I posted comments from someone who did 5-MeO orally with caapi extracts on a youtuber's blog post[1] and he immaturely replied, "no you didn’t. That combination is deadly". He also deleted my comment and he may have blocked me. That makes me very angry, especially because he advertises himself as an open-minded person. He also said
taking LSD with harmalas is "an extremely dangerous idea". He also posted debunking videos of new age gurus…why doesn't he also debunk himself?
So, I would really appreciate if two people would post these two quotes, below, on his channel (one each cuz YouTube automatically sees lengthy comments as spam, in my experience, and shadow deletes them (i.e., making you think they were posted, which is absurd and malicious)).
“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.”
Alexander Shulgin. TiHKAL (part 1). Shulgin A, Shulgin A. 1997 16. Hoasca vs. Ayahuasca, pg. 302
“For his study, Markus mixed a representative of the β-Carbolins (harmin, harmalin, or 6-MeO-harmalan) with a tryptamine (5-MeO-DMT). He found a domain of optimal mixtures in which marked psychoactive productivity was associated with hallucinatory effects. Within certain specific ranges of dosage, the mixture was well-tolerated and there were no serious side-effects.”
‘A report on the symposium “On the Current State of Research in the Area of Psychoactive Substances”’. Hanscarl Leuner & Michael Schlichting [The Gateway to Inner Space: A Festschrift in Honor of Albert Hofmann. Christian Rätsch (ed.), 1989. Bridport, England: Prism Press] page 237
I also just found out about a mice experiment that supports the view that 5MeO is safe with an MAOI within a certain dosage range:
5 different dosage combos were used, i.e., (1) 2 mg/kg harmaline + 2 mg/kg 5-MeO-DMT, (2) 5mg/2mg, (3) 15 mg/2 mg, (4) 5 mg/10 mg, (5) 15 mg/10 mg
… and only the highest two combos resulted in "signs of dying"; no mentions of adverse effects are mentioned for the other combos.
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
I've come across a handful of comments on reddit from people who have done the combo and there are 15 Erowid reports of the combo, one from the famed, Murple:
https://www.shroomery.org/forums/showflat.php/Number/28924278#28924278
Indeed,
Murple said that he found the effect on his heart to be too concerning, but he obviously didn't die.
Someone even tried it with a moclobemide.
On a larger note, there is reason to question the taboo of combining MAOIs with serotonin boosters:
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.
itsokaytowishtodie, May 29, 2023,
reddit
MAOI + SSRI was explored in humans in a few studies, some adverse outcomes, some positive outcomes. I don't think there is any adverse data from the moclobemide trials, so something about reversible MAOIs makes them safer in this context. 5MeO is a serotonin reuptake inhibitor.[2][3] 5MeO's serotonin reuptake value is almost identical to methamphetamine's (5MeO: 4.1 µM, meth: 4 µM[3]) and I've come across some reports of meth safely being used in combination with irreversible MAOIs;[4] I even made a thread in r/MAOIs specifically asking for such reports:
Curious to hear from people who have used meth, specifically, with MAOIs. Amphetamines are seldom prescribed with MAOIs.[5][6] Indeed, meth has been described as a "weak" serotonin reuptake inhibitor,[7] not to mention that it is also a noradrenaline releaser and has caused death when combined with MAOIs[8] (serotonin and noradrenaline are the primary two things that are contraindicated with MAOIs[9]). So people have taken methamphetamine in combination with
irreversible MAOIs and people think that 5-MeO-DMT in combination with harmine and harmaline is extremely risky…
Studies of combined moclobemide-SSRI therapy have shown this combination to be safe and well tolerated [1, 10, 11, 23, 49], although this treatment strategy should be approached with caution. However, these studies were performed on selected populations and sample sizes were small.
