Gabapentinoids Kratom and Gabapentin and Valium

[lightthespark]

My partner has severe chronic anxiety/grief/addiction issues. He cut down from heavy daily Kratom use - stopping everything briefly - and now to this list below. Is it a safe combination:

On alternating days he takes:

• Day 1: 4g Kratom (caps)
• Day 2: 2 x 300g Gabapentin (unprescribed)
• Plus 10mg Valium every night
• Plus prescribed 40mg daily Fluoxetine (antidepressant).

Please, I need to know if this is going to work for him or if it's likely to spiral again.

 

[plumbus-nine]

Kratom and gabapentin should be ok, there's theoretical risk of respiratory depression like always when combining downers + opioids but I was prescribed 600mg pregabalin which is stronger mg to mg than gabapentin together with 600mg morphine and had no issues. Given that he will have tolerance, the dosages are low-ish and when he doesn't take them together but on different days I see no problem.

Gabapentin can be addictive / causing withdrawal when used for longer and stopped abruptly, not everybody gets it, me not for example.

How much kratom was he/she using? I think that the fluoxetine potentially helps against the withdrawal of kratom, gabapentin as well.

 

[lightthespark]

Thanks @plumbus-nine

His breathing is heavy, so the respiratory depression is what concerns me most - he's quite a large guy and I've noticed he's 'mouth breathing' lately and snoring really loudly.

Not sure exactly how much Kratom he was taking before, but it was a lot.

He got really bad stomach symptoms when he stopped the Kratom, that's why he's gone back on to both.

 

[emkee_reinvented]

Hard to answer. However from personal experience both seem nauseating. Fluoxetine and Kratom. A annoying but not so life threatening effect.

But what you really wanna be looking into is enzyme inhibition or dis-inhibition. And the possible risk of serotonin syndrome, which is rare read this on Bluelight so don't quote me on this. Its rarewhen you are not using any MAOI's.

But Fluoxetine has definetly a great effect on enzyme's and 5-HT receptor's. So there is def gonna be some interaction.

And so does some of the Alkaloid's in Kratom.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309668/

Me personally would rather be on Kratom as a single anti-depressant agent. Instead of combining SSRI's with it. Some dextro-Amphetamine would be a nice add on. But not a necessity. But YMMV

 

[plumbus-nine]

Kratom afaik is a serotonin antagonist, not agonist which could lead to theoretical sero syndrome, at least at 5ht2a. Don't know for sure but I think it isn't a SSRI, I've combined high doses of kratom with diverse S/NRIs including 60mg fluoxetine, without problems or increased side effects but this is just a personal anecdote which doesn't need to be true for you. According to the linked paper it binds to 5-HT2C and 5-HT7 receptors, they don't say if agonist or antagonist. In another paper 5ht2a is mentioned and when they say it works as antipsychotic then probably antagonist.

Fluoxetine is a strong CYP2D6 inhibitor, think on some other enzymes as well but less pronounced. Does anybody know how kratom is metabolized?

Is/was the heavy breathing while using high dose kratom + valium for sleep, or in sober state? Did you notice any difference when he was using vs. not?
I had respiratory depression which looked like sleep apnea, from morphine alone, according to a friend who watched me.

Oh btw, @lightthespark - Welcome to Bluelight!

 

[emkee_reinvented]

Kratom afaik is a serotonin antagonist, not agonist which could lead to theoretical sero syndrome, at least at 5ht2a. Don't know for sure but I think it isn't a SSRI, I've combined high doses of kratom with diverse S/NRIs including 60mg fluoxetine, without problems or increased side effects but this is just a personal anecdote which doesn't need to be true for you. According to the linked paper it binds to 5-HT2C and 5-HT7 receptors, they don't say if agonist or antagonist. In another paper 5ht2a is mentioned and when they say it works as antipsychotic then probably antagonist.

Fluoxetine is a strong CYP2D6 inhibitor, think on some other enzymes as well but less pronounced. Does anybody know how kratom is metabolized?

