Limiting the excessive NRI effects of Tapentadol (hypothesis)

[NatalieC1993]

Hey Guys,

I am currently prescribed Low Dose Buprenorphine (0.5-3mg per day), Low Dose Gabapentin (800mg per day), specially compounded Ketamine nasal spray (5mg per spray), and Medical Marijuana for my treatment resistant depression. It is working astoundingly well so far. The only thing is--I would like to achieve opioid euphoria some days and the buprenorphine at any dose won't cut it. I have some tapentadols I ordered coming in, and I was wondering if I could counteract the NRI effects? I have taken tapentadol in the past before, and at dosages above around ~175mg, dysphoric, deliriant-like effects started popping up. I have been reducing my opioid tolerance through the usage of proglumide, ultra low dose naltrexone, and dissociatives, but, like I said, the buprenorphine just isn't euphoric enough. Back to the tapentadol--I have always loved its little sister tramadol quite a lot. For some reason, at any dose (even dangerous 1500mg dosages), I never became delirious on tramadol. I hypothesize that, although tapentadol has less serotonin releasing activity, it actually has more nor epinephrine effects than tramadol. I have a prescription that I never use for metoprolol (beta blocker). From my research, it has the ability to block nor epinephrine. What I am wondering is: if I take a normal dosage of metoprolol (12.5mg-25mg) with my tapentadol, do you guys believe that it will have enough anti-adrenergic activity to counteract the excessive re-uptake of nor epinephrine from the tapentadol thus reducing the dysphoric deliriant side effects and allowing the opioid effects to dominate? When my tapentadol gets in next week, I am planning on not taking any buprenorphine that day or the day before, as well as taking 300mg proglumide, 1mcg naltrexone, and 12.5mg metoprolol 30 minutes before the tapentadol to both potentiate its opioid effects and (hopefully) eliminate the horrible NRI effects.

What are your thoughts on this idea?

Sincerely,

Nat

 

[d1nach]

Well know nothing about opioids but i believe there are alpha and beta adrenic receptors and each of these have subtypes. So i dont think taking a beta blocker would work at all the effects of nri

 

[NatalieC1993]

Thanks for the quick response, d1nach. I see what you mean. I do have Gabapentin, which I know limits the over stimulation with tramadol and makes for a pleasant experience. What are your thoughts on Gabapentin with the tapentadol? Also, I was wondering if maybe hydroxyzine (Vistaril) could limit some of the psychotomimetic effects of high dose tapentadol?

 

[d1nach]

I have no idea what im talking about from what ive briefly read, i am surprised tapentadol would cause psychotomimetic effects esp at 175 mg (given the drugs.com dosage range for pain) due to nri activity.

Are you sure it is the nri causing the effects

For example
Reboxetine is a NRI pretty selectively but the side effects dont seem to really mention much of psychotic like side effects rather general stimulant like effects.

"Very common (>10% incidence) adverse effects include insomnia, dizziness, dry mouth, constipation, nausea, and excessive sweating.[25]

Common (1?10%) adverse effects include loss of appetite, agitation, anxiety, headache, restlessness, tingling sensations, distorted sense of taste, difficulty with seeing near or far (problems with accommodation), fast heart beat, heart palpitations, " (wiki)

What exactly do you mean by psychotomimetic?

It may be possible delta kappa and o- opioid receptors could be playing a role in psychosis like effects idk how strongly if at all it interacts with them.

If i was experiancing so much noradrenaline i was feeling psychotic boardlining on a stimulant like psychotic episode i highly doubt hydroxyzine would be of much help. I honestly can barely even tell h1 antagonism after taking effexor (snri) and adderall. And, its possible 5ht2 additional antianxiety effects are in my experience unable to detect vs just idk 1 or 2 benadyrl.

However, i might just be blunted to the calming effects of hydroxyzine due to years of benzo use.

If hydroxyzine works for you id use it.