s240779 said:

It's because bufotenine is a serotonin releaser[1] and 5-MeO-DMT is a serotonin reuptake inhibitor[1] (and 5-MeO-DMT partially metabolizes into bufotenine[2]). I was curious to see what substituting bufotenine for DMT would be like in an ayahuasca preparation. I didn't know that it was a releaser when I tried this. I just tried low doses of both, the two doses were seperated, harmine first. You better believe I was surprised when all of a sudden I felt "high". Psychedelics don't get me high. They just alter my perception and usually they make me feel worse than I did, even in low doses.

I've never tried 5-MeO-DMT, but someone else who did try it in the same manner I tried "bufohuasca" said the same thing.[3]

Some of you may be concerned about serotonin syndrome, either because you know that the two aforementioned mechanisms are contraindicated with MAOIs or because you've specifically heard that one or both of these tryptamines is contraindicated with MAOIs. Indeed, it is a concern, but the truth is that certain dosage ranges are safe:

I have heard very mixed reports from trials employing P. harmala and the second of the biotic tryptamines, 5-methoxy-N,N-dimethyl-tryptamine, or 5-MeO-DMT. Apparently, modest amounts of both components gives a modest experience, but I have had two reports of truly toxic crises with larger quantities.

TiHKAL (part 1). Alexander Shulgin. 1997. 16. Hoasca vs. Ayahuasca, p. 302

Researchers have warned about the combo: https://www.shroomery.org/forums/showflat.php/Number/28979413#28979413

Now it gets really controversial, so I think right now I have just tell you in a maybe nice way what is already known, what is already outside, and what a lot of other people also say: All people say never do it with harmala, never combine it with MAO blockers, it's highly dangerous and you will die, and this is right: don't do it. But I would be lying on you if I not say this is my favorite combination. [laughter]

[...]

And if you combine it with harmala, you should only do it if you start really slow, you know what you're doing, and you find your own level, then I could not say it's so risky. I would say driving a car, what we usually do in Germany with the speed is much more dangerous.

5meoDMT - Joe Schraube talk at copenhagen. psychedelic society. May 16, 2019 (1:02:56-1:11:59)

In the post above the 'warnings from researchers' link, there are links to 15 Erowid reports of the combo as well as additional quotes from reddit.


More info that argues against MAOI paranoia:

People have combined low doses of MDx with harmalas without ill effect. One of these people was the psychedelic pioneer, Claudio Naranjo (probably administered to volunteer(s); no details, unfortunately): Combining MDx with harmalas (also includes a report of MDMA with moclobemide, but the person who posted it also referenced a few case reports where people died from that combo)

However, I think even a low dose of MDx could easily cause serotonin syndrome, as this is probably one of the riskiest combos there is!

Some MAOIs are also serotonin reuptake inhibitors, i.e., pirlindole and brofaromine, and one researcher goes so far as to say that the combination should be explored:

In mental depression, new approaches could also combine both MAO inhibition and serotonin reuptake inhibition to increase extracellular 5-HT concentration at the synapses.

Structural Aspects of Monoamine Oxidase and its Reversible Inhibition. Johan Wouters. 1998. Current Medicinal Chemistry, vol. 5, #2, 136-162 (Conclusions and Perspectives, p. 159)

B. caapi is both an MAOI and an SRI, i.e., it contains predominantly harmine, which is an MAOI, and tetrahydroharmine, which is a weak MAOI, but is believed to be predominantly an SRI.[4]

Indeed, there were two clinical trials where MAOIs and SSRIs were combined, they're referenced in this[5] article. Didn't read them but here's a comment from someone else who did:

but the only citation for  Moclobemide + SSRI describes one smaller trial that appeared successful and a larger trial with 50 patients that saw response but notes a "high rate of adverse effects many of which were severe".

Glossawy, Jun 21, 2024, Re: Someone tried 30 mg of Celexa with 60 mg of Parnate (as you can see, that comment was made in a post about someone who tried the combo without ill effect, I'll copy his statement in reference [6])

I, myself, tried Zoloft w/ harmine and Lexapro w/ harmine. Harmine doses were low, first time was with ¼ of a Zoloft and I got a very impressive stimulant effect comparable to MDMA; next day, nothing (ended up doubling the dose or something), suggesting neurotransmitter depletion as with amphetamines. During the Lexapro trial, I ended up pushing the Lexapro very high, at least 120 mg, cuz I was expecting a synergy like I got with the Zoloft, but I never got an effect from the Lexapro.