Refs:
1. Bakish D, Hooper CL, West DL, Miller C, Blanchard A et al.
(1995) Moclobemide and specific serotonin re-uptake inhibitor combination treatment of resistant anxiety and depressive disorders.Hum Psychopharmacol 10:105-109
10. Dingemanse J (1993) An update of recent moclobemide interaction data. Int Clin Psychopharmacol 7:167-180
11. Ebert D, Albert R, May A, Stosiek I, Kaschka W (1995) Combined SSRI-RIMA treatment in refractory depression. Safety data and efficacy. Psychopharmacology (Berl) 119(3): 342-344
23. Joffe RT, Bakish D (1994) Combined SSRI-moclobemide treatment of psychiatric illness. J Clin Psychiatry 55(1): 24-25
49. Wallnoefer A, Guentert TW, Eckemas SA, Dingemanse J (1995) Moclobemide and fluvoxamine co-administration: a prospective study in healthy volunteers to investigate the potential development of the serotonin syndrome. Hum Psychopharmacol 10:25-31
Serotonin syndrome and drug combinations: focus on MAOI and RIMA.. Hilton, S. E., Maradit, H., Möller, H. J. 1997. Eur Arch Psychiatry Clin Neurosci, 247(3), 113-9, doi: 10.1007/BF03033064
Although risks of combination treatment certainly exist with selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, or clomipramine, the current literature supports cautious use of combining MAOIs with other antidepressants in patients with [treatment-resistant depression] who have failed multiple treatment modalities.
Thomas, S. J., Shin, M., McInnis, M. G., & Bostwick, J. R. 2015. Combination therapy with monoamine oxidase inhibitors and other antidepressants or stimulants: strategies for the management of treatment-resistant depression. Pharmacotherapy, 35(4), 433–449. doi: 10.1002/phar.1576 Abstract
This one is a literature review of 29 patients who were on an MAOI with one or more contraindicated medications, specifically, 15 using the selective, irreversible MAO-B inhibitor selegiline and 14 using nonselective, irreversible MAOIs. Findings showed 21% of patients improved significantly without complications, while 45% experienced adverse effects (e.g., hypotension, fatigue, suspected serotonin syndrome) necessitating discontinuation, although no severe outcomes were reported. The study merely described the MAOI-SSRI/SNRI combos as risky and that the benefits are outweighed by the risks.
Some details about #23, above, from
Grok and an additional moclobemide-SSRI study and one that involved SSRIs with the irreversibles:
Joffe 1994
Study Details: This 5-week trial combined moclobemide with the selective serotonin reuptake inhibitors (SSRIs) sertraline or fluvoxamine in 11 patients.
Results: Eight out of 11 patients responded, and the combination was reportedly well-tolerated.
Adverse Events: Some reports of insomnia were noted, but no other significant adverse events were highlighted.
Hawley, C. J., Quick, S. J., Ratnam, S., Pattinson, H. A., McPhee, S. 1996. Safety and tolerability of combined treatment with moclobemide and SSRIs: a systematic study of 50 patients. International clinical psychopharmacology, 11(3), 187–191. DOI: 10.1097/00004850-199609000-00005
Study Details: This 6-week trial involved 50 TRD patients treated with moclobemide combined with the SSRIs paroxetine or fluoxetine.
Results: The combination appeared efficacious for treating depression.
Adverse Events: There was a high rate of adverse events, many of which were severe, though specific events were not detailed in the summary.
Amsterdam, J. D., García-España, F., Rosenzweig, M. 1997. Clomipramine augmentation in treatment-resistant depression. Depression and anxiety, 5(2), 84–90.
Study Details: This 6-week trial involved 27 patients with [treatment-resistant depression]. It compared:
▪ MAOI (phenelzine, tranylcypromine, or isocarboxazid) + clomipramine (N=9),
▪ Fluoxetine + clomipramine (N=11),
▪ MAOI + conventional TCA (desipramine, amitriptyline, imipramine, or nortriptyline) (N=7).
Results: Response rates were low: 2 of 9 responded to MAOI + clomipramine, 4 of 11 to fluoxetine + clomipramine, and 3 of 7 to MAOI + conventional TCA.
Adverse Events: The MAOI + clomipramine combination was associated with more adverse events than the other groups, including several cases of serotonin syndrome.
There are even reports of people taking MAOIs, weak SRI tricyclics, and stimulants all at once! Thomas 2015, above, mentions two people and references this study:
Combined MAOI, TCA, and direct stimulant therapy of treatment-resistant depression. Feighner, J. P., Herbstein, J., & Damlouji, N. F. 1985. The Journal of Clinical Psychiatry, 46(6), 206–209.
