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Genotoxic effects of beta-carboline alkaloids

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dreamer042

dreamer042

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Picada, J., da Silva, K., Erdtmann, B., Henriques, A., & Henriques, J. (1997). Genotoxic effects of structurally related beta-carboline alkaloids. Mutation Research, 379(2), 135-149.


Boeira, J., da Silva, J., Erdtmann, B., & Henriques, J. (2001). Genotoxic effects of the alkaloids harman and harmine assessed by comet assay and chromosome aberration test in mammalian cells in vitro. Pharmacology & Toxicology, 89(6), 287-294.
 

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Upon first inspection this seems like potentially unfortunate news.

However, it might actually lend some support to an ongoing theory I've had which I believe many on this site would also support or already have suggested. Perhaps the change in consciousness one experiences after working with entheogens reflects a change in DNA or in DNA's transcriptional behavior, i.e. protein expression.

In my personal experience, my body fat composition noticeably improved after using ayahuasca and freebase DMT heavily for a year or more (I use them very seldom nowadays).

The news that beta carbolines may be "genotoxic" certainly indicates that DNA may be perturbed by an important class of entheogenic molecules, which in my opinion supports the notion that these medicines "improve" consciousness by a mechanism involving "DNA upgrades" - a very far out and exciting idea!
 
These papers are what gave me a strange uncomfortable gut-feeling when I was smoking lots and lots of pure freebase Harmala Alkaloids (gram wise)
 
..don't panic..not exactly a strong or absolutely conclusive result..
The present results may suggest that these alkaloid b-carbolines probably do not carry long-term genetic risk, although further support is necessary to decide whether those chemicals can be hazardous to human health.
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[1997]
Although these compounds induced chromosome damage in mammalian cells, they must be considered weak clastogenic agents.
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In contrast, Sasaki et al. (1992) observed that both harman and harmine do not induce chromosome aberrations by themselves in CHO-K1 cells. In their study, harman and harmine were used at doses greater than in the present study.
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In conclusion, this work provides evidence for the genotoxicity of harman and harmine, and confirms the usefulness of the Comet assay in V79 cells for evaluation of drugs. However, their biological effect still cannot be fully undertood and more studies are needed in order to evaluate the safe dose-limit of b-carboline alkaloids consumption.
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[2001]
 
Thinking about the thousands of years of Ayahuasca use in South America and seeing the happy tribes down there.

I have a feeling geno"toxic" isn't the right word.
 
I once had a huge dose of rue tea (30 grams of seed). It felt horrible; OEV and vomiting with diarrhea. The OEV were of white-colored lightning.

I had the perception that the dose I had ingested was toxic. I feel lucky I did not have a worse outcome, and will do much more reading about dosages next time I try a new substance.

I hope I have not messed up worse than I had previously thought.

Next time, I will also read advice I am given more carefully, as to not skip over an important note about dosing.


* I must note that just minutes before it became horrible, it was very pleasant.
 
..the implication of the papers linked is that, at very high doses, harmalas may cause some DNA breakage, however they are not very relatively strong in this regard..

there is a fair body of research indicating the beneficial medicinal effects of ayahuasca, so it would probably be fair to say that, like any medicine, there is a safe dosage level..

..it also should be noted (and the above paper has not taken this into account) that due to the action of harmalas as MAOIs, it is impossible in most cases to rule out the role of dietary amines in any apparent negative effects at high doses (MAOIs allow these into the bloodstream) ..in other words, only after a highly restricted diet of several weeks or more could the effects of harmalas be seen 'on their own'..
..funny how this is what traditional indigenous ayahuasqueros recommend..
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Nen, maybe the effects of genotoxicity is related to the ability of b-carbolines to intercalate with DNA (Source ) instead of the MAOI/other amines hypothesis. But certainly everything would add up in the case of humans.

As for the traditional diet comment, it is often different in different places (e.g. Shuar drinking alcohol with aya while for others this is a big no-no), and in many aspects does not really have a relationship with potential tyramine/etc build up...


But the big factor here, as nen correctly mentioned, is that there is enough research on ayahuasca to show that it is not harmful in any reasonable dosage. Even in high and regular doses, which is common with traditional use, it seems harmless, toxicity-wise.

Note that none of the studies were done with humans, it was one in vitro and one with live rats... I'd like someone with more knowledge to translate what the amount of alkaloids mean in terms of human scale.
 
..certainly the intercalation is the main factor being looked at, however the authors' specifically set out to relate harmala toxicity in humans (in their intro) ..

i didn't mean to induce the diet debate:) ..i just want to say, while many traditional diets may not be logical, it is logical that if you have a potentially toxic amine in your gut/system (there are many in foods, not necessarily tyramine..it has been over-stated IMO), and then take an MAOI, then this will allow the toxicty of that amine to express itself to differing extents..
MAOI acts on a whole range of compounds to prevent them from entering the bloodstream..
the 'dieta' in some cases i believe may not be to target anything specific (like tyramine, which is not that toxic) but to simply the intake, hence minimising the risk of toxic amine intake..

low weight molecular amines are toxic..http://en.wikipedia.org/wiki/Amine

also, the inability to break down an amine when MAO inhibiting renders it potentially more toxic..e.g. nicotine overdose as a cause of death on ayahuasca..
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peganum harmala decoctions are used to treat tumors in the east, by washing the tumors with the decoction.

I sort of doubt that they will find carcinogenic effects in humans from the use of these plants/alakloids at reasonable doses. Animals studies are not always a good indication. Look at dogs who eat too much cannabis etc..
 
Nen, but then wouldn't it be a contradiction? If the dietas had anything to do with diminishing risk of excess amine build up, then by your very example you'd think they'd avoid mixing substances for example high dose tobacco during ayahuasca usage?

I'm not sure what is the root of dietas (and if there even is a common root), I think maybe it could be more symbolic, but so far I never found a coherent argument that explains the reason for the specific aspects of spiritual dietas.
 
..i don't want to veer off topic..what i essentially mean is that there are a lot of potential synergistic effects that can occur with MAO-A or B inhibitors and other compounds in the system..

back to beta-carbolines and DNA..:)

this paper is more recent (don't have full-text yet)
'β-Carboline alkaloids bind DNA' [2010] Journal of Photochemistry and Photobiology
Shohreh Nafisia, Mahyar Bonsaiia, Pegah Maalia, Mohammad Ali Khalilzadehb, Firouzeh Manouchehria
β-Carboline alkaloids present in Peganum harmala (harmal) have recently drawn attention due to their antitumor activities. The mechanistic studies indicate that beta-carboline derivatives inhibit DNA topoisomerases and interfere with DNA synthesis. They interact with DNA via both groove binding and intercalative modes and cause major DNA structural changes.
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The affinity of alkaloids–DNA binding is in the order of harmine > harmalol > harmaline > harmane > tryptoline.
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..so, certainly Harmals affect DNA..but there is no conclusive evidence that this is negative (especially at normal doses)
and anti-tumor activity has been demonstrated..
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A lot of antibacterial and antiprotozoal compounds from natural sources (plants, fungi especially) exhibit genotoxicity... It just selectively targets the "bad guys" in the human body.

It's a matter of dose dependent activity, and I'm not too sure about the value of comparing rodent lung tissue isolate to whole organism exposure. All the in vivo assessments indicate beneficial results in humans, as others have posted above, I'm not too worried yet.
 
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