Is/was the heavy breathing while using high dose kratom + valium for sleep, or in sober state? Did you notice any difference when he was using vs. not?
I had respiratory depression which looked like sleep apnea, from morphine alone, according to a friend who watched me.

Oh btw, @lightthespark - Welcome to Bluelight!

"Mitragynine has a low oral bioavailability of 3% [28-30], which may be a result of high first-pass metabolism via cytochrome P450 (CYP) enzymes in the intestines and the liver."

Say's the paper i posted. And:


"Metabolism of mitragynine mainly occurs in the liver where in vitro experiments indicate that mitragynine interacts with other medications and substances via CYP enzymes [9]. Mitragynine and 7-HMG may inhibit the activity of CYP2D6 and CYP3A4. Moderate inhibitory effects are seen with CYP1A2 and mild inhibition of CYP2C19. In vitro, it has been shown that mitragynine and 7-HMG also act as inhibitors of P-glycoprotein (P-gp). Although the clinical significance of the inhibitory effect on CYP enzymes by kratom and its alkaloids has not been determined, kratom is often reported together with drugs that are substrates for CYP3A4 (alprazolam, carbamazepine, phenobarbital, phenytoin, quetiapine, oxycodone), CYP2D6 (amitriptyline, fluoxetine, haloperidol, codeine), and CYP1A2 (theophylline, clozapine) [2,9,33]."

same one as you mentioned. I noticed. But the combo of Pregabalin and Kratom in reasonable dosages at least in me caused no problem's that I noticed.

 

[plumbus-nine]

"Mitragynine has a low oral bioavailability of 3% [28-30], which may be a result of high first-pass metabolism via cytochrome P450 (CYP) enzymes in the intestines and the liver."

Oh, that's how snorted extract brings you much higher than oral kratom. I want to get pure mitragynine or 7-HMG, once I had a black tar like extract which was so strong that I overdosed and blacked out, the hardest nod I ever had. The company doesn't exist any more, was from Switzerland where they banned kratom among many other nice substances.

Interesting that mitragynine inhibits P-gp. Maybe add some loperamide to kratom (NO safer use!), but likely the effect isn't significant enough. That it inhibits 2D6 and 3A4 doesn't necessarily mean that it's potentiated by other inhibitors, does it?

I'm right now on 10g white kratom and 600mg pregabalin, together with paroxetine (also an inhibitor of 2D6 afaik) no issues or sedation so far.

 

[emkee_reinvented]

Oh, that's how snorted extract brings you much higher than oral kratom. I want to get pure mitragynine or 7-HMG, once I had a black tar like extract which was so strong that I overdosed and blacked out, the hardest nod I ever had. The company doesn't exist any more, was from Switzerland where they banned kratom among many other nice substances.

Interesting that mitragynine inhibits P-gp. Maybe add some loperamide to kratom (NO safer use!), but likely the effect isn't significant enough. That it inhibits 2D6 and 3A4 doesn't necessarily mean that it's potentiated by other inhibitors, does it?

I'm right now on 10g white kratom and 600mg pregabalin, together with paroxetine (also an inhibitor of 2D6 afaik) no issues or sedation so far.

Afaik-goes no idea what two inhibitor's of the same enzyme, CYP-2D6, would do.

Especially as they also are opposite in action on 5-HT-C receptor's. Fluoxetine antagonises then something in Kratom agonises them. please correct me when i'am wrong.

 

[plumbus-nine]

Especially as they also are opposite in action on 5-HT-C receptor's. Fluoxetine antagonises then something in Kratom agonises them. please correct me when i'am wrong.

Both fluoxetine and kratom are antagonists at 5-HT2c: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC20038/ an activity which disinhibits norepinephrine and dopamine afaik, 60mg+ of fluoxetine are increasingly physically stimulating but in a pretty stressed way so I went down to 40mg again. If they had opposite action then that one with stronger affinity would 'win' the receptors in effective dosages. In lower ones they might cancel each other out I assume.

Bad is kratom's antagonism at D2, so the released dopamine can't work - this might be why kratom isn't as euphoric as other opioids or even dysphoric from time to time.

 

[emkee_reinvented]

That Kratom antagonises the 5-HT-c receptor is findeable but Fluoxetine doing the same seems a bit harder to find.

Do you have a link Plumbus-nine?

 

[Mureceptor]

I am surprised no one has mentioned the 10 mg of nightly valium, the most dangerous aspect of this protocol.

 

[Conky]

I am surprised no one has mentioned the 10 mg of nightly valium, the most dangerous aspect of this protocol.

10mg is quite a low dose

 

[Mureceptor]

10mg is quite a low dose

I know...but I find, and this is just me, even if I take 5mg....if I do it daily I get addicted. I get an anxiety rebound. That is why I limit Benzos to twice a week. That is just me.

 

[Sewardsfolly]

Gabapentin seems to potentiate the Kratom for me. Works well that I forget to take my 2mg Xanax ER.

 

[plumbus-nine]

Do you have a link Plumbus-nine?

I think it was this paper. They don't explicitely mention that kratom was an antagonist at D2 but that the activity was similar to antipsychotics which means the same. I also get dysphoria similar to APs when taking kratom on top of memantine being also a D2 agonist and thus probably tachyphylaxis going on, and/or autoreceptor agonism which inhibits release and then kratom on top leads to reduced dopamine levels.

But I might be wrong, it's interesting that kratom does agonize 5ht2c, which would also limit dopamine and norepinephrine output - opposite of fluoxetine but then again that one causes very limited physical stimulation at 40+mg but it's nowhere near what I'd have imagined by 'D/N disinhibition' and increasing dose over 60mg doesn't strengthen the effects.

Gabapentin seems to potentiate the Kratom for me. Works well that I forget to take my 2mg Xanax ER.

Yeah, pregabalin (so probably all gabapentins) shares cross-tolerance with kratom. It's not very strong but certainly present. There's also probably cross-tolerance with dissociatives, I have high tolerance to them which just doesn't go down even over a year of abstinence and pregabalin does next to nothing for me, as does kratom, I require high dosages of these to induce recreational effects but lower ones still help against withdrawal.

 

[Sewardsfolly]

I think it was this paper. They don't explicitely mention that kratom was an antagonist at D2 but that the activity was similar to antipsychotics which means the same. I also get dysphoria similar to APs when taking kratom on top of memantine being also a D2 agonist and thus probably tachyphylaxis going on, and/or autoreceptor agonism which inhibits release and then kratom on top leads to reduced dopamine levels.

But I might be wrong, it's interesting that kratom does agonize 5ht2c, which would also limit dopamine and norepinephrine output - opposite of fluoxetine but then again that one causes very limited physical stimulation at 40+mg but it's nowhere near what I'd have imagined by 'D/N disinhibition' and increasing dose over 60mg doesn't strengthen the effects.


Yeah, pregabalin (so probably all gabapentins) shares cross-tolerance with kratom. It's not very strong but certainly present. There's also probably cross-tolerance with dissociatives, I have high tolerance to them which just doesn't go down even over a year of abstinence and pregabalin does next to nothing for me, as does kratom, I require high dosages of these to induce recreational effects but lower ones still help against withdrawal.

 

[Sewardsfolly]

I’ve found out that Gold Bali strain of Kratom Is the best for me. There are thousands using the strains that work best for their particular needs. I know the horrors of many types of detox and they freaking suck but remember, it doesn’t last and soon you’ll feel well again. Give it a try and don’t be afraid to down 20g tid. Or more I’d needed. There’s no od. You’ll just throw up if your body says it’s too much. I’ve haven’t known of any visits to hospital for Kratom. It’s a cofffee plant is harmless on its own.