N&PD Moderators: Skorpio
A Second Look at MAOI's?
Allylbenzene
Bluelighter
via 5-HT1A agonism.
The point was to restore normal production of anti-glucocorticoid hormones by addressing impaired metabolic/mitochondrial function (inadequete T3, statin use, hypothyroid etc).
Caffeine is the most popular metabolic stimulant that people self-medicate with:
Aside, on StAR:
https://pubmed.ncbi.nlm.nih.gov/29303051/
https://www.tandfonline.com/doi/full/10.1080/09168451.2015.1123612
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That really feels like burying the lede considering the 5HT2A and 5HT2C activities.
Both of those papers are by the same group. The open access one is done in cell lines, which is not super convincing to me, and the other one is a review. I’ve found that JBC tier journals or better tend to be a lot more reliable, and their review processes often ask for experiments to clarify the story.
Is GGOH supposed to be an activator of AC9 in the vein of forskolin? Or does it bind to a GPCR? Also is it going to reach appreciable concentrations in the blood if dosed in an animal, or will it get shunted into cholesterol metabolism.
StAR is upregulated by PKA dependent processes, and it’s phosphorylation at serine 195 is crucial for activity.
Plenty of Gs coupled GpCR agonists induce this.
red22
Bluelighter
They recently deleted most of my posts on DMT-Nexus. Below is a copy of my post, "Understanding the safety profile of MAOIs". Thankfully, that one is still up…for now…but I figured I'd copy it here just in case. ⇩
…And I see you were just banned from DMT-Nexus as well, @Allylbenzene. Do you know why you were banned?
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red22
Bluelighter
"90% of MAO activity in the intestine involves the MAO-A isoform."
Effects of tyramine administration in Parkinson’s disease patients treated with selective MAO-B inhibitor rasagiline. deMarcaida JA, Schwid SR, White WB, Blindauer K, Fahn S, Kieburtz K, Stern M, Shoulson I. 2006. Movement Disorders, 21(10), 1716–1721. doi:10.1002/mds.21048 (Introduction)
Do selectivity and reversibility matter?
Classic MAO inhibitors such as tranylcypromine and phenelzine are neither reversible (binding to the enzyme for the extent of its lifetime of 14–28 days) nor selective for the subtypes. These drugs were used extensively several decades ago to treat atypical depression, anxiety, and phobias. The only selective MAO inhibitor now available in the United States is selegiline, which inhibits MAO-B at low doses but loses its selectivity at dosages greater than 20 mg/day.
Experimental studies suggest that inhibition of more than 70% of MAO-A activity is necessary for the antidepressant effect of selegiline.12 At oral doses that selectively inhibit MAO-B (5–10 mg/day), selegiline does not seem to have potent antidepressant activity, although it does show success as an adjunctive treatment for Parkinson disease and does not necessitate any dietary restriction. Only at higher oral doses (20–60 mg/day), at which MAO-B selectivity is lost, is the antidepressant effect seen. But the higher doses necessitate dietary restrictions. Therefore, patients who are taking the oral selective MAO inhibitor selegiline have to follow the same dietary restrictions as patients taking the nonselective ones.
Reversible inhibitors of MAO-A have the distinction of being easily displaced by ingested tyramine in the gut and thus do not cause the cheese reaction. However, the only reversible agent available in the world market is moclobemide. It is not available in the United States, and appears to be less effective than older, nonselective MAO inhibitors.13
■ SELEGILINE TRANSDERMAL SYSTEM
The selegiline transdermal system (Emsam) is the first FDA-approved transdermal patch for treatment of major depression. Patients who are using Emsam at its lowest effective dose of 6 mg/24 hours do not need to follow the dietary restrictions that are needed for all oral MAO inhibitors.
MAO Inhibitors: Risks, benefits, and lore. Wimbiscus, Molly MD; Olga Kostenk, MD; Donald Malone, MD. Dec 2010. Cleveland Clinic Journal of Medicine. 77 (12) 859-882. DOI: 10.3949/ccjm.77a.09103 (Do selectivity and reversibility matter?, p. 861)
https://www.poison.org/articles/making-sense-of-mao-inhibitors See bottom of page.
Tyramine
"Very few individuals will ingest more than 25 mg of tyramine, even when consuming high-tyramine foods. For patients on MAOIs, ingestion of amounts under 50 mg are unlikely to cause significant blood pressure effects. Even in the early 1960s, when food tyramine was much higher and MAOI users received no dietary guidance, only 14 deaths were reported among an estimated 1.5 million patients who took MAOIs."
Meyer, J.M. Modern Use of MAOIs. Psychopharmacology Institute, 2019-07-01 (3. Dietary Restriction: What to Tell Patients About Tyramine)
The dietary restrictions classically advised for patients taking oral MAO inhibitors were established to prevent hypertensive crises associated with tyramine ingestion. However, some of these restrictions were unsubstantiated,[38] and evidence from more recent studies suggests that they are unnecessarily strict[39]
[...]
