Tryptamines Using the endogenous chemical, pinoline, in place of herbal MAOIs in ayahuasca

[red22]

Pinoline (6-methoxy-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole) is an endogenous β-carboline thought to be synthesized in the pineal gland from serotonin. It is a strong inhibitor of MAO-A...

Synthesis of [3H]pinoline, an endogenous tetrahydro-β-carboline. Journal of Labelled Compounds and Radiopharmaceuticals. Callaway, J. C., Morimoto, H., Gynther, J., Airaksinen, M. M., & Williams, P. G. (1992). Labelled Compounds and Radiopharmaceuticals, 31(5), 355-364. DOI: 10.1002/jlcr.2580310504 (Abstract)


An alternate name for harmine, the predominant MAOI in B. caapi, shows its similarity to pinoline: 7-Methoxy-1-methyl-9H-pyrido[3,4-b]indole


It needs to mentioned that pinoline is a tetrahydro-beta-carboline because THβCs are weaker than βCs (regarding MAOI action).

“[Udenfriend et al. (1958)] showed that the fully aromatic β-carbolines were the most effective inhibitors, and that activity decreased with increasing saturation of the piperidine ring; tetrahydro-β-carbolines still showed significant activity, however.”

Monoamine oxidase inhibitors in South American hallucinogenic plants: Tryptamine and β-carboline constituents of Ayahuasca. McKenna DJ, Towers GHN, Abbott F. Apr 1984. Journal of Ethnopharmacology, vol 10, 2, 195-223. DOI: 10.1016/0378-8741(84)90003-5 (‘Function and properties of MAO’, p. 215)

Indeed, in another thread, I recently posted evidence that harmine's MAO-A IC50 is ~25x stronger than tetrahydroharmine's (another chem in caapi) (lower #s = stronger effect):

harmine: 0.06
THH: 1.52

Identification of harmine and β-carboline analogs from a high-throughput screen of an approved drug collection; profiling as differential inhibitors of DYRK1A and monoamine oxidase A and for in vitro and in vivo anti-cancer studies. Tarpley, M., Oladapo, H. O., Strepay, D., Caligan, T. B., Chdid, L., Shehata, H., … Williams, K. P. (2021). European Journal of Pharmaceutical Sciences, 162, 105821. doi: 10.1016/j.ejps.2021.105821

See table 2 on page 5.


So, I don't know if it would be strong enough for oral DMT, but if it is, this needs to be known. How fascinating that using a laboratory, we can make a verion of ayahuasca that's more natural than what can be obtained from the jungle (i.e. substituting B. caapi with a chemical that's already inside us).

There are other beta-carbolines that are endogenous as well, but I featured pinoline, since it gets the most mentions:

harman[1]
tetrahydronorharman (a.k.a. tryptoline)[2]
6-Hydroxytetrahydroharman[2]

Possibly 6-MeO-harmalan a.k.a. 10-MeO-harmalan[3][4]


1. Harman in human platelets. Bidder TG, Shoemaker DW, Boettger HG, Evans M, Cummins JT. Life Sci. 1979 Jul 9;25(2):157-64. doi: 10.1016/0024-3205(79)90387-4

2. Tetrahydronorharmane (THN) and 6-hydroxy-norharmane [sic]: physiological components in platelets and urine of man. Honecker, H. & H. Coper: Naunyn-Schmiedebergs Arch. Pharmacol. 1978, 302, R63

3. From what is available in the scientific literature, 10-MH seems to be an anti-metabolite of both melatonin and serotonin and is present endogenously in the body. In other words, out bodies synthesized it from melatonin probably as part of a negative feedback mechanism to put the brakes on excessive serotonin/melatonin production/effects.

haidut, Jan 10, 2021, https://lowtoxinforum.com/threads/10-methoxy-harmalan-an-anti-serotonin-chemical.38190/post-595359

4. One more substance, 6- methoxyharmalan, has been shown to derive, at least in vitro, from melatonin (9), which in turn results from the methylation of acetylserotonin. The enzyme which makes this methylation possible, hydroxyindole-0-methyltransferase (HIOMT), has only been found in the pineal body. (See Fig. 1.)

Naranjo C. Ayahuasca, caapi, yage. Psychotropic properties of the harmala alkaloids. Psychopharmacol Bull. 1967 Dec;4(3):16-7. PMID: 5615550.

https://www.claudionaranjo.net/pdf_files/psychedelics/psychotropic_properties_of_the_harmala_alkaloids_english.pdf

 

[Pfafffed]

Interesting. I didn't know there were any endogenous beta-carbolines. Even if it were available, I don't know that I would be in a hurry to self-administer without considerable reassurances as to its safety. I do find it interesting that different MAO inhibitors and RIMAs seem to impart different flavors to the oral DMT experience.

