Mixing MAOI with cacao?

[red22]

As indicated below, cacao already contains an MAOI. Would taking an MAOI medication be contraindicated with large doses of cacao (supplemental cacao)?

Again, although theorized for some time, it has now been proven that cacao contains MAO inhibitors known as tetrahydro-beta-carbolines that potentiate and positively flavor entheogenic compounds. (Naked Chocolate, David Wolfe & Shazzie) | http://books.google.com/books?id=6wHYcIds-2kC&pg=PT135

Tomas Herraiz. "Tetrahydro-β-carbolines, Potential Neuroactive Alkaloids, in Chocolate and Cocoa", J. Agric. Food Chem., 2000, 48 (10), pp 4900–4904 | http://freakshare.com/files/s1120te...ive-alkaloids-in-chocolate-and-cocoa.pdf.html

 

[sekio]

The major alkaloids in chocoalate are still caffeine and theobromine... I would not expect to find high levels of harmine/harmaline (B-carbolines) in cacao, as those compounds are potent enough MAOIs that they would allow oral DMT to be used. (and cacao is not an effective MAOI dfor that purpose).. they are the active alkaloids in Peganum harmala, aka syrian rue...

I suppose if you were playing around with extracts or concentrates it would be an issue, but I cannot see anything less than massive quantities of cacao being needed for MAOI action.

(Also, in general, MAOIs do not play well with alkaloidal drugs)

 

[red22]

At the end of the paper I linked to is the statement that he doesn't know if the tetrahydro-beta-carbolines are in substantial quantities. Cacao also contains catechin & epicatechin, which are MAO-B inhibitors, according to Wikipedia. Based on my reading, these are found in substantial quantities in cacao. The following article goes into these catechins, including some citations about them (does not go into MAOI activity, though): The truth is often bittersweet ...: chocolate does a heart good. Alspach G. Crit Care Nurse. 2007;27(1):11–5

More:


di Tomaso E, Beltramo M, Piomelli D. Brain cannabinoids in chocolate, Nature 1996, 382(6593):677-678

http://www.scienceinschool.org/repository/docs/issue2_nature_ditomasi1996.pdf

The isoquinolinoid salsolinol (17) has been investigated extensively over the last ten years. This compound is found in chocolate and is derived from the cocoa bean and the seeds of Theobroma cacao L. The addictive properties of chocolate have been ascribed to the dopaminergic activity of this compound,¹⁹ which also occurs as an endogenous catechol in the brain. (17) is dopaminergic at the D2 receptor and has a protective effect against neurodegeneration.²⁰


19. Melzig MF, Putscher I, Henklein P, In vitro pharmacological activity of the tetrahydroisoquinoline salsolinol present in products from Theobroma cacao L. like cocoa and chocolate, J Ethnopharmacol 73:153–159, 2000.

20. Antkiewicz-Michaluk L, Wardas J, Michaluk J, Protective effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline against dopaminergic neurodegeneration in the extrapyramidal structures produced by intracerebral injection of rotenone, Int J Neuropsychopharmacology 7:153–163, 2004.


Selected Topics in the Chemistry of Natural Products (Raphael Ikan, 2008 ), p. 406

 

[AlphaMethylPhenyl]

Its still probably only present in tiny amounts. Do you have a study which affirms that this compound is responsible for the chocolate being addictive or just that its there? A lot of supposedly addictive constituents exist in chocolate but comprise such a tiny amount that even the aggregate pleasure of all of them probably pales in comparison to what the xanthines in chocolate do.

 

[sekio]

This perhaps does not bode well then:

Brain Res. 2004 Apr 16;1005(1-2):67-76
Salsolinol, a dopamine-derived tetrahydroisoquinoline, induces cell death by causing oxidative stress in dopaminergic SH-SY5Y cells, and the said effect is attenuated by metallothionein.
Wanpen S, Govitrapong P, Shavali S, Sangchot P, Ebadi M.

As chocolate is widely considered to be non-neurotoxic I would be pretty hesitant to say that salsolinol is an "active component". Maybe it's just M&M brain lint, but here is further reading. I don't think there are other alkaloids in such a high concentration as theobromine in chocolate.

Epicachetins are also present in tea, coffee, and other flavonoid rich sources.

The addictive properties of chocolate

You ever suck a man's dick for chocolate?

have been ascribed to the dopaminergic activity of this compound

And not the dopaminergic activity of a sensorially pleasurable mixture of sugar, saturated fat, and caffeine?

 

[red22]

lol.