Also, speaking of amphetamines, they're contraindicated with MAOIs, but not because of serotonin syndrome, i.e., classical amphetamines aren't highly serotonergic; they're dopaminergic and noradrenergic and the noradrenaline boost poses a risk of hypertension with MAOIs...and yet sometimes the two are actually prescribed together:

There is now a lot of accumulated experience of the concurrent administration of MAOIs and amphetamine for therapeutic purposes in depression. It is safe when done carefully. Early concerns about frequent hypertension have not materialized and recent clinical reviews indicate judicious use is safe [354, 355].

Monoamine oxidase inhibitors: A review concerning dietary tyramine and drug interactions. Ken Gillman, MD. PsychoTropical Commentaries (2020) 1:1–71 (Releasers (indirectly acting sympatho-mimetics ISAs)) Code:

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https://psychotropical.com/wp-content/uploads/2020/03/9.2-MAOI_diet_drug_interactions_2020_current_v.pdf

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Numerous reports from people who have tried the combo: https://www.shroomery.org/forums/showflat.php/Number/28919078

Lastly, someone tried 5-MeO-DMT with moclobemide:

I have taken 5-meo-dmt with moclobemide. Actually, I have taken everything under the sun, with moclobemide. It's all potentiated in a very safe manner. LSD is a tiny bit blunted not like on parnate.

MezDez, Jun 13 2024, https://www.reddit.com/r/MAOIs/comments/1dfcm9k/comment/l8it95s/


[1] The 5-methoxylated version of DMT (5-MeO-DMT, 7) was a weak 5-HT uptake inhibitor (IC50 value=2,184 nM). This was somewhat surprising since the 5-hydroxy analog, 16, was a potent SERT-mediated releaser with an EC50 value of 30.5 nM. 5-OH-DMT (16), also known as bufotenin,

Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes. Blough BE, Landavazo A, Decker AM, Partilla JS, Baumann MH, Rothman RB. Psychopharmacology (Berl). 2014 Oct;231(21):4135-44. doi: 10.1007/s00213-014-3557-7 (Discussion)

[2] Pharmacokinetic interactions between monoamine oxidase A inhibitor harmaline and 5-methoxy-N,N-dimethyltryptamine, and the impact of CYP2D6 status. Jiang XL, Shen HW, Mager DE, Yu AM. Drug Metab Dispos. 2013 May;41(5):975-86. doi: 10.1124/dmd.112.050724

[3] i did it several times with caapi extract at retreats in spain and france.

zll2244, Mar 29, 2024, re: Can i take 5-MeO-DMT orally with a MAOI?

was with “inner mastery”, they operate in different countries but are based out of spain. (Apr 26, 2024, private message)

it was administered by this french guy, was a group of 7 of us that did it. i don’t think it was a regular thing. i ended up doing it again in france at a private retreat with 6 people. be careful about it however. dosage is important so i don’t know how safe it is. (Apr 26, 2024, private message)

we took 1 capsule which was the same capsules that have the bufo we would vaporize at the retreats. i do not know what dosage that was but it was a vaporization dosage ingested with caapi extract.

the actual bufo in the capsule looked like tiny plastic/glass fragments.

it was an “experimental” offer so yes was not normal. i was staying in one of their communes in madrid. later i was in france with a different group of people i met backpacking in kind of a crazy situation i don’t want to go into detail about.

definitely a euphoric mdma type effect feeling with strange organic type stuff over my vision that was not like a visual hallucination but more like something different i cannot describe well. i noticed the girl next to me the first time get pretty overwhelmed and i had to hold her up. (Apr 26, 2024, private message)

Did you experience any ego loss?

no (Apr 26, 2024, private message)

I should also ask you, do you get that MDMA-like effect from vaped/smoked 5-MeO?

maybe a little but 5meo vaped hits so fast it’s kind of hard to tell before you go to that impossible to explain state of being comfortably nothing and everything at once. (Apr 28, 2024, private message)

Speaking of which, I think the reason you didn’t get there from oral is because you took both the 5-MeO and the caapi at the same time, am I wrong? Whether you’re using tea or extracts, DMT is more effectively absorbed if the MAOI is ingested first (u/Sabnock101 recommends waiting a full hour*), amd I suspect that it’s especially wasteful to ingest extracts together.