Among the many foods determined to be unnecessarily restricted are avocados; bananas; beef or chicken bouillon; chocolate; fresh and mild cheeses, eg, ricotta, cottage cheese, cream cheese, processed cheese slices; fresh meat, poultry, or fish; meat gravy (fresh); monosodium glutamate; peanuts; properly stored pickled or smoked fish (eg, herring); raspberries; and yeast extracts (except Marmite).[39]
[...]
Absolute dietary restrictions include[39]:
• Aged cheeses and meats
• Banana peels
• Broad bean (fava) pods
• Spoiled meats
• Marmite
• Sauerkraut
• Soybean products
• Draft beers.
From the ‘Diet can be more lenient than in the past’ section (pg. 873) in the article that contains the selectivity-reversibility section quoted above.
if the conclusion is anything other than tyramine and all mess that goes along with it is anything other than Hocus Pocus old science then it's meaningless collectively. I have been [tranylcypromine] for like 30 years and long ago I forgot entirely about all that tyramine and preserved sausages and stuff like that, and yet here I am, happy and healthy
pumbungler, 2024-06-03, reddit
It's very rare to have a hypertensive crisis while on MAOIs, but the danger is there and you can get one when you least expect it. Took me two years to find out how it felt like. I ate spoiled meat and it gave me a splitting headache, felt like my head was about to explode. Before that incident i had been eating everything and paid the diet no concern at all.
I still don't care about the diet, but gourmet cheese and spoiled food should be avoided at all costs.
ChopSuey, 2014-09-22, Re: MAOI "diet" by psychiatrists - a joke?
I don't drink beer on tap, eat artesian cheeses, or consume homemade fermented goods. I also don't eat much soy sauce. I didn't consume these foods pre MAOI anyway. Most of the information regarding food restrictions is dated and inaccurate. I've used MAOI's for about two years. After the first 2 weeks or so I don't really even think about diet restrictions.
TechnicalCatch, 2024-05-13, reddit
Follow-up ⇩
Yup. 2.5 years on an irreversible MAOI (Nardil and Parnate separately) and I don't even think about the diet to a significant degree. Tap beer, artesian cheeses, rotten meat (ew), don't eat excess soy sauce (ew) and don't guzzle back homemade kombucha (ew). So far, it's had a minor negative impact on me maybe 1-2 times when I was offered part of a beer on tap and i declined. It would likely be fine at a good bar with kegs/lines that are maintained and used frequently but I personally don't bother. But hey, It was garbage beer anyway so...blessing in disguise i guess?
Had some loaded up pizza at dinner, and a couple of glasses of red wine today lol.
TechnicalCatch, 2024-05-26, reddit
red22
Bluelighter
"The urgent need for clearer guidance is further underscored by recent survey data, illustrating that medication interactions (e.g. ADs) with psychedelics was among the most commonly desired educational topics reported by psychiatrists (Barnett et al., 2022). Secondly, while psilocybin has been relatively well-studied, data for LSD is limited (Becker et al., 2025) and exists primarily for the concomitant use of MAOIs that is also very old (DeMaar et al., 1960; Grof and Dytrych, 1965; Resnick et al., 1964), albeit showing a good safety profile and no signs of serotonin syndrome."
Concomitant use of antidepressants and classic psychedelics: A scoping review. Tap SC, Thomas K, Páleníček T, et al. 2025. Journal of Psychopharmacology, 0(0). doi: 10.1177/02698811251368360 (Discussion)
red22
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"… It's quite stimulating; people like taking Parnate—people will abuse Parnate sometimes …"
Dr. Josef Witt-Doerring, CEO and Medical Director of TaperClinic.
Worst Psychiatric Medications (Tier-List). @taperclinic. 2025-07-15. YouTube. [18:48]
red22
Bluelighter
"Occasionally imipramine and an MAO inhibitor may be combined or one may be substituted for the other in order to produce a more effective therapeutic response. Potentiation or addition of toxic and possibly lethal effects may become a serious practical matter and pose many problems in management."
Luby, E. D., Domino, E. F. 1961. Toxicity from large doses of imipramine and an MAO inhibitor in suicidal intent. JAMA, 177(1), 68–69. doi: 10.1001/jama.1961.73040270050013b
red22
Bluelighter
Psychedelics Today uploaded this video this morning, which featured a comment I made on one of their IG posts. They just took the video down and blocked me.
6.32 MB file on MEGA
mega.nz
My comment:
I would never take MDMA again without harmalas. Seems to be a rather dangerous and superficial substance without something "spiritual" to give it a base and some substance. Murple was a fan of the aforementioned combo.