Well, I'm supplementing cacao by mixing it in warm water; it's pretty bitter and unpleasant. So, I'm not playing in terms of the last thing you said. Using one tablespoon, I notice a tiny, but significant mood boost as well as a painkilling effect similar to ibuprofen and a feeling of improved blood flow, body feels "freer." No doubt due to the significant vasodilating properties stated in that Crit. Care Nurse article. Free of edginess or any kind of crash. The vasodilation is caused by catechin, et al. which probably means they're found in large amounts and according to wikipedia, they're MAO-B inhibitors. So cacao is a significant MAO-B inhibtor, right?

 

[AlphaMethylPhenyl]

I think we're trying to liberate you from the conception that you're getting off on anything other than sugar, fat, and caffeine; might as well go to Mickey D's.

Significant? Not in the quantity possessed within any chocolate I've heard of.

 

[red22]

According to the following paper, catechin & epicatechin are more powerful MAO-Bs than selegiline.

Wen-Chi H... Monoamine oxidase B (MAO-B) inhibition by active principles from Uncaria rhynchophylla, J Ethnopharmacology

Analyses quantifying their content in cacao:

Rimbach, G... Polyphenols from Cocoa and Vascular Health... Int. J. Mol. Sci. 2009
Maleyki, A... Polyphenols in Cocoa and Cocoa Products... Molecules 2008
Kofink, M... (-)-Catechin in Cocoa and Chocolate... Molecules 2007
Hii, C. L... Polyphenols in cocoa... As, J. Food Ag-Ind. 2009
Freudenberg, K... The Catechin of the Cacao Bean. J. Am. Chem. Soc., 1932


Download all papers here: https://docs.google.com/file/d/0B3BBccfPNsX8NGoxUE4xNkh4UTA/edit?usp=sharing

 

[bloodshed344]

I think we're trying to liberate you from the conception that you're getting off on anything other than sugar, fat, and caffeine; might as well go to Mickey D's.

Significant? Not in the quantity possessed within any chocolate I've heard of.

Don't be a smart ass, he said he was using cacao powder, or do you not even know what that is?

 

[elucidator]

I buy full spectrum 25x cacao extract and I find it quite potent.
Half a tablespoon is good, 2 heaped tablespoons is too much. This has made me curious as to how it will react to a MAOI so I will try it with some Syrian rue extract and report back.

 

[red22]

According to the following paper, catechin & epicatechin are more powerful MAO-Bs than selegiline.

Wen-Chi H... Monoamine oxidase B (MAO-B) inhibition by active principles from Uncaria rhynchophylla, J Ethnopharmacology

Analyses quantifying their content in cacao:

Rimbach, G... Polyphenols from Cocoa and Vascular Health... Int. J. Mol. Sci. 2009
Maleyki, A... Polyphenols in Cocoa and Cocoa Products... Molecules 2008
Kofink, M... (-)-Catechin in Cocoa and Chocolate... Molecules 2007
Hii, C. L... Polyphenols in cocoa... As, J. Food Ag-Ind. 2009
Freudenberg, K... The Catechin of the Cacao Bean. J. Am. Chem. Soc., 1932


Download all papers here: https://docs.google.com/file/d/0B3BBccfPNsX8NGoxUE4xNkh4UTA/edit?usp=sharing

Bump. So, yeah, it seems like I did come across evidence that cacao is a powerful MAO-B inhibitor. I only gave the literature in question a cursory read, though. Would someonemore experienced in this territory be willing to review the docuemnts? Note that the papers listed under "Analyses quantifying their content in cacao" are basically redundant. And the only paper that talks about MAO-B inhibition by the chemicals in question is the first one.

 

[sekio]

The problem is that, although some of these flavonoids are indeed MAO inhibitors in cell culture, their rapid metabolism, poor BBB penetration, and relatively low natural abundance make them hundreds to thousands fold less effective than selegiline per milligram in humans.

Catechin and epicatechin are present in many fruits and veg. (Also, e.g. tea) There's not much evidence that the levels consumed in food are active as MAO-B inhibitors though.

 

[red22]

Thanks for the insight.

 

[bob_arctor]

I've had success with a full spectrum cacao extract called "Rapture" (which contains some weak natural MAOI:s as well) and low dose deprenyl for a gentle energy and mood boost. 25x Cacao extract has been even gentler, but felt worth it after giving up coffee.

 

[bloodshed344]

cocoa has primarily xanthine, caffeine, and phenethylamine in it if I remember correctly, making it definitely active once enough is taken, especially with an extract. It may have even more active chemicals in it.

 

[atara]

The problem is that, although some of these flavonoids are indeed MAO inhibitors in cell culture, their rapid metabolism, poor BBB penetration, and relatively low natural abundance make them hundreds to thousands fold less effective than selegiline per milligram in humans.