 

[Esperighanto]

Interesting. I didn't know there were any endogenous beta-carbolines. Even if it were available, I don't know that I would be in a hurry to self-administer without considerable reassurances as to its safety. I do find it interesting that different MAO inhibitors and RIMAs seem to impart different flavors to the oral DMT experience.

Scorpions glow under UV light iirc because of beta carbolines in their shell, fun fact.

The way that harm(al)ine used to be called telepathine, it's interesting to me that what appears to be a structural isomer is originating from the pineal gland, often believed to relate to misunderstood neuroscience surrounding studies of ESP and the sort. It's really kooky to even say but my mother often gets visuals from 1,500 miles away if I miss harmalas and serotonergics, it's weird that she can tell. The says she sees neon lightning spinning around like clouds with her eyes shut, which is the same shit I see and I've never told her that. I feel like the guy in the horror movie saying "I know what I saw!" hahaha

 

[red22]

“Using the standards applied to any other area of science, it is concluded that psychic functioning has been well established.”

An Assessment of the Evidence for Psychic Functioning. Jessica Utts.1995. University of California Division of Statistics. (Abstract)

https://www.irva.org/docs/public/bibliography/pdfs/utts1995assessment.pdf

Dr. Jessica Utts was a member of the CIA review panel on Remote Viewing.


“I never liked to get into debates with the skeptics, because if you didn’t believe that remote viewing was real, you hadn’t done your homework.” - Major General Edmund R. Thompson, U.S. Army Assistant Chief of Staff for Intelligence, 1977-81, Deputy Director for Management and Operations, Defense Intelligence Agency 1982-84

Remote Viewers: The Secret History of America's Psychic Spies. Jim Schnabel, 1997



The Long, Strange Relationship Between Psychedelics and Telepathy. Shayla Love, Jul 18, 2022. Motherboard

 

[red22]

It looks like it may be too weak to work.

“Most harmala alkaloids potently inhibit the MAO-A isoform in the low nanomolar range,²² whereas pinoline barely showed any significant monoamine oxidase inhibitory effect (MAO-A; IC50 = 41.5 ± 6.3 μM).⁴⁸ The MAO-A inhibition of pinoline could be of relevance at pharmacological doses but not if pinoline occurs in trace amounts under physiological conditions. The inhibitory effect in MAO-A is more pronounced in 1, the nor-isomer of tetrahydroharmine. Both 1 (IC50 = 1.3 ± 0.3 μM) and tetrahydroharmine show a similar IC50 in the low micromolar range.⁴⁹”

Neurogenic Potential Assessment and Pharmacological Characterization of 6-Methoxy-1,2,3,4-tetrahydro-β-carboline (Pinoline) and Melatonin–Pinoline Hybrids. Revenga MF, Pérez C, Morales-García JA, Alonso-Gil S, Pérez-Castillo A, Caignard DH, Yáñez M, Gamo AM, Rodríguez-Franco MI. 2015. ACS Chemical Neuroscience, 6, 5, 800-810. DOI: 10.1021/acschemneuro.5b00041 (Discussion, page F)

As stated, pinoline is substantially weaker than tetrahydroharmine and someone recently stated that he wasn't even able to get that to work for oral DMT:

I couldn't get 300mg of THH on its own to make DMT orally active personally,

However, what's fascinating is the idea of β-carboline RCs (“βIHKaL”), which is the subject of the above study.

“Based on these observations and in our interest in melatonin-based potential drugs,²⁵⁻²⁸ we wished to develop a series of melatonin-restricted analogues by integrating the main structural features of melatonin within the carboline scaffold of pinoline, thus hybridizing both structures (Figure 1). The synthesized compounds 1−5 were pharmacologically characterized and compared to their parent and related structures in serotonergic and melatonergic receptors, metabolic enzymes (monoamine oxidases), and in two models related to assess their antioxidant potential and blood-brain barrier permeability. Provided the neurogenic potential of melatonin^29,30 and our interest in developing new potential brain-repairing agents,²⁵ we also explored the neurogenic potential of the orthodox melatonin−pinoline hybrid 2 and the parent compound pinoline, in neural stem cells.”


6-MeO-harmalan probably works though:

“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.”

The Gateway to Inner Space: A Festschrift in Honor of Albert Hofmann. Christian Rätsch (ed.), 1989. Bridport, England: Prism Press (‘A report on the symposium “On the Current State of Research in the Area of Psychoactive Substances”’. Hanscarl Leuner & Michael Schlichting, page 237)