⇨ Using MDMA as a substitute for DMT in ayahuasca [Bluelight]
"I think that more and more people will increasingly understand that a vine heavy brew, with relatively small amounts of DMT, is about the best preventive medicine a human being can ever take."
Julian Palmer. Articulations: On the Utilisation and Meanings of Psychedelics. 2014. Chapter 4. Ayahuasca / The Religion of Ayahuasca
red22
Bluelighter
"But there’s more to ancient Haoma than just harmala. As some scholars note, the Iranian beverage frequently combined Syrian rue with Ephedra—rich in the stimulant ephedrine—adding a wakeful, energizing quality to the brew."
"What emerges is a multi-layered drink: on the one hand, harmala compounds produce a dreamlike, introspective state; on the other, ephedrine provides a stimulating, wakeful energy. [ … ] This synergy reflects a carefully choreographed path toward spiritual insight—one requiring both heightened awareness (thanks to ephedrine) and inward-turning visions (thanks to harmala and possibly atropine)."
One Compound, Three Sacred Drinks: Harmala Alkaloids. Shauheen Etminan. 2025-04-08. Magi Ancestral Supplements Inc.
red22
Bluelighter
Adverse consequences of fluoxetine-MAOI combination therapy. Feighner, J. P., Boyer, W. F., Tyler, D. L., & Neborsky, R. J. 1990. The Journal of clinical psychiatry, 51(6), 222–225. PMID: 2347858
The authors describe two series of patients: 12 treated simultaneously with fluoxetine and a monoamine oxidase inhibitor and 6 patients started on treatment with an MAOI 10 days or more after stopping fluoxetine treatment. All patients had extremely refractory depression and were treated in open fashion before general knowledge was obtained of the side effects that may accompany the fluoxetine-MAOI combination. During the fluoxetine-MAOI trial, most patients continued to receive other psychotropic combinations that had been partially helpful. The use of fluoxetine and an MAOI, either together or in close succession, was accompanied by a very high incidence of adverse effects, especially the "serotonergic syndrome." This syndrome was characterized by mental status changes, such as hypomania and confusion, and physical symptoms, such as myoclonus, hypertension, tremor, and diarrhea. Because of the high incidence of side effects and the lack of definite efficacy, the concurrent use of fluoxetine and MAOIs should generally be avoided. The long half-lives of fluoxetine and norfluoxetine, as well as the prolonged metabolic effects of MAOIs, may also dispose patients to an interaction if one of the drugs is started soon after stopping the other.
red22
Bluelighter
Quote:
A remarkable characteristic of AMPH is that subtle structural variations can produce drastic changes in its pharmacodynamics, and lead to compounds that interact differentially with several biogenic amine target proteins. Consequently, the AMPH skeleton has served as a privileged scaffold for the design and synthesis of hundreds of derivatives with many different and often useful activities, but also conveying misuse potential (Biel and Bopp, 1978; Nichols, 1994; Glennon, 1999; Rothman and Baumann, 2003; Welter-Luedeke and Maurer, 2016). Thus, the diversity of mechanisms of action of AMPH derivatives determines a many-colored palette of pharmacological activities in humans, including psychostimulant, entactogenic, psychedelic, anorectic, nootropic, and antidepressant effects. It is noteworthy that the structural changes also modify toxicological properties and abuse liability of AMPH derivatives (Fleckenstein et al., 2007; Rothman et al., 2007; Simmler et al., 2013; Barbosa et al., 2015).
Amphetamine Derivatives as Monoamine Oxidase Inhibitors. Reyes-Parada, M., Iturriaga-Vasquez, P., & Cassels, B. K. 2020. Frontiers in pharmacology, 10, 1590. doi: 10.3389/fphar.2019.01590 (Introduction)
red22
Bluelighter
"I think it depends on the person and the amount of harmala taken.
I experienced very high blood pressure, an extreme headache, and seizures after a harmala + DMT trip following hard cheese and olives. It was absolute hell! I thought I was going to die then. I've never had anything like that with a proper MAOI diet."
Bra, 2025-11-18, https://www.shroomery.org/forums/showflat.php/Number/29404718#29404718
Follow-up:
About 200 g of hard cheese and about 50 g of gorgonzola. I had about 200 g of olives. I also had seaweed during the day and some dried fruit.
I don’t know how long the episode lasted. I didn’t really pay attention to time during that hellish experience. My guess is about 2 hours. After that, I had a severe headache for a few days, and my body felt exhausted as almost every muscle had been contracted for a very long period. This was terrible.
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red22
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red22
Bluelighter
Some ayahuasca retreats use diazepines in case of emergencies.