*“You can even take the Harmalas regularly (been dosing them on a daily/near daily basis for 12 years myself in heavy dosages) and exactly an hour in when gut MAO-A is maximally inhibited (also the best time for consuming the DMT),”

[reddit]

good info thanks (Apr 28, 2024, private message)

[4] While not a strong inhibitor of MAO, THH possibly contributes neuroactivity by weakly inhibiting the uptake of serotonin (5-hydroxytryptamine, 5-HT) at presynaptic sites, like other 1-methyl-tetrahydro-β-carbolines (Airaksinen et al., 1980). Subsequently, concentrations of 5-HT increase in the body when both its metabolism by MAOA and presynaptic uptake are simultaneously blocked by these harmala alkaloids.

Airaksinen, M.M., Svensk, H., Tuomisto, J., Komulainen, H., 1980. Tetrahydro-b-carbolines and corresponding tryptamines: in vivo inhibition of serotonin and dopamine uptake by human blood platelets. Acta Pharmacologia et Toxicologia 46, 308–313.

Pharmacokinetics of Hoasca alkaloids in healthy humans. J.C Callaway, D.J McKenna, C.S Grob, G.S Brito, L.P Raymon, R.E Poland, E.N Andrade, E.O Andrade, D.C Mash. Jun 1999. Journal of Ethnopharmacology, 65(3), 243–256. DOI: 10.1016/S0378-8741(98)00168-8 (1. Introduction)

[5] Combining antidepressants: a review of evidence. Palaniyappan L, Insole L, Ferrier N. Advances in Psychiatric Treatment. 2009. 15(2):90-99. doi: 10.1192/apt.bp.107.004820 (See 'SSRI with moclobemide')

[6] “I should probably not mention this, but the most stupid thing was probably taking 30mg Citalopram in addition to 60mg [tranylcypromine] because I was wondering if I would even get Serotonin syndrome. That certainly didn't feel good. But aside from some nausea I didn't really have any adverse effects. Nothing serious and no myoclonus, either.”

u/itsokaytowishtodie, May 29 2023, https://www.reddit.com/r/MAOIs/comments/13uy65z/comment/jm3utli/

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s240779 said:

I mean the feeling isn't an exaggeration. Why do you have to come into my thread and add static to it? No one wants to read your ridiculous comments.

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Quote:

Contraindication : 5-MeO-DMT and MAOIs Although 5-MeO-DMT is present in some plants used in ayahuasca and in some ayahuasca brews, Erowid has received several reports of very troubling physical reactions in people who have ingested 5-MeO-DMT with MAOI harmala alkaloids. There appears to be the risk of severe hypertensive symptoms, overheating, serotonin syndrome, etc. It is important to note that the profile of these risks are not fully understood, because the long history of use of brews containing some amount the two in combination.

A case of a 17-year-old male was reported to us in December 2002. He ingested an extract of Syrian Rue and then smoked an unknown (but large) dose of powdered, chemical 5-MeO-DMT. He quickly became non-responsive and fell to the ground, began convulsing (myoclonic jerking), and his sitter called an ambulance for help. He was found to have had a pulse of 180, blood pressure 200/125, and temperature 106.0 F. These levels are dangerously high. He was minimally responsive but became wildly agitated upon stimulation (even just speaking to him). He was treated with diazepam and transferred by helicopter to a Boston area hospital. The patient may have suffered lasting damage to his kidneys and rhabdomyolysis. A formal case report of this incident was published in a 2004 issue of the Journal of Toxicology & Clinical Toxicology titled "Monoamine Oxidase Inhibitor Poisoning Resulting from Internet Misinformation on Illicit Substances".

In December 2004, we received an unconfirmed report of a death related to the ingestion of 200 mg of 5-MeO-DMT with some amount of "yage". This death was later described in the case report "A Fatal Intoxication Following the Ingestion of 5-Methoxy-N,N-Dimethyltryptamine in an Ayahuasca Preparation" in the November/December 2005 issue of the Journal of Analytical Toxicology, and the follow-up commentary "A Demand for Clarity Regarding a Case Report on the Ingestion of 5-Methoxy-N,N-Dimethyltryptamine in an Ayahuasca Preparation" was published in the July/August 2006 issue.

We have also received some reports from groups experimenting with making pharmahuasca using 5-MeO-DMT who have said that they had much higher incidence of bad reactions with 5-MeO-DMT than with N,N-DMT. They discontinued using the 5-MeO-DMT.

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s240779 said:

I mean the feeling isn't an exaggeration. Why do you have to come into my thread and add static to it? No one wants to read your ridiculous comments.

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TrusyTripper said:

He Made a logical point of discussion

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He made a nerdy point of discussion.  Why can't he just appreciate that I'm saying the combo has a similar effect. Why does he have to be so nitpicky? And why is his English so poor?