Examined retrospectively the medical records of 5 male and 11 female patients treated with a combination of direct stimulants (DSs), monoamine oxidase inhibitors (MAOIs), and tricyclic antidepressants (TCAs) or DSs and MAOIs without TCAs. Results indicate that 5 Ss were given a combination of DSs and MAOIs, 3 were given an MAOI–TCA combination, and 8 were given all 3 classes (MAOI, TCA, and DSs). Side effects included orthostatic hypotension, anxiety, restlessness, irritability, dizziness, nausea, and hypomania.
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)
Relevant:
Ayahuasca and cocaine includes a study of low dose selegiline and IV cocaine and a report from someone who smoked crack while on Nardil
Combining MD𝘹 with harmalas includes a report of someone who got away with using MDMA while on moclobemide (there are reported deaths from that combo, which he links to)
[1] This is the account:
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)
[2]
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
[3] The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain. Nagai, F., Nonaka, R., & Satoh Hisashi Kamimura, K. 2007. European journal of pharmacology, 559(2-3), 132–137. doi: 10.1016/j.ejphar.2006.11.075 Table 2. The effects of drugs on monoamine re-uptake into rat brain synaptosome
The SERT IC50 value for 5-MeO-DMT is 4.1±0.91×10
–6. SERT IC50s for other psychedelics analyzed in the study below. Lower values equal stronger inhibiton.*
| 2C-I | 7.9±1.9 × 10–5 |
| 2C-E | 7.2±1.6 × 10–5 |
| 2C-C | 3.1±0.78 × 10–5 |
| AMT | 3.8±0.74 × 10–7 |
| 5-MeO-AMT | 2.9±0.71 × 10–6 |
| DPT | 2.9±0.69 × 10–6 |
| 5-MeO-DiPT | 2.2±0.41 × 10–6 |
| 5-MeO-MiPT | 6.4±1.8 × 10–6 |
And methamphetamine and cocaine:
| Cocaine | 2.1±0.52 × 10–6 |
| Methamphetamine | 4.0±0.97 × 10–6 |
[4]
Stimulants with MAOIs
[5]
Among antidepressant augmentation strategies, the addition of a stimulant to a monoamine oxidase inhibitor (MAOI) has received little attention in the literature in recent years because of the diminished clinical use of the latter and concerns of precipitating a hypertensive crisis or other serious complication. Despite that fact, experienced clinicians continue to use this combination for a variety of indications after other options have failed.
Feinberg S. S. (2004). Combining stimulants with monoamine oxidase inhibitors: a review of uses and one possible additional indication. The Journal of clinical psychiatry, 65(11), 1520–1524. doi: 10.4088/jcp.v65n1113
[6]
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. 2020. PsychoTropical Commentaries 1:1–71 Releasers (indirectly acting sympatho-mimetics ISAs), pg. 34
[7]
Studies using rat brain synaptosomes [63] show that 5-MeO-DMT also inhibits 5-HT re-uptake with an IC50 value comparable to other psychostimulants such as cocaine and methamphetamine, whereas it has little effect on dopamine re-uptake or the release of monoamine neurotransmitters.
[63] Nagai F, Nonaka R, Kamimura K. Satoh Hisashi. The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain. Eur J Pharmacol. 2007;559:132–137. [PubMed] [Google Scholar]
Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions. Shen HW, Jiang XL, Winter JC, Yu AM. Curr Drug Metab. 2010 Oct;11(8):659-66. doi: 10.2174/138920010794233495 PHARMACO/TOXICOLOGICAL EFFECTS AND DRUG ACTIONS OF 5-MEO-DMT
[8] Lloyd, J. T., Walker, D. R. (1965). Death After Combined Dexamphetamine and Phenelzine. British medical journal, 2(5454), 168–169. doi: 10.1136/bmj.2.5454.168-c
[9]
With the appropriate dietary restrictions and attention to potential drug interactions with serotonin and noradrenaline agents this class of drugs can be used effectively and safely.
Shulman, K. I., Herrmann, N., & Walker, S. E. (2013). Current place of monoamine oxidase inhibitors in the treatment of depression. CNS drugs, 27(10), 789–797. doi: 10.1007/s40263-013-0097-3
*"IC50 represents the concentration of a substance needed to inhibit a biological process by 50%, so lower values indicate higher potency." (Grok)