Indeed. I once tried to use cat's claw extract, which contains high levels of catechin -- a putative MAO-B inhibitor -- to permit the recreational use of phenethylamine. However, at no feasible dose of catechin -- even taking several grams at a time -- was I able to experience any activity from oral PEA. I can only conclude that catechin is basically useless as a MAO-B inhibitor.

I've been meaning to try the same experiment with Rhodiola rosea.

 

[sekio]

I seem to recall that rhodiola flavonoids (rosiridin etc), while they are in fact MAOIs, are micromolar as opposed to nanomolar level efficacy. So I have doubts how effective they are.

Here's a chart with figures I sourced from various bits of the internet. Clearly there are some MAOIS that are more effective than others.

 

[red22]

cocoa has primarily xanthine, caffeine, and phenethylamine

Quote:

Can craving for chocolate be explained by its sensory properties – a high sugar and fat content, and a pleasant mouth feel due to the fact that it melts at body temperature? Or can it be explained by the presence of pharmacologically active substances, such as caffeine, phenylethylamine or magnesium, in chocolate?
A 50g bar of chocolate contains between 9mg (milk chocolate) and 31mg (dark chocolate) of caffeine. From the experiments presented by previous speakers, Professor Benton considered it unlikely that the dosage contained in a typical bar of chocolate would have much of an effect on altering mood, but it might contribute to a cumulative effect with other substances.
Another substance present in chocolate is phenylethylamine, which is also found in low concentrations in the brain. Phenylethylamine releases dopamine and therefore acts in the same way as amphetamines. One might predict that it is this which is ‘addictive’. Studies have demonstrated that 2-3g of phenylethylamine is needed to have anti-depressant properties, but a 50g bar of chocolate contains only a third of a milligram. Moreover, phenylethylamine is broken down readily by monoamine oxidase, so a monoamine oxidase inhibitor would be needed to stop it being broken down in the digestive system.

British Nutrition Foundation (1998) BNF conference report. Stimulating thoughts: caffeine and food. BNF Nutrition Bulletin. 23, Winter, 226-233.


The last two posts were wonderful, especially yours, atara. Thank you.

 

[atara]

I seem to recall that rhodiola flavonoids (rosiridin etc), while they are in fact MAOIs, are micromolar as opposed to nanomolar level efficacy. So I have doubts how effective they are.

Here's a chart with figures I sourced from various bits of the internet. Clearly there are some MAOIS that are more effective than others.

Quercetin's affinity is higher than I remember. Unfortunately it's probably protonated (flavylium) at stomach pH, which should lead to quick hydrolysis (destruction). So any effective use would have to be parenteral, and -- of course -- dose titration becomes important.

EDIT:
As for those quercetin supplements:

Twenty years after Gugler et al (23, 24) failed to find quercetin in plasma or urine from volunteers challenged with 4 g pure aglycone, the team of Hollman et al (23, 24) showed that quercetin was indeed absorbed in humans. They demonstrated that glucosides of quercetin were more efficiently absorbed than quercetin itself, whereas the rhamnoglucoside (rutin) was less efficiently and less rapidly absorbed (Table 2⇓). This difference in absorption rates was confirmed by others (33, 34). When pure compounds were given, the bioavailability of rutin was ∼20% that of quercetin glucosides, on the basis of area under the plasma concentration-time curve values and relative urinary excretions (30, 34). The biochemical explanation for the better absorption of quercetin glucosides has been discussed elsewhere (1). It is clear that, for quercetin, bioavailability differs among food sources, depending on the type of glycosides they contain. For example, onions, which contain glucosides, are better sources of bioavailable quercetin than are apples and tea, which contain rutin and other glycosides.

http://ajcn.nutrition.org/content/81/1/230S.full

So oral quercetin supplements hydrolyse, and do nothing. Quercetin glycosides are absorbed but are not converted to the active form, which means no MAOI activity is likely:

The presence of intact glycosides of quercetin in plasma was debated a few years ago, but it is now accepted that such compounds are absent from plasma after nutritional doses (34, 37–40). Quercetin is not present as an aglycone and occurs only in conjugated forms.

 

[red22]

Exactly how strong is Rhodiola's MAOI activity? How is this to be interpreted?


The methanol and water extracts exhibited respectively inhibitions of 92.5% and 84.3% on MAO A and 81.8% and 88.9% on MAO B, at a concentration of 100 μg/ml.

Daphne van Diermen, Andrew Marston, Juan Bravo, Marianne Reist, Pierre-Alain Carrupt, Kurt Hostettmann, Monoamine oxidase inhibition by Rhodiola rosea L. roots, Journal of Ethnopharmacology, Volume 122, Issue 2, 18 March 2009, Pages 397-401, ISSN 0378-8741, 10.1016/j.jep.2009.01.007.
(http://www.sciencedirect.com/science/article/pii/S037887410900021X)