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5-MeO-DMT and Harmalas

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UgraKarma

UgraKarma

Esteemed member
For some time now, I've come to consider 5-MeO-DMT a major no-no, rife with contraindications, when used in tandem with harmalas, or MAOIs. Because 5-MeO is so physical, and seems to share tactile qualities with phenthylamines which also have harsh reactions when combined with MAOI's, this seemed to make perfect sense to me and I didn't dig into it much further.

On a very old thread, 69ron comments on the efficacy of 5-MeO-DMT and harmalas taken sublingually, and it has piqued my interest. As far as I can tell, there's no guide for dosing, as one might easily find Googling for heroic dose/psilohuasca, ayahuasca, pharmahuasca, etc... If anyone is able to come up with a working dosage scale, or even share odds and ends notes on their subjective experience, I'd be interested in reading about the experience, and how the signature of the rue imprints itself onto the 5-MeO experience, (i.e. if you found MAOIs to enhance the low-dose empathogenic/entactogenic effects, and if its synergies could be considered desirable all the way through to the "release dose".)

A few notes on where I'm coming from:
I have about 30-60mgs (eyeballed) of HCL 5-MeO, which would be much better for sublingual administration than the larger amount of freebase I have, however I'm without freebase harmalas at the moment. Would you consider this experience warrant the trouble of running a rue extract? I enjoy low-dose intranasal administration for the HCL, so if it's not a tremendous difference experientially, I'll probably not rush to try this combo before the end of the year, and simply continue to use it in this fashion.
 
Thanks Nen - that thread successfully confirmed my reservations. Simply not stacking up enough "positives" in my cost-benefit analysis to try this myself. Maybe some day, but not for now.
 
Is 5-MeO not strong enough for you? If the answer is yes, you most likely don't really have 5-MeO. I really don't think harmalas are necessary. If it is a consumption issue, then I would freebase the 5-MeO (very simple process) or just smoke the HCl form - it works. I'm not sure what oral dose range for 5-MeO is, but I would be very careful about looking that kind of a thing up. If you smoke it, surely smoke no more than 10mg, which is already kinda asking for trouble.
 
69ron was speaking about 5mg dose of 5meo dmt ( which he suposedly extracted from virola resin, and to date, we couldn't back up these claims ). This is an active dose already which top with a very low dfose of sublingual harmalas was better he used to say.
Now I think, even if the reality is questionable, these sort of dose are more on the safety side anyway.

Few poeple dared to oral 5 MeO-DMT with harmalas as it has been successful but seems pretty risky ( at least one fatal report of such combination in a apparently healthy young adult was reported).

I did such experiecne by accident too ( didn't lable my jars and took 5Meo instead of n,n ) and I can tell you it wasn't fun for the first hour AT ALL.
Maybe thankfully I was taken by strong nausea and I had to puke ( I might as well have thrown up some excess 5 meo ).
I had a hard time chilling and I thoght my life was threatened.
I eventually chilled up, and at least enjoyed a very good afterglow. All I can say, it didn"t went as smooth as a good n,n-DMT oral ( pharmahuasca style with harmalas ).

I never dare to repeat the experiecne even on low doses. Nonetheless I did make some kind of enhanced leaves ( no harmalas but n,n and 5 meo combined ).
You can ingest those tryptamines alternatively via rectal route sans harmalas too.
There has been good report ( look up at arimane for intance) for this ROA which seems safer.

5 MeO-dmt might well be active by itself as low as 30 mg oral too. so combining a dose of more than 15 mg with harmalas could be risky.

Please, enjoy the molecules safely, and report back your findings, impressions ..
 
Global said:
If it is a consumption issue, then I would freebase the 5-MeO (very simple process) or just smoke the HCl form - it works.
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Hi Global. Just noticed your comment above about the HCl being smoalkable. Is this from your own experience? Do you need to compensate with a larger quantity? I've been going through the process of freebasing my 5-meo-dmt:HCl which is a bit of a hassle and loses me a percentage each time. I'd love to know I didn't need to process it first :)
 
No you will dose a bit heavier with HCL than with FB but FB is heavier so if you have FB you dose a tad bit less. Well, really try smoking HCL. I think I did both and didn't mind the low loss when freebasing but HCL smoking works and maybe you'd dose 2 mg up than FB given the smoking doses.
Hope this is clearn enough :)
 
NotTwo said:
Global said:
If it is a consumption issue, then I would freebase the 5-MeO (very simple process) or just smoke the HCl form - it works.
Click to expand...