"It won’t kill you. Even traditional places keep it around for SERIOUS psychotic episodes. But I would highly highly recommend she doesn’t rely on Xanax or use it before or after. I take lorazepam daily and when i went on my retreat i tapered off for several weeks leading up and didn't take any for a week after. (I also tapered off Prozac after 13 years and have not restarted it. It's been 2 years since my retreat)."
"I remember one night after ceremony I opened my pill box and looked at my lorazepam. It's always been my go-to after a drug trip to help me calm down and rest. But I felt Aya telling me NO, almost like I would make her unhappy and we would need to "talk" about it in the next ceremony. Truthfully she wont need it and should maybe even speak to the facilitators about it. My maestro told me my soul was "shaky" from all my anti depressants over the years and that they were blocking my emotions." RealLiveGirl, 2023-12-30, r/Ayahuasca re: Has anyone taken Xanax on ayahuasca
red22
Bluelighter
"These drugs’ property of significant, prolonged,
almost complete suppression of rapid eye movement (REM) sleep is believed to be responsible for their therapeutic effect in narcolepsy (31)."
Pharmacist Toolkit: Monoamine Oxidase Inhibitors. Rex Lott, PharmD, BCPP. American Association of Psychiatric Pharmacists (Lincoln, NE). 2021, revised, Sep 27, 2022. (Other Disorders, page 7)
Smyth2
Bluelighter
I found some interesting MAOI's to look at in this article:
Van Dyk AS, Petzer JP, Petzer A, Legoabe LJ. 3-Coumaranone derivatives as inhibitors of monoamine oxidase. Drug Des Devel Ther. 2015 Oct 3;9:5479-89. doi: 10.2147/DDDT.S89961. PMID: 26491258; PMCID: PMC4599074.
Pisani L, Muncipinto G, Miscioscia TF, Nicolotti O, Leonetti F, Catto M, Caccia C, Salvati P, Soto-Otero R, Mendez-Alvarez E, Passeleu C, Carotti A. Discovery of a novel class of potent coumarin monoamine oxidase B inhibitors: development and biopharmacological profiling of 7-[(3-chlorobenzyl)oxy]-4-[(methylamino)methyl]-2H-chromen-2-one methanesulfonate (NW-1772) as a highly potent, selective, reversible, and orally active monoamine oxidase B inhibitor. J Med Chem. 2009 Nov 12;52(21):6685-706. doi: 10.1021/jm9010127. PMID: 19810674.
An all natural one in spice: Noro, Tadataka; Miyase, Toshio; Kuroyanagi, Masanori; Ueno, Akira; Fukushima, Seigo (1983). "Monoamine oxidase inhibitor from the rhizomes of Kaempferia galanga L.". CHEMICAL & PHARMACEUTICAL BULLETIN. 31 (8): 2708–2711. doi:10.1248/cpb.31.2708.
Matos MJ, Viña D, Picciau C, Orallo F, Santana L, Uriarte E. Synthesis and evaluation of 6-methyl-3-phenylcoumarins as potent and selective MAO-B inhibitors. Bioorg Med Chem Lett. 2009 Sep 1;19(17):5053-5. doi: 10.1016/j.bmcl.2009.07.039. Epub 2009 Jul 10. PMID: 19628387.
"Compound 4, with the methoxy group in meta position, is the most active of this series, with an IC50 against MAO-B of 0.80 nM, and is
several times more potent and MAO-B selective than the R-(-)-deprenyl (reference compound)."
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I had treatment resistant depression, prescribed 150 mg + 75mg of Effexor for many years. Not suggesting but for the record I started micro-dosing Metocin came to realize I no longer needed an antidepressant and stopped without side effects. A few months later, I stopped taking prescribed antipsychotic, had a few nights of insomnia but was able to stop completely. 5 months later no depression or intrusive thoughts.
I assume by taking Metocin I was able to stop taking these medications although I don't have proof that Metocin cured my symptoms, however, I believe it is more than coincidence.
red22
Bluelighter
Low-dose daily caapi causing paradoxical anxiety/insomnia
"Has anyone had intense sleep / dream interactions when taking harmala salts ~2-3 hours before sleeping?"
…
"Examples of what I experience: a recurring white light that triggers me to bolt awake, intricate pattern / geometry tracers whenever sleep is interrupted, tossing and turning, fatigue the next day (as if I didn’t sleep through the night). I could hypothesize why this happens, though it’s probably best not to make unsubstantiated claims."
stuartroelke 2026-05-18 https://www.reddit.com/r/harmalas/comments/1tgmguu/sleep_dream_interactions/
"I took some too soon before sleeping last night. Even though quite tired, CEVs and even OEVs kept me awake for a couple of hours. I won't be doing that again.....))"
Axlerion 2026-05-22 https://www.reddit.com/r/harmalas/comments/1tgmguu/sleep_dream_interactions/onah5zi/
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