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Safety concern about harmalas - Interaction with DNA and neurotoxicity Options
 
orlin1
#1 Posted : 8/6/2022 1:31:44 PM
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Hi just read some article about harmalas and found this:
Should i be concerned ?

article link: https://www.academia.edu...e_and_Related_Alkaloids

Interaction with DNA and RNA
Some of the mutagenic and carcinogenic effects of
b-carboline alkaloids have beenstudied in prokaryotic and eukaryotic cells related to their ability to intercalate intoDNA [54, 55]. The b-carboline derivatives inhibit DNA topoisomerases and inter-fere with DNA synthesis. Harmine-, harmaline-, harman-, and norharman-inhibitedDNA excisions repair directly or indirectly and lead to altered DNA replicationfidelity and enzymatic activities in DNA-repair processes [56, 57]. These alkaloidsconsequently enhance UV or chemically induced mutagenesis [58]. Harman- andharmine-induced chromosome aberrations in Chinese hamster ovary cells after treatment with the clastogens mitomycin C and UV light [59] while in humanneuroblastoma SH-SY5Y cells harman and norharman induced apoptosis as wellas necrosis [60]. Aminophenylnorharman, a newly identified beta-carbolinealkaloid induced sister chromatid exchange and chromosome aberrations incultured Chinese hamster lung cells. The different types of b-carbolinealkaloids showed variation in affinity to bind DNA, and it is in the order of harmine
>harmalol>harmaline>harmane>tryptoline [61]. These alkaloids also bind with yeast RNA [62].

Neurotoxic Effects
Administration of b-carboline alkaloids to human being and a wide varietyof laboratory animals produces an intense and generalized action tremor [74]. Harmane is a potent, tremor-producing
b-carboline alkaloid and is usedin epidemiological studies. It is one of the most abundant of all dietary heterocyclicamines, and human exposure to harmane through diet is greater than that of other heterocyclic amines [9, 67]. Due to its high-lipid solubility, harmane accumulates inbrain tissue [75]. It provides the rationale for an in-depth scrutiny of their potentialrole in the etiology of essential tremor (ET), the most common tremor disorder [76].
b-carboline alkaloids are highly neurotoxic.


Anybody here with more knowledge about this ?
Plan to read related studies but is not my area so i probably dont get much from it.
 

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L-dreamer
#2 Posted : 8/6/2022 5:29:49 PM

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Are the articles interesting? Yes

Can they be used to extrapolate what happens when people ingest them? Most likely not. Beta-carbolines in themselves are unpleasant, no one will ever do a large scale study on them because people don't like taking them, and no one ingests them frequently enough. I'd be more careful if there were reports of side-effects observed in animals exposed long-term to them, but again I don't see this happening. I don't know how much harmane is in a caapi tea or syrian rue seed.

Do we put ourselves at risk by ingesting random teas or eating extracted beta-carbolines since we don't have a good picture about their long-term effects? Sure

Will this stop most people here from taking them? No

Should you be concerned? Well you can be if that is what you want
 
dreamer042
#3 Posted : 8/6/2022 5:33:01 PM

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At the doses we use, harmalas display both protective and repairative properties. These compounds have very potent anti-cancer and anti-tumor properties, and much of what you read about DNA strand breaks and neurotoxicity is in regard to how harmalas fight disease. That said, very very high doses far beyond those we would ever take, do display worrying in vivo effects (tremors, cellular damage, host organism DNA damage).

Here are a few more resources demonstrating these mechanisms of action:
https://link.springer.co...1007/s12272-020-01283-6
https://www.sciencedirec...s/pii/S0304394014007599
https://www.tandfonline....0/02791072.2016.1260189
https://www.mdpi.com/2227-9059/10/5/997
https://link.springer.co....1007/s12288-016-0770-z
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Visual diagram for the administration of dimethyltryptamine

Visual diagram for the administration of ayahuasca
 
Jagube
#4 Posted : 8/6/2022 5:35:56 PM

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People take them (not necessarily harmane as the main alkaloid, but harmine, harmaline and THH) often enough as part of ayahuasca and the most thorough study of it so far, The Hoasca Project, didn't give us any reasons to be concerned.

It *may* be prudent to avoid sun exposure on tea.
 
orlin1
#5 Posted : 8/6/2022 6:49:16 PM
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Thanks for reply

Plan to read thought articles when i have more time to get better picture.
So far i mainly have positive effects from harmalas and plan to continue to use it.

Use of harmalas as UV paint on body / stains on hands probably was not good idea Smile and i avoid in future to increase safety.
 
dragonrider
#6 Posted : 8/6/2022 7:05:56 PM

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dreamer042 wrote:
At the doses we use, harmalas display both protective and repairative properties. These compounds have very potent anti-cancer and anti-tumor properties, and much of what you read about DNA strand breaks and neurotoxicity is in regard to how harmalas fight disease. That said, very very high doses far beyond those we would ever take, do display worrying in vivo effects (tremors, cellular damage, host organism DNA damage).

Here are a few more resources demonstrating these mechanisms of action:
https://link.springer.co...1007/s12272-020-01283-6
https://www.sciencedirec...s/pii/S0304394014007599
https://www.tandfonline....0/02791072.2016.1260189
https://www.mdpi.com/2227-9059/10/5/997
https://link.springer.co....1007/s12288-016-0770-z

Yes. I wanted to say:"the dose makes the poison", but dreamer042 beat me to it.
 
Voidmatrix
#7 Posted : 8/6/2022 7:09:42 PM

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dragonrider wrote:
dreamer042 wrote:
At the doses we use, harmalas display both protective and repairative properties. These compounds have very potent anti-cancer and anti-tumor properties, and much of what you read about DNA strand breaks and neurotoxicity is in regard to how harmalas fight disease. That said, very very high doses far beyond those we would ever take, do display worrying in vivo effects (tremors, cellular damage, host organism DNA damage).

Here are a few more resources demonstrating these mechanisms of action:
https://link.springer.co...1007/s12272-020-01283-6
https://www.sciencedirec...s/pii/S0304394014007599
https://www.tandfonline....0/02791072.2016.1260189
https://www.mdpi.com/2227-9059/10/5/997
https://link.springer.co....1007/s12288-016-0770-z

Yes. I wanted to say:"the dose makes the poison", but dreamer042 beat me to it.


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Jees
#8 Posted : 8/8/2022 3:01:09 PM

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Perhaps, if the harmalas were 1000% safe at very high doses, then it might lack the weapons-potential to battle tumors and be neuro regenerative/protective at normal doses. Some most deadly poisons are in stern diluted form the most wonderful medicine unmatched by others.
I'm cutting big corners here I know Embarrased

Should you be worried? Type "long term ayahuasca users study" in google.

One potential thing to take into account is people who use SSRI meds, should be careful not to flood in serotonine. Too much is too much.
 
dithyramb
#9 Posted : 8/8/2022 4:27:10 PM

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I wonder if the tropane containing plants could be healthy in the long term with chronic use in appropriate doses also.
 
 
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