Hi Global. Just noticed your comment above about the HCl being smoalkable. Is this from your own experience? Do you need to compensate with a larger quantity? I've been going through the process of freebasing my 5-meo-dmt:HCl which is a bit of a hassle and loses me a percentage each time. I'd love to know I didn't need to process it first :)
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I have smoked the HCl in my own experience (it definitely works). If you need to compensate for weight, it's marginal because a tiny crumb of the stuff is still overwhelming. I wouldn't worry about losing a percentage though with 5-MeO. That's me personally. I honestly don't know if I'll ever finish my half a gram.
 
Global said:
I have smoked the HCl in my own experience (it definitely works). If you need to compensate for weight, it's marginal because a tiny crumb of the stuff is still overwhelming. I wouldn't worry about losing a percentage though with 5-MeO. That's me personally. I honestly don't know if I'll ever finish my half a gram.
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Many thanks for the advice Global and rOm.
 
A number of years ago, I was stupid enough to try this combo and had a rather severe hypertensive episode. Thankfully, I guess I was at least smart enough to attempt it at somewhat low doses (~20mg sublingual caapi harmalas and 2mg IM 5-MeO-DMT), so I lived to tell the tale. It created an absolute state of panic involving extreme tension, heart rate anomalies, breathing issues, and the general sense that I was on the edge of actually physically dying.

Just wanted to post this here to reaffirm the warnings. For anyone who comes across this and is curious, the risks are real.
 
bk2492 said:
These are interesting comments ⇩

"While I have not personally added it in my own changa blends, I have smoked blends made by a trusted and very experienced friend that does. It is not something to be played with lightly as adding harmalas to 5 can go wrong, very quickly. It is far too easy to go too far. While the experience of this smoke was incredible, I cannot stress enough how potentially dangerous it could be. My friend took years to work on this blend very... very slowly. Using far less than you would ever think is necessary. I again, DO NOT RECOMMEND attempting this."

uhnope_didnthappen, 2024-06-07, reddit.com/r/Ayahuasca


"My concern comes from not knowing the mentality/experience level of whoever is considering adding it to the mix. It is definitely not as forgiving as nn-dmt. As I stated, the blends I have smoked with 5 (not made by me) have been incredible. If someone has plenty of experience with 5, and working with harmalas, and doses accordingly then everything should be fine. But I don't want to go encouraging just anyone to dive in and experiment wildly."

uhnope_didnthappen, 2024-06-07, reddit.com/r/Ayahuasca
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Right, it was these kinds of reports that convinced me to take a chance and try it. Perhaps it is possible for some people to use the combo without incident, and perhaps it's somewhat safe to use when the harmala dose is kept very low, but I definitely wouldn't recommend risking it to find out. If a longer experience is desired, re-dosing works well enough.
 
Here&Now2 said:
Right, it was these kinds of reports that convinced me to take a chance and try it. Perhaps it is possible for some people to use the combo without incident, and perhaps it's somewhat safe to use when the harmala dose is kept very low, but I definitely wouldn't recommend risking it to find out. If a longer experience is desired, re-dosing works well enough.
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Makes me wonder if relationship and the time put in doing the work with both molecules is necessary, similar to datura acclimation.

One love
 
Voidmatrix said:
Makes me wonder if relationship and the time put in doing the work with both molecules is necessary, similar to datura acclimation.

One love
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Maybe so. I've scoured the internet in the past looking for successful uses of the combo, and I found quite a few, so there may be something more at play than a simple contraindication.

But now that I've discovered 5-MeO-MALT, that'd be my go-to for a longer lasting 5-MeO-DMT-like trip which is about double the length and offers a slightly different flavor of god-like revelation.
 
Here&Now2 said:
Maybe so. I've scoured the internet in the past looking for successful uses of the combo, and I found quite a few, so there may be something more at play than a simple contraindication.

But now that I've discovered 5-MeO-MALT, that'd be my go-to for a longer lasting 5-MeO-DMT-like trip which is about double the length and offers a slightly different flavor of god-like revelation.
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Some of the risks regarding 5-MeO-DMT and harmalas may arise through interactions in the cyt-p450 metabolic pathways. Harmalas inhibit CYP2D6, which, iirc, also plays a role in 5-MeO-DMT clearance. All the same, I'm yet to grasp exactly how this would play out in terms of the adverse reactions, other than prolonging elevated concentrations of the active compounds and possibly leading to excessive serotonin build up, 'or something'.
 
Transform said:
Some of the risks regarding 5-MeO-DMT and harmalas may arise through interactions in the cyt-p450 metabolic pathways. Harmalas inhibit CYP2D6, which, iirc, also plays a role in 5-MeO-DMT clearance. All the same, I'm yet to grasp exactly how this would play out in terms of the adverse reactions, other than prolonging elevated concentrations of the active compounds and possibly leading to excessive serotonin build up, 'or something'.
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This reminds me of the document in one of the 5-MeO-DMT stickied threads: Research - FIVE GUIDE: Pharmacology and Drug Interactions of 5-MeO-DMT

The author also mentions serotonin syndrome as a potential outcome of mixing with MAOIs, which certainly seems possible to me. Whatever the case, I'll reiterate that it was a harrowing experience, and it was probably my closest brush with actual death when using psychedelics.
 
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Here&Now2 said:
This reminds me of the document in one of the 5-MeO-DMT stickied threads: Research - FIVE GUIDE: Pharmacology and Drug Interactions of 5-MeO-DMT

The author also mentions serotonin syndrome as a potential outcome of mixing with MAOIs, which certainly seems possible to me. Whatever the case, I'll reiterate that it was a harrowing experience, and it was probably my closest brush with actual death when using psychedelics.
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Ah, yes:

7

Metabolism and Drug Interaction Potential

5-MeO-DMT has two major metabolic enzymes or routes of metabolism [22]. In the brain as well as peripherally 5-MeO-DMT is metabolized by MAO-A to an inactive indole acetic acid (5-MeO-IAA) whereas in the liver it’s metabolized by CYP2D6 to the active metabolite bufotenine (5-hydroxy-N,N-dimethyltryptamine) [23].
Upon inhalation or other parenteral delivery route, 5-MeO-DMT is absorbed directly into systemic circulation. This is important because it may signify that metabolism at the neuronal synapse or 5-MeO-DMT’s site of action is more significant for 5-MeO-DMT than CYP2D6-mediated hepatic metabolism (where most oral drugs are primarily metabolized) [3]. Drugs that inhibit MAO-A are higher risk in combination with 5-MeO-DMT than those that inhibit CYP2D6. This is both because MAO-A may play a larger role in metabolism and due to the differential risks of inhibiting either enzyme [3].
Users of 5-MeO-DMT that take drugs that inhibit CYP2D6 or those with slow metabolizer phenotypes of the CYP2D6 enzyme would be predicted to have less bufotenine formed and slightly higher exposure to 5-MeO-DMT, yet could still metabolize 5-MeO-DMT to 5-MeO-IAA with MAO which is the predominant metabolic route [24]. On the other hand, inhibition of MAO with MAOIs blocks the metabolism of 5-MeO-DMT and serotonin, which could lead to excessive accumulation of serotonin in synapses as well as increased formation of bufotenine and Serotonin Toxicity [9]. Of note, harmaline found in ayahuasca can inhibit both MAO-A and CYP2D6 and has the worst reported toxicities in combination with 5-MeO-DMT including death.
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Transform said:
Some of the risks regarding 5-MeO-DMT and harmalas may arise through interactions in the cyt-p450 metabolic pathways. Harmalas inhibit CYP2D6, which, iirc, also plays a role in 5-MeO-DMT clearance. All the same, I'm yet to grasp exactly how this would play out in terms of the adverse reactions, other than prolonging elevated concentrations of the active compounds and possibly leading to excessive serotonin build up, 'or something'.
Click to expand...
Thougt about the interaction of enzymes and drug potency the same way but in a different context. My aim was to reduce a drugs effect with the same approach, lowering their effect using a second drug which pushes or lowers the enzyme necessary to eliminate the specific drug. Meaning the effect of drug A will be lowered (and so adverse effects) by the side effect on enzymes by drug B. Many drugs are metabolized the same way. Logically this makes sense but I think this way to interact with a drug can be considered mostly irrelevant because the resulting change of effect is "too low" this way. (Even if sufficient to activate n,n-DMT orally). What I found more affecting the effect are interactions with neurotransmitters. Instead of looking at the metabolization, the interactions between two substances will be more serious if the neurotransmitters are involved.

In this case the change on metabolization enzymes of 5-Meo-DMT and Harmalas, MAO-A inhibitor, for sure interact in some way but the result is weaker then the main effect of MAO-A on serotonin in combination with 5-meo-DMT.

In one sentence, the interaction between the effects on the metabolization enzymes by 5-Meo-DMT and Harmalas have a lower risk for serotonin syndrome in comparison to the serotonin based interaction from 5-Meo-DMT and MAO-A inhibitors.
(Exactly this is way I dropped to look into the matter of reducing the potency by manipulating metabolic pathways. Using neurotransmitters to interact between substances had a bigger impact. But still nice to give it try.)

Serotonin-Syndrome is horrible and also the partner Neuro-Maligne-Syndrome.
 
One possible inference about this is that there may sometimes arise a sort of metabolic "sour spot", where some of the 5-MeO-DMT has been metabolised to bufotenine so that there's both a serotonin release and seotonin reuptake inhibition. This starts to look bad alongside MAO inhibition.

I get the feeling that there's some capricious pharmacodynamics to be unpicked as well - but it's rather tricky to study this ethically.
 
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