DXM after an harmala sublingual dosage

[thikal]

Hello every one.

I took 200mg sublingual harmalas syrian rue extract (manske style), so with harmine (1 to 3h half life) and harmaline (3 to 9h half-life). I'm considering taking a DXM two level trip in 48h. Is it safe ? I think so because it will be 9hx5 half life of harmaline, so I won't die. Do you agree with me ?

 

[polymath]

I recommend you wait a few more days, because some people unknowingly have dysfunctional enzymes because of genetic reasons, and the half-life of some substances can be unusually long in that situation. Harmala is a reversible MAOI, though, so the risk isn't as large as when taking serotonergics after an irreversible MAOI.

 

[thikal]

I'm aware that polymorphism in the CytP450 2D6 can affect, prolong harmaline metabolism. I found an article on this subject. But I took a lot of DXM (an codein) an have a total normal response to it both, so I know that i'm not cytP450 deficient. And the 9h half-life is at the end of the spectrum, so 5 half life of 9h seems safe for me enough. But I wanted other advices. I did the same experiment with speed two day after an oral dose of harmalas (longer duration than the sublingual that I took) this summer and didn't notice any interaction, but I know that DXM is more dangerous than speed with is serotoninergic profile. I have benzodiazepines (etizolam) on hand in case of hypertension/serotonin syndrom.

Maybe I have forgotten something ? Anyways, thanks a lot for your fast answer !

In summary, CYP2D6 drug-metabolizing enzyme plays an important role in harmaline clearance. Compared to human CYP2D6 EM (extensive metaboliser) hepatocytes, PM (poor metaboliser) hepatocytes showed defective harmaline O-demethylase capacity, leading to lower rate of substrate depletion.

I can't find the 3-9h half-life values right now i've found a fews weeks ago to back up my claims ! But maybe the large differences reflect already the difference in polymorphism ?

Edit : I found the picture of harmine, harmaline and THH metabolism.

According to these graphs, the only think that bother me is the harmalol apparent long half-life... And as harmaline is metabolised in harmalol, mabye this could be a problem ?

http://jpet.aspetjournals.org/content/306/1/73

 

[serotonin2A]

It is true that DXM can interact with irreversible MAOIs. But you can't extrapolate to a reversible MAOI. The main problem with irreversible MAOIs is that they can achieve very high levels of MAO inactivation, especially when given chronically. With reversible MAOIs, occupation of CNS MAO doesn't usually exceed 50% when reasonable doses are taken (ie, below the overdose level), and occupation would be much lower after 24-48 h. The reason why ayahuasca is effective is because the point is to inhibit MAO in the gut and liver, and that is where the highest concentration of beta-carbolines would occur after ingestion of ayahuasca.

 

[thikal]

It is true that DXM can interact with irreversible MAOIs. But you can't extrapolate to a reversible MAOI. The main problem with irreversible MAOIs is that they can achieve very high levels of MAO inactivation, especially when given chronically. With reversible MAOIs, occupation of CNS MAO doesn't usually exceed 50% when reasonable doses are taken (ie, below the overdose level), and occupation would be much lower after 24-48 h. The reason why ayahuasca is effective is because the point is to inhibit MAO in the gut and liver, and that is where the highest concentration of beta-carbolines would occur after ingestion of ayahuasca.

Thanks a lot for this precision. The informations about harmalol are fucking scarce, but I found that IMAO-A inhibition of harmalol was 60x less powerfull than harmaline or harmine (in rat liver), so it doesn't sound that harmalol can be dangerous as a metabolite of a normal dose of harmaline. Furthermore, I saw that harmaline is metabolised in harmine too with a different cytochrome than the Cyt P450 2D6, so the actual harmalol content may be really little finally. I'm a little too much afraid to take my usual dose of DXM in one shot, 520mg. Will fractionate it bit by bit and see how it feels, with my benzos at hand.

 

[d1nach]

Hey shuligan , i would measure your etizolam out before taking the dxm so you dont have to try to measure with a hand tremor or god knows what else seeing double

 

[thikal]

Hey shuligan , i would measure your etizolam out before taking the dxm so you dont have to try to measure with a hand tremor or god knows what else seeing double

Yeah your so right haha, I had etizolam pellets !

So for the record, I didn't had any problems from DXM roughly 50h after my sublingual harmine + harmaline dose, for my metabolism. I was a little bit underwhelmed thanks to my tolerance. Stay safe guys !