, I am one of the lucky few that has trouble coming off clonazepam. I ended up in a much worse state for almost the whole year, with inner tremors, deep crazy despair, nausea, exhaustion, burning skin, jitteriness and awful anxiety (which never troubled me before, and I'm 70!)

It's my understanding that a big cause of the misery came from down-regulated GABA receptors from the clonazepam. My question is, will the oxycodone stop the GABA receptors from up-regulating? Does anyone know?

[Rustsmith]

I don't know, but I would be surprised to find out that oxy had much interaction with the GABA receptors. The opioids generally work on the mu-opioid receptors and these somehow bypass the dopamine and glutamate receptors (which are related to the GABA receptors). The scientists still don' know exactly how the opioids work even though they were the first treatment used by Dr Willis in the late 1600's).

[Valthinking]

Thank you for responding! I was hoping you would. The recovery from clonazepam has been brutal. I thought it was bad going off pramipexole, but that was just the start.

Were you ever on oxycodone? If so, was it difficult going off of it?

I don't know where all these people are finding doctors that will help them. My doctor only gives me oxycodone because Dr. Silber at the Mayo Clinic recommended it. Things like Suboxone and bupenorephine aren't on the radar.

Thanks again, Steve!
Val

[Oozz]

After augmenting on Mirapex, my doctor tried many meds (gabapentin, pregabalin, horizon, tramadol, Tylenol #3) and clonazepam. Then I was given oxycodone, which worked. However, it took me six months to get off of clonazepam and it's taken another year to climb out of that hell. For some reason, I am one of the lucky few that has trouble coming off clonazepam. I ended up in a much worse state for almost the whole year, with inner tremors, deep crazy despair, nausea, exhaustion, burning skin, jitteriness and awful anxiety (which never troubled me before, and I'm 70!)

It's my understanding that a big cause of the misery came from down-regulated GABA receptors from the clonazepam. My question is, will the oxycodone stop the GABA receptors from up-regulating? Does anyone know?

I’m not sure if upregulate/down regulate is the right word. Opioids reduce gaba transmission which causes the increase in dopamine. It’s more complicated but that’s the high level.

[Rustsmith]

Were you ever on oxycodone? If so, was it difficult going off of it?

I have not been on oxycodone, but have been on methadone and Tramadol ER. Tramadol ER requires a slow taper over a month, not due to the opioid side of it but because it is also an anti-depressant and stopping one of them can cause SNRI Withdrawal Syndrome (a nasty side effect that causes severe depression and anxiety that lasts for months, I know because I went through it).

As for difficulty getting off of methadone and the opioid side of tramadol, they are not all that difficult compared to the dopamine agonists. I went through the sort of classic opioid withdrawal for a couple of hours and then by the next morning, was fine except for soreness in my muscles caused by the withdrawal shakes. I have been through methadone withdrawal twice and would be willing to do it again if there was a good reason.

[Valthinking]

I wish I understood more about all of this. It's very isolating to never have a good doctor you can confer with, and I just can't wrap my head around all the different receptors etc. Ever since coming off pramipexole I've had withdrawal after withdrawal (first from clonazepam, which was and still is brutal) and from the mirtazepine and lamectal I was given during clonazepam withdrawal.

I've been on a combination of 10 MG OxyContin and 8.75 MG oxycodone for the past year, and my RLS is pretty well under control, with a few breakouts here and there. BUT since I've weaned myself off of most of the antidepressants and am on tiny doses at this point, it's becoming clear that the major dizziness I struggle with is probably due to the Oxy.

So I guess I'll be going through another withdrawal from it onto something else. I'm thinking of asking my neurologist about Suboxone, since I've also been depressed for the past three years and was never able to get up to a therapeutic level on any AD. Hence my question about GABA receptors! Whatever it takes to feel good or somewhat normal, I don't seem to have.

Thanks for your responses! I'm still in the wilderness, trying to find my way out. It's nice to hear from people on this journey!

Warmly,
Valthinking

[Rustsmith]

Switching from oxy to Suboxone should not result in any withdrawal. Both work on the opioid receptors, so that switch should be FAR easier than getting off of clonazepam or any of the anti-depressants.

[Valthinking]

Well that's good to hear! I was reading about it last night and it sounds like an awful 24-36 hours and then some relief. I'm not on a super-high dose of oxy although I don't know if that matters. God willing, this will work for me!
Thank you Steve